National Academy of Sciences Annual Meeting

The National Academy of Sciences held its 106th Annual Meeting inWashington, D.C., on April 28-30, 1969. Academy Awards were pre-sented on Monday evening. The Academy Dinner on Tuesday eveningwas highlighted by an address by Lee A. DuBridge, Special Assistant tothe President for Science and Technology. Four symposia and threegroups of contributed papers comprised the scientific sessions. Abstractsof contributed papers are printed in this issue.

PRESENTATION OF ACADEMY AWARDS

Henryk Arctowski Award

J. PAUL WILD, Commonwealth Scientific and Industrial Research Organi-zation, Australia

EUGENE NEWMAN PARKER, University of Chicago

U.S. Steel Foundation Award in Molecular Biology

WILLIAM BARRY WOOD III, California Institute of Technology

Alexander Agassiz Medal

FREDERICK C. FUGLISTER, Woods Hole Oceanographic Institution

James Craig Watson Medal

JURGEN KURT MOSER, New York University

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Monday Morning:

SYMPOSIUM ON ORGAN TRANSPLANTATION IN MAN

Chairman: ANDRh COURNANDColumbia University

College of Physicians and SurgeonsNew York, New York

RUPERT E. BILLINGHAM, University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania: Genetical and Immunological Considerations Essential to the Under-standing of the Biological Problems Related to Homo- and Heterotransplantation.

FRITZ H. BACH, University of Wisconsin School of Medicine, Madison, Wisconsin:Biological Methods for the Study of Genetico-, Immuno-, and Histocompatibility, andVarious Therapeutic Resources Applicable to the Suppression or Control of Immunologi-cal Responses.

JOHN P. MERRILL, Peter Bent Brigham Hospital, Boston, Massachusetts: Experiencewith and Lessons from Transplantation of a Paired Organ, the Kidney.

NORMAN E. SHUMWAY, Stanford University School of Medicine, Palo Alto, California:Experimental and Clinical Aspects of Transplantation of an "Unpaired" Organ, theHeart.

VINCENT P. DOLE, Rockefeller University Hospital, New York, New York: EthicalAspects and Sociological Implications of Organ Transplantation as a TherapeuticProcedure.

Monday Afternoon:

SYMPOSIUM ON PLASMA LIPOPROTEINS

Chairman: DONALD S. FREDRICKSON

JOHN L. ONCLEY and NANCY R. HARVIE, University of Michigan, Ann Arbor, Michigan:Lipoproteins-A Current Perspective of Methods and Concepts.

ANTONIO M. Gorro, JR., National Heart Institute, Bethesda, Maryland: The Structureof Plasma Lipoproteins.

ALEXANDER V. NICHOLS, University of California and Lawrence Radiation Laboratory,Berkeley, California: Functions and Interrelationship of Different Classes of PlasmaLipoproteins.

DONALD S. FREDRICKSON, National Heart Institute, Bethesda, Maryland: Application ofPlasma Lipoproteins to the Study of Human Mutants and Disease.

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Wednesday Morning:

SYMPOSIUM ON PULSARS

Chairman: THOMAS GOLD

THOMAS GOLD, Cornell-Sydney University Astronomy Center, Cornell University, Ithaca,New York: Introduction.

FRANK D. DRAKE, Cornell-Sydney University Astronomy Center, Cornell University,Ithaca, New York: The Radio Observations.

F. GRAHAM SMITH, Nuffield Radio Astronomy Laboratories, University of Manchester,Macclesfield, Cheshire, England: The Radio Observations.

BART J. BOK, Steward Observatory, University of Arizona, Tucson, Arizona: The OpticalObservations.

Kip S. THORNE, Kellogg Radiation Laboratory, California Institute of Technology,Pasadena, California: Rotation and Pulsation of Superdense Stars.

PETER GOLDREICH, California Institute of Technology, Pasadena, California: Electro-dynamics of a Rapidly Rotating Magnetosphere.

Wednesday Afternoon:

SYMPOSIUM* ON SOCIAL SCIENCE PERSPECTIVESON OUR URBAN CONDITION

Chairman: WILLIAM GORHAM

WILLIAM GORHAM, The Urban Institute, Washingtoii, D).C.: Introduction.

KENNETH J. ARROW, Harvard University, Cambridge, Massachusetts: The Role of theMarket and Its Inadequacies.

JAMES G. MARCH, University of California, Irvine, California: Political Solutions andFailures.

ANTHONY DOWNS, Real Estate Research Corporation, Chicago, Illinois: An IntegrativeView of Future Options.

