scientific american 2001 - 89pp

Medical NanoprobesBuckytube Electronics

Living Machinery

Atom-Moving ToolsNew Laws of PhysicsNano Science Fiction

SPECIALISSUE

NANOTECHThe Science of the Small Gets Down to Business

S E P T E M BE R 20 01 $ 4. 95W W W. S CI A M. C OM

Eric Drexler on Nanorobotsand

Richard Smalley on Why They Won’t Work

ALSO

Copyright 2001 Scientific American, Inc.Copyright 2001 Scientific American, Inc.

SCIENTIFIC AMERICAN Volume 285 Number 3

N A N O V I S I O N S

74 Machine-Phase NanotechnologyB Y K . E R I C D R E X L E RThe leading visionary in the field forecasts how nanorobots will transform society.

N A N O F A L L A C I E S

76 Of Chemistry, Love and NanobotsB Y R I C H A R D E . S M A L L E YA Nobel Prize winner explains why self-replicating nanomachines won’t work.

N A N O I N S P I R A T I O N S

78 The Once and Future NanomachineB Y G E O R G E M . W H I T E S I D E SLessons from nature on building small.

N A N O R O B O T I C S

84 Nanobot Construction CrewsB Y S T E V E N A S H L E YOne company’s quest to develop nanorobots.

N A N O F I C T I O N

86 Shamans of SmallB Y G R A H A M P . C O L L I N SNanotechnology has become a favorite topic of science-fiction writers.

O V E R V I E W

32 Little Big ScienceB Y G A R Y S T I XNanotechnology is all the rage. Will it meet its ambitious goals? And what is it, anyway?

N A N O F A B R I C A T I O N

38 The Art of Building SmallB Y G E O R G E M . W H I T E S I D E S A N D J . C H R I S T O P H E R L O V EThe search is on for cheap, efficient ways to makestructures only a few billionths of a meter across.

N A N O P H Y S I C S

48 Plenty of Room, IndeedB Y M I C H A E L R O U K E SThere is plenty of room for practical innovation atthe nanoscale—once the physical rules are known.

N A N O E L E C T R O N I C S

58 The Incredible Shrinking CircuitB Y C H A R L E S M . L I E B E RResearchers have built nanoresistors andnanowires. Now they have to find a way to put them together.

N A N O M E D I C I N E

66 Less Is More in MedicineB Y A . P A U L A L I V I S A T O SNanotechnology’s first applications may includebiomedical research and disease diagnosis.

contentsMagnified tip of an atomic force microscope

features

september 2001

SPECIALNANOTECHNOLOGYISSUE

w w w . s c i a m . c o m S C I E N T I F I C A M E R I C A N 5

Copyright 2001 Scientific American, Inc.

6 S C I E N T I F I C A M E R I C A N S E P T E M B E R 2 0 0 1

departments

columns

8 SA PerspectivesThe National Nanotechnology Initiative brings a welcome boost to the physical sciences and engineering.

10 How to Contact SA10 On the Web12 Letters16 50, 100 & 150 Years Ago18 News Scan

� Solved: the solar neutrino problem.� Drawbacks of the cancer-fighting drug Gleevec.� Retinal displays for pilots.� How snowball Earth got rolling.� No more anonymous Web surfing?� Hunting jaguars with darts.� By the Numbers: Reliability of crime statistics.� Data Points: Believers in the paranormal.

30 Profile: Elizabeth GouldThis neurobiologist looks at how memory and healing in the brain may rely on the growth of new neurons.

92 Working KnowledgeFleas flee from new “spot” treatments used on pets.

94 VoyagesGeological tours expose the innermost secrets of New York City and beyond.

98 ReviewsScience, Money, and Politics: Political Triumph andEthical Erosion depicts American “Big Science” as abloated, whiny, self-important bureaucracy.

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SCIENTIFIC AMERICAN Volume 285 Number 3

29 Skeptic B Y M I C H A E L S H E R M E RThe new religion of cryonics offers to raise its faithful dead.

102 Puzzling Adventures B Y D E N N I S E . S H A S H ASquare dancing without collisions.

103 Anti Gravity B Y S T E V E M I R S K YNever take off your shoes near a Komodo dragon.

104 Endpoints

A B O U T T H E P H O T O G R A P H E R : The work of Felice Frankel appears throughoutthis issue. Collaborating with scientists, Frankel creates film and digitalimagery related to diverse areas of science, including nanotechnology. Herimages have appeared in major national magazines and technical journals. InJanuary 2002 the MIT Press will publish her guide to photographing science.Recently she received a three-year grant from the Alfred P. Sloan Foundation toco-author a book on nanotechnology with Harvard University’s George M.Whitesides. She and Whitesides wrote a previous book, On the Surface ofThings: Images of the Extraordinary in Science (Chronicle Books, 1997).

Cover image and preceding page: Felice Frankel, with technical help from J. Christopher Love; this page, clockwise from top left: Lawrence BerkeleyNational Laboratory; Robert Young Pelton/Corbis; Felice Frankel, with technicalhelp from K. F. Jensen, M. G. Bawendi, C. Murray, C. Kagan, B. Dabbousi and J. Rodriguez-Viego of M.I.T.


Biologists sometimes stand accused of physics envy:a yearning for irreducible, quantifiable laws sufficientto explain the complex workings of life. But the jeal-ousy goes both ways. Physicists, chemists and othernonbiologists have long suffered from what can onlybe called NIH envy: the longing for the hefty increas-es in research funding that seem to go every year to theNational Institutes of Health.

From 1970 through 2000,federal backing for the life sci-ences more than tripled in con-stant dollars, whereas money forthe physical sciences and engi-neering has by comparison re-mained flat. But last year theClinton administration delivereda valentine to the physics, chem-istry and materials science com-munities: the National Nano-technology Initiative provided abig boost in funding for the sci-ence and engineering of the small.The initiative, moreover, seemsto have staying power. The Bush

White House has targeted a more modest but still sub-stantial increase for nanotech. If the president’s bud-get request passes, federal funding for nanotechnol-ogy, at $519 million, will have nearly doubled in thepast two years, more than quadrupling since 1997.

The initiative may prove to be one of the most bril-liant coups in the marketing of basic research since theannouncement, in 1971, of the “War on Cancer.”Nanotechnology—the study and manufacture ofstructures and devices with dimensions about the sizeof a molecule—offers a very broad stage on which theresearch community can play. Nanometer-scale physicsand chemistry might lead directly to the smallest and

fastest transistors or the strongest and lightest mate-rials ever made. But even if the program gives specialemphasis to the physical sciences and engineering, ithas something for everyone. Biologists, of course,have their own claim on the molecular realm. Andnanotechnology could supply instrumentation tospeed gene sequencing and chemical agents to detecttumors that are only a few cells in size.

Of course, a program that tries to accommodateeveryone could end up as a bottomless money sink. Inhis new book Science, Money and Politics (reviewedin this issue on page 98), journalist Daniel S. Green-berg warns of the dangers inherent in an indiscrimi-nate, all-encompassing approach to research that eatsup money. Skeptics have wondered whether sizableincreases are warranted for such a nascent field. ACongressional Research Service report last year raisedquestions about why nanotechnology merited suchgenerosity, given that some of its research objectivesmay not be achievable for up to 20 years.

But the initiative is more than mere marketing. Aportfolio of diverse ideas—unlike a program focusedon, say, high-temperature superconductivity—mayhelp ensure success of a long-term agenda. The vari-ety of research pursuits increases the likelihood thatsome of these projects will actually survive and flour-ish. Industry, in contrast, is generally reluctant to in-vest in broad-based research programs that may notbear fruit for decades.

Because the development of tools and techniquesfor characterizing and building nanostructures may havefar-reaching applicability across all sciences, nano-technology—the focus of this issue of Scientific Amer-ican—could serve as a rallying point for physicists,chemists and biologists. As such, it could become amodel for dousing NIH envy and the myriad other skir-mishes that occur in the yearly grab for research dollars.


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THE EDITORS [email protected]

Megabucks for Nanotech

NANOMACHINES


We often assume that extraterrestrials possess theintelligence and the technology to contact us. But whatif they aren’t that smart? How would we find them? In fact, many scientists are now suggesting that whenwe discover alien life—if we do—it won’t resemble thecunning eight-eyed rivals of Star Trek episodes. Instead,they say, it will most likely come in the form of tinymicrobes. With that in mind, scientists at NASA’s JetPropulsion Laboratory are now developing ways tosearch for cells among the stars.

www.sciam.com/explorations/2001/071601alien/

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YOUR OIL OR YOUR WILDLIFE?Those who refer to the Arctic NationalWildlife Refuge (ANWR) as the last pris-tine wilderness in America [“The ArcticOil & Wildlife Refuge,” by W. WaytGibbs] either are purposely misrepre-senting the facts or have never visited theregion.

In truth, it is 100 miles of flat, barren,frozen tundra, a small part of the 1,100-mile coastline of Alaska on the ArcticOcean. It is predicted to hold about thesame quantity of oil as we have importedfrom Saudi Arabia during the past 30years. It will keep the Alaska pipeline fullfor at least the next 30 years.

TED STEVENSU.S. Senator, Alaska

The U.S. Geological Survey estimatesthat between six billion and 16 billionbarrels of recoverable oil are in ANWR.Even if the mean estimate were discov-ered, it would be the largest oil fieldfound worldwide in the past 40 years.

At a time when we face a significantenergy crisis and our dependence on oth-er nations for energy is rising, we mustlook here at home for solutions. Al-though ANWR alone is not the answer,we cannot ignore the tremendous re-sources that exist there. It can be safelyexplored and should be a part of our na-tional energy strategy.

FRANK MURKOWSKIU.S. Senator, Alaska

Chairman, U.S. Senate Energy and Natural Resources Committee

Gibbs noted the findings of several re-searchers who speculate that oil develop-ment and caribou cannot mix. But hefailed to cite published, peer-reviewed sci-entific studies indicating that oil develop-ment in Alaska’s Arctic has not affectedcalving success or herd growth. Any billpermitting oil development will requirethe highest degree of wildlife protection.

DON YOUNGU.S. Congressman, Alaska

GIBBS REPLIES: According to the 2000 AnnualReport of the U.S. Energy Information Admin-istration, Saudi Arabia sent 10.7 billion barrelsof oil to the U.S. from 1969 to 1999. That is halfagain as much as the best guess for the 30-year production from the 1002 Area. EIA ana-lysts predict a maximum production rate fromthe refuge of about half a million barrels a day10 years after development begins, with a peakof nearly a million barrels a day about a decadeafter that. To “keep the Alaska pipeline full” re-quires 2.1 million barrels a day, but only 1.1million barrels flowed through it in 1999, andproduction is falling steadily. Alaska’s Divisionof Oil and Gas estimates that 20 years fromnow North Slope oil fields outside of the 1002Area will produce only 408,000 barrels a day.

There are large natural variations in thepopulations and breeding patterns of the ani-mals that live on the North Slope, so any effectof human activities on those trends may notbe visible until many years of data have beencollected and many confounding factors havebeen studied and appropriately controlled for.Moreover, some of the studies that examinedeffects on caribou from North Slope oil devel-


WRITES FORMER PRESIDENT JIMMY CARTER, “I read withgreat interest ‘The Arctic Oil & Wildlife Refuge,’ by W. Wayt Gibbs.I had the privilege of signing the 1980 Alaska National InterestLands Conservation Act, which established the Arctic NationalWildlife Refuge and specifically prohibited oil development in its1.5-million-acre coastal plain. I also had the opportunity to visitthe area and witness its great herds of caribou, muskoxen andother wildlife. I feel that those in Congress who soon will rendertheir own judgment on whether to protect or drill the Arctic refugewould benefit from reading your article.”

For further comments on this and other articles from the Mayissue, please read on.

EDITOR IN CHIEF: John RennieEXECUTIVE EDITOR: Mariette DiChristinaMANAGING EDITOR: Michelle PressASSISTANT MANAGING EDITOR: Ricki L. RustingNEWS EDITOR: Philip M. YamSPECIAL PROJECTS EDITOR: Gary StixSENIOR WRITER: W. Wayt GibbsEDITORS: Mark Alpert, Steven Ashley, Graham P. Collins, Carol Ezzell, Steve Mirsky, George Musser, Sarah SimpsonCONTRIBUTING EDITORS: Mark Fischetti, Marguerite Holloway, Madhusree Mukerjee, Paul Wallich

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LettersE D I T O R S @ S C I A M . C O M


opment are not immediately applicable to the1002 Area because of differences in geogra-phy, herd size and the distribution of vegeta-tion. Nevertheless, much of the older peer-reviewed research relevant to this debate wasin fact cited in the article.

“The Arctic Oil & Wildlife Refuge” over-states the benefits of drilling by askinghow much oil might ultimately be eco-nomically recovered if the cost of findingit were already sunk. But explorationcosts—economic as well as environmen-tal—also have to be considered whenjudging whether to allow drilling. If find-ing costs are included, then at a sustainedWest Coast price of $24 a barrel (in 1996dollars), the mean expected economical-ly recoverable reserve is 5.2, not 7, billionbarrels; at $18, about 2.4, not 5, billionbarrels; and at $15, zero, not a few hun-dred million barrels. Both ways of con-sidering recoverable reserves are legiti-mate, but I think the lower figure, count-ing finding costs, is the right one for thepublic policy decision.

AMORY B. LOVINSChief Executive Officer (Research)

Rocky Mountain InstituteSnowmass, Colo.

The question before us appears to bewhether our rapacious appetite for oil willlead to the destruction of vast expanses ofuntouched wilderness, an irreplaceablesanctuary for polar bears, white wolvesand caribou. For 20,000 years, the nativeGwich’in people have inhabited this sa-cred place, following the caribou herd andleaving the awe-inspiring landscape just asthey found it. For the sake of future gen-erations, I hope the answer is no todrilling, despite advances in technology.

ROBERT REDFORDSundance, Utah

ALL ABOUT INKBLOTSScott O. Lilienfeld, James M. Wood andHoward N. Garb [“What’s Wrong withThis Picture?”] do not present a balancedanalysis of the Rorschach; they overem-phasize studies that do not support the

test’s reliability and validity and ignorethose that demonstrate its merits andsound psychometric properties.

They also fail to recognize that no psy-chological measure should be used in iso-lation when making clinical decisions.Well-trained Rorschachers know that in-terpretations based on any given test mustbe supplemented by information obtainedthrough other methods. The Rorschachhas prevailed because it captures the com-plexity of human functioning in a waythat self-report measures alone do not.

LISA MERLODOUGLAS BARNETT

Department of Psychology Wayne State University

LILIENFELD REPLIES: Despite thousands ofstudies conducted on the Rorschach, only ahandful of indices have received consistentempirical support. Merlo and Barnett are cor-rect that the Rorschach should not be usedin isolation when making clinical decisions,but they erroneously assume that addingthe Rorschach to existing test informationnecessarily increases validity. In fact, in sev-eral studies validity decreased when clini-cians with access to other test informationwere provided with Rorschach data.

There is little evidence that Rorschachdata contribute statistically to the assess-ment of personality or mental illness beyondquestionnaire data. Although the Rorschachyields immensely detailed and complex data,we should not make the mistake of assumingthat these data are necessarily valid or useful.

SEMANTIC WEB: NOT FUZZYWhat struck me as a curious omission in“The Semantic Web,” by Tim Berners-Lee, James Hendler and Ora Lassila, wasany mention of the notion of fuzzy logic.Even today’s relatively primitive searchengines attempt to rate the relevance ofhits to the supplied search terms.

ROB LEWISLangley, Wash.

BERNERS-LEE REPLIES: I deliberately didn’tmention fuzzy logic, as fuzzy logic itself doesnot work for the Web. I see fuzzy logic and oth-

er heuristic systems as being used withinagents that trawl the Semantic Web. I see theoutput of such systems as being very usefuland sometimes so valuable that it is reenteredinto the Semantic Web as trusted data. But itcan’t be the basis for the Semantic Web. In thebasic Semantic Web you have to be able to fol-low links successively across the globe with-out getting fuzzier.

E. COLI–FREE COOKOUTSIn “Antimicrobe Marinade” [StakingClaims], Gary Stix presents three new,high-tech methods to decrease E. coli0157:H7 in meat. I, for one, plan on con-tinuing to fall back on an older (Nean-dertals used it), low-tech but foolproofmethod to kill the bacteria: cooking. If allthe effort at developing high-tech meansof control were redirected at educatingeveryone about known control meth-ods—avoiding cross-contamination andcooking the inside of burgers to 160 de-grees or higher (“cook the pink out”)—the E. coli problem we have now mightjust go away.

WINKLER G. WEINBERGSection Chief, Infectious Disease Service

Kaiser PermanenteAtlanta

SUPERCAVITATION, SWIMMINGLYIn reading “Warp Drive Underwater,”by Steven Ashley, I tripped over the state-ment that “swimming laps entirely under-water is even more difficult” than swim-ming on the water’s surface. Actually, itis much easier to swim several laps under-water with a single breath than it is toswim on the surface, because the air/wa-ter boundary friction is even greater thanthe water friction. In fact, competitiveswimming rules for years stipulated thatswimmers could not become entirely sub-merged during the breaststroke.

JON TOBEYMonroe, Wash.

ERRATUM To determine how far you’ve dri-ven, multiply (not divide, as was incorrectlystated in “Rip Van Twinkle,” by Brian C. Chaboy-er) the fuel supply by the gas mileage.


Letters


SEPTEMBER 1951HOW SALMON GET HOME—“An explana-tion of one of the most engaging phe-nomena of nature—the salmon’s returnfrom hundreds of miles at sea to its nativecreek—has been proposed by ArthurHasler and Warren Wisby of the Univer-sity of Wisconsin. They believe that thefish can smell its way back home. ‘It ap-pears that substances in the water, prob-ably coming from the vegetation andsoils in the area through which thestream runs, give each stream an odorwhich salmon can smell, remember andrecognize even after a long period of non-exposure.’ The damming of many Pacif-ic Coast salmon streams is resulting in aprogressive decline of the yearly catch, ashuge numbers of salmon batter them-selves to death trying to get over thedams and back home.”

ENGINEERS—“In 1850 a little more than5 per cent of America’s industrial powerwas supplied by machines; 79 per centwas furnished by animals and 15 per centby human muscles. Today 84 per cent ofour power is supplied by machines andonly 12 per cent by animals and 4 percent by men. As a consequence the engi-neer has become an increasingly impor-

tant factor in our civilization. There are400,000 of them in the U.S., and engi-neering is now our third-largest profes-sion, exceeded only by teaching andnursing. However, engineers are in acute-ly short supply, and the number of grad-uates in the next few years will be farshort of the need for new engineers.”

SEPTEMBER 1901OXYGEN FOR AERONAUTS—“An appara-tus has been devised by a Frenchman,Louis-Paul Cailletet, for the purpose ofsupplying aeronauts with pure oxygenwhen poised at a high altitude, where theextreme rarefaction of the air rendersthem liable to asphyxiation. When theaeronauts experience the nausea arisingfrom rarefied air, they have recourse toan oxygen supply. His device consists ofa double glass bottle containing liquidoxygen. From the reservoir extends aflexible tube communicating with a smallmetal mask covered externally with vel-vet to protect it from the cold.”

THE OKAPI DISCOVERED—“Sir HarryJohnston’s discoveries in Uganda are ofgreat importance. One of the new animalswhich he found was the ‘Okapi.’ It be-longs to a group of ruminants represent-

ed at the present time only by the giraffeand the prong-horned antelope, so-called,of North America. So far as it can be as-certained, the okapi is a living represen-tative of the Hellatotherium genus, whichis represented by an extinct form foundfossilized in Greece and Asia Minor. Theanimal is about the size of a large ox. Thecoloration is, perhaps, unique amongmammals. The body is of a reddish color,the hair is short and extremely glossy.Only the legs and hind quarter of the an-imal appear to be striped.”

SEPTEMBER 1851MECHANICAL REAPER—“The IllustratedNews, London, says: ‘McCormick’s reap-ing machine had a fair trial, at the annualgathering at Mechi’s farm. It rained in tor-rents, and mud and wet straw soonclogged the other instruments; but wehave the authority of, among others, Mr.Fisher Hobbes, the well-known agricul-turalist, for stating that McCormick’s ma-chine performed its work perfectly, andproved itself one of the most valuable agri-cultural inventions of the age. It has ar-rived at the fortunate period, when thesteady emigration of Irish laborers threat-ens to leave our farmers short of hands atevery harvest. The proprietor will be readyto bear witness that he found no impedi-ments from British jealousy, and that hissuccess was hailed with as much enthusi-asm as the damp weather would allow.’”[Editors’ note: Cyrus McCormick is con-sidered to be the inventor of the first suc-cessful mechanical reaping machine.]

OUR EARLY YEARS—“From small begin-nings, six years ago, the Scientific Amer-ican has attained a very honorable posi-tion in point of circulation, and conse-quent influence and usefulness. No mancan spend two dollars to better advan-tage than by subscribing for it. We mayconfidently expect over 20,000 patronsto our new volume. The more we have tofeed, the better fare we will serve you.”


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50, 100 & 150 Years Ago50, 100 & 150 Years AgoSalmon Sense � Okapi Surprise � Yankee Ingenuity

THE ENGINEER, 1951: pen, ink, French curve, cigarette



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T elltale flashes of light within a 1,000-ton sphere of ultrapure heavy water,deep underground in a nickel mine near

Sudbury, Ontario, have resolved a 33-year-old puzzle. In June the Sudbury Neutrino Ob-servatory (SNO) collaboration announcedfirm evidence that elusive ghostly particlescalled neutrinos morph from one subspeciesto another during their flight from the sun to

Earth. The result reassuresastrophysicists that their pre-cision solar models do notcontain a lurking blunder,and it gives particle physi-cists further clues to whatlies beyond their beloved butincomplete Standard Modelof particle physics.

The mystery of solar neu-trinos has haunted physicistssince 1968, when the first ex-periment to count those neu-trinos came up with less thanhalf of the expected number.Three decades of experimentsand more refined theories

have only confirmed the discrepancy.The SNO project is unique in that it uses

heavy water, containing the deuterium iso-tope of hydrogen, to observe neutrinos (de-noted by the Greek letter “nu”). A similar de-tector, Super-Kamiokande in Kamioka, Japan,

has been counting neutrinos in ordinary wa-ter for about five years. As Super-K memberEdward Kearns of Boston University ex-plains, “Although SNO is 10 times smaller,because the deuterium reaction is prettystrong, it has a comparable total event rate asSuper-Kamiokande.”

More important than the gross numbers,however, is the variety of interactions possi-ble at SNO, giving the detector new ways todistinguish subspecies, or flavors, of solar neu-trinos. In both heavy and ordinary water, aneutrino can hit an electron, sending it ca-reering through the liquid fast enough to pro-duce a flash of Cherenkov radiation. But suchelectron scattering can be caused by any of thethree neutrino flavors: the tau-neutrino, themuon-neutrino and the electron-neutrino.(The sun’s nuclear reactions produce electron-neutrinos exclusively.) SNO’s heavy water cansingle out electron-neutrinos, because that fla-vor alone can be absorbed by a deuterium nu-cleus, transforming it into two protons and anelectron that fly apart at high energy.

SNO’s count of just the electron-neutrinosis lower than Super-K’s count of all flavors.The conclusion: some of the sun’s electron-neutrinos turn into muon- or tau-neutrinos.Because muon- and tau-neutrinos scatter elec-trons much less efficiently than electron-neu-trinos do, the small excess of scatterings at Su-per-K translates into a large number of muon-

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SNO Nus Is Good NewsTHE LATEST ON MUTATING NEUTRINOS SOLVES THE SOLAR NEUTRINO PROBLEM BY GRAHAM P. COLLINS

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TO SEE NEUTRINOS from the sun,the underground Sudbury NeutrinoObservatory (SNO), shown hereduring construction, relies on 9,456sensors to monitor a 1,000-tonsphere of water. Physicists use theGreek letter “nu” to denote neutrinos.


In the next few months SNO researchers will:

� Determine whether the amountof solar neutrino oscillationvaries according to the time ofday and the season. Suchvariations, not discerned atSuper-Kamiokande, would resultfrom extra oscillations whenneutrinos pass through Earth orbecause of Earth’s varyingdistance from the sun.

� See if the oscillation depends onthe neutrinos’ energy. The datawill further constrain theneutrino masses and the so-called mixing angle (whichdefines how much oscillation canoccur) and might eliminate someoscillation theories.

TO COME:MORE NU NEWS

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Approved for use this past May, Gleevecwas celebrated as the first in a wave ofsupremely effective cancer drugs that

home in on tumors without harming healthycells. In clinical trials, 90 percent of patientsin early stages of chronic myelogenousleukemia (CML), a rare blood cancer, wentinto remission within six months of first tak-ing Gleevec. Despite its promise, however,Gleevec and drugs like it may be only a pro-visional measure. More recent reports havefound that patients in late-stage CML relapsebecause their tumors become drug-resistant.

Gleevec, made by Novartis, belongs to aclass of drugs called small molecules. Theyare designed to either target specific receptorson cancer cells or disrupt their signaling path-ways, thereby marking a major departurefrom radiation and chemotherapy, the broadeffects of which can be toxic to healthy cells.

CML is caused when chromosomes 9 and22 swap genes. This produces a mutation inthe Abl protein, a type of internal signalingenzyme known as a tyrosine kinase that is in-volved in normal cell growth. Once mutated,however, the Abl protein becomes hyperac-tive and drives white blood cells to divide in-cessantly. In either form, Abl needs to bind amolecule of a cell’s ATP to function. Gleevecworks by docking into the pocket ordinarilyoccupied by ATP, thereby stopping the func-tion of the signaling protein. The CML cellsthen pack up and die.

But why are CML cells the only oneskilled, given that there are hundreds of othertyrosine kinases and similar enzymes that relyon ATP for their activation? Why doesn’tGleevec block these? Years ago scientists be-lieved that all ATP binding sites were identi-cal. Actually, they are all slightly different,

Cancer in the CrosshairsWHY SOME TUMORS WITHSTAND GLEEVEC’S TARGETED ASSAULT BY DIANE MARTINDALE

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or tau-neutrinos present. Two thirds of theelectron-neutrinos from the sun are trans-formed by the time they reach Earth—pre-cisely the right number to agree with the pre-dictions made using solar models. Arthur B.McDonald, head of the SNO project, saysthat the result “provides a very good confir-mation that we understand how the sun isgenerating energy with great accuracy.”

Changes, or oscillations, of neutrino fla-vors can occur only between flavors havingunequal masses. In essence, a subtle mass dif-ference causes the quantum waves of two dif-ferent flavors to oscillate in and out of syncwith each other, like two close musical notesproducing beats. If the peak of each beat cor-responds to an electron-neutrino, then theminimum in each cycle is, say, a muon-neu-trino. The first strong evidence for such os-cillations came in 1998 from Super-K’s studyof high-energy cosmic-ray neutrinos.

In the simplest version of the StandardModel of particle physics, neutrinos are mass-less and cannot oscillate. Most theorists view

neutrino masses as something to be explainedby whichever theory supersedes the StandardModel. The masses are tiny: the SNO results,combined with other data, imply that all threeneutrino flavors have masses less than 1⁄ 180,000

of an electron mass, the next heavier particle. SNO’s results put sterile neutrinos—a pe-

culiar hypothetical fourth flavor—on shakierground. All the observed SNO and Super-Kdata can be explained by electron-muon-tauoscillations. Contributions by sterile neutri-nos are not yet ruled out, “but the fraction ofsterile neutrinos is not expected to be large,”McDonald says.

The SNO experiment will continue for afew more years. Since June the detector hasbeen running with ultrapure salt (sodiumchloride) added to the heavy water. The chlo-rine atoms in the salt greatly enhance the de-tection of neutrons, produced when neutrinossplit a deuterium nucleus without being ab-sorbed. Accurate counts of those reactionsshould be a recipe for further tasty resultsabout neutrinos.

REASON TO SMILE: Gleevec’s pioneerBrian Druker at a May press conferenceannouncing the cancer drug’s approval.



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EDINBURGH, SCOTLAND—Once upon atime ice as much as a kilometer thick en-gulfed the earth. Glaciers scoured the

nearly lifeless continents, and sea ice encap-sulated the oceans—even in the tropics. Theplanet’s only solution to the deep freeze wasto wait for volcanoes to release enough heat-

trapping carbon dioxideto create a runaway green-house effect. A brutal epi-sode of warming ensued,not only melting the icebut also baking the planet.

Three years ago agroup of Harvard Univer-sity researchers proposedthis revolutionary idea—

dubbed the snowball earthhypothesis—about the po-tential of the planet for severe climate reversals.Since then, scientists have

hotly debated the details of the events, whichoccurred as many as four times between 750million and 580 million years ago, in a timeknown as the Neoproterozoic. But just howthe earth first plunged into a snowball-style iceage has been unknown. Now the original pur-veyors of the snowball earth hypothesis haveproposed a trigger: methane addiction.

At a scientific conference in Edinburghthis past June, geochemist Daniel P. Schragdescribed the addiction scenario: Just beforethe first snowball episode, the ancient earthkept warm by relying on methane—a green-house gas 60 times more powerful than car-bon dioxide. The methane had begun leakingslowly into the atmosphere when massive, icymethane hydrate deposits within the seafloorbecame destabilized somehow. As a result,carbon dioxide levels decreased, and methanebecame the world’s dominant greenhouse gas.

The trouble with the planet’s dependenceon methane is that the gas disappears quickly

Triggering a SnowballDID METHANE ADDICTION SET OFF EARTH’S GREATEST ICE AGES? BY SARAH SIMPSON

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says Brian J. Druker, a cancer researcher atOregon Health Sciences University who helpedto develop Gleevec: “This was unpredicted,but good for the targeted approach.”

Moreover, such molecules strike a blow attumor cells’ weak spot: their almost exclusivedependence on the mutated protein. Blockingthe errant Abl cuts off the tumor cells’ lifeline,but normal cells are unaffected because theypossess redundancy in protein function; theirbackup pathways kick in, Druker explains.

The targeted approach offers much hope—

Gleevec also blocks protein receptors in twoother malignancies—but it is no magic bullet,warns Tony Hunter, a molecular biologist atthe Salk Institute for Biological Studies in SanDiego. Gleevec has been used for a short time(its approval came after clinical trials that be-gan in 1998), and some patients have alreadydeveloped resistance to it—the Abl protein’sATP pocket mutates so the drug can no longerbind to it. In other instances, production ofthe Abl protein is so great that the drug—evenat the highest dose—cannot keep up. “Cancer

cells are genetically malleable,” Hunter notes,“and they find ways to escape, no matter howclever we think we’ve been.”

Small-molecule therapy is being viewed asa treatment, not a cure, Hunter adds. In somepatients, particularly those in advanced stagesof disease, the drugs may work only to keepthe tumor in check, transforming it into achronic condition, much as diabetes is.

Still, Gleevec is a milestone not just forwhat it does but for the revolutionary strate-gy it represents, says Larry Norton, head ofsolid-tumor oncology at Memorial Sloan-Ket-tering Cancer Center in New York City. Hepredicts that because of the new understand-ing of tumors at the molecular level, cancerswill soon be classified by their molecularmakeup rather than by their location in thebody, as is done today. Researchers mightthen build molecules to attack them—a tall or-der, Norton says, “but one that is possible.”

Diane Martindale is a science writer basedin New York City.

Small-molecule drugs such asGleevec are not the only targeted

therapy. Another is monoclonalantibodies, which are created from

a single cell and are designed torespond to a specific antigen. In

cancer therapy, most block growthfactors from activating cell

division. For example, themonoclonal antibody Herceptin

targets an epidermal growth factoron certain types of breast cancer

cells. Although early results areencouraging, monoclonal antibodies

are not nearly as impressive asGleevec. Moreover, antibodies will

bind to the same receptors onnormal cells, thereby causing more

severe side effects.

SMALL MOLECULES’BIG BROTHER

MASSIVE GLACIERS entombed the earth hundreds of millions of years ago, but how?



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C AOBAS, MEXICO—Hunting jaguars is allabout keeping your head low whilerunning through the jungle—the better

to duck spike-covered vines and saw-toothedpalm leaves that infest this remote area of

Mexico’s Quintana Roo state in the YucatánPeninsula. It’s a several-million-acre patch-work of rain forest between two protectednational parks that is rapidly being cut downby farmers, ranchers and small-scale loggers.As the forest goes, so does habitat for this re-gion’s most charismatic animal: Pantheraonca, known locally as el tigre.

Catching the nocturnal jaguars means en-tering the jungle in the early hours beforedawn; otherwise, heat and sunlight evaporatethe cat’s scent trail. After alternately runningand stumbling for two hours, the hunting par-ty stops and listens to the sound of barkingdogs. “They’ve treed him,” concludes TonyRivera, who is leading us. “That’s it!” Twotrackers with machetes run ahead.

Soon we see a female jaguar, weighingperhaps 70 pounds, nestled 30 feet above theforest floor. It gazes impassively at us withhuge brown-yellow eyes. The jaguar’s beauti-ful golden, black-spotted fur keeps it well hid-den in the forest canopy. Mayan kings wore

Into the Jaguar’s DenHUNTING AS A MEANS TO PRESERVE THE JUNGLE’S FOREMOST PREDATOR BY ERIC NIILER

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TAKEN DOWN: Wildlife veterinarianMarcela Araiza checks a darted jaguar’shealth and genetic information.

in an oxygen-rich atmosphere. An interrup-tion in the methane leak left the earth in direneed of greenhouse gases, and the climatetumbled into a deep freeze before volcanoescould release enough carbon dioxide to makeup for the lost methane. “I’m not sure I total-ly buy this idea—it’s outrageous,” Schrag ad-mitted at the conclusion of his presentation.“But it’s the only idea that explains the carbonisotope crash just before the glaciations.”

Such bizarre drops in carbon isotope val-ues have been recorded in the rocks beneaththe jumbled layers deposited by the glaciers ofsnowball events at several locations aroundthe world. But as provocative as the methaneaddiction hypothesis may be, it left the con-ference audience with many questions.

Alan Jay Kaufman, a University of Mary-land geochemist who first measured some ofthe carbon isotope crashes, pointed out that adramatic decrease in biological productivity

in the oceans can also cause carbon isotopevalues to fall and remain low over periods ofa million years or so. But based on estimatesof sedimentation rates of the rocks in ques-tion, Schrag and others think the crash couldhave occurred over a shorter time frame. Still,Kaufman is skeptical: “We don’t have anyway to look into the rock record and see amethane buildup.”

“It’s difficult to test anything that old,”Schrag says. But you can look for carbon iso-tope crashes in places where their durationmay be more certain, he adds. Several work-ers have already correlated the carbon iso-tope values among Neoproterozoic rocks inNamibia, Australia, California, Canada andthe Arctic islands of Svalbard. Dozens of oth-er deposits of similar age exist but have not yetbeen analyzed. The potential triggers of asnowball earth, it seems, may be as contro-versial as the details of the event itself.

