scientific american - 1993 11 - reading the genes of extinct species

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NOVEMBER 1993

$3.95

Silicon switch provides deft control over electrical power ßow, enhancing grid eÛciency and reliability.

Reading the genes of extinct species.

Observing cannibal stars.

Can the environment survive free trade?

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November 1993 Volume 269 Number 5

environmen-Unless all producers and consumers are directly liable for the cost of mental damage, free trade can seriously endanger the ecosystem Manufacturerscan move capital to regions unprotected by strong environmental laws JobsÑand degradation of air, water and the biosphereÑwill rapidly be exported there

environ-Every thought, every voluntary action, begins when a neurotransmitter, releasedinto a synapse, locks with its corresponding receptor The receptor changesshape, causing the neuron to become permeable to ions As the ions move, theychange the electrical potential of the cell, causing a wave of current to run down

it How binding to a receptor can induce ionic ßow is now becoming clear

Most of the stars that pierce the night sky glow because of the fusion of atomicnuclei But some double stars produce outpourings of x-rays through an evenmore eÛcient process These systems often contain a tiny neutron star and amuch larger companion The neutron starÕs powerful gravitational Þeld pulls gasfrom the other star As the material gathers, it grows so hot that it emits x-rays

4

72

X-ray Binaries

Edward P J van den Heuvel and Jan van Paradijs

A half century ago this ŽmigrŽ from Ukraine began to fashion his vision of century civilization, in which humans and machines grew to resemble each oth-

20th-er as the agents of war and peace shaped their mast20th-ersÕ lives

S CIENCE IN PICTURES

The Art of Boris ArtzybasheÝ

Domenic J Iacono

D EBATE: DOES FREE TRADE HARM THE ENVIRONMENT?

The Case for Free Trade

Jagdish Bhagwati

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After decades of sincere, earnest eÝort to engage women in science, the sion resists their admission into its informal clubs and networks more com-pletely than does almost any other The reasons range from sexism and the tra-ditions of mentoring to the expectations that teachers and other adults harborfor girls and boys in the earliest years of school.

profes-D E PARTM E N T S

50 and 100 Years Ago

1893: The Edison inventionthat didnÕt get oÝ the ground

Letters to the Editor

Gnashings over nature versusnurture Normal abnormals

Science and the Citizen

Science and Business

Book Reviews

A cultivated look at the ical roots of mental illness

biolog-Essay :Bruce Russett

Rxfor global peace: a world

Research chemists seek kinder lysts Hardening airliners Soft-ware skipper A one-horse race for

cata-an AIDS vaccine Regenerate thedentin and pass the Godiva THEANALYTICAL ECONOMIST: Ivy Leaguebonus babies

T RENDS IN THE SOCIOLOGY OF SCIENCE

A Lab of Her Own

Marguerite Holloway, staÝ writer

High-Power Electronics

Narain G Hingorani and Karl E Stahlkopf

Consumers of electrical power demand both quality and quantity The existingtechnology for controlling the ßow of power through the nationÕs grid presents

a choice between economy and spotty performance or waste and reliability Tothe rescue come semiconductor switching devices

rights reserved No part of this issue may be reproduced by any mechanical, photographic or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted or otherwise copied for public or private use without written permission of the publisher Second-class postage paid at New York, N.Y., and at additional mailing offices Authorized as second-class mail by the Post Office Department, Ottawa, Canada, and for payment of postage in cash Canadian GST No R 127387652 Subscription rates: one year

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60 Jean-Louis Dubois/ Jacana

60FÐ62 Dimitry Schidlovsky

65 Alfred T Kamajian

66Ð70 Jared Schneidman

72Ð73 Courtesy of the University

Art Collection, Syracuse

University

74Ð75 Courtesy of Dodd, Mead

(top center ), Syracuse

University (left and right)

92 Thomas Stephan/Black Star

94Ð95 The MIT Museum (left),

Jessica Boyatt (right)

96Ð97 top: Courtesy of Cheryl

Ann Butman; Chris Smith/

U.S Department of Healthand Human Services; JimStarford/Black Star ; Mar-guerite Holloway ; GeorgiaLitwack ; courtesy of Deb-

orah Gordon; bottom:

Bett-mann Archive; courtesy

of …Ýentliche lung Kupferstichkabinett,Basel ; Steve Murez/BlackStar ; painting by HermioneDassel (1851), courtesy

Kunstamm-of Vassar College Archives;

Bettmann Archive; Caroline

L Hunt, The Life of Ellen H

Richards, Boston (1912)

98Ð99 top: Georgia Litwack ;

Georgia Litwack ; GeorgiaLitwack ; Ricardo Azoury/

SABA; John Reader, SciencePhoto Library/Photo Re-searchers, Inc.; Sam Mc-Naughton, courtesy ofNYZS The Wildlife Con-

servation Society; bottom:

Bettmann Archive; mann Archive; UPI /Bett-mann; UPI /Bettmann;

Bett-Bettmann Archive; courtesy

of Marine Biology tory, Woods Hole, Mass

Labora-100Ð101 top: AP World Wide Photos;

Schurlock Studio; KatherineLambert ; Per Breiehagen/

Black Star ; Georgia wack; courtesy of Carol

Lit-Wood ; bottom: Joseph ner from Nobel Prize Women

Lar-in Science, by Sharon Bertsch

McGrayne, Birch Lane Press,1993; UPI /Bettmann; UPI /Bettmann; UPI /Bettmann;

UPI /Bettmann; Donald L D

Caspar from Nobel Prize

Women in Science

112 Patricia J Wynne114Ð115 Johnny Johnson

THE ILLUSTRATIONS

Cover image by Michael Goodman

EDITOR: Jonathan Piel

BOARD OF EDITORS: Michelle Press, Managing

Editor ; John Rennie, Russell Ruthen, Associate Editors; Timothy M Beardsley ; W Wayt Gibbs;

Marguerite Holloway ; John Horgan , Senior

Writ-er ; Philip Morrison, Book Editor ; Corey S Powell;

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THE COVER image depicts an trolled thyristor, a device for handling high-voltage electricity Current entering andleaving the device is represented by thebright, glowing regions Thyristors combinehigh-power electronics with the same kinds

MOS-con-of silicon fabrication techniques used tomake integrated circuits By increasing thecapacity of high-voltage transmission lines,utilities could defer up to $50 billion inspending over the next 30 years (see Ị High-Power Electronics,Ĩ by Narain G Hingoraniand Karl E Stahlkopf, page 78)

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LETTERS TO THE EDITORS

Genes and Behavior

John HorganÕs article ỊEugenics

Re-visitedĨ [SCIENTIFIC AMERICAN, June], as

its title suggests, would rather try to

embarrass behavioral geneticists and

impugn their motives as politically

sus-pect than enlighten the reader about a

long-standing controversy

The two boxes and the captions of

the Þve illustrations betray HorganÕs

in-tent: claims of genetic inßuence on

psy-chological characteristics are alleged to

be overblown or doubtful and to have

been recently retracted or deemed

un-publishable One half-page box reminds

the reader that Hitler was an

enthusias-tic eugenicist and thus, presumably,

had much in common with the modern

behavioral genetics researcher But as

those who are familiar with

contempo-rary behavioral genetics literature will

know, these baseless accusations are

merely an attempt to win with scare

tactics that which has not been won in

the research laboratory

Apart from direct assessments, the

status of an individualÕs identical twin

is the single best predictor of risk for

schizophrenia, manic-depressive illness,

alcoholism, IQ and personality

More-over, evidence from twin studies is

consistent with both adoption studies,

which show that adoptees resemble

psychologically their biological parents

more than their adoptive parents, and

family studies, which demonstrate that

the psychological similarity among

rel-atives is directly related to their degree

of genetic relatedness

Explanations for behavioral genetics

Þndings summarized in HorganÕs

arti-cle are either laughable (as when he

says the similarity in sexual orientation

between twins owes to having been

dressed alike as children), disingenuous

(as when twins reared apart are said to

owe their similarity to contact between

the twins even though both the

Min-nesota and the Karolinska groups have

tested and rejected that possibility), or

misleading (as when Horgan features

the only study of alcoholism in male

twins that failed to report signiÞcantly

greater concordance between identical

than nonidentical twinsĐeven though

that study involved a far smaller

sam-ple than any of the Þve other studies)

Ironically, a case for behavioral

ge-netics is made in the article on

ỊAu-tism,Ĩ by Uta Frith, in the same issue A

generation ago behavioral scientists cribed autism to, among other things,the inadequacies of Ịrefrigerator moth-ers.Ĩ As Frith points out, twin studieshave shown that Ịautism can have a ge-netic basis,Ĩ and biobehavioral models

as-of autism are now favored Horgan, andthe select group of critics he promotes,may long for the bygone days of radi-cal environmentalism, but thankfullythose days are past

MATT MCGUEDepartment of PsychologyUniversity of Minnesota

Co-signers include 16 scientists from eight institutions in the U.S., Australia, Sweden and the Netherlands; list available from McGue.

Horgan replies:

IÕll respond to just three points made

by McGue et al First, nowhere did I pugn their motives as politically sus-pect But since they raise the issue, let

im-me note that the major sponsor of theMinnesota twin studies is the PioneerFund, a private foundation that has alsosupported William Shockley and otherproponents of racial theories of intelli-gence Second, the chief critics of theMinnesota twin studies are not ỊradicalenvironmentalistsĨ but other behavior-

al geneticists, who believe the methods

of the Minnesota group are biased ward high heritability Finally, a grow-ing number of investigators suspectthat viral infections or physical trau-mas occurring during pregnancy mightcause autismĐpossibilities that do notfall neatly into either the nature or nur-ture category

to-Cochlear Implants

I commend John Rennie on ỊWho IsNormal?Ĩ [ỊScience and the Citizen,Ĩ

SCIENTIFIC AMERICAN, August] As one

of a few audiologists who respect andactively elicit the view of the Americandeaf community, I am thrilled to see atlast such an unbiased article about thiscontroversial topic of cochlear implants

I would have to agree with RobertShannon, who stated so assuredly, ỊIdonÕt think that deaf people are wellintegrated into society at large.Ĩ Iwould have to add that this is true forAfrican-Americans, Hispanic-Americans,

female Americans, gay Americans, poorAmericans, handicapped Americans andother oppressed minorities ỊSociety atlargeĨ in this country means white, up-per middle class, Protestant, well edu-cated and male We, as a country, shape,coerce and even demand our inhabi-tants to conform to this mold or be clas-siÞed as a second-class citizen How un-fortunate How sad

We should no more be trying to makedeaf children hearing or Little Peopletaller than we should try to make Afri-can-Americans white or women intomen If we can stop making assump-tions long enough to listen to thosewho are deaf, listen to those who areLittle People, listen to those who areAfrican-American then we can hear

the truth.

HOLLY M GEESLINIndianapolis, Ind

CanÕt Get There from Here

In ỊAustraliaÕs Polar DinosaursĨ [SENTIFIC AMERICAN, July], Patricia Vick-ers-Rich and Thomas Hewitt Rich spec-ulate that the tendency toward dwarf-ism shown by populations on islandsmay be a response to selective pressure

CI-to increase the number of individuals

so as to ensure a diverse gene pool Yetselective pressure can reduce the aver-age size of a population only if a smallindividual achieves greater reproduc-tive Þtness than its larger cousins Theprospect of retaining a diverse genepool many generations into the futurecannot have the eÝect of increasing thefrequency of a gene for small size

ANDREW PAGELangport, England

Vickers-Rich and Rich reply:

You are correct Space considerationsforced us to abbreviate our presenta-tion of the mechnisms causing dwarf-ism in island populations Page 196 of

our book Wildlife of Gondwana ( Reed

Books, Sydney, 1993) has a more ough treatment of this topic

thor-8 SCIENTIFIC AMERICAN November 1993

Because of the volume of mail, letters

to the editor cannot be acknowledged Letters selected for publication may be edited for length and clarity.

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50 AND 100 YEARS AGO

0NOVEMBER 1943

ỊAir-conditioning of submarines is

now possible through use of a

non-tox-ic, non-explosive ßuid, called ƠFreon-12,Õ

ßuorine refrigerant, which is

non-poi-sonous, has no odor, and will not

sup-port ßame It does not explode should

it come into contact with the electric

stoves of a subÕs galley, nor does it

in-terfere with the chemicals which purify

the air The men aboard the underseas

vessels so equipped can even smoke.Ĩ

ỊGlass with non-reßecting surfaces,

developed for military uses by

Ameri-can Optical and RCA, Ameri-can be applied,

with desirable results, to post-war

man-ufacture of many useful items Among

the new products are windshields sans

dangerous reßections, less conspicuous

spectacle lenses, more easily read

in-struments, faster camera lenses, shop

windows free from reßections, more

eÛcient microscopes and other

light-transmitting instruments.Ĩ

ỊNewspapers and magazines of

to-day frequently predict a post-war

fu-ture including a private airplane in

ev-ery garage General Aircraft

Corpora-tion has opened up a bit in regard to

its plans Here is a

prophet-ic quotation: ƠOur business

man leaves his home in the

morning in his Ơcar,Õ drives

to the airport While having

his ƠcarÕ Þlled with gas, the

attendants put on the wings,

a Þve-minute job After

ßy-ing to his destination, he has

the wings removed, drives

his ƠcarÕ downtown, makes

his necessary calls, drives

back to the airport, and,

don-ning his wings, goes on to

his next destination by air.Õ Ĩ

ỊRayon and other Þbers

are cutting deeply into

cot-tonÕs tire-cord monopoly and

are threatening other

strong-holds Science, however, is

starting to alter the situation

Designs for cotton goods are

being developed in many

forms; chemical treatments

are being worked out to

change the feel, the

appear-ance, and the quality of

cot-ton fabrics; cotcot-ton is being

made water-proof, rot-proof, Þre-proof,and spot-proof; agricultural experts aredeveloping plants which will producebetter grades of the Þber in largerquantities.Ĩ

NOVEMBER 1893ỊIf ordinary placental mammals haveevolved from pouched animals like themodern marsupials, rudiments of thepouch ought certainly to be recogniz-able in some of them Dr H Klaatschhas just made the interesting announce-ment that such rudiments can actually

be observed in most placentals thing of the kind has already beenfound in the lemurs, and one author hassupposed that rudiments of the pouchcan also be detected in the sheep.Ĩ

Some-Ị ƠOnce I placed an aerial motor on apair of Fairbanks scales and set it going,Õsays Thomas A Edison ƠIt lightened thescales, but it didnÕt ßy Another time Irigged up an umbrella-like disk of shut-ters and connected it with a rapid pis-ton in a perpendicular cylinder These

shutters would open and shut If I couldhave got suÛcient speed, say a mile asecond, the inertia or resistance of theair would have been as great as steel,and the quick operation of these shut-ters would have driven the machine, but

I couldnÕt get the speed I believe thatbefore the air ship men succeed theywill have to do away with the buoyancychamber.Õ Ĩ

ỊThe American Telephone and graph Company recently gave an exhi-bition of their long-distance telephonelines to a small party of guests who as-sembled at the Telephone building inCortlandt Street Among those assem-bled were Dr Von Helmholtz and Prof.Alexander Graham Bell A number ofreceivers were arranged so as to giveeach of the party a connection to theline Connection was made with Bos-ton, Chicago, and Washington in turn,and conversations were held with theoÛcers at those points A cornet wasalso played which was heard through

Tele-500 miles of wire as distinctly as though

it were in an adjoining room.ĨỊIt is indispensable for the sake ofeconomy, and especially for safety, toshut oÝ the gas at the meter for the

night in every house Themovable night lamp, whichoperates at an expense ofbut one cent a night, pre-sents the advantage of ac-companying those who go

up or down stairs after thegas has been put out It suf-Þces to grasp at the bottom

of the staircase a light terpoise Þxed to the lamp by

coun-a cord, coun-and the lcoun-amp thenascends with the person andaÝords him light progres-sively When the story atwhich one is to stop isreached, the lamp, upon theweight being released, de-scends of itself to the bot-tom of the stairway In order

to descend with a light, itsuÛces to raise the lampthrough the chain that sup-ports it (an operation thatrequires three seconds) and

to grasp the counterpoise.The lamp then follows theperson to the bottom of thestaircase.Ĩ

Movable lamp for stairway

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Grim Statistics

GunÞre may surpass auto

accidents as a cause of death

The European tourists who

were shot by highway

Òhun-tersÓ in Florida were

driv-ing cars that were legally required

to have seat belts and may even

have been equipped with airbags

Whereas nationwide concern

with automobile safety has led to

improved crash-worthiness and

tougher laws for drunken driving,

the number of deaths caused by

gunfire continues to increase Will

the declining curve of

auto-relat-ed mortality intersect with the rising

curve of deaths from firearm use?

