scientific american - 1994 02 - do aerosols slow climatic warming

Arms Reductions COST BILLIONS OF CURRENT DOLLARS NONNUCLEAR FORCES AIR-LAND BATTLE 5 ACTIVE ARMY DIVISIONS 5 RESERVE ARMY DIVISIONS 400 ACTIVE AIRCRAFT 400 RESERVE AIRCRAFT 10 SHIPS AND

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FEBRUARY 1994

$3.95

Digital forgery can create photographic evidence for events that never happened.

Do aerosols slow climatic warming?

Halting the spread of AIDS.

Can particle physics come back?

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February 1994 Volume 270 Number 2

38

48

58

68

The Future of American Defense

Philip Morrison, Kosta Tsipis and Jerome Wiesner

Sulfate Aerosol and Climatic Change

Robert J Charlson and Tom M L Wigley

The Molecular Architects of Body Design

William McGinnis and Michael Kuziora

4

Ermanno F Borra

S CIENCE IN PICTURES When Is Seeing Believing?

William J Mitchell

As the only superpower in a world of brushÞre wars, the U.S needs armed forcesthat can be deployed quickly They must also be reorganized according to mis-sionÑa strategy that proved itself during the Gulf War The trend toward collec-tive security and the absence of a world-class foe mean that the overall size of thearmed forces can be sharply reduced, freeing resources for other public needs

Compounds of sulfur give the earthÕs atmosphere a built-in thermostat They ter sunlight back into space before it can contribute to global warming Unhappily,sulfate aerosol complicates the problem rather than solving it Distributionaround the world is uneven, and aerosol has no eÝect during the night Eliminat-ing sulfur emissions could greatly accelerate the warming by greenhouse gases

scat-They are a family of genes, many of which appear in a broad, diverse array ofspecies that ranges from yeast to human beings Misplaced activity by thesegenes can turn a healthy embryo into a monster That phenomenon and the abili-

ty to transfer genes between species provide researchers with a powerful way ofbringing into sharp focus the process by which genes control development

George Bush and Margaret Thatcher nuzzling in a garden? Marilyn Monroeecstatically taking Abraham LincolnÕs arm? Digital manipulation of photographscan produce seemingly incontrovertible evidence of events that never happened

Great, glass telescope mirrors have enabled astronomers to make breathtakingdiscoveries But such tools have real drawbacks Beyond a certain size, gravitywarps them They are also costly and diÝicult to manufacture An alternative is aliquid lens of mercury or gallium When spun, the metal naturally assumes a para-bolic shape The construction of the vessel and other components is inexpensive

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Letters to the Editors

Raising the Vasa Questions of

power Credit due Fermat.Science and the Citizen

Science and Business

Book Reviews

Eyeing trilobites Nuclearenergy Chemical reactions

Essay :Gerard Piel

Population growth: development,not AIDS, is the answer

The Amateur Scientist

How to build a telescope mirror

by spinning a liquid

T RENDS IN PHYSICS Particle Metaphysics

John Horgan, senior writer

AIDS and the Use of Injected Drugs

Don C Des Jarlais and Samuel R Friedman

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 Canada Post International Publications Mail (Canadian Distribution) Sales Agreement No 242764 Canadian GST No R 127387652 Subscription rates: one year $36 (outside U.S and possessions add $11 per year for postage) Subscription inquiries: U.S and Canada (800 ) 333-1199; other (515) 247-7631 Postmaster : Send address changes to Scientific American, Box 3187, Harlan, Iowa 51537 Reprints available: write Reprint Department, Scientific American, Inc., 415 Madison Avenue, New York, N.Y 10017-1111, or fax : (212) 355-0408.

Hypodermic needles and syringes serve as major vectors for the human deÞciency virus (HIV) among drug users Distribution of clean needles, treatmentand education have been found to curb behavior that spreads the deadly virus.Yet, the authors say, public oÝicials have hesitated to implement such programs

immuno-A typical specimen stood almost 10 feet tall, had a massive beak, sported greatshredding talons, ran like a racehorse and doted on fresh, raw meat About 65million years ago they perched atop the food chain on the emerging continents

of the Atlantic Basin Then mammalian predators dislodged them

Only recently, physicists seemed on the verge of Þnding a uniÞed theory of all ofnatureÕs forces Yet now they have reached a serious impasse Even if the Super-conducting Super Collider were to be built, it could not achieve the energies atwhich uniÞcation is thought to occur There is scant hope that low-energy experi-ments will yield progress The latest theories do not generate testable predictions

Master genes Clear need for busters Fertility: the new ethics

clot-Bye-bye, greenhouse eÝect? Morequantum puzzlement Time ma-chines? Cash in your ticket PRO-FILE: Bruce M Alberts, laid-back leader

of the National Academy of Sciences

Electrons terrorize newsroom!

Ecocars Is health reform an agent

of Big Brother? Here come theknowbots Tragedy of the lawns

THE ANALYTICAL ECONOMIST: Doesthe market always make the bestchoice? A view from the Chunnel

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50Ð51 JeÝrey T Kiehl and Bruce

P Briegleb, National Center

for Atmospheric Research;

color manipulations by

Jason KŸÝer

52 Runk/Schoenberger, Grant

Heilman Photography, Inc

53 Tad Anderson, University

of Washington

60 William McGinnis (top ),

Tomo Narashima (bottom)

64 William McGinnis (bottom)

65 Jared Schneidman/JSD

68Ð69 Original photograph by AP/

World Wide Photos (left ),

image from Paul Higdon/

New York Times (center ),

image from Angela Perkins

(right ), color manipulations

by Jack Harris/Visual Logic

(top center, top right

NASA; digitally manipulated

version courtesy of Time,

Inc., Picture Collection

72 Original photograph of

Abraham Lincoln by

Alex-ander Gardner, Bettmann

Archive; original

photo-graph of Marilyn Monroe

courtesy of Personality

Photos, Inc.; digital images

by Jack Harris/Visual Logic

73 Image by Wade Hokoda

77 Robert J Sica, University

of Western Ontario

78 Boris Starosta

79 Guy Plante, Laval University

80 Boris Starosta (top ), Terry

Byers, Lockheed

Corpora-tion (left ), Guy Plante (right )

81 Robert J Sica

82 Andrew Lichtenstein/

Impact Visuals

83 Peter Haley/Morning News

Tribune, Tacoma, Wash.

84Ð86 Guilbert Gates/JSD

87 Andrew Lichtenstein/

Impact Visuals

88 Guilbert Gates/JSD (left ),

courtesy of Directie tariaat GG&GD, Amsterdam

Super Collider Laboratory

102 David Sams/Texas Inprint

(top ), Fermilab Visual Media Services (bottom )

103 CERN Media Services

(top and bottom )

Digital image by Jack Harris/Visual Logic; original photograph of Abraham Lincoln

by Alexander Gardner, Bettmann Archive; original photograph of Marilyn Monroe

courtesy of Personality Photos, Inc

6 SCIENTIFIC AMERICAN February 1994

THE COVER image was created in a

comput-er by blending an 1863 photograph of ham Lincoln with a publicity shot of MarilynMonroe made in 1955 Both images werescanned and then digitally manipulated; adescription of the process appears on page

Abra-72 of the article ỊWhen Is Seeing Believing?Ĩ

by William J Mitchell The ability to form photographs in this way has brought

trans-to an end the 150-year period during whichphotography seemed unassailable And ithas left us with the task of learning to viewphotographs with a new wariness

¨

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LETTERS TO THE EDITORS

A Sunken Treasure

In ỊRaising the VasaĨ [SCIENTIFIC

AMERICAN, October 1993], Lars-Ake

Kvarning makes the point that many of

the items on board the Vasa were still

intact when the shipÕs hull was

re-vealed It is interesting that the sails,

though water damaged, had not

entire-ly decomposed What materials were

used to make them? Were they

protect-ed by the sail locker?