Information about the chemicalmakeup of the ancient atmosphere

can sometimes be gleaned from theremains of bacteria trapped in

rocks. If the number of fossilizedmethane-loving bacteria is

unusually high, for instance,scientists can reasonably assume

that the atmosphere was rich inthat particular gas. But rocks from

snowball earth times haveexperienced the heat and pressureof metamorphism, which have long

since destroyed any biological cells.

THE DISTANT PAST’SELUSIVE CLUES



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One of the controversial aspects ofthe dart hunting of jaguars is theuse of live bait: goats are tied upat night to entice the predator, à la Jurassic Park, says MarceloAranda, a biologist at Mexico’sEcology Institute in Veracruz.Perhaps as a result of the practice,one jaguar that was collared andreleased in April was caught at anearby farm in late May after it hadkilled four sheep, a cow and a youngcalf. The 150-pound male wasrelocated to the Sian Ka’anBiosphere Reserve, about 100 milesaway. Project defenders say thatthe problem jaguar was ananomaly—so far none of the othercollared jags has attacked livestock.

WHEN ANIMALS AREEASY PICKINGS

jaguar skins as battle tunics; modern-daypoachers prize them as proof of vanquishingthe jungle’s most powerful predator.

Joe Bojalad, a big-game hunter, rests fora minute and squints through the rifle scope.Hunters like him have paid upward of $5,000for this opportunity. He steadies the rifle,pulls the trigger and pfffftt—the shot misses.“It didn’t go in?” he asks. In this case, big-game hunting does not mean killing. Bojaladhas an air-powered rifle that fires tranquiliz-er darts. Once asleep, the jaguar will be ex-amined and tagged.

Scientists don’t know exactly how manyjaguars survive in the tropical forests of LatinAmerica. The cats once flourished from thesouthern U.S. all the way to Argentina. To-day only a few significant populations re-main, mostly in Mexico, Belize and Brazil. Darthunting is part of a unique program sponsoredby Unidos para la Conservación, a MexicoCity–based conservation group, the NationalAutonomous University of Mexico (UNAM),and Safari Club International, a U.S.-basedoutfit that recruits American big-game hunt-ers to fund conservation and research. AMexican cement company and a cellular-phone firm donate additional funds to theproject, which has been run by Unidos para laConservación since 1997.

Twice again, Bojalad fires. But no luck.The gun is passed to one of the trackers, whoshimmies up a nearby tree to get a better an-gle, takes aim and nails the jaguar. Disorient-ed by the ketamine tranquilizer, the cat scram-bles down the tree and stumbles through thejungle with three dogs at its heels before plop-ping over.

For the next 45 minutes, CuauhtemocChavez, a graduate student from MexicoCity, and Marcela Araiza, a wildlife veteri-narian, take skin, muscle and blood samples.They remove more than 30 botfly larvae thathave burrowed into the animal’s hide andthen attach a GPS radio collar. Over the nextyear and a half, the collar will record the an-imal’s location.

Not everyone is convinced that dart hunt-ing is a good idea. In Africa, where rhinos,warthogs and other game are targeted, someconservationists have complained that ani-mals often get darted more than once, poten-tially resulting in tranquilizer poisoning, andthat partial injections from poor shots merely

frighten animals and could lead them to injurethemselves. As for the jaguars, Alan Rabino-witz, director of the New York City–basedWildlife Conservation Society’s Global Car-nivore Program, claims that science isn’t thetop priority. “The project is being driven froma hunting perspective,” says Rabinowitz, whohas visited the Mexican project. “Don’t tellme it’s a scientific project.”

The jaguar project’s principal investigator,UNAM’s Gerardo Ceballos Gonzales, de-fends the program. He says that its early prob-lems with U.S. hunters—their wish to shootalready collared animals, for example—havebeen corrected with stricter protocols.

According to Ceballos,the project plans to captureeight to 10 jaguars insidethe nearby Calakmul Bio-sphere Reserve and another10 in the mixed forest andfarming country around itin the next year. Close to 20animals have been collaredsince the project began; theteam is currently trackingfive animals.

Once the collaring pro-gram is completed, Ceballos plans to set up anetwork of motion-detecting cameras acrosstrails. These cameras will record both preda-tor and prey and will help determine the sizeof the jaguar population, now estimated at400 to 500 within the reserve. OutsideBrazil’s Pantanal region, this may be theworld’s largest jaguar population. “The hopeis that we can have a sustainable populationof jaguars not only inside but outside the re-serve,” Ceballos remarks.

Yet Rabinowitz and others also worryabout the presence of guides such as the 50-year-old Rivera, a former poacher. In the late1980s Rivera ran afoul of the U.S. Fish andWildlife Service for transporting jaguar skinsinto the U.S. Rivera says he’s changed hisspots and no longer kills jaguars, although hebelieves there are enough jaguars in this partof Mexico to sustain limited hunting.

The problem here is not illegal hunting orthe possibility of its return but rather defor-estation, according to Carlos Manterola, di-rector of Unidos para la Conservación. Man-terola recently began working with localcommunity landowners to start a mahogany-

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YUCATÁN FORESTS harbor one of the few remainingpopulations of jaguars.



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As counterculturalist Stewart Brandhas said, anonymity can be toxic

to community, because it canfoster irresponsible activity andsow mistrust. But an experiment

some years back on the WELL, theSan Francisco–based electronic

conferencing system, showed thatpeople typically wanted anonymityfor themselves—just not for others.

FOR MEBUT NOT FOR YOU?

In the U.S., the right to beanonymous is protected under the

First and Fourth amendments.According to Mike Godwin, author of

Cyber Rights, two significantSupreme Court cases establish

the precedents.

NAACP v. Alabama The 1958 rulingupheld the NAACP’s refusal to

disclose its membership lists onthe grounds that this type ofprivacy is part of the right to

freedom of assembly.

McIntyre v. Ohio ElectionsCommission The 1995 ruling struck

down a requirement, instituted tocontrol campaign spending, that

political pamphlets include thename and address of their issuer.

PRECEDENTSFOR PRIVACY

LONDON—A legislative move in Europethat would also affect the U.S. is threat-ening the sometimes controversial abil-

ity of Internet users to mask their real-worldidentities. The move, which is heavily backedby the U.S. Department of Justice, is the cy-bercrime treaty, designed to make life easy forlaw enforcement by requiring Internet serviceproviders (ISPs) to maintain logs of users’ ac-tivities for up to seven years and to keep theirnetworks tappable. The Council of Europe,a treaty-building body, announced its supportof the cybercrime effort in June.

Anonymity is a two-edged sword. It doesenable criminals to hide their activities. But itis also critical for legitimate citizens: whistle-blowers, political activists, those pursuing al-ternative lifestyles, and entrepreneurs whowant to acquire technical information with-out tipping off their competitors.

Even without the proposed legislation,anonymity is increasingly fragile on the Net.Corporations have sued for libel to force ser-vices to disclose the identities of those whoposted disparaging comments about themonline. Individual suits of this type are rarer,but last December, Samuel D. Graham, a for-mer professor of urology at Emory Universi-ty, won a libel judgment against a Yahoo userwhose identity was released under subpoena.

Services designed to give users anonymi-ty sprung up as early as 1993, when Julf Helsingius founded Finland’s anon.penet.fi,which stripped e-mail and Usenet postings ofidentifying information and substituted a

pseudonymous ID. Users had to trust Hel-singius. Many of today’s services and soft-ware, such as the Dublin-based Hushmail andthe Canadian company Zero Knowledge’sFreedom software, keep no logs whatsoever.

But if the cybercrime treaty is ratified, willthey still be able to? Would they have to movebeyond the reach of the law to, say, Anguilla?More than that, will the First Amendmentcontinue to protect us if anonymity is effec-tively illegal everywhere else? Says Mike God-win, perhaps the leading legal specialist in civ-il liberties in cyberspace: “I think it becomes alot harder for the U.S. to maintain protectionif the cybercrime treaty passes.” Godwin callsthe attempt to pass the cybercrime treaty“policy laundering”—a way of using interna-tional agreements to bring in legislation thatwould almost certainly be struck down byU.S. courts. (On its Web site, the U.S. De-partment of Justice explains that no support-ing domestic legislation would be required.)

In real-world terms, the equivalent of thetreaty would be requiring valid return ad-dresses on all postal mail, installing camerasin all phone booths and making all cashtraceable. People would resist such a regime,but surveillance by design in the electronicworld seems less unacceptable, perhaps be-cause for some people e-mail still seems op-tional and the Internet is a mysterious, darkforce that is inherently untrustworthy.

Because ISPs must keep those logs andthat data, your associations would becomean open book. “The modern generation of

Surveillance by DesignWILL A NEW CYBERLAW BYPASS THE U.S. CONSTITUTION? BY WENDY M. GROSSMAN

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furniture workshop that will boost the valueof the region’s timber and perhaps slow itscutting. He also pays local farmers if thejaguars eat livestock, an insurance policy de-signed to cut poaching. “This is not just a sci-entific project for jaguars,” Manterola insists.“We are using the jaguar as a flagship speciesfor conservation of the Mayan jungles.”

Eric Niiler, based in San Diego, writesfrequently about conservation issues.

TAKING AIM at a treed jaguar is Joe Bojalad; TonyRivera (center) and Carlos Manterola (right) look on.



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The heart of the Nomad technologylies in a microelectromechanicalsystem (MEMS)—specifically, aMEMS light-beam scanner, whichhas a tiny mirror 1.5 millimeterswide. A red laser diode bounces apulsed beam off the MEMS mirror,which uses an electromagneticsystem to move in two directions,creating a scanning pattern similarto those on television screens. An optical combiner modifies thebeam to create an image 800pixels wide by 600 pixels long.

NEED TO KNOW:INSIDE VIEW

M att Nichols, director of communica-tions for Microvision, has just ar-rived from his crosstown walk. He’s

hurried from New York City’s upcoming Mu-seum of Sex, where he showed off the sameequipment that he wants to demonstrate now.No, please—it’s called Nomad, a retinal scan-ning device that can beam words and graph-ics directly into the viewer’s eye. “They’re try-ing to figure out how to create a fully interac-tive museum,” Nichols sheepishly explains.

The U.S. Army is also interested in No-mad, for a less titillating function: equippingits helicopter pilots. When coupled with theproper software, the headset can display alti-tude, heading, speed, course and weapons sta-tus, all presented in a nice monochrome lightbeam that doesn’t hamper the pilot’s view. “Itprojects the image desired into the visual fieldof the pilot’s eye, and that image is seen at op-tical infinity,” says Thomas Lippert, chief sci-entist at Microvision, based in Bothell, Wash.“That means the pilot can keep his gaze outthe windscreen while keeping this augmentedinformation sharply in focus.”

Such technology could replace head-updisplays on windscreens and virtual-realityhelmets—a goal of the U.S. Air Force fordecades. Nomad is lightweight (the produc-tion version could weigh in at about onepound), and because it is worn, it will swivelwith the pilot’s head. That makes it ideal forhelicopters, which are inherently unstableand difficult to fly under instrument-only con-

ditions. “It also means that in aheavy-vibration environment—the thump-thump-thumping ofthe rotors—the image remainsstabilized in space,” Lippert adds.“It doesn’t bounce around like abad newsreel.” Other manufac-turers have built head-mounteddisplays in the past, but Nomadsuperimposes images withoutblocking the view (the images arein outline form).

In late June the company conducted No-mad’s first flight tests; eventually, Nicholsstates, the system will incorporate a voice-op-erated computer. Microvision intends to sella commercial version as early as this fall forbetween $8,000 and $10,000.

Helicopter pilots aren’t the only ones whomight take advantage of the technology,Nichols adds. Air-traffic controllers couldwatch airplanes while their headsets broad-cast the flight data. Surgeons might have a pa-tient’s medical images alongside real-timereadouts of vital signs. Firefighters could en-ter smoke-filled buildings with overlaid roomdiagrams. The system has even allowed pa-tients with macular degeneration to read onceagain. And of course, there’s the Museum ofSex. But we’ll let you fill in your own uses forthe headset there.

Phil Scott is a science and technology writerin New York City.

Eye SpyFORGET MONITORS—NOMAD PUTS TEXT AND GRAPHICS RIGHT ONTO THE RETINA BY PHIL SCOTT

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YStraffic-analysis software not only can link toconventional police databases but can give acomprehensive picture of a person’s lifestyleand communications profile,” says SimonDavies, director of Privacy International. “Itcan automatically generate profiles of thou-sands of users in seconds and accurately cal-culate friendship trees.”

In the not too distant future, nearly every-thing that is on hard copy today will travel viae-mail and the Web, from our medical recordsto the music we listen to and the books we

read. Whatever privacy regime we create nowwill almost certainly wind up controlling thebulk of our communications. Think careful-ly before you nod to the mantra commonlyheard in Europe at the moment: “If you havenothing to hide, you have nothing to fear.”Do you really want your medical records senton the electronic equivalent of postcards?

Wendy M. Grossman, who writes aboutcyberspace issues from London, is also onthe board of Privacy International.

PILOT’S-EYE VIEW using Nomadwould show an overlaid flight path.


P S Y C H O L O G Y

You Forgot to RememberRecent studies illustrate how easy it isto create false memories. Jacquie Pick-rell and Elizabeth Loftus of the Uni-versity of Washington reported at a re-cent American Psychological Societyconference in Toronto that many visi-tors to Disneyland concluded that theyhad met Bugs Bunny, a Warner Bros.character ordinarily not seen at thehappiest place on Earth. The psychol-ogists had subjects read fake Disneyads, some of which mentioned Bugs—

and sometimes in the presence of a card-board cutout of him. About one thirdof those later exposed to Bugs believedthat they had encountered and evenshook hands with the rascally rabbit atDisneyland. Other researchers foundthat people can fabricate false imagesbecause of “causal inference.” Viewingthe result of an action (oranges on theground, say), people will recall spottingthe cause (someone reaching for an or-ange at the bottom to upset the stack)even if they never saw such an image.The study, which helps to explain er-rors in eyewitness accounts, is availableat www.apa.org/journals/xlm/press_releases/july_2001/xlm274931.html

—Philip Yam


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Built for SpeedIBM attested in June to building the world’s fastestsilicon-based transistor. Potentially able to operateat 210 gigahertz, this silicon germanium transistorperforms 80 percent faster than previous technol-ogy, breaking the 200-GHz speed barrier thoughtto exist for silicon-based transistors. Transistorspeed depends largely on the distance electricitymust travel within the device, and IBM researchers

were able to shrinkthis distance in so-called heterojunctionbipolar transistors,in which electronsflow along a verticalpath rather than tak-ing the horizontalroute in convention-al transistors. IBMexpects that withintwo years the tran-sistors will drivechips used in com-

munications equipment to 100 GHz—five timesfaster than today’s chips. (The transistors, though,are incompatible with computer processors.) Thelittle super-silicon transistors still have a way to gobefore they can switch quickly enough to keep upwith the theoretical limit of fiber-optic communica-tions. In the June 28 Nature, researchers at LucentTechnologies calculated the limit to be approxi-mately 100 terabits per strand of fiber. Current datatransmission rates run as high as 1.6 terabits per sec-ond over a single strand. —Mariama Orange

A S T R O N O M Y

Moons over SaturnSaturn’s family has gotten bigger. Re-searchers using 11 different telescopesaround the world have reported finding12 new moons, ranging from six to 32kilometers in diameter and orbiting Saturnin highly eccentric paths, quite unlike thegenerally circular orbits of its major moons, such as Titan. These tiny moons seem to be clus-tered in groups of three or four, suggesting that they are remnants of larger bodies that werefractured, probably by collisions, early in the planet’s formation. Such irregular bodies maybe common for the gas giants; in the past few years astronomers have found five irregularsaround Uranus and 12 around Jupiter. The latest finding, in the July 12 Nature, brings Sat-urn’s satellite brood to 30: six major moons and 24 minor ones. —Philip Yam

Belief in some paranormal phenomena is on the rise in the U.S.

Percent Percentwho change

believe from 1990

Psychic or 54 +8spiritual healing

Extrasensory 50 +1perception

Haunted houses 42 +13

Ghosts or spirits 38 +13

Telepathy 36 0

Extraterrestrials 33 +6have visited the earth

Astrology 28 +3

Communication 28 +10with the dead

Reincarnation 25 +4

Percent change in the Nielsen ratings of The X-Files from its peak season: –29.8

S O U R C E S : G a l l u p O r g a n i z a t i o n ; N i e l s e n M e d i aR e s e a r c h , 2 0 0 0 – 0 1 s e a s o n a v e r a g e c o m p a r e d

w i t h 1 9 9 7 – 9 8 a v e r a g e . P s y c h i c - h e a l i n gc a t e g o r y i n c l u d e s b e l i e f i n t h e p o w e r o f t h e

m i n d t o h e a l t h e b o d y .

UNFILLED FIBER

MOST MOONS, so far.



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� In Ethiopia, researchersuncovered the fossils of whatappears to be humanity’soldest ancestor, who is thoughtto have lived between 5.2 millionand 5.8 million years ago./071201/3.html

� Scientists have createdpatterned glass surfaces onwhich living nerve cells can wirethemselves to electrodes; theresearch may lead to betterimplants, prosthetics andbiosensors. /071001/1.html

� The friction-free superfluidhelium 3 can act as a quantumgyroscope, producing awhistling sound that gets louderor quieter depending on theorientation of the earth’s axis ofrotation. /070901/3.html

� A study has found that clonesare not genetically identical tothe donor animals; in fact, theclones sometimes exhibitdangerously different patterns ofgene expression. /070601/1.html

WWW.SCIAM.COM/NEWSBRIEF BITS

G E O C H E M I S T R Y

More Than ShadeWhen trees first took over the continents about 380 million years ago, they changed the worldin an unexpected way. Researchers knew that trees absorbed much more carbon dioxide fromthe atmosphere than their moss and alga predecessors. But according to computer models ofthe long-term carbon cycle by Yale University geochemist Robert A. Berner and his colleagues,as photosynthesis hit an unprecedentedhigh, the atmosphere also became twice asrich in oxygen as it is today—40 percent rel-ative to 21 percent. That means trees couldhave been responsible for the evolution ofgigantic insects, such as the dragonflies with70-centimeter wingspans known to exist atthe time. An insect’s size depends in part onhow much atmospheric oxygen is availableto diffuse passively into its body. Bernerpresented the findings in June at the EarthSystem Processes conference in Edinburgh,Scotland. —Sarah Simpson

E V O L U T I O N

Infectious SelectionInfectious disease can be a powerful driving forcein evolution. Recently scientists led by SarahTishkoff of the University of Maryland found thatchanges in the frequency of certain forms, or alleles,of the gene for glucose-6-phosphate dehydrogenase(G6PD) within human populations roughly mirrorthe history of malaria. Somemutations of the gene resultin reduced activity of G6PD,producing anemia and,more advantageously, mod-erate resistance to malaria.Looking at the history ofthe various forms of theG6PD gene within popula-tions most affected bymalaria, such as those inAfrica and India, the re-searchers discovered thatthe alleles that encode forG6PD deficiency arose during the same approxi-mate time that malaria became more deadly. More-over, the alleles spread more rapidly within hard-hit populations than chance alone would suggest.These results, in the July 20 Science, indicate thatselective pressure from malaria can maintain andpromote otherwise deleterious alleles in the humangene pool. —Alison McCook

M E D I C I N E

Peace in theNonobeseA simple treatment might one day re-lieve type 1 diabetics of daily fingerpricking and insulin injections. In type1 diabetes, immune cells wage war oninsulin-secreting islet cells in the pan-creas, resulting in improper blood glu-cose levels. (Type 2 diabetes resultsfrom cells’ becoming insensitive to in-sulin, often as a result of obesity.)Working with what they call non-obese diabetic mice, researchers atMassachusetts General Hospital re-trained the attacking immune systemto ignore any surviving islet cells. Theinvestigators first killed off the attackcells, which are abnormal, and then in-jected normal immune cells fromhealthy donor mice. As a result, dia-betic mice began producing islet-friendly immune cells. The approachseemed to effect a permanent reversal:the glucose levels of some 75 percentof the mice returned to normal. Thestudy appears in the July 1 Journal ofClinical Investigation.

—Mariama Orange

TREES may have been harbingers of big bugs.

MALARIA PARASITEattacks red blood cells.



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� Criminal homicide—excludesattempted homicide

� Rape of women by force or threat of force—excludes

statutory rape

� Robbery: taking by force or threat of force anything of value—

includes attempted robbery

� Aggravated assault: attack withintent of inflicting severe bodilyinjury, usually with a weapon—

excludes simple assault (assaultwithout a weapon resulting

in little or no injury)

� Burglary: unlawful entry orattempted entry to commit

a felony or theft

� Larceny, theft: unlawful taking orattempted taking of property—

excludes motor vehicles

� Motor vehicle theft—includesattempted theft

� Arson—includes attempted arson

The Bureau of Justice Statistics’sNational Crime Victimization

Surveys provide data on the samecrimes except for homicide, arson,

crimes committed againstcommercial establishments and

crimes against children younger than 12.

THE FBI’SINDEX CRIMES

The Uniform Crime Reports (UCR), pro-duced by the Federal Bureau of Investi-gation, have figured prominently in dis-

cussions of crime since at least the Nixon era,but their reliability has long been suspect. Amajor reason is substantial underreporting.For a variety of reasons, including distrust oflaw-enforcement officials, many crimes arenot reported to local police departments, thesource of the FBI data. Furthermore, the num-ber of crimes that police departments reportcan vary from year to year depending on bud-gets. The FBI cannot legally enforce the coop-eration of local police departments and stateagencies, and so it is not surprising that forseveral years in the 1990s, six states (the largestin terms of population was Illinois) suppliedno data, forcing the FBI to estimate the num-ber of crimes in those states.

Local police sometimes cook the books,either underreporting to make crime in theirarea appear to be under control or overre-porting to support requests for more funding.Fabrication of this kind has presumably de-clined as police departments have becomemore publicly accountable in the past fewdecades, but it still persists, as recent reports ofdata manipulation in New York City, Phil-adelphia and Boca Raton, Fla., testify.

To supplement the UCR, the Bureau ofJustice Statistics in 1973 started an annualsurvey of about 50,000 households designedto count the number of crime victims. Manyrespondents did not correctly recall when acrime was committed, putting it in the wrongyear, for example, and some even failed to re-call crimes in which they were known to bevictims. Despite such limitations, however,the National Crime Victimization Surveys, asthey are called, are a reasonably good guideto overall crime trends, as shown by theirrough concordance with data on homicide,the best recorded of the UCR categories.

The chart compares the UCR and victim-ization data in terms of serious violent crime.The UCR numbers are not only much lowerbecause of incomplete reporting but are mis-leading as an indicator of violent crime trendsbecause reporting improved over the pastseveral decades. The extent of the improve-ment is suggested by the growing conver-gence of the UCR with the victimization sur-vey: In 1973 the number of violent crimes re-ported by the UCR totaled only 38 percent of those reported by the survey but increasedgradually to between 80 and 84 percent in thesecond half of the 1990s and is expected torise further. Improved reporting, togetherwith a newly introduced system that providesgreater detail on crime incidents, has in-creased the usefulness of the UCR as an ana-lytic tool, but as an indicator of nationalcrime trends it still remains deficient.

The UCR covers eight types of violent andproperty offenses—so-called index crimes—

but excludes others, such as drug violations,simple assault, vandalism, prostitution, statu-tory rape, child abuse, and white-collar of-fenses such as embezzlement, stock fraud,forgery, counterfeiting and cybercrime. Thesetypes of infractions are excluded from the in-dex because they are not readily brought tothe attention of the police (for example, em-bezzlement), are rare (kidnapping) or are notserious enough to warrant inclusion (disor-derly conduct).

Rodger Doyle can be reached [email protected]

Measuring Bad BehaviorFBI CRIME STATISTICS: USE WITH CAUTION BY RODGER DOYLE

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Cryonicists believe that people can be frozen immedi-ately after death and reanimated later when the cure forwhat ailed them is found. To see the flaw in this system,thaw out a can of frozen strawberries. During freezing,the water within each cell expands, crystallizes, and rup-tures the cell membranes. When defrosted, all the in-tracellular goo oozes out, turning your strawberries intorunny mush. This is your brain on cryonics.

Cryonicists recognize this detriment and turn tonanotechnology for a solution. Microscopic machineswill be injected into the defrosting “patient” to repairthe body molecule by molecule until the trillions of cellsare restored and the person can be resuscitated. Everyreligion needs its gods, and this scientistic vision has atrinity in Robert C. W. Ettinger (The Prospect of Im-mortality), K. Eric Drexler (Engines of Creation) andRalph C. Merkle (The Molecular Repair of the Brain),who preach that nanocryonics will wash away the sinof death. These works are built on the premise that ifyou are cremated or buried, you have zero probabilityof being resurrected—cryonics is better than everlastingnothingness.

Is it? That depends on how much time, effort andmoney ($120,000 for a full-body freeze or $50,000 forjust the head) you are willing to invest for odds of suc-cess only slightly higher than zero. It takes a blindly op-timistic faith in the illimitable power of science to solveany and all problems, including death. Look how farwe’ve come in just a century, believers argue—from theWright brothers to Neil Armstrong in only 66 years.Extrapolate these trends out 1,000 years, or 10,000,and immortality is virtually certain.

I want to believe the cryonicists. Really I do. I gaveup on religion in college, but I often slip back into myformer evangelical fervor, now directed toward thewonders of science and nature. But this is precisely whyI’m skeptical. It is too much like religion: it promiseseverything, delivers nothing (but hope) and is based al-most entirely on faith in the future. And if Ettinger,

Drexler and Merkle are the trinity of this scientistic sect,then F. M. Esfandiary is its Saul. Esfandiary, on the roadto his personal Damascus, changed his name to FM-2030 (the number signifying his 100th birthday and theyear nanotechnology is predicted to make cryonics suc-cessful) and declared, “I have no age. Am born and re-born every day. I intend to live forever. Barring an ac-cident I probably will.”

Esfandiary forgot about cancer, a pancreatic formof which killed him on July 8, 2000. FM-2030—or moreprecisely, his head—now resides in a vatof liquid nitrogen at the Alcor Life Ex-tension Foundation in Scottsdale, Ariz.,but his legacy lives on among his fellow“transhumanists” (they have moved be-yond human) and “extropians” (they areagainst entropy).

This is what I call “borderlands sci-ence,” because it dwells in that fuzzy re-gion of claims that have yet to pass anytests but have some basis, however re-mote, in reality. It is not impossible forcryonics to succeed; it is just exceptionally unlikely. Therub in exploring the borderlands is finding that balancebetween being open-minded enough to accept radicalnew ideas but not so open-minded that your brains fallout. My credulity module is glad that some scientistsare devoting themselves to the problem of mortality.My skepticism module, however, recognizes that trans-humanistic-extropian cryonics is uncomfortably closeto religion. I worry, as Matthew Arnold did in his 1852poem “Hymn of Empedocles,” that we will “feign abliss/ Of doubtful future date, /And while we dream onthis/ Lose all our present state, /And relegate to worldsyet distant our repose.”

Michael Shermer is publisher of Skeptic magazine(www.skeptic.com) and author of How We Believeand The Borderlands of Science.


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Nano Nonsense and CryonicsTrue believers seek redemption from the sin of death By MICHAEL SHERMER

Skeptic

The rub is findingthat balancebetween beingopen-mindedenough to acceptradical new ideasbut not so open-minded that yourbrains fall out.


PRINCETON, N.J.—Reunion weekend at Princeton Uni-versity, and the shady Gothic campus has been inun-dated by spring showers and men in boaters and nattyorange seersucker jackets. Tents and small groups ofmurmuring alumni dot the courtyards. Everythingproper, seemingly in its place. In Green Hall, however,the same order does not prevail. Elizabeth Gould’s lab-oratory is undergoing construction, and the neurosci-entist herself would not be mistaken for an alum: herplaid blue workman’s shirt hangs loosely and unbut-toned over a T-shirt and jeans, and she confesses sheoften feels out of place on the conservative campus.

Against a backdrop of tidy ideas about the brain,Gould and her colleagues have been messing things upand, in the process, contributing to some of the most ex-citing findings of the past decade. Her work—and thatof several other neuroscientists—has made clear thatnew neurons are produced in certain areas of the adultbrains of mammals, including primates. Moreover, thesecells can be killed off by stress and unchallenging envi-ronments but thrive in enriched settings where animalsare learning, and they may play a role in memory.

Until recently, dogma held that mature brains werestatic: no cells were born, except in the olfactory bulb.One of the cornerstones of this understanding camefrom studies by Pasko Rakic of Yale University, who ex-amined macaque monkeys and found no evidence of thecreation of nerve cells, a process called neurogenesis.The prevailing view has since held that primates—and,indeed, mammals in general—are born with all the neu-rons they are going to have. Such neural stability wasconsidered necessary for long-term memory. So in thelate 1980s when Gould, who was then researching theeffect of hormones on the brain as a postdoctoral fellowin the laboratory of Bruce S. McEwen at the RockefellerUniversity, saw evidence of new neurons in the rat hip-pocampus, she was perplexed. Gould knew from the pi-oneering work of Fernando Nottebohm, also at Rock-efeller, that neurogenesis occurred in adult birds—ca-


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Young Cells in Old BrainsThe paradigm-shifting conclusion that adult brains can grow new neurons owes a lot to Elizabeth Gould’s rats and monkeys By MARGUERITE HOLLOWAY

� Past thinking: Memories are stored by locked-in neural connections.Present: The brain can add neurons, perhaps to establish new memories.

� Hope for dementia: New neurons seem able to migrate, suggesting thattherapeutic cells can be guided to areas damaged by disease or injury.

� Use it or lose it: In lab animals not kept in a stimulating cognitiveenvironment, “most new neurons will die within a few weeks.”

ELIZABETH GOULD: CHANGING MINDS



naries and zebra finches, for instance,grow nerve cells to learn new songs—

but she and her lab mates knew of nomammalian parallel. “We were reallypuzzled,” she recalls. “It wasn’t untilwe delved far enough back into the lit-erature that we found evidence thatnew neurons are produced in thehippocampus.”

Those earlier studies had neverbeen widely noticed. Beginning in the1960s Joseph Altman, now professoremeritus at Purdue University, andneurologist Michael S. Kaplan inde-pendently recorded neurogenesis in rats and other mammals.They saw growth in the olfactory bulb, in the hippocampus—aregion important to memory—and, most strikingly, in the neo-cortex, which is the part of the brain involved in higher thinking.“But nobody picked up on the results,” Gould says. “It is a clas-sic example of something appearing before its time.”

In her work with rats, Gould verified that when she alteredthe normal hormonal bath the hippocampus received, cells diedand, apparently to compensate, more cells were born. “Thatwas really the beginning of my interest in neurogenesis and myrealization that it happened,” she says. Her first papers on thephenomenon, published in 1992 and 1993, did not attractmuch attention.

Gould went on to do experiments clarifying aspects of neuro-genesis. She found that stress suppressed the creation of neuronsand that lesions in the hippocampus triggered the developmentof new cells—something she considers significant because it im-plies that the brain can heal, or be induced to heal, after injury.

In 1997 Gould moved to Princeton as an assistant professor.Over the next few years she and her co-workers reported thatnew neurons survived if animals lived in complex environmentsand learned tasks, findings also documented in mice by Fred H.Gage of the Salk Institute for Biological Studies in La Jolla, Calif.

Gould’s work in rats contradicting the status quo had al-ready put her out on a limb. Then she observed that new neu-rons are found in the hippocampus of marmoset monkeys andmacaques. News of neurogenesis in primates was met with skep-ticism and stiff opposition, and some suggested her methodswere flawed. She was soon vindicated, however, thanks to con-firmatory work by Rakic in macaques and by Gage in the hu-man hippocampus. The findings catalyzed widespread interestbecause they introduced the possibility of repairing the brain andelucidating memory formation.

For Gould, the sudden splash of attention has been disori-enting—and she does not relish it, particularly when it takes heraway from her experiments. She says she is happiest in the lab,working under the microscope with brain slices, which she findsbeautiful and which recall a childhood interest in being an artist.

And she has liked being in a quiet fieldof research, one she chose when study-ing psychology at the University ofCalifornia at Los Angeles. “I have nointerest in doing experiments thatsomeone else is going to do a monthlater if I don’t get around to it,” shesays. “You have to pick things to dothat are really intriguing to you, thingsthat you are really curious about—notjust because you want to publish onthem before anyone else does.”

Her curiosity is taking her in sev-eral directions these days. An out-

standing question centers on what role new hippocampal neu-rons play. Do they establish new circuits or memories? Or dothey replace old neurons in established circuits? This year Gouldand her colleagues reported that the neurons are involved in thecreation of trace memories—memories important to temporalinformation. “We had evidence that the new cells were affect-ed by learning, and this is evidence that the new cells are neces-sary for learning,” Gould explains. She now intends to do sim-ilar studies in marmosets, to see whether her discoveries aboutrats will prove true for primates.

The 39-year-old Gould is also repeating and extending workof a few years ago in which she found neurogenesis in the neo-cortex of macaques, a finding that remains controversial and thatwould be highly significant because of the importance of the cor-tex. Although no one has published a replication so far, WilliamT. Greenough of the University of Illinois says Gould’s findings“do not surprise me. We have unpublished data in rats that sup-port the same thing.”

In addition, Gould has begun investigating the role of sleepdeprivation in neurogenesis, an interest triggered by the birth ofher third child last year. “I never really thought about the sleepaspect until I wasn’t getting any,” she says, laughing. And sheis intrigued by the possibility that much of what we have cometo understand from laboratory settings may be skewed.

“Our laboratory animals are very abnormal,” Gould notes.“They have unlimited access to food and water, and they haveno interesting cognitive experiences at all. We know that if youhouse an animal in that setting, most of its new neurons will diewithin a few weeks after they are produced.” Gould is design-ing environments that are closer to the ones rats and marmosetsexperience in the wild, hoping to get closer to the truth aboutthe brain. “It really raises the issue of whether a lot of the thingswe are looking at are really deprivation effects.”

Potentially shifting another paradigm doesn’t faze Gould.“There has to be some fresh perspective, something new that youcan bring to the work that other people wouldn’t see,” she says.“Otherwise you are not making a real contribution, and youmight as well just step aside and find something else to do.”

VISIBLE RAT BURROWS enable Gould to observe behaviorand experiences that might lead to new neurons.



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OVEAlbert Einstein, as part of his doctoral disserta-

tion, calculated the size of a single sugar molecule from exper-imental data on the diffusion of sugar in water. His workshowed that each molecule measures about a nanometer in di-ameter. At a billionth of a meter, a nanometer is the essenceof small. The width of 10 hydrogen atoms laid side by side, itis one thousandth the length of a typical bacterium, one mil-lionth the size of a pinhead, one billionth the length of MichaelJordan’s well-muscled legs. One nanometer is also precisely thedimension of a big windfall for research.

Almost 100 years after Einstein’s insight, the nanometerscale looms large on the research agenda. If Einstein were agraduate student today probing for a career path, a doctoraladviser would enjoin him to think small: “Nanotech, Albert,nanotech” would be the message conveyed.