The most authoritative statistics

in-dicate that the question is not Òwill?Ó

but Òwhen?Ó According to Garen mute of the University of California atDavis, guns may move into first placeduring the next decade

Winte-WintemuteÕs comparison of gunand automobile mortality statis-

tics (left) was published in the

Journal of the American Medical Association The date on which the

nation achieves the crossoverÑsome reports reveal that Louisi-ana and Texas have already donesoÑdepends on the stability ofcurrent trends Deaths from gun-shot wounds have increased rap-idly during the past Þve years (af-ter a decade of decline), whereasautomobile fatalities are fallingfaster than usual, as they tend to

do in bad economic times If thisnew pattern persists, more peo-ple will die from gunfire than inauto accidents during 1994 But

if long-term historical trends reassertthemselves, the crossover will wait un-til a few years after the turn of the

SCIENCE AND THE CITIZEN

14 SCIENTIFIC AMERICAN November 1993

DotÕs Incredible

Controlling single electrons

in a quantum dot

Manipulating small numbers of

atomic particles seems to have

become a standard part of the

repertoire of physics So devotees of the

art are being dazzled by a supreme feat

of nanoscale sleight of hand, which has

been achieved by researchers at AT&T

Bell Laboratories

The Bell Labs workers, Raymond C

Ashoori, now at the Massachusetts

In-stitute of Technology, and

Horst L Stormer and their

col-leagues, report in Physical

Re-view Letters that they can

con-trol the behavior of as few

as one or two electrons in a

patch of semiconducting

ma-terial that is only a few tens

of nanometers square This

lev-el of resolution was

previous-ly thought to be unattainable

The success should enable

in-vestigators to explore

quan-tum phenomena that have

nev-er been obsnev-erved in an expnev-eri-

experi-mental setting and might serve

as a basis for signiÞcant

tech-nological advances

The semiconductor specks

are known as quantum dots,

or artiÞcial atoms Although many realatoms actually constitute a quantumdot, the electronic properties of a dotmake it the equivalent of an individualatom Like a real atom, a quantum dotharbors distinct numbers of electrons

But rather than being held in place bythe charge of a nucleus, the electrons

in an artiÞcial atom are conÞned byboundaries of a material Trapped insuch a box, the electrons occupy dis-crete energy levels, just as they dowhen bound by a real nucleus A quan-tum dot is constructed from a Þlm ofsemiconducting material, such as galli-

um arsenide, sandwiched between two

insulating layers The lithographic cesses used to etch circuit patterns canform the artiÞcial atoms [see ÒDimin-ishing Dimensions,Ó by Elizabeth Cor-coran; SCIENTIFIC AMERICAN, November1990; and ÒQuantum Dots,Ó by Mark A.Reed, January]

pro-Detailed studies of the properties ofquantum dots have been diÛcult Thestandard method of examining theirelectronic characteristicsÑmeasuringthe charge ßowing through themÑwaslimited in resolution ÒThe current issmall, and you have to put 30 to 40 elec-trons into the artiÞcial atom before cur-rent ßows,Ó according to Marc A Kast-

ner, an M.I.T investigator whoalso explores artiÞcial atoms.But Ashoori had a dream oflooking at electrons one byone as they accumulate toform an artiÞcial atom Whileworking at Bell Labs, he andhis colleagues decided to trymeasuring changes in theamount of charge (that is, thecapacitance) caused by the dotrather than the amount of cur-rent ßowing though it Thetechnique, single-electron ca-pacitance spectroscopy, callsfor placing an artiÞcial atombetween two electrically con-ducting plates ÒWe then apply

a ÔticklingÕ voltage to induce anelectron from one of the plates

LONG-TERM MORTALITY TRENDS for motor cles and firearms (colors) converge in 2003, short- term ones (black ) in 1994.

vehi-QUANTUM DOTS are fabricated inside metal disks about one micron in diameter A contact loop collars the middle disk and transmits the signals from the tunneling electrons inside to measurement devices.

302520151050

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to tunnel,Ó Ashoori explains The laws

of quantum physics give the electron,

which does not have enough energy to

move from the plate to the

semiconduc-tor, a temporary boost The particle can

then tunnel through the energy barrier

to make the trip When it does so, it

be-comes bound to the artiÞcial atom The

electron does not bond to a real atom,

because according to the quantum

me-chanics of solids it is a free electron

Free electrons do not feel the presence

of real atoms in the material

Ashoori knows when an electron has

tunneled to the artiÞcial atom, because

the particleÕs movement induces a nuscule but detectable charge to form

mi-in the other plate By changmi-ing the age across the plates, the investigatorscan make electrons tunnel one by one

volt-to the artiÞcial avolt-tom Only the perature of the sample, which must

tem-be kept near absolute zero, limits theresolution

The physicists grant that the tance technique may have some practi-cal use It might, for instance, act as afoundation for a photodetector thatcounts single electrons The device would

capaci-be superior in performance to existing

detectors by a factor of 10 The dotsthemselves might also be employed asthe ultimate tiny circuit element Ash-oori and Stormer point out, however,that the true strength of the work lies

in basic research ÒIt is a toy box, an credibly powerful microscope,Ó Ash-oori says

in-But why look at artiÞcial atoms whenthere are plenty of natural ones lyingaround? The answer is that an artiÞcialatom diÝers in promising ways fromthe real McCoy Quantum dots are sever-

al hundred times larger (a hydrogenatom is about 0.1 nanometer in diame-ter), and the ÒwallsÓ that trap electrons

in a dot are not as symmetric as thenuclear charge that holds electrons.Such diÝerences, the researchers say,open a new realm of physics

For example, tests of quantum fects that require temperatures, Þeldstrengths and other conditions well be-yond those achievable with todayÕsequipment become possible in artiÞcialatoms One is the inßuence a magneticÞeld exerts on conÞned electrons Ac-cording to the Pauli exclusion principle,

ef-no two electrons can occupy preciselythe same state The two electrons in ahelium atom, lying in their lowest ener-

gy state, distinguish themselves by enting their ÒspinsÓ in opposite direc-tions An external magnetic Þeld, how-ever, tends to force the spins to align,which would put the two electrons inthe same quantum state So, theory pre-dicts, one electron must jump to a high-

ori-er enori-ergy level

To conduct the experiment on real oms, workers would have to use a mag-net that would generate an external Þeld

at-of about 400,000 teslas Even the sundoes not produce such a mighty Þeld.The superconducting magnets used inmagnetic resonance imaging typicallycreate Þelds of about 0.5 to 1.5 teslas

In an artiÞcial atom, Ashoori notes, aÞeld of less than two teslas suÛces tomake an electron jump to a new energylevel Using quantum dots, physicistsmay also be able to probe much morerigorously such unusual phenomena asquantum chaos and the quantum HalleÝect

Customizing quantum dots is also apossibility ÒThe nice thing is,Ó Stormercomments, Òyou can make any kind ofartiÞcial atomÑlong, thin atoms and big,round atoms.Ó Then, one can string to-gether many of these quantum dots, cre-ating an artiÞcial molecule The artiÞcialmolecules can in turn be joined to makeartiÞcial solidsÑan intriguing prospect

to many physicists ÒWhat is drivingthe excitement,Ó Kastner explains, Òisthe hope that there is something there

we didnÕt expect.Ó ÑPhilip Yam

Were Four Corners Victims Biowar Casualties?

ould a mysterious disease that has taken at least 16 lives in the Four

Corners region of the Southwest since this past May be related to the

U.S biological warfare program? In June, federal and state investigators

blamed the outbreak on hantaviruses Although hantavirus-related illnesses

were unknown in the U.S before this year, they have been studied by

mili-tary and civilian researchers since the 1950s, when U.S troops fighting in

Korea became infected with a flulike disease that attacks the kidneys

The virus, named after Korea’s Hantaan River, is carried by rodents and is

transmitted by airborne particles of the feces or urine of infected animals

The Four Corners illnesses were almost certainly caused in this way, asserts

C Mack Sewell, an epidemiologist for the state of New Mexico, who notes

that the virus had previously been detected in deer mice in the area

Rumors have nonetheless persisted among Native Americans and others

in the Four Corners region that Fort Wingate, an army base near the

epicen-ter of the epidemic, was somehow involved In June, Senator Jeff Bingaman

of New Mexico queried the Pentagon about possible biological warfare

ac-tivities at the base The Pentagon acknowledged that the fort was once used

as a storage depot for chemical weapons but denied that biological weapons

were ever held or tested there

Yet Fort Wingate has served as a target site, or “impact zone,” for missiles

launched from other military bases, according to a former congressional

in-vestigator who requested anonymity One possible launch site is the

Dug-way Proving Grounds in Utah, several hundred miles to the north The army

has conducted experiments at Dugway with both chemical and biological

agents for decades Dugway earned notoriety in 1968 when a jet aircraft

from the site accidentally released nerve gas over a nearby ranch and killed

thousands of sheep

The investigator suggests that tests initiated at Dugway may have

infect-ed the Fort Wingate region with biological agents years ago The epidemic

may then have been triggered by demolition or other disturbances related to

the decommissioning of Fort Wingate early this year

There is also reason to doubt that all the Four Corners illnesses stemmed

from hantavirus, the investigator notes Fewer than half of the victims tested

positive for hantavirus Moreover, deaths were attributed not to kidney

fail-ure—the usual outcome of hantavirus infection—but from hemorrhaging of

the lungs Congress recently appropriated $6 million for a study of the Four

Corners outbreak

Whatever the conclusions of the study, the suspicion engendered by the

incident shows the need for greater openness within—and perhaps

demili-tarization of—the biological defense program, argues Leonard A Cole of

Rutgers University, an authority on the history of biological warfare “It

would be in the army’s interest to eliminate the conspiratorial attitude

to-ward these outbreaks,” he points out This year, Congress required the

De-partment of Health and Human Services to examine the feasibility of

shift-ing some biological defense research from the army to the National

C

Trang 9

Insects Are Forever

Staying power, not ﬂower

power, made bugs diverse

Anyone who has ever shared an

apartment with cockroaches has

suspected as much, but now it’s

o¤cial : insects almost never go away

After surveying the fossil literature, two

researchers have concluded that at the

family level, insects have shrugged o›

catastrophes that exterminated fragile,

dainty creatures—such as the dinosaurs

“Because of the low rate of extinction,

you have insect lineages that are very

long lived, approaching 100 million

years in some cases,” notes Conrad C

Labandeira, one of the new study’s

au-thors and a paleoentomologist at the

National Museum of Natural History of

the Smithsonian Institution That

fami-ly durability seems to explain why bugs

are so numerous and varied today

By almost any standard, insects are

phenomenally successful They were

the ﬁrst animals to invade the land

and, later, the air They are the most

di-verse group, too: by some estimates,

about 876,000 insect species have been

identiﬁed, and entomologists believe a

full tally would be in the millions ( By

comparison, taxonomists know of only

about 4,000 mammal species.)

Accord-ing to Douglas Futuyma, an expert on

insect evolution at the State University

of New York at Stony Brook, insects’

success has often been attributed to

a presumably exceptional talent for becoming new species Agricultural sci-entists know, for example, that insects can readily evolve new traits, such as resistance to pesticides Some experi-ments also suggested that speciﬁc groups

of insects, such as the fruit ﬂies in theHawaiian Islands, also diverged intoseparate species very quickly

But the report recently appearing in

Science indicates that adaptability may

have been less important for insectsthan sheer, stubborn endurance Sincethe mid-1980s, Labandeira and J JohnSepkoski, Jr., of the University of Chica-

go have been searching the fossil recordfor evolutionary patterns in insect diver-sity and survival They note that manyscientists have assumed that insects donot fossilize well “There’s been this received wisdom that because insectsaren’t durably calciﬁed like mollusks orthe bones of vertebrates, there wouldn’t

be much of a fossil record,” Labandeiraremarks In fact, the literature from oldGerman, Russian and Chinese sourceswas rich enough for Labandeira andSepkoski to gather information about1,263 extinct and extant insect fami-lies Only about 825 families of four-legged animals (vertebrate tetrapods)have been documented as fossils

Those data demonstrated that

fami-lies of insects rarely disappeared, evenwhen other animal groups were perish-ing en masse The researchers found, forexample, that 84 percent of the insectfamilies living 100 million years ago,during the Cretaceous period, are alsopresent today In contrast, only 20 per-cent of the Cretaceous tetrapod familiesare still around The mass extinctions

at the end of the Cretaceous destroyedabout one quarter of the tetrapod fami-lies (including all the dinosaurs), but theeffect on insects was negligible Indeed,the only extinction event that had amajor impact on insect diversity wasthe huge one at the end of the Permianperiod, 250 million years ago It wipedout 65 percent of the insect familiesthen living, probably because nearly allvegetation died at the same time.Labandeira and Sepkoski’s ﬁndings

do not contradict the possibility of

rap-id speciation in insects Labandeira saysthat, if anything, long-term survivorship

of families and rapid turnover of speciesmay go hand in hand Because great-

er species diversity promotes the vival of a family and surviving groupshave more opportunities to diversify,the trend is self-perpetuating : nothingsucceeds like success

sur-To the surprise of some biologists, bandeira and Sepkoski also observedthat the appearance of ﬂowering plants,

La-or angiosperms, 125 million years agodid not cause a burst of insect diversi-

ty “As a matter of fact, the rate of versification abated,” Labandeira em-phasizes That finding was unexpectedbecause insects and flowering plantsoften live in intimate, species-specificassociations

di-One explanation, the researchers

pos-it, is that the evolutionary effects of theangiosperms might have been invisible

to their study : the diversity they moted might have been at the speciesrather than the family level And Futuy-

pro-ma notes that the order Lepidoptera(butterﬂies and moths) is underrepre-sented in the fossil record Because lep-idopteran insects have some of the clos-est associations with ﬂowering plants,

he thinks their absence might disguisesome diversiﬁcation

Yet Labandeira and Sepkoski also fer the theory that for insects, the angio-sperms were not very novel challenges.They discovered that most types ofmouthparts found in modern insectswere present 100 million years beforeangiosperms evolved Insects that werealready dining on gymnosperms, coni-fers and other seed plants did not needradical adaptations to take advantage

of-of the new ﬂora “We live in an sperm-dominated world,” Labandeirareﬂects “It’s hard for us to picture how

angio-18 SCIENTIFIC AMERICAN November 1993

FOSSILS OF INSECTS suggest that their taxonomic families are highly resistant to

extinction, which may explain why insects are so diverse today This snake ﬂy fossil

from a limestone deposit in Brazil is 120 million years old.

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Goldilocks Cosmology

Theorists toss another

ingredient into the cosmic recipe

At times, the story of modern

cos-mology sounds oddly like the

tale of Goldilocks and the three

bears Some theorists have proposed

that the mass of the universe is

domi-nated by fast-moving invisible particles

known as hot dark matter; others

fa-vor a universe dominated by sluggish

cold dark matter In either case, the

un-seen material helps to explain how large

structures (such as galaxies and clusters

of galaxies) emerged from the hot, panding mass that existed after the bigbang But neither kind of dark matterseems entirely able to account for theobserved organization of the cosmos

ex-A number of researchers are thereforeexploring a third scenario in which theuniverse contains a nearly even blend

of hot and cold dark matter And ingood Goldilocks fashion, they arguethat such a mix may work “just right.”