JEFFREY ENDY

Dauphin, Pa

Kvarning says the helmsman steered

the Vasa by tilting the whip staÝ and

moving it up and down He rightly

de-scribes this practice as strangely

awk-ward According to the references I

have seen, during the 17th century the

whip staÝ was used this way to steer

ships in Þne weather, but the tiller was

also controlled by tackles attached to

the sides of the ship Is there any

evi-dence that on the Vasa the whip staÝ

was not used primarily as a telltale for

indicating the position of the tiller?

R B ELLIOTT

Dublin, Ireland

Kvarning replies:

The sail locker on board the Vasa did

little to protect the sails during their

centuries under water, but the

condi-tion of the cloth improved the deeper

we went into the folded layers The

sail-cloth was of two types The one used

in the smaller sails was close-textured

The other was coarser The condition

of the Þbers was so poor that it was

not possible to determine their

materi-al, but the coarser cloth was probably

hemp and the Þner one linen

There are no signs that below the

helmsmanÕs deck the tiller had been

at-tached to the shipÕs sides by tackles

On the other hand, this was the VasaÕs

maiden voyage, and supporting tackles

could easily have been attached laterĐ

had there been an opportunity

AIDS and Heterosexuals

Warner C Greene, author of ỊAIDS

and the Immune SystemĨ [SCIENTIFIC

AMERICAN, September 1993], should be

commended for his remarkably clear,

concise description of viral mechanics

But his reference to Ịnew infectionsĐthe majority now from heterosexualcontactĨ is misleading The majority ofnew infections have always been fromheterosexual contact, as far back as theAIDS epidemic can be traced Althoughhomosexuals, hemophiliacs and peoplewho inject drugs have borne the brunt

of the epidemic in industrial countries,they have always constituted a minori-

ty of the worldÕs HIV infections Thus,AIDS was, is and will continue to beprimarily a heterosexual disease

RUSSELL MILLSSan Francisco, Calif

Overdue CreditỊSentries and Saboteurs,Ĩ by W WaytGibbs [ỊScience and the Citizen,Ĩ SCIEN-TIFIC AMERICAN, October 1993], is anexcellent review of new tumor thera-pies I would like to point out, however,that the idea of inserting a herpesvirusgene into tumor cells and killing themwith ganciclovir, which was attributed

to Kenneth W Culver, was generatedseveral years earlier by our group Al-though Culver may have had the ideaindependently, at least one of his col-laborators attended a meeting whereour work was presented in 1990, atleast a year before Culver claims tohave had the idea

XANDRA O BREAKEFIELDDepartment of NeurologyMassachusetts General HospitalBoston, Mass

Energetic ThinkerLet me add a historical note to theinteresting and informative article byNarain G Hingorani and Karl E Stahl-kopf [ỊHigh-Power Electronics,Ĩ SCIEN-TIFIC AMERICAN, November 1993] In

1967, very early in the history of tors, Richard Cassel (now at the Stan-ford Linear Accelerator Center ) pro-posed the thyristor-based magnet pow-er-supply system used by the FermilabMain Ring

thyris-At its peak capacity of 400 tron volts, that system can store morethan 100 megajoules of energy and has

gigaelec-a power dissipgigaelec-ation of more thgigaelec-an 20

megawattsĐa giant step beyond tional synchrotron power supplies Byusing the utility grid for energy stor-age, CasselÕs system avoided all themaintenance and safety problems oftraditional systems It also had greateroperational ßexibility (which made itpossible to tune the particle oscilla-tions over a wide range) and a learningcapability (so the power regulation im-proved from pulse to pulse)

tradi-CasselÕs magniÞcent power supplywas a great help in the initial operation

of an accelerator more than 10 timeslarger than any of its predecessors Ithas been copied for almost every syn-chrotron built since then, so it must bedoing something right

FRANCIS T COLENaperville, Ill

Here We Go Again

I now see that Fermat has played thegreatest practical joke of all time on usfor 350 years! But even with his hastyretreat at the end of ỊFermatÕs LastTime-Trip,Ĩ by Ian Stewart [ỊMathemat-ical Recreations,Ĩ SCIENTIFIC AMERICAN,November 1993], he could not get back

to the 17th century fast enough towrite the proof in the book margins!P.S I have found a truly remarkablemethod for time travel, but this post-card is too small for its description

VIKTORS BERSTISAustin, Tex

Because of the volume of mail, letters

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

˚

ERRATAThe credits for the September 1993 is-sue neglected to mention that the illus-tration on page 69 was based in part onwork by Karen Jacobsen and Dennis G.Osmond of McGill University

ỊNever Give a Sucker an Even BreakĨ[ỊScience and the Citizen,Ĩ October1993] should have attributed the gamestrategy ỊPavlovĨ to David Kraines ofDuke University and Vivian Kraines ofMeredith College, who coined that name

to refer to a class of learning rules

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50 AND 100 YEARS AGO

FEBRUARY 1944

ỊIf your tire treads are wearing thin

and you think something should be

done about it, you are dead right And

something is being done Synthetic tires

are good now, but will be excellent

Af-ter performing the astounding miracle

of creating in little more than two years

a totally new complex industry able to

produce synthetic rubber at a rate

fast-er than Amfast-ericans have evfast-er used the

product of rubber trees, American

en-terprise and ingenuity are now busy

with the next task : That of making

syn-thetics so good and so cheap that we

shall never wish to return to NatureÕs

rubber again.Ĩ

ỊThe automatic pilot has deservedly

earned a great reputation for itself But

there has always been the feeling that

it would not quite do the job in very

rough weather Now Wright Field has

permitted the announcement to be

made of a new electronically controlled

automatic pilot developed by the

Min-neapolis-Honeywell Company The

sen-sitivity of the electronic mechanism is

such that it returns the plane almost

immediately to its course despite cross

currents, wind variations, and air blasts

from exploding anti-aircraft shells.Ĩ

ỊThe recent decline in the rate of

dis-covery of new petroleum Þelds in this

country has given rise to the question

of what we can do to meet the demands

of an air-minded and automotive

post-war age Great Britain, Germany, and

Ja-pan are making synthetic oil and

gaso-line Now is the time to conduct a

rigor-ous research program so that methods

will be available to supply necessary

liquid fuels from American coals when

the petroleum supply begins to fail.Ĩ

FEBRUARY 1894

ỊOn the 30th day of January, 1894,

the Bell telephone patent expired and

the invention became the property of

the public; so that whoever desires to

do so can make, buy or sell telephones

without fear of infringing on the rights

of any one This applies only to the

hand instrument now used as a

receiv-er Patents for other telephone tus still remain in force; but enough isavailable for actual service With twohand instruments and a suitable call,telephone communication may be main-tained, under favorable conditions, over

appara-a line eight or ten miles long, no bappara-at-tery being required.Ĩ

bat-ỊA solution to the problem of necting the European continent withEngland by railway seems to be meet-ing with favor in England It consists inthe establishment, under water, of one

con-or mcon-ore metallic tubes capable of ing passage to a railway According tocalculations, the total cost of the tu-bular railway ought not to exceed 375millions at a maximum, and the con-struction of it might be eÝected in Þveyears.Ĩ

giv-ỊWe now know that the cholera germ

is found in the human body only in theintestines; that it is not communicateddirectly from person to person, but thealvine evacuations of the victims Þndtheir way, generally through water, intothe bowels of susceptible persons, whothen become additional victims; thatthis germ Þnds a breeding place indamp soil and in stagnant pools and

in running streams containing organicmatter; that it is quickly destroyed bythe oÛcial germicides, by drying, byacids, and by temperature below 56 de-grees or above 126 degrees F It is theapplication of exact knowledge that hasconÞned the cholera to the quarantinedominions at New York, thus prevent-ing its diÝusion in the United States.ĨỊThe need of the day is rapid transit