After biomedical research and defense—fighting cancer andbuilding missile shields still take precedence—nanotechnologyhas become the most highly energized discipline in science and

technology. The field is a vast grab bag of stuff that has to dowith creating tiny things that sometimes just happen to be use-ful. It borrows liberally from condensed-matter physics, engi-neering, molecular biology and large swaths of chemistry. Re-searchers who once called themselves materials scientists or or-ganic chemists have transmuted into nanotechnologists.

Purist academic types might prefer to describe themselvesas mesoscale engineers. But it’s “nano” that generates the buzz.Probably not since Du Pont coined its corporate slogan “bet-ter things for better living through chemistry” have scientistswho engage in molecular manipulation so adeptly capturedand held public attention—in this case, the votes of lawmakersin Washington who hold the research purse strings. “You needto come up with new, exciting, cutting-edge, at-the-frontierthings in order to convince the budget- and policy-making ap-paratus to give you more money,” remarks Duncan Moore, aformer White House official who helped to organize the Clin-ton administration’s funding push for nanotechnology.

Nanotechnology is all the rage. But will it meetits ambitious goals? And what the heck is it?

OVERVIEW

By Gary Stix

BigLittle

Science


With recognition has come lots of money—lots, that is, forsomething that isn’t a missile shield. The National Nanotech-nology Initiative (NNI), announced early last year by PresidentBill Clinton, is a multiagency program intended to provide a bigfunding boost to nanoscience and engineering. The $422-mil-lion budget in the federal fiscal year that ends September 30marks a 56 percent jump in nano spending from a year earlier.The initiative is on track to be augmented for fiscal year 2002 byanother 23 percent even while the Bush administration has pro-posed cuts to the funding programs of most of the federal agen-cies that support research and development (see the NNI Website at www.nano.gov). Nano mania flourishes everywhere.More than 30 nanotechnology research centers and interdisci-plinary groups have sprouted at universities; fewer than 10 ex-isted two years ago. Nanoism does not, moreover, confine itselfto the U.S. In other countries, total funding for nanotechnologyjumped from $316 million in 1997 to about $835 million thisyear, according to the National Science Foundation (NSF).

Interest in nano is also fueled, in an aberrant way, by thevisions of a fringe element of futurists who muse on biblical lifespans, on unlimited wealth and, conversely, on a holocaustbrought about by legions of uncontrollable self-replicating ro-bots only slightly bigger than Einstein’s sugar molecules.(Check out the Web site for NanoTechnology magazine—

http://planet-hawaii.com/nanozine/—if you want to learnabout an “era of self-replicating consumer goods, super-health,super-economy and inventions impossible to fabricate withfirst wave industrialization.”)

When Clinton introduced the nanotechnology initiative ina speech last year, he was long on vision and short on specifics:nanotech, he noted, might one day store the Library of Con-gress on a device the size of a sugar cube or produce materialswith 10 times the strength of steel at a mere fraction of its


TIP OF ATOMIC FORCE MICROSCOPE used to probe surfaces and

manipulate molecules symbolizes the nanotechnology revolution.


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weight. But this wasn’t just the meanderings of a starry-eyedpolitician. Surprisingly, the science establishment itself is a lit-tle unclear about what it really means when it invokes nano.“It depends on whom you ask,” Stanford biophysicist StevenM. Block told a National Institutes of Health symposium onnanotechnology last year in a talk that tried to define the sub-ject. “Some folks apparently reserve the word to mean what-ever it is they do as opposed to whatever it is anyone else does.”

What’s in a Name?THE DEFINITION is indeed slippery. Some of nanotechnol-ogy isn’t nano, dealing instead with structures on the micronscale (millionths of a meter), 1,000 times or more larger thana nanometer. Also, nanotechnology, in many cases, isn’t tech-nology. Rather it involves basic research on structures havingat least one dimension of about one to several hundred nano-meters. (In that sense, Einstein was more a nanoscientist thana technologist.) To add still more confusion, some nanotech-nology has been around for a while: nano-size carbon blackparticles (a.k.a. high-tech soot) have gone into tires for 100years as a reinforcing additive, long before the prefix “nano”ever created a stir. For that matter, a vaccine, which often con-sists of one or more proteins with nanoscale dimensions, mightalso qualify.

But there is a there there in both nanoscience and nano-technology. The nanoworld is a weird borderland between therealm of individual atoms and molecules (where quantum mechanics rules) and the macroworld (where the bulk prop-erties of materials emerge from the collective behavior of tril-lions of atoms, whether that material is a steel beam or thecream filling in an Oreo). At the bottom end, in the region ofone nanometer, nanoland bumps up against the basic buildingblocks of matter. As such, it defines the smallest natural struc-tures and sets a hard limit to shrinkage: you just can’t buildthings any smaller.

Nature has created nanostructures for billennia. But MihailC. Roco, the NSF official who oversees the nanotechnology ini-tiative, offers a more restrictive definition. The emerging field—

new versus old nanotech—deals with materials and systemshaving these key properties: they have at least one dimensionof about one to 100 nanometers, they are designed throughprocesses that exhibit fundamental control over the physicaland chemical attributes of molecular-scale structures, and theycan be combined to form larger structures. The intense inter-est in using nanostructures stems from the idea that they mayboast superior electrical, chemical, mechanical or optical prop-erties—at least in theory. (See “Plenty of Room, Indeed,” byMichael Roukes, on page 48, for a discussion of why smalleris not always better.)

Real-world nano, fitting Roco’s definition, does exist. Sand-wiching several nonmagnetic layers, one of which is less thana nanometer thick, between magnetic layers can produce sen-sors for disk drives with many times the sensitivity of previ-ous devices, allowing more bits to be packed on the surface ofeach disk. Since they were first introduced in 1997, these gi-

Macro, Micro, Nano How small is a nanometer? Stepping down in size by powers of 10 takes you from the back of a hand to, at one nanometer, aview of atoms in the building blocks of DNA. The edge of each imagedenotes a length 10 times longer than its next smallest neighbor.The black square frames the size of the next scene inward.

10 centimeters

1 2

3 41 centimeter

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From the classic book Powers of Ten,by Philip and Phylis Morrison and theoffice of Charles and Ray Eames.

10 microns 1 micron

DNA

100 nanometers

1 nanometer

10 nanometers

1 millimeter 100 microns

WHITE BLOOD CELL


ant magnetoresistive heads have served as an enabling tech-nology for the multibillion-dollar storage industry.

New tools capable of imaging and manipulating single mol-ecules or atoms have ushered in the new age of nano. The iconsof this revolution are scanning probe microscopes—the scan-ning tunneling microscope and the atomic force microscope,among others—capable of creating pictures of individual atomsor moving them from place to place. The IBM Zurich ResearchLaboratory has even mounted the sharp, nanometer-scale tipsused in atomic force microscopes onto more than 1,000 mi-croscopic cantilevers on a microchip. The tips in the Millipededevice can write digital bits on a polymer sheet. The techniquecould lead to a data storage device that achieves 20 times ormore the density of today’s best disk drives.

Varied approaches to fabricating nanostructures haveemerged in the nanoworld. Like sculptors, so-called top-downpractitioners chisel out or add bulk material to a surface. Mi-crochips, which now boast circuit lines of little more than 100nanometers, are about to become the most notable example.In contrast, bottom-up manufacturers use self-assembly pro-cesses to put together larger structures—atoms or moleculesthat make ordered arrangements spontaneously, given the rightconditions. Nanotubes—graphite cylinders with unusual elec-trical properties—are a good example of self-assembled nano-structures [see “The Art of Building Small,” by George M.Whitesides and J. Christopher Love, on page 38].

Beyond SiliconTHE DWINDLING SIZE of circuits in electronic chips drivesmuch of the interest in nano. Computer companies with largeresearch laboratories, such as IBM and Hewlett-Packard, havesubstantial nano programs. Once conventional silicon electron-ics goes bust—probably sometime in the next 10 to 25 years—

it’s a good bet that new nanotechnological electronic devices willreplace them. A likely wager, though not a sure one. No oneknows whether manufacturing electronics using nanotubes orsome other novel material will allow the relentless improvementsin chip performance without a corresponding increase in costthat characterizes silicon chipmaking [see “The IncredibleShrinking Circuit,” by Charles M. Lieber, on page 58].

Even if molecular-scale transistors don’t crunch zeroes andones in the Pentium XXV, the electronics fashioned by nano-technologists may make their way into devices that reveal thesecrets of the ultimate small machine: the biological cell. Bio-nano, in fact, is finding real applications before the advent ofpostsilicon nanocomputers [see “Less Is More in Medicine,”by A. Paul Alivisatos, on page 66]. Relatively few nanotagsmade of a semiconductor material are needed to detect cellu-lar activity, as opposed to the billions or trillions of transis-

tors that must all work together to function in a nanocomput-er. One company, Quantum Dot Corporation, has alreadyemerged to exploit semiconductor quantum dots as labels inbiological experiments, drug-discovery research, and diagnos-tic tests, among other applications.

Outside biology, the earliest wave of products involves us-ing nanoparticles for improving basic material properties. Forinstance, Nanophase Technologies, one of the few companiesin this field that are publicly traded, produces nano-size zincoxide particles for use in sunscreen, making the usually white-colored cream transparent because the tiny particles don’t scat-ter visible light.


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Once conventional silicon electronics goes bust, new nanoelectronic devices are a goodbet to replace them. A likely wager, though not a sure one.

UPTICK: The National Nanotechnology Initiative (NNI), begun in fiscal year

2001, helps to keep the U.S. competitive with world spending (top). It also

provides a monetary injection for the physical sciences and engineering,

where funding has been flat by comparison with the life sciences (bottom).

1970

Rese

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(b

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1975 1980 1985

U.S. Government Fiscal Year

LIFE SCIENCES

1990 1995 20000

5

10

15

20

ENGINEERING

PHYSICAL SCIENCES

TRENDS IN FEDERAL RESEARCH FOR SELECTED DISCIPLINES

SOURCE: National Science Foundation

1997 1998 1999 2000 2001 2002*

Government Fiscal Year

SOURCES: U.S. Senate briefing on nanotechnology, May 24, 2001,and National Science Foundation

DOCUMENTED SPENDING BY NON-U.S. GOVERNMENTS

U.S. GOVERNMENT SPENDING

FUNDING FOR NANOTECHNOLOGY

*ProposedSpending

0

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NNI Begins


The government’s nanotech initiative goes beyond sun-screen. It envisages that nanostructured materials may help re-duce the size, weight and power requirements of spacecraft,create green manufacturing processes that minimize the gen-eration of unwanted by-products, and form the basis of mole-cularly engineered biodegradable pesticides. The field has sucha broad scope—and basic research is still so new in somenanosubspecialties—that worries have arisen about its abilityto deliver on ambitious technology goals that may take 20 yearsto achieve. “While nanotechnology may hold great promise,some scientists contend that the field’s definition is too vagueand that much of its ‘hype’ may not match the reality of pres-ent scientific speculation,” noted a Congressional Research Ser-vice report last year.

NanodreamsANY ADVANCED RESEARCH carries inherent risks. Butnanotechnology bears a special burden. The field’s bid for re-spectability is colored by the association of the word with a ca-bal of futurists who foresee nano as a pathway to a techno-utopia: unparalleled prosperity, pollution-free industry, evensomething resembling eternal life.

In 1986—five years after IBM researchers Gerd Binnig andHeinrich Rohrer invented the scanning tunneling microscope,which garnered them the Nobel Prize—the book Engines ofCreation, by K. Eric Drexler, created a sensation for its depic-tion of godlike control over matter. The book describes self-replicating nanomachines that could produce virtually any ma-terial good, while reversing global warming, curing disease anddramatically extending life spans. Scientists with tenured fac-ulty positions and NSF grants ridiculed these visions, notingthat their fundamental improbability made them an absurdprojection of what the future holds.

But the visionary scent that has surrounded nanotechnol-ogy ever since may provide some unforeseen benefits. To manynonscientists, Drexler’s projections for nanotechnology strad-dled the border between science and fiction in a compellingway. Talk of cell-repair machines that would eliminate agingas we know it and of home food-growing machines that couldproduce victuals without killing anything helped to create afascination with the small that genuine scientists, consciouslyor not, would later use to draw attention to their work on moremundane but eminently more real projects. Certainly labelinga research proposal “nanotechnology” has a more alluring ringthan calling it “applied mesoscale materials science.”

Less directly, Drexler’s work may actually draw people intoscience. His imaginings have inspired a rich vein of science-fiction literature [see “Shamans of Small,” by Graham P.


Nanotechnology’s bid for respectability is colored by the word’s association with a cabalof futurists who foresee nano as a pathway to utopia.

3.5 billion years ago The first living cells emerge. Cellshouse nanoscale biomachines that perform such tasks asmanipulating genetic material and supplying energy.400 B.C. Democritus coins the word “atom,” which means“not cleavable” in ancient Greek.1905 Albert Einstein publishes a paper that estimates thediameter of a sugar molecule as about one nanometer.1931 Max Knoll and Ernst Ruska develop the electronmicroscope, which enables subnanometer imaging.1959 Richard Feynman gives his famed talk “There’s Plentyof Room at the Bottom,” on the prospects for miniaturization.1968 Alfred Y. Cho and John Arthur of Bell Laboratories andtheir colleagues invent molecular-beam epitaxy, a techniquethat can deposit single atomic layers on a surface.1974 Norio Taniguchi conceives the word “nanotechnology”to signify machining with tolerances of less than a micron.1981 Gerd Binnig and Heinrich Rohrer create the scanningtunneling microscope, which can image individual atoms.1985 Robert F. Curl, Jr., Harold W. Kroto and Richard E.Smalley discover buckminsterfullerenes, also known asbuckyballs, which measure about a nanometer in diameter.1986 K. Eric Drexler publishes Engines of Creation, afuturistic book that popularizes nanotechnology.1989 Donald M. Eigler of IBM writes the letters of hiscompany’s name using individual xenon atoms.1991 Sumio Iijima of NEC in Tsukuba, Japan, discoverscarbon nanotubes.1993 Warren Robinett of the University of North Carolina and R. Stanley Williams of the University of California at Los Angeles devise a virtual-reality system connected to a scanning tunneling microscope that lets the user see and touch atoms.1998 Cees Dekker’s group at the Delft University of Technology in the Netherlands creates a transistor from a carbon nanotube.1999 James M. Tour, now at Rice University, and Mark A.Reed of Yale University demonstrate that single moleculescan act as molecular switches.2000 The Clinton administration announces the NationalNanotechnology Initiative, which provides a big boost infunding and gives the field greater visibility.2000 Eigler and other researchers devise a quantum mirage.Placing a magnetic atom at one focus of an elliptical ring ofatoms creates a mirage of the same atom at another focus, apossible means of transmitting information without wires.

A Few 10−9 Milestones


Collins, on page 86]. As a subgenre of science fiction—ratherthan a literal prediction of the future—books about Drexler-ian nanotechnology may serve the same function as Star Trekdoes in stimulating a teenager’s interest in space, a passion thatsometimes leads to a career in aeronautics or astrophysics.

The danger comes when intelligent people take Drexler’spredictions at face value. Drexlerian nanotechnology drew re-newed publicity last year when a morose Bill Joy, the chief sci-entist of Sun Microsystems, worried in the magazine Wiredabout the implications of nanorobots that could multiply un-controllably. A spreading mass of self-replicating robots—whatDrexler has labeled “gray goo”—could pose enough of a threatto society, he mused, that we should consider stopping devel-opment of nanotechnology. But that suggestion diverts atten-tion from the real nano goo: chemical and biological weapons.

Among real chemists and materials scientists who havenow become nanotechnologists, Drexler’s predictions have as-sumed a certain quaintness; science is nowhere near to beingable to produce nanoscopic machines that can help revivefrozen brains from suspended animation. (Essays by Drexlerand his critics, including Nobel Prize winner Richard E. Smal-ley, appear in this issue.) Zyvex, a company started by a soft-ware magnate enticed by Drexlerian nanotechnology, has rec-ognized how difficult it will be to create robots at the nano-meter scale; the company is now dabbling with much largermicromechanical elements, which Drexler has disparaged inhis books [see “Nanobot Construction Crews,” by Steven Ash-ley, on page 84].

Even beyond meditations on gray goo, the nanotech fieldstruggles for cohesion. Some of the research would have pro-ceeded regardless of its label. Fusing “nano” and “technolo-gy” was an after-the-fact designation: IBM would have forgedahead in building giant magnetoresistive heads whether or notthe research it was doing was labeled nanotechnology.

For the field to establish itself as a grand unifier of the ap-plied sciences, it must demonstrate the usefulness of groupingwidely disparate endeavors. Can scientists and engineers do-ing research on nanopowders for sunscreens share a commonset of interests with those working on DNA computing? Insome cases, these crossover dreams may be justified. A semi-conductor quantum dot originally developed for electronicsand now being deployed to detect biological activity in cells isa compelling proof of principle for these types of transdisci-plinary endeavors.

If the nano concept holds together, it could, in fact, lay thegroundwork for a new industrial revolution. But to succeed,it will need to discard not only fluff about nanorobots thatbring cadavers back from a deep freeze but also the overheat-ed rhetoric that can derail any big new funding effort. Mostimportant, the basic nanoscience must be forthcoming to iden-tify worthwhile nanotechnologies to pursue. Distinguishing be-tween what’s real and what’s not in nano throughout this pe-riod of extended exploration will remain no small task.

Gary Stix is Scientific American’s special projects editor.

Nano for SaleNot all nanotechnology lies 20 years hence, as the following sampling of already commercialized applications indicates.

APPLICATION: CATALYSTSCOMPANY: EXXONMOBIL DESCRIPTION: Zeolites, minerals with pore sizes of less than one nanometer, serve as more efficient catalyststo break down, or crack, large hydrocarbon molecules to form gasoline.

APPLICATION: DATA STORAGECOMPANY: IBMDESCRIPTION: In the past few years, disk drives have added nanoscale layering—which exploits the giant magneto-resistive effect—to attain highly dense data storage.

APPLICATION: DRUG DELIVERYCOMPANY: GILEAD SCIENCESDESCRIPTION: Lipid spheres, called liposomes, whichmeasure about 100 nanometers in diameter, encase ananticancer drug to treat the AIDS-related Kaposi’s sarcoma.

APPLICATION: MANUFACTURE OF RAW MATERIALSCOMPANY: CARBON NANOTECHNOLOGIESDESCRIPTION: Co-founded by buckyball discoverer Richard E.Smalley, the company has made carbon nanotubes moreaffordable by exploiting a new manufacturing process.

APPLICATION: MATERIALS ENHANCEMENTCOMPANY: NANOPHASE TECHNOLOGIESDESCRIPTION: Nanocrystalline particles are incorporatedinto other materials to produce tougher ceramics, transparentsunblocks to block infrared and ultraviolet radiation, andcatalysts for environmental uses, among other applications.


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artNANOFABRICATION

The

of

RESEARCHERS ARE DISCOVERING CHEAP,

EFFICIENT WAYS TO MAKE STRUCTURES

ONLY A FEW BILLIONTHS OF A METER ACROSS

BY GEORGE M. WHITESIDES AND J. CHRISTOPHER LOVE

BuildingSmall

INTRICATE DIFFRACTION PATTERNS are created by nanoscale-width rings

(too small to see) on the surface of one-centimeter-wide hemispheres made

of clear polymer. Kateri E. Paul, a graduate student in George M. Whitesides’s

group at Harvard University, fashioned the rings in a thin layer of gold on the

hemispheres using a nanofabrication technique called soft lithography.


“Make it small!”is a tech-nological edict that has changed theworld. The development of microelec-tronics—first the transistor and then theaggregation of transistors into micro-processors, memory chips and con-trollers—has brought forth a cornucopiaof machines that manipulate informa-tion by streaming electrons through sil-icon. Microelectronics rests on tech-niques that routinely fabricate structuresalmost as small as 100 nanometersacross (that is, 100 billionths of a meter).This size is tiny by the standards ofeveryday experience—about one thou-sandth the width of a human hair—butit is large on the scale of atoms and mol-ecules. The diameter of a 100-nanome-ter-wide wire would span about 500atoms of silicon.

The idea of making “nanostruc-tures” that comprise just one or a fewatoms has great appeal, both as a scien-tific challenge and for practical reasons.A structure the size of an atom repre-sents a fundamental limit: to make any-thing smaller would require manipulat-ing atomic nuclei—essentially, transmut-ing one chemical element into another. Inrecent years, scientists have learned var-ious techniques for building nanostruc-tures, but they have only just begun to

investigate their properties and potentialapplications. The age of nanofabricationis here, and the age of nanoscience hasdawned, but the age of nanotechnol-ogy—finding practical uses for nano-structures—has not really started yet.

The Conventional ApproachRESEARCHERS may well develop nano-structures as electronic components, butthe most important applications couldbe quite different: for example, biolo-gists might use nanometer-scale particlesas minuscule sensors to investigate cells.Because scientists do not know whatkinds of nanostructures they will ulti-mately want to build, they have not yetdetermined the best ways to constructthem. Photolithography, the technologyused to manufacture computer chipsand virtually all other microelectronicsystems, can be refined to make struc-tures smaller than 100 nanometers, butdoing so is very difficult, expensive andinconvenient. In a search to find betteralternatives, nanofabrication researchershave adopted the philosophy “Let a thou-sand flowers bloom.”

First, consider the advantages anddisadvantages of photolithography. Man-ufacturers use this phenomenally pro-ductive technology to churn out three bil-

lion transistors per second in the U.S.alone. Photolithography is basically anextension of photography. One firstmakes the equivalent of a photographicnegative containing the pattern requiredfor some part of a microchip’s circuitry.This negative, which is called the mask ormaster, is then used to copy the patterninto the metals and semiconductors of amicrochip. As is the case with photogra-phy, the negative may be hard to make,but creating multiple copies is easy, be-cause the mask can be used many times.The process thus separates into twostages: the preparation of the mask (aone-time event, which can be slow andexpensive) and the use of the mask tomanufacture replicas (which must berapid and inexpensive).

To make a mask for a part of a com-puter chip, a manufacturer first designsthe circuitry pattern on a convenientlylarge scale and converts it into a patternof opaque metallic film (usually chromi-um) on a transparent plate (usually glassor silica). Photolithography then reducesthe size of the pattern in a process anal-ogous to that used in a photographicdarkroom [see illustration on oppositepage]. A beam of light (typically ultravi-olet light from a mercury arc lamp)shines through the chromium mask, thenpasses through a lens that focuses the im-age onto a photosensitive coating of or-ganic polymer (called the photoresist) onthe surface of a silicon wafer. The partsof the photoresist struck by the light canbe selectively removed, exposing parts ofthe silicon wafer in a way that replicatesthe original pattern.

Why not use photolithography tomake nanostructures? The technologyfaces two limitations. The first is that theshortest wavelength of ultraviolet lightcurrently used in production processes isabout 250 nanometers. Trying to makestructures much smaller than half of thatspacing is like trying to read print that is


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� The development of nanotechnology will depend on the ability of researchers toefficiently manufacture structures smaller than 100 nanometers (100 billionthsof a meter) across.

� Photolithography, the technology now used to fabricate circuits on microchips,can be modified to produce nanometer-scale structures, but the modificationswould be technically difficult and hugely expensive.

� Nanofabrication methods can be divided into two categories: top-down methods,which carve out or add aggregates of molecules to a surface, and bottom-upmethods, which assemble atoms or molecules into nanostructures.

� Two examples of promising top-down methods are soft lithography and dip-penlithography. Researchers are using bottom-up methods to produce quantum dotsthat can serve as biological dyes.

Overview/Nanofabrication


too tiny: diffraction causes the features toblur and meld together. Various techni-cal improvements have made it possibleto push the limits of photolithography.The smallest structures created in massproduction are somewhat larger than100 nanometers, and complex micro-electronic structures have been madewith features that are only 70 nanome-ters across. But these structures are stillnot small enough to explore some of themost interesting aspects of nanoscience.

The second limitation follows fromthe first: because it is technically difficultto make such small structures using light,it is also very expensive to do so. The pho-tolithographic tools that will be used tomake chips with features well below 100nanometers will each cost tens to hun-dreds of millions of dollars. This expensemay or may not be acceptable to manu-facturers, but it is prohibitive for the bi-ologists, materials scientists, chemists andphysicists who wish to explore nanosci-ence using structures of their own design.

Future NanochipsTHE ELECTRONICS industry is deeplyinterested in developing new methods fornanofabrication so that it can continue itslong-term trend of building ever smaller,faster and less expensive devices. It wouldbe a natural evolution of microelectron-ics to become nanoelectronics. But be-cause conventional photolithography be-comes more difficult as the dimensions ofthe structures become smaller, manufac-turers are exploring alternative technolo-gies for making future nanochips.

One leading contender is electron-beam lithography. In this method, thecircuitry pattern is written on a thin poly-mer film with a beam of electrons. Anelectron beam does not diffract at atom-ic scales, so it does not cause blurring ofthe edges of features. Researchers haveused the technique to write lines withwidths of only a few nanometers in a lay-er of photoresist on a silicon substrate.The electron-beam instruments current-ly available, however, are very expensiveand impractical for large-scale manufac-turing. Because the beam of electrons isneeded to fabricate each structure, theprocess is similar to the copying of a

manuscript by hand, one line at a time.If electrons are not the answer, what

is? Another contender is lithography us-ing x-rays with wavelengths between 0.1and 10 nanometers or extreme ultravio-let light with wavelengths between 10and 70 nanometers. Because these formsof radiation have much shorter wave-lengths than the ultraviolet light current-ly used in photolithography, they mini-mize the blurring caused by diffraction.These technologies face their own set ofproblems, however: conventional lensesare not transparent to extreme ultravio-let light and do not focus x-rays. Fur-thermore, the energetic radiation rapid-

ly damages many of the materials used inmasks and lenses. But the microelectron-ics industry clearly would prefer to makeadvanced chips using extensions of fa-miliar technology, so these methods arebeing actively developed. Some of thetechniques (for example, advanced ul-traviolet lithography for chip produc-tion) will probably become commercialrealities. They will not, though, make in-expensive nanostructures and thus willdo nothing to open nanotechnology to abroader group of scientists and engineers.

The need for simpler and less expen-sive methods of fabricating nanostruc-tures has stimulated the search for un-

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GEORGE M. WHITESIDES and J. CHRISTOPHER LOVE work together on unconventional meth-ods of nanofabrication in the department of chemistry at Harvard University. Whitesides,a professor of chemistry, received his Ph.D. from the California Institute of Technology in1964 and joined the Harvard faculty in 1982. Love is a graduate student and a member ofWhitesides’s research group. He received his bachelor’s degree in chemistry from the Uni-versity of Virginia in 1999 and his master’s degree from Harvard in 2001.TH

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A laser beam writes the

circuit pattern for a

microchip on a layer of

light-sensitive polymer

that rests atop a layer

of chromium and a

glass substrate. The

sections of polymer

struck by the beam can

be selectively removed.

1

2

3

CONVENTIONAL PHOTOLITHOGRAPHY

The exposed sections of

chromium are also removed,

and the rest of the polymer

is dissolved. The result is a

mask—the equivalent of a

photographic negative.

When a beam of ultraviolet light is directed at

the mask, the light passes through the gaps

in the chromium. A lens shrinks the pattern by

focusing the light onto a layer of photoresist

on a silicon wafer.

The exposed parts of the photoresist are

removed, allowing the replication of the pattern

in miniature on the silicon chips.

4

LASER BEAM1

23

4

GLASS SUBSTRATE

CHROMIUM LAYER

ULTRAVIOLET LIGHT

MASK

SILICON WAFER WITH LAYER OF PHOTORESIST

SILICON CHIPS

LENS

w w w . s c i a m . c o m S C I E N T I F I C A M E R I C A N 41Copyright 2001 Scientific American, Inc.


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SOFT LITHOGRAPHY

MAKING AN ELASTIC STAMP

MICROMOLDING IN CAPILLARIES

1 A liquid precursor to

polydimethylsiloxane (PDMS) is

poured over a bas-relief master

produced by photolithography or

electron-beam lithography.

2 The liquid is cured into a rubbery solid that

matches the original pattern. 3 The PDMS stamp is peeled off the master.

The PDMS stamp is placed on a hard surface,

and a liquid polymer flows into the recesses

between the surface and the stamp.

The polymer solidifies into the

desired pattern, which may contain

features smaller than 10 nanometers.

21

LIQUID PRECURSOR TO PDMS

SOLIDIFIED POLYMER

2 The thiols form a self-assembled monolayer on the gold

surface that reproduces the stamp’s pattern; features in the

pattern are as small as 50 nanometers.

MICROCONTACT PRINTING

PDMS STAMP

PHOTORESISTMASTER

SELF-ASSEMBLEDMONOLAYER

Printing, molding and other mechanical processescarried out using an elastic stamp can producepatterns with nanoscale features.

Such techniques can fabricate devices that might be used in optical communications orbiochemical research.

LIQUID POLYMER

GOLD SURFACE

THIOL INK

The PDMS stamp is inked with a solution consisting of

organic molecules called thiols and then pressed against

a thin film of gold on a silicon plate.

1


conventional approaches that have notbeen explored by the electronics indus-try. We first became interested in the top-ic in the 1990s when we were engaged inmaking the simple structures required inmicrofluidic systems—chips with chan-nels and chambers for holding liquids.This lab-on-a-chip has myriad potentialuses in biochemistry, ranging from drugscreening to genetic analysis. The chan-nels in microfluidic chips are enormousby the standards of microelectronics: 50microns (or 50,000 nanometers) wide,rather than 100 nanometers. But thetechniques for producing those channelsare quite versatile. Microfluidic chips canbe made quickly and inexpensively, andmany are composed of organic polymersand gels—materials not found in theworld of electronics. We discovered that

we could use similar techniques to cre-ate nanostructures.

The methods represented, in a sense,a step backward in technology. Insteadof using the tools of physics—light andelectrons—we employed mechanical pro-cesses that are familiar in everyday life:printing, stamping, molding and em-bossing. The techniques are called softlithography because the tool they have incommon is a block of polydimethyl-siloxane (PDMS)—the rubbery polymerused to caulk the leaks around bathtubs.(Physicists often refer to such organicchemicals as “soft matter.”)

To carry out reproduction using softlithography, one first makes a mold or astamp. The most prevalent procedure isto use photolithography or electron-beam lithography to produce a pattern ina layer of photoresist on the surface of asilicon wafer. This process generates abas-relief master in which islands of pho-toresist stand out from the silicon [seetop illustration on opposite page]. Thena chemical precursor to PDMS—a free-flowing liquid—is poured over the bas-relief master and cured into the rubberysolid. The result is a PDMS stamp that

matches the original pattern with aston-ishing fidelity: the stamp reproduces fea-tures from the master as small as a fewnanometers. Although the creation of afinely detailed bas-relief master is expen-sive because it requires electron-beamlithography or other advanced techniques,copying the pattern on PDMS stamps ischeap and easy. And once a stamp is inhand, it can be used in various inexpen-sive ways to make nanostructures.

The first method—originally devel-oped by Amit Kumar, a postdoctoral stu-dent in our group at Harvard Universi-ty—is called microcontact printing. ThePDMS stamp is “inked” with a reagentsolution consisting of organic moleculescalled thiols [see middle illustration onopposite page]. The stamp is then broughtinto contact with an appropriate sheet of

“paper”—a thin film of gold on a glass,silicon or polymer plate. The thiols reactwith the gold surface, forming a highlyordered film (called a self-assembledmonolayer, or SAM) that replicates thestamp’s pattern. Because the thiol inkspreads a bit after it contacts the surface,the resolution of the monolayer cannotbe quite as high as that of the PDMSstamp. But when used correctly, micro-contact printing can produce patternswith features as small as 50 nanometers.

Another method of soft lithography,called micromolding in capillaries, in-volves using the PDMS stamp to moldpatterns. The stamp is placed on a hardsurface, and a liquid polymer flows bycapillary action into the recesses betweenthe surface and the stamp [see bottom il-lustration on opposite page]. The poly-mer then solidifies into the desired pat-tern. This technique can replicate struc-tures smaller than 10 nanometers. It isparticularly well suited for producingsubwavelength optical devices, wave-guides and optical polarizers, all ofwhich could be used in optical fiber net-works and eventually perhaps in opticalcomputers. Other possible applications

are in the field of nanofluidics, an exten-sion of microfluidics that would involveproducing chips for biochemical researchwith channels only a few nanometerswide. At that scale, fluid dynamics mayallow new ways to separate materialssuch as fragments of DNA.

These methods require no specialequipment and in fact can be carried outby hand in an ordinary laboratory. Con-ventional photolithography must takeplace in a clean-room facility devoid ofdust and dirt; if a piece of dust lands on themask, it will create an unwanted spot onthe pattern. As a result, the device beingfabricated (and sometimes neighboringdevices) may fail. Soft lithography is gen-erally more forgiving because the PDMSstamp is elastic. If a piece of dust getstrapped between the stamp and the sur-

face, the stamp will compress over thetop of the particle but maintain contactwith the rest of the surface. Thus, the pat-tern will be reproduced correctly exceptfor where the contaminant is trapped.

Moreover, soft lithography can pro-duce nanostructures in a wide range ofmaterials, including the complex organ-ic molecules needed for biological stud-ies. And the technique can print or moldpatterns on curved as well as planar sur-faces. But the technology is not ideal formaking the structures required for com-plex nanoelectronics. Currently all inte-grated circuits consist of stacked layers ofdifferent materials. Deformations anddistortions of the soft PDMS stamp canproduce small errors in the replicatedpattern and a misalignment of the pat-tern with any underlying patterns previ-ously fabricated. Even the tiniest distor-tions or misalignments can destroy amultilayered nanoelectronic device.Therefore, soft lithography is not wellsuited for fabricating structures withmultiple layers that must stack preciselyon top of one another.

Researchers have found ways, how-ever, to correct this shortcoming—at


These methods require no special equipment and in factcan be carried out by hand in an ordinary lab.



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least in part—by employing a rigid stampinstead of an elastic one. In a techniquecalled step-and-flash imprint lithogra-phy, developed by C. Grant Willson ofthe University of Texas, photolithogra-phy is used to etch a pattern into a quartzplate, yielding a rigid bas-relief master.Willson eliminated the step of making aPDMS stamp from the master; insteadthe master itself is pressed against a thinfilm of liquid polymer, which fills themaster’s recesses. Then the master is ex-posed to ultraviolet light, which solidifiesthe polymer to create the desired replica.A related technique called nanoimprintlithography, developed by Stephen Y.Chou of Princeton University, also em-ploys a rigid master but uses a film ofpolymer that has been heated to a tem-perature near its melting point to facilitatethe embossing process. Both methods canproduce two-dimensional structures withgood fidelity, but it remains to be seenwhether the techniques are suitable formanufacturing electronic devices.