Cosmologists have tended to shyaway from mixed dark matter models,

in part because “the subject is oftenguided by aesthetic simplicity Most peo-ple thought mixed dark matter was veryugly,” reﬂects Nick Kaiser of the Insti-tute for Theoretical Astrophysics at theUniversity of Toronto Kaiser and his co-workers Robert A Malaney and Glenn

D Starkman think they have addressedsuch reservations by ﬁnding an attrac-tive way to create two kinds of darkmatter through a single mechanism

In a recent paper in Physical

Re-view Letters, the researchers envision a

universe that initially contained a ulation of massive neutrinos, neutralparticles that barely interact with nor-mal matter Physicists commonly as-sume that neutrinos have no mass, butmounting evidence suggests otherwise

pop-Kaiser and his collaborators proposethat the massive neutrinos could havedecayed in such a way as to stimu-late the formation of slow-moving (andhence “cold” in cosmological parlance)

dark matter particles The workers callthis mechanism “neutrino lasing,” byanalogy to the stimulated creation ofphotons of light in a conventionallaser The heavy neutrinos themselvesdecay into lighter, high-speed particles(possibly another form of neutrino) thatconstitute a component of hot darkmatter In this way, a single, fairly ele-gant set of events can account for theexistence of two separate components

of dark matter

Neutrino lasing occurs at such highenergies that “it could be very very dif-ﬁcult indeed” to devise a laboratory test

to prove the existence of the enon, Kaiser admits “ What we are pre-senting here is a new piece of physics,”

phenom-he explains; now it is up to tphenom-he particlephysicists to ﬁnd a place for it in thebroader context of their theories.Even if the idea does not pan out, neu-trino lasing is far from the only way tocreate mixed dark matter “There arelots of more mundane ways to do it,”says Robert K Schaefer of the BartolResearch Institute at the University ofDelaware Indeed, from a particle phys-ics point of view, “ it’s sort of natural”

to have both hot and cold dark matter,

he says Schaefer sees great promise intwo-component dark matter cosmologi-cal models New observations have com-peting models “scrambling after datapoints,” he claims, whereas the latestﬁndings are “settling more and moretoward mixed dark matter.”

Some cosmologists still object to thenotion of mixed dark matter on aesthet-

ic grounds “I’ve seen people get up ter talks and say, ‘This is the ugliestmodel I’ve ever seen’—there’s no scien-tiﬁc rationalization,” Schaefer reports.Jeremiah P Ostriker of Princeton Uni-versity agrees that the lack of simplicity

af-is a poor argument against mixed darkmatter models “Who’s to say that na-ture will be simple? Biological systemsare a mess,” he laughs

Ostriker objects to the simplest mixeddark matter models for a very di›er-ent reason: in his opinion, “they don’twork.” Astronomical observations re-veal that galaxies and quasars existedwithin a couple of billion years after thebig bang and large clusters of galaxiesnot long thereafter Mixed dark mattercosmologies cannot readily explain howsuch objects could have formed so soonafter the big bang

Kaiser readily concedes that di¤cultybut thinks the various bits of evidenceindicating at what era large galaxy clus-ters began to form remain equivocal

“ You pay your money, and you takeyour choice,” as he puts it Ostriker, incontrast, feels the inability of mixeddark matter to account for the appear-

well insects thrived in a world with

dif-ferent vegetation.”

He and Sepkoski end their paper with

a warning that humanity’s extensive

de-forestation e›orts might trigger a

calam-itous loss of insect diversity That

state-ment might seem paradoxical, given

in-sects’ historical resilience Labandeira

acknowledges that it was more of a

cau-tionary speculation than an analysis and

that “anything that’s happening today

may be mild compared with what

hap-pened during the late Permian.” Still,

some insect groups are highly

impor-tant to ecosystems, and deforestation

can eliminate them ruthlessly If hardy

insect clans are su›ering, other fauna

and ﬂora may be even more

debilitat-ed Think about that the next time you

reach for a ﬂyswatter —John Rennie

CLUSTERS OF GALAXIES, such as this one in the constellation Hercules, may have

assembled under the gravitational coercion of vast clumps of unseen dark matter.

But the simplest dark matter models do not match the observed cosmic structure.

Trang 11

Sausage Factory

How Congress passes

the pork to Back-Home U.

Back in 16th-century England, when

livestock grazed on a common,

farmers would identify their swine

by special marks on the animals’ ears

In 20th-century America, earmarks of a

di›erent kind are increasingly being

used to distribute federal pork to

col-leges and universities

An investigation conducted by

Con-gressman George E Brown, Jr., of

Cali-fornia, chairman of the House

Commit-tee on Science, Space and Technology,

shows that during the 1980s the

prac-tice of cajoling Congress into

support-ing academic projects that had not

been requested by the executive branch,

subjected to competitive review or

scru-tinized by any congressional

authoriz-ing committee grew to majestic

propor-tions—at least by university standards

A select but expanding group of leges now routinely taps federal funds

col-by lobcol-bying inﬂuential members of gress to insert special provisions, ear-marked to fund speciﬁc projects, intothe appropriations bills and reports forfederal agencies More than $700 mil-lion so earmarked was appropriated in

Con-1992 In 1980 the total was $11 lion Brown points out that individualearmarked appropriations ranged invalue from a few hundred thousanddollars to more than $40 million thispast year

mil-In general, authorizing committees inCongress approve the overall direction

of agencies’ spending, and then priations committees vote the funds to

appro-be used But by sliding in an earmarkedprovision at a late stage in the appropri-ation process—often in the conferencecommittee, which reconciles House andSenate versions of a bill—a member cansecure funds for a project that mightnot survive a measured consideration

Brown complains that the practice

“destroys rational e›orts to set ties tied to national needs” and “fails

priori-to protect the taxpayers’ investment.”

Many unreviewed allocations, he notes,were forced onto unwilling federal agen-cies that consequently had little choicebut to spend the money or risk a con-frontation In this way, the Department

of Energy was pushed into buildinghospitals, for example, and the FederalAviation Administration was directed tospend $30 million this past year on an

“airway science” program that it wouldlike to terminate

Although less than 5 percent of

high-er education institutions receive marked funds, Brown’s “just say no”

ear-campaign faces an uphill battle Thenumber of universities retaining lob-byists in Washington—at fees of up to

$60,000 a month, according to Brown’ssta›—is escalating Brown found that

21 out of 50 academic institutions thatreceived allocated funds in ﬁscal 1993had employed registered lobbyists theprevious year Moreover, the sameschools keep showing up time and again

in the chow line Thus, eight of the top

10 recipients in 1992 were among thetop 20 between 1980 and 1992 IowaState University, the University of Alas-

ka, Oregon Health Sciences Universityand Louisiana State University head thelist of all-time winners

Martin C Jischke, president of IowaState, says the earmarked projects at hisuniversity, which include a center for ad-vanced technology development and anexperimental food irradiation facility, are

“important and defensible.” Moreover, heasserts, “there was no competitive fed-

eral program to which we could apply.”Other recipients of unreviewed tar-geted funds responded to Brown’s sur-vey by saying they as lesser lights in thescholastic ﬁrmament would be unable tocompete with better-established schools.But that plea does not stand up in mostcases Many of the institutions that re-ceive the largest of such allocations fall

in the top 25 percent of recipients ofpeer-reviewed research grants from theNational Science Foundation, according

to Brown’s sta›

Recipients insist on their right to

lob-by Congress and point out that cause some funds are “leveraged”—that

be-is, the institution itself provides funds

to match the federal dollars—they sent cost-e¤cient federal spending Butmany such funds are not leveraged Andthe contention that they send federal dol-lars to poor states is contradicted byanother of Brown’s ﬁndings What manyrecipients have in common, Brown’sstudy shows, is a senator or congress-man in an inﬂuential position on an ap-propriations subcommittee

repre-Some political tides may be ﬂowing inBrown’s favor Congressman William H.Natcher of Kentucky, the new chairman

of the House Appropriations tee, has set his cap ﬁrmly against ear-marking funds for academic groups.And as budgets get tighter, members

Commit-of authorizing committees in the Houseare becoming increasingly sensitive tothe threat that such appropriationspose, observes Peter Smith of the Asso-ciation of American Universities.But universities themselves seem toﬁnd it hard to speak with one voice

on the subject In 1987 members of the association, which represents ma-jor research institutions, voted 43 to

10 to observe a moratorium on ing earmarked funds Since then, sev-eral members who voted in favor of the moratorium have “slipped” andnow accept earmarked money, Smithsays —Tim Beardsley

seek-SCIENTIFIC AMERICAN November 1993 23

ance of the early universe means “it is

probably not correct.”

Mixed dark matter represents only

one of a number of theoretical tweaks

that cosmologists are using to

ﬁne-tune their models to ﬁt the

observa-tions Some workers posit that cosmic

strings—hypothetical, extremely dense

defects in the structure of space left

over from the ﬁrst moments of

crea-tion—could have acted as seeds around

which galaxies formed Other theories

invoke alternative but equally

hypo-thetical mechanisms for creating dense

structures very early in the history of

the universe

Each time new data come in, Ostriker

notes, the easiest thing to do is “just add

another epicycle” to existing

cosmolog-ical theory Mixed dark matter adds one

layer of complexity to the previous

mod-els, most of which incorporated cold

dark matter alone “But nature could be

nasty ; there could be cold dark matter,

hot dark matter plus strings,” Ostriker

muses Or the universe could be far

simpler than most astronomers

imag-ine Despite many claims to the

con-trary, Ostriker maintains that there is

still no solid evidence for exotic dark

matter If such dark matter does not

ex-ist, then one could build a model “based

on hydrogen, tables and chairs—stu›

we know about,” he comments

The joy of speculating about the early

history of the universe—as well as the

frustration—is that the possibilities are

nearly endless Goldilocks had but three

bowls of porridge to sample Only the

human imagination limits the menu of

cosmology —Corey S Powell

“ Pollution, Pollution ”

Federal air standards permit dangerous particulate levels

It’s enough to make Tom Lehrer sit

down at the piano again Findingsfrom a recent study indicate thatloopholes in government standards havelet one of the most harmful forms ofair pollution become a dangerous fact

of everyday urban life

The study, presented at the annualmeeting of the American Lung Associa-tion by C Arden Pope, a visiting scientist

Trang 12

at the Harvard School of Public Health,measured the e›ects of air pollution onresidents in six U.S cities Pope found a

26 percent higher risk of prematuredeath in the city most polluted with am-bient particles as compared with theleast polluted city surveyed The work-ers also noted “robust associations” be-tween chronic exposure to airborne par-ticulate matter and increased mortality

As disturbing as the results is the factthat the air in all six cities carried parti-cles whose density per volume of atmo-sphere was well below legal thresholds.The current Environmental ProtectionAgency regulations mandate that densi-

ty of particles less than 10 microns indiameter shall not exceed 150 micro-grams per cubic meter of air during a24-hour period The Harvard data corre-late morbidity and mortality statisticswith the presence of particles one quar-ter the size specified in the EPA regula-tions The density of such particles didnot on average exceed one third thatspeciﬁed by the EPA benchmark.The Harvard team culled its statisticsfrom an analysis of 8,111 residents inthe six cities, whom it followed for 14

to 16 years Pope, who came fromBrigham Young University to partici-pate in the Six Cities Study, says theconclusions point toward ﬁne particlesand particles from the combustion offossil fuels as the most pernicious airpollutants

Such pollutants include carbon, drocarbons, dust, acid aerosols and sul-fates Common respiratory problemsthat can develop from exposure to thesepollutants are chronic obstructive pul-monary disease, cardiovascular diseaseand asthma

hy-“If you ask the average layperson,these results would probably come as

no surprise, but it has taken a while for science to catch up with commonsense,” says Alfred Munzer, president ofthe American Lung Association ( ALA )

“This is the ﬁrst time that we havehard data to show not just the morbid-ity caused by particle pollution but theincrease in mortality as well.”

A 1992 report by Joel Schwartz, anepidemiologist at the EPA, and Douglas

W Dockery of Harvard, who also uted to the Six Cities Study, estimatedthat respirable particles may cause some60,000 premature deaths in the U.S.every year Previous accounts compiled

contrib-by Pope, Schwartz and Dockery havelinked death rates and particulate pollu-tion levels around the country fordecades Critics argued that these stud-ies did not adequately control for indi-vidual risk factors, such as tobaccosmoking, and so did not warrant reme-dial legislation or regulatory action

Trang 13

But the Six Cities Study directly dressed such factors The ﬁndings haveforced doubters out of that defensiveditch Indeed, the statistics have prompt-

ad-ed the ALA to announce that it intends

to ﬁle suit against the EPA to demand atimely review of policy regarding parti-cle pollution “It is imperative that werevise our standards, particularly when

it comes to particles,” Munzer says

The EPA has not reviewed its dards for particulate matter since 1987,even though the Clean Air Act of 1970requires it to do so every ﬁve years

stan-Schwartz, who was one of the ﬁrst demiologists to document the dangers

epi-of particles, is frustrated with the lay He notes that EPA o¤cials have tar-geted 1999 as the earliest possible datefor a policy change regarding particulatematter “I think the di›erence betweenreviewing particle standards at Thanks-giving 1999 and Christmas 1999 is moreimportant than all the other regulationsthe EPA plans to put out between nowand then,” he emphasizes

de-EPA o¤cials say they are moving asfast as they can “We have planned toset up an expedited schedule to reviewparticle standards,” says Robert D Bren-

ner, chief of policy for the EPA’s O¤ce

of Air Pollution “Now we know thatthere is a serious particulate problem,but that doesn’t necessarily tell youhow to set the standards,” he cautions.Schwartz points out that to speed thereview process, funds and workerswould have to be reallocated from oth-

er projects

One problem for scientists, both inacademia and at the EPA, is that theseparticles, no more than 10 microns indiameter (less than half the width of

an average human hair), are

extreme-ly difficult to examine They come from

a variety of sources: construction work,cars driving over dirt and paved roads,wind erosion, tobacco smoke, ﬁreplac-

es and even backyard barbecues over, chemical reactions catalyzed bysunlight create harmful particle concoc-tions that are di¤cult to isolate fromother forms of air pollution

More-Or so argue the investigators Theskeptics want more proof Some criticscontend that a biological explanation ofhow particles cause disease or deathmust be demonstrated before the policycan be changed One unanswered ques-tion is whether the particles themselves

PARTICLE MONITOR , which neighbors a midtown Manhattan bus stop, was moved back from the curb in 1990 to meet site criteria of the Environmental Protection Agency In its previous position, the equipment consistently collected ﬁne particle levels from diesel exhaust far exceeding federal standards.