JAMES S. COLEMAN, The Johns Hopkins University, Baltimore, Maryland: The SocialBasis for Markets and Governments.

* Jointly sponsored by the National Academy of Sciences and the National Academy ofEngineering.

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CONTRIBUTED PAPERS

Monday Morning Session

Regeneration of Oxidative Phosphorylation in Aged Mitochondria by Prostaglandin B1:B. DAVID POLIS, ANNA MARIE PAKOSKEY, and H. W. SHMUKLER

Energy and Anesthetic-Responsive Regions of Mitochondrial Membranes: BRITTON CHANCE,C. P. LEE, L. MELA, A. AZZI, and C. K. RADDA

The Relation of the Inhibitory and the Misreading Effects of Streptomycin (SM) on Ribo-somes: BERNARD D. DAVIS and JUAN MODOLELL

The Function of C-Terminal Tyrosine Residues in Aldolases: B. L. HORECKER, R. GRACY,A. LACKO, L. DAVIS, and R. ADELMAN

Role of Reversed Electron Transfer and Pyridine Nucleotide Redox State in the Control of Cel-lular Metabolism: JOHN R. WILLIAMSON and R. SCHOLZ

Electrical Analogues for Tissues: KENNETH S. COLE, CHOH-LUH Li, and ANTHONY F.BAK

Monday Afternoon Session

Tricarbonates Derived from t-Butyl Alcohol and t-Butyl Mercaptan: D. STANLEY TARBELLand CHRISTOPHER S. DEAN

The Conductivity of Strong Electrolytes at Finite Dilution: LARS ONSAGER and MOU-SHANCHEN

Geometric Programming, Chemical Equilibrium, and the Anti-Entropy Function:CLARENCE ZENER and R. J. DUFFIN

Uncertainties in Tests of Long-Range Charge Independence: GREGORY BREIT

A Polymolecular Interpretation of Growth Rates of Social Problems: W. SHOCKLEY

Toward a Theory of Mind: ROGER W. SPERRY

Wednesday Morning SessionMechanisms of Hormonal Regulation of Enzyme Synthesis: FRANCIS T. KENNEY, KAI-LIN

LEE, and JERRY R. REEL

The Effect of Protoplasmic Acidity and of Light on the Bioelectric Potential of Valonia andBoergesenia: LAWRENCE R. BLINKS

In vitro Action of Ecdysone: CARROLL M. WILLIAMS and MICHAEL P. KAMBYSELLIS

The Role of Ecdysone and Neurosecretion in Puparium Formation (Pupariation) of Flies:G. FRAENKEL and JAN ZDAREK

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Abstracts of Papers Presented at theAnnual Meeting, Washington, D. C., 28-30 April 1969

The Effect of Protoplasmic Acidityand of Light on the BioelectricPotential of Valonia and Boergesenia

Valonia and Boergesenia normallydisplay a small potential differenceof 10 to 20 mv across the protoplasm,the vacuole being positive to the seawater. This is only slightly increasedby illumination, or by the raising of thepH of the sea water, if the latter is freefrom ammonia. However, the addi-tion of 10-4 to 10-3M NH4Cl increasesthe potential difference, the increasebeing further promoted by raising thepH, and even more rapidly in turn bylight (100 mc). A potential differenceof +50 to +60 mv can be so produced.Light presumably further decreasesthe acidity outside the cell by fixingC02 and permits more undissociatedammonia to penetrate the cell. Thereare very large light and dark transients.The effect of the ammonia (or of the

increased pH resulting from it withinthe cytoplasm) seems in turn to be dueto its influence on the plasmalemma,increasing the mobility of K ion in thelatter. The pH, ammonia, and lighteffects are almost completely abolishedin K-free sea water, but markedlyenhanced by increased KCI. A poten-tial difference of more than +100 mvhas been observed in Boergesenia ex-posed to a combination of light, highpH, ammonia, and increased KCI(0.05 M).Opposite effects are produced by

penetrating weak acids or by inhibitorswhich presumably increase proto-plasmic acidity. When the sea water

is bubbled with 5 per cent C02in air, prompt reversal of the po-tential difference to -5 or -10 mvis usually brought about. Light over-comes this, but in subsequent darkperiods the potential difference mayincrease to -20 or -30 mv, usuallyafter complicated transients with 2 ormore cusps. A still greater negativepotential difference (up to -90 mv) isproduced by low concentrations ofcyanide, azide, or dinitrophenol, pre-sumably by the production of organicacids in fermentation. Light over-comes the effect of these agents byC02 fixation, increase of the externalpH, and decrease of the penetrationof the inhibitors, which are weak acids.Anoxia also produces a small negativepotential difference, presumably againby fermentation; it is light-reversibleas well. Although the potassiummobility is often decreased by thesetreatments, it is probably not responsi-ble for the large reversals. It seemsmore likely that there is an effect uponthe tonoplast by the protoplasmicacidity, which leaves the plasmalemmapotential more or less unchanged.