The illustration (below ) shows one of

the last developments in true rapidtransitĐthe Boynton Electric BicycleRailroadĐof which a line is now in pro-cess of erection across Long Island,from Bellport to the Sound The idea ofthe bicycle railroad is to provide a sys-tem of transit whose speed may befrom seventy-Þve to one hundred ormore miles an hour In the railroad inquestion, a narrow car with sharpenedends is employed, and is mountedupon two wheels, one at each end, andtravels upon a single rail It has theequilibrium of a bicycle, and like thelatter disposes at once of the violenttransverse wrenching strains which af-fect four-wheeled vehicles of everydaytype It is peculiarly well adapted forelectric propulsion, the overhead railgiving a place for the current main.Ĩ

The Boynton elevated bicycle railroad

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SCIENCE AND THE CITIZEN

Nobel Notes

Our man in Stockholm

reports on the ceremonies

In early December the city of

Stock-holm enjoys only about six hours

of daylight But the concentration

of scientiÞc, economic and literary

lu-minaries that descends on its charming

19th-century precincts to celebrate the

awarding of the Nobel Prizes renders

solar radiation superßuous

A prize as famous as the Nobel

car-ries with it the power of celebrity,

whether the winners like it or not Each

laureate must adapt to the signiÞcance

and implications of that power

Rich-ard J Roberts of New England Biolabs,

who shared a Nobel with Phillip A

Sharp of the Massachusetts Institute

of Technology for discovering that the

genes of higher animals are split into

active and inactive parts, referred to

himself as a Òprize virginÓ and

ex-pressed a quiet joy at being selected as

a Nobel winner But when asked if the

award gave new impetus to his work,

he was quite emphatic: ÒOh, no, no

The research is its own reward.Ó

Douglass C North of Washington

University took the Nobel as a

particu-larly personal triumph He and his

co-winner, Robert W Fogel of the

Univer-sity of Chicago, have followed an

un-traditional methodology of applying

quantitative methods to economic

his-tory ÒAt the press conference after the

Nobels were announced, people asked

me, ÔDoes this prize validate your

ap-proach?Õ and I told them, ÔYou bet it

does!Õ Ó he exclaimed, his eyes glowing

and Þst clenched

Joseph H Taylor of Princeton

Univer-sity, who co-discovered an unusual

bi-nary pulsar that has proved to be a

val-uable laboratory for studying EinsteinÕs

theory of relativity, has been quick to

share credit with his many

collabora-tors He also made a point of inviting

Jocelyn Bell Burnett of BritainÕs Open

University to attend the Nobel

festivi-ties In 1967, as Jocelyn Bell, she

de-tected the Þrst pulsars in collaboration

with her thesis adviser at the

Universi-ty of Cambridge, Antony Hewish She

did not share in the subsequent Nobel

Prize, howeverÑa sharp reminder that

the Nobel FoundationÕs power to

ele-vate also confers the power to exclude

The personalities of the laureatesshowed up strongly in their Nobel lec-tures as well Michael Smith of the Uni-versity of British Columbia began hischemistry prize lecture with a method-ical, technically phrased survey of thehistory of genetics He gradually fo-cused on his own work in site-directedmutagenesis, a process that allows thestudy and manipulation of proteins

by speciÞc alteration of the DNA thatcodes their structure

The preceding lecture, by Kary B lis, a biotechnology consultant, could

Mul-hardly have struck a more diÝerenttone He presented a resoundingly per-sonal story of his discovery of the poly-merase chain reaction (invariably short-ened to PCR ) The process provides afast and easy way for biologists to makebillions of copies of a single strand ofDNA PCR has tremendously facilitatedwork in virtually all aspects of molecu-lar biology, from DNA Þngerprinting tothe diagnosis of genetic disease.Mullis described the research that led

to PCR as just one component of hislife He recounted that after graduate

JOSEPH TAYLOR receives a Nobel Prize in Physics from King Carl XVI Gustaf, an

hon-or he shared with Russell Hulse of Princeton University, his fhon-ormer graduate student

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school he had hoped to become a

writ-er, Ịbut my characters were ßat, so I had

to get a job as a scientist.Ĩ Above all,

Mullis ran against the grain by relating

that, in the end, the thrill of the

discov-ery of PCR could not compensate for

the emotional devastation produced by

the disintegration of his relationship

with his girlfriend

MullisÕs lecture aroused strong

re-action from the audience, especially

among the group of young studentsĐ

mostly femaleĐwho mobbed him

af-terward Is this kind of adulation more

satisfying than winning the Nobel

Prize? ỊThe two go hand in hand,Ĩ he

said, grinning, Ịbut I had groupies even

before the Nobel Prize.Ĩ

The formal awarding of the Nobels

took place on December 10, the

an-niversary of Alfred NobelÕs death, in

the Stockholm Concert Hall There the

laureates joked nervously with one

an-other as they awaited their turn to

re-ceive their diploma and medal from

King Carl XVI Gustaf of Sweden

A feast in the Stockholm City Hall

sealed the celebration Torches

illumi-nating the path to the entryway

reßect-ed ecstatically oÝ the surface of Lake

MŠlaren Inside, 1,300 guests sat at 63

tables distributed through the vast Blue

Hall At one point, the stewards

pour-ing the wine abruptly drew back and

began to sing; they turned out to be

Orphei DrŠngar, the renowned menÕs

choir from Uppsala Just before

des-sert, soprano Barbara Hendricks

per-formed amid an artiÞcial snowfall,

be-neath a convincing canopy of stars

After dinner, Þve of the laureates

gave the traditional speech of thanks,

among them writer Toni Morrison, who

poetically conjured up the spirits of

lit-erature winners yet to come When the

banquet dispersed at midnight, dents and some of the Nobelists foundtheir way to the Medical StudentsÕ recep-tionĐa traditional but unoÛcial event

stu-at the Karolinska Institute In a

crowd-ed room vaguely resembling a mcrowd-edie-val beer hall, students entertained thelaureates with, among other things, Þre

medie-juggling, a beer-bottle orchestra and askit explaining the possible signiÞcance

of split genes

Two of the laureates returned the vor Taylor donned a funny nose, glass-

fa-es and a guitar; his wife joined him for

a spirited if slightly wobbly rendition

of ỊThis Land Is Your Land.Ĩ Mullis

lat-er contributed some hoarse singing ofhis own, along with a bit of free-formstand-up comedy that included a briefparody of the King of Sweden

A light snow was falling as the Nobellaureates and their families gathered inthe lobby of the Grand Hotel to departfrom Stockholm The quietly familiarconversation and warm smiles attested

to the shared intensity of the pastweekÕs events But representatives fromthe South African government and theAfrican National Congress had begun

to Þll the Grand Hotel, and the mood

of the lobby had started to change Thetime had come for the Nobel cycle tobegin anew ĐCorey S Powell

LATE-NIGHT FESTIVITIES following the Nobel banquet brought out the laureatesÕ less serious side Here Taylor treats the medical students to some fancy pickinÕ.