Trang 14

Unraveling AlzheimerÕs

A major cause of the disease yields to researchers

Workers at the Duke University

Medical Center have identiÞedwhat seems to be a critical fac-tor in the development of AlzheimerÕsdisease, the degenerative brain disorderthat aÜicts four million people in theU.S The factor may be associated withabout 80 percent of the cases of the ill-ness IdentiÞcation of the factor, a form

of a gene responsible for the ture of a lipoprotein, has been con-Þrmed by 10 other laboratories.The Duke researchersÑMargaret A.Pericak-Vance, Ann M Saunders andAllen D Roses, among othersÑhavefound a strikingly clear association be-tween the onset of AlzheimerÕs and aparticular variant of a gene that codesfor a known blood protein, apolipopro-

manufac-tein E The suspect gene, APOE-ε4, can

be detected with a test that is alreadywidely used for diagnosing a seriouscholesterol-transport disorder

Investigators had previously ered in a few cases of the relatively rareearly-onset form of AlzheimerÕs a muta-tion in the gene responsible for the pro-duction of amyloid beta-protein, which

discov-is deposited in the brains of patients.Some other cases appeared to be linked

to a diÝerent unknown gene But theseÞndings had not seemed relevant tothe majority of patients

The Þrst clue that a variant of the lipoprotein E gene might be involvedfell to a group in RosesÕs laboratory led

apo-by Warren J Strittmatter They foundlast year that apolipoprotein E binds tothe beta-amyloid deposited in the brain

of patients suÝering from AlzheimerÕs.The gene for apolipoprotein E is onchromosome 19 Pericak-Vance had justidentiÞed some cases of AlzheimerÕs infamilies in which the disease was inher-ited along with the section of chromo-

cause damage or whether blame belongs

to the chemicals they carry deep intothe lungs

Many researchers feel policy sions cannot be left up in the air un-til the biological grounds for damageassociated with particles are pinneddown Munzer hopes the threat of anALA lawsuit will put pressure on the EPA

deci-to make a change soon ÒThese thingsusually work, but it shouldnÕt be nec-essary,Ó he laments ÒThe process forincluding scientiÞc progress in publicpolicy needs to be a much more rap-

id one.Ó ÑKristin Leutwyler

Trang 15

some 19 that includes the

apolipopro-tein E gene

RosesÕs group immediately started

studying apolipoprotein E The payoÝ

was not long in coming Saunders

dis-covered that patients in families

aÜict-ed with AlzheimerÕs are more likely

than are other people to have the

par-ticular form of the apolipoprotein E

gene known as APOE-ε4

In August, Saunders published a

conÞrming report in Neurology that

the association holds in so-called

spo-radic cases, in which there are no other

affected family members Other

work-ers have found evidence of the

asso-ciation in autopsied patients, in living

patients and in pilot epidemiological

surveys ÒUntil this, there hadnÕt been

a lot of progress since Alois

Alzheim-er found plaques and tangles in the

brains of his patients in 1907,Ó Roses

comments

ÒThis is a major Þnding ItÕs not only

right, itÕs important, too,Ó remarks John

A Hardy of the University of South

Florida ÒAll the papers suggest that

having one APOE-ε4 gene increases

your risk of AlzheimerÕs threefold to

fourfold and that people with two

APOE-ε4 genes are very likely to

devel-op AlzheimerÕs.Ó About 15 percent of

the U.S population has one APOE-ε4

gene and are thus at elevated risk

Be-tween 1 and 1.5 percent of the elderly

has two such genes, and Roses has

found that they tend to acquire

Alz-heimerÕs earlier than do people with

one APOE-ε4 gene

Although nobody is sure exactly why

APOE-ε4 makes the development of

AlzheimerÕs more likely, Roses says he

has deÞnite ideas, whose therapeutic

potential he plans to pursue Dennis J

Selkoe, an AlzheimerÕs researcher at

Harvard University and founding

scien-tist of Athena Neurosciences, a South

San Francisco biotechnology company,

suggests an explanation He speculates

that the protein made by APOE-ε4

inter-feres with the removal of amyloid

beta-protein from the brain Or possibly,

Selkoe says, the apolipoprotein

encour-ages deposition of the material

A drug that inhibited the interaction

of the two proteins might slow down

or eliminate whatever goes wrong in

AlzheimerÕs, according to Ivan

Lieber-burg of Athena LieberLieber-burg has

dis-cussed a collaboration on a therapeutic

approach with RosesÕs group The need

for therapies is urgent The only

exist-ing drug for AlzheimerÕs,

Warner-Lam-bertÕs Cognex, which the Food and Drug

Administration approved in September,

beneÞts just a small proportion of

pa-tients, points out Mark J Alberts, a Duke

researcher Cognex inhibits an enzyme

SCIENTIFIC AMERICAN November 1993 29

Trang 16

that, in turn, destroys acetylcholine, an

important neurotransmitter that is in

short supply in the brains of

Alzheim-erÕs patients But Cognex, whose

chem-ical name is tacrine hydrochloride,

does not slow the cell death that

caus-es the shortage Other approachcaus-es to

therapy now under investigation share

this limitation

Until the hope for a satisfactory

ther-apy is realized, the Þndings raise an

ethical problem that has previously

emerged only in the context of rarer

conditions, such as HuntingtonÕs

dis-ease To wit, should researchers tell

those who ask whether they have the

predisposing gene? The millions of

people in the U.S with two APOE-ε4

genes appear to have a risk for

Alz-heimerÕs of more than 80 percent,

ac-cording to RosesÕs and othersÕ data

Learning that such a fate was probably

in store could cause people great

an-guish, the Duke researchers

acknowl-edge Yet already the Duke team has

had ÒhundredsÓ of requests from

indi-viduals who want to be tested, mainly

relatives of AlzheimerÕs patients,

Saun-ders says The group has obliged some

of them

ÒWeÕre not encouraging people to

get tested,Ó Saunders cautions The

in-vestigators fear that insurance

compa-nies may want to use the test to

iden-tify individuals who have the APOE-ε4

gene Some insurers have already

ap-proached the Duke team, Saunders

states

Nobody is claiming that APOE-ε4

is the one true cause of AlzheimerÕs

Still, the Þnding could catalyze other

breakthroughs A worker at the

Nation-al Institute of NeurologicNation-al Disease and

Stroke, who is pursuing an entirely

dif-ferent line of research on the disease,

thinks his Þndings could be linked to

the Duke discovery Daniel L Alkon,

who studies mechanisms of memory,

has, together with RenŽ Etcheberrigaray

and others, proposed in a paper in the

Proceedings of the National Academy of

Sciences that skin-tissue cells from

Alz-heimerÕs suÝerers have defective

mo-lecular channels of a particular type

The channels in question move

potassi-um ions across cell walls, and Alkon

says he was able to identify accurately

as victims of AlzheimerÕs 70

individu-als by examining their Þbroblast

potas-sium channels

Alkon already has ideas about

how aberrations causing the defective

channels might be linked to unusual

processing of amyloid beta-protein

and, thus, indirectly to its binding

part-ner apolipoprotein E The mystery of

AlzheimerÕs may be slowly coming

unraveled ÑTim Beardsley

Trang 17

Marvin MinskyÕs ideas about the

mind mayĐor may notĐoÝer

lasting insights But they

certain-ly reveal much about the mind of

Min-sky According to Minsky, the mind is

not a uniÞed entity but a ỊsocietyĨ of

el-ements that both complement and

com-pete with one another MinskyÕs

empha-sis on multiplicity seems to transcend

science; he views single-mindedness

with a kind of horror ỊIf thereÕs

some-thing you like very much,

then you should regard this

not as you feeling good but

as a kind of brain cancer,Ĩ

he explains, Ịbecause it means

that some small part of your

mind has Þgured out how

to turn oÝ all the other

things.Ĩ

Minsky even recoils at the

tendency of ordinary mortals,

once they have invested the

time in learning to do

some-thing, to keep doing it To

counter this trait, which he

calls the investment principle,

Minsky has trained himself

to Ịenjoy the feeling of

awk-wardnessĨ aroused by

con-fronting an entirely new

prob-lem ỊItÕs so thrilling not to

be able to do something,Ĩ he

remarks

This credo has served

Min-sky well in his role as a

founding father of artiÞcial

intelligence Called AI by

in-siders, the Þeld is dedicated

to the proposition that brains

are nothing more than

ma-chines, albeit extremely

com-plicated ones, whose abilities

will someday be duplicated

by computers In pursuit of

the goals of AI, Minsky, who

turned 66 in August, has

drawn on computer science, robotics,

mathematics, neuroscience, psychology,

philosophy and even science Þction His

ideas have in turn inßuenced all these

Þelds as well as AI itself Colleagues

were scheduled to honor him on

Octo-ber 18 at the Massachusetts Institute of

Technology, from which he has ruled

the AI roost for more than 30 years

But the same traits that made Minsky

a successful pioneer of AI have led him

to become increasingly alienated fromthe Þeld as it matures Before my meet-ing with Minsky, in fact, other AI work-ers warn me that he might be somewhatcranky; if I do not want the interviewcut short, I should not ask him too di-rectly about the current slump in AI orwhat some workers characterize as hisown waning inßuence in the Þeld Oneprominent theorist pleads with me not

to take advantage of MinskyÕs

pen-chant for hyperbole ỊAsk him if hemeans it, and if he doesnÕt say it threetimes, you shouldnÕt use it,Ĩ the theo-rist urges

Minsky is rather edgy when I meethim in his oÛce at the ArtiÞcial Intelli-gence Laboratory He Þdgets ceaseless-

ly, blinking, waggling his foot, pushingthings about his desk Unlike most sci-entiÞc celebrities, he gives the impres-sion of conceiving ideas and tropes from

scratch rather than retrieving them frommemory He is often but not always in-cisive ỊIÕm rambling here,Ĩ he saysglumly after a riÝ on the nature of veri-Þcation in AI collapses in a heap of sen-tence fragments Even his physical ap-pearance has an improvisational air Hislarge, round head seems entirely baldbut is actually fringed by hairs as trans-parent as optical Þbers He wears a cro-cheted belt that supports, in addition tohis pants, a belly pack and a holstercontaining pliers with retractable jaws.With his paunch and vaguely Asian fea-

tures, he resembles a tech Buddha

high-Minsky is unable, or ling, to inhabit any emotionfor long Early on, as predict-

unwil-ed, he plays the geon His only rival in grasp-ing the mindÕs complexity isdead: Ị Freud has the besttheories so far, next to mine,

curmud-of what it takes to make amind,Ĩ Minsky declares If AIhas not progressed as fast

as it should have, that is cause modern researchershave succumbed to ỊphysicsenvyĨĐthe desire to reducethe intricacies of the brain tosimple formulaeĐand to thedreaded investment principle.ỊThey are deÞning smallerand smaller subspecialtiesthat they examine in moredetail, but theyÕre not open todoing things in a diÝerentway.Ĩ Even M.I.T.Õs own AI lab,which he founded, is guilty

be-ỊI donÕt consider this to be aserious research institution

at the moment,Ĩ he sneers.But a metamorphosis oc-curs when, touring the AI lab,

we stop to chat with some searchers in a lounge Minskyengages in amiable shoptalkabout chess-playing comput-ers He then recounts how the sciencefictionist Isaac Asimov, who just died, al-ways refused MinskyÕs invitations tosee the robots being built at M.I.T out

re-of fear that his imagination Ịwould beweighed down by this boring realism.ĨOne lounger, noticing that he andMinsky have the same pliers, yanks hisinstrument from its holster and with aßick of his wrist snaps the retractablejaws into place ỊEn garde,Ĩ he says Min-

PROFILE : MARVIN L MINSKY

The Mastermind of ArtiÞcial Intelligence

Trang 18

sky, grinning, draws his weapon, and

he and his challenger whip their pliers

repeatedly at each other, like punks

practicing their switchblade technique

Minsky expounds on both the

versatili-ty andĐan important point for himĐ

the drawbacks of the pliers; his pair

pinches him during certain maneuvers

ỊCan you take it apart with itself ? Ĩ

someone asks Minsky and his

col-leagues share a laugh at this reference

to a fundamental problem in robotics

Returning to MinskyÕs oÛce, we

en-counter a young, extremely pregnant

graduate student She is scheduled for

an oral doctoral exam the next day

ỊAre you nervous? Ĩ Minsky inquires ỊA

little,Ĩ she replies ỊYou shouldnÕt be,Ĩ he

says and gently touches his forehead to

hers I realize, watching this scene, that

there are many Minskys

Too many, according to Minsky As a

child, the son of a New York City

sur-geon, he was a prodigy in both

mathe-matics and music Minsky still

occasion-ally Þnds himself composing ỊBach-like

thingsĨĐan electric organ crowds his

officeĐbut he tries to resist the impulse

by convincing himself that music

sup-presses thought ỊI had to kill the

musi-cian at some point,Ĩ he says ỊIt comes

back every now and then, and I hit it.Ĩ

Minsky started to think about

think-ingĐor, more speciÞcally, about

learn-ingĐin high school Although he

re-ceived undergraduate and graduate

de-grees in mathematics (from Harvard

and Princeton universities, respectively),

he scavenged in other disciplines for

ideas he felt could illuminate the mind

In 1951 he and a colleague built a

ma-chine, made of vacuum tubes, motors

and servomechanisms, that could ỊlearnĨ

how to navigate a maze It was the Þrst

neural network ever built Minsky

fol-lowed this engineering project with a

doctoral thesis on automated learning

In 1959 he and John McCarthyĐwho

is credited with having coined the term

ỊartiÞcial intelligenceĨĐfounded what

became the M.I.T ArtiÞcial Intelligence

Laboratory McCarthy left four years

later to found his own laboratory at

Stanford University, and since then, he

and Minsky have had an intellectual

parting of the ways McCarthy has

cham-pioned AI models based on logic,

where-as Minsky contends that logic requires

precise deÞnitions that the real world

fails to respect The deÞnition of a bird

as a feathered animal that ßies, he

points out, does not apply if the bird is

dead or caged or has had its feet

en-cased in concrete Ịor has been

meditat-ing and decided ßymeditat-ing is egotistical.Ĩ

He has been even harder on neural

networks, the technology he helped to

nurture In 1969 he and Seymour Papert

of M.I.T presented a detailed critique of

a then popular neural network in a

book entitled Perceptrons The book is

often said to have dealt neural works a nearly mortal blow; funding fell

net-oÝ rapidly, and the Þeld languished formore than a decade before it slowly be-gan regenerating MinskyÕs intentionwas not to destroy the Þeld, as someobservers have claimedĐỊThatÕs crazy,Ĩ

he snapsĐbut to outline the limits ofthe technology

Although Minsky applauds the cent resurrection of neural networks, hecharges that some ỊsemicommercialĨresearchers are not as forthcoming asthey should be ỊThey write a paper say-ing, ƠLook, it did this,Õ and they donÕtconsider it equally wonderful to say,ƠLook, it canÕt do that.Õ Most of them arenot doing good science, because theyÕrehiding the deÞciencies.Ĩ Minsky insiststhat no single approach can reproducethe intricacies of the mind, because themind itself employs many fallible meth-ods that back up and check one anoth-

re-er The mind, he muses, is a tractor-trailer,rolling on many wheels, but AI workersỊkeep designing unicycles.Ĩ

Some aspects of the mind have provedharder to understand or reproduce thanMinsky expected He conÞrms the often-told anecdote that in the early 1960s heassigned artiÞcial vision, now recognized

as a profoundly diÛcult problem, to astudent as a summer project But heexpects all the major questions in AI to

be solved as imaging and electrodetechniques reveal the brain in everÞner detail ỊEverything weÕve done up

to now I regard as like chemistry beforeLavoisier,Ĩ he remarks

Minsky poured his thoughts about

thinking into The Society of Mind,

pub-lished in 1985 The book consists of 270essays, most of them only one pagelong, which range from rather technicaldiscussions of neural wiring to philo-sophical excursions into the nature ofhuman identity In the bookÕs prologue,Minsky contended that the workÕs at-omized structure reßects its majortheme, that Ịyou can build a mind frommany little parts, each mindless by it-self.Ĩ ỊAs far as I know, nobody readthe book,Ĩ Minsky grumbles

Minsky has nothing but contempt forthose who believe that computers, whilethey may be able to mimic certain as-pects of human intelligence, can neverbecome truly conscious ỊTheyÕre idiots,Ĩ

he fumes (Minsky is kinder to me when

I make the mistake of suggesting thatthere might always be a qualitative dif-ference between humans and artiÞcialmachines; he calls me a Ịracist.Ĩ)The mystery of consciousness is Ịtriv-ial,Ĩ Minsky declares ỊIÕve solved it, and

I donÕt understand why people donÕt ten.Ĩ Consciousness, Minsky explains,involves one part of the mind monitor-ing the behavior of other parts Thisfunction requires little more than short-term memory, or a Ịlow-grade systemfor keeping records.Ĩ In fact, computerprograms such as LISP, which havememory features that allow their pro-cessing steps to be retraced, are Ịex-tremely conscious,Ĩ Minsky assertsĐmore so than humans, who have piti-fully shallow short-term memories.Like many AI practitioners, Minskypredicts that computers will somedayevolve far beyond humans, who arenothing but Ịdressed-up chimpanzees.ĨHumans may be able to ỊdownloadĨtheir personalities into computers andthereby become smarter and more reli-able This trick may yield inÞnite life,among other perks Minsky envisionsmaking copies of himself that could un-dergo experiences he would otherwiseshun ỊI regard religious experience asvery risky, because it can destroy yourbrain But if I had a backup copyĐĨ

lis-Meanwhile the Ur-Minsky remains

restless Hollywood may provide one let for his energies That becomes clearwhen Laurel, an administrator at the AIlab, sticks her head in the oÛce to askwhatÕs new Minsky replies that the Dis-ney corporation has hired him to design

out-a Ịmout-agic cout-arpet ride,Ĩ bout-ased on its hit

movie Aladdin, for one of its theme

parks Minsky has been working on a tual-reality scheme at a laboratory Disneyhas set up for special effects ỊI loveit,Ĩ Minsky says of the laboratory ỊItÕsjust like the AI lab used to be.ĨNoting that Stephen W Hawking, theEnglish cosmologist, recently appeared

vir-on ỊStar Trek,Ĩ Laurel suggests that sky is well suited for playing Ịan aliengeniusĨ on the television show Evil orbenign? I ask ỊOh, either,Ĩ Laurel replies.Minsky seems intrigued, but he worriesthat he may be unable to rehearsescenes properly ỊI canÕt say the samething twice,Ĩ he confesses

Min-Minsky is also working on a new

book, The Emotion Machine ỊThatÕs a

person,Ĩ Minsky says of the title Onegoal of the book, he notes, is to helppeople think constructively about think-ing ỊIÕm interested in people who aretrying to do some work but keep watch-ing television or going to baseballgames.Ĩ The book will advise such peo-ple to make Ịa little block diagramĨ oftheir minds, with diÝerent, competingagents labeled I try to imagine Minsky

as a self-help guru, propounding his oriented program on ỊDonahue.Ĩ Then,recalling the way he comforted thepregnant graduate student, I think,Why not? ĐJohn Horgan

Trang 19

AI-SCIENTIFIC AMERICAN November 1993 41

econciling economic growth with environmental protection is one of the greatest challenges now facing policymakers Unfortunately, these twin goals are widely seen as antithetical: the prescriptions for promoting one often seem to discourage the other In the following pages, two economists

debate whether unrestricted international trade, as embodied in proposals for

the General Agreement on Trade and TariÝs ( GATT ) and the North American

Free Trade Agreement ( NAFTA ), will harm or help the environment Jagdish

Bhagwati of Columbia University argues that freeing trade from ineÛcient

re-strictions may be the best way to achieve environmental protection while also

safeguarding prosperity and liberty To the contrary, insists Herman E Daly of

the World Bank : free trade left to itself may harm both the environment and

human welfare The authors oÝer starkly diÝerent predictions about the

pos-sible consequences of the new trade agreements.