LAWRENCE R. BLINKS

Hopkins Marine Stationof Stanford University

Uncertainties in Tests of Long-Range Charge Independence

Usual comparisons of the pion-nucleon coupling constant g obtainedfrom distant collisions in proton-proton(p-p) and neutron-proton (n-p) scatter-

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ing employing pseudoscalar couplingtheory do not consider nucleon-nucleon(N-N) pair formation in the pion'svicinity sufficiently. Vector mesons(w,p) provide N-N interactions leading(Breit, G., Proceedings of the Inter-national Conference on Nucleon Struc-ture, Stanford University, 1963, ed. R.Hofstadter and L. I. Schiff (Stanford,California: Stanford Univ. Press),to a pion picture similar to that ofFermi and Yang (Phys. Rev., 76, 1739(1949)) without the questionable"weak" type N-N coupling. Absorp-tion of physical pions by nucleons isnot expected therefore to be purelypseudoscalar even if this should applyto bare pions. Universal presence offactor (mT/M)2 characteristic of pseu-doscalar one-pion exchange (OPE)phase-shift formula (m,, M for pion,nucleon masses) is thus questionablefor actual OPE effects. This factor is6.7 per cent larger for ir+ and or- thanfor r0. Further, (a) employment ofmeasured pion masses is justifiable forphysical rather than bare pions, (b) theOPE potential depends on m, expo-nentially, (c) p-p and n-p interactionsdepend on charged and neutral pionsdifferently. Therefore, precision testsof isotropy of basic symmetry of 7r-Ninteraction in isotopic spin space byN-N and N-N scattering should con-sider admixtures of other than pseudo-scalar pion-physical-nucleon couplings.Some empirical differences (Breit, G.,Rev. Mod. Phys., 39, 560 (1967);Seamon, R. E., K. A. Friedman, G.Breit, R. D. Haracz, J. M. Holt, andA. Prakash, Phys. Rev., 165, 1579(1968)) in effective g's for physicalpions on physical nucleons have rightorder to fit reasonable admixtures ofinteractions with OPE potential freeof (mJM) 2 Better knowledge ofcorrections for isobar formation and oftwo-pion, vector meson and eta ex-changes is needed to ascertain theadmixtures reliably.

Supported by the Atomic EnergyCommission (NYO4022-3).

G. BREIT

State University of New York atBuffalo

Energy and Anesthetic-ResponsiveRegions of Mitochondrial Membranes

The possibility of probing hydro-phobic regions of membranes with 8-anilino-1-naphthalene sulfonate (ANS)(Weber, G., and D. R. Laurence,Biochem. J., 56, 31-P (1956)) hasrecently been realized (Azzi, A., B.Chance, G. K. Radda, and C. P. Lee,N. A. S. PROCEEDINGS, 62, no. 2 (1969);Chance, B., A. Azzi, L. Mela, G. K.Radda, and H. Vainio, FEBS Letters,in press; Tasaki, I., A. Watanabe, R.Sandlin, and L. Carnay, N. A. S.PROCEEDINGS, 61,883 (1968); Vander-kooi, J., and T. Martonosi, Biophys.Soc. Abstr., A-235 (1969)); two activ-ity-related membrane transitions arenow resolvable by kinetic studies. Afast-flow fluorometer (Chance, B., andM. Pring, Mosbach Coll., 19, 102(1968)) reads out fluorescence changesof membranes from 2 msec onward,with excitation at 405/366 nm andemission at 530-510 nm. Protein con-centrations of 30 ,ug/ml are adequate.