Pushing Atoms AroundTHE CURRENT REVOLUTION innanoscience started in 1981 with the in-vention of the scanning tunneling micro-scope (STM), for which Heinrich Rohrerand Gerd K. Binnig of the IBM Zurich

Research Laboratory received the NobelPrize in Physics in 1986. This remark-able device detects small currents thatpass between the microscope’s tip andthe sample being observed, allowing re-searchers to “see” substances at the scaleof individual atoms. The success of theSTM led to the development of otherscanning probe devices, including theatomic force microscope (AFM). Theoperating principle of the AFM is simi-lar to that of an old-fashioned phono-graph. A tiny probe—a fiber or a pyra-mid-shaped tip that is typically betweentwo and 30 nanometers wide—is broughtinto direct contact with the sample. Theprobe is attached to the end of a can-tilever, which bends as the tip movesacross the sample’s surface. The deflec-tion is measured by reflecting a beam oflaser light off the top of the cantilever.The AFM can detect variations in verti-cal surface topography that are smallerthan the dimensions of the probe.

But scanning probe devices can domore than simply allow scientists to ob-serve the atomic world—they can also beused to create nanostructures. The tip onthe AFM can be used to physically movenanoparticles around on surfaces and toarrange them in patterns. It can also beused to make scratches in a surface (or

more commonly, in monolayer films ofatoms or molecules that coat the surface).Similarly, if researchers increase the cur-rents flowing from the tip of the STM, themicroscope becomes a very small sourcefor an electron beam, which can be usedto write nanometer-scale patterns. TheSTM tip can also push individual atomsaround on a surface to build rings andwires that are only one atom wide.

An intriguing new scanning probefabrication method is called dip-pen lith-ography. Developed by Chad A. Mirkinof Northwestern University, this tech-nique works much like a goose-featherpen [see illustration at left]. The tip of theAFM is coated with a thin film of thiolmolecules that are insoluble in water butreact with a gold surface (the same chem-istry used in microcontact printing).When the device is placed in an atmo-sphere containing a high concentrationof water vapor, a minute drop of watercondenses between the gold surface andthe microscope’s tip. Surface tensionpulls the tip to a fixed distance from thegold, and this distance does not changeas the tip moves across the surface. Thedrop of water acts as a bridge over whichthe thiol molecules migrate from the tipto the gold surface, where they are fixed.Researchers have used this procedure towrite lines a few nanometers across.

Although dip-pen lithography is rel-atively slow, it can use many differenttypes of molecules as “inks” and thusbrings great chemical flexibility to nano-meter-scale writing. Researchers havenot yet determined the best applicationsfor the technique, but one idea is to usethe dip-pen method for precise modifica-tions of circuit designs. Mirkin has re-cently demonstrated that a variant of theink used in dip-pen lithography can writedirectly on silicon.

An interesting cousin to these tech-niques involves another kind of nano-structure, called a break junction. If youbreak a thin, ductile metal wire into twoparts by pulling sharply, the processseems abrupt to a human observer, but itactually follows a complex sequence.When the force used in breaking the wireis first applied, the metal begins to yieldand flow, and the diameter of the wire

DIP-PEN LITHOGRAPHY

PYRAMIDAL TIP

of an atomic force micro-

scope (AFM) is coated with

a thin film of thiol molecules.

A minute drop of water

condenses between the

microscope’s tip and a gold surface.

The thiols migrate from the tip to the surface,

where they form a self-assembled monolayer.

AFM CANTILEVER

AFM TIP

GOLD SURFACE

THIOL MOLECULES

SELF-ASSEMBLEDMONOLAYER

DROP OF WATER


decreases. As the two ends move apart,the wire gets thinner and thinner until, inthe instant just before breaking, it is a sin-gle atom in diameter at its narrowestpoint. This process of thinning a wire toa break junction can be detected easily bymeasuring the current that flows throughthe wire. When the wire is slender enough,current can flow only in discrete quanti-ties (that is, current flow is quantized).

The break junction is analogous totwo STM tips facing each other, and sim-ilar physical rules govern the current thatflows through it. Mark A. Reed of YaleUniversity has pioneered a particularly in-ventive use of the break junction. He builta device that enabled a thin junction to bebroken under carefully controlled condi-tions and then allowed the broken tips tobe brought back together or to be heldapart at any distance with an accuracy ofa few thousandths of a nanometer. By ad-justing the distance between the tips in thepresence of an organic molecule thatbridged them, Reed was able to measurea current flowing across the organicbridge. This experiment was an impor-tant step in the development of technolo-

gies for using single organic molecules aselectronic devices such as diodes and tran-sistors [see “Computing with Mole-cules,” by Mark A. Reed and James M.Tour; Scientific American, June 2000].

Top-Down and Bottom-UpALL THE FORMS of lithography wehave discussed so far are called top-downmethods—that is, they begin with a pat-tern generated on a larger scale and re-duce its lateral dimensions (often by afactor of 10) before carving out nano-structures. This strategy is required infabricating electronic devices such as mi-crochips, whose functions depend moreon their patterns than on their dimen-sions. But no top-down method is ideal;none can conveniently, cheaply andquickly make nanostructures of any ma-terial. So researchers have shown grow-ing interest in bottom-up methods,which start with atoms or molecules andbuild up to nanostructures. These meth-ods can easily make the smallest nano-structures—with dimensions betweentwo and 10 nanometers—and do so in-expensively. But these structures are usu-

ally generated as simple particles in sus-pension or on surfaces, rather than as de-signed, interconnected patterns.

Two of the most prominent bottom-up methods are those used to makenanotubes and quantum dots. Scientistshave made long, cylindrical tubes of car-bon by a catalytic growth process thatemploys a nanometer-scale drop ofmolten metal (usually iron) as a catalyst[see “Nanotubes for Electronics,” byPhilip G. Collins and Phaedon Avouris;Scientific American, December 2000].The most active area of research inquantum dots originated in the labora-tory of Louis E. Brus (then at Bell Labo-ratories) and has been developed by A. Paul Alivisatos of the University ofCalifornia at Berkeley, Moungi G.Bawendi of the Massachusetts Instituteof Technology, and others. Quantumdots are crystals containing only a fewhundred atoms. Because the electrons ina quantum dot are confined to widelyseparated energy levels, the dot emitsonly one wavelength of light when it isexcited. This property makes the quan-tum dot useful as a biological marker [see


PhotolithographyAdvantages: The electronics industry is already familiar withthis technology because it is currently used to fabricatemicrochips. Manufacturers can modify the technique to producenanometer-scale structures by employing electron beams,x-rays or extreme ultraviolet light.Disadvantages: The necessary modifications will be expensiveand technically difficult. Using electron beams to fashionstructures is costly and slow. X-rays and extreme ultravioletlight can damage the equipment used in the process.

Scanning Probe MethodsAdvantages: The scanning tunneling microscope and the atomicforce microscope can be used to move individual nanoparticlesand arrange them in patterns. The instruments can build ringsand wires that are only one atom wide.Disadvantages: The methods are too slow for mass production.Applications of the microscopes will probably be limited to thefabrication of specialized devices.

Soft LithographyAdvantages: This method allows researchers to inexpensivelyreproduce patterns created by electron-beam lithography orother related techniques. Soft lithography requires no specialequipment and can be carried out by hand in an ordinarylaboratory.Disadvantages: The technique is not ideal for manufacturing themultilayered structures of electronic devices. Researchers aretrying to overcome this drawback, but it remains to be seenwhether these efforts will be successful.

Bottom-Up MethodsAdvantages: By setting up carefully controlled chemicalreactions, researchers can cheaply and easily assemble atomsand molecules into the smallest nanostructures, withdimensions between two and 10 nanometers.Disadvantages: Because these methods cannot producedesigned, interconnected patterns, they are not well suited forbuilding electronic devices such as microchips.

Nanofabrication: Comparing the MethodsResearchers are developing an array of techniques for building structures smaller than 100 nanometers. Here is a summary of the advantages and disadvantages of four methods.


“Less Is More in Medicine,” on page 66].One procedure used to make quan-

tum dots involves a chemical reaction be-tween a metal ion (for example, cadmi-um) and a molecule that is able to donatea selenium ion. This reaction generatescrystals of cadmium selenide. The trick isto prevent the small crystals from stick-ing together as they grow to the desiredsize. To insulate the growing particlesfrom one another, researchers carry outthe reaction in the presence of organicmolecules that act as surfactants, coatingthe surface of each cadmium selenideparticle as it grows. The organic mole-cules stop the crystals from clumping to-gether and regulate their rate of growth.The geometry of the particles can be con-trolled to some extent by mixing differ-ent ratios of the organic molecules. Thereaction can generate particles with a va-riety of shapes, including spheres, rodsand tetrapods (four-armed particles sim-ilar to toy jacks).

It is important to synthesize the quan-tum dots with uniform size and composi-tion, because the size of the dot deter-mines its electronic, magnetic and opticalproperties. Researchers can select the sizeof the particles by varying the length oftime for the reaction. The organic coatingalso helps to set the size of the particles.When the nanoparticle is small (on thescale of molecules), the organic coating isloose and allows further growth; as theparticle enlarges, the organic moleculesbecome crowded. There is an optimumsize for the particles that allows the moststable packing of the organic moleculesand thus provides the greatest stabiliza-tion for the surfaces of the crystals.

These cadmium selenide nanoparti-cles promise some of the first commercialproducts of nanoscience: Quantum DotCorporation has been developing thecrystals for use as biological labels. Re-searchers can tag proteins and nucleicacids with quantum dots; when the sam-ple is illuminated with ultraviolet light,the crystals will fluoresce at a specificwavelength and thus show the locationsof the attached proteins. Many organicmolecules also fluoresce, but quantumdots have several advantages that makethem better markers. First, the color of


QUANTUM DOT ASSEMBLY

When the crystal reaches its

optimum size, the organic

molecules coat its surface in

a stable packing.

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A chemical reaction brings

together cadmium ions

(purple), selenium ions

(green) and organic

molecules (red spheres

with blue tails).

The organic molecules act

as surfactants, binding to

the surface of the cadmium

selenide crystal as it grows.

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Crystals called quantum dots contain only a few hundred atoms andemit different wavelengths of light, depending on their size. They maybecome useful as biological markers of cellular activity.


a quantum dot’s fluorescence can be tai-lored by changing the dot’s size: the larg-er the particle, the more the emitted lightis shifted toward the red end of the spec-trum. Second, if all the dots are the samesize, their fluorescence spectrum is nar-row—that is, they emit a very pure color.This property is important because it al-lows particles of different sizes to beused as distinguishable labels. Third, thefluorescence of quantum dots does notfade on exposure to ultraviolet light, asdoes that of organic molecules. Whenused as dyes in biological research, thedots can be observed for convenientlylong periods.

Scientists are also investigating thepossibility of making structures from col-loids—nanoparticles in suspension. Chris-topher B. Murray and a team at the IBMThomas J. Watson Research Center areexploring the use of such colloids to cre-ate a medium for ultrahigh-density datastorage. The IBM team’s colloids con-tain magnetic nanoparticles as small as

three nanometers across, each composedof about 1,000 iron and platinum atoms.When the colloid is spread on a surfaceand the solvent allowed to evaporate,the nanoparticles crystallize in two- orthree-dimensional arrays. Initial studiesindicate that these arrays can potential-ly store trillions of bits of data per squareinch, giving them a capacity 10 to 100times greater than that of present mem-ory devices.

The Future ofNanofabricationTHE INTEREST in nanostructures is sogreat that every plausible fabricationtechnique is being examined. Althoughphysicists and chemists are now doingmost of the work, biologists may alsomake important contributions. The cell(whether mammalian or bacterial) is rel-atively large on the scale of nanostruc-tures: the typical bacterium is approxi-mately 1,000 nanometers long, and

mammalian cells are larger. Cells are,however, filled with much smaller struc-tures, many of which are astonishinglysophisticated. The ribosome, for exam-ple, carries out one of the most importantcellular functions: the synthesis of pro-teins from amino acids, using messengerRNA as the template. The complexity ofthis molecular construction project farsurpasses that of man-made techniques.Or consider the rotary motors of the bac-terial flagella, which efficiently propel theone-celled organisms [see “The Once andFuture Nanomachine,” on page 78].

It is unclear if “nanomachines” tak-en from cells will be useful. They willprobably have very limited application inelectronics, but they may provide valu-able tools for chemical synthesis andsensing devices. Recent work by Carlo D.Montemagno of Cornell University hasshown that it is possible to engineer aprimitive nanomachine with a biologicalengine. Montemagno extracted a rotarymotor protein from a bacterial cell and

connected it to a metallic nanorod—acylinder 750 nanometers long and 150nanometers wide that had been fabricat-ed by lithography. The rotary motor,which was only 11 nanometers tall, waspowered by adenosine triphosphate(ATP), the source of chemical energy incells. Montemagno showed that the mo-tor could rotate the nanorod at eight rev-olutions per minute. At the very least,such research stimulates efforts to fabri-cate functional nanostructures by demon-strating that such structures can exist.

The development of nanotechnologywill depend on the availability of nano-structures. The invention of the STMand AFM has provided new tools forviewing, characterizing and manipulat-ing these structures; the issue now is howto build them to order and how to de-sign them to have new and useful func-tions. The importance of electronics ap-plications has tended to focus attentionon nanodevices that might be incorpo-rated into future integrated circuits. Andfor good technological reasons, the elec-tronics industry has emphasized fabri-cation methods that are extensions ofthose currently used to make micro-chips. But the explosion of interest innanoscience has created a demand for abroad range of fabrication methods,with an emphasis on low-cost, conve-nient techniques.

The new approaches to nanofabrica-tion are unconventional only becausethey are not derived from the microtech-nology developed for electronic devices.

Chemists, physicists and biologists arerapidly accepting these techniques as themost appropriate ways to build variouskinds of nanostructures for research.And the methods may even supplementthe conventional approaches—photo-lithography, electron-beam lithographyand related techniques—for applicationsin electronics as well. The microelec-tronics mold is now broken. Ideas fornanofabrication are coming from manydirections in a wonderful free-for-all ofdiscovery.


More information about nanofabrication can be found at the following Web sites:

International SEMATECH: www.sematech.org/public/index.htm

The Whitesides group at Harvard University: gmwgroup.harvard.edu

The Mirkin group at Northwestern University: www.chem.northwestern.edu/~mkngrp/

The Willson group at the University of Texas at Austin:willson.cm.utexas.edu/Research/research.htm

The Alivisatos group at the University of California at Berkeley: www.cchem.berkeley.edu/~pagrp/

The Bawendi group at M.I.T.: web.mit.edu/chemistry/nanocluster/

The Montemagno group at Cornell University: falcon.aben.cornell.edu/

M O R E T O E X P L O R E

Bottom-up methods start from atomsor molecules and build up to nanostructures.


Back in December 1959, futureNobel laureate Richard Feynman gave avisionary and now oft-quoted talk enti-tled “There’s Plenty of Room at the Bot-tom.” The occasion was an AmericanPhysical Society meeting at the Califor-nia Institute of Technology, Feynman’sintellectual home then and mine today.Although he didn’t intend it, Feynman’s7,000 words were a defining moment innanotechnology, long before anything“nano” appeared on the horizon.

“What I want to talk about,” hesaid, “is the problem of manipulatingand controlling things on a smallscale. . . . What I have demonstrated isthat there is room—that you can de-crease the size of things in a practicalway. I now want to show that there is

plenty of room. I will not now discusshow we are going to do it, but only whatis possible in principle.. . .We are not do-ing it simply because we haven’t yet got-ten around to it.”

The breadth of Feynman’s vision isstaggering. In that lecture 42 years agohe anticipated a spectrum of scientificand technical fields that are now well es-tablished, among them electron-beamand ion-beam fabrication, molecular-beam epitaxy, nanoimprint lithography,projection electron microscopy, atom-by-atom manipulation, quantum-effectelectronics, spin electronics (also calledspintronics) and microelectromechanicalsystems (MEMS). The lecture also pro-jected what has been called the “magic”Feynman brought to everything he turned

his singular intellect toward. Indeed, ithas profoundly inspired my two decadesof research on physics at the nanoscale.

Today there is a nanotechnologygold rush. Nearly every major fundingagency for science and engineering hasannounced its own thrust into the field.Scores of researchers and institutions arescrambling for a piece of the action. Butin all honesty, I think we have to admitthat much of what invokes the hallowedprefix “nano” falls a bit short of Feyn-man’s mark.

We’ve only just begun to take thefirst steps toward his grand vision of as-sembling complex machines and circuitsatom by atom. What can be done now isextremely rudimentary. We’re certainlynowhere near being able to commercial-


RoomPlenty

By Michael Roukes

There is plenty of room forpractical innovation at the nanoscale.

But first, scientists have to understandthe unique physics that governs matter there

NANOPHYSICS

of

Indeed,


ly mass-produce nanosystems—integrat-ed multicomponent nanodevices thathave the complexity and range of func-tions readily provided by modern mi-crochips. But there is a fundamental sci-ence issue here as well. It is becoming in-creasingly clear that we are only begin-ning to acquire the detailed knowledgethat will be at the heart of future nano-technology. This new science concerns theproperties and behavior of aggregates ofatoms and molecules, at a scale not yetlarge enough to be considered macro-scopic but far beyond what can be calledmicroscopic. It is the science of the meso-scale, and until we understand it, practicaldevices will be difficult to realize.

Today’s scientists and engineersreadily fashion nanostructures on a scale

of one to a few hundred nanometers—

small indeed, but much bigger than sim-ple molecules. Matter at this mesoscaleis often awkward to explore. It containstoo many atoms to be easily understoodby straightforward application of quan-tum mechanics (although the funda-mental laws still apply). Yet these sys-tems are not so large as to be complete-ly free of quantum effects; thus, they donot simply obey the classical physicsgoverning the macroworld. It is precise-ly in this intermediate domain, the meso-world, that unforeseen properties of col-lective systems emerge.

Researchers are approaching this

transitional frontier using complemen-tary top-down and bottom-up fabrica-tion methods. Advances in top-downnanofabrication techniques such as elec-tron-beam lithography (used extensivelyby my own research group) yield almostatomic-scale precision, but achieving suc-cess, not to mention reproducibility, aswe scale down to the single-digit-nano-meter regime becomes problematic. Al-ternatively, scientists are using bottom-up techniques for self-assembly of atoms.But the advent of preprogrammed self-assembly of arbitrarily large systems—

with complexity comparable to thatbuilt every day in microelectronics, in


NOVEL NANOTECH DEVICES, such as these nanoelectromechanical resonators, are enabling scientists

to discover the laws of physics that regulate the unique properties of matter at the mesoscale.

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MEMS and (of course) by Mother Na-ture—is nowhere on the horizon. It ap-pears that the top-down approach willmost likely remain the method of choicefor building really complex devices for agood while (for more, see “The Art ofBuilding Small,” on page 38).

Our difficulty in approaching themesoscale from above or below bespeaksa basic challenge of physics. Lately, theessence of Feynman’s “Plenty of Room”talk seems to be taken as a license for lais-sez faire in nanotechnology. Yet Feyn-man never asserted that “anything goes”at the nanoscale. He warned, for in-stance, that the very act of trying to“arrange the atoms one by one the waywe want them” is subject to fundamen-tal principles: “You can’t put them sothat they are chemically unstable, for ex-ample.” Accordingly, today’s scanningprobe microscopes can move atoms fromplace to place on a prepared surface, butthis ability does not immediately conferthe power to build complex molecular as-semblies at will. What has been accom-plished so far, though impressive, is stillquite limited. We will ultimately developoperational procedures to help us coaxthe formation of individual atomic bondsunder more general conditions. But as wetry to assemble complex networks ofthese bonds, they certainly will affect one

another in ways we do not yet understandand, hence, cannot yet control.

Feynman’s original vision was clear-ly intended to be inspirational. Were heobserving now, he would surely bealarmed when people take his projec-tions as some sort of gospel. He deliv-ered his musings with characteristicplayfulness as well as deep insight. Sad-ly for us, the field that would be callednanotechnology was just one of manythat intrigued him. He never really con-tinued with it, returning to give but oneredux of his original lecture, at the JetPropulsion Laboratory in 1983.

New Laws Prevail IN 1959, and even in 1983, the com-plete physical picture of the nanoscalewas far from clear. The good news for re-searchers is that, by and large, it still is!Much exotic territory awaits explo-ration. As we delve into it, we will un-cover a panoply of phenomena that wemust understand before practical nano-technology will become possible. Thepast two decades have seen the elucida-tion of entirely new, fundamental physi-cal principles that govern behavior at themesoscale. Let’s consider three impor-tant examples.

In the fall of 1987 graduate studentBart J. van Wees of the Delft University

of Technology and Henk van Houten ofthe Philips Research Laboratories (bothin the Netherlands) and collaboratorswere studying the flow of electric currentthrough what are now called quantum-point contacts. These are narrow con-ducting paths within a semiconductor,along which electrons are forced to flow[see illustration on page 54]. Late oneevening van Wees’s undergraduate assis-tant, Leo Kouwenhoven, was measuringthe conductance through the constrictionas he varied its width systematically. Theresearch team was expecting to see onlysubtle conductance effects against anotherwise smooth and unremarkablebackground response. Instead there ap-peared a very pronounced, and now char-acteristic, staircase pattern. Further analy-sis that night revealed that plateaus wereoccurring at regular, precise intervals.

David Wharam and Michael Pepperof the University of Cambridge observedsimilar results. The two discoveries rep-resented the first robust demonstrationsof the quantization of electrical conduc-tance. This is a basic property of smallconductors that occurs when the wave-like properties of electrons are coherent-ly maintained from the “source” to the“drain”—the input to the output—of ananoelectronic device.

Feynman anticipated, in part, suchodd behavior: “I have thought aboutsome of the problems of building electriccircuits on a small scale, and the problemof resistance is serious. . . .” But the ex-perimental discoveries pointed out some-thing truly new and fundamental: quan-tum mechanics can completely governthe behavior of small electrical devices.

Direct manifestations of quantummechanics in such devices were envi-sioned back in 1957 by Rolf Landauer,a theoretician at IBM who pioneeredideas in nanoscale electronics and in thephysics of computation. But only in themid-1980s did control over materials


� Smaller than macroscopic objects but larger than molecules, nanotechnologicaldevices exist in a unique realm—the mesoscale—where the properties of matterare governed by a complex and rich combination of classical physics andquantum mechanics.

� Engineers will not be able to make reliable or optimal nanodevices until theycomprehend the physical principles that prevail at the mesoscale.

� Scientists are discovering mesoscale laws by fashioning unusual, complexsystems of atoms and measuring their intriguing behavior.

� Once we understand the science underlying nanotechnology, we can fully realize the prescient vision of Richard Feynman: that nature has left plenty ofroom in the nanoworld to create practical devices that can help humankind.

Overview/Nanophysics

It is becoming increasingly clear that we are only beginning to acquire the detailed knowledge that

will be at the heart of future nanotechnology.


and nanofabrication begin to provideaccess to this regime in the laboratory.The 1987 discoveries heralded the hey-day of “mesoscopia.”

A second important example of new-ly uncovered mesoscale laws that haveled to nascent nanotechnology was firstpostulated in 1985 by Konstantin Likha-rev, a young physics professor at MoscowState University working with postdoc-toral student Alexander Zorin and un-dergraduate Dmitri Averin. They antic-ipated that scientists would be able tocontrol the movement of single electronson and off a so-called coulomb island—

a conductor weakly coupled to the restof a nanocircuit. This could form the ba-sis for an entirely new type of device,called a single-electron transistor. Thephysical effects that arise when puttinga single electron on a coulomb island be-come increasingly robust as the island isscaled downward. In very small devices,these single-electron charging effects cancompletely dominate the current flow.

Such considerations are becomingincreasingly important technologically.

Projections from the International Tech-nology Roadmap for Semiconductors,prepared by long-range thinkers in theindustry, indicate that by 2014 the min-imum feature size for transistors in com-puter chips will decrease to 20 nanome-ters. At this dimension, each switchingevent will involve the equivalent of onlyabout eight electrons. Designs that prop-erly account for single-electron chargingwill become crucial.

By 1987 advances in nanofabrica-tion allowed Theodore A. Fulton andGerald J. Dolan of Bell Laboratories toconstruct the first single-electron tran-sistor [see illustration on page 56]. Thesingle-electron charging they observed,now called the coulomb blockade, hassince been seen in a wide array of struc-tures. As experimental devices get small-

er, the coulomb blockade phenomenonis becoming the rule, rather than the ex-ception, in weakly coupled nanoscaledevices. This is especially true in experi-ments in which electric currents arepassed through individual molecules.These molecules can act like coulomb is-lands by virtue of their weak coupling toelectrodes leading back to the macro-world. Using this effect to advantageand obtaining robust, reproducible cou-pling to small molecules (in ways thatcan actually be engineered) are amongthe important challenges in the new fieldof molecular electronics.

In 1990, against this backdrop, I wasat Bell Communications Research study-ing electron transport in mesoscopicsemiconductors. In a side project, mycolleagues Larry Schiavone and AxelScherer and I began developing tech-niques that we hoped would elucidatethe quantum nature of heat flow. Thework required much more sophisticatednanostructures than the planar devicesused to investigate mesoscopic electron-ics. We needed freely suspended devices,structures possessing full three-dimen-sional relief. Ignorance was bliss; I hadno idea the experiments would be so in-volved that they would take almost adecade to realize.

The first big strides were made afterI moved to Caltech in 1992, in a collab-oration with John Worlock of the Uni-versity of Utah and two successive post-docs in my group. Thomas Tighe devel-oped the methods and devices that gen-erated the first direct measurements ofheat flow in nanostructures. Subsequent-ly, Keith Schwab revised the design ofthe suspended nanostructures and put inplace ultrasensitive superconducting in-strumentation to interrogate them at ul-tralow temperatures, where the effectscould be seen most clearly.

In the late summer of 1999 Schwabfinally began observing heat flow through


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NANOBRIDGE DEVICE allowed Caltech physicists to first observe the quantization of thermal

conductance—a fundamental limit to heat flow in minute objects. Four holes (black) etched into a silicon

nitride membrane defined an isolated thermal reservoir (central green square) suspended by four narrow

bridges. One gold transducer (yellow) electrically heated this reservoir; the second measured its

temperature. Thin superconducting films (blue) on top of the bridges electrically connected the

transducers to off-chip instrumentation but carried no heat. The reservoir therefore cooled only through

the silicon nitride bridges, which were so narrow that they passed only the lowest-energy heat waves.

MICHAEL ROUKES, professor of physics at the California Institute of Technology, heads agroup studying nanoscale systems. Among the holy grails his team is chasing are a po-tential billionfold improvement in present-day calorimetry, which would allow observationof the individual heat quanta being exchanged as nanodevices cool, and a potentialquadrillion-fold increase in the sensitivity of magnetic resonance imaging, which would en-able complex biomolecules to be visualized with three-dimensional atomic resolution. TH

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silicon nitride nanobridges [see illustra-tion on page 51]. Even in these first datathe fundamental limit to heat flow inmesoscopic structures emerged. Themanifestation of this limit is now calledthe thermal conductance quantum. It de-termines the maximum rate at whichheat can be carried by an individualwavelike mechanical vibration, span-ning from the input to the output of ananodevice. It is analogous to the elec-trical conductance quantum but governsthe transport of heat.

This quantum is a significant para-meter for nanoelectronics; it representsthe ultimate limit for the power-dissipa-tion problem. In brief, all “active” de-vices require a little energy to operate,and for them to operate stably withoutoverheating, we must design a way toextract the heat they dissipate. As engi-neers try to ever increase the density of

transistors and the clock rates (frequen-cies) of microprocessors, the problem ofkeeping microchips cool to avoid com-plete system failure is becoming monu-mental. This will only become furtherexacerbated in nanotechnology.

Considering even this complexity,Feynman said, “Let the bearings run dry;they won’t run hot because the heat es-capes away from such a small device very,very rapidly.” But our experiments indi-cate that nature is a little more restrictive.The thermal conductance quantum canplace limits on how effectively a verysmall device can dissipate heat. WhatFeynman envisioned can be correct onlyif the nanoengineer designs a structure soas to take these limits into account.

From the three examples above, wecan arrive at just one conclusion: we areonly starting to unveil the complex andwonderfully different ways that nano-

scale systems behave. The discovery ofthe electrical and thermal conductancequanta and the observation of the cou-lomb blockade are true discontinuities—

abrupt changes in our understanding.Today we are not accustomed to callingour discoveries “laws.” Yet I have nodoubt that electrical and thermal con-ductance quantization and single-elec-tron-charging phenomena are indeedamong the universal rules of nano-design. They are new laws of the nano-world. They do not contravene but aug-ment and clarify some of Feynman’soriginal vision. Indeed, he seemed tohave anticipated their emergence: “Atthe atomic level, we have new kinds offorces and new kinds of possibilities,new kinds of effects. The problems ofmanufacture and reproduction of mate-rials will be quite different.”

We will encounter many more suchdiscontinuities on the path to true nano-technology. These welcome windfallswill occur in direct synchrony with ad-vances in our ability to observe, probeand control nanoscale structures. Itwould seem wise, therefore, to be rathermodest and circumspect about forecast-ing nanotechnology.

The Boon and Bane of NanoTHE NANOWORLD is often portrayedby novelists, futurists and the popularpress as a place of infinite possibilities.But as you’ve been reading, this domainis not some ultraminiature version of theWild West. Not everything goes downthere; there are laws. Two concrete il-lustrations come from the field of nano-electromechanical systems (NEMS), inwhich I am currently active.

Part of my research is directed to-ward harnessing small mechanical de-vices for sensing applications. Nanoscalestructures appear to offer revolutionarypotential; the smaller a device, the moresusceptible its physical properties to al-teration. One example is resonant de-tectors, which are frequently used forsensing mass. The vibrations of a tinymechanical element, such as a small can-tilever, are intimately linked to the ele-ment’s mass, so the addition of a minuteamount of foreign material (the “sam-

ONE STEP AT A TIMETHE QUANTIZATION OF ELECTRICAL CONDUCTANCEIn 1987 Bart J. van Wees and his collabo-rators at the Delft University of Technolo-gy and Philips Research Laboratories(both in the Netherlands) built a novelstructure (micrograph) that revealed abasic law governing nanotech circuits.Gold gate electrodes (bright areas) wereplaced atop a semiconductor substrate(dark background). Within the substrate,a planar sheet of charge carriers, called atwo-dimensional electron gas, was creat-ed about 100 nanometers below the sur-face. The gates and the gas acted like theplates of a capacitor.

When a negative voltage bias wasapplied to the gates, electrons within thegas underneath the gates, and slightlybeyond the gates’ periphery, werepushed away. (The diagram shows thisstate.) When increasing negative voltagewas applied, this “depletion edge” be-came more pronounced. At a certain threshold, carriers on either side of the constric-tion (between points A and B) became separated, and the conductance through thedevice was zero. From this threshold level, conductance did not resume smoothly. In-stead it increased in stepwise fashion, where the steps occurred at values deter-mined by twice the charge of the electron squared, divided by Planck’s constant. Thisratio is now called the electrical conductance quantum, and it indicates that electriccurrent flows in nanocircuits at rates that are quantized.

REGION DEPLETEDOF ELECTRONS

(BELOW SURFACE)

ELECTRON GAS(BELOW SURFACE)

DEPLETIONEDGE

ELECTRON FLOWTHROUGH CONSTRICTION

GOLD GATE B

A



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ple” being weighed) will shift the reso-nant frequency. Recent work in my labby postdoc Kamil Ekinci shows thatnanoscale devices can be made so sensi-tive that “weighing” individual atomsand molecules becomes feasible.

But there is a dark side. Gaseousatoms and molecules constantly adsorband desorb from a device’s surfaces. Ifthe device is macroscopic, the resultingfractional change in its mass is negligi-ble. But the change can be significant fornanoscale structures. Gases impingingon a resonant detector can change theresonant frequency randomly. Appar-ently, the smaller the device, the less sta-ble it will be. This instability may posea real disadvantage for various types offuturistic electromechanical signal-pro-cessing applications. Scientists might beable to work around the problem by, forexample, using arrays of nanomechani-cal devices to average out fluctuations.But for individual elements, the problemseems inescapable.

A second example of how “noteverything goes” in the nanoworld re-lates more to economics. It arises fromthe intrinsically ultralow power levels atwhich nanomechanical devices operate.Physics sets a fundamental threshold forthe minimum operating power: the ubiq-uitous, random thermal vibrations of amechanical device impose a “noise floor”below which real signals become in-creasingly hard to discern. In practicaluse, nanomechanical devices are opti-mally excited by signal levels 1,000-foldor a millionfold greater than this thresh-old. But such levels are still a millionth toa billionth the amount of power used forconventional transistors.

The advantage, in some future nano-mechanical signal-processing system orcomputer, is that even a million nano-mechanical elements would dissipateonly a millionth of a watt, on average.Such ultralow power systems could leadto wide proliferation and distribution of

cheap, ultraminiature “smart” sensorsthat could continuously monitor all ofthe important functions in hospitals, inmanufacturing plants, on aircraft, andso on. The idea of ultraminiature devicesthat drain their batteries extremely slow-ly, especially ones with sufficient com-putational power to function autono-mously, has great appeal.

But here, too, there is a dark side. Theregime of ultralow power is quite foreignto present-day electronics. Nanoscale de-vices will require entirely new system ar-chitectures that are compatible withamazingly low power thresholds. Thisprospect is not likely to be received hap-pily by the computer industry, with itsoverwhelming investment in current de-vices and methodology. A new semicon-ductor processing plant today costs

more than $1 billion, and it would prob-ably have to be retooled to be useful. ButI am certain that the revolutionaryprospects of nanoscale devices will even-tually compel such changes.

Monumental ChallengesCERTAINLY A HOST of looming is-sues will have to be addressed before wecan realize the potential of nanoscale de-vices. Although each research area hasits own concerns, some general themesemerge. Two challenges fundamental tomy current work on nanomechanicalsystems, for instance, are relevant tonanotechnology in general.

Challenge I: Communication betweenthe macroworld and the nanoworld.NEMS are incredibly small, yet their mo-tion can be far smaller. For example, ananoscale beam clamped on both endsvibrates with minimal harmonic distor-tion when its vibration amplitude is keptbelow a small fraction of its thickness.For a 10-nanometer-thick beam, this am-plitude is only a few nanometers. Build-ing the requisite, highly efficient trans-ducers to transfer information from sucha device to the macroworld involves read-ing out information with even greaterprecision.

Compounding this problem, the nat-ural frequency of the vibration increasesas the size of the beam is decreased. Soto usefully track the device’s vibrations,the ideal NEMS transducer must be ca-pable of resolving extremely small dis-placements, in the picometer-to-fem-tometer (trillionth to quadrillionth of ameter) range, across very large band-widths (extending into the microwaverange). These twin requirements pose atruly monumental challenge, one muchmore significant than those faced so farin MEMS work. A further complicationis that most of the methodologies fromMEMS are inapplicable; they simply do not scale down well to nanometer dimensions.

The difficulties in communication between the nanoworld and the macroworld represent a central issuein the development of nanotechnology.

RICHARD FEYNMAN predicted the rise of nano-

technology in a landmark 1959 talk at Caltech.

“The principles of physics,” he said, “do not

speak against the possibility of maneuvering

things atom by atom.” But he also anticipated

that unique laws would prevail; they are finally

being discovered today.


These difficulties in communicationbetween the nanoworld and the macro-world represent a generic issue in the de-velopment of nanotechnology. Ulti-mately, the technology will depend onrobust, well-engineered informationtransfer pathways from what are, in

essence, individual macromolecules. Al-though the grand vision of futurists mayinvolve self-programmed nanobots thatneed direction from the macroworldonly when they are first wound up andset in motion, it seems more likely thatmost nanotechnological applications re-

alizable in our lifetimes will entail someform of reporting up to the macroworldand feedback and control back down.The communication problem will re-main central.

Orchestrating such communicationimmediately invokes the very real pos-sibility of collateral damage. Quantumtheory tells us that the process of mea-suring a quantum system nearly alwaysperturbs it. This can hold true evenwhen we scale up from atoms and mol-ecules to nanosystems comprising mil-lions or billions of atoms. Coupling ananosystem to probes that report backto the macroworld always changes thenanosystem’s properties to some degree,rendering it less than ideal. Introducingthe transducers required for communi-cation will do more than just increasethe nanosystem’s size and complexity.They will also necessarily extract someenergy to perform their measurementsand can degrade the nanosystem’s per-formance. Measurement always has itsprice.

Challenge II: Surfaces. As we shrinkMEMS to NEMS, device physics be-comes increasingly dominated by the sur-faces. Much of the foundation of solid-state physics rests on the premise that thesurface-to-volume ratio of objects is in-finitesimal, meaning that physical prop-erties are always dominated by thephysics of the bulk. Nanoscale systemsare so small that this assumption breaksdown completely.

For example, mechanical devices pat-terned from single-crystal, ultrapure ma-terials can contain very few (even zero)crystallographic defects and impurities.My initial hope was that, as a result,there would be only very weak dampingof mechanical vibrations in monocrys-talline NEMS. But as we shrink mechan-ical devices, we repeatedly find thatacoustic energy loss seems to increase inproportion to the increasing surface-to-


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In each new regime, some wonderful scientificphenomenon emerges. But then a thorny host of underlying,

equally unanticipated problems appear.

TAKING CHARGE

SINGLE ELECTRONICSAdvances in nanofabrication allowed Theodore A. Fulton and Gerald J. Dolan to build a single-electron transistor at Bell Laboratories in 1987 (micrograph). In thisstructure the controlled movement of individual electrons through a nanodevice wasfirst achieved. At its heart was a coulomb island, a metallic electrode isolated fromits counter-electrodes by thin insulating oxide barriers (diagram). The counter-electrodes led up to the macroscale laboratory instrumentation used to carry out theexperiments. An additional gate electrode (visible in the diagram but not themicrograph) was offset from the coulomb island by a small gap; it allowed directcontrol of the charge introduced to the island. Electric current flowed through thedevice from one counter-electrode to another, as in a conventional circuit, but here itwas limited by the stepwise hopping of electrons onto and off the coulomb island.

Fulton and Dolan’s experiments demonstrate both the fundamental physics ofsingle-electron charging and the potential of these devices as ultrasensitiveelectrometers: instruments that can easily detect individual electron charges.Circuits that switch one electron at a time could someday form the basis for anentirely new class of nanoelectronics. The advent of such single electronics,however, also presages problems that will have to be faced as conventionalelectronic circuits are shrunk to the nanoscale.

GATE ELECTRODE

COULOMB ISLAND

INSULATING BARRIER

COUNTER-ELECTRODE

ELECTRON


volume ratio. This result clearly impli-cates surfaces in the devices’ vibrationalenergy-loss processes. In a state-of-the-artsilicon beam measuring 10 nanometerswide and 100 nanometers long, morethan 10 percent of the atoms are at ornext to the surface. It is evident that theseatoms will play a central role, but under-standing precisely how will require a ma-jor, sustained effort.

In this context, so-called nanotubestructures, which have been heraldedlately, look ideal. A nanotube is a crys-talline, rodlike material perfect for build-ing the miniature vibrating structures ofinterest to us. And because it has nochemical groups projecting outwardalong its length, one might expect that in-teraction with “foreign” materials at itssurfaces would be minimal. Apparentlynot. Although nanotubes exhibit idealcharacteristics when shrouded withinpristine, ultrahigh vacuum environments,samples in more ordinary conditions,where they are exposed to air or watervapor, evince electronic properties thatare markedly different. Mechanical prop-erties are likely to show similar sensitiv-ity. So surfaces definitely do matter. Itwould seem there is no panacea.

Payoff in the GlitchesFUTURISTIC THINKING is crucial tomaking the big leaps. It gives us somewild and crazy goals—a holy grail tochase. And the hope of glory propels usonward. Yet the famous 19th-centurychemist Kekulé once said, “Let us learnto dream, gentlemen, then perhaps weshall find the truth. . . . But let us bewareof publishing our dreams before theyhave been put to the proof by the wak-ing understanding.”

This certainly holds for nanoscience.While we keep our futuristic dreamsalive, we also need to keep our expecta-tions realistic. It seems that every time wegain access to a regime that is a factor of10 different—and presumably “better”—

two things happen. First, some wonder-ful, unanticipated scientific phenomenonemerges. But then a thorny host of un-derlying, equally unanticipated newproblems appear. This pattern has held

true as we have pushed to decreased size,enhanced sensitivity, greater spatial res-olution, higher magnetic and electricfields, lower pressure and temperature,and so on. It is at the heart of why pro-jecting forward too many orders of mag-nitude is usually perilous. And it is whatshould imbue us with a sense of humili-ty and proportion at this, the beginningof our journey. Nature has already setthe rules for us. We are out to understandand employ her secrets.

Once we head out on the quest, na-ture will frequently hand us what initial-ly seems to be nonsensical, disappoint-ing, random gibberish. But the science inthe glitches often turns out to be evenmore important than the grail motivat-ing the quest. And being proved the foolin this way can truly be the joy of doingscience. If we had the power to extrapo-late everything correctly from the outset,the pursuit of science would be utterlydry and mechanistic. The delightful truthis that, for complex systems, we do not,and ultimately probably cannot, knoweverything that is important.

Complex systems are often exquis-itely sensitive to a myriad of parametersbeyond our ability to sense and record—

much less control—with sufficient regu-larity and precision. Scientists have stud-ied, and in large part already understand,matter down to the fundamental parti-cles that make up the neutrons, protonsand electrons that are of crucial impor-tance to chemists, physicists and engi-neers. But we still cannot deterministi-cally predict how arbitrarily complex as-semblages of these three elementalcomponents will finally behave en masse.For this reason, I firmly believe that it ison the foundation of the experimentalscience already under way, in intimatecollaboration with theory, that we willbuild the road to true nanotechnology.Let’s keep our eyes open for surprisesalong the way!


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Nanoelectromechanical Systems Face the Future. Michael Roukes in Physics World, Vol. 14, No. 2;February 2001. Available at physicsweb.org/article/world/14/2/8

The author’s group: www.its.caltech.edu/~nano

Richard Feynman’s original lecture “There’s Plenty of Room at the Bottom” can be read atwww.its.caltech.edu/~feynman


NANOMECHANICAL AMPLIFIER overcomes the vexing problem of communication with the macroworld

by providing up to 1,000-fold amplification of weak forces. Two suspended bridges ( left and right) of

monocrystalline silicon carbide support the central crossbridge, to which the signal force is applied.

Thin-film electrodes (silver) atop these structures provide very sensitive readouts of nanoscale motion.



NANOELECTRONICS

RESEARCHERS HAVE BUILT

NANOTRANSISTORS AND NANOWIRES.

NOW THEY JUST NEED TO FIND A WAY

TO PUT THEM ALL TOGETHER

BY CHARLES M. LIEBER

IncredibleThe

Shrinking

Circuit

NANOWIRES, each about five to 10 nanometers in diameter, may

represent the future of electronics. They are the brown lines, made of

indium phosphide, connecting the gold electrodes in this micrograph.

These wires have been put to truly diverse uses—as memory and logic

and as arrays of light-emitting diodes.



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Do we really need to keep on making circuitssmaller? The miniaturization of silicon microelectronics seemsso inexorable that the question seldom comes up—exceptmaybe when we buy a new computer, only to find that it be-comes obsolete by the time we leave the store. A state-of-the-art microprocessor today has more than 40 million transistors;by 2015 it could have nearly five billion. Yet within the nexttwo decades this dramatic march forward will run up againstscientific, technical and economic limits. A first reaction mightbe, So what? Aren’t five billion transistors enough already?

Yet when actually confronted with those limits, people willno doubt want to go beyond them. Those of us who work tokeep computer power growing are motivated in part by thesheer challenge of discovering and conquering unknown ter-ritory. But we also see the potential for a revolution in medi-

cine and so many other fields, as extreme miniaturization en-ables people and machines to interact in ways that are not pos-sible with existing technology.

As the word suggests, microelectronics involves compo-nents that measure roughly one micron on a side (althoughlately the components have shrunk to a size of almost 100nanometers). Going beyond microelectronics means more thansimply shrinking components by a factor of 10 to 1,000. It alsoinvolves a paradigm shift for how we think about puttingeverything together.

Microelectronics and nanoelectronics both entail three lev-

els of organization. The basic building block is usually the tran-sistor or its nanoequivalent—a switch that can turn an electriccurrent on or off as well as amplify signals. In microelectron-ics, transistors are made out of chunks of semiconductor—amaterial, such as impure silicon, that can be manipulated toflip between conducting and nonconducting states. In nano-electronics, transistors might be organic molecules or nano-scale inorganic structures.

The next level of organization is the interconnection—thewires that link transistors together in order to perform arith-metic or logical operations. In microelectronics, wires are met-al lines typically hundreds of nanometers to tens of micronsin width deposited onto the silicon; in nanoelectronics, they arenanotubes or other wires as narrow as one nanometer.

At the top level is what engineers call architecture—the over-

all way the transistors are interconnected, so that the circuit canplug into a computer or other system and operate independentlyof the lower-level details. Nanoelectronics researchers have notquite gotten to the point of testing different architectures, butwe do know what abilities they will be able to exploit and whatweaknesses they will need to compensate for.

In other ways, however, microelectronics and nanoelec-tronics could not be more different. To go from one to the oth-er, many believe, will require a shift from top-down manufac-turing to a bottom-up approach. To build a silicon chip today,fabrication plants start with a silicon crystal, lay down a pat-tern using a photographic technique known as lithography,and etch away the unwanted material using acid or plasma.That procedure simply doesn’t have the precision for devicesthat are mere nanometers in width. Instead researchers use themethods of synthetic chemistry to produce building blocks bythe mole (6 × 1023 pieces) and assemble a portion of them intoprogressively larger structures. So far the progress has been im-pressive. But if this research is a climb up Mount Everest, wehave barely just reached the base camp.

Smallifying MachinesTHE USE OF MOLECULES for electronic devices was sug-gested more than a quarter of a century ago in a seminal pa-per by Avi Aviram of IBM and Mark A. Ratner of North-western University. By tailoring the atomic structures of or-ganic molecules, they proposed, it should be possible toconcoct a transistorlike device. But their ideas remained large-ly theoretical until a recent confluence of advances in chem-istry, physics and engineering.

Of all the groups that have turned Aviram and Ratner’s

� Silicon chips, circuit boards, soldering irons: these are theicons of modern electronics. But the electronics of the futuremay look more like a chemistry set. Conventional techniquescan shrink circuits only so far; engineers will soon need toshift to a whole new way of organizing and assemblingelectronics. One day your computer may be built in a beaker.

� Researchers have created nanometer-scale electroniccomponents—transistors, diodes, relays, logic gates—

from organic molecules, carbon nanotubes andsemiconductor nanowires. Now the challenge is to wirethese tiny components together.

� Unlike conventional circuit design, which proceeds fromblueprint to photographic pattern to chip, nanocircuit designwill probably begin with the chip—a haphazard jumble of asmany as 1024 components and wires, not all of which willeven work—and gradually sculpt it into a useful device.

Overview/Nanoelectronics

The use of molecules for electronic devices remained theoretical until a recent confluence of advances

in chemistry, physics and engineering.


ideas into reality, two teams—one at the University of Califor-nia at Los Angeles and Hewlett-Packard, the other at Yale, Riceand Pennsylvania State universities—stand out. Within the pastyear, both have demonstrated that thousands of molecules clus-tered together can carry electrons from one metal electrode toanother. Each molecule is about 0.5 nanometer wide and oneor more nanometers long. Both groups have shown that theclusters can behave as on/off switches and might thus be usablein computer memory; once on, they will stay on for 10 min-utes or so [see “Computing with Molecules,” by Mark A. Reedand James M. Tour; Scientific American, June 2000]. Thatmay not sound like a long time, but computer memory typical-ly loses its information instantly when the power is turned off;even when the power is on, the stored information leaks awayand must be “refreshed” every 0.1 second or so.

Although the details differ, the switching mechanism forboth molecules is believed to involve a well-understood chem-ical reaction, oxidation reduction, in which electrons shuffleamong atoms within the molecule. The reaction puts a twist inthe molecule, blocking electrons as surely as a kink in a hoseblocks water [see illustration above]. In the “on” position, theclusters of molecules may conduct electricity as much as 1,000times better than in the “off” position. That ratio is actuallyrather low compared with that of typical semiconductor tran-sistors, whose conductivity varies a millionfold. Researchers arenow looking for other molecules with even better switchingproperties and are also working to understand the switchingprocess itself.

My own research group at Harvard University is one of sev-eral that have focused not on organic molecules but on long,thin inorganic wires. The best-known example is the carbonnanotube, which is typically about 1.4 nanometers in diame-ter [see “Nanotubes for Electronics,” by Philip G. Collins andPhaedon Avouris; Scientific American, December 2000].Not only can these nanoscale wires carry much more current,atom for atom, than ordinary metal wires, they can also act astiny transistors. By functioning both as interconnections and ascomponents, nanowires kill two birds with one stone. Anoth-er advantage is that they can exploit the same basic physics asstandard silicon microelectronics, which makes them easier tounderstand and manipulate.

In 1997 Cees Dekker’s group at the Delft University ofTechnology in the Netherlands and Paul L. McEuen’s group,then at the University of California at Berkeley, independent-ly reported highly sensitive transistors made from metallic car-bon nanotubes. These devices could be turned on and off by a


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CHARLES M. LIEBER spent much of his childhood building—andbreaking—stereos, cars and model airplanes. He is now the MarkHyman Professor of Chemistry at Harvard University, where he di-rects a group of 25 undergraduate, graduate and postdoctoral re-searchers who focus on nanoscale science and technology.Lieber recently founded NanoSys, Inc., with Larry Bock of CW Ven-tures and Hongkun Park of Harvard. Their modest goal: to revolu-tionize chemical and biological sensing, electronics, optoelec-tronics, and information storage.

THE

AU

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NANOTRANSISTORS

MOLECULAR TRANSISTORS

could be the building

blocks of electronics on the

nanometer scale. Each of

the two molecules shown

here conducts electricity

like a tiny wire once a

chemical reaction—

oxidation reduction—alters

its atomic configuration

and switches it on. In the

diagram, each stick

represents a chemical

bond; each intersection of

two sticks represents a

carbon atom; and each ball

represents an atom other

than carbon.

ROTOXANE BENZENETHIOL

SWITCH OFF

SWITCH ON

SWITCH OFF

SWITCH ON ADDEDELECTRON


single electron but required very low temperatures to operate.This past July Dekker’s team swept away this limitation. Theresearchers used an atomic force microscope to create a single-electron transistor that could function at room temperature.Dekker and his co-workers have also fashioned a more con-ventional field-effect transistor, the building block of most in-tegrated circuits today, out of a carbon nanotube, and McEuen’sgroup has combined metallic and semiconductor nanotubes into

a diode, which allows electric current to pass in one directiononly. Finally, my group has demonstrated a very different typeof switch, a nanoscale electromechanical relay.

Hot WireA MAJOR PROBLEM with nanotubes is that they are difficultto make uniform. Because a slight variation in diameter canspell the difference between a conductor and a semiconductor,


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DNA ComputingWHY LIMIT OURSELVES TO ELECTRONICS? Most effortsto shrink computers assume that these machines will continue to operate much as they do today, usingelectrons to carry information and transistors toprocess it. Yet a nanoscale computer could operate bycompletely different means. One of the most excitingpossibilities is to exploit the carrier of geneticinformation in living organisms, DNA.

The molecule of life can store vast quantities ofdata in its sequence of four bases (adenine, thymine,guanine and cytosine), and natural enzymes canmanipulate this information in a highly parallel manner.The power of this approach was first brought to light bycomputer scientist Leonard M. Adleman in 1994. Heshowed that a DNA-based computer could solve a typeof problem that is particularly difficult for ordinarycomputers—the Hamiltonian path problem, which isrelated to the infamous traveling-salesman problem[see “Computing with DNA,” by Leonard M. Adleman;SCIENTIFIC AMERICAN, August 1998].

Adleman started by creating a chemical solution ofDNA. The individual DNA molecules encoded everypossible pathway between two points. By going througha series of separation and amplification steps, Adleman weeded out the wrong paths—those, forexample, that contained points they were not supposedto contain—until he had isolated the right one. Morerecently, Lloyd M. Smith’s group at the University ofWisconsin–Madison implemented a similar algorithmusing gene chips, which may lend themselves better topractical computing (diagram).

Despite the advantages of DNA computing forotherwise intractable problems, many challengesremain, including the high incidence of errors causedby base-pair mismatches and the huge number of DNA nanoelements needed for even a modestcomputation. DNA computing may ultimately mergewith other types of nanoelectronics, taking advantageof the integration and sensing made possible bynanowires and nanotubes. —C.M.L.

Other processes melt away the added complementarystrands. These steps are repeated with all the clauses of the equation.

Single DNA strands are attached to a silicon chip.They encode all possible values of the variables in anequation that the researchers want to solve.

Copies of a complementary strand—which encodes the first clause of the equation—are pouredonto the chip. These copies attach themselves to any strand that represents a valid solution of the clause.Any invalid solutions remain a single strand.

The DNA strand that survives this whole processrepresents the solution to the whole equation.

1

2

4

5

SINGLE-STRANDEDDNA

VALIDSOLUTION

INVALIDSOLUTION

CHIP

ENZYME

COMPLEMENTARYSTRAND

An enzyme removes all the single strands.3


a large batch of nanotubes may contain only a few working de-vices. In April of this year Phaedon Avouris and his colleaguesat the IBM Thomas J. Watson Research Center came up witha solution. They started with a mixture of conducting andsemiconducting nanotubes and, by applying a current betweenmetal electrodes, selectively burned away the conducting onesuntil just semiconducting ones were left. The solution is onlypartial, however, because it requires the use of conventionallithography to wire up the random nanotube array and thentest and modify each of the individual elements, which wouldultimately number in the billions.

My group has also been working on a different type ofnanoscale wire, which we term the semiconductor nanowire. Itis about the same size as a carbon nanotube, but its composi-tion is easier to control precisely. To synthesize these wires, westart with a metal catalyst, which defines the diameter of thegrowing wire and serves as the site where molecules of the de-sired material tend to collect. As the nanowires grow, we in-corporate chemical dopants (impurities that add or remove elec-trons), thereby controlling whether the nanowires are n-type(having extra electrons) or p-type (having a shortage of elec-trons or, equivalently, a surfeit of positively charged “holes”).

The availability of n- and p-type materials, which are theessential ingredients of transistors, diodes and other electron-ic devices, has opened up a new world for us. We have assem-bled a wide range of devices, including both major types oftransistors (field-effect and bipolar); inverters, which transforma “0” signal to a “1”; and light-emitting diodes, which pavethe way for optical interconnections. Our bipolar transistorswere the first molecular-scale devices ever to amplify a current.A recent advance in my lab by Xiangfeng Duan has been theassembly of memory from crisscrossing n- and p-typenanowires. The memory can store information for 10 minutesor longer by trapping charge at the interface between the cross-ing nanowires [see illustration on next page].

Breaking the LogjamBUILDING UP AN ARSENAL of molecular and nanoscaledevices is just the first step. Interconnecting and integratingthese devices is perhaps the much greater challenge. First, thenanodevices must be connected to molecular-scale wires. Todate, organic-molecule devices have been hooked up to con-ventional metal wires created by lithography. It will not be easyto substitute nanowires, because we do not know how to makea good electrical connection without ruining these tiny wiresin the process. Using nanowires and nanotubes both for the de-vices and for the interconnections would solve that problem.

Second, once the components are attached to nanowires, the

wires themselves must be organized into, for example, a two-dimensional array. In a report published earlier this year, Duanand another member of my team, Yu Huang, made a very sig-nificant breakthrough: they assembled nanocircuits by meansof fluid flows. Just as sticks and logs can flow down a river,nanoscale wires can be drawn into parallel lines using fluids.In my lab we have used ethanol and other solutions and con-trolled the liquid flow by passing it through channels moldedinto polymer blocks, which can be easily placed on the substratewhere we wish to assemble devices.

The process creates interconnections in the direction of thefluid flow: if the flow is along only one channel, then parallelnanowires are formed. To add wires in other directions, weredirect the flow and repeat the process, building up addition-al layers of nanowires. For instance, to produce a right-anglegrid, we first lay down a series of parallel nanowires, then ro-tate the direction of flow by 90 degrees and lay down anotherseries. By using wires of different compositions for each layer,we can rapidly assemble an array of functional nanodevices us-ing equipment not much more sophisticated than a high schoolchemistry lab. A grid of diodes, for example, consists of a lay-er of conducting nanotubes above a layer of semiconductornanotubes, or a layer of n-type nanowires atop a layer of p-type nanowires. In both cases, each junction serves as a diode.

Our approach, which is similar to that being pursued by theteam at U.C.L.A. and Hewlett-Packard, is deterministic. We aretrying to create arrays with a certain predictable behavior. Formfollows function. An alternative proposed by the group at Rice,Yale and Penn State is to allow blocks of devices and wires tointerconnect at random. Later, the ensemble can be analyzed todetermine how it might be used for storage or computation. Inthis case, function follows form. The problem with this proce-dure is that it would take a huge effort to map a complex net-work and figure out what use it could be put to.

Intimately linked to all these efforts is the development ofarchitectures that best exploit the unique features of nanoscaledevices and the capabilities of bottom-up assembly. Althoughwe can make unfathomable numbers of dirt-cheap nanostruc-tures, the devices are much less reliable than their microelec-tronic counterparts, and our capacity for assembly and orga-nization is still quite primitive.

In collaboration with André DeHon of the California In-stitute of Technology, my group has been working on highlysimplified architectures that can be generalized for universalcomputing machines. For memory, the architecture starts witha two-dimensional array of crossed nanowires or suspendedelectromechanical switches in which one can store informationat each cross point. The same basic architecture is being pur-


Soon nanodevices may have useful applications—for example, as ultrasensitive detectors of gas

molecules and biological compounds.



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sued by researchers at U.C.L.A. and Hewlett-Packard, and itresembles the magnetic-core memory that was common incomputers of the 1950s and 1960s.

Law of Large NumbersTO OVERCOME the unreliability of individual nanodevices,we may rely on sheer numbers—the gizmos are so cheap thatplenty of spares are always available. Researchers who workon defect tolerance have shown that computing is possible evenif many of the components fail, although identifying and map-ping the defects can be slow and time-consuming. Ultimatelywe hope to partition the enormous arrays into subarrays whosereliability can be easily monitored. The optimum size of thesesubarrays will depend on the defect levels typically present inmolecular and nanoscale devices.

Another significant hurdle faced by nanoelectronics is“bootstrapping.” How do engineers get the circuit to do whatthey want it to? In microelectronics, circuit designers work likearchitects: they prepare a blueprint of a circuit, and a fabrica-tion plant builds it. In nanoelectronics, designers will have towork like computer programmers. A fabrication plant will cre-ate a raw nanocircuit—billions on billions of devices and wireswhose functioning is rather limited. From the outside, it willlook like a lump of material with a handful of wires stickingout. Using those few wires, engineers will somehow have toconfigure those billions of devices. Challenges such as this arewhat keeps me tremendously excited about the field as a whole.

Even before we solve these problems, nanodevices may haveuseful applications. For example, semiconducting carbon nano-tubes have been used by Hongjie Dai’s group at Stanford Uni-versity to detect gas molecules, and Yi Cui in my group has usedsemiconductor nanowires as ultrasensitive detectors for a wide

range of biological compounds. In our work at Harvard, wehave converted nanowire field-effect transistors into sensors bymodifying their surfaces with molecular receptors. This tech-nology has the potential of detecting single molecules using onlya voltmeter from a hardware store. The small size and sensitiv-ity of nanowires also make possible the assembly of extremelypowerful sensors that could, for instance, sequence the entirehuman genome on a single chip and serve in minimally invasivemedical devices. In the nearer term, we could see hybrids of mi-cro and nano: silicon with a nano core—perhaps a high-densi-ty computer memory that retains its contents forever.

Although substantial work remains before nanoelectronicsmakes its way into computers, this goal now seems less hazy thanit was even a year ago. As we gain confidence, we will learn notjust to shrink digital microelectronics but also to go where nodigital circuit has gone before. Nanoscale devices that exhibitquantum phenomena, for example, could be exploited in quan-tum encryption and quantum computing. The richness of thenanoworld will change the macroworld.

The author’s Web site: cmliris.harvard.eduThe Avouris group: www.research.ibm.com/nanoscienceThe Dai group: www-chem.stanford.edu/group/daiThe DeHon group: www.cs.caltech.edu/~andreThe Dekker group: www.mb.tn.tudelft.nl/user/dekkerThe McEuen group:www.lassp.cornell.edu/lassp_data/mceuen/homepage/welcome.htmlThe Penn State team: stm1.chem.psu.eduThe Rice / Yale team: www.jmtour.com and www.eng.yale.edu/reedlabThe Smith group: www.chem.wisc.edu/~smithThe U.C.L.A./Hewlett-Packard team: www.chem.ucla.edu/~schung/hgrpand www.hpl.hp.com/research/qsr/staff/kuekes.html


NANOWIRE ARRAY

ELECTRODE

INSULATOR

NANOTUBE

CRISSCROSSING NANOWIRES

neatly solves a major problem in

molecular-scale electronics:

How do you connect wires to

components such as transistors

or diodes? The wires do

double duty, serving both as

wires and as components. Each

junction is a component, in this case, a

miniature relay—an electromechanical

switch that is either on (touching) or

off (separated). To flip a switch on or

off, you apply a certain voltage to the two nanowires.

The switch will then stay in that position indefinitely. Crisscrossed

semiconductor nanowires have also been used to create switches that are turned

on and off electrically, without mechanical motion. And they can form memory and

logic arrays—key steps toward the assembly of a nanocomputer.

“ON” JUNCTION

SUPPORT

“OFF” JUNCTION



SOPHISTICATED FORMS OF NANOTECHNOLOGY

WILL FIND SOME OF THEIR FIRST REAL-WORLD

APPLICATIONS IN BIOMEDICAL RESEARCH,

DISEASE DIAGNOSIS AND, POSSIBLY, THERAPYBY A. PAUL ALIVISATOS

The 1966 film Fantastic Voyage treated movie-goers to a bold vision of nanotechnology applied to medicine:through mysterious means, an intrepid team of doctors andtheir high-tech submarine were shrunk to minute size so thatthey could travel through the bloodstream of an injured patientand remove a life-threatening blood clot in his brain. In the past35 years, great strides have been made in fabricating complexdevices at ever smaller scales, leading some people to believethat such forms of medical intervention are possible and thattiny robots will soon be coursing through everyone’s veins. In-deed, in some circles the idea is taken so seriously that worrieshave emerged about the dark side of such technology: Could

self-replicating nanometer-scale automatons run amok and de-stroy the entire biological world?

In my view, shared by most investigators, such thoughts be-long squarely in the realm of science fiction. Still, nanotech-nology can potentially enhance biomedical research tools—forexample, by providing new kinds of labels for experimentsdone to discover drugs or to reveal which sets of genes are ac-tive in cells under various conditions. Nanoscale devices could,moreover, play a part in quick diagnostic screens and in genet-ic tests, such as those meant to determine a person’s suscepti-bility to different disorders or to reveal which specific genes aremutated in a patient’s cancer. Investigators are also studyingthem as improved contrast agents for noninvasive imaging andas drug-delivery vehicles. The emerging technologies may not beas photogenic as a platelet-size Raquel Welch blasting away ata clot with a laser beam, but they are every bit as dramatic be-cause, in contrast, the benefits they offer to patients and re-searchers are real.

HIGHLY MAGNIFIED VIALS contain solutions of quantum dots—semiconduc-

tor nanocrystals—of specific sizes. The precise size of a quantum dot deter-

mines the color it emits after exposure to light. By attaching different sizes

of dots to different biological molecules, investigators can track the activities

of many tagged molecules simultaneously.

moreLess is

inMedicine

NANOMEDICINE


How exactly can nanotechnology doall these things? The answer hinges onone’s definitions. All of biology is ar-guably a form of nanotechnology. Afterall, even the most complicated creature ismade up of tiny cells, which themselvesare constructed of nanoscale buildingblocks: proteins, lipids, nucleic acids andother complex biological molecules. Butby convention the term “nanotechnol-ogy” is usually restricted to artificial con-structions made, say, from semiconduc-tors, metals, plastic or glass. A few inor-ganic structures of nanometer scale—

minute crystals, for instance—have al-ready been commercialized, notably ascontrast agents.

Magnetic AttractionNATURE ITSELF provides a beautifulillustration of the usefulness of such in-organic crystals in a biological context:humble magnetotactic (magnetic-sens-ing) bacteria. Such organisms, which livein bodies of water and their muddy bot-toms, thrive only at one depth in the wa-ter or sediment. Above this position, oxy-gen is too abundant for their liking; be-low, too scarce. A bacterium that driftsaway from the right level must swimback, and so, like many of its cousins, themicrobe wields a whiplike tail for pro-pulsion. But how does the buoyant celltell up from down when gravity has es-sentially no effect on it?

The answer is that this bacterium hasfixed within it a chain of about 20 mag-netic crystals that are each between 35and 120 nanometers in diameter. To-gether these crystals constitute a minia-ture compass. Because the magnetic fieldof the earth is inclined in most places (itpoints not only north but also down-ward in the Northern Hemisphere andupward in the Southern), a magnetotac-tic bacterium can follow a magnetic fieldline up or down to its desired destination.

This compass is a marvel of naturalnanoscale engineering. For one, it is madeof the perfect material—either magnetiteor greigite, both highly magnetic ironminerals. The use of multiple crystals isalso no accident. At very small scales, thelarger a magnetic particle is, the longerit stays magnetized. But if the particle be-comes too large, it will spontaneouslyform two separate magnetic domainswith oppositely directed magnetizations.Such a crystal has little overall magneti-zation and does not make for a very ef-fective compass needle. By building itscompass out of crystals that are of justthe right size to exist as stable, singlemagnetic domains, the bacterium makesthe best use of every bit of iron it laysdown. Interestingly, when people designmedia for hard-disk storage, they followexactly the same strategy, using magnet-ic nanocrystals that are of the proper sizeto be both stable and strong.

Artificial magnetic crystals of similardimension might soon serve biomedicalresearch in a novel way. Two groups,one in Germany and the other at my in-stitution, the University of California atBerkeley, are exploring the use of mag-netic nanoparticles to detect particularbiological entities, such as microorgan-isms that cause disease.

Their method, like many of the tech-niques applied today, requires suitableantibodies, which bind to specific targets.The magnetic particles are affixed, as la-bels, to selected antibody molecules,which are then applied to the sample un-der study. To detect whether the anti-bodies have latched onto their target, aninvestigator applies a strong magneticfield (which temporarily magnetizes theparticles) and then examines the speci-men with a sensitive instrument capableof detecting the weak magnetic fields em-anating from the probes. Labeled anti-bodies that have not docked to the sam-ple tumble about so rapidly in solutionthat they give off no magnetic signal.Bound antibodies, however, are unableto rotate, and together their magnetictags generate a readily detectable mag-netic field.

Because the unbound probes produceno signal, this approach does away withthe time-consuming washing steps usual-ly required of such assays. The sensitivi-ty demonstrated with this experimentaltechnique is already better than with stan-dard methods, and anticipated improve-ments in the apparatus should soon boostsensitivity by a factor of several hundred.

Despite these advantages, the mag-netic method probably will not com-pletely replace the widespread practice oflabeling probes with a fluorescent tag,typically an organic molecule that glowswith a characteristic hue when it is ener-gized by light of a particular color. Col-ors are very useful in various diagnosticand research procedures, such as whenmore than one probe needs to be tracked.


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The technologies may not be as photogenicas a minute Raquel Welch blasting away at a clot, but they are

just as dramatic because their benefits are real.

� Nanometer-scale objects made ofinorganic materials can serve inbiomedical research, diseasediagnosis and even therapy.

� Biological tests measuring thepresence or activity of selectedsubstances become quicker, moresensitive and more flexible whencertain nanoscale particles are put towork as tags, or labels.

� Nanoparticles could be used todeliver drugs just where they areneeded, avoiding the harmful sideeffects that so often result frompotent medicines.

� Artificial nanoscale building blocksmay one day be used to help repairsuch tissues as skin, cartilage andbone—and they may even helppatients to regenerate organs.

Overview/Nanomedicine


The world of modern electronics isalso full of light-emitting materials.Every CD player, for instance, reads thedisc with light from a solid-state laserdiode, which is made of an inorganicsemiconductor. Imagine carving out avanishingly small piece of that material,a scoop the size of a protein molecule.The result is a semiconductor nanocrys-tal, or, in the talk of the trade, a “quan-tum dot.” Like nanoscale magnetic crys-tals, these minuscule dots have much tooffer biomedical researchers.

As the name suggests, quantum dotsowe their special properties to the weirdrules of quantum mechanics, the same

rules that restrict the electrons in atomsto certain discrete energy levels. An or-ganic dye molecule absorbs only photonsof light with just the right energy to lift itselectrons from their quiescent state toone of the higher levels available to them.That is, the incident light must be exact-ly the right wavelength, or color, to dothe job. The molecule will subsequently

emit a photon when the electron fallsback to a lower energy level. This phe-nomenon is quite different from whathappens in bulk semiconductors, whichallow electrons to occupy two broadbands of energy. Such materials can ab-sorb photons in a broad range of colors(all those that have enough energy tobridge the gap between these two bands),


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R A. PAUL ALIVISATOS is a professor in the department of chemistry at the University of Cal-ifornia, Berkeley, where he received his doctorate in physical chemistry in 1986. A Fellowof both the American Association for the Advancement of Science and the American Physi-cal Society, Alivisatos has received many awards for his research on the physical proper-ties of nanocrystals. He is a founder of Quantum Dot Corporation, which is working to com-mercialize the use of semiconductor nanocrystals as fluorescent labels in biomedical tests.

GOAL: Superior Implants

The National Nanotechnol-ogy Initiative includes

among its goals, or “grandchallenges,” a host offuturistic improvements inthe detection, diagnosis and treatment of disease.Some are depicted here. Thegoals, many of which are farfrom being realized, alsofeature new aids for visionand hearing, rapid tests for detecting diseasesusceptibility and responsesto drugs, and tiny devicesable to find problems—suchas incipient tumors,infections or heart problems—

and to relay the informationto an external receiver or fixthem on the spot.

Nanoparticles would deliver treatments to specifically targeted sites, including places thatstandard drugs do not reach easily. For example, gold nanoshells (spheres) that were targeted totumors might, when hit by infrared light, heat upenough to destroy the growths.

A GRAND PLAN FOR MEDICINE

GOAL: New Ways to Treat Disease

Nanometer-scale modifications of implant surfaceswould improve implant durability and biocompat-ibility. For instance, an artificial hip coated withnanoparticles might bond to the surrounding bonemore tightly than usual, thus avoiding loosening.

GOAL: Improved ImagingImproved or new contrast agentswould detect problems at earlier,more treatable stages. They might,for instance, reveal tumors (red)only a few cells in size.

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but they emit light only at one specificwavelength, corresponding to the band-gap energy. Quantum dots are an inter-mediate case. Like bulk semiconductors,they absorb photons of all energies abovethe threshold of the band gap. But thewavelength of light a quantum dotemits—its color—depends very stronglyon the dot’s size. Hence, a single type ofsemiconducting material can yield an en-tire family of distinctly colored labels.

Physicists first studied quantum dotsin the 1970s, thinking that they mightone day fashion new electronic or opticaldevices. Few of the pioneering investiga-tors had any idea that these objects couldhelp diagnose disease or discover new

drugs. And none of them would havedreamed that the first real-world appli-cations of quantum dots would be in bi-ology and medicine. Making quantumdots that would function properly in bi-ological systems did indeed require yearsof research, but they are now a reality.

The Rainbow CoalitionTHE COMPANY LEADING the pushto commercialize this technology, Quan-tum Dot Corporation, has licensed tech-niques developed in my lab and at theMassachusetts Institute of Technology,Indiana University, Lawrence BerkeleyNational Laboratory and the Universityof Melbourne in Australia. I helped tofound this company, so my assessmentsmay be biased, but I view the prospectsfor quantum dots as, well, bright.

Semiconductor nanocrystals haveseveral advantages over conventional dyemolecules. Small inorganic crystals canwithstand significantly more cycles of ex-citation and light emission than can typ-ical organic molecules, which soon de-compose. And this stability allows inves-tigators to track the goings-on in cellsand tissues for longer intervals than cannow be achieved. But the greatest benefitsemiconductor nanocrystals offer is lesssubtle—they come in more colors.

Biological systems are very complex,and frequently several components mustbe observed simultaneously. Such track-ing is difficult to achieve, because eachorganic dye must be excited with a dif-ferent wavelength of light. But quantumdots make it possible to tag a variety ofbiological molecules, each with a crystalof a different size (and hence color). Andbecause all of these crystals can be ener-gized with a single light source, they canall be monitored at once.

This approach is being pursued ac-tively, but quantum dots offer even moreinteresting possibilities. Imagine a smalllatex bead filled with a combination ofquantum dots. The bead could, for in-

stance, contain five different sizes of dots,or five colors, in a variety of concentra-tions. After the bead is illuminated, it willgive off light, which when spread out bya prism will produce five distinct spectrallines with prescribed intensities—a spec-tral bar code, if you like. Such beads al-low for an enormous number of distinctlabels (billions, potentially), each ofwhich could be attached, say, to DNAmolecules composed of different se-quences of genetic building blocks.

With these kinds of beads, technicianscould easily compare the genetic materi-al in a sample against a library of knownDNA sequences, as might be done if aninvestigator wanted to find out whichgenes were active in certain cells or tis-sues. They would simply expose the sam-ple to the full beaded library and read thespectral bar codes of the library DNAsthat bind to sequences in the sample. Be-cause binding takes place only when ge-netic sequences match closely (or moreprecisely, when one sequence comple-ments the other), the results would im-mediately reveal the nature of the genet-ic material in the sample.

Semiconductor quantum dots shouldsoon serve biomedical researchers in thisway, but they are not the only nano-structures useful for optically sensing thegenetic composition of biological speci-mens. Another example emerges fromthe work of Chad A. Mirkin and RobertL. Letsinger of Northwestern University,who recently developed an ingeniousmethod to test for the presence of a spe-cific genetic sequence in solution. Theirscheme employs 13-nanometer gold par-ticles studded with DNA.

The trick here is to use two sets ofgold particles. The first set carries DNAthat binds to one half of the target se-quence; the second set carries DNA thatbinds to the other half. DNA with thecomplete target sequence readily attach-es to both types of particles, linking themtogether. Because each particle has mul-


For therapy, one might encapsulate drugs within nanometer-scale packages that control the

medicines’ release in sophisticated ways.

LATEX BEADS filled with quantum dots of single

colors glow at nearly the same wavelengths as

the dots themselves. Researchers have also

loaded selections of different dots into single

beads. Their aim is to create a huge variety of

distinct labels for biological tests. (See also “Nano

Bar Codes” in the box on the opposite page.)



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GOLD PARTICLESGold nanoparticles studded with short segments of DNA couldform the basis of an easy-to-read test for the presence of a genetic sequence (black) in a sample under study. DNAcomplementary to half of such a sequence (red) is attached to one set of particles in solution, and DNA complementary to theother half (blue) is attached to a second set of particles. If the sequence of interest is present in the sample, it will bind to the DNA tentacles on both sets of spheres, trapping the balls in a dense web. This agglomeration will cause the solution tochange color ( from red to blue).

NANO BAR CODESLatex beads filled with several colors of nanoscale semiconductorsknown as quantum dots can potentially serve as unique labels forany number of different probes. In response to light, the beadswould identify themselves (and, thus, their linked probes) byemitting light that separates into a distinctive spectrum of colorsand intensities—a kind of spectral bar code.

CLEVER CANTILEVERSBiological samples can be screened for the presence ofparticular genetic sequences using small beams (cantilevers)of the type employed in atomic force microscopes. The surfaceof each cantilever is coated with DNA able to bind to oneparticular target sequence. A sample is then applied to thebeams. Binding induces a surface stress, which bends theaffected beams by nanometers—not much, but enough to revealthat the bent beams found their specific targets in a sample.

BIO-NANOTECH IN ACTION

The items here could one day enhance the speed and power of biomedical tests, such as those used to

screen small samples of material for the presence of particular genetic sequences. For clarity, the imageshave not been drawn to scale.

MAGNETIC TAGSMany tests reveal the presence of a molecule or disease-causing organism by detecting the binding of an antibody tothat target. When antibodies labeled with magnetic nano-particles bind to their target on a surface (foreground), briefexposure to a magnetic field causes these probes collectively to give off a strong magnetic signal. Meanwhile unbound anti-bodies tumble about in all directions, producing no net signal.This last property makes it possible to read the results withoutfirst washing away any probes that fail to find their target.

MAGNETICNANOPARTICLES

ANTIBODY BOUND TO TARGET

DIRECTION OFMAGNETIZATION

PROBE DNA

GOLD NANOPARTICLE

QUANTUM DOTS

BEADPROBE

DNA

BENT CANTILEVER

DNAFROM

SAMPLE

TARGET DNA

ANTIBODY


tiple DNA tentacles, bits of genetic ma-terial carrying the target sequence canglue many particles together. And whenthese gold specks aggregate, their opticalproperties shift markedly, changing thetest solution from red to blue. Becausethe outcome of the test is easy to seewithout any instrumentation at all, sucha system might be particularly useful forhome DNA testing.

Feeling the ForceNO DISCUSSION of bio-nanotechnol-ogy would be complete without at leasta brief mention of one of the hottest in-struments in science today—the atomicforce microscope. Such devices probematerials in the same way an old-fash-ioned phonograph reads the grooves in arecord: by dragging a sharp point overthe surface and detecting the resulting de-flections. The tip of an atomic force mi-croscope is, however, much finer than aphonograph needle, so it can sense farsmaller structures. Regrettably, fabricat-ing tips that are both fine and sturdy for

these microscopes has proved to be quitedifficult.

The solution appeared in 1996, whenworkers at Rice University affixed a slen-der carbon nanotube to the tip of anatomic force microscope, making it pos-sible to probe samples just a few nano-meters in size. In 1998 Charles M. Lieberand his co-workers at Harvard Univer-sity applied this approach to probing bio-molecules, providing a very high resolu-tion means to explore complex biologi-cal molecules and their interactions at themost basic level.

But atomic force microscopy maysoon be applied to more than just mak-ing fundamental scientific measurements.Last year James K. Gimzewski, then atthe IBM Zurich Research Laboratory,showed with collaborators at IBM andthe University of Basel that an array ofmicron-scale arms, or cantilevers, muchlike the ones employed in atomic forcemicroscopes, could be used to screensamples for the presence of certain ge-netic sequences. They attached short

strands of DNA to the tops of the can-tilevers. When genetic material carryinga complementary sequence binds to theanchored strands, it induces a surfacestress, which bends the cantilevers sub-tly—by just nanometers—but enough tobe detected. By fabricating devices withmany cantilevers and coating each witha different type of DNA, researchersshould be able to test a biological sam-ple rapidly for the presence of specificgenetic sequences (as is now done rou-tinely with gene chips) by nanomechan-ical means without the need for labeling.

This example, like the others de-scribed earlier, illustrates that the con-nections between nanotechnology andthe practice of medicine are often indi-rect, in that much of the new workpromises only better research tools oraids to diagnosis. But in some cases, nano-objects being developed may themselvesprove useful for therapy. One might, forinstance, encapsulate drugs within nano-meter-scale packages that control themedicines’ release in sophisticated ways.

Consider a class of artificial mole-cules called organic dendrimers. Twodecades ago Donald A. Tomalia of theMichigan Molecular Institute in Mid-land fashioned the first of these intrigu-ing structures. A dendrimer moleculebranches successively from inside to out-side. Its shape resembles what one wouldget by taking many sprigs from a tree andpoking them into a foam ball so that theyshot out in every direction. Dendrimersare globular molecules about the size ofa typical protein, but they do not comeapart or unfold as easily as proteins do,because they are held together withstronger chemical bonds.

Like the lush canopies of maturetrees, dendrimers contain voids. That is,they have an enormous amount of inter-nal surface area. Interestingly, they canbe tailored to have a range of differentcavity sizes—spaces that are just perfectfor holding therapeutic agents. Den-drimers can also be engineered to trans-port DNA into cells for gene therapy,and they might work more safely thanthe other leading method: geneticallymodified viruses.

Other types of nanostructures pos-


Petite Plumbing JobsMicrofluidics enhances biomedical research

Most of the nanotechnologies now being developed for biomedical use take theform of minute objects immersed in comparatively large quantities of fluid, be it

water, blood or a complex experimental concoction. But investigators are alsobuilding devices to manipulate tiny amounts of such liquids. These so-calledmicrofluidic systems pump solutions through narrow channels, controlling the flowwith diminutive valves and intense electric fields.

The ability to handle vanishingly small quantities of a solution in this way allowsbiomedical researchers to carry out many different experiments on what might beonly a modest amount of sample—and to do so in an efficient manner, with hundredsof tests being performed, say, on the surface of a single glass slide. Microfluidicdevices also offer researchers the means to carry out experiments that could nototherwise be done; for example, to deliver test solutions of specific compositions todifferent parts of a cell under study.

Although many of the components being created for these systems areconsiderably larger than a micron, some experimental devices include nanoscaledimensions. Notably, Harold G. Craighead’s team at Cornell University has devisedmethods for sorting different sizes of DNA fragments in water according to how fastthe fragments traverse passages measuring 100 nanometers across or travelthrough microchannels that repeatedly narrow to a depth of 75 to 100 nanometers.These or other nanofluidic devices could potentially increase the speed and reducethe costs of separating DNA molecules for sequencing and could in theory be adaptedfor separating proteins or other molecules. —A.P.A.


sess high surface area, and these too may prove useful for delivering drugswhere they are needed. But dendrimersoffer the greatest degree of control andflexibility. It may be possible to designdendrimers that spontaneously swelland liberate their contents only when the appropriate trigger molecules arepresent. This ability would allow a cus-tom-made dendrimer to release its loadof drugs in just the tissues or organsneeding treatment.

Other drug-delivery vehicles on thehorizon include hollow polymer capsulesunder study by Helmuth Möhwald of theMax Planck Institute of Colloids and In-terfaces in Golm, Germany. In responseto certain signals, these capsules swell orcompress to release drugs. Also intrigu-ing are so-called nanoshells, recently in-vented by the researchers at Rice.

Nanoshells are extremely small beadsof glass coated with gold. They can befashioned to absorb light of almost anywavelength, but nanoshells that captureenergy in the near-infrared are of mostinterest because these wavelengths easilypenetrate several centimeters of tissue.Nanoshells injected into the body cantherefore be heated from the outside us-ing a strong infrared source. Such ananoshell could be made to deliver drugmolecules at specific times by attaching itto a capsule made of a heat-sensitivepolymer. The capsule would release itscontents only when gentle heating of theattached nanoshell caused it to deform.

A more dramatic application envi-sioned for nanoshells is in cancer thera-py. The idea is to link the gold-platedspheres to antibodies that bind specifi-cally to tumor cells. Heating the nano-shells sufficiently would in theory destroythe cancerous cells, while leaving near-by tissue unharmed.

It is, of course, difficult to know forcertain whether nanoshells will ultimate-ly fulfill their promise. The same can besaid for the myriad other minuscule de-vices being developed for medical use—

among them, one-nanometer buckyballsmade from just a few dozen carbonatoms. Yet it seems likely that some ofthe objects being investigated today willbe serving doctors in the near future.

Even more exciting is the prospect thatphysicians will make use of nanoscalebuilding blocks to form larger struc-tures, thereby mimicking the naturalprocesses of biology. Such materialsmight eventually serve to repair dam-aged tissues. Research on these boldstrategies is just beginning, but at leastone enterprise already shows that thenotion has merit: building scaffoldingson which to grow bone. Samuel I. Stuppof Northwestern is pioneering this ap-proach using synthetic molecules thatcombine into fibers to which bone cellshave a strong tendency to adhere.

What other marvels might the futurehold? Although the means to achievethem are far from clear, sober nanotech-

nologists have stated some truly ambi-tious goals. One of the “grand challenges”of the National Nanotechnology Initia-tive is to find ways to detect canceroustumors that are a mere few cells in size.Researchers also hope eventually to de-velop ways to regenerate not just boneor cartilage or skin but also more com-plex organs, using artificial scaffoldingsthat can guide the activity of seeded cellsand can even direct the growth of a va-riety of cell types. Replacing hearts orkidneys or livers in this way might notmatch the fictional technology of Fan-tastic Voyage, but the thought that suchmedical therapies might actually becomeavailable in the not so distant future isstill fantastically exciting.


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Ultrasensitive Magnetic Biosensor for Homogeneous Immunoassay. Y. R. Chemla, H. L. Grossman,Y. Poon, R. McDermott, R. Stevens, M. D. Alper and J. Clarke in Proceedings of the National Academy ofSciences USA, Vol. 97, No. 27, pages 14268–14272; December 19, 2000.

The author’s Web site is at www.cchem.berkeley.edu/~pagrp/

Information on using gold nanoparticles for DNA testing is available atwww.chem.nwu.edu/~mkngrp/dnasubgr.html

Information on nanoshells is available at www.ece.rice.edu/~halas/

Information about quantum dots and their use in biomedicine is available at www.qdots.com


ORGANIC DENDRIMER, shown in an artist’s conception, could be roughly the size of a protein

molecule. Dendrimers harbor many internal cavities and are being eyed as drug-delivery vehicles.


IN 1959 PHYSICIST Richard Feynmangave an after-dinner talk exploring thelimits of miniaturization. He set out fromknown technology (at a time when anadding machine could barely fit in yourpocket), surveyed the limits set by phys-ical law and ended by arguing the possi-bility—even inevitability—of “atom byatom” construction.

What at the time seemed absurdlyambitious, even bizarre, has recently be-come a widely shared goal. Decades oftechnological progress have shrunk mi-croelectronics to the threshold of the mo-lecular scale, while scientific progress atthe molecular level—especially on the

molecular machinery of living systems—

has now made clear to many what wasenvisioned by a sole genius so long ago.

Inspired by molecular biology, stud-ies of advanced nanotechnologies havefocused on bottom-up construction, inwhich molecular machines assemble mo-lecular building blocks to form products,including new molecular machines. Biol-ogy shows us that molecular machinesystems and their products can be madecheaply and in vast quantities.

Stepping beyond the biological anal-ogy, it would be a natural goal to be able

to put every atom in a selected place(where it would serve as part of some ac-tive or structural component) with no ex-tra molecules on the loose to jam theworks. Such a system would not be a liq-uid or gas, as no molecules would moverandomly, nor would it be a solid, inwhich molecules are fixed in place. In-stead this new machine-phase matterwould exhibit the molecular movementseen today only in liquids and gases aswell as the mechanical strength typicallyassociated with solids. Its volume wouldbe filled with active machinery.

The ability to construct objects withmolecular precision will revolutionize

manufacturing, permitting materialsproperties and device performance to begreatly improved. In addition, when aproduction process maintains control ofeach atom, there is no reason to dumptoxic leftovers into the air or water. Im-proved manufacturing would also drivedown the cost of solar cells and energystorage systems, cutting demand for coaland petroleum, further reducing pollu-tion. Such advances raise hope that thosein the developing world will be able toreach First World living standards with-out causing environmental disaster.

Low-cost, lightweight, extremelystrong materials would make transporta-tion far more energy efficient and—final-ly—make space transportation economi-cal. The old dreams of expanding thebiosphere beyond our one vulnerableplanet suddenly look feasible once more.

Perhaps the most exciting goal is the

molecular repair of the human body.Medical nanorobots are envisioned thatcould destroy viruses and cancer cells,repair damaged structures, remove ac-cumulated wastes from the brain andbring the body back to a state of youth-ful health.

Another surprising medical applica-tion would be the eventual ability to re-pair and revive those few pioneers nowin suspended animation (currently re-garded as legally deceased), even thosewho have been preserved using the crudecryogenic storage technology availablesince the 1960s. Today’s vitrificationtechniques—which prevent the forma-

tion of damaging ice crystals—shouldmake repair easier, but even the originalprocess appears to preserve brain struc-ture well enough to enable restoration.

Those researchers most familiar withthe field of molecular nanotechnologysee the technology base underpinningsuch capabilities as perhaps one to threedecades off. At the moment, work fo-cuses on the earliest stages: finding outhow to build larger structures with atom-ic precision, learning to design molecularmachines and identifying intermediategoals with high payoff.

To understand the potential of mo-lecular manufacturing technology, ithelps to look at the macroscale machinesystems used now in industry. Picture arobotic arm that reaches over to a con-veyor belt, picks up a loaded tool, appliesthe tool to a workpiece under construc-tion, replaces the empty tool on the belt,


Machine-Phase NanotechnologyA molecular nanotechnology pioneer predicts that the tiniest robots will revolutionizemanufacturing and transform society

By K. Eric Drexler

K. ERIC DREXLER is chairman of the Foresight

Institute, research fellow of the Institute for

Molecular Manufacturing, and author of Engines

of Creation and Nanosystems: Molecular

Machinery, Manufacturing, and Computation.

NANOVISIONS

In principle, Drexler says, a molecular construction system called an assembler could build almost anything, including copies of itself.

ABOUT THEAUTHOR


picks up the next loaded tool, and soon—as in today’s automated factories.

Now mentally shrink this entire mech-anism, including the conveyor belt, to themolecular level to form an image of ananoscale construction system. Given asufficient variety of tools, this systemwould be a general-purpose building de-vice, nicknamed an assembler. In princi-ple, it could build almost anything, in-cluding copies of itself.

Molecular nanotechnology as a fielddoes not depend on the feasibility of thisparticular proposal—a collection of lessgeneral building devices could carry outthe functions mentioned above. But be-cause the assembler concept is still con-troversial, it’s worth mentioning the ob-jections being raised.

One prominent chemist speaking at arecent event sponsored by the AmericanAssociation for the Advancement of Sci-ence asked how one could power and di-rect an assembler and whether it couldreally break and re-form strong molecu-lar bonds. These are reasonable ques-tions that can be answered only by de-

scribing designs and calculations toobulky to fit in this essay. Fortunately,technical literature providing seeminglyadequate answers has been availablesince at least 1992, when my bookNanosystems was published.

Another well-known chemist objectsthat an assembler would need 10 robot-ic “fingers” to carry out its operationsand that there isn’t room for them all.The need for such a large number of ma-nipulators, however, has never been es-tablished or even seriously argued. Incontrast, the designs that have received(and survived) the most peer review useone tool at a time and grip their toolswithout using any fingers at all.

These examples point to the difficultyof finding appropriate critiques of nano-technology designs. Many researcherswhose work seems relevant are actuallythe wrong experts—they are excellent intheir discipline but have little expertise in

systems engineering. The shortage of mo-lecular systems engineers will probably bea limiting factor in the speed with whichnanotechnology can be developed.

It is important that critiques of nano-technology are well executed, because vi-tal societal decisions depend on them. Ifmolecular nanotechnology as describedhere is correct, policy issues can lookquite different from what is generally ex-pected. Today most people believe thatglobal warming will be hard to correct—with nanotechnology, excess greenhousegases could be inexpensively removedfrom the atmosphere. Current Social Se-curity projections assume increasingnumbers of aged citizens in poor health.With advanced medical nanotechnology,tomorrow’s seniors could be more activeand healthy than they are now, bringingnew meaning to the “golden years.”

Likewise, we need to focus now onavoiding accidents and preventing abuseof this powerful technology. Solid workhas been done on the problem of headingoff major nanotechnology accidents. TheForesight Guidelines, available on theWorld Wide Web, sketch out proposedsafety rules [see below].

But the challenge of preventingabuse—the exploitation of this technol-ogy by aggressive governments, terroristgroups or even individuals for their ownpurposes—still looms large. The closestanalogy to this problem these days is thedifficulty of controlling the proliferationof chemical and biological weapons. Theadvance toward molecular nanotechnol-ogy highlights the urgency in finding ef-fective ways to manage emerging tech-nologies that are powerful, valuable andopen to misuse.


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Engines of Creation: The Coming Era of Nanotechnology. K. E. Drexler. FourthEstate, 1990.

Nanosystems: Molecular Machinery,Manufacturing, and Computation. K. E. Drexler. John Wiley & Sons, 1992.

The Foresight Institute and the ForesightGuidelines: www.foresight.orgRichard Feynman’s lecture “There’s Plenty ofRoom at the Bottom” can be found atwww.zyvex.com/nanotech/feynman.html

MORE TOEXPLORE

NANOSCRIBE K. Eric Drexler conceived the

concept of molecular machine systems

(a component of one is shown in the background).


WHEN A BOY AND A GIRL fall in love, it isoften said that the chemistry betweenthem is good. This common use of theword “chemistry” in human relationscomes close to the subtlety of what actu-ally happens in the more mundane cou-pling of molecules. In a chemical reactionbetween two “consenting” molecules,bonds form between some of the atomsin what is usually a complex dance in-volving motion in multiple dimensions.Not just any two molecules will react.They have to be right for each other. Andif the chemistry is really, really good, themolecules that do react will all producethe exact product desired.

Near the center of the typical chem-ical reaction, the particular atoms thatare going to form the new bonds are notthe only ones that jiggle around: so doall the atoms they are connected to andthe ones connected to these in turn. Allthese atoms must move in a precise wayto ensure that the result of the reactionis the one intended. In an ordinary chem-ical reaction five to 15 atoms near the re-action site engage in an intricate three-di-mensional waltz that is carried out in a

cramped region of space measuring nomore than a nanometer on each side.

In recent years, it has become popu-lar to imagine tiny robots (sometimescalled assemblers) that can manipulateand build things atom by atom. Imaginea single assembler: working furiously,this hypothetical nanorobot would makemany new bonds as it went about its as-signed task, placing perhaps up to a bil-lion new atoms in the desired structureevery second. But as fast as it is, that ratewould be virtually useless in running a nanofactory: generating even a tinyamount of a product would take a soli-tary nanobot millions of years. (Making

a mole of something—say, 30 grams, orabout one ounce—would require at least6 × 1023 bonds, one for each atom. Atthe frenzied rate of 109 per second itwould take this nanobot 6 × 1014 sec-onds—that is, 1013 minutes, which is 6.9× 109 days, or 19 million years.) Al-though such a nanobot assembler wouldbe very interesting scientifically, itwouldn’t be able to make much on itsown in the macroscopic “real” world.

Yet imagine if this one nanobot wereso versatile that it could build anything,as long as it had a supply of the rightkinds of atoms, a source of energy anda set of instructions for exactly what tobuild. We could work out these detailedinstructions with a computer and thenradio them to the nanobot. If the nano-bot could really build anything, it could

certainly build another copy of itself. Itcould therefore self-replicate, much asbiological cells do. After a while, we’dhave a second nanobot and, after a lit-tle more time, four, then eight, then 16and so on.

For fun, suppose that each nanobotconsisted of a billion atoms (109 atoms)in some incredibly elaborate structure. Ifthese nanobots could be assembled at thefull billion-atoms-per-second rate imag-ined earlier, it would take only one sec-ond for each nanobot to make a copy ofitself. The new nanobot clone wouldthen be “turned on” so that it could startits own reproduction. After 60 seconds

of this furious cloning, there would be 260

nanobots, which is the incredibly largenumber of 1 × 1018, or a billion billion.This massive army of nanobots wouldproduce 30 grams of a product in 0.6millisecond, or 50 kilograms per second.Now we’re talking about something verybig indeed!

Nanobots in general may not be ter-ribly interesting as a way of makingprodigious amounts of things, but self-replicating nanobots are really interest-ing. If they are feasible, then the notionof a machine that can build anythingfrom a CD player to a skyscraper in a remarkably short time doesn’t seem sofar-fetched.

But these self-replicating nanobotscan also be quite scary. Who will controlthem? How do we know that some sci-


Of Chemistry,Love and NanobotsHow soon will we see the nanometer-scale robots envisaged by K. Eric Drexler and other molecular nanotechologists? The simple answer is never

By Richard E. Smalley

RICHARD E. SMALLEY is the Gene and Norman

Hackerman Professor of Chemistry and

Physics at Rice University. He received the

1996 Nobel Prize in Chemistry for the

discovery of fullerenes.

ABOUT THEAUTHOR

Manipulator fingers on the hypothetical self-replicating nanobot are not only too fat; they are also too sticky.

Both these problems are fundamental, and neither can be avoided.

NANOFALLACIES


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entist or computer hacker won’t designone that is truly autonomous, carrying acomplete set of instructions for itself?How do we know that these nanobotswon’t mutate and that some of these mu-tants won’t achieve the ability, like can-cer cells, to disregard any signals thatwould otherwise trigger self-destruction?How could we stop them once theyreached this malignant state? Self-repli-cating nanobots would be the equivalentof a new parasitic life-form, and theremight be no way to keep them from ex-panding indefinitely until everything onearth became an undifferentiated mass ofgray goo.

Still more frightening, they would byeither design or random mutation devel-op the ability to communicate with oneanother. Maybe they would form groups,constituting a primitive nervous system.Perhaps they would really become “alive”by any definition of that term. Then, inthe memorable words of Bill Joy, thechief scientist at Sun Microsystems and

someone who has worried in print aboutthe societal implications of proliferatingnanobots, the future simply would notneed us.

But how realistic is this notion of aself-replicating nanobot? Let’s thinkabout it. Atoms are tiny and move in adefined and circumscribed way—a chem-ist would say that they move so as tominimize the free energy of their localsurroundings. The electronic “glue” thatsticks them to one another is not local toeach bond but rather is sensitive to theexact position and identity of all theatoms in the near vicinity. So when thenanomanipulator arm of our nanobotpicks up an atom and goes to insert it inthe desired place, it has a fundamentalproblem. It also has to somehow controlnot only this new atom but all the exist-ing atoms in the region. No problem,you say: our nanobot will have an addi-

tional manipulator arm for each one ofthese atoms. Then it would have com-plete control of all the goings-on that oc-cur at the reaction site.

But remember, this region where thechemistry is to be controlled by the nano-bot is very, very small—about one nano-meter on a side. That constraint leads toat least two basic difficulties. I call onethe fat fingers problem and the other thesticky fingers problem. Because the fin-gers of a manipulator arm must them-selves be made out of atoms, they have acertain irreducible size. There just isn’tenough room in the nanometer-size re-action region to accomodate all the fin-gers of all the manipulators necessary tohave complete control of the chemistry.In a famous 1959 talk that has inspirednanotechnologists everywhere, Nobelphysicist Richard Feynman memorablynoted, “There’s plenty of room at the bot-tom.” But there’s not that much room.

Manipulator fingers on the hypo-thetical self-replicating nanobot are notonly too fat; they are also too sticky: theatoms of the manipulator hands will ad-here to the atom that is being moved. Soit will often be impossible to release thisminuscule building block in precisely theright spot.

Both these problems are fundamen-tal, and neither can be avoided. Self-replicating, mechanical nanobots aresimply not possible in our world. To putevery atom in its place—the vision artic-ulated by some nanotechnologists—

would require magic fingers. Such ananobot will never become more than afuturist’s daydream.

Chemistry is subtle indeed. You don’tmake a girl and a boy fall in love by push-ing them together (although this is oftena step in the right direction). Like thedance of love, chemistry is a waltz withits own step-slide-step in three-quartertime. Wishing that a waltz were a mer-engue—or that we could set down eachatom in just the right place—doesn’tmake it so.

The author’s Web site can be accessed at

cnst.rice.edu/reshome.html

MORE TOEXPLORE

NOBELIST Richard E. Smalley dismisses the

notion of out-of-control nanorobots.



AMONG THE PROMISED FRUITS of nano-technology, small machines have alwaysstood out. Their attraction is straightfor-ward. Large machines—airplanes, sub-marines, robotic welders, toaster ovens—

are unquestionably useful. If one couldtake the same ideas used to design thesedevices and apply them to machines thatwere a tiny fraction of their size, whoknows what they might be able to do?

Imagining two types of small ma-chines—one analogous to an existingmachine, the second entirely new—hascaptured broad attention. The first is ananoscale submarine, with dimensionsof only a few billionths of a meter—the

length of a few tens or hundreds ofatoms. This machine might, so the argu-ment goes, be useful in medicine by nav-igating through the blood, seeking outdiseased cells and destroying them.

The second—the so-called assem-bler—is a more radical idea, originallyproposed by futurist K. Eric Drexler.This machine has no macroscopic ana-logue (a fact that is important in consid-

ering its ultimate practicality). It wouldbe a new type of machine—a universalfabricator. It would make any structure,including itself, by atomic-scale “pick andplace”: a set of nanoscale pincers wouldpick individual atoms from their envi-ronment and place them where theyshould go. The Drexlerian vision imag-ines society transformed forever by smallmachines that could create a television setor a computer in a few hours at essential-ly no cost. It also has a dark side. The po-tential for self-replication of the assemblerhas raised the prospect of what has cometo be called gray goo: myriads of self-replicating nanoassemblers making un-

countable copies of themselves and rav-aging the earth while doing so.

Does the idea of nanoscale machinesmake sense? Could they be made? If so,would they be effectively downsized ver-sions of their familiar, large-scale cousins,or would they operate by different prin-ciples? Might they, in fact, ravage theearth?

We can begin to answer these in-triguing questions by asking a more or-dinary one: What is a machine? Of themany definitions, I choose to take a ma-chine to be “a device for performing atask.” Going further, a machine has a de-sign; it is constructed following someprocess; it uses power; it operates ac-cording to information built into it whenit is fabricated. Although machines are

commonly considered to be the productsof human design and intention, whyshouldn’t a complex molecular systemthat performs a function also be consid-ered a machine, even if it is the productof evolution rather than of design?

Issues of teleology aside, and accept-ing this broad definition, nanoscale ma-chines already do exist, in the form of thefunctional molecular components of liv-ing cells—such as molecules of protein orRNA, aggregates of molecules, and or-ganelles (“little organs”)—in enormousvariety and sophistication. The broadquestion of whether nanoscale machinesexist is thus one that was answered in the

affirmative by biologists many years ago.The question now is: What are the mostinteresting designs to use for future nano-machines? And what, if any, risks wouldthey pose?

Cells include some molecular ma-chines that seem similar to familiar hu-man-scale machines: a rotary motor fixedin the membrane of a bacterium turns ashaft and superficially resembles an elec-tric motor. Others more loosely resemblethe familiar: an assembly of RNA andprotein—the ribosome—makes proteinsby an assembly line–like process. Andsome molecular machines have no obvi-ous analogy in macroscopic machines: aprotein—topoisomerase—unwinds dou-ble-stranded DNA when it becomes tootightly wound. The way in which these

By George M. Whitesides

The charm of the assembler is illusory: it is more appealing as metaphor than as reality, and less the solution

of a problem than the hope for a miracle.

NANOINSPIRATIONS

The Once and Future NanomachineBiology outmatches futurists’ most elaborate fantasies for molecular robots

GEORGE M. WHITESIDES is a professor in the

chemistry department of Harvard University.

This is his third article for Scientific American.

He is grateful to graduate students Kateri Paul

and Abraham Stroock, who made many helpful

suggestions on this essay.

ABOUT THEAUTHOR


organelles are fabricated in the cell—anefficient synthesis of long molecules, com-bined with molecular self-assembly—is amodel for economy and organization,and entirely unlike the brute-force meth-od suggested for the assembler.

And as for ravaging the earth: in asense, collections of biological cells al-ready have ravaged the earth. Before lifeemerged, the planet was very differentfrom the way it is today. Its surface wasmade of inorganic minerals; its atmo-sphere was rich in carbon dioxide. Liferapidly and completely remodeled theplanet: it contaminated the pristine sur-face with microorganisms, plants and or-

ganic materials derived from them; itlargely removed the carbon dioxide fromthe atmosphere and injected enormousquantities of oxygen. Overall, a radicalchange. Cells—self-replicating collectionsof molecular nanomachines—complete-ly transformed the surface and the atmo-sphere of our planet. We do not normal-ly think of this transformation as “rav-aging the planet,” because we thrive inthe present conditions, but an outside ob-server might have thought otherwise.

So the issue is not whether nanoscalemachines can exist—they already do—orwhether they can be important—we of-ten consider ourselves as demonstrations

that they are—but rather where weshould look for new ideas for design.Should we be thinking about the Gener-al Motors assembly line or the interior ofa cell of E. coli? Let’s begin by compar-ing biological nanomachines—especiallythe ultimate self-replicating biologicalsystem, the cell—with nanoscale ma-chines modeled on the large machinesthat now surround us. How does the bi-


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WHIPLIKE TAILS, found on many bacteria, are

propelled by nanomotors. The tiny biochemical

motor turns a rotary shaft that spins the tails, or

flagella, and allows the bacteria, such as these

E. coli, to move through liquid.


ological strategy work, and how wouldit compare with a strategy based on mak-ing nanoscale versions of existing ma-chines, or a new strategy of the type sug-gested by the assembler?

Molecular Copy MachinesTHE CELL is a self-replicating structure.It takes in molecules from its environ-ment, processes some of them for fuel,and reworks others into the pieces it usesto make, maintain, move and defend it-self. DNA stores the information need-ed for fabrication and operation fromone generation to the next. One kind ofRNA (messenger RNA, or mRNA) servesas the temporary transcript of this infor-mation, “telling” ribosomes which pro-tein to make. Membranes provide com-partments that enclose the working parts,house portals that control the flux ofmolecules into and out of the cell, andhold molecules that sense the cell’s envi-ronment. Proteins (often cooperatingwith other molecules) build everything inthe cell and move its parts when theymust be moved.

The strategy adopted by the cell tomake its parts—and thus to replicate andmaintain itself—is based on two ideas.The first is to use a single, conceptually

straightforward chemical process—poly-merization—to create large, linear mol-ecules. The second is to build moleculesthat spontaneously fold themselves intofunctional, three-dimensional structures.This two-part strategy does not require adifficult and sophisticated three-dimen-sional pick-and-place fabrication: it sim-ply strings beads (for example, aminoacids) together into a necklace (a poly-peptide) and lets the necklace self-assem-ble into a machine (a protein). Thus, theinformation for the final, functional,three-dimensional structure is coded inthe sequence of the beads. The three mostimportant classes of molecules in thecell—DNA, RNA and proteins—are allmade by this strategy; the proteins thenmake the other molecules in the cell. Inmany instances proteins also sponta-neously associate with other molecules—

proteins, nucleic acids, small molecules—

to form larger functional structures. As astrategy for building complex, three-di-mensional structures, this method of lin-ear synthesis followed by various levelsof molecular self-assembly is probablyunbeatable for its efficiency.

The cell is, in essence, a collection ofcatalysts (molecules that cause chemicalreactions to occur without themselves

being consumed) and other functionalspecies—sensors, structural elements,pumps, motors. Most of the nanoma-chines in the cell are thus, ultimately, mo-lecular catalysts. These catalysts do mostof the work of the cell: they form thelipids (fats, for instance) that in turn self-assemble into the flexible sheet that en-closes the cell; they make the molecularcomponents necessary for self-replica-tion; they produce the power for the celland regulate its power consumption;they build archival and working infor-mation storage; and they maintain the in-terior environment within the proper op-erating parameters.

Among the many marvelous molecu-lar machines employed by the cell, fourare favorites of mine. The ribosome,made of ribosomal RNA (rRNA) andprotein, is a key: it stands at the junctionbetween information and action—be-tween nucleic acids and proteins. It is anextraordinarily sophisticated machinethat takes the information present inmRNA and uses it to build proteins.

The chloroplast, present in plant cellsand algae, is a large structure that con-tains arrays of molecules that act astuned optical antennas, collect photonsfrom sunlight and employ them to gen-erate chemical fuel that can be stored inthe cell to power its many operations.The chloroplast, incidentally, also con-verts water to the oxygen that so conta-minated the atmosphere when life firstemerged: the stuff on which our lives de-pend was originally a waste product ofcellular light-harvesting!

The mitochondrion is the power sta-tion: it carries out controlled combustionof organic molecules present in the cell—typically glucose—and generates powerfor the system. Instead of pumping elec-trons through wires to run electric mo-tors, it generates molecules of ATP thatmove through the cell by diffusion andthat are essential contributors to manybiological reactions.

The flagellar motor of bacteria is aspecialized but particularly interestingnanomachine, because it seems so simi-lar to human-scale motors. The flagellarmotor is a highly structured aggregate ofproteins anchored in the membrane of


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STANDARD-ISSUE electric motor bears a superficial—albeit striking—resemblance to the

biochemical rotary motor (top right) that turns the flagella in a bacterium.

A TALE OF TWO MOTORS


many bacterial cells that provides the ro-tary motion that turns the flagella—thelong whiplike structures that act as thepropeller for these cells and allow themto propel themselves through water. Ithas a shaft, like an electric motor, and astructure around the shaft, like the ar-

mature of a motor. The similarity be-tween flagellar and electrical motors is,however, largely illusory. The flagellarmotor does not act by using electric cur-rent to generate moving magnetic fields;instead it uses the decomposition of ATPto cause changes in the shape of the mol-ecules that, when combined with a so-phisticated molecular ratchet, make theprotein shaft revolve.

Nanomachines That MimicHuman-Scale MachinesCAN WE EVER APPROACH the ele-gant efficiency of cellular nanomachinesby creating tiny cousins of the larger ma-chines we have invented? Microfabrica-tion has developed as an extraordinarilysuccessful technology for manufacturingsmall, electronically functional devices—

transistors and the other components ofchips. Application of these techniques tosimple types of machines with movingparts—mechanical oscillators and mov-able mirrors—has been technically suc-cessful. The development of these so-called microelectromechanical systems(MEMS) is proceeding rapidly, but thefunctions of the machines are still ele-mentary, and they are micro, not nano,machines. The first true nanoscale MEMS(NEMS, or nanoelectromechanical sys-tems) have been built only in the past fewyears and only experimentally [see “Plen-ty of Room, Indeed,” on page 48].

Many interesting problems plaguethe fabrication of nanodevices with mov-ing parts. A crucial one is friction andsticking (sometimes combined in talkingabout small devices in the term “stic-tion”). Because small devices have very

large ratios of surface to volume, surfaceeffects—both good and bad—becomemuch more important for them than forlarge devices. Some of these types ofproblems will eventually be resolved if itis worthwhile to do so, but they providedifficult technical challenges now. We

will undoubtedly progress toward morecomplex micromachines and nanoma-chines modeled on human-scale ma-chines, but we have a long path to travelbefore we can produce nanomechanicaldevices in quantity for any practical pur-pose. Nor is there any reason to assumethat nanomachines must resemble hu-man-scale machines.

Could these systems self-replicate? Atpresent, we do not know how to buildself-replicating machines of any size ortype. We know, from recent biologicalstudies, something about the minimumlevel of complexity in a living cell thatwill sustain self-replication: a system ofsome 300 genes is sufficient for self-repli-cation. We have little sense for how totranslate this number into mechanicalmachines of the types more familiar tous, and no sense of how to design a self-sustaining, self-replicating system of ma-chines. We have barely taken the firststeps toward self-replication in nonbio-logical systems [see “Go Forth and Repli-cate,” by Moshe Sipper and James A.Reggia; Scientific American, August].

And other problems cast long shad-ows. Where is the power to come fromfor an autonomous nanomachine? Thereare no electric sockets at the nanoscale.The cell uses chemical reactions of specif-ic compounds to enable it to go about itsbusiness; a corresponding strategy fornanoscale machines remains to be devel-oped. How would a self-replicating nano-machine store and use information? Biol-ogy has demonstrated a strategy based onDNA, so it can be done, but if one want-ed a different strategy, it is not clear whereto start.

The assembler, with its pick-and-place pincers, eliminates the many diffi-culties of fabricating nanomachines andof self-replication by ignoring them:positing a machine that can make anycomposition and any structure by simplyplacing atoms one at a time dismisses the

most vexing aspects of fabrication. Theassembler seems, however, from the van-tage of a chemist, to be unworkable.Consider just two of the constraints.

First is the pincers, or jaws, of the as-sembler. If they are to pick up atoms withany dexterity, they should be smallerthan the atoms. But the jaws must bebuilt of atoms and are thus larger thanthe atom they must pick and place.(Imagine trying to build a fine watch withyour fingers, unaided by tools.) Second isthe nature of atoms. Atoms, especiallycarbon atoms, bond strongly to theirneighbors. Substantial energy would beneeded to pull an atom from its place (aproblem for the energy supply) and sub-stantial energy released when it is put inplace (a problem of cooling). More im-portant, a carbon atom forms bondswith almost everything. It is difficult toimagine how the jaws of the assemblerwould be built so that, in pulling theatoms away from their starting material,they would not stick. (Imagine trying tobuild your watch with parts salvagedfrom another watch in which all theparts were coated with a particularlysticky glue: if you could separate thepieces at all, they would stick to your fin-gers.) Problems with the assembler arealso discussed by Richard E. Smalley inhis essay on page 76.

Would a nanosubmarine work if itcould be built? A human-scale subma-rine moves easily in water by a combina-tion of a rotating propeller—which, inspinning, forces the water backward andthe submarine forward—and movableplanes that guide its direction. Bacteriathat swim actually use structures—fla-


Considering the many constraints on the construction and operation of nanomachines, it seems that new systems for building them might ultimately look much like the ancient systems of biology.


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gella—that look more like flexible spiralsor whips but serve a function similar to apropeller. They typically do not steer avery purposeful path but rather dashabout, with motion that, if all goes well,tends in the general direction of a sourceof food. For nanoscale objects, even ifone could fabricate a propeller, a newand serious problem would emerge: ran-dom battering by water molecules.

These water molecules would besmaller than a nanosubmarine but notmuch smaller, and their thermal motionis rapid on the nanoscale. Collisionswith them make a nanoscale objectbounce about rapidly (a process calledBrownian motion) but in random direc-tions: any effort to steer a purposefulcourse would be frustrated by the re-lentless collisions with rapidly movingwater molecules. Navigators on thenanoscale would have to accommodateto the Brownian storms that wouldcrash against their hulls. For ships of ap-proximately 100 nanometers in scale,the destination of most voyages wouldbe left to chance, because the tiny craftwould probably be impossible to steer,at least in a sense familiar to a sub-mariner. Cells in the bloodstream—ob-jects 10 or 100 times more massive thana nanosubmarine—do not guide them-selves in it: they simply tumble alongwith it. At best, a nanosubmarine mighthope to select a general direction but nota specific destination. Regardless ofwhether one could make or steer devicesat the nanoscale, they would not workfor the sophisticated tasks required todetect disease if one could make them.

Parts of the “little submarine” strat-egy for detecting and destroying diseasedcells in the body, such as cancer cells,would have to focus on finding theirprey. In doing so, they would probablyhave to mimic aspects of the immune sys-tem now functioning in us. The recogni-tion of a cell as “normal” or “pathogen”or “cancer” is an extraordinarily com-plex process—one that requires the fullpanoply of our immune system, includ-ing the many billions of specialized cellsthat constitute it. No simple markers onthe outside of most cancer cells flag themas dangerous. In many of their charac-

teristics, they are not enormously differ-ent from normal cells. A little submarinethat was to be a hunter-killer for cancercells would have to carry on board a lit-tle diagnostic laboratory, and becausethat laboratory would require samplingdevices and reagents and reaction cham-bers and analytical devices, it wouldcease to be little. Operating this devicewould also require energy. The cells ofthe immune system use the same nutri-ents as do other cells; a little submarinewould probably have to do the same.

Outdesigning EvolutionSMALL MACHINES will eventually bemade, but the strategy used to makethem, and the purposes they will serve,remain to be devised. Biology providesone brilliantly developed set of exam-ples: in living systems, nanomachines doexist, and they do perform extraordinar-ily sophisticated functions. What is strik-ing is how different the strategies used inthese nanometer-scale machines are fromthose used in human-scale machines.

In thinking about how best to makenanomachines, we come up against twolimiting strategies. The first is to take ex-isting nanomachines—those present inthe cell—and learn from them. We will

undoubtedly be able to extract fromthese systems concepts and principlesthat will enable us to make variants ofthem that will serve our purposes, andothers that will have entirely new func-tions. Genetic engineering is already pro-ceeding down this path, and the devel-opment of new types of chemistry mayenable us to use biological principles inmolecular systems that are not proteinsand nucleic acids.

The second is to start from scratchand independently to develop funda-mental new types of nanosystems. Biol-ogy has produced one practical meansfor fabrication and synthesis of func-tional nanomachines, and there is no rea-son to believe that there cannot be oth-ers. But this path will be arduous. Look-ing at the machines that surround us andexpecting to be able to build nanoscaleversions of them using processes analo-gous to those employed on a large scalewill usually not be practical and in manycases impossible. Machining and weld-ing do not have counterparts at nano-meter sizes. Nor do processes such asmoving in a straight line through a fluidor generating magnetic fields with elec-tromagnets. Techniques devised to man-ufacture electronic devices will certainly


RIBOSOME reads along a strand of RNA ( purple) to get instructions for stringing together the amino

acids that constitute a protein (gold). This assembly-line process brings to mind the robotic welders

in an automotive factory (opposite page).


be able to make some simple types of me-chanical nanodevices, but they will belimited in what they can do.

The dream of the assembler holds se-ductive charm in that it appears to cir-cumvent these myriad difficulties. Thischarm is illusory: it is more appealing asmetaphor than as reality, and less the so-lution of a problem than the hope for amiracle. Considering the many constraintson the construction and operation ofnanomachines, it seems that new systemsfor building them might ultimately look

much like the ancient systems of biology.It will be a marvelous challenge to see ifwe can outdesign evolution. It would bea staggering accomplishment to mimicthe simplest living cell.

Are biological nanomachines, then,the end of the line? Are they the mosthighly optimized structures that can ex-ist, and has evolution sorted through allpossibilities to arrive at the best one? Wehave no general answer to this question.Jeremy R. Knowles of Harvard Universi-ty has established that one enzyme—

triose phosphate isomerase, or TIM—is“perfect”: that is, no catalyst for the par-

ticular reaction catalyzed by this enzymecould be better. For most enzymes, andall structures more complicated than en-zymes, we have made no effort to dis-cover the alternatives.

Biological structures work in water,and most work only in a narrow range oftemperatures and concentrations of salts.They do not, in general, conduct elec-tricity well (although some, such as thechloroplast and the mitochondrion,move electrons around with great so-phistication). They do not carry out bi-

nary computation and communications.They are not particularly robust me-chanically. Thus, a great many types offunction must be invented if nanoma-chines are to succeed in nonbiologicalenvironments.

And what have we learned from allthis about the doomsday scenario of graygoo? If a hazard were to arise from nano-machines, it would lie in a capability forself-replication. To be self-replicating, asystem must contain all the informationit needs to make itself and must be able tocollect from its environment all the mate-rials necessary both for energy and for

fabrication. It must also be able to manu-facture and assemble (or allow to assem-ble) all the pieces needed to make a copyof itself. Biology has solved all these prob-lems, and self-replicating biological sys-tems—from pathogenic bacteria to can-cer cells—are a danger to us. In comput-er systems, self-replicating strings of bits(computer viruses), although not materi-al objects, are also at least a great nui-sance, but only indirectly a danger, to us.

If a new system—any system—wereable to replicate itself using materialspresent in the environment, it would because for concern. But we now knowenough to realize how far we are from re-producing self-replication in a nonbio-logical system. Fabrication based on theassembler is not, in my opinion, a work-able strategy and thus not a concern. Forthe foreseeable future, we have nothingto fear from gray goo. If robust self-repli-cating micro (or perhaps nano) struc-tures were ultimately to emerge, theywould probably be chemical systems ascomplex as primitive bacteria. Any suchsystem would be both an incredible ac-complishment and a cause for careful as-sessment. Any threat will not be from as-semblers gone amok but from currentlyunimaginable systems of self-catalyzingreactions.

So biology and chemistry, not a me-

chanical engineering textbook, point inthe direction we should look for an-swers—and it is also where our fearsabout organisms or devices that multiplyuncontrollably are most justified. Inthinking about self-replication, and aboutthe characteristics of systems that makethem “alive,” one should start with biol-ogy, which offers a cornucopia of designsand strategies that have been successfulat the highest levels of sophistication. Intackling a difficult subject, it is sensible tostart by studying at the feet of an accom-plished master. Even if they are flagella,not feet.


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MOLECULAR MANUFACTURING—the headynotion of assembling almost anything,from computers to caviar, from individ-ual molecules—would change the world,if someone could just find a way to makeit work. Imagine nanoassemblers: busywork gangs of “pick and place” roboticmanipulator arms, each one tens ofnanometers in size. Controlled from onhigh by a powerful computer, these sim-ple devices would arrange blocks of mol-ecules to make copies of themselves—

and these machines would, in turn, buildstill other nanomachines, which, in turn,would create others, and so on in an ex-ponential expansion. These nanobotconstruction crews could then be direct-ed to accomplish astonishing tasks suchas curing diseases from inside the bodyand fabricating intricately engineeredmaterials from basic bulk feedstocks atextraordinarily low cost.

For years, futurist K. Eric Drexler andhis colleague Ralph C. Merkle, the notedcryptographer, nurtured this vision, usingcomputer simulations of nanometer-scalegears, pumps and other molecular ma-chine subsystems. In these images, col-ored spheres indicate the position of eachcomponent atom. Several analytical cri-tiques of these elaborate simulations sug-gested that the devices simply wouldn’twork as hoped. But perhaps the most bit-ing criticism focused on their status asmere digital representations and not real-world objects interacting with complexchemical bonding forces in the nanoscaleenvironment, where macroscale physicsdoesn’t always apply and quantum me-chanics often prevails.

Then, in 1999, Merkle decided toleave a long-term position at the XeroxPalo Alto Research Center to try to give

real substance to his computer-concoct-ed concepts. He joined software mogulJames R. Von Ehr II, an admirer ofDrexler’s ideas, who had decided tospend part of the “low-nine-figure” for-tune he garnered from the sale of hiscompany, Altsys, to start the first “mo-lecular nanotechnology” company.

Zyvex, the Richardson, Tex.–basedcompany Von Ehr founded, is aiminghigh. “We’d love to be the Applied Ma-terials for the manufacturing base of theworld,” he says, referring to the world’sleading semiconductor equipment man-ufacturer. But his molecular nanotech-nology company is still in the early stages

of its quest. Its experience has alreadydemonstrated the difficulty of movingfrom software-wrought molecular ma-chines to a real-world nanoassembler.One of the first things the company hadto do was to pull back from the idea ofbuilding things atom by atom. Today thelong-term focus is on fabricating nano-scale machine systems from large mole-cules or blocks of molecules. To that end,company scientists are experimentingwith the bottom-up approach to makingassemblers with molecular nanotechnol-

By Steven Ashley

TOP-DOWN FABRICATION is one pathway Zyvex

is taking toward molecular manufacturing.

Nanobot Construction CrewsNanotechnology visionaries find out how difficult it is to develop minuscule robots that can treatdiseases or perform pollution-free manufacturing

NANOROBOTICS


ogy—learning to put together structuresmolecule by molecule using atomic forcemicroscopes and the like.

In the near term, Zyvex researchersare developing microelectromechanicalsystems (MEMS), whose structures mea-sure in tens of microns. MEMS devicesare manufactured using a top-down ap-proach. They are lithographically pat-terned and etched out from silicon sub-strates or other materials.

Richard Feynman, the ur-guru of thefield, did say that bigger machines couldbe used to make smaller machines. Andthat’s where MEMS comes in. Accord-ing to Merkle, MEMS fabrication meth-ods can be used to build robotic assem-bly arms. These microelectromechanical“hands” can assemble submicron handsthat can build even tinier hands, and soforth, step by step until the ultimate inmechanical smallness is achieved: thenanoassembler, a nanometer-scale man-ufacturing device. For Zyvex to accom-plish its goal, the MEMS robots that itcreates must be shrunk by a factor of1,000 or so. Once the requisite down-sizing has been completed, nanobots, asenvisaged, will be used for “atomicallyprecise manufacturing” to make virtual-ly anything. Universal constructors couldmanufacture a Rolex watch, followedby a computer memory and then bynanomachines that can treat diseases.

Two basic ideas underlie Zyvex’sroad to nanorobotics, Merkle says. Inpositional assembly, mechanical manip-ulators pick up and precisely place ob-jects into assemblies. Accurate position-al control at scales of tens of nanometersmeans moving large molecules or blocksof molecules where you want them andcausing them to bond to an assembly asdesired.

A machine that can build a complexmaterial or device from the bottom up—

using an Erector set of molecules orchunks of molecules for components—

will require one other critical technolo-gy: the machine must be able to make acopy of itself. “If you wish to achieveeconomical production of molecular de-vices in large numbers, some form of self-replication is necessary,” Merkle explains.And unless you had hordes of nano-

constructors on the job, building macro-scale objects molecule by moleculewould take a very long time. Zyvex re-searchers note that a fully self-replicatingmachine would not be necessary to man-ufacture an assembler. Still, the task is amonumental one: any machine outsidethe biological sphere that could makeany number of copies of itself wouldprobably lead to a NobelPrize, possibly several.

So how does Zyvex getto an assembler? RecentlyZyvex joined with Stan-dard MEMS in Burling-ton, Mass.—a companythat fabricates microsys-tems—in a two-year col-laborative program to develop litho-graphically formed micron-scale manip-ulator arms and grippers that can as-semble smaller manufacturing devicesfrom pallets of precisely positioned “ac-tive” parts produced on silicon wafers. “Ifthe positional accuracy is good enough,the arm simply has to reach down andpick the part up. You don’t need an elab-orate sensing system,” Merkle says.

According to Von Ehr, Zyvex re-searchers have developed a method bywhich the MEMS manipulator can de-tach the parts from the substrate so theyare ready for microassembly using self-centering snap-connectors—a useful, ifnot exactly new, capability. Manipulatorparts would be created lithographically,etched out and then disconnected fromthe surface substrate so they could bepicked up by the MEMS manipulatorand attached to the device by snappingthem into place. Von Ehr hopes theseMEMS manipulators will prove to be anintermediate technology that could serveas a moneymaking product, such as a de-vice to align a fiber-optic cable, as thecompany pursues its goals.

Unfortunately, it’s hard to find any-one in the MEMS field who would be in-terested in this kind of technology or any-one who can contemplate what kind ofproduct it would actually be used tobuild, says Kaigham J. Gabriel, now pro-fessor of electrical and computer engi-neering and robotics at Carnegie MellonUniversity and former director of the

MEMS program at the Defense Ad-vanced Research Projects Agency.

And what about the nanoscale as-sembler? “There is significant contro-versy about how long it will take toachieve ultimate control at the molecu-lar level,” Merkle notes, adding that “itcould take a decade or two.”

So Zyvex has its work cut out for it.But it has embarked on a mission to achieve thenanoequivalent of a moonshot in relative isolationwith a staff of only 37. Ingeneral, the scientific re-search community hasdistanced itself from thisproject. Several scientists

working in the field of nanotechnologyderided Zyvex’s scheme but requestedanonymity to avoid protests from ama-teur nanotech enthusiasts. Says one re-searcher, “We’ve seen no experimentalproof that any portion of their schemecan actually be accomplished. We thinkit’s a lot of nonsense.” Merkle respondsthat “nothing we propose contradictsthe laws of physics.”

Meanwhile, with Von Ehr’s fortunebacking up the research effort, Zyvex cancontinue to function for many years with-out having to market a product, but theentrepreneur allows that it would be niceto make some money. “This whole thingis a lot harder than it first seemed,” he ad-mits. Von Ehr has reportedly alreadyspent about $20 million on the project,but considering last year’s stock marketfall and the reality of the task looming onthe horizon, he says he is planning to seekoutside investment once financial condi-tions improve. “If we’re going to grow,”he says, “we’ll need more money.”

No matter how big the envisionedpayoff, however, given the dauntingtechnical difficulties and a 10- to 20-yeartimeline to possible success, one won-ders just who would be willing to put upsignificant investment funds. PerhapsZyvex’s trek toward molecular nanotechcould be financed by small contributionsfrom its legions of true believers.

Steven Ashley is a staff editor andwriter.

w w w . s c i a m . c o m S C I E N T I F I C A M E R I C A N 85Copyright 2001 Scientific American, Inc.


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“READING DREXLER’S Engines of Cre-ation in 1990 went into the making ofthe world in Queen City Jazz, my firstnovel, though the book drew from manyother sources: Shakers, ragtime, jazz,American literature, even Krazy Kat.” Sowrites Kathleen Ann Goonan in the Sum-mer 2001 SFWA Bulletin, the quarterlyof the Science Fiction and Fantasy Writ-ers of America, in a brief essay about heraward-nominated novel Crescent CityRhapsody, the third book of her musi-cally structured Nanotech Quartet.

Unsurprisingly, Goonan is far fromthe only science-fiction writer to take in-spiration from K. Eric Drexler’s visionof molecular nanotechnology, for it is avision that connects to numerous preex-isting themes of science fiction and offerswriters an extraordinarily broad paletteof capabilities, all imbued with the ap-pearance of scientific plausibility. Tout-

ed by its proponents to be upon us with-in a decade or few, nanotechnology alsogives science-fiction writers a chance toengage in the art of predicting and warn-ing about possible futures. This role asan ad hoc think tank is one that innu-merable science-fiction writers and fanstake on enthusiastically, not only in theirfiction but also in endless earnest paneldiscussions at conventions, in onlinenewsgroups and discussion boards, andin articles labeled (sometimes optimisti-cally) nonfiction. It is the culture of theintensely technophilic—even those whowrite of techno-dystopias and apoca-lypses are enrapt in a love-hate relation-ship with science and technology. Theborders between four dominions—thoseof scientists, writers, readers and science-fiction fans—are hopelessly blurred,with countless individuals holding jointcitizenships.

But it would be a mistake to thinkthat science fiction’s central role is one ofserious prognostication. The question“What if . . .?” lies at the heart of sciencefiction, but what comes after the ellipsisand the answers that stories give are ulti-mately not science but literature—thatstrange mix of entertainment and mean-ingful enrichment of life. The art of anyfiction writer is the art of the storyteller.As Kathryn Cramer (writer and anthol-ogist and daughter of physicist and fic-tion writer John G. Cramer) writes inThe Ascent of Wonder:

The majority of science fiction storiesare not plausible extrapolations uponour current situation, using available in-formation; rather they are Escheresqueimpossible objects which use the princi-ples of science in much the same way

that Escher used rules of geometric sym-metry—the rules give form to the im-possible imaginative content.

Antediluvian NanotechMANY OF DREXLER’S imaginings haveantecedents in science fiction and feedinto old potent themes of the genre. Sci-ence fiction has long been fascinated withmachines in general, such as in the storiesof Jules Verne. The absolute control ofmatter promised by nanomachines is avariant of the dream that Homo sapienscan achieve complete mastery over natureand has utter freedom to shape its owndestiny. The dark vision of nanobots run-ning amok is a new wrinkle on the oldgolem/Frankenstein myth, the dangers ofmeddling with godlike powers or bring-ing too much hubris to science. Thebright vision of the world, and indeed thenature of humanity, being transformedinto something transcendent and new isanother science-fiction standby.

Nanotech burst into the collectiveconsciousness of technology aficionadosat a good time to interface neatly withthe mid-1980s wave of cyberpunk sto-ries, in which characters experience thecompletely programmable virtual reali-ties of cyberspace. With full-scale mo-lecular nanotech it is not just virtual re-ality that is programmable. The intelli-gent agents and viruses of cyberspacebecome free to roam about in the air thatwe breathe and within our bodies—a cu-rious inversion of people loading theirconsciousnesses into machines.

Shamans of SmallLike interstellar travel, time machines and cyberspace, nanotechnology has become one of the core plot devices on which science-fiction writers draw

By Graham P. Collins

QUEEN CITY JAZZ. Kathleen Ann Goonan.

Tor, 1994.

CRESCENT CITY RHAPSODY. Kathleen Ann

Goonan. Avon Eos, 2000.

FANTASTIC VOYAGE: MICROCOSM. Kevin

J. Anderson. Onyx Books, 2001.

MICROCOSMIC GOD: THE COMPLETE STORIES

OF THEODORE STURGEON, Vol. 2. Theodore

Sturgeon. Edited by Paul Williams. North

Atlantic Books, 1995.

BLOOD MUSIC. Greg Bear. Arbor House, 1985.

NANOWARE TIME. Ian Watson. Tor, 1991.

QUEEN OF ANGELS. Greg Bear. Warner Books,

1990.

/ [SLANT]. Greg Bear. Tor, 1997.

THE DIAMOND AGE. Neal Stephenson.

Bantam, 1995.

NANOTITLESDISCUSSED

MICROSCOPIC CRAFT, built using nanotech,

battle foreign invaders the way an immune

system does. Even the implant-enhanced eye

sees only a fog sparkling with laser light.

NANOFICTION


Elements suggestive of now commonnanotech themes appeared in science fic-tion well before the advent of the term“nanotech.” The concept of microscop-ic surgery appeared in the 1966 movieFantastic Voyage, novelized by Isaac Asi-mov. Of course, instead of using molec-ular machinery built of real atoms, alarge scientific-looking contraption mag-ically reduces people and machinery tomicroscopic scale by shrinking their veryatoms, in violation of numerous physicalprinciples. Interestingly, the 2001 novelFantastic Voyage: Microcosm, by KevinJ. Anderson, uses the miniaturizationtechnology of Fantastic Voyage to ex-

plore the dormant body of an alien froma shot-down UFO. Lo and behold, theLilliputian explorers find themselves con-fronting alien nanotechnology.

Progenitors of nanotech fiction ex-tend back even further. In the classic 1941story by Theodore Sturgeon, “Microcos-mic God,” a scientist creates a society ofminiature creatures (“Neoterics”) thatevolve at a rapid pace and produce tech-nological wonders. This theme is pickedup in a modern way in Blood Music, byGreg Bear, first published as a novelettein the magazine Analog in 1983 and ex-panded into a novel in 1985. Despitepredating the popularization of nano-tech, Blood Music is frequently cited asa seminal nanotech story and includedin nanotech anthologies. In the story, aresearcher creates intelligent cells, “no-ocytes,” that escape from confinementand spread like an epidemic through hu-manity, destroying it but also seeminglybringing about a transcendental changeto a new form of existence. It’s the endof the world as we know it, but we’ll allfeel fine afterward.

Television has also picked up on Stur-geon’s concept. In the 1996 Halloweenepisode of The Simpsons, Lisa acciden-tally creates a microscopic society (ingre-dients: a tooth, Coca-Cola and an electricshock delivered by Bart) that rapidly ad-vances from the Stone Age through theRenaissance and then far beyond ourown technology. The theme is combinedmore soberly with the modern concept ofnanotech in the episode “Evolution” ofStar Trek: The Next Generation, whichaired in 1989, just three years afterDrexler’s Engines of Creation hit thebookstores. Boy wonder Wesley Crusheraccidentally releases some “nanites,” tinyrobots designed to work in living cells,which proceed to evolve into a highly in-telligent society that invisibly infests thesystems of the starship Enterprise andstarts wreaking havoc. Fortunately, inclassic Next Generation style, at the lastminute, contact is made with the evolved

nanites, and a mutually acceptable peace-ful outcome is negotiated: they are placedon a convenient planet where they’ll havemore room to live and grow. If only everyconflict, plague or technological disasterin the real world were solvable with suchease and rationality.

The central feature of molecularnanotechnology, precise manipulationof atoms, crops up in a classic sciencefantasy of 1965:

The stuff was dancing particles withinher[. . . . ] She began recognizing famil-iar structures, atomic linkages: a car-bon atom here, helical wavering . . . aglucose molecule. An entire chain ofmolecules confronted her and she rec-ognized a protein . . . a methyl-proteinconfiguration.

[. . . ] she moved into it, shifted anoxygen mote, allowed another carbonmote to link, reattached a linkage ofoxygen . . . hydrogen.

The change spread . . . faster andfaster as the catalysed reaction openedits surface of contact.

The novel? Dune, by Frank Herbert,in which computers are banned through-out the empire and spaceship pilots nav-igate through hyperspace by means ofdrug-induced precognition. While PaulAtreides is on his way to becoming themessianic ruler of the known universe,his mother, Lady Jessica, takes part in aritual involving “the water of life”—adeadly poison related to the “melange,”or “spice,” that feeds supernatural pow-ers of intuition and prescience. To sur-vive the ritual, Jessica’s consciousnessdives down into inner space and slowstime to a crawl to analyze the chemicalcomposition of the poison on her tongueand, using a “psychokinesthetic exten-sion of herself,” transform it into a cata-lyst that rapidly detoxifies all the rest ofthe poison, turning it into a potent butnot deadly narcotic.

Yet except for the use of psychoki-


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The prospect of absolute control of matter using nanomachines is a variant of the dream that Homo sapiens can achieve complete mastery over nature.

WE WERE OUT OF OUR MINDS WITH JOY,

BY DAVID MARUSEK (from Asimov’s Science

Fiction, November 1995)

I held patents for package applications in

many fields, from emergency blankets and

temporary skin, to military camouflage and

video paint. But my own favorites, and

probably the public’s as well, were my novelty

gift wraps. My first was a video wrapping paper

that displayed the faces of loved ones (or

celebrities if you had no loved ones) singing

“Happy Birthday” to the music of the New York

Pops. That dated back to 2025 when I was a

molecular engineering student.

My first professional design was the old

box-in-a-box routine, only my boxes didn’t

get smaller as you opened them, but larger,

and in fact could fill the whole room until you

chanced upon one of the secret commands,

which were any variation of “stop” (whoa,

enough, cut it out, etc.) or “help” (save me,

I’m suffocating, get this thing off me, etc.).

Next came wrapping paper that

screamed when you tore or cut it. That led to

paper that resembled human skin. It molded

itself perfectly and seamlessly (except for a

belly button) around the gift and had a shelf

life of fourteen days. You had to cut it to open

the gift, and of course it bled. We sold

mountains of that stuff.

STORY EXCERPT:EVERYDAY NANO-NOVELTIES


nesis in place of a technological frame-work, the entire process sounds like ananotech engineer working at a virtual-reality station to design a molecule. Orlike a scenario from Unbounding the Fu-ture: The Nanotechnology Revolution,by Drexler, Chris Peterson and GaylePergamit, in which a tourist experiencesa museum exhibit that simulates the mo-lecular-scale world, complete with scal-ing (slowing down) of time. In essence,nanotechnology offers to make Dune’sfantasy of complete human control overthe self and the rest of the universe intoa reality but in a mass-produced indus-trial fashion rather than through inten-sive individual training and drug-en-hanced psychic powers.

Nanotech is also prefigured in Dunethrough the Ixians, traders from a rarehigh-tech corner of the universe who are“supreme in machine culture. Noted for

miniaturization.” Indeed, devices fromDune such as the “hunter-seeker,” a tinypoison-tipped flying needle, would becompletely at home in nanotech stories.

Hot StuffNANOTECHNOLOGY’S use in sciencefiction takes many forms, classifiable bya number of measures. The role of nano-tech ranges from a central part of theplot to a relatively incidental part of thefictional world. The nanotech may bedeveloped by humans, or it may be a giftfrom aliens, or it may be the aliens. Thetechnology may work according to well-defined rules, or it may be arbitrary mag-ic, scantily clad in trappings of science.The rules may be expressly mentioned inthe text (perhaps even laboriously de-scribed), or the work may rely on thereader to tap into a science-fictional con-sensus reality, acquired from reading ear-

lier stories, of what generic Acme nano-tech can and can’t do.

Both of the latter alternatives relateto two approaches to presenting tech-nology in science fiction. At one ex-treme, the text practically contains a re-search paper on the author’s hyperspacetheory and blueprints of the first starship(rather like some of the letters ScientificAmerican receives). At the other, fa-mously pioneered by Robert A. Hein-lein, the technology is dropped in with-out explanation: “The door dilated.” Inthree words we know we are in a futurewith strange new technologies, and weare really there because in the futurecommonplace devices such as dilatingdoors need no more explanation thancellular phones do today.

When you read a large number ofnanotechnology stories in a short spaceof time, some amusing recurring themes


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INVISIBLE NANOTECH pervades this scene from Greg Bear’s

novel / [Slant]. Mary Choy has transformed her features

back to her original Asian look. The pyramidal building is

reinforced with flexfuller and contains cryopreserved bodies

of the rich and privileged. The swanjet has no conventional

ailerons; instead nanodevices on each wing surface control

the lift forces by forming thousands of tiny vanes or humps.


appear. On the one hand, nanotechnol-ogy often becomes a means to accom-plish anything within the realm of theimagination, while conveniently ignor-ing the constraints of physical laws. Cu-riously, on the other hand, these storiesreveal some of the actual technical chal-lenges that molecular nanotechnologistsmight confront if they ever were to exe-cute their designs for real-world nano-bots. For example, it seems that mosteveryone writing nanotech fiction isaware that highly active nanocritters willgenerate heat, a problem of some con-cern when said nanocritters are func-tioning inside your body.

In one of the early stories, the 1989novella Nanoware Time, by Ian Watson,the nanoware has been brought to hu-mankind by seemingly benevolent aliensthat look like giant golden centipedes.When the nanoware is injected into aperson, it takes root in the subject’sbrain, supplying him or her with thepower to . . . (can you guess?) harness“demons” from a parallel dimension.These demons have no will of their ownbut possess extraordinary powers thatthe nanowired person can then use, for

instance, to shield himself from the vac-uum of space, propel a starship acrossthe galaxy, fire bolts of energy for goodor ill, and so on. The nanoware is reallyjust a technological cloak for supernat-ural magic. In another era the alien de-vice would have been some other mind-enhancing black box or injectable drug.Yet because this is nanoware—nanobotsthat rewire the hardware and softwareof your “wetware” (your brain)—onedoes have to worry about the heat gen-erated by its functioning. A few of theearly human volunteers fried their brainsbefore the right parameters for humanswere worked out:

Heat was a byproduct of all the rapidmolecular activity in the skull while thebusy little nanomachines built the nano-ware. Thus some brains got cooked.

Vance was among the survivors.[His] brain damage was repaired byother nanos; sort of repaired. He’dbeen rehabilitated, retrained as a wasterecycler.

In one of the many plot threads inthe 1997 novel / [Slant], by Greg Bear,

a sequel to the landmark Queen of An-gels (1990), four people are found deadin an illicit body-modification clinic:they were cooked, literally, when thebody-modifying nanotech ran amok. Thecause is promptly uncovered by investi-gators when they examine the jars ofpastelike “nano” on the shelf:

Mary picks up a bottle, reverses it toread the label.[. . . ] The label confirmsher suspicions.[. . . ]

“This isn’t medical grade,” Marysays. “It’s for gardens.[. . . ] Any real ex-pert could reprogram it. Apparentlythey didn’t have a real expert.”

Presumably the victims were broiled be-cause a bug in the badly reprogrammedgarden-grade nano made it run wild, gen-erating far too much heat in the process.

Later in the book a group of crimi-nals who have infiltrated a huge tetrahe-dral building make use of some illicitlyobtained MGN—military-grade nano.Sprayed from a canister like fire-extin-guisher foam, the nano deconstructs ob-jects present in the building’s garage andrebuilds the atoms into intelligent ro-botic weaponry. During this process thegarage heats up like an oven, but not toohot, because “at about four hundred de-grees, nano cooks itself.”

A spectacular case of spontaneoushuman nanocombustion occurs in oneof the most surreal sections of NealStephenson’s tour de force The Dia-mond Age. A secluded cult known as theDrummers is infected with millions ofnanoprocessors. When two processorsmeet in someone’s bloodstream, theycompare notes, perform a computationand then go on their way: a kind of dis-tributed, Internet-like supercomputer.The computation proceeds mostly at asteady pace, but occasionally it advancesin a spurt of activity when myriad par-allel threads of the computation arebrought together for synthesis by anorgy (exchange of bodily fluids is the keymeans of transferring these processorsand their data between people). Theorgy culminates when the nanoproces-sors are loaded into one unlucky womanwho is promptly incinerated by the heat


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MINIATURIZED PEOPLE in the 1966 movie Fantastic Voyage

swim like nanobot surgeons in a patient’s bloodstream.


of the nano-orgy that ensues in herbloodstream. To access the computa-tion’s result, the other Drummers mixher ashes into a soup—highly reminis-cent of the Martian process of “grokking”the dead (in essence, ritual cannibalismto honor and fully appreciate the de-ceased) in Robert A. Heinlein’s 1961novel Stranger in a Strange Land, butwith the patina of a scientific rationale.

Stephenson’s The Diamond Age and

Bear’s Queen of Angels are comprehen-sive depictions of societies completelychanged by nanotechnology. In Queenof Angels, a large proportion of the pop-ulace has been “therapied,” in which in-jected nanotech devices infiltrate a per-son’s brain to correct psychological im-balances and weaknesses. Many peopleundergo extensive nano-enabled bodymodification, ranging from practical en-hancements for their occupation to beau-tification and the addition of exotic fea-tures. A complex tension runs throughthe society because of prejudices and at-titudes about “transforms,” “high natu-rals,” and “therapied” and “simple un-therapied” individuals.

In Bear’s world, nano comes in jarslike paste. In Stephenson’s The Dia-mond Age, the key to nano is “the feed,”a type of nanopipeline that runs intoevery household, supplying atoms asneeded by matter compilers, which areas common as microwave ovens are to-day. Anyone can obtain free food frompublic matter compilers, but they’re notup to the cordon bleu standards of StarTrek’s replicators; rice they can do, butgreen vegetables come out as a paste.Airborne nanotech is ubiquitous, rang-ing from almond-size surveillance mon-itors to microscopic attack and defensecraft engaged in a constant struggle, likean immune system battling invaders. Onbad days in the poor section of town,this ongoing contest looks like a fog shotthrough with firefly sparkles of laserlight. A sootlike coating composed of ca-sualties from this conflict settles oneverything and everyone. Wealthier en-claves, such as that of the Vickys (neo-Victorians), are protected from suchtroubles by a deep defensive perimeter ofairborne nanobots.

Nanofiction is not without humor.The Diamond Age, particularly early inthe book, is told with abundant wit anddrollery. The story opens with the ex-ploits of a spectacularly stupid lowlifenamed Bud. A parody of the Walkman

generation, Bud gets around on in-lineskates capable of a top speed of morethan 100 kilometers an hour, and hismusic system is “a phased acoustical ar-ray splayed across both eardrums likethe seeds on a strawberry.” He’s some-times a little “hinky” on the skates: im-planted nanosites incessantly twitch hismuscle fibers to maximize their bulk.Together with a testosterone pump inhis forearm, “it was like working out ata gym night and day, except you didn’thave to actually do anything and younever got sweaty.”

And isn’t that, in the end, what muchof nanotech is about? A quasi-scientificway to get what you want effortlesslyand at minimal cost. Instant gratificationthrough the ultimate in high technology.Compile your dreams and gather abunch of atoms. Just add nano.

Graham P. Collins is a staff editor and writer. He is also an occasionalscience-fiction writer and thewebmaster of the Science Fiction and Fantasy Writers of America.


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Anyone can obtain free food from public nanotech matter compilers, but they’re not up to the cordon bleu standards of Star Trek’s replicators.

MORE TOEXPLORE

NO LOVE IN ALL OF DWINGELOO, BY TONY

DANIEL (from Asimov’s Science Fiction,

November 1995)

[We lived] on Kokopelli Station. There were

more people living up-cable, thousands and

thousands more. Still, this was just a trickle

of refugees compared with the billions who

had died below. Earth was horribly worse, and

it was then that I realized I was seeing the

future.

The squabbles and wars of the present

had played themselves out and we’d done it,

we’d ruined the planet. The seas were

biohazard cauldrons, seething with an

ecology of war viruses. The land was haunted

by nanoplasms, the primal form that life had

taken, been reduced to. Sea and land were at

war—over nothing, any longer—just a

meaningless perpetual struggle between

viral life and nano algorithms caught in a

perpetual loop. Those who crafted the

weaponry were dead.

A few million humans survived on the

coasts, in the land between the warring

elements. They were temporarily immune to

the nano, but none could say for how long,

since the nano evolved, its sole purpose

finding ways to beat back the living, zombie

sea—and, incidentally, to remake whatever

people remained into a substance that could

not wield a gun and could not think to use one.

Yet I found myself completely,

unshakably content. Kokopelli was safe. We

had severed all but one cablelift, and created

defenses that kept the muck below at bay.

STORY EXCERPT:DYSTOPIAN NANO-FUTURE

The Encyclopedia of Science Fiction. Secondedition. Edited by John Clute and PeterNicholls. Palgrave, 1993. Also available fromGrolier on CD-ROM as The MultimediaEncyclopedia of Science Fiction.

The Ascent of Wonder: The Evolution of HardScience Fiction. Edited by David G. Hartwelland Kathryn Cramer. Tor Books, 1997. The introduction is available online atebbs.english.vt.edu/exper/kcramer/aow.html

Locus magazine’s online index of sciencefiction: www.locusmag.com/index/

Science Fiction and Fantasy Writers ofAmerica: www.sfwa.org

Analog Science Fiction and Fact:www.analogsf.com

Asimov’s Science Fiction: www.asimovs.com

Magazine of Fantasy & Science Fiction:www.sfsite.com/fsf/

Sci Fiction: www.scifi.com/scifiction/


FLEA TREATMENTS

Shampoos, powders, sprays and collars all aim to con-trol fleas on pets, but the most popular treatments to-day are the “spot” medications. Squeeze a few dropson the skin along a dog’s or cat’s back, and the insec-ticide will control fleas for a month. The products areavailable only from veterinarians, in doses adjustedfor an animal’s weight.

The formulations spread by mixing with a pet’sskin oils, which migrate as a result of body movementand gravity. Some products flow into the sebaceousglands of hair follicles, where they are stored and se-creted over time; others remain on the skin’s surface.Advantage (imidacloprid) from Bayer and Frontline(fipronil) from Merial—the two market leaders—willfan out across the body in less than 12 hours and killmore than 90 percent of fleas by then. Tests by Bayershow that after 28 days, concentrations across a dog’sbody decrease to as little as one part per million, butless than one tenth of that amount is needed to killfleas, according to Bob Arther, Bayer’s manager ofparasitology. And because they reside in or on skin,spot compounds do not readily wash off like treat-ments that stick to an animal’s hair.

Pets can be given anti-flea pills, sending medica-tion into their bloodstream. But a flea must bite the petto be exposed to the insecticide. Some pills do not killadult fleas but make their eggs unviable. The spottreatments kill virtually all fleas within 18 hours andprevent eggs from being laid. Buyers should be wary ofover-the-counter knockoffs; many contain permethrin,which is less effective on dogs and is toxic to cats.

Some critics claim that pets can be harmed by in-gesting small amounts of spot treatments as theygroom themselves (although the same could be said ofa spray, collar or pill). But tests required by the Envi-ronmental Protection Agency show that “animals thathad received even gross overdosages had no change intheir kidney or liver values,” says Bruce Klink, man-ager of veterinary services at Merial. Manufacturerssay the active ingredients do not affect people.

No insecticide is 100 percent safe. But be skepticalabout “natural” or “chemical-free” alternatives suchas vitamin B or garlic. There is little scientific proof thatthe potions send fleas fleeing. —Mark Fischetti

Killer Drops

WORKINGKNOWLEDGE

“SPOT” FLEA TREATMENTSmix with a pet’s skin oils. A few dropsdisperse readily. Tests by makerMerial on midsize dogs given therecommended dose of the treatmentfipronil show that concentrationsquickly spread across the body. Andalthough concentrations are lowafter 56 days, they are still highenough to kill fleas (95 percent of fleas die when exposed to 0.7 microgram per gram of fur).

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INSECTICIDE(blue) is storedin a hair’s sebaceousgland, which can secretethe compound for amonth or more.


➤ FADING FAD: When a flea bites, it deposits saliva

in the skin. Pets can have an allergic reaction that

causes redness and severe itching. As they scratch,

they develop flea-allergy dermatitis. For years, FAD

was the leading skin problem in dogs and cats, but

veterinarians report that “spot” treatments, because

of their quick kills, have dramatically reduced the in-

cidence of the disorder.

➤ BLACK DEATH: Rat fleas carry bacteria that can

cause plague, such as the bubonic plague that wiped

out one third of Europe’s population in the 14th cen-

tury. In 1999 microbiologists identified plague in

flea-infested squirrels, chipmunks and other wild ro-

dents in 22 counties surrounding Sacramento, Calif.;

in 2000 state health officials began issuing regular

warnings about plague-prone areas there.

➤ MAN BEFORE BEAST: The French established the

world’s first veterinary school, in Lyon in 1762. Vet-

erinary science was originally developed not so

much to help animals but to improve the under-

standing of zoonotic diseases in order to prevent

their transfer to humans.

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Typical concentration:30.9 mcg /g at 24 hours; 1.8 mcg /g at 56 days

Typical concentration:91.5 mcg /g at 24 hours; 1.6 mcg /g at 56 days

Typical medication concentration:308 micrograms/gram at 24 hours; 7.4 mcg /g at 56 days

FLEA’S NERVE CELLis the target of the spot medication’s activeingredient, which binds to a specificreceptor there. The treatment fipronil (shownat right) blocks the flow of chloride ions thatotherwise interrupts nerve signals. Thishyperexcites a flea’s central nervous system,sending it into a deadly seizure.

Flow of chloride ions blockedFipronil

Spot of application

Nerve cell membrane


VOYAGES

Continents collided—northwestern Africacrashed and ground against North Amer-ica—and mountains as tall as the Alpsrose in New England. Wind and rainbeat at the peaks and wore them down,and then the land on which they stoodsank below the sea. Waves and tides hadtheir turn, and the towering ranges werelargely leveled. The land lifted. Thebalmy weather turned cold. Ice sheetsscraped across bedrock, pushing a wallof rubble before them. The climatewarmed again, and glaciers melted, cre-ating a huge lake that lapped behind thewall of glacial till. Ice sheets kept melting;the lake swelled and stretched and, ulti-mately, broke through the wall at its low-est part. Rivers began to flow throughvalleys that the glaciers had carved.

Before politics, culture and high fi-nance, these were the forces that shapedNew York City. To see New York thus isto see it with the eyes of a geologist, to seethe sweep of millions of years, and to un-derstand why certain things look the waythey do and stand where they do. Thescar where continents ground togetherruns down the Bronx River; the remnantof the mountains is the city’s bedrock; therubble pushed by the glaciers gave rise toLong Island; the great lake spilled over atthe Verrazano Narrows; the Hudson andEast rivers fill valleys deepened by glaciers.Wall Street and Midtown raised modernmountains of glass and granite becausethere was solid bedrock to build on, butin between lay insufficient foundation forskyscrapers—hence low-slung Green-wich Village and Soho. Before garbageand landfill were strewn in its wetlands,

Manhattan was cut in two when veryhigh tides swelled the rivers and they meteach other in the middle of the island, at125th Street, where a fault slices the city.

All this insight and more can comefrom a three-hour cruise up the HudsonRiver—or the East River or through NewYork Harbor—with Sidney Horensteinof the American Museum of NaturalHistory. “Since geology is the basis ofeverything, you just cannot help, onceyou get involved in this, to go beyond thegeology,” says Horenstein, author of the

Audubon Society’s guide to Familiar Fos-sils of North America and coordinator ofenvironmental programs at the museum.“Because if you look at the landscape,you can’t help saying, ‘What is that?’ and‘How did this happen?’”

Horenstein’s Circle Line trips, which


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Seeing the Earth for Its FaultsGEOLOGICAL TOURS AND GUIDES EXPOSE THE SECRETS OF NEW YORK CITY AND BEYOND BY MARGUERITE HOLLOWAY

NEW YORK SKYLINE owes everything to geology.The financial district and Midtown support toweringbuildings because bedrock is no more than 38 to 80 feet below the surface. In GreenwichVillage, however, it is about 260 feet down.


for about a decade have taken place inearly summer, are as renowned for hisobservations about geology as they arefor his historical anecdotes, questionablepuns (“The reason all the lights are lit uphere is that we are approaching the Bat-tery”) and sayings. On a recent sunsetcruise packed with passengers and theirpicnics, Horenstein explains his answerto the controversial question of how theBig Apple got its name: from a bordelloowner named Eve and the “apples” whoworked for her. He describes how 300-million-year-old invertebrate fossils end-ed up in the walls of Riverside Church’sbell tower: the sandstone was brought infrom Indiana, site of an ancient tropicalsea. And a discussion about New York’smain rock formations gives Horenstein achance to quote a favorite refrain: “TheBronx is gneiss, but Manhattan is full ofschist. Inwood has lost its marbles, andNew York is full of faults.”

During other parts of the year, Hor-enstein gives talks and leads regional ge-ological field trips. “Boats are just one as-pect of it,” Horenstein says. “I lead toursall over, just like a gypsy cab.” One, for ex-ample, is a walking tour of Central Park,

where participants can see the scratchescarved in schist by roving glaciers andsome of the boulders left behind by melt-ing ice. Another lecture series covers geol-ogy and travel: how to recognize geologicfeatures wherever you find yourself. (Forinformation about scheduling, check theAmerican Museum of Natural History’sWeb site at www.amnh.org or call themain reservations line at 212-769-5200.)

Many other paths also wander intoNew York’s geologic past. Charles Mer-guerian of Hofstra University, author withJohn E. Sanders of myriad papers on theregion’s geology, has designed virtual fieldtrips of the city and environs, which canbe viewed or ordered at www.duke-labs.com. The Parks Department orga-nizes some excursions as well. And theSouth Street Seaport Museum’s off-sitepermanent exhibit “New York Un-earthed” provides a window into thecity’s archaeology. For those who want toexplore the rocks and faults alone, thereis a general site for New York (www. albany.net/~go/newyorker/index.html),with references and materials, as well asseveral good books, including John Kie-ran’s A Natural History of New YorkCity and Wild New York, by MargaretMittelbach and Michael Crewdson.

If you prefer instead to conjure the


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GLACIAL MOVEMENTS left marks on rocks thatcan be seen in Central Park.


creatures that lumbered through the land-scape—to envision the ground sloths,hairy tapirs, saber-toothed tigers, woollymammoths and mastodons that were theregion’s wildlife during the Pleistocene—

you can find fossil hunters to follow. TheNew York Paleontological Society, whichHorenstein founded in 1970, has month-ly meetings most of the year and orga-nizes field trips to look for fossils. Onesuch tour this summer took members toHamburg, N.Y., to observe Devonianfossils, such as trilobites, in a quarry. An-other tour entailed visiting fossil track-ways in Connecticut’s Dinosaur StatePark. (Go to www.nyps.org.)

But no matter which city or state orregion or country you are in—or whetheryou have easy access to a natural histo-ry or related museum—you are free tosee with a geologist’s eyes. Many stateshave a paleontological society, and al-though you might have to join to be ableto participate in the field trips, mem-bership is typically only about $20 for afamily. A number of states also have amineral society that leads tours—oftenthese societies are members of the Amer-ican Federation of Mineralogical Soci-eties (www.amfed.org)—as well as a sur-vey that details the geology of the region.The Utah Geological Survey, for in-stance, provides local information on di-nosaur fossils.

In addition, Horenstein and other ex-perts recommend a helpful series of books.Published by Mountain Press in Missoula,Mont., the Roadside Geology books arewritten by geologists for laypeople (seewww.mountainpresspublish.com). Al-most half the 50 states have a guide, fromRoadside Geology of Alaska to RoadsideGeology of Wyoming. The press alsopublishes books on various regions of theU.S., several national parks and a fewcountries, including Canada and Argenti-na. To see familiar places against thebackdrop of aeons is truly a grand view,both humbling and haunting; in the riseand fall of the land in your mind’s eye,you can see the earth breathe.


VOYAGES


REVIEWS


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Bloated, Whiny and Self-ImportantIS THE SCIENTIFIC BUREAUCRACY THE QUINTESSENTIAL SPECIAL-INTEREST GROUP? BY KEAY DAVIDSON

Dan Greenberg’s profoundly importantnew book depicts American “Big Sci-ence” as a classic self-perpetuating bu-reaucracy—bloated, whiny and self-im-portant. This bureaucracy defends big(and sometimes indefensible) budgets byweaving scare stories about national sci-entific “illiteracy,” questionable “short-ages” of scientific personnel, and imag-inary threats from foreign competitors.Greenberg quotes an official of the U.S.Office of Management and Budget:“With the possible exception of veterans,farmers, and college students, there is nogroup that squeals more loudly over a re-duction of federal subsidies than scien-tists. They are the quintessential specialinterest group, and in effect, they makethe oil industry look like a piker.”

Startling words? Isn’t American sci-ence struggling to survive on meagerfunds, the result of post–cold war budgetcuts inspired, in part, by the Americanpeople’s alleged indifference, even hostil-ity, toward science?

Poppycock, Greenberg replies in abook that is better documented than

most National Academy of Sciences re-ports yet reads as briskly as a DashiellHammett detective story. (I devoured ituntil 4 A.M.) The federal science budgethas gone up, not down, he argues—andpresents the statistics to prove it. TheAmerican people are not anti-science; infact, they are very pro-science, almost un-critically so. “By virtually every relevantmeasure, the United States leads theworld in the financing, quality, and vol-ume of research; it has held this lead sincethe end of World War II, and appearsbound to maintain, and increase, its su-premacy far into the new century.”

So what, Greenberg asks, are scien-tists griping about? And why do theirprime beneficiaries, federal scientificagencies, increasingly act like MadisonAvenue hype factories?

“There is too much hype,” he quotesMaxine Singer, one of the few female

members of the National Academy ofSciences, as saying. “Every gene that isdiscovered will lead to a cure for cancer.Maybe, but not for a long time. Even theSuperconducting Super Collider was saidto have important implications for im-proving human health.”

For anyone naive about the politics ofscience, Science, Money, and Politics isthe perfect curative. The military namessubs and aircraft carriers after friendlylegislators; likewise, federal science bu-reaucrats affix the names of helpfulpoliticians to their buildings. The Na-tional Institutes of Health’s “namedbuildings recognize the good works ofsenators Warren Magnuson, Lister Hill,Lowell Weicker, Lawton Chiles, andMark Hatfield, and representatives JohnFogarty, William Natcher, Silvio Conte,and Claude D. Pepper.”

Politics makes strange bedfellows. In

SCIENCE, MONEY, ANDPOLITICS: POLITICALTRIUMPH AND ETHICAL EROSIONby Daniel S. GreenbergUniversity of ChicagoPress, 2001 ($35)

EXTINCT BIRDSby Errol Fuller. Revised edition. Comstock PublishingAssociates, Cornell University Press, Ithaca, N.Y., 2001($49.95)“Never send to know for whom the bell tolls; it tolls for thee.”John Donne’s line, which appears on the dedicatory page,sets the tone for this elegantly written book by British painterErrol Fuller. The author of two other books on birds, Fuller de-scribes here the lives, times and disappearances of more than80 avian species since 1600. These accounts are illustratedprimarily by beautifully reproduced paintings (from a variety of artists, including JohnJames Audubon, J. G. Keulemans and the author) as well as by early photographs andengravings. This revised edition updates the original 1987 publication, reinstating a fewbirds found not to have disappeared and, sadly, adding a few more that have.

THE EDITORS RECOMMEND

Keay Davidson is a science writer for theSan Francisco Chronicle and author ofCarl Sagan: A Life (John Wiley, 1999).



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TIME TRAVEL IN EINSTEIN’S UNIVERSE: THE PHYSICAL POSSIBILITIES OF TRAVEL THROUGH TIME by J. Richard Gott III. Houghton Mifflin, Boston, 2001 ($25)

DARK REMEDY: THE IMPACT OF THALIDOMIDE AND ITS REVIVAL AS A VITAL MEDICINEby Trent Stephens and Rock Brynner. Perseus Publishing, Cambridge, Mass., 2001 ($26)

“One reason that time travel is so fascinating is that we have such agreat desire to do it,” Gott writes. And so he explores the possibilitiesof travel to the past and to the future. Being a professor of astro-physics at Princeton University, he does not stray from the laws ofphysics in constructing this stimulating odyssey. Being also the manwho has made a number of intriguing predictions based on the Coper-nican idea that “your location is not special,” Gott offers several pre-

dictions here. The future duration of the humanspecies, for one—more than 5,100 years but lessthan 7.8 million. And because “one of the things weshould understand about time is that we have just alittle,” he argues that “the goal of the human space-flight program should be to increase our survivalprospects by colonizing space.”

Marketed in 1957 as a sedative by Chemie Grünenthal, a Germancompany the authors describe as “notorious forrushing drugs to market with inadequate testing,”thalidomide soon launched its ghastly procession ofdeformed babies. It was removed from the marketand appeared to be permanently in limbo. But in1964 an Israeli physician treating victims of leprosytried it on a patient with a severe complication of thedisease. The patient’s condition improved dramati-

cally. Since then, thalidomide has proved effective in treating morethan 130 disorders, many of them autoimmune diseases. But be-cause of its menace to reproduction, “everyone involved in the re-vival of this dark remedy hopes that it will be a short one”—fivemore years, perhaps—to be followed by a safe analog. Stephens,professor of anatomy and embryology at Idaho State University, andhistorian Brynner tell this haunting story well.

All the books reviewed are available for purchase through www.sciam.com


the 1980s, as the cold war waned, theU.S. Energy Department, which runs thenuclear weapons complex, feared a ma-jor slash in its budget. So it began lookingfor a new enterprise and found it: the Hu-man Genome Project. Naturally, this up-set the NIH, whose officials reasoned thatthey were more suited to map the ge-nome. But the weapons labs are masterlobbyists for their own interests.

President Gerald Ford’s science advis-er Guy Stever told Greenberg, “I guaran-tee you, if somebody really had completecontrol of the quality of our system, andcould cut out everything at the low level,we could survive beautifully on less mon-ey.” In any case, Greenberg says, there isno consistent evidence of a strong corre-lation between American scientific-tech-nological leadership and the fortunesspent seeking it: “Great Britain has ac-complished a great deal scientifically onrelatively modest science budgets; the So-viet Union had relatively little to show forits enormous spending on research.”

For four decades, Greenberg has beenthe conscience of American science writ-ers. He was the first news editor of Sciencemagazine. In 1967 he established himselfas the Jessica Mitford of science when hewrote The Politics of Pure Science, anacerbic analysis of science-government re-lations after World War II. He spent 26years running the acclaimed gadfly news-letter Science & Government Report.

We need more Greenbergs. Too manyscience writers cover science as uncriti-cally as fashion reporters cover fashion. (Iam as guilty of this as many of my peers.)Science, Money, and Politics rightly blasts“doting science journalists who faithfullyecho the paranoid fears and alarms of thescientific leadership and its publicists.”He scolds medical reporters for their“bait-and-switch” coverage of allegedbreakthroughs in the war against cancerand other diseases. Typically, an excitingdiscovery leads the evening news or is bal-lyhooed on the front page. Follow-up re-search often undermines the claim, but doyou see that in the paper? Not likely.

As Greenberg reminds us, science is abig, expensive and all-too-human enter-prise, as prone to shams and hucksterismas any human endeavor. Shams and huck-sterism are “news,” too; they deserve to becovered alongside NASA’s latest circus

stunts. This admirable book should berequired reading for science policy mak-ers, science journalists and any Americanwho gives a damn whenever science—

one of the nation’s crown jewels—fallsinto irresponsible hands.


REVIEWS



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PUZZLINGADVENTURES

Striding gracefully, her white cape undulatingslowly behind her, the director of a famous dancecompany enters my office. “You’ve heard of ghostwriters,” she says. “I need a ghost choreographer.”I motion for her to sit, and she outlines the partic-ulars of her problem.

The dance company consists of 12 men (coloredblue in the illustrations below) and 20 women (col-ored red). At a key point in their dance, they gofrom a configuration in which the men surroundthe women to one in which the women surroundthe men. The transition has three stages. During

each stage, each dancer can either stand in place ortake one step in one of four directions: to the left,to the right, forward or backward. There are twoimportant conditions: two dancers cannot swappositions during a step, nor can two dancers occu-py the same space at the end of a step. Above all,the dancers want to avoid collisions.

The starting and ending configurations of thedancers are shown below. Can you design theirmoves at each step so that they reach the final po-sition without violating the conditions? It may helpto plot the moves on a piece of graph paper.

Square Dancing BY DENNIS E. SHASHA

Answer to LastMonth’s PuzzleThe solution to thefirst problem of the unreliable oracleis that you canconvert your initialstake of $100 to at least $9,309 if youuse the optimumbetting strategy,which calls for mak-ing a first bet of justunder $81.82. The strategy is fullyexplained at thePuzzling Adventurespage at www.sciam.com. For the secondproblem, in whichyou must make allthe bets in advance,the best strategycan guarantee youonly $1,600. Again,see the Web site forthe full explanation.

Web SolutionFor a peek at theanswer to thismonth’s problem,visit www.sciam.com

STARTING CONFIGURATION ENDING CONFIGURATION


ANTIGRAVITY

Journalists often cite an old bromide:“Dog Bites Man” is not news, but, on theother hand, “Man Bites Dog” is news.And on the other foot, which is exactlywhere it happened, “Komodo DragonBites Newspaper Editor” is definitelynews. Especially when the newspaper ed-itor in question is the San FranciscoChronicle’s semi-celebrity executive edi-tor Phil Bronstein, who was bitten whilegetting a special up-close-and-periloustour of the Los Angeles Zoo’s Komodoexhibit in early June, arranged for him byhis full-celebrity wife, the beautiful ac-tress Sharon Stone. The visit was Stone’sidea of an early Father’s Day celebration,which often includes dinner out.

Evidently, a zookeeper advised Bron-stein to remove his white sneakers so theywouldn’t be confused with the dragon’scustomary meal of white rat. This strat-egy clearly backfired. A letter to theChronicle asked, “Whose bright idea wasit to remove the white shoes from thewhite feet of a white man in the hopes ofnot confusing a nearsighted, simplemind-ed, ravenously hungry lizard?”

I take umbrage at this reader’s um-brage, and I feel I am in a unique positionto comment on this incident. That posi-tion is seated, in front of my computer,far away from any Komodos. For onething, the Komodo dragon is not merelya lizard. It is “the world’s largest livinglizard—a ferocious carnivore—found onthe steep-sloped island of Komodo in theLesser Sunda chain of the Indonesianarchipelago,” according to the hilariousand completely accurate bit by the leg-endary radio comedians Bob and Ray.

For another thing, the dragon was nodoubt well fed, which zoo animals tendto be. As for nearsightedness, ClaudioCiofi of the Zoological Society of Lon-don, writing in the March 1999 issue ofthis magazine, revealed that “monitors[the Komodo is a species of monitorlizard] can see objects as far away as 300meters, so vision does play a role in hunt-ing, especially as their eyes are better atpicking up movement than at discerningstationary objects.”

For my final rejoinder to the Chroni-cle reader, I note that Komodos are moresingle-minded than simpleminded—as anambush-predator, the Komodo must becunning and stealthy. And it shouldprobably stay downwind of its prey,what with its amazing body funk. In alecture, Walter Auffenberg, the world’sforemost Komodo expert and author ofThe Behavioral Ecology of the Komodo

Monitor (which, by the way, makes a ter-rific Father’s Day present), rememberedthe first dragon he met on Komodo:“God, he stank. Oh my goodness. God,he was smelly. I called him Stinky. I wentback and told the family that I metStinky.” Auffenberg later learned thatStinky was a “psychotic animal that hadprobably killed two people on Komodoprior to our visit.” Ahhh, good times.(The entire lecture can be found at http://natzoo.si.edu/hilights/lectures.htm.)

Anyway, my interest in Komodoswas born while working with Ciofi on hisarticle. And even though I learned thatthe dragons’ saliva harbors numerousspecies of septic bacteria that can killeven if the bite itself doesn’t, I was stilldumb enough to get next to a Komodo atthe National Zoo in Washington, D.C. Ifyou look very closely at the Ciofi story’sphoto credits, you’ll see that I snappedthe dragon. (By the way, my visit to thezoo’s dragon enclosure was arranged forme by my beautiful actress wife, uh, Mor-gan Fairchild. Yeah, that’s the ticket.)

Back in the glamorous world ofcelebrity maulings, Bronstein underwentsurgery to reattach a few tendons, andboth his foot and sense of humor seem in-tact. He told his own paper, “That’s howit goes when a movie star and a dragonare involved.” Meanwhile Stone’s view ofthe foot-and-mouth business was moreGrimm: “Very few women get to seetheir knight wrestle the dragon. And Ithink he’s kind of fabulous. And kind ofhot.” With the raging infection that usu-ally follows a Komodo bite, perhaps thatheat is just a fever.


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Enter the Dragon ExhibitONCE UPON A TIME THERE WAS A DRAGON AND A BEAUTIFUL PRINCESS, I MEAN ACTRESS, WHO FORGOT THAT LARGE CARNIVORES HAVE A BASIC INSTINCT BY STEVE MIRSKY


Q

Veterinary ophthalmologist J. Phillip Pickett of the Virginia-Maryland Regional College of Veterinary Medicine explains:

“Red eye,” the nemesis of amateur photographers, occurswhen someone looks directly at the camera while a picture istaken. If the flash is on the same axis as the visual axis of thecamera, the reflection off the blood vessels in the person’s reti-na can produce an eerie, satanic look, the so-called red reflex.

Dogs, cats and almost all domestic animals have a specialreflective layer in the back of the eye termed the tapetum. In-coming light passes through the animal’s retina and is thenreflected back through the retina a second time from thetapetal layer. This double stimulation helps these species tosee better in dim light. The color of this tapetal layer variesto some extent with an animal’s coat color. A black Labradorretriever, for example, will usually have a green tapetal re-

flection. A buff-colored cocker spaniel will generally show ayellow tapetal reflection. Most young puppies and kittenshave a blue tapetal reflection until the structures in the backof the eye fully mature at six to eight months of age. “Colordilute” dogs and cats, such as red Siberian huskies and bluepoint Siamese cats, may have no tapetal pigment and maytherefore exhibit a red reflex just like human beings.

If a used needle can transmit HIV, why can’t a mosquito?

—P. Smith, Masclat, France Laurence Corash, chief medical officer of Cerus Corporation,explains:

The AIDS virus (HIV) on used needles is infectious wheninjected into a human because the virus can bind to T cellsand start to replicate. The human T cell is a very specific hostcell for HIV. When a mosquito feeds on a person with HIV,the HIV enters the insect’s gut, where it cannot find a host.

The malaria parasite, in contrast, can survive, multiplyand mature in the mosquito’s gut. The parasites then migrateto the insect’s salivary glands. Because mosquitoes inject theirsaliva when they bite, the parasite is passed along to the nexthuman on whom the insect feeds. The complex interactionbetween the infectious agent and the mosquito is thus re-quired for malaria transmission. HIV, however, deterioratesin the gut before the mosquito bites again and therefore is nottransmitted to the insect’s next victim.

For the complete text of these and many other answers,visit Ask the Experts (www.sciam.com/askexpert).

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ENDPOINTS

QWhy do dogs get blue, not red, eyes in flash photos?—B. Sloot, Mount Prospect, Ill.


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