Debate: Does Free Trade Harm the Environment?

R

D EBATE

Trang 20

Economists are reconciled to the

conßict of absolutes: that is why

they invented the concept of

trade-oÝs It should not surprise them,

there-fore, that the objective of

environmen-tal protection should at times run afoul

of the goal of seeking maximum gains

from trade In fact, economists would be

suspicious of any claims, such as those

made by soothsaying politicians, that

both causes would be only mutually

beneÞcial They are rightly disconcerted,

however, by the passion and the

feroci-ty, and hence often the lack of logic or

facts, with which environmental groups

have recently assailed both free trade

and the General Agreement on TariÝs

and Trade ( GATT ), the institution that

oversees the world trading system

The environmentalistsÕ antipathy to

trade is perhaps inevitable Trade has

been central to economic thinking since

Adam Smith discovered the virtues of

specialization and of the markets that

naturally sustain it Because markets do

not normally exist for the pursuit of

en-vironmental protection, they must be

specially created Trade therefore

sug-gests abstention from governmental

in-tervention, whereas environmentalism

suggests its necessity Then again, trade

is exploited and its virtues extolled bycorporate and multinational interests,whereas environmental objectives areembraced typically by nonproÞt orga-nizations, which are generally wary ofthese interests Trade is an ancient occu-pation, and its nurture is the objective

of institutions crafted over many years

of experience and reßection Protection

of the environment, on the other hand,

is a recent preoccupation of nationaland international institutions that arenascent and still evolving

Last year the environmentalistsÕ tility to trade exploded in outrage when

hos-an impartial GATT Dispute SettlementPanel ruled in favor of Mexico and freetrade and against the U.S and the wel-fare of the dolphin The U.S had placed

an embargo on the import of Mexicantuna on the grounds that the Þsh hadbeen caught in purse-seine nets, whichkill dolphins cruelly and in greater num-bers than U.S law permits The GATTpanel ruled, in eÝect, that the U.S couldnot suspend MexicoÕs trading rights byproscribing unilaterally the methods bywhich that country harvested tuna

This decision spurred the tionistsÕ subsequent campaigns againstfree trade and GATT GATT has noshortage of detractors, of course In fact,some of its recent critics have feared its impotence and declared it Ịdead,Ĩ re-ferring to it as the General Agreement toTalk and Talk But the environmentalistattacks, which presume instead GATTÕsomnipotence, are something else again

conserva-An advertisement by a coalition of

environmental groups in the New York

Times on April 20, 1992, set a new

stan-dard for alarmist, even scurrilous, ing, calculated to appeal to oneÕs in-stincts rather than oneÕs intellect It talks

writ-of Ịfaceless GATT bureaucratsĨ ing a Ịsneak attack on democracy.Ĩ Thisveiled reference to Pearl Harbor pro-

mount-vides an example of a common tactic intrade controversy : Japan-bashing Theinnuendos have continued unabatedand are manifest in the endless battles

in Congress over the supplemental ronmental accords for the North Amer-ican Free Trade Agreement ( NAFTA ).The hostility is also intruding on theconclusion of the Uruguay Round ofGATT talks, now in their seventh year,with the environmentalists opposing theestablishment of the new MultilateralTrade Organization, which is meant toprovide eÝective discipline and a nec-essary institutional structure for GATT

envi-It is surely tragic that the proponents

of two of the great causes of the 1990s,trade and the environment, should be

JAGDISH BHAGWATI is Arthur Lehman

Professor of Economics and professor of

political science at Columbia University

and was Ford International Professor of

Economics at the Massachusetts Institute

of Technology He has served as the

eco-nomic policy adviser to the

director-gen-eral of the Gendirector-gen-eral Agreement on TariÝs

and Trade Five volumes of his

collect-ed essays have been publishcollect-ed by MIT

Press His most recent books are

Protec-tionism (MIT Press, 1988) and The World

Trading System at Risk (Princeton

Uni-versity Press, 1991) He also writes

fre-quently for the New York Times, the Wall

Street Journal and the New Republic.

The Case for Free Trade

Environmentalists are wrong to fear

the e›ects of free trade Both causes

can be advanced by imaginative solutions

by Jagdish Bhagwati

DOLPHIN VERSUS FREE TRADE : the U.S.outlaws Þshing methods that result inthe death of dolphins such as this one,

Trang 21

locked in combat The conßict is

large-ly gratuitous There are at times

philo-sophical diÝerences between the two

that cannot be reconciled, as when some

environmentalists assert natureÕs

au-tonomy, whereas most economists see

nature as a handmaiden to humankind

For the most part, however, the

diÝer-ences derive from misconceptions It is

necessary to dissect and dismiss the

more egregious of these fallacies

be-fore addressing the genuine problems

The fear is widespread among

envi-ronmentalists that free trade increases

economic growth and that growth harms

the environment That fear is misplaced

Growth enables governments to tax and

to raise resources for a variety of

objec-tives, including the abatement of tion and the general protection of theenvironment Without such revenues, lit-tle can be achieved, no matter how pureoneÕs motives may be

pollu-How do societies actually spend theseadditional revenues? It depends on howgetting rich aÝects the desire for a bet-ter environment Rich countries todayhave more groups worrying about en-vironmental causes than do poor coun-tries EÛcient policies, such as freertrade, should generally help environ-mentalism, not harm it

If one wants to predict what growthwill do to the environment, however,one must also consider how it will aÝectthe production of pollution Growth af-

fects not only the demand for a goodenvironment but also the supply of thepollution associated with growth Thenet eÝect on the environment will there-fore depend on the kind of economicgrowth Gene M Grossman and Alan B.Krueger of Princeton University foundthat in cities around the world sulfur di-oxide pollution fell as per capita incomerose The only exception was in coun-tries whose per capita incomes fell be-low $5,000 In short, environmentalistsare in error when they fear that trade,through growth, will necessarily increasepollution

Economic eÝects besides those butable to rising incomes also help toprotect the environment For example,freer trade enables pollution-Þghtingtechnologies available elsewhere to beimported Thus, trade in low-sulfur-con-tent coal will enable the users of localhigh-sulfur-content coal to shift fromthe latter to the former

attri-Free trade can also lead to better

environmental outcomes from ashift in the composition of pro-duction An excellent example is provid-

ed by Robert C Feenstra of the

Universi-ty of California at Davis He has shownhow the imposition of restraints on Jap-anese automobile exports to the U.S.during the 1980s shifted the compo-sition of those exports from small tolarge cars, as the Japanese attempted

to increase their revenues without creasing the number of units they sold.Yet the large cars were fuel ineÛcient.Thus, protective eÝorts by the U.S ef-fectively increased the average amount

in-of pollution produced by imported cars,making it more likely that pollutionfrom cars would increase rather thandiminish in the U.S

Although these erroneous objections

to free trade are readily dismissed (butnot so easily eliminated from public dis-course), there are genuine conßicts be-tween trade and the environment Tounderstand and solve them, economistsdraw a distinction between two kinds

of environmental problems: those thatare intrinsically domestic and those thatare intrinsically transnational

Should Brazil pollute a lake lying

whol-ly within its borders, the problem would

be intrinsically domestic Should it lute a river that ßows into Argentina,the matter would take on an intrinsi-cally transnational character Perhapsthe most important examples of trans-national pollution are acid rain, createdwhen sulfur dioxide emissions in onecountry precipitate into rain in anoth-

pol-er, and greenhouse gases, such as bon dioxide, which contribute to globalwarming wherever they are emitted

car-SCIENTIFIC AMERICAN November 1993 43

ensnared oÝ the U.S Atlantic coast But when the U.S attempted to apply its

stan-dard to Mexico by imposing an embargo on tuna imported from that country, an

international tribunal rejected the policy last year as an illegal restriction of trade

Trang 22

Why do intrinsically domestic

envi-ronmental questions create

internation-al concern? The main reason is the belief

that diversity in environmental

stan-dards may aÝect competitiveness

Busi-nesses and labor unions worry that their

rivals in other countries may gain an

edge if their governments impose lower

standards of environmental protection

They decry such diÝerences as unfair

To level the playing Þeld, these

lob-bies insist that foreign countries raise

their standards up to domestic ones In

turn, environmental groups worry that

if such Òharmonization upÓ is not

un-dertaken prior to freeing trade,

pres-sures from uncompetitive businesses

at home will force down domestic

stan-dards, reversing their hard-won

victor-ies Finally, there is the fear,

drama-tized by H Ross Perot in his criticisms

of NAFTA, that factories will relocate

to the countries whose environmental

standards are lowest

But if the competitiveness issue makes

the environmentalists, the businesses

and the unions into allies, the

environ-mentalists are on their own in other

ways Two problem areas can be

distin-guished First, some environmentalists

are keen to impose their own ethical

preferences on others, using trade

sanc-tions to induce or coerce acceptance

of such preferences For instance, tunaÞshing with purse-seine nets that killdolphins is opposed by U.S environmen-tal groups, which consequently favorrestraints on the importation of suchtuna from Mexico and elsewhere Sec-ond, other environmentalists fear thatthe rules of free trade, as embodied inGATT and strengthened in the UruguayRound, will constrain their freedom topursue even purely domestic environ-mental objectives, with GATT tribunalsoutlawing disputed regulation

Environmentalists have cause for

concern Not all concerns are gitimate, however, and not all thesolutions to legitimate concerns are sen-sible Worry over competitiveness hasthus led to the illegitimate demand that environmental standards abroad betreated as Òsocial dumping.Ó OÝendingcountries are regarded as unfairly sub-sidizing their exporters through lax en-vironmental requirements Such implic-

le-it subsidies, the reasoning continues,ought to be oÝset by import duties

Yet international diÝerences in ronmental standards are perfectly nat-ural Even if two countries share the

envi-same environmental objectives, the

spe-ciÞc pollutions they would attack, and

hence the industries they would

hin-der, will generally not be identical ico has a greater social incentive thandoes the U.S to spend an extra dollarpreventing dysentery rather than re-ducing lead in gasoline

Mex-Equally, a certain environmental goodmight be valued more highly by a poorcountry than by a rich one Contrast, forinstance, the value assigned to a lakewith the cost of cleaning up eÜuentsdischarged into it by a pharmaceuticalcompany In India such a lakeÕs watermight be drunk by a malnourished pop-ulation whose mortality would increasesharply with the rise in pollution In theU.S the water might be consumed byfew people, all of whom have the means

to protect themselves with privately chased water Þlters In this example,India would be the more likely to pre-fer clean water to the pharmaceuticalcompanyÕs proÞts

pur-The consequences of diÝering dards are clear : each country will haveless of the industry whose pollution itfears relatively more than other coun-tries do Indeed, even if there were nointernational trade, we would be shrink-ing industries whose pollution we de-ter This result follows from the policy

stan-of forcing polluters stan-of all stripes to payfor the harm they cause To object, then,

to the eÝects our negative valuation ofpollution have on a given industry is to

be in contradiction: we would be ing to face the consequences of our en-vironmental preferences

refus-Nevertheless, there is sentiment forenacting legislation against social dump-ing Senator Davil L Boren of Oklaho-

ma, the proponent of the InternationalPollution Deterrence Act of 1991, de-manded import duties on the groundsthat Òsome U.S manufacturers, such asthe U.S carbon and steel alloy industry,spend as much as 250 percent more onenvironmental controls as a percentage

of gross domestic product than do

oth-er countries I see the unfair tage enjoyed by other nations exploit-ing the environment and public healthfor economic gain when I look at manyindustries important to my own state.ÓSimilarly, Vice President Al Gore wrote

advan-in Earth advan-in the Balance: Ecology and the

Human Spirit that Òjust as government

subsidies of a particular industry aresometimes considered unfair under thetrade laws, weak and ineÝectual enforce-ment of pollution control measuresshould also be included in the deÞni-tion of unfair trading practices.ÓThese demands betray lack of eco-nomic logic, and they ignore politicalreality as well Remember that the so-called subsidy to foreign producersthrough lower standards is not givenbut only implied According to Senator

PERVERSE CONSEQUENCES for the environment may result from trade restrictions

This graph shows Japanese car exports to the U.S before and after JapanÕs

acqui-escence in voluntary export restraints Sales of small , fuel-eÛcient models declined,

whereas those of the larger Ògas guzzlersÓ soared

HONDA CIVICMAZDA GLCDATSUN 310

MAZDA 626

SOURCE: Robert C Feenstra, University of California, Davis

Trang 23

Boren, the subsidy would be calculated

as Ịthe cost that would have to be

in-curred by the manufacturer or

produc-er of the foreign articles of mproduc-erchandise

to comply with environmental standards

imposed on U.S producers of the same

class of merchandise.Ĩ Anyone familiar

with the way dumping calculations are

made knows that the Environmental

Protection Agency could come up with

virtually any estimates it cared to

pro-duce Cynical politics would inevitably

dictate the calculations

Still, there may be political good

sense in assuaging

environmen-talistsÕ concerns about the

relo-cation of factories to countries with

lower standards The governments of

higher-standards countries could do

so without encumbering free trade by

insisting that their businesses accede

to the higher standards when they go

abroad Such a policy lies entirely

with-in the jurisdictional powers of a

higher-standards country Moreover, the

gov-ernments of lower-standards countries

would be most unlikely to object to

such an act of good citizenship by theforeign investors

Environmentalists oppose free tradefor yet another reason: they wish to usetrade policy to impose their values onother communities and countries Manyenvironmentalists want to suspend thetrading rights of countries that sanc-tion the use of purse-seine nets in tunaÞshing and of leg-hold traps in trap-ping Such punishments seem an in-appropriate use of state power, howev-

er The values in question are not

wide-ly accepted, such as human rights, butidiosyncratic One wonders when theopponents of purse-seine nets put theinterests of the dolphin ahead of those

of MexicoÕs people, who could prosperthrough more productive Þshing Toborrow the campaign manifesto of Pres-ident Bill Clinton: Should we not putpeople Þrst?