(1) Membrane fragments that showenergy coupling reactions exhibit twotypes of ANS environment: one in-volves a region of the membrane oc-cupiable by a large number of looselybound ANS molecules (>200 nmoles/mg pr) that react rapidly (--350 sec1),the other by a smaller number oftightly bound ANS molecules (<10nmoles/mg pr) that react slowly (0.2sec1). Both regions shown similar

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fluorescence depolarization. The slowregion enhances ANS fluorescence onlywhen the membrane is energized byATP or by electron flow from substrateto oxygen; at low [ANS] (<50 AM),membrane energization causes a dou-bling of ANS fluorescence at a similarrate (N. A. S. PROCEEDINGS, 62, no. 2(1969)). Thus, the change of state ofthe membrane identified by the fluo-resence probe technique is here shownto involve a structural reorganizationwith a 0.2 sec-' rate constant. Thisreadily reversible structural alterationoccurs in membrane fragments that arenot osmotically responsive and do notshow matrix space reorganization, as inthe case of intact mitochondria studiedby Hackenbrock (N. A. S. PROCEED-INGS, 61, 598 (1968)).

(2) Structural reorganization is ob-served when local anesthetics such asbutacaine accelerate energy-dependentcalcium uptake in intact mitochondria(Mela, B., Biochemistry, in press).ANS labeling of these membranesshows approximately doubled fluores-cence caused by butacaine addition(.100 pM). Kinetic studies againshow two types of ANS binding: onewith a first-order constant in excess of350 sec-' and the other with a constantof approximately 2.0 sec'. Bothfast and slow reactions involve regionsof the membrane with similar ANSaffinities and fluorescence depolariza-tion. Thus, low butacaine concentra-tions induce a first-order transitionbetween membrane states of high andlow calcium transport activity. Thesetwo activity-related structural changesreported by ANS in mitochondrialmembranes are found to lie in the timeregion 0.2 to 2.0 sece1.

B. CHANCE, C. P. LEEL. MELA, A. Azzi

C. K. RADDA

Electrical Analogues for Tissues

The equations of Maxwell and Ray-leigh for the electrical resistance ofsuspensions of spheres and cylindershave been widely used to calculatethe volume concentration of non-conducting cells in several tissues. Theassumptions made in the derivations ofthese equations are not valid over atleast part of the concentration rangefrom 50 to 100 per cent, so that suchcalculations are without analyticalbasis.

Approximations for uniform, uni-formly separated, space-filling figuresand for randomly oriented, uniform,and uniformly distributed conductingplanes showed that each of the equa-tions was correct for volume concentra-tions approaching 100 per cent.Analogue measurements were made

with conducting paper for circularcylinders in square and hexagonalarrays and with an electrolytic tankfor spheres in simple and face centeredcubic arrays. The available theoriesare not entirely satisfactory.

Similar analogue measurements weremade for a square array of squarecylinders and a hexagonal array ofhexagonal cylinders and for a cubicarray of cubes and a hexagonal arrayof tetra-kai decahedra. In all cases itwas found that the measured volumeconcentrations agreed with those givenby the simple Rayleigh and Maxwellequations, to within the experimentalaccuracies of about 1 per cent, overall the concentration ranges measuredfrom 30 per cent or less to 90 per centor more. These analogue calculationsthus provide a basis for the use of theequations over the entire range.

KENNETH S. COLECHOH-LUH Li

ANTHONY F. BAK

National Institutes of Health

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University of Penn&ylvania

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The Relation of the Inhibitory andthe Misreading Effects ofStreptomycin on Ribosomes

The mechanism by which strepto-mycin inhibits ribosomes has been moreobscure than its misreading effect,which evidently involves distortion ofthe recognition region. Using phageMS2 RNA as messenger in E. coliextracts, we have found that strepto-mycin immediately blocks polypeptidechain extension (N. A. S. PROCEEDINGS,61, 1279 (1968)). However, the re-sulting stabilization of the polysomes,in contrast to that produced by variousother inhibitors of the ribosome, is onlytransient: nascent polypeptide andmessenger- slowly fall off the ribosome,with a half time of about four minutesat 34°. During the transient stabiliza-tion the nascent polypeptides appearto be in the P site, since they are allrapidly released by puromycin; andtheir eventual release by streptomycinevidently requires transfer to the Asite, since this release is halted by drugsthat block the transfer either directly(chloramphenicol) or by interferingwith aminoacyl-tRNA binding in theA site (tetracycline). These observa-tions may be explained if streptomycindistorts the A site in a way that (a)hinders the binding of aminoacyl-tRNA (or at least its binding in aposition where it can accept peptidyltransfer), and (b) weakens retentionof the peptidyl-tRNA formed in theA site by this transfer. Thus the in-hibitory action of streptomycin maywell be due to distortion of the sameregion that is responsible, under othercircumstances, for misreading.