Like matchmaking relatives, physicists have for many years been trying to marry superconductors with semiconductors, in the hope of having resistanceless elec-tronic circuits as offspring Although they will not be sending out birth announce-ments soon, the mating attempts themselves are proving to be a fascinating study.Recent results by Herbert Kroemer, Chanh Nguyen and Evelyn L Hu of the University

of California at Santa Barbara have demonstrated that an unexpected mechanism diates superconductivity across a thin piece of semiconductor The mechanism, calledmultiple Andreev reflections, also offers researchers a bonus mystery: the reflectionsbehave inexplicably when exposed to a magnetic field

me-Superconductors carry electricity without resistance because the electrons in themcombine in twos to form so-called Cooper pairs By dancing in step, the members of apair manage to avoid bumping into each other and thus to move without resistance.The Cooper pairs can also “leak” through the superconductor, penetrating an ordinaryconductor to some extent This leakage, referred to as the proximity effect, enablestwo superconductors to transmit the resistanceless flow of current across an inter-vening substance

Kroemer and his colleagues decided to see what would happen if they stretched thedistance between superconducting contacts beyond that at which the proximity ef-fect can happen To do so, they created a “super-semi-super double heterostructure.”That is, they sandwiched an indium arsenide semiconductor between two supercon-ducting niobium contacts spaced a few tenths of a micron apart The indium arsenidewas structured as a quantum well—essentially a thin channel that confines electrons

to two dimensions of movement The quantum well permitted high concentrations ofmobile electrons (in effect, creating a “sea” of negative charge)

The workers expected to see a certain level of resistance Instead they found an usual conductance peak that could not have been caused by Cooper pairs entering thequantum well “Our contact resistance data are incompatible with the proximity effect

un-as currently understood,” Kroemer says “The idea that the Cooper pairs penetrateinto the semiconductor itself is suddenly in question and needs to be reexamined.”Rather what may mediate the superconductivity are multiple Andreev reflections, a

Reflections in a Quantum Well

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Too Little, Too Late?

A treatment for heart attack

may be dangerously underused

Athrombolytic agent can save your

life if you suÝer a heart attack

But in the U.S., if you are old or

slow in getting to the hospital, your

chances of getting one may be

dis-turbingly worse than youÕd like

Sur-veys show that only about a third of all

heart attack patients receive a

throm-bolyticÑroughly half of those who may

be eligible and far below the 85 percent

mark attained in parts of the U.K

Moreover, even patients who do get a

thrombolytic must often wait almost

an hour and a half for it, a delay that

signiÞcantly reduces the drugÕs

eÝec-tiveness By one estimate, 14,000 more

lives might be saved annually if

physi-cians used thrombolytics sooner and

more liberally ÒI think the situation

is improving, but itÕs woefully

inade-quate,Ó remarks Andrew J Doorey of

the Medical Center of Delaware

Streptokinase, tissue plasminogen

activator ( TPA ) and other

thrombolyt-ics work by dissolving the blood clots

that block coronary arteries and causeheart attacks At least one study foundthat administering these agents within

an hour of the onset of chest pain cutmortality by 90 percent, although mostestimates put the beneÞt at a moremodest 50 percent Unfortunately, thatgain decreases when treatment is post-poned, and most patients do not reach

an emergency room until at least fourhours after their heart attack begins

Still, thrombolytics reduce mortality by

30 percent when given within the Þrstsix hours and by about 15 percent be-tween the sixth and 12th hours

The drawback of the drugs is thatthey promote bleeding and raise theodds of a potentially fatal stroke from

an intracranial hemorrhage Physicianshave therefore tended to prescribe clot-busters only for the minority of pa-tients who oÝered the best ratio ofbeneÞts to risks ÒInterfering with thebodyÕs blood-clotting mechanism is aserious business,Ó cautions H VernonAnderson of the University of TexasHealth Science Center ÒYou want to bevery, very careful.Ó

Last fall in the New England Journal

of Medicine, Anderson and James T.

Willerson of the Texas Heart Institute

SCIENTIFIC AMERICAN February 1994 21

phenomenon the existence of which Aleksander F Andreev of the Institute for Physical

Problems in Moscow proposed in 1964 At the super-semi interface, an electron from

the well enters a superconductor to form a Cooper pair As it does so, it leaves behind

a positively charged “hole” in the sea of electrons in the well The hole is a kind of

mir-ror image of the electron According to theory, the hole moves along a time-reversed

path of the original electron—that is, the hole travels to the other side of the well

Once the hole reaches the other interface, it breaks up a Cooper pair in the other

superconducting contact One of the Cooper electrons destroys the hole; the other

takes up this annihilation energy and shoots across the well back to the other side

The process can repeat once this electron moves across the interface and forms a

Cooper pair In theory, the cycle can go on forever

More startling was the effect’s dependence on an external magnetic field Kroemer

found that a rising magnetic field caused resistance to increase episodically instead of

smoothly The jerkiness or bumpiness of the increasing resistance should involve a

fundamental parameter—the flux quantum The flux quantum dictates that bundles

of magnetic-field lines penetrating a sample must take on a particular, discrete value

Instead, Kroemer reports, the measured value is smaller than the predicted one by a

factor of four to five

So far no good explanation exists for the oscillations One speculation is that the

magnetic-flux lines assume the form of a lattice as they penetrate the semiconductor

When the magnetic field is increased, the entire lattice shifts suddenly to

accommo-date the new flux bundles Kroemer plans to look for the effect in new samples before

submitting his results for publication

Multiple Andreev reflections may be more common than previously observed For

instance, Alan W Kleinsasser of the IBM Thomas J Watson Research Center and his

colleagues will report their observations of the reflections in a quantum structure

known as a tunnel junction So whereas the birth of superconducting computers

re-mains distant, investigators are finding plenty of excitement during the courtship

pe-riod Kroemer explains: “The physics for now takes precedence over the hypothetical

Trang 10

in Houston pointed out just how

care-ful physicians have been Thirty

per-cent of all patients with heart attacks

do not get thrombolytic therapy,

be-cause they arrive at the hospital more

than six hours after pain beginsÑtoo

late, in the physicianÕs opinion Because

the elderly are at higher risk for stroke,

15 percent are considered too old

An-other 25 percent are disqualiÞed

be-cause their electrocardiograms do not

suggest that thrombolytic therapy

would be helpful or because they seem

prone to bleeding

Are those criteria too conservative?