Moreover, once such values intrude

on free trade, the way is opened for

an endless succession of demands vironmentalists favor dolphins; Indi-ans have their sacred cows Animal-rights activists, who do not prefer one

En-species over another, will object to ourslaughterhouses

The moral militancy of talists in the industrialized world hasbegun to disillusion their closest coun-terparts in the undeveloped countries.These local environmentalists accusethe rich countries of Ịeco-imperialism,Ĩand they deny that the Western nationshave a monopoly on virtue The mostradical of todayÕs proenvironment mag-

environmen-azines in India, Down to Earth,

editorial-ized recently : ỊIn the current world ality trade is used as an instrument en-tirely by Northern countries to disciplineenvironmentally errant nations Surely, ifIndia or Kenya were to threaten to stoptrade with the U.S., it would hardly af-fect the latter But the fact of the mat-ter is that it is the Northern countriesthat have the greatest [adverse] impact

re-on the worldÕs envirre-onment.Ĩ

If many countries were to play thisgame, then repeated suspensions oftrading rights would begin to underminethe openness of the trading system andthe predictability and stability of interna-tional markets Some environmentalists

EMPLOYMENT IN MEXICAN TUNA FISHERY may oÝset the

sav-ing of dolphins that would result were the industry to forgo

purse-seine nets Countries should not be faulted for placinghuman welfare ahead of our culture-speciÞc concerns

Trang 24

assert that each country should be free

to insist on the production methods

of its trading partners Yet these

envi-ronmentalists ignore the certain

con-sequence of their policy: a PandoraÕs box

of protectionism would open up

Rare-ly are production methods in an

indus-try identical in diÝerent countries

There are certainly better ways to

in-dulge the environmentalistsÕ propensity

to export their ethical preferences The

U.S environmental organizations can

lobby in Mexico to persuade its

govern-ment to adopt their views Private

boy-cotts can also be undertaken In fact,

boycotts can carry much clout in rich

countries with big markets, on which

the targeted poor countries often

de-pend The frequent and enormously

ex-pensive advertisements by

environmen-tal groups against GATT show also that

their resources far exceed those of the

cash-strapped countries whose policies

they oppose

Cost-beneÞt analysis leads one to

con-clude that unilateral governmental

sus-pension of othersÕ trading rights is not

an appropriate way to promote oneÕslesser ethical preferences Such sanc-tions can, on the other hand, appropri-ately be invoked multilaterally to defenduniversal moral values In such casesĐ

as in the censure of apartheid, as ticed until recently in South AfricaĐit

prac-is possible to secure widespread ment for sanctions With a large major-ity converted to the cause, GATTÕs waiv-

agree-er procedure can be used to suspendthe oÝending countryÕs trading rights

Environmentalists are also worried

about the obstacles that the rent and prospective GATT rulespose for environmental regulationsaimed entirely at domestic productionand consumption In principle, GATTlets a country enforce any regulationthat does not discriminate against oramong foreign suppliers One can, forexample, require airbags in cars, provid-

cur-ed that the rule applies to all bile makers GATT even permits rulesthat discriminate against trade for thepurpose of safety and health

automo-GATT, however, recognizes threeways in which regulations may be set

in gratuitous restraint of trade; in lowing procedures aimed at avoidingsuch outcomes, GATT upsets the envi-ronmentalists First, the true intentionĐand eÝectĐof a regulation may be toprotect not the environment but localbusiness Second, a country may im-pose more restrictions than necessary

fol-to achieve its stated environmental jective Third, it may set standards thathave no scientiÞc basis

ob-The issue of intentions is illustrated

by the recently settled Ịbeer warĨ tween Ontario and the U.S Five yearsago the Canadian province imposed a10-cents-a-can tax on beer, ostensibly

be-to discourage littering The U.S arguedthat the law in fact intended to discrim-inate against its beer suppliers, whoused aluminum cans, whereas local beercompanies used bottles Ontario hadomitted to tax the use of cans for juic-

es and soups, a step that would haveaÝected Ontario producers

The second problem is generally

PURE DRINKING WATER is essential for Mexican villagers,

who wait in line to collect it rather than risk contracting

chol-era from local sources The relative value of environmental

beneÞts varies in diÝerent countries: Mexico can better prove public health by concentrating its resources on the puri-Þcation of water than by reducing the lead in gasoline

Trang 25

im-tougher because it is impossible to Þnd

alternative restrictions that accomplish

exactly the same environmental results

as the original policy at lower cost An

adjudicating panel is then forced to

eval-uate, implicitly or explicitly, the

trade-oÝs between the cost in trade disruption

and the cost in lesser fulÞllment of the

environmental objective It is therefore

likely that environmentalists and trade

experts will diÝer on which weights the

panel should assign to these divergent

interests

Environmentalists tend to be fearful

about the use of scientiÞc tests to

de-termine whether trade in a product can

be proscribed The need to prove oneÕs

case is always an unwelcome burden to

those who have the political power to

take unilateral action Yet the trade

ex-perts have the better of the argument

Imagine that U.S growers sprayed

ap-ples with the pesticide Alar, whereas

Eu-ropean growers did not, and that

Euro-pean consumers began to agitate against

Alar as harmful Should the European

Community be allowed to end the

im-portation of the U.S apples without

meeting some scientiÞc test of its health

concerns? Admittedly, even hard science

is often not hard enoughÑdiÝerent

studies may reach diÝerent conclusions

But without the restraining hand of

sci-ence, the itch to indulge oneÕs fearsÑ

and to play on the fears of othersÑ

would be irresistible

In all cases, the moderate

environ-mentalists would like to see GATT adopt

more transparent procedures for

adjudi-cating disputes They also desire

great-er legal standing to Þle briefs when ronmental regulations are at issue Thesegoals seem both reasonable and feasible

envi-Not all environmental problems

are local ; some are truly global,such as the greenhouse eÝectand the depletion of the stratosphericozone They raise more issues that re-quire cooperative, multilateral solutions

Such solutions must be both eÛcientand equitable Still, it is easy to see thatrich countries might use their econom-

ic power to reach protocols that mize eÛciency at the expense of poor-

maxi-er countries

For instance, imagine that the ers of a protocol were to ask Brazil torefrain from cutting down its rain for-ests while allowing industrialized coun-tries to continue emitting carbon diox-ide They might justify this request onthe grounds that it costs Brazil less tokeep a tree alive, absorbing a unit ofcarbon dioxide every year, than it wouldcost the U.S or Germany to save a unit

draft-by burning less oil Such a trade-oÝwould indeed be economically eÛcient

Yet if Brazil, a poorer country, were thenleft with the bill, the solution would as-suredly be inequitable

Before any group of countries

impos-es trade sanctions on a country thathas not joined a multilateral protocol,

it would be important to judge whetherthe protocol is indeed fair Nonmemberstargeted for trade sanctions should havethe right to get an impartial hearing of

their objections, requiring the strong todefend their actions even when they ap-pear to be entirely virtuous

The simultaneous pursuit of the twocauses of free trade and a protectedenvironment often raises problems, to

be sure But none of these conßicts isbeyond resolution with goodwill and

by imaginative institutional innovation.The aversion to free trade and GATTthat many environmentalists display isunfounded, and it is time for them toshed it Their admirable moral passionand certain intellectual vigor are betterdevoted to building bridges between thecauses of trade and the environment

FURTHER READING

FOR THE COMMON GOOD H E Daly and

J B Cobb, Jr Beacon Press, 1989

INTERNATIONAL TRADE AND THE RONMENT Edited by Patrick Low WorldBank, 1992

ENVI-POPULATION, TECHNOLOGY AND STYLE: THE TRANSITION TO SUSTAIN-ABILITY Edited by Robert Goodland et

LIFE-al Island Press, Washington, D.C., 1992.MYTHS AND MISCONCEPTIONS OF FREE

TRADE Ravi Batra ScribnerÕs, 1993.INTERNATIONAL TRADE AND ENVIRON-MENT Edited by Carl Folke et al Special

issue of Ecological Economics, Vol 9,

No 1; February 1994 (in press)

NATIONAL SELF-SUFFICIENCY is a good commonly overlooked

by free traders Just as nations are better oÝ having their own

symphony orchestras and other cultural oÝerings, they shouldalso keep their vital industries local

Trang 32

As long ago as 1904, the British

sci-entist T R Elliot proposed

cor-rectly that neurons (nerve cells)

often communicate with one another

and with other cell types not

electrical-ly but chemicalelectrical-ly He suggested that an

action potential, or electrical impulse,

propagating along an excited neuron

triggers the release of chemicals (now

called neurotransmitters) from the

ex-cited cell In turn, the liberated

chemi-cals may cause another cell to take in or

extrude selected ions By thus altering

the ßow of charge across the membrane

of this second cell, the

neurotransmit-ters can give rise to a new impulse

Since then, investigators have

identi-fied perhaps 50 neurotransmitters and

have learned that a single neuron may

secrete several of them Workers have

also struggled to explain just how

neu-rotransmitters, particularly those in the

brain, manage to regulate ionic

trans-port, and hence impulse production, in

the cells they inßuence

The solution to this last problem has

emerged slowly, but research in my

laboratory at the Pasteur Institute in

Paris and in other laboratories during

the past 25 years has made great

head-way We have ascertained that

recep-tors for neurotransmittersÑwhich

pro-trude from cell membranesÑplay a

piv-otal role in mediating the conversion of

chemical signals into electrical activity

And we have begun to clarify how

cer-tain major receptors carry out this

challenging task Those molecules have

been found to constitute a remarkablesuperfamily of neurotransmitter recep-tors that are known as neurotransmit-ter-gated ion channels

Much of this insight derives from tensive study in the 1970s and 1980s

in-of a receptor initially isolated from theelectricity-generating organ of an elec-tric Þsh Yet the story of how investiga-tors solved the mysteries of impulsetransmission by chemicals more prop-erly begins decades earlier, with the pi-oneering contributions of John New-port Langley of the University of Cam-bridge In 1906 he proposed that bodilytissues bear receptors for drugs In sodoing, he provided one of the Þrst sig-niÞcant clues to the means by whichneurotransmitters exert their eÝects

Langley based his proposal on ies he conducted into how the poisoncurare kills its victims When he under-took these investigations, he was awarethat curare causes asphyxiation: itblocks motor nerves from inducing con-traction of respiratory muscles Hewondered, though, whether it acted onthe nerves or on the muscles To Þndout, he placed large doses of nicotine, asubstance that normally induces con-traction, directly onto strips of skeletalmuscle from chicken (at a site wheremotor nerves are normally connected)

stud-A contraction followed Then he appliedcurare The drug blocked nicotineÕs ac-tion Langley concluded that curare in-teracts directly with muscle tissue,which displays on its surface an Òespe-cially excitable component,Ó or Òrecep-tive substance,Ó capable of combiningwith either nicotine or curare

Neurobiologists now understand thatnicotine and curare couple with the part

of the receptor molecule designed tobind to the neurotransmitter acetylcho-line Bound nicotine serves as an ago-nist : it mimics the stimulatory eÝect

of a naturally produced substance,

ace-tylcholine Bound curare, in contrast, is

a competitive antagonist: it issues nostimulatory signal and, at the sametime, prevents acetylcholine and nico-tine from doing so

Despite the brilliance of the

re-ceptor concept, its value eludedthe scientific community for de-cades Skepticism arose in part becausescientists lacked the tools for isolatingreceptors Moreover, they had troubleimagining how binding of a chemical to

a receptor molecule at the cell surfacecould inßuence the ßow of ions throughchannels in the cell membrane

I helped to ease these objections inthe mid-1960s, when, as a graduate stu-dent working on my doctoral disser-tation, I suggested a theoretical solu-tion to this conceptual diÛculty A fewyears earlier, structural studies of hemo-globin and various enzymes had indi-cated that these molecules includedseveral separate sites capable of associ-ating with other substances IÑtogeth-

er with my teachers Jacques Monod andFran•ois Jacob and their colleague JeÝ-ries WymanÑpostulated that certain en-zymes may be activated by allosteric,

or indirect, means, by which binding atone site inßuences behavior of anothersite without any assistance from an ad-ditional source of energy We assumed

Chemical Signaling

in the Brain

Studies of acetylcholine receptors in the electric organs

of fish have generated critical insights into how neurons in the human brain communicate with one another

by Jean-Pierre Changeux

JEAN-PIERRE CHANGEUX has been

di-rector of the molecular neurobiology

unit of the Pasteur Institute in Paris since

1972 He is also a professor at the

insti-tute and at the College of France

Chang-eux has won many awards for his

contri-butions to neuroscience

ACETYLCHOLINE RECEPTOR, which

con-sists of five subunits (left), was the first

neurotransmitter receptor to be isolated.Later work showed it to include not onlyneurotransmitter binding sites but also

an ion-transporting channel (right) ( The

beta and delta subunits and part of onealpha subunit have been cut away forclarity.) The channel is closed when thereceptor is at rest, but it opens rapidlywhen the two alpha subunits both com-bine with acetylcholine

Trang 33

that attachment of some substance to

a docking site on an enzyme could

prop-agate a conformational change

through-out the enzyme, thereby rendering a

dis-tant site able to act on a substrate (the

substance transformed by an enzyme)

In my dissertation I noted brießy that

receptors for neurotransmitters might

function similarly They might contain

both a neurotransmitter binding site

and a separate region that forms an ion

channel Attachment of the

neurotrans-mitter to the binding site could elicit a

conformational change in the molecule

that would culminate in the opening of

its channel component To evaluate the

merit of this idea, my co-workers and I

had to analyze the composition of some

kind of receptor in detail For this, we

needed a good supply Unfortunately,

no receptor had yet been isolated, and

so that task became our mission

Our choice of receptor was inspired

by discoveries made by David

Nachman-sohn after he ßed Nazi Germany In the

late 1930s, while at the University of

ParisÐSorbonne, Nachmansohn and his

colleagues showed that acetylcholine

not only induces muscle to contract, it

also causes electricity-generating organs

of electric Þsh to produce current

Fur-thermore, the organs oÝer two lar advantages for researchers The con-stituent cells, called electrocytes, arehuge and thus relatively easy to handle

particu-Additionally, they number in the billions,which means electric organs harbor anabundance of acetylcholine receptormolecules

With these advantages in mind,

we decided to isolate the tylcholine receptor in the elec-

ace-tric organ of the elecace-tric eel

(Electropho-rus electricus) First, we had to break up

the electrocytes in the organ to createpreparations that could be analyzedchemically Michiki Kasai, now at OsakaUniversity, and I therefore ground upelectric tissue Then we separated outmicron-sized fragments of membranesfrom the innervated regions of electro-cytes LangleyÕs studies of muscle tis-sue suggested we would Þnd a highconcentration of the receptor in the in-nervated areas These membrane frag-ments have a wonderfully useful prop-erty: they close up into microsacs, ortiny vesicles, that can be Þlled with ra-dioactively labeled sodium (Na+) andpotassium (K+) ions

As would be expected if functional

copies of the receptor were present inthese microsacs, addition of acetylcho-line to a suspension of the vesicles dra-matically altered the ßow of ions intoand out of the vesiclesÑjust as occurs

in intact electrocytes when they respond

to acetylcholine Moreover, in agreementwith early suggestions of an allostericmechanism, no additional energy sup-ply was required for the reaction to takeplace Hence, we felt reasonably surethat the receptor was present and func-tional in the microsac membranes.Still, we needed some way to distin-guish the receptor from the rest of thematerial in the membranes At that time,the only way to pinpoint a molecularspecies on a membrane was to radio-actively label a substance that homed

to it and bound tightly We were havingdiÛculty Þnding a suitable homing ma-terial when Chen-Yuan Lee of the Na-tional Taiwan University came to ourrescue

Lee happened to visit my

laborato-ry in the spring of 1970 to present hisresearch on the structure and action

of snake venom The bites of several

snakes, such as the banded krait

(Bun-garus multicinctus) and the cobra, are

fatal because their venom contains

BINDING SITE

CELL

POTASSIUM ION

ION CHANNEL

Trang 34

ic molecules that, like curare, block

sig-nal transmission by motor neurons

Among these molecules are alpha

tox-ins Lee reported that even at low

con-centrations, alpha-bungarotoxin from

the banded krait almost irreversibly

blocks the eÝects of acetylcholine on

the muscles of evolutionarily advanced

vertebrates I realized then that

alpha-bungarotoxin might provide the

speci-Þcity we needed for identifying the

ace-tylcholine receptor on the microsacs

we derived from the electric eel To our

delight, toxin supplied by Lee did our

bidding perfectly

We could Þnally take up the

task of purifying the receptor,

which we soon found was a

protein By 1974 our group and several

others had succeeded My team reached

this goal by applying a technique called

aÛnity chromatography We created

in-soluble beads to which arms that

end-ed in a structural analogue of curare

had been attached Then we doused

the beads with microsac membranes

that had been dissolved in a detergent

solution to separate the constituent

molecules The free receptor molecules

bound to the analogue, and the rest of

the solution ßoated away Next we

poured copies of the curare analogue

over the beads Now the receptor

mole-cules bound preferentially to the added

analogue and came oÝ the beads By

passing the resulting complexes of

re-ceptor and analogue through a

mem-brane permeable only to the curare

sub-stitute, we eliminated the analogue andacquired a pure supply of the receptor

Eager to learn something about thestructure of our prize, we presentedJean Cartaud of the Jacques Monod In-stitute in Paris with samples to view in

an electron microscope He found thatwhen observed from above, the recep-tor resembled a rosette with a depres-sion in the center Other analyses, by Ar-thur Karlin of the Columbia UniversityCollege of Physicians and Surgeons and

by Michael Raftery of the California stitute of Technology, revealed that theoverall molecule is composed of Þveprotein chains, or subunits: two alphachains, which have an identical molecu-lar weight, and three chains called beta,gamma and delta, which vary in molec-ular weight Moreover, Karlin demon-strated that the alpha subunits bear theprimary responsibility for recognizingacetylcholine (Today it is clear that thebinding site on each of the two alphasubunits must be occupied in order forthe ion channel to open.)