BERNARD D. DAVISJUAN MODOLELL

Harvard Medical School

Tricarbonates Derived from t-ButylAlcohol and t-Butyl Mercajtan

After studies on the preparation ofcarbonic-phosphoric anhydrides (cf.Tarbell, D. S., and M. A. Insalaco,N. A. S. PROCEEDINGS, 57, 233 (1967)),we found that treatment of sodium t-butyl thiolcarbonate with phosgeneyielded the crystalline tricarbonate I,RSCOOCOOCOSR, which decomposedon heating to the dicarbonate II,RSCOOCOSR, and this in turn to themonocarbonate III, RSCOSR, eachwith the loss of carbon dioxide (R =(CH8)3C) (Friederang, A. W., and D. S.Tarbell, Tetrahedron Letters, 5535(1968)). We now find that the corre-sponding oxygen tricarbonate IV,ROCOOCOOCOOR, can be obtainedas a crystalline solid, m.p. 64.5-65°, bytreatment of potassium t-butoxide,(CH3)aCOK, with carbon dioxide, fol-lowed by phosgene; IV yields 3 molesof carbon dioxide, 1 mole of isobutene,and 1 mole of t-butyl alcohol, whenheated without solvent above themelting point. The dicarbonate,ROCOOCOOR (Howe, J. H., andL. R. Morris, J. Org. Chem., 27, 1901(1962)), is an intermediate in this de-composition. The tricarbonates I andIV appear to be the first examples oftheir class, and their chemistry will bediscussed.

CHRISTOPHER S. DEAND. STANLEY TARBELL

Vanderbilt University

Geometric Programming,Chemical Equilibrium, and theAntientropy Function

The culmination of this paper is thefollowing duality principle of thermo-dynamics

maximum S = minimum S*. (1)

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The left side of (1) is the classicalcharacterization of equilibrium. Itsays to maximize the entropy functionS with respect to extensive variableswhich are subject to certain con-straints. The right side of (1) is a newcharacterization of equilibrium andconcerns minimization of an anti-entropy function S* with respect tointensive variables. Relation (1) isapplied to the chemical equilibrium ofa mixture of gases at constant tem-perature and volume. Then (1) spe-cializes to

minimum F = maximum F*, (2)where F is the Helmholtz function forfree energy and F* is an anti-Helm-holtz function. It results that theright side of (2) is an unconstrainedmaximization problem and gives asimplified practical procedure for calcu-lating equilibrium concentrations. Wealso give a direct proof of (2) by theduality theorem of geometric pro-gramming. The duality theorem ofgeometric programming states thatminimum cost = maximum anticost.

(3)We complete this circle of ideas byexhibiting an intimate relation betweengeometric programming and the Dar-win-Fowler method in statistical ther-modynamics.

R. J. DUFFINC. ZENER

Carnegie-Mellon University

The Role of Ecdysone andNeurosecretion in PupariumFormation (Pupariation) of Flies

During pupariation fly larvae firstcontract to form the barrel-shapedpuparium, and then the cuticle darkensand hardens by phenolic tanning.That tanning which one of us (G. F.)

demonstrated 35 years ago is inducedby a hormone (known as ecdysone):Larvae of Calliphora erythrocephala wereligated into two parts before a criticalperiod. The hind parts which wouldremain untanned were induced to tanby the injection of blood from pu-pariating larvae. The validity of thisexperiment has recently been ques-tioned by Ohtaki et al. (Biol. Bull.,135, 322 (1968)) who failed to re-produce it with the use of a memberof a different family (Sarcophagaperegrina) and a different technique.On reinvestigation, the original resultswere readily reproduced with Phormiaregina, but not with Sarcophaga bul-lata. The following observations pos-sibly explain these conflicting data.When larvae of S. bullata are ligaturedafter the critical period, injection ofbrain extracts into the hind partsgreatly accelerates pupariation. Thefollowing preparations have the sameeffect: Extracts from pars intercere-bralis, or from corpora cardicaca fromfly larvae, Periplaneta, or Pyrrhocoris.Injection of additional ecdysone doesnot have this effect. Thus the activematerial is neurosecretory and does notact via releasing ecdysone from thering gland. These data suggest thatqualitative or quantitative effects ofecdysone cannot be gauged without aconsideration of neurosecretory activ-ity. The active factor is different frombursicon, but it may be identical withthe ("activating") brain hormone.