The mortality for patients in clinical

trials of thrombolytic therapy is

typical-ly 2 to 10 percent; for those excluded

from therapy, it is 15 to 30 percent

These alarming numbers suggest that

unless the risks of stroke and bleeding

would be far higher in the excluded

groupsÑan assumption that is

espe-cially questionable for people who have

just arrived too lateÑthose patients,

too, would beneÞt from thrombolytic

therapy Indeed, Anderson and

Willer-son note that patients older than 75

years were among the groups who

most beneÞted in clinical trials because

they suÝer the most heart attacks

Doorey believes perhaps as many as

60 percent of all heart attack victims

might qualify for thrombolytic therapy

In the December 1992 issue of the

Journal of the American Medical ation, he, Eric L Michelson of Hahne-

Associ-mann University and Eric J Topol of theCleveland Clinic Foundation tried to es-timate the potential impact of throm-bolytics They concluded that expand-

ed use of thrombolytics could triplethe number of lives saved, from 7,200

to 21,950 annually

Some advocates insist that pelling evidence for a broader use ofthrombolytics has existed since at least

com-1988, when the Second InternationalStudy of Infarct Survival ( ISIS-2) was re-leased And many physicians in Europeseem to have concluded that aggressiveuse of thrombolytics is warranted A

report in the Lancet last October claims

that 85 percent of the heart attack tients in some English hospitals re-ceived thrombolytics It also points out,however, that regional hospitals variedgreatly in their practices: some hospi-tals used them only half that often

pa-ÒItÕs hard to have a handle on howmuch underutilization there is rightnow,Ó Topol argues ÒIt appears to bemuch less than it was even a couple ofyears ago.Ó For patients older than 75years, he says, the rate of treatment hasjumped from 2 to 15 percent Clinicalrecords from the Global Utilization ofStreptokinase and TPA for Occluded

Coronary Arteries ( GUSTO ) trial, which

he supervised, suggested that ÒweÕretreating well over 80 percent of the ap-propriate patients.Ó

But Rory Collins of RadcliÝe ary at the Clinical Trial Service Unit ofthe University of Oxford dissents fromthat view A leader of the ISIS-4 trial re-leased last November, Collins states thatÒthe U.S was down in the lower endand the U.K was up in the top endÓ infrequency of thrombolytic use ÒI think

InÞrm-a lot of people InÞrm-are still uncertInÞrm-ain InÞrm-aboutwhether they should be treating be-yond six hours,Ó he ventures ÒThat ischanging, but it may be changing atdiÝerent rates in diÝerent places.ÓResistance to a therapy that may rou-tinely kill one or two out of every 1,000patients is understandable in a profes-

sion trained to obey the motto primum non nocere, ÒÞrst do no harm.Ó Emer-

gency room internists must make rapiddecisions, on the basis of incompleteinformation, about the care of patientsthey have usually never seen before.They often weight their own experienceand that of their colleagues more heav-ily than clinical reportsÑwhich may ex-plain why the use of thrombolyticstends to be higher in hospitals thathave participated in clinical trials Fear

of liability also haunts some U.S tors, Doorey observes

doc-Better prescriptive guidelines maysoon appear in an upcoming paper in

the Lancet, in which Collins and his

col-leagues make new recommendationsfor giving thrombolytic therapy to theelderly, people with histories of strokesand other categories of patients ÒItputs together all the data on the sub-groups we have from the large-scaletrials, and it helps to guide treatmentfor individuals,Ó he says

Quite aside from the issue of

wheth-er more categories of patients shouldreceive thrombolytics, most experts be-lieve the therapy should be adminis-tered much more promptly Studiesshow that from the time eligible pa-tients in the U.S reach an emergencyroom, they must wait an average ofabout 85 minutes before their throm-bolytic therapy begins That delay notonly lowers the beneÞt of the thrombo-lytics, at some hospitals it pushes pa-tients outside the accepted interval fortreatment

Doorey and others are convinced thisÒdoor-to-needle timeÓ can and should

be cut to 20 minutes or less To tate the treatment, Òmost good hospi-tals are setting up multidisciplinary, in-terdepartmental teams,Ó Doorey ex-plains ÒTheyÕre like the code-blue teamsthat treat trauma.Ó Some proponentshave suggested that thrombolytic ther-

facili-22 SCIENTIFIC AMERICAN February 1994

HEART ATTACK PATIENTS can often beneÞt from getting clot-busting drugs, but

many who should be eligible may still not be receiving them

Trang 11

No Global Warming?

CO2readings on Mauna Loa

show declining emissions

Since 1958, when researchers Þrst

began to measure the rate at

which carbon dioxide

accumu-lates in the atmosphere, they have seen

a consistent increase, perturbed only

by minor seasonal ßuctuations Then,

about four years ago, the trend began

to waver First a decline set in, followed

by a plateau After that, the decline

re-sumedÑsharply The event has left

sci-entists, including those at the

observa-tory on Mauna Loa in Hawaii,

estab-lished by the late Harry Wexler to make

the measurements, wondering what

has happened

Adding to the confusion, says Charles

D Keeling of the University of

Califor-nia at San Diego, who has operated a

gas analyzer at the observatory since

its founding, is the fact that

accumula-tion started to slump while the

atmo-sphere was in the throes of an El Ni–o,

a periodic shift in the circulation of

trade winds over the PaciÞc that aÝectsglobal weather and ocean currents Dur-ing an El Ni–o, such as those of 1982Ð

83 and 1986Ð87, atmospheric carbondioxide levels tend to rise faster thanthey do at other times Keeling suspectsthat plants and soils release more car-bon dioxide during an El Ni–o becausewhen an Asian monsoon collapses, itcauses drought conditions Whateverhas been reducing contributions of car-bon dioxide to the atmosphere hadsuch an impact that it entirely overrodethe eÝects of an El Ni–o

Any number of events might havehad such climatic clout Scientists caneliminate only one explanation imme-diately: the amount of carbon dioxidereleased from burning fossil fuels hasnot declined The next most obviouscandidate is the June 1991 eruption ofMount Pinatubo in the Philippines ÒThelink to the eruption is pretty specula-tive, but itÕs an attractive thing to thinkabout because of the coincidence intime,Ó says Ralph F Keeling, CharlesKeelingÕs son and colleague at U.C.S.D

Of course, discovering whether the tery source existed at land or at seawould narrow the search further Un-fortunately, diÝerent tests have yieldedconßicting clues

mys-The ratio of carbon 13 to carbon 12

in the atmosphere is one such sure Photosynthesis on land prefersthe lighter isotope, whereas gas ex-change at sea discriminates only slight-

mea-ly between the two ÒWe saw the ratio

go up, which would imply an increasedcarbon dioxide uptake by the terrestri-

al biosphere,Ó says Pieter P Tans of theNational Oceanic and Atmospheric Ad-ministration ÒBut there could be con-

siderable error in that It is very dent on how good our calibration is.ÓIndeed, researchers measuring the car-bon isotope ratio have reported diÝer-ent results at various meetings over thepast year Charles KeelingÕs data initial-

depen-ly indicated a large sink at sea Aftercorrections were made to his calibra-tion, the results instead pointed to asink predominantly on land

Oxygen emissions, on the other hand,support yet another idea ÒItÕs fairlyclear that the land did not behave in atypical way for an El Ni–o, but the oxy-gen data suggest that maybe the oceansalso behaved strangely,Ó Ralph Keelingsays Just as diÝerent ßavors of carbonisotopes are preferred by surf-and-turfreactions, so, too, varying proportions

of oxygen and carbon are engagedthrough the formation and consump-tion of organic matter In addition, car-bon is quite reactive at sea, whereasoxygen is chemically neutral

After considerable number ing, these facts taken together implythat if the sink were primarily on land,

crunch-as the carbon isotope readings suggest,the change in the growth rate of atmo-spheric oxygen should be nearly equiv-alent to the recent change for carbondioxide In fact, Ralph Keeling has ob-served oxygen emissions that roseabout twice as sharply as the rate bywhich carbon dioxide emissions fell af-ter the Pinatubo event This Þnding in-dicates that signiÞcant changes tookplace in the oceans