In-These results intrigued us They gested that each subunit might formone ỊpetalĨ of the rosette and that thecentral depression might reßect the ex-tracellular entryway to a membrane-spanning ion channel We needed moredata in order to test that idea, but inthe interim we had to cope with anoth-

sug-er nagging problem Could we be surethat receptor molecules contained anion channel, not solely the site thatbound acetylcholine?

In 1974 my co-worker Gerald L

Ha-zelbauer and I tackled this question byincorporating proteins from puriÞedextracts of microsacs into lipid mem-branes that enclosed radioactively la-beled sodium or potassium ions Aswould be predicted if the channel werepresent, binding by acetylcholine trig-gered the ßow of ions, and binding byalpha-bungarotoxin and curare blockedchanges in ionic ßux Later we con-Þrmed the results with puriÞed recep-tors themselves Hence, by 1980 weand other groups had clearly shownthat the pure protein does indeed con-tain all the structural elements neededfor the chemical transmission of anelectrical signalĐnamely, an acetylcho-line binding site, an ion channel and amechanism for coupling their activity

To attack the deeper problem of howthe acetylcholine receptor worked, wehad to decipher the sequence of its con-stituent amino acid Such informationprovides clues to the shape adoptedwhen a protein, which is little more than

a string of amino acids, folds in on self And knowledge of the folded struc-ture oÝers clues to the functions of thevarious domains in that structure.Introduction of automated sequenc-ing and genetic engineering techniques

it-in the late 1970s facilitated this eÝort

In 1979 my colleague Anne ThiŽry, Donny Strosberg of the JacquesMonod Institute and I elucidated thesequence of the Þrst 20 amino acids atone end (called the amino terminal ) ofthe alpha subunit in the acetylcholinereceptor of the European, or marbled,

Devillers-electric ray (Torpedo marmorata)

Sub-sequently, Raftery and Leroy E Hoodand their colleagues at Caltech identi-Þed essentially the same sequence in

the Californian electric ray (T

californi-ca) and went further When they

char-acterized the 54 amino acids abuttingthe amino terminal of the alpha, beta,gamma and delta subunits, they unex-pectedly found striking similarity: 35 to

50 percent of the sequence was cal, or homologous, in all four subunits.Molecular biologists interpret suchidentity to mean that the genes specify-ing the amino acid sequences of thesubunits are descendants of some an-cestral gene that duplicated twice (andunderwent subsequent alteration) inthe course of evolution The homologyfurther implied that the complete sub-units were similar to one another andtherefore probably did arrange them-selves quasisymmetrically around acentral axis, forming the petals on therosette seen in the electron microscope

identi-By 1983 more complete informationhad emerged Shosaku Numa and histeam at Kyoto University had solvedthe full sequences of the alpha and then

ELECTRIC RAY from the Torpedo genus harbors an electricity-generating organ

that contains billions of copies of an acetylcholine receptor Identification of the

re-ceptorÕs amino acid sequence led to the discovery that acetylcholine receptors in

the muscle and brain of humans are structurally similar to the Torpedo receptor.

Trang 35

SCIENTIFIC AMERICAN November 1993 60A

Major structural features of the

ace-tylcholine receptor have begun to

yield to scrutiny Its five subunits (inset

in top panel ), which can be depicted

schematically as cylinders (top, center ),

are each formed from a protein that has

folded in on itself (detail at top right ).

Every subunit includes a large

hydro-philic (water-loving) region abutting the

amino (NH2) terminal, as well as four

hydrophobic (water-hating)

membrane-spanning segments: M1, M2, M3 and

M4 The neurotransmitter binding sites,

viewed from above in the middle panel

(inset), consist primarily of amino acids

(yellow spheres in detail ) residing in the

large hydrophilic region of the alpha

subunits (Letters in the spheres

repre-sent specific amino acids.) Neighboring

subunits contribute as well (pink sphere).

The ion channel is composed of five M2

segments (inset in bottom panel ) and

contains several rings of amino acids that

affect the functioning of the receptor

Among these, three negatively charged

rings (blue in detail showing two M2

segments in a specific acetylcholine

re-ceptor ) draw positively charged ions

(not shown ) through the channel An

un-charged, leucine ring (green ) at the

cen-ter, where M2 segments probably bend,

participates in closing the ion channel

when the receptor becomes

desensi-tized to acetylcholine The electron

den-sity map (bottom left ), showing a slice

through the receptor, indicates the

prob-able orientation of two M2 segments

(dark bars ) Nigel Unwin of the Medical

Research Council in Cambridge,

En-gland, supplied that image

Anatomy of the Acetylcholine Receptor

M2

ATTACHED PROTEIN MEMBRANE

Y

A

V V

F F

E

S S

A E E

– –

–

– –

–

– –

–

– E

L L

L

L L

C C YY

δ δ

β β

α

δ γ

M2

M4

M4 COOH

Trang 36

the beta, gamma and delta subunits of

the T californica receptor Three other

laboratories, including mine, had also

identiÞed the sequence of the T

cali-fornica gamma subunit and supplied

that of the T marmorata alpha subunit.

Then Numa published the sequences of

all the subunits in the acetylcholine

re-ceptor on human muscle The muscle

receptor turned out to differ little from

those of electrocytes

These studies put workers in an

excellent position to ascertain

something about the architecture

of the folded subunits and how they

might Þt together In trying to predict

the structure of a folded protein,

scien-tists often scan the linear amino acid

sequence for stretches that are rich in

either hydrophilic or hydrophobic

ami-no acids Hydrophilic substances are

attracted to water, such as that in

cyto-plasm or in the ßuids that bathe cells;

hydrophobic, or water-hating,

substanc-es prefer to associate with other

hy-drophobic entities, such as the lipids

that form cell membranes

Every subunit that had been

se-quenced began at the amino-terminal

side with a large hydrophilic region

and housed four separate hydrophobic

segments of about 20 amino acids The

hydrophobic areas are referred to,

be-ginning with the one closest to the

lengthy hydrophilic domain, as M1, M2,

M3 and M4 This arrangement

suggest-ed that every subunit chain snaksuggest-ed

through the thickness of the cell

mem-brane four times, so that all four of the

hydrophobic regions spanned the

mem-brane [see box on preceding page].

In one model, at least, the large

hy-drophilic domain protruded into the

extracellular space So situated, that

domain on the alpha subunits (the

sub-units primarily responsible for

grasp-ing acetylcholine) would be well

posi-tioned to serve as a neurotransmitter

binding site It further seemed

reason-able to guess that one

membrane-span-ning segment from each of the Þve

sub-units associated with its counterparts

in the other subunits to form the ion

channel The like segments could form

such a channel if together they

encir-cled the central axis of the rosette

Later research conÞrmed this

scenar-io and added important details More

immediately, though, the sequencing of

the subunit proteins enabled

research-ers to dispel confusion over the

opera-tion of acetylcholine receptors in the

brain The trouble derived from the

re-sponse of certain of these receptors to

snake venoms

By the early 1980s investigators knew

that nicotine-sensitive, or nicotinic,

ace-tylcholine receptors were present in thebrain of higher vertebrates Neurobiol-ogists were puzzled, however, when al-pha-bungarotoxin seemed to block thefunctioning of certain of the receptors

but not others What is more, a

Bungar-us toxin called neuronal bungarotoxin

apparently attached to some cerebralreceptors but, again, not to others (Thepicture is actually more complicated

The brain additionally includes a class

of acetylcholine receptors named carinic receptors that I shall not discusshere Those receptors are very diÝerentfrom the nicotinic types They areformed from a single protein chain and

mus-do not include an ion channel They ert their eÝects through such intracel-lular mediators as G proteins.)

ex-The smoke cleared when James

W Patrick and Stephen F mann and their colleagues at theSalk Institute for Biological Studies inSan Diego and Marc Ballivet of the Uni-versity of Geneva used their knowledge

Heine-of the structure Heine-of electrocyte and cle subunits to decipher the amino acidsequences of cerebral subunits The investigators guessed that the aminoacid sequences of the cerebral subunitsprobably resembled those of electro-cytes and muscle even though certaincerebral receptors behaved somewhatdiÝerently from their counterparts inelectrocytes and muscle If the proteinswere similar, then the genes specifyingtheir amino acid sequences would besimilar as well That being the case, aprocess called DNA hybridization could

mus-be expected to help isolate the cerebralsubunit genes and thereby uncover theamino acid sequences of the corre-sponding subunits

DNA hybridization techniques italize on a prominent characteristic

cap-of genes Genes consist cap-of two strands

of nucleotides (the building blocks ofDNA) One strand from a gene will read-ily combine, or hybridize, with the oth-

er strand from the same or a closely lated gene Aware of this propensity,the investigators hoped they could re-trieve the cerebral subunit genes from

re-a lre-arger pool of brre-ain-derived DNA byÒÞshingÓ for them with ÒhooksÓ made

of nucleotide sequences that actuallydirect the synthesis of electrocyte ormuscle subunits The procedure workedbeautifully Seven alpha-subunit types(each of which is numbered) were found

to be produced in the brains of brates, including humans Three nonal-pha types, often classiÞed as beta sub-units, were discovered as well This di-versity suggested that the variable re-sponses of cerebral receptors to snakevenoms derive from slight diÝerences

verte-in the amverte-ino acid sequences of one ormore subunits

Subsequent studies have

demonstrat-ed that the protein products of most ofthe subunit genes identiÞed to date canyield functional receptors in living cells

if the cells make at least one alpha andone nonalpha variant The experimentsyielding this conclusion often involvedinjecting the genes into the nucleus ofoocytes, or immature eggs, from the

frog Xenopus In response, the

protein-making machinery of the oocytes scribed the genes into messenger RNAand, after transporting the RNA to thecytoplasm, translated it into the speci-Þed proteins Then the proteins associ-ated with one another in groups of Þve

tran-to produce receptran-tors

Evaluations of many receptors

pro-duced by Xenopus oocytes also

demon-strated that substitution of one unit variant for another in a receptorcan indeed change some properties ofthe receptor As an example, neuronalbungarotoxin blocks the response toacetylcholine receptors composed ofbeta-2 and either alpha-3 or alpha-4subunits, but the toxin does not inter-fere with the activity of molecules com-posed of beta-2 and alpha-2 subunits

sub-At about the same time as the

het-erogeneity of nicotinic line receptors was emerging, re-searchers were busy attempting to de-cipher the structure and operation ofreceptors for other neurotransmitters.When that work began, few would haveguessed that the receptors for gamma-aminobutyric acid ( GABA ) and glycinewould have much in common with ace-tylcholine receptors After all, nicotinicacetylcholine receptors excite cells byopening a channel permeable to cations(positively charged ions) Receptors forGABA and glycine, in contrast, facili-tate transport of chloride anions ( ClÐ);the ßow of chloride anions into cellsinhibits generation of electrical impuls-

acetylcho-es and can thereby counteract the fects of excitatory receptors

ef-Nevertheless, studies conducted inthe 1980s revealed that glycine andGABA receptors consist of multiple sub-units That in itself was not remark-able More strikingly, however, HeinrichBetz of the University of Heidelbergand Eric A Barnard of the Medical Re-search Council in Cambridge, England,respectively determined the completesequences of the glycine and GABA re-ceptors and found that the distribution

of hydrophilic and hydrophobic mains strongly resembled that of nico-tinic acetylcholine receptors

do-In other words, it began to seem

like-ly that the subunits in the GABA and

Trang 37

glycine receptors, in common with

those of nicotinic acetylcholine

recep-tors, weave through the cell membrane

four times Evidence also indicated that

the complete receptors for GABA and

glycine carry both a neurotransmitter

binding site and an ion channel More

recent work suggests that some

sero-tonin receptors have a similar

architec-ture as well These receptors, like

ace-tylcholine receptors, control the

cross-membrane transport of cations and are

thus excitatory

The architectural similarities among

the receptors explain why

neurobiolo-gists now consider acetylcholine, GABA,

glycine and serotonin receptors to

con-stitute the superfamily of genetically

and structurally related

neurotransmit-ter-gated ion channels ( Receptors for

the prevalent neurotransmitter

gluta-mate may be distantly related They

in-clude a neurotransmitter binding site

and an ion channel but differ in

struc-ture.) There is also evidence that

neu-rotransmitter-gated ion channels are

allosteric proteins As would be

expect-ed for allosteric molecules, the

estimat-ed distance between the

neurotransmit-ter binding site and the ion channel is

largeĐabout 30 angstroms

As was found for acetylcholine

recep-tors, the subunits of other members of

the superfamily come in multiple

vari-eties Hence, a GABA receptor in one

part of the brain might well have

some-what diÝerent properties than does a

variant elsewhere in that organ For

in-stance, benzodiazepines, which are so

abundantly consumed as tranquilizers

by industrialized populations, ate the inhibitory action of only certainGABA receptor species They do so bybinding to a site that is distinct fromthe GABA binding site

potenti-As the precise inßuence on behavior

of every subspecies of every subunit inneurotransmitter-gated ion channels isdeciphered, pharmacologists should beable to design drugs that will selectivelyimpede or enhance those eÝects Suchagents, in turn, might help ameliorateany number of debilitating conditions,including mood disorders, tissue dam-age associated with stroke and, perhaps,AlzheimerÕs disease

Of course, to devise such drugs,

researchers require a rather fullunderstanding of receptor struc-ture They need to know the speciÞcamino acids responsible for bindingneurotransmitters, for directing the ßow

of ions in and out of cells and for wise modulating receptor function Oneuseful way to gather such information

other-is known as aÛnity labeling Sometraceable version of a molecule that in-teracts with a receptor is allowed to bindirreversibly to that target; the boundsubstance thus highlights the aminoacids that constitute the binding site

Between 1988 and 1990, my leagues Michael Dennis, JŽr™me Girau-dat, Jean-Luc Galzi and I uncoveredmuch of the acetylcholine binding site

col-by identifying amino acids in a Torpedo

receptor that were labeled by the

com-pound pÐ(N,NÐ dimethyl)

aminoben-zenediazonium ßuoroborate, also called

DDF We learned that several aromaticamino acids (those carrying ring-shapedside chains) are critical to DDF binding,and we conÞrmed binding by a pair of

cysteine amino acids identiÞed in a

Tor-pedo receptor by Karlin The labeled

ami-no acids are distributed within threedistinct regions of the large hydrophil-

ic domain of the amino-terminal region

It became evident that they collectivelyform a kind of negatively charged cup

in which the positively charged part ofacetylcholine could lodge

What is even more exciting, we went

on to show that these amino acids tually do play a critical role in receptorfunction With Daniel Bertrand of theUniversity of Geneva Medical Center, weproved this point in a receptor that con-sists entirely of alpha-7 subunits fromthe chicken brain (This receptor is oneexception to the rule requiring the pres-ence of both alpha and beta subunitsfor receptor formation.) SpeciÞc muta-tion, by what is called site-directed mu-tagenesis, of the amino acids that DDF

ac-labeled in the Torpedo receptor

strik-ingly impeded the alpha-7 receptorÕsresponse to acetylcholine

Taken together, the aÛnity-labelingand mutagenesis studies conÞrm thatthe large hydrophilic region of the al-pha subunit is exposed to the extracel-lular environment There it sits, ready

to receive acetylcholine released fromnerve endings and to trigger the open-ing of the ion-transporting channel.Ảnity labeling also delineated the

structure of the ion channel in a

Torpe-do receptor DiÛcult analyses convinced

us by the end of 1985 that the drugchlorpromazine attaches to amino acids

on the membrane-crossing, M2 phobic segment of at least one sub-unitĐthe delta chain This work, and asimilar report by Ferdinand Hucho andhis co-workers at Berlin University, sug-gested that the channelÕs inner wall isformed by Þve M2 segments, one con-tributed by every subunit

hydro-Numa and Bert Sakmann, then at theMax Planck Institute for BiophysicalChemistry in Gšttingen, conÞrmed thispossibility By site-directed mutagene-sis, they determined that at least threerings of negatively charged amino acids(especially glutamate) participate intransporting ions through the channel.Each ring lies in a plane parallel to thesurface of the cell and consists of Þveamino acids, one supplied by the M2segment of every subunit A single ringresides at the extracellular surface ofthe membrane (at the top of the chan-nel) A second, termed the intermediatering, lies at the bottom of the channel,and the third ring lies directly belowthe second, in the cytoplasm proper.60F SCIENTIFIC AMERICAN November 1993

UNFOLDED PROTEIN CHAINS (multicolored bars) that constitute subunits in

re-ceptors for acetylcholine, GABA and glycine have much in common All harbor a

large, extracellular hydrophilic domain, a smaller, cytoplasmic hydrophilic domain

and four hydrophobic segments (M1, M2, M3 and M4) believed to span the cell

membrane These similarities suggest that the molecules all belong to one

super-family of structurally related neurotransmitter receptors

CYTOPLASMIC HYDROPHILIC DOMAIN

FROM GLYCINE RECEPTOR

Trang 38

Given that the distribution of

hy-drophobic subunits in the GABA,

gly-cine and serotonin receptors matches

that of acetylcholine receptors, we

won-dered if their M2 segments formed the

channel in those receptors as well They

do, even though those receptors

trans-port negatively, rather than positively,

charged ions The diÝerence in charge

preference apparently stems from

vari-ance in just a few amino acids When

BertrandÕs team and mine transferred

into the alpha-7 receptor three M2

ami-no acids from a GABA receptor

(includ-ing the one giv(includ-ing rise to the

intermedi-ate ring), those few changes converted

the alpha-7 receptor channel from a

cationic to an anionic transporter

Whether a receptor carries an

anion- or cation-transporting

channel, its main function is

to open that channel in response to

sig-nals from a neurotransmitter Yet

neu-rotransmitter receptors have another

fascinating skill as well By altering

their conformation, they can

apparent-ly increase or decrease their readiness

to respond to neurotransmitters In that

way, they can regulate the pool of

re-ceptors available to respond to

exter-nal sigexter-nals and can thus inßuence the

eÛciency of signal transmission

My associates and I realized that

re-ceptors could possess this regulatory

power when we began to consider a

phenomenon noted by several

investi-gators over the years Receptors react

diÝerently to discrete pulses of

high-ly concentrated acetylcholine (such as

those usually delivered by neurons)

than they do to the continuous

avail-ability of lower concentrations (such

as is provided in many experiments)

Excited neurons secrete large

concen-trations of acetylcholine in discrete

bursts at synapses, the specialized

junc-tions now known to connect neurons

The molecules freed during a single

pulse pour into the synaptic cleft (the

space separating communicating cells)

Many of them make their way from the

excited, presynaptic cell to receptors on

the surface of a postsynaptic cell Under

normal circumstances, the aÛnity of

most receptor molecules for the

neuro-transmitter is low Consequently,

imme-diately after acetylcholine binds to

re-ceptors and causes the channel to open,

the receptors release their hold on the

neurotransmitter, which is promptly

degraded Within milliseconds of being

bound, the receptors revert to their

closed, unbound state and are ready to

react once again

In contrast, when acetylcholine is

sup-plied continuously to receptors, the

receptor molecules begin to lose their

responsiveness After initially openingthe ion channel, they slowly take on aỊdesensitizedĨ conformation over thecourse of seconds or minutes That is,they bind avidly to acetylcholine butmaintain a closed channel and do nottransport ions Even small concentra-tions of acetylcholine will be held bythese closed-channel receptors for rela-tively long periods, during which thereceptors cannot react to new signals

So it seems that acetylcholine tors can adopt at least three intercon-vertible states that can diÝer in theiraÛnity for the neurotransmitter and

recep-in the eÛciency of signal transmission

In addition to the high-aÛnity, sitized state, in which the channel re-mains closed, there is a low-aÛnity,resting (but activable) state in whichthe channel is closed but easily opened

desen-if both alpha subunits are bound denly by acetylcholine The low-aÛni-

sud-ty, open-channel condition is the thirdstate All three states switch back andforth spontaneously but at diÝerentrates than occur when acetylcholine ispresent

Site-directed mutagenesis has helpedclarify the process by which desensi-tization occurs; it appears that leucineamino acids are involved In aÛnity-la-beling studies carried out by my group,chlorpromazine labeled a ring of un-charged leucine amino acids near thecenter of the ion channel When Ber-trandÕs team and mine replaced theleucines in this ring with a smaller un-charged amino acid, we created a recep-tor that resembled a normal desensi-tized receptor in that it bound tightly

to acetylcholine Yet its channel wasfixed in an open state This result im-plies that the leucine ring locks the ionchannel closed when the receptor is inthe desensitized conformation

My associates and I have long

pondered the beneÞts thatmight accrue to an organismfrom bearing receptors able to adoptmultiple states Of course, a desensiti-zation mechanism would protect recep-tor-bearing cells from becoming over-excited in response to dangerously highlevels of acetylcholine But I believe that

DYNAMIC NATURE of the acetylcholine receptor is evident in its ability to adopt

multiple conformations In the resting state (a), the receptor has low affinity for

acetylcholine, and its ion channel is closed If it is exposed briefly to a high centration of the neurotransmitter, it assumes the active, open-channel conforma-

con-tion for milliseconds (b) before releasing the acetylcholine and reverting to the

resting state If acetylcholine is supplied continuously, resting and activated

re-ceptors can slowly assume a desensitized state (c ) In this condition, the receptor

holds acetylcholine with high affinity for seconds or minutes, maintains a closedchannel and will not respond to new pulses of acetylcholine

ACETYLCHOLINE

CLOSED, RESTINGSTATE

c

OPEN, ACTIVESTATE

FASTTRANSITION

SLOWTRANSITION

CLOSED, DESENSITIZEDSTATE

Trang 39

there is another explanation as well.

In 1982 my colleague Thierry

Heid-mann and I further proposed that the

ability of acetylcholine receptors to

alter their conformation slowly could

more routinely serve to increase or

de-crease the eÛciency of signal

transmis-sion at a synapse In so doing, such

re-ceptors could participate in learning

Many theorists, following the lead of

Donald O Hebb, postulate that

learn-ing depends on changes in the

eÛcien-cy of signal transmission across the

synapses linking two neurons that are

activated simultaneously

Our hypothesis is far from proved,

but it is plausible If the ability to adopt

many states were important to

regulat-ing signal transmission, this ßexibility

should appear in other

neurotransmit-ter receptors as well Research showsthat GABA, glycine and serotonin re-ceptors also are able to assume desen-sitized conformations

The demonstration of state changes

in other receptors is not the only port for the possibility that receptorsregulate synaptic eÛciency These mol-ecules sit in a particularly good posi-tion to control the degree of respon-siveness needed at any given moment

sup-Crossing the cell membrane as they do,they are exposed to chemical and elec-trical signals issued both from outsideand from within the cell If each ofthese signals pushed the receptor to-ward one conformation or another, theÞnal arrangement would reßect thesummed, or integrated, inßuence ofvarious, possibly contradictory, forces

Among the signals that impinge onreceptors are the intracellular concen-tration of calcium ions and changes inthe electrical potential across the cellmembrane Hyperpolarization of themembrane and elevation of the calci-

um concentration in muscle acceleratedesensitization of the acetylcholine re-ceptor Richard L Huganir and PaulGreengard of the Rockefeller Universityfurther established in 1986 that phos-phorylation of the receptor promotesdesensitization

If neurotransmitter receptors did infact control the eÛcacy of intercellularsignaling, we would anticipate that theywould be capable of increasing, notmerely decreasing, their sensitivity toneurotransmitters Such potentiationhas been observed Extracellular calci-

um enhances the stimulatory effect ofnicotinic acetylcholine receptors in thebrain, and glycine enhances the effect

of glutamate receptors

In general, then, we suspect that if areceptor is tottering between two con-formations, one of which is sensitiveand the other of which is refractory tostimulation, the balance can be shiftedtoward one of the two states by chemi-cal or electrical signals The resultingconformation, in turn, enhances or de-presses the ability of the receptor toconvey signals promptly

Clearly, our understanding of

chemical signaling in the brainhas advanced dramatically in thepast quarter century The decision toisolate the acetylcholine receptor from

a Þsh organ was risky: if the eÝortfailed or if that receptor was unrelated

to any others, we would have wastedtime and energy Fortunately, the gam-ble paid oÝ more than we could havehoped The acetylcholine receptor inelectric Þsh was identiÞed, and its se-quence was deciphered Then biotech-nology, especially recombinant DNAmethodology, enabled workers to char-acterize related receptors in humanmuscle and in the brain and to learnthat nicotinic acetylcholine receptorsare structurally related to, and form asuperfamily with, those responsive toGABA, glycine and serotonin

Meanwhile it became clear that thesubunits composing each type of recep-tor are themselves variable: a receptor

in one part of the brain may well sess properties that diÝer from those

pos-of their immediate kin elsewhere in rebral tissue This likelihood raises thetantalizing possibility that drugs tar-geted to speciÞc receptors on deÞnedcategories of neurons can be developedfor the highly selective treatment ofsignaling disorders in the brain

ce-62 SCIENTIFIC AMERICAN November 1993

MANY FORCES can affect the conformation of a neurotransmitter receptor and

hence the efficiency with which it responds to signals received from a neuron

act-ing on it Aside from the concentration and delivery rate of the neurotransmitter

(a ), some influences include binding by additional neurotransmitters or other

ex-tracellular chemicals (b ), changes in the electrical potential across the cell

mem-brane (c ) and binding by intracellular signaling molecules (d ), such as ions.

NEURONAL MAN: THE BIOLOGY OF MIND

J P Changeux Translated by Laurence

Garey Pantheon Books, 1985

FUNCTIONAL ARCHITECTURE AND

DYNAM-ICS OF THE NICOTINIC ACETYLCHOLINE

RECEPTOR: AN ALLOSTERIC

LIGAND-GAT-ED ION CHANNEL J P Changeux in

FIDIA Research Foundation Neuroscience

Award Lectures, Vol 4 Raven Press,

1990

EXPLORATIONS OF THE NICOTINIC

ACE-TYLCHOLINE RECEPTOR A Karlin in

Harvey Lectures: 1989Ð1990, Vol 85,

pages 71Ð107; 1991

THE FUNCTIONAL ARCHITECTURE OF THEACETYLCHOLINE NICOTINIC RECEPTOR EX-PLORED BY AFFINITY LABELLING AND SITE-DIRECTED MUTAGENESIS J P Changeux,

J L Galzi, A Devillers-ThiŽry and D

Ber-trand in Quarterly Reviews of Biophysics,

Vol 25, No 4, pages 395Ð432; November1992

NICOTINIC ACETYLCHOLINE RECEPTOR AT

9 A RESOLUTION N Unwin in Journal of

Molecular Biology, Vol 229, No 4, pages

NEUROTRANSMITTER

CHANGE

IN MEMBRANEPOTENTIAL

c

CELLMEMBRANE

INTRACELLULARSIGNALING MOLECULE

Trang 40

All the shimmering stars that pierce

the night sky shine because of

the same fundamental process:

nuclear fusion When two or more

atom-ic nuclei collide and fuse into one, they

release virtually unimaginable amounts

of energy The fusion of one gram of

hy-drogen, for example, liberates as much

energy as the combustion of 20,000

lit-ers of gasoline In stars such as the

sun, fusion reactions burn brilliantly

for billions of years They are not the

only source of stellar energy, however

In 1971 astronomers recognized a class

of bizarre, x-ray-emitting stars, known

as x-ray binaries, whose intense

emis-sions require an energy source far more

eÛcient than even fusion

Theorists have deduced that these

objects consist of a normal star

orbit-ing a collapsed stellar corpse, usually

a neutron star Neutron stars are so

dense that the entire mass of the star is

squeezed into what is essentially a

sin-gle atomic nucleus 20 kilometers across

The stars in these binaries lie so close

together that gas can ßow from the

nor-mal star to the neutron star That

cap-tured material forms a rapidly swirling

disk whose inner edge, just above the

neutron starÕs surface, races around at

nearly the speed of light Friction

with-in the disk eventually causes the gas to

fall inward, or accrete, onto the tron star In the process, violent colli-sions between particles heat the gas totemperatures of 10 million to 100 mil-lion kelvins Under such incredibly hotconditions, the gas emits torrents of en-ergetic x-rays Pound for pound, accre-tion unleashes 15 to 60 times as muchenergy as does hydrogen fusion

neu-Astronomers now recognize that cretion powers a rich diversity of astro-physical objects These range from in-fant stars to quasars, objects about thesize of the solar system that outshineentire galaxies, most likely as a result ofgas spiraling into a supermassive blackhole X-ray binaries serve as ideal show-cases for learning in detail how the ac-cretion process works They are brightand relatively nearby, residing well with-

ac-in our galaxy

The study of x-ray binaries also vides a glimpse into the life cycle ofsome of the most exotic and dynamicstellar systems in the sky In these stel-lar duos, one or both members spendssome time feeding oÝ its partner Thattransfer of material stunningly altersboth starsÕ development One star maypay for its gluttony by prematurely end-ing its life in a spectacular supernovaexplosion On the other hand, placid,

pro-elderly neutron stars may receive an fusion of rotational energy that causesthem to become a prominent source ofrapidly pulsed radio waves

in-Despite their prominence in the

x-ray sky, x-x-ray binaries escapedthe notice of researchers untilthe dawn of the space age in the 1960s.Celestial x-rays are absorbed high inthe upper atmosphere, precluding theirdetection from the ground The advent

of space technology opened up an tirely new Þeld of investigation by mak-ing it possible to loft telescopes abovethe obscuring layers of the earthÕs atmosphere

en-In 1962 Riccardo Giacconi, now thedirector of the European Southern Ob-servatory, and his associates at Ameri-can Science and Engineering in Cam-bridge, Mass., placed an x-ray detector

on board a rocket and discovered theÞrst known celestial x-ray source, Scor-pius X-1 The name indicates that it isthe brightest x-ray-emitting object inthe constellation Scorpius Scorpius X-1shines about 1,000 times brighter inx-rays than in visible light The identi-

ty of the object emitting this radiationwas a total mystery

In the following years, x-ray

detec-X-ray Binaries

In these systems, ultradense neutron stars feed on their more sedate companions Such stellar cannibalism produces brilliant outpourings

of x-rays and drastically alters the evolution of both stars

by Edward P J van den Heuvel and Jan van Paradijs

EDWARD P J VAN DEN HEUVEL and

JAN VAN PARADIJS have collaborated on

the study of celestial x-ray sources since

the late 1970s Van den Heuvel received

his Ph.D in mathematical and physical

science from the University of Utrecht

in 1968 In 1974 he joined the faculty of

the University of Amsterdam, where he is

now chairman of the astronomy

depart-ment He is also a co-founder and the

di-rector of the Center for High-Energy

As-trophysics, operated jointly by the

Uni-versity of Amsterdam and the UniUni-versity

of Utrecht Van Paradijs earned his Ph.D

in astronomy from the University of

Am-sterdam in 1975 He has been a professor

of astronomy at the university since 1988

X-RAY BINARIES comprise two very diÝerent classes of double-star systems Inboth cases, a neutron star lies at the heart of the x-ray source Most young x-ray bi-

naries, such as Centaurus X-3 (top right), contain a bright blue star having 10 to 40

times the mass of the sun The youthful neutron star emits pulses of x-rays as it

rotates (below, left) Low-mass x-ray binaries usually contain far older, sunlike stars.

In the tiny low-mass system 4U 1820Ð30 (bottom right), both stars must be

com-pact objects, presumably a neutron star and a larger but less massive white dwarf.Erratic bursts of x-rays occur when gas collects on the surface of an old neutron

star and undergoes a thermonuclear detonation (below, right).

X-RAY BURST(LOW-MASS X-RAY BINARY)

X-RAY PULSES(MASSIVE X-RAY BINARY)

TIME (SECONDS)TIME (SECONDS)

RELATIVE X-RAY INTENSITY

Tiêu đề	Reading the Genes of Extinct Species
Tác giả	Svante PŠŠbo
Năm xuất bản	1993

Định dạng
Số trang	93
Dung lượng	6,01 MB