G. FRAENKELJAN ZDAREK

University of Illinois

The Function of C-Terminal TyrosineResidues in Aldolases

The C-terminal tyrosine residues inrabbit muscle aldolase have previouslybeen shown to be essential for full

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activity with fructose-1,6-P (FDP) butnot for activity with fructose 1-P(F1P), suggesting that these tyrosineresidues play a role in the recognitionof the 6-phosphate group. We havenow shown that the presence of sub-strate or substrate analogues, such ashexitol diphosphate, renders thesetyrosine residues resistant to the actionof carboxypeptidase. Reciprocal ef-fects can also be demonstrated for theinteraction of the enzyme with alde-hyde phosphate substrates such asglyceraldehyde 3-P or erythrose 4-P.The native enzyme is inactivated by thelatter substrate, with the incorporationof one equivalent per active site. Theinactivated enzyme, which containsbound phosphate, is resistant to car-boxypeptidase. After tyrosine hasbeen removed from the native enzyme,the enzyme is no longer inactivated byglyceraldehyde 3-P. The rabbit liverenzyme is not inactivated by glycer-aldehyde 3-P, nor does it show en-hanced activity with FDP (as com-pared with F1P). We have nowshown that the C-terminal residues inthe rabbit liver enzyme are glycine,rather than tyrosine. In the case ofaldolase from spinach leaves, C-termi-nal tyrosines are present and areessential for activity with FDP. Thekinetics of inactivation by carboxy-peptidase suggest that interaction be-tween the subunits plays a role inmaintaining the catalytic activity.

B. L. HORECKER, R. GRACYA. LACKO, L. DAVIS

R. ADELMAN

Albert Einstein College of Medicine

Mechanisms of Hormonal Regulationof Enzyme Synthesis

Synthesis of the enzyme, tyrosine-a-ketoglutarate transaminase, is acceler-

ated by both steroid (hydrocortisone)and polypeptide (glucagon) hormonesin cultures of Reuber (H35) hepatomacells. The two hormones togetheryield additive or synergistic effects.Label and chase experiments show thatthe enzyme undergoes turnover inthese cells with a half life of aboutthree hours, and measurements of thedecline in enzyme synthesis afteractinomycin indicate that the trans-aminase mRNA decays at about thesame rate. With these data it waspossible to show that induction byhydrocortisone involves production ofa substance with a lifetime like thatof the transaminase mRNA, whileglucagon induction does not. Sec-ondly, induction by hydrocortisoneis completely sensitive to actinomycin,whereas glucagon induction is insensi-tive for a period of time correspondingto the lifetime of the transaminasemRNA. Finally, preinduction withhydrocortisone removes a limitation inthe response to glucagon; the latterhormone effects a very rapid and largeinduction which is insensitive to actino-mycin in cells pretreated with hydro-cortisone. Preinduction with glucagondoes not alter the response to hydro-cortisone. We conclude that thesteroid hormone acts on genetic tran-scription to promote synthesis oftransaminase-specific messenger RNA,while glucagon acts at some post-transcriptional step in enzyme syn-thesis.

FRANCIS T. KENNEY, KAI-LIN LEEJERRY R. REEL

Oak Ridge National Laboratory

The Conductivity of StrongElectrolytes at Finite Dilution

The electrostatic forces between theions in an electrolyte affect their

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migration velocities by two niecha-nisms: A distortion of the shieldingcharge cloud around each ion producesa field which usually retards its motion,and the force of an electric field oil thecharge cloud, transmitted to the sol-vent, produces a countercurrent. Infirst approximation the effects areproportional to the square root C1"2 ofthe concentration; the appropriatecoefficients were computed long since.Second-order terms are proportionalto Cl12 log C; again with predictablecoefficients, these have been computedfor arbitrary mixtures of ions. Pre-vious computations for simple binaryelectrolytes were found incomplete.To be specific, a term El arises from amore accurate computation of thecharge asymmetry causedby migration,and a term E2 from a modification ofthe charge asymmetry by hydro-dynamic flow. Both remain un-changed, but an effect reciprocal to thelatter produces a significant term E3.In the simplest case the two cross-terms are equal; in general, E2 and E3are reciprocal in the sense of irreversi-ble thermodynamics.

LARS ONSAGERMOU-SHAN CHEN

Yale University

Regeneration of OxidativePhosphorylation in AgedMitochondria by Prostaglandin B1

Studies on humans subjected tophysical or psychic stress revealedcommon plasma increments in the levelof phosphatidyl glycerol. Similarchanges were found in the plasma andtissues of acceleration-stressed rats.The effects of acceleration on theplasma level of phosphatidyl glycerol

could be reproduced by the injection ofprostaglandin El. Experiments in vivoshowed exceptionally fast turnoverrates of p32 in phosphatidyl glycerolisolated from liver mitochondria ofrats. These observations led to studieson the possible role of prostaglandinsand phosphatidyl glycerol in phos-phorylation mechanisms. When agedmitochondria were further "un-coupled" with Triton X-100 and re-acted with adenosine diphosphate andp32 under conditions for oxidativephosphorylation, analysis of the re-action products by ion exchange chro-matography gave increased levels ofadenylic acid and inorganic phosphate.Addition of prostaglandin El andphosphatidyl glycerol to the reactionreversed the dephosphorylation andyielded a net increase in adenosinetriphosphate correlated with a decreasein inorganic phosphate. In the pres-ence of Triton X-100, both prosta-glandin El and prostaglandin B1 wereequally effective in reactivating phos-phorylation. In the absence of TritonX-100, prostaglandin El was inactive,but prostaglandin B1 was effectivealone. Thin-layer chromatography onsilica of the one-minute reaction prod-ucts extracted by chloroform-methanolseparated a radioactive phosphate-labeled lipid component derived pre-sumptively from prostaglandin B1.The implication of prostaglandin B1

as a possible intermediate in mito-chondrial phosphorylation offers anew probe to the mechanisms involvedin the transformation of oxidativeenergy.

B. DAVID. POLISANNA MARIE PAKOSKEY

H. W. SHMUKLER

Aerospace Medical Research Depart-ment,

U. S. Naval Air Development Center,Warminster, Pennsylvania

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A Polymolecular Interpretation ofGrowth Rates of Social Problems

Are the decreases in the socialquality of our citizens evidenced byrising crime and riot rates environ-mental or hereditary? Can any quan-titative method be developed to reducethe environment-heredity-uncertainty?The proposed analysis compares therates of growth of social problems tothose of possibly relevant segments ofour population. Estimated rates ofgrowth of riots and of violent crime are,respectively, about 50 and 10 per centa year (see Shockley, W., "Humanquality problems and research taboos,"in Proceedings of the 1968 Conference ofthe Educational Records Bureau). Twopersonality traits, neuroticism (emo-tional instability) and extraversion(carefreeness), are almost as heritableas intelligence (see Eysenck, H. J., inCrime and Personality (Houghton Miff-lin, 1964)), about 70 to 80 per cent ofthe variance in IQ under normal con-

ditions being genetically controlled(Jensen, A. R., Harvard EducationalReview, Winter 1968). Eysenck re-

ports that neuroticism and extraver-sion are significantly high for unwedmothers and women prisoners, suggest-ing that unwed mothers can transmitgenetically controlled antisocial be-havior traits. If so, the compound-interest-like rates of increase of 7 per

cent a year for white illegitimate birthsand 3 per cent for nonwhite may berelated to the 10 and 50 per cent ratesfor violent crime and riots: If a violentcrime requires the interaction of twopersons, and the nucleation of a riot16 persons, then the rates quoted forthe increase of illegitimacy would ac-

cord with the growth rates of 14 percent for white violent crime and 48per cent for Negro riots if these socialphenomena involve bringing antisocialindividuals together by mechanisms

equivalent to the random collision ofmolecules in a chemical reaction.

W. SHOCKLEYStanford University

Toward a Theory of Mind

Efforts to cope with problems ofmental experience in the bisected brainhave led to a modified interpretationof consciousness. The current con-cept departs from prevailing materialistapproaches of 20th century neuro-science in postulating that consciousphenomena play an active directiverole in shaping the flow pattern ofcerebral excitation. Instead of beingparallelistic and noninterventionist,consciousness in the present schemebecomes an integral part of the brainprocess itself and an essential andpotent constituent of the action.Consciousness is put to work and givena use and a reason for having beenevolved. Subjective experience in thisinterpretation is conceived to be anemergent dynamic property of cerebralexcitation, inseparable from the ma-terial brain process, but different from,and more than, the collected sum ofof the physicochemical components.Compared to the elementary physi-ological properties, the conscious prop-erties are more molar; they encompassand transcend the details of nerve im-pulse action in the same sense thatcellular properties transcend the mo-lecular, the molecular transcend theatomic, etc. The mental forces do notviolate or intervene in neuronal ac-tivity; however, they do supervene.The brain process must accordinglydetect and react to the pattern proper-ties of its own excitations, respondingto the gestalt qualities and forces of agiven excitation pattern as an entityrather than to its individual excitatoryelements. It follows that a full ex-

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plaiiatioii of a conscious sequence ofcerebral activity would not be possiblesolely in terms of the biochemical andelectrophysiological data; the pattern-derived qualities that constitute con-scious experience must be included.