No matter where this carbon sink existed, scientists face the additionalchallenge of Þguring out how it hap-pened There are several models based

on the fallout from Pinatubo that couldconceivably illustrate why carbon diox-ide emissions plummeted Global cool-ing, measured in the low tropospherevia satellite, provides one compellingpathway Such cooling could aÝect thebalance between photosynthesis andrespiration on land and could lead to

an increased net uptake of carbon oxide in the oceans ÒIt could cause

di-a big, short-term jolt to the cdi-arbon balance In 1994, if the temperaturecomes back to normal, we should getnormal carbon dioxide growth again,ÓTans notes

So, is global warming on the way out?Tans does not think so The decline inatmospheric carbon dioxide accumula-tion, he believes, is temporary RalphKeeling agrees ÒThat the carbon diox-ide growth will stay low is doubtful,Ó

he says ÒBut this is relevant at least inthe sense that it shows we donÕt reallyknow whatÕs happening with respect tothe most important man-made green-house gas.Ó ÑKristin Leutwyler

apy could be started in ambulances en

route to the hospital, but the evidence

for the beneÞt of this controversial

practice is uncertain

ÒWeÕre talking about up to a 90

per-cent reduction in mortality from the

biggest killer in the Western world,Ó

Doorey insists ÒThat, I think, is the

biggest medical advance in this century

outside of antibiotics.Ó But it cannot

live up to that potential unless

physi-cians use it more often ÑJohn Rennie

ERUPTION of Mount Pinatubo in June 1991 may be responsible for lower carbon

dioxide emissions measured in the atmosphere since then.

Trang 12

Fertile Ground

IVF researchers pioneer

the bioethical frontier

When researchers at George

Washington University cloned

17 dysfunctional human

em-bryos last summer, they were testing a

possible new tool for in vitro

fertiliza-tion ( IVF ) Their experiment opened a

PandoraÕs box of hypothetical moral

concernsĐan increasingly familiar

ex-perience in IVF researchĐamong them

the prospect that many identical copies

of an individual might someday be

cre-ated But the public uproar that

fol-lowed has obscured a much more

im-mediate ethical issue: how and when to

test embryos for genetic disorders

ỊWe have developed tests for cystic

Þbrosis, DuchenneÕs muscular

dystro-phy, myotonic dystrodystro-phy, Lesch-Nyhan

syndrome, which is a vicious

neurolog-ical disorder, Tay-Sachs disease, and

he-mophilia A, which is a clotting

deÞcien-cy And we are working on fragile X,

an inherited mental retardation

syn-drome,Ĩ reports Mark R Hughes,

direc-tor of the Baylor College of MedicineÕs

prenatal genetics center

From a technological perspective, this

is a remarkable feat The technique

in-volves retrieving eggs from a womanÕs

ovary, fertilizing them in vitro and

let-ting them grow to the eight-cell stage

One or two of the cells are then

re-moved from the embryo and analyzed

by making millions of copies of one bit

of the gene of interest or by injectingßuorescent DNA probes that can bemade to home in on certain mutations

If the embryo is judged acceptable, it istransferred (often with several others)back into the woman The analysis istypically performed in a single day tomaximize the odds that at least oneembryo will attach itself to the uterinewall and launch a pregnancy

As of December, researchers couldboast of at least 18 such pregnancies

Despite worries about accuracyĐthetests have reportedly failed to diagnoseaÜicted embryos in three casesĐthescreening techniques are moving rapid-

ly toward clinical use in IVF centers

There are more than 300 such centers

in the U.S., most of them private andlargely unregulated Carlene W Elsner,

a clinician at Reproductive Biology sociates in Atlanta, plans to oÝer genet-

As-ic embryo testing to patients later thisyear ỊWe could do it next treatmentcycle if we wanted to,Ĩ she says

But some clinical researchers thinkthe tests are not yet ready for commer-cial use ỊThe way they are done in theacademic setting wouldnÕt work in theclinic,Ĩ says Donald S Wood, vice pres-ident of science and technology for IVFAmerica, which operates six fertilityclinics Having to produce conclusiveresults in a single day places a lot ofpressure on doctorsĐỊThis is not some-thing you want to rush,Ĩ he argues

Wood says IVF America has workedout a way to freeze embryos after a cellhas been removed so that researcherscan do their analysis at a more leisure-

ly pace Acceptable embryos can then

be thawed and returned to their

moth-er during a latmoth-er menstrual cycle Thecompany is planning three clinical tri-als to test the idea

Meanwhile Hughes is collaboratingwith Alan H Handyside of Hammer-smith Hospital in London to increasethe number of disorders for which asingle embryonic cell can be screenedsimultaneously ỊWe can currently ex-amine 10 diÝerent genetic locationsfrom one cell,Ĩ Hughes says ỊIt looks

as though you may be able to do asmany as 28Ĩ using DNA ampliÞcation

In the private sector, research is ceeding along slightly diÝerent lines to-ward a similar goal Wood thinks thepolymerase chain reaction currentlyused to search for mutations is tooslow and destructive ỊIt would be farbetter to be able to drop the sampledcell in a cocktail of probes and have theresults in 30 minutes,Ĩ he says, addingthat IVF America is developing probesfor chromosomal defects that could

pro-do just that Although they could notidentify mutations in individual genes,Wood claims that the probes could beremoved without damaging the cell, sothat another battery of diÝerent testscould be run ỊWeÕre still three to Þveyears away from clinical use,Ĩ he says,Ịbut weÕre far enough along that weknow itÕs going to happen.Ĩ

The emerging capability to test formany diÝerent genetic and chromoso-mal disorders has some ethicists wor-ried that the technology might be usedfor screening embryos regardless of

any known risk of inheriteddisease This is particularlydisturbing in the absence of aconsensus about what is and

is not a disorder A 1990 vey conducted by Dorothy C.Wertz, a senior scientist withthe Shriver Center for MentalRetardation, found that 12percent of those polled wouldterminate a pregnancy if theydiscovered that the fetus pos-sessed a gene for untreat-able obesity ( No such gene

sur-is known.) Most physicianswould consider that unethi-cal Yet, Wertz reports, in a

1985 poll the Ịvast majorityĨ

of practitioners said theywould perform amniocentesisand chromosome analysis of

a fetus at a patientÕs requestwithout any medical reason

A few IVF clinics have portedly begun oÝering to se-lect embryos of a particulargender even for those whohave no history of sex-linked

re-GENETIC MUTATIONS can be identiÞed before pregnancy begins by sucking one cell out of an

eight-cell embryo and amplifying bits of DNA The remainder can grow into a healthy baby.

Trang 13

disease ÒThis is inevitable,Ó Wood

warns ÒYouÕre going to see sex

selec-tion become more widespread.Ó Wertz,

who is tallying the results of a recent

survey, claims it indicates that Òperhaps

half of the geneticists in the U.S have

had a request for sex selection.Ó John

C Fletcher, a bioethicist at the

Univer-sity of Virginia, worries about

Òselect-ing embryos for traits that donÕt have

anything to do with disease Society

has an interest in trying to help people

sober up rather than entertaining

fan-tasies about the ideal child,Ó he says

Hughes dismisses the notion that

embryo testing might lead to an

in-crease in unethical reproductive

choic-es ÒRight now you can terminate any

pregnancy for almost any reason up

until 20 weeks,Ó he argues ÒWe think

of testing as an alternative to abortion,

because it allows you to make the

deci-sion before a pregnancy even begins.Ó

If the debate were limited to test-tube

babies, many ethical questions might

be moot After all, of the more than

three million couples in the U.S thought

to be unable to reproduce without IVF,

only about 20,000 go to clinics every

year Costs of $6,000 to $10,000 per

treatment keep many away Others

re-coil when they learn that 85 percent of

IVF treatments fail to produce babies

Rapid advances in the art of

fertiliza-tion promise to improve these odds,

primarily in the 50 percent of cases

with male factor infertility By cutting

holes in the eggÕs tough coating or by

injecting sperm directly into the ovum,

researchers can now fertilize eggs with

even the weakest sperm If such tricks

improve IVFÕs dismal success rate,

de-mand for the procedure and for

em-bryo testing could increase

But John E Buster of the University

of TennesseeÐMemphis College of

Medi-cine, among others, is working on a

technique that might have a far greater

impact Called uterine lavage, the idea

is to wash a naturally conceived

em-bryo from the uterus before it has a

chance to become implanted, then test

it for genetic defects and return it only

if it is healthy Unfortunately, the

chanc-es that just one returned embryo will

develop into a pregnancy are slim If

this technical hurdle can be cleared,

however, uterine lavage might allow

parents to look for mutations in

em-bryos produced the old-fashioned

wayÑat a fraction of the cost of IVF

As the pace of innovation continues

to accelerate, concern is growing among

researchers, clinicians and regulators

alike that there needs to be more

dis-cussion of the issues raised by genetic

screening and more oversight of its

de-velopment Wood reports that leading

Trang 14

Design for Living

A signaling pathway found

in many species is mapped

An ancient tale describes how three

blind men try to identify a

curi-ous object using their sense of

touch The object is an elephant, but

the men fail to recognize it because

each feels a diÝerent part of the

ani-mal Cell biologists working in such

dis-parate areas as oncogenesis, cell

divi-sion in yeast and the sexual anatomy

of Caenorhabditis elegans (a

micro-scopic worm) have for the past decade

or so been groping their way around a

molecular elephant And like the blind

men of the fable, they have been able to agree on what they are examin-ing Until now, that is

un-A remarkable convergence of mental results has suddenly made theinvestigators realize they are all looking

experi-at diÝerent parts of the same thingĐand it is a coveted prize What they havestarted to discern is one of the cellÕsprincipal control mechanisms: a chain

of molecular reactions that conveyssignals from the cellÕs surface into thedepths of the nucleus There the sig-nals empower the genes, which change

a cellÕs shape, its activity or its growth

ỊWe are starting to understand the lecular circuitry of the cell,Ĩ commentsRobert A Weinberg of the Massachu-setts Institute of Technology

mo-The essential molecule in the process

is the Ras protein, which normally liesjust under the cell membrane The se-quence of events is therefore beingcalled the Ras pathway The key eventthat starts the dominoes falling is thebinding of an extracellular signalingmolecule to its surface receptor Thatbinding causes the receptors to aggre-gate The parts of the receptors that lieinside the cell then assume a distinc-tive enzymatic role: they attach phos-phate groups to themselves and to oneanother at the sites of the amino acidtyrosine That chemical modiÞcationmakes the phosphorylated moleculesattractive to proteins that carry a spe-ciÞc motif of amino acids called SH2.Some also carry another motif, SH3,that attracts a third set of molecules,which in turn activates Ras

Until last year, the chain ended there:nobody knew what Ras did But an ar-ray of elaborate experiments by Xian-feng Zhang and Joseph Avruch of Har-vard University and Ulf R Rapp of theNational Cancer Institute and othershas caught Ras red-handed The mole-cule binds to and excites another pro-tein called Raf And to cell biologiststhat is a remarkable Þnding, becauseRaf in its excited form triggers a cas-cade of enzymes that ends up in thenucleus Enzymes called MAP kinasesare among this alphabet soup of play-ers, and they, it is thought, can activateDNA binding proteins in the cell nucle-

us that in turn switch on genes

An unexpected feature is that themolecules of this bucket brigade appar-ently physically aggregate to form amacromolecular complex Tony Pawson

of the Mount Sinai Hospital in Torontospeculates that making such complex-

es Ịis the only way the cell has resolvedhow it is going to respond to and inte-grate a large variety of signals witheÝects on cell growth.Ĩ

At the bottom end of the Ras

path-IVF clinics have drawn up guidelines

for the industry and are searching for a

professional society to enforce them

Self-policing has not worked in the

past, however The American Fertility

SocietyÕs guidelines tend to lag behind

research and have been given no teeth

According to recent reports by the

Ỏce of Technology Assessment (OTA)

and the Institute of Medicine, all the

necessary rules and laws are already on

the booksĐthey are simply not being

followed The Food and Drug

Adminis-tration has the authority to review all

genetic tests before they can be sold for

use by doctors But most genetic

test-ing is oÝered as a service by research

labs and so falls outside FDA purview

Nevertheless, Steven I Gutman, tor of the division of clinical laboratorydevices, says the FDA is Ịconsideringthe possibility of involvement.ĨMany researchers and clinicianswould like to see a permanent nation-

direc-al ethics advisory board set up to mote public debate and oÝer ethicalguidelines for research Four suchboards have been set up in the past 20years Even the most durable operatedfor just three years, however

pro-According to the OTA report, federalregulations have required since 1978that an advisory board exist in order toreview funding requests for research

on human IVF But the Reagan andBush administrations refused to ap-prove the boardÕs charter, thus impos-ing a de facto ban on federal fundingfor human embryo research that stooduntil it was repealed last June

In December the National Institutes

of Health set up a Human Embryo search Panel to work out ethical guide-lines in a series of public meetings thisspring If the recent cloning controver-

Re-sy and the growing use of genetic ing spawn wider public education anddiscussion about the proper use of ge-netic technology, IVF will have been atrue pioneer indeed

test-ĐW Wayt Gibbs and Tim Beardsley

XIAN-FENG ZHANG of Harvard University sketches part of the Ras pathway, a

mo-lecular cascade that controls growth and division in a wide variety of cells.

Trang 15

way, there is a good deal more hand

waving over details than in the

well-worked-out earlier steps ÒThe pathway

through which MAP kinase aÝects

tran-scription is poorly deÞnedÑit may

work in some general manner, but we

certainly donÕt know at the moment,Ó

cautions James E Darnell, Jr., of the

Rockefeller University

There are still question

marksÑactu-ally more of them than ever beforeÑ

but there is also Òthe backbone of a

storyÓ to connect receptors to genes, in

the words of H Robert Horvitz, a

re-searcher at M.I.T who has been one of

the contributors to the recent insights

ÒThe big news is that the pathway is

conservedÓ over the eons of evolution

that separate man from yeast, Horvitz

says, who studies mutations that aÝect

development in Caenorhabditis: ÒWhat

has emerged is a consensus pathway.Ó

Other pathways to the nucleus

be-sides the one that features Ras are

certainly important But what has

im-pressed many researchers is that

inde-pendent lines of work using very ferent organisms have all stumbledonto what seems to be the same bio-chemical contrivance

dif-Ras was originally identiÞed morethan a decade ago as the product of anoncogene, a gene that in mutated formcan cause a cell to become cancerous

Perhaps unsurprisingly, many proteinsproduced by oncogenes have turnedout to be involved in conveying signals,including those that tell cells when togrow and divide Several oncogenesproduce proteins suspected of beingconnected to the Ras pathway, and bi-ologists are now becoming comfortablewith the notion that a fault in a signal-ing pathway could cause a cell to divideincessantly, as in cancer, or to malfunc-tion in other ways

Many big pharmaceutical companies,including Ciba, Sandoz, PÞzer andGlaxo, are now working to Þnd simplemolecules that interfere with one ormore steps in the Ras pathway And,unlike some drug discovery eÝorts, ev-

idence exists that the principle canwork The important immunosuppres-sant cyclosporine is a natural productthat blocks an intracellular signalingpathway, as is the experimental immu-nosuppressant FK506 Ariad Pharma-ceuticals in Cambridge, Mass., a com-pany specializing in drugs aimed atdisrupting intracellular signaling, is try-ing to develop an allergy medicineaimed at a Ras pathway target Peter L.Myers of Onyx Pharmaceuticals in Rich-mond, Calif., says he is Òstarting to seehitsÓÑthat is, chemicals that seem toblock interactions in the Ras chain.Products that work by interfering withsteps in the Ras pathway are probablysome years away But, as Weinberg andSean E Egan of the Imperial Cancer Re-search Fund in London noted in a re-

cent issue of Nature, Òthe satisfaction

to be had from the recent discoverieswill endureÑthat of reducing extraor-dinarily complex phenomenology down

to simple, apparently universally vant, truths.Ó ÑTim Beardsley

rele-32 SCIENTIFIC AMERICAN February 1994

Instructions for building a time machine: Take two

cos-mic strings Throw them together so that each moves at

a speed close to that of light Fly around both of them,

and you will return to the time and place from which you

started (Suggested by J Richard Gott of Princeton

Univer-sity.) Sounds simple enough But don’t try it, warns Gerard

’t Hooft of the University of Utrecht in the Netherlands

You won’t just fail—you might destroy the entire universe

That Nature somehow protects herself from the

contra-dictions of time travel has been conjectured by many

physicists Just how far she will go in self-defense and

what means she will employ are questions that now have

answers—answers that would make even the most

opti-mistic time traveler cash in his or her ticket

In principle, the Gott time machine is quite

straightfor-ward The traveler need only induce two infinitely long,

parallel cosmic strings, presumed threadlike relics of the

big bang, to sweep by each other at speeds near that of

light The strings’ center of mass then moves faster than

light The vast amounts of energy entailed are equivalent

to an intense concentration of mass (remember E = mc2?)

The mass warps space-time so acutely that a path looping

around the strings can take one back in time

The problem arises when one attempts to build a Gott

time machine in the context of an actual universe

Uni-verses appear to come in two varieties: open and closed

Sean M Carroll, Edward Farhi, Alan H Guth and Ken D

Olum of the Massachusetts Institute of Technology have

tried to create Gott pairs in an open universe First, they

say, find two slowly moving cosmic strings Then split

each by an explosion The explosion serves to accelerate

two of the resulting four fragments toward one another at

relativistic velocity Unfortunately, in the open universe,

which is unbounded, as would be an infinite sheet of

pa-per, there is not enough energy available to push the

strings to the needed velocities

All right, the time-machine builder says, why not start

out in a closed universe? In a series of papers in Classical and Quantum Gravity, ’t Hooft attempts just that—and

finds a truly violent outcome The members of the Gottpair do not pass each other, forming time loops Insteadthey trace out chaotic orbits as they move closer and clos-

er together at increasing speed The tremendous tional stresses generated make the universe crumple andfall in toward the strings As their kinetic energy grows in-finite, the universe finally collapses in a catastrophic bigcrunch A time-machine ticket-holder will see massivewalls closing in while being shredded to spaghetti by thestrings speeding through

gravita-Hard times, indeed, but ’t Hooft offers some tion “Quantum effects,” he says, “will probably dilute thebig crunch to a big bounce.” Out of the shreds of the lastuniverse may be born a new one, albeit a bit late for thetime traveler

consola-So the Gott time machine can never be built For thosehopefuls now looking to wormholes, the chutes connect-ing distant regions of space-time—oops, there they go,too A wormhole can be sustained only by negative ener-gy—a no-no Thus, it will squeeze in and collapse like apunctured balloon, probably forming a black hole, beforeanything—even light—can traverse it

Any other new designs that may be dreamed up for atime machine will have to contend with powerful theo-rems propounded by Frank J Tipler of Tulane Universityand Stephen W Hawking of the University of Cambridge.These theorems attest that within finite regions of space-time, time loops are always accompanied by negative en-ergy—disallowed as unphysical—or by violent objectssuch as black holes and imploding universes The scenesketched by ’t Hooft shows how such objects can act asNature’s dragons, guarding time machines from fools who

Time-Trippers Beware

Trang 16

The National Academy of Sciences

in Washington, D.C., is indeed a

temple of science The Great

Hall, a domed chamber decorated with

Þligreed murals and inspirational

quo-tations, houses conclaves of the

na-tionÕs greatest scientiÞc talents From

the meeting rooms and oÛces opening

oÝ the Great Hall pour reports about

the state of the scientiÞc enterprise

and how it aÝects the society that

sus-tains it Recently the academy, an

insti-tution chartered when Abraham

Lin-coln was in the White House, has been

rattled by a new and decidedly

un-stuÝy presence

A professor of biochemistry and

bio-physics from the University of

Califor-nia at San Francisco, Bruce M Alberts,

who has been the academyÕs president

since last summer, has brought to the

hallowed halls an activist agenda, West

Coast informality and a penchant for

self-deprecatory humor that has

mor-tiÞed the institutionÕs more straitlaced

oÛcials His public aÝairs staÝ has yet

to recover from the occasion last fall

when Alberts told a group of reporters

how he had explained to a senator :

ỊThe academy is 1,600 scientists who

elect each other We have a party in

April Otherwise, we donÕt do anything.ĨAlberts, who is 54 years old and hasbeen an academy member since 1981,

is recognized for his research on teins instrumental in the replication ofchromosomes He was something of anunknown quantity when he arrived inWashington, because unlike his imme-diate predecessors at the academyÕshelm he had not previously occupiedany top science post Indeed, Albertswas not the Þrst choice of the searchcommittee charged with Þnding a suc-cessor to Frank Press, a geophysicistwho was president for two consecutivesix-year terms (the maximum) starting

pro-in 1981

Despite the $250,000-plus salary andthe Watergate apartment that comewith the job, several other scientiÞc lu-minaries with more administrative ex-perience than Alberts declined to lettheir names go forward as candidates

Among them were Ralph E Gomory,president of the Alfred P Sloan Foun-dation in New York City, and Maxine F

Singer, president of the Carnegie tution of Washington It would seemthat questions about funding and achanging relationship with the federalgovernment have begun to create a se-

Insti-ries of problems daunting even to themost politically adept mandarin.According to Donald D Brown, a re-searcher at the Carnegie InstitutionÕsdepartment of embryology, who served

as co-chairman of the search tee, Alberts Þlled the bill because he is

commit-an active scientist with broad expertisewho had also earned high marks as anadministrator when he was chairman

of his department at San Francisco.And Alberts was, Brown points out, anenergetic chairman of the commission

on life sciences of the National search Council, which is the organiza-tion, formally distinct from the acade-

Re-my, that performs its scientiÞc ments Moreover, he had been a forcebehind the federal Human GenomeProