faulty memory: long-term immunity isn't always beneficial

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JPL/NASA SCIENCE NEWS mised that by 1969, whalers essentially wiped out the fin, sei, and sperm whales within 370 kilometers of the Aleutian Islands and the Gulf of Alaska coast. Then, the numbers of smaller marine mammals began declining, Springer says. The harbor seal population crashed in the late 1970s. In the following years, fur seals and Steller sea lions disappeared in droves. In the 1990s, sea otter numbers plummeted. Those trends point to killer whales, says Springer. He proposes that these spry pred- ators would first hunt the fat, docile har- bor seals. Once those prey dwindled, orcas would settle for the smaller fur seals and aggressive sea lions. Finally, killer whales would snack on otters. In what may be a further iteration of this ecological cascade, sea urchins—a favorite food for otters— have thrived (SN: 10/17/98, p. 245). “Monkeying around with the system could lead to things you would have never predicted would happen,” Springer says. By estimating the number of otter and pinniped deaths during the declines and determining how many of these creatures would be required to feed a killer whale, Springer and his colleagues calculated that the population crashes could have occurred even if the orca population had shifted its diet less than 1 percent. “I think it’s the best hypothesis out there” for these declines, says Jeremy B.C. Jackson of the Scripps Institution of Oceanography in La Jolla, Calif. Andrew W. Trites of the University of British Columbia in Vancouver questions whether great whales ever constituted major portions of orcas’ diets. He adds that in computer models of marine ecosystems, removing great whales had no significant effect on pinnipeds. Springer acknowledges that the mys- tery of these declines may be hard to solve with confidence, since much of the rele- vant data disappeared with the missing animals. —K. RAMSAYER Galileo’s Demise A planetary plunge, by Jove The Galileo spacecraft ended an 8-year tour of Jupiter and its moons on Sept. 21, when it dove into the planet’s atmosphere, as sci- entists had planned. Minutes after the craft disintegrated, Earth received Galileo’s swan song, a radio signal suggesting that rocky debris lies along the orbit of the small Jov- ian moon Almalthea. During its sojourn, Galileo overcame several obstacles, notably the failure of a main communications antenna. The craft took the first close-up portraits of Jupiter’s four largest moons: Io, Ganymede, Europa, and Callisto. In 1995, a Galileo probe para- chuted into Jupiter. Data from several fly- bys of Europa suggested that the icy moon hides a vast ocean. That finding ultimately dictated how Galileo would die. To make sure that the aging craft wouldn’t crash into a body that might harbor life, scientists 2 years ago put Galileo on a collision course with the planet it had explored so intimately. —R. COWEN Faulty Memory Long-term immunity isn’t always beneficial Come down with a case of chicken pox and, after you recover, your body seems to wear an invisible suit of armor that protects you from getting the disease again. Catch a cold, on the other hand, and the protective armor seems to fall away quickly. Common sense indicates that the longer your immune memory lasts, the healthier you will be. Now, a mathematical model indicates that there may be a good reason that you quickly lose your protection against the sniffles. The endless succession of colds that results may protect you from far nas- tier bugs. When a person becomes infected by most pathogens, the immune system instantly goes on the attack. After the infec- tion is vanquished, the immune response subsides, but not all the way down to its original level. Long-lived sentries called memory cells remain ready to pounce if the bug reappears. Dominik Wodarz of the Fred Hutchin- son Cancer Research Center in Seattle has considered a scenario in which two different pathogens—call them A and B—threaten a host population. He assumed that pathogen A is far more deadly to its host than pathogen B is. Pathogen B, he also assumed, is fitter than pathogen A, meaning that if the two pathogens in the host have to compete for resources on an even playing field, pathogen B will win out. If an individual becomes infected with pathogen B, the immune system will cre- ate memory cells against B, but that will tilt the playing field in A’s favor. This makes the host vulnerable to the more virulent A. Thus, long-lasting memory of pathogen B can actually work against the health of the host. Wodarz carried out calculations show- ing that, in this scenario, the host popula- tion will indeed evolve toward a short immunological memory of pathogen B infections. He reports his findings in the Sept. 16 Current Biology. “Wodarz’ paper suggests that the naive assumption—that the longer memory lasts, the better—may be wrong,” says Charles Bangham, an immunologist at Imperial College in London. Over the long term, Wodarz says, a host population would probably cycle between long and short immune memory. In the above scenario, for instance, once the host population evolved to have a short mem- ory of pathogen B, pathogen A might become extinct. That would eliminate the competition and permit the host’s mem- ory of pathogen B to gradually lengthen. Eventually, the door would open for another pathogen like A to spring up, and the cycle would begin again. The findings could have important pub- 196 SEPTEMBER 27, 2003 VOL. 164 SCIENCE NEWS This Week GRAND FINALE Depiction of Galileo plowing into Jupiter near the planet’s equator.

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Page 1: Faulty memory: Long-term immunity isn't always beneficial

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S C I E N C E N E W S

mised that by 1969, whalers essentiallywiped out the fin, sei, and sperm whaleswithin 370 kilometers of the AleutianIslands and the Gulf of Alaska coast.

Then, the numbers of smaller marinemammals began declining, Springer says.The harbor seal population crashed in thelate 1970s. In the following years, fur sealsand Steller sea lions disappeared in droves.In the 1990s, sea otter numbers plummeted.

Those trends point to killer whales, saysSpringer. He proposes that these spry pred-ators would first hunt the fat, docile har-bor seals. Once those prey dwindled, orcaswould settle for the smaller fur seals andaggressive sea lions. Finally, killer whaleswould snack on otters. In what may be afurther iteration of this ecological cascade,sea urchins—a favorite food for otters—have thrived (SN: 10/17/98, p. 245).

“Monkeying around with the systemcould lead to things you would have neverpredicted would happen,” Springer says.

By estimating the number of otter andpinniped deaths during the declines anddetermining how many of these creatureswould be required to feed a killer whale,Springer and his colleagues calculated thatthe population crashes could have occurredeven if the orca population had shifted itsdiet less than 1 percent.

“I think it’s the best hypothesis out there”for these declines, says Jeremy B.C. Jacksonof the Scripps Institution of Oceanographyin La Jolla, Calif.

Andrew W. Trites of the University ofBritish Columbia in Vancouver questionswhether great whales ever constitutedmajor portions of orcas’ diets. He adds thatin computer models of marine ecosystems,removing great whales had no significanteffect on pinnipeds.

Springer acknowledges that the mys-tery of these declines may be hard to solvewith confidence, since much of the rele-vant data disappeared with the missinganimals. —K. RAMSAYER

Galileo’sDemiseA planetary plunge, by Jove

The Galileo spacecraft ended an 8-year tourof Jupiter and its moons on Sept. 21, whenit dove into the planet’s atmosphere, as sci-

entists had planned. Minutes after the craftdisintegrated, Earth received Galileo’s swansong, a radio signal suggesting that rockydebris lies along the orbit of the small Jov-ian moon Almalthea.

During its sojourn, Galileo overcameseveral obstacles, notably the failure of amain communications antenna. The crafttook the first close-up portraits of Jupiter’sfour largest moons: Io, Ganymede, Europa,and Callisto. In 1995, a Galileo probe para-chuted into Jupiter. Data from several fly-bys of Europa suggested that the icy moonhides a vast ocean.

That finding ultimately dictated howGalileo would die. To make sure that theaging craft wouldn’t crash into a body thatmight harbor life, scientists 2 years ago putGalileo on a collision course with the planetit had explored so intimately. —R. COWEN

Faulty MemoryLong-term immunity isn’t always beneficial

Come down with a case of chicken poxand, after you recover, your body seems towear an invisible suit of armor that protectsyou from getting the disease again. Catch acold, on the other hand, and the protectivearmor seems to fall away quickly.

Common sense indicates that the longeryour immune memory lasts, the healthieryou will be. Now, a mathematical modelindicates that there may be a good reasonthat you quickly lose your protection againstthe sniffles. The endless succession of coldsthat results may protect you from far nas-tier bugs.

When a person becomes infected bymost pathogens, the immune systeminstantly goes on the attack. After the infec-tion is vanquished, the immune responsesubsides, but not all the way down to its

original level. Long-lived sentries calledmemory cells remain ready to pounce ifthe bug reappears.

Dominik Wodarz of the Fred Hutchin-son Cancer Research Center in Seattlehas considered a scenario in which twodifferent pathogens—call them A andB—threaten a host population. Heassumed that pathogen A is far moredeadly to its host than pathogen B is.Pathogen B, he also assumed, is fitterthan pathogen A, meaning that if the twopathogens in the host have to competefor resources on an even playing field,pathogen B will win out.

If an individual becomes infected withpathogen B, the immune system will cre-ate memory cells against B, but that willtilt the playing field in A’s favor. Thismakes the host vulnerable to the morevirulent A. Thus, long-lasting memory ofpathogen B can actually work against thehealth of the host.

Wodarz carried out calculations show-ing that, in this scenario, the host popula-tion will indeed evolve toward a shortimmunological memory of pathogen Binfections. He reports his findings in theSept. 16 Current Biology.

“Wodarz’ paper suggests that the naiveassumption—that the longer memory lasts,the better—may be wrong,” says CharlesBangham, an immunologist at ImperialCollege in London.

Over the long term, Wodarz says, a hostpopulation would probably cycle betweenlong and short immune memory. In theabove scenario, for instance, once the hostpopulation evolved to have a short mem-ory of pathogen B, pathogen A mightbecome extinct. That would eliminate thecompetition and permit the host’s mem-ory of pathogen B to gradually lengthen.Eventually, the door would open foranother pathogen like A to spring up, andthe cycle would begin again.

The findings could have important pub-

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SCIENCENEWSThis Week

GRAND FINALE Depiction of Galileo plowing into Jupiter near the planet’s equator.

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lic health implications, Wodarz says, sincevaccines are essentially humanmadeimmune-memory boosters against diseases.“If you vaccinate a population, it may back-fire and allow the invasion of pathogensthat are more virulent,” he says.

However, he notes, it would be hard totest this hypothesis in people, since epi-demiological studies of immune memoryare difficult and slow. “It is hard even tomeasure the duration of memory in a con-trolled way,” Wodarz says. “You have toidentify when a person is infected, thendraw blood every year.”

For now, mathematical modeling may bethe best way to gain insight into the dura-tion of immune memory, says Derek Smith,a computational biologist at the Universityof Cambridge in England. For instance, hesays, it would be interesting to figure outtime scales on which a population wouldcycle between short and long memory.

The current study is a good start, Smithsays. “It’s a very sound and well-worked-outanalysis.” —E. KLARREICH

Letting the DogGenome Out Poodle DNA comparedwith that of mice, people

Chihuahuas, Irish wolfhounds, pit bulls,beagles, greyhounds, and more. Man’s bestfriend comes in a range of sizes, shapes, andtemperaments unmatched by any othermammalian species. Biologists have nowtaken a step toward understanding thatdiversity by conducting a limited, but rela-tively quick and inexpensive, scan of onedog’s full DNA sequence, or genome.

The data from this scan should ultimatelyhelp researchers study the more-than-300human diseases, such as cancer andepilepsy, that also afflict dogs. The new workhas already enabled scientists to comparethe mouse, dog, and human genomes.

“The sequence of our genome is moresimilar to the dog’s, despite the fact that thedog lineage split off first from the commonancestor” of all three mammals, says EwenF. Kirkness of The Institute for GenomicResearch (TIGR) in Rockville, Md., wholed the dog-genome project. The rodent’sunusually high mutation rate has made itsDNA diverge more from people’s than thedog’s DNA has, he explains.