ROGER W. SPERRYCalifornia Institute of Technology

In vitro Action of Ecdysone

When the spermatocytes of dia-pausing silkworm pupae (Samia cyn-thia) have been removed from thetestes and cultured in vitro, they showno detectable response after the addi-tion of a- or ,3-ecdysone. By contrast,a rapid differentiation into sperma-tozoa takes place when an extractable,heat-labile, nondialyzable blood factoris present or is added to ecdysone-freeculture medium. The "macromolec-ular factor" could not be detected inthe blood of pupae during the firstseveral months of diapause. However,it swiftly appears in the blood of ab-domens isolated from diapausing pu-pae subjected to integumentary in-jury or injected with a-ecdysone.

Unlike the "naked" spermatocytes,the cells within intact testes show nodetectable response when either themacromolecular factor or ecdysone isadded to the medium. But when bothsubstances are added, the spermato-cytes within the intact testes undergorapid differentiation into spermatozoa.Testes cultured for one hour in thepresence of a-ecdysone show the de-velopmental response when rinsed andsubsequently cultured in ecdysone-free medium containing the macro-molecular factor.These observations suggest that

ecdysone alters the permeability ofthe testicular walls to allow the macro-molecular factor to enter the testes.The macromolecular factor, as demon-strated in the cultures of "naked"

spermatocytes, then provokes the de-velopmental response. We suspectthat this "permissive" mode of actionof ecdysone may not be peculiar to thetestes.

CARROLL MAl. WILLIAMSMICHAEL P. KAMBYSELLIS

Harvard University

Role of Reversed Electron Transferand Pyridine Nucleotide RedoxState in the Control of CellularMetabolism

Studies with perfused rat liver on thecontrol of gluconeogenesis and citricacid cycle have clarified the role of theNAD redox state in metabolic regula-tion. Addition of fatty acids to liversincreased the redox state of flavin andpyridine nucleotides. These changesare greatly diminished when oxidativephosphorylation is uncoupled. Byanalogy with studies on isolated mito-chondria, it is suggested that duringA-oxidation, the mitochondrial NAD-system is maintained more reduced asa consequence of reversed electrontransfer from the highly reduced flavinpool. Gluconeogenesis from alanine islimited by the transfer of reducingequivalents from mitochondria to cy-tosol. This process is mediated by amalate H-shuttle, which is facilitatedby an increased mitochondrial NADH/NAD ratio. Thus, enhanced fattyacid oxidation stimulates the glycer-aldehyde dehydrogenase reaction inthe direction of glucose synthesis.Simultaneous ethanol oxidation in-creases the NADH/NAD ratio in thecytosol, but it also increases the rate ofNADH delivery to the respiratorychain. The further increase of themitochondrial NADH/NAD ratio de-presses the oxalacetate concentrationand inhibits citrate production. A fallof citrate, however, activates phospho-fructokinase, so that finally glucose

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production is inhibited due to in-creased glycolytic activity. The roleof malate in the H-shuttle was revealedby experiments with n-butylmalonatewhich inhibited both ethanol oxidationand gluconeogenesis from pyruvate.These studies illustrate both the ther-modynamic control function of NADredox systems and the kinetic control

function of net hydrogen flux acrossthe mitochondrial membrane whichregulates gluconeogenesis by outwardtransport, and citric acid cycle activityby inward transport.

JOHN R. WILLIAMSONR. SCHOLZ

University of Pennsylvania

Blinks, Lawrence R...............................................Breit, G..........................................................Chance, B., C. P. Lee, L. Mela, A. Azzi, and C. K. Radda..............Cole, Kenneth S., Choh-Luh Li, and Anthony F. Bak..................Davis, Bernard D., and Juan Modolell.............................Dean, Christopher S., and D. Stanley Tarbell........................Duffin, R. J., and C. Zener........................................Fraenkel, G., and Jan Zdarek ....................................

Horecker, B. L., R. Gracy, A. Lacko, L. Davis, and R. Adelman.Kenney, Francis T., Kai-Lin Lee, and Jerry R. Reel...................Onsager, Lars, and Mou-Shan Chen................................Polis, B. David, Anna Marie Pakoskey, and H. W. Shmukler...........Shockley, W......................................................Sperry, Roger W..................................................Williams, Carroll M., and Michael P. Kambysellis ....................Williamson, John R., and R. Scholz.................................

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