In the strategy pursued by Kirkness’team, biologists isolate copies of an ani-mal’s genome and break the strands ofDNA into millions of short fragments.After determining the sequence ofnucleotides making up each such piece ofDNA, biologists use a computer to matchoverlapping sequences and piece together

as much of the animal’s full DNA sequenceas possible. The more DNA analyzed, thebetter the chance that the final genomesequence will be accurate and have fewgaps. For the human and mouse genomes,geneticists sequenced fragments equaling6 to 10 times the DNA in the actualgenome of each.

The National Institutes of Health inBethesda, Md., is sponsoring a similarlythorough dog-genome project, but Kirk-ness and his colleagues wonderedwhether they could glean important infor-mation from a substantially smalleramount of DNA. If so, researchers mightthen consider sequencing the genomes ofone animal from each of the 18 orders ofmammals.

In the Sept. 26 Science, Kirkness and hiscolleagues describe their survey of the doggenome. They ultimately sequenced DNAequal to only 1.5 times the genome. Fromthat work, they determined 77 percent ofthe dog genome and found canine DNAfragments corresponding to 18,473 of the24,567 previously documented humangenes. “We got more than we expected,”says Kirkness.

The newly available dog genome is “justa wonderful resource,” says Gustavo D.Aguirre of Cornell University.

The canine DNA analyzed came from amale standard poodle belonging to two ofthe coauthors on the new report, TIGR’sClaire M. Fraiser and J. Craig Venter of TheCenter for Advancement of Genomics, alsoin Rockville. That selection isn’t surprisinggiven that Venter used his own DNA whenhis former company, Celera, performed itscommercial sequencing of the humangenome (SN: 5/23/98, p. 334). NIH’s dog-genome project, scheduled to finish nextyear, uses DNA from a boxer. —J. TRAVIS

A Soft TouchImaging technique reveals hidden atoms

One of today’s celebrity scientific instru-ments, the atomic force microscope(AFM), is valued despite some quirks.Famous for rendering atoms visible, it canalso be blind.

That shortfall has been particularly glar-ing when it comes to graphite. AFMimages reveal only three of the six carbonatoms in each of the material’s basichexagonal units. In an upcoming Pro-ceedings of the National Academy of Sci-ences, a team of German physicistsdescribes how it solved that problem. Theadvance may lead to techniques to imagebiological materials, the physicists say.

In graphite, the hexagonal units fuse intosheets resembling miniaturized chicken wire.

Loose connections between these sheetsmake graphite soft; it’s these sheets that apencil leaves behind on paper. When intact,the sheets stack such that every other car-bon in each ring rests directly above a car-bon in the sheet below. These are known asalpha atoms. The other carbons, called betaatoms, have nothing directly underneath.

When the AFM’s cantilever tip passesover the graphite, it gently tugs on each car-bon atom but can detect the attractive forcesonly between the tip and the beta atoms.That’s because electrons in the alpha atomsoverlap with those of the atoms below,restricting interactions between the elec-trons and the AFM tip. In contrast, the less-fettered electrons of the beta atoms show upin AFM images.

Jochen Mannhart and his colleagues

at the University of Augsburg in Germanymodified their AFM to measure repul-sive forces instead of attractive ones. Thetip pushes down on each atom “like anatomic braille system,” explains Yip-WahChung at Northwestern University inEvanston, Ill.

The researchers needed to make sure theAFM tip wasn’t pushing down on thegraphite surface too forcefully. “Otherwise,the carbon [atom] will disappear inside thematerial,” says Mannhart.

As the tip approaches a carbon atom, theelectron clouds and the tip repel each other,changing the cantilever’s vibration fre-quency. In this mode, both alpha and betaatoms become visible.

The procedure is slow. To prevent subtlemotions in the sample and instrument thatwould blur the images, the measurementsmust be carried out at just a few degreesabove absolute zero.

Other types of microscopes can imagehard, electrically conducting materials withatomic resolution, but soft, nonconductingmaterials such as graphite and biologicalmolecules have been difficult to image.

To probe DNA and proteins, says North-western’s Mark Hersam, the German tech-

HIDE-AND-SEEK New technique shows allsix atoms of graphite’s basic structural unit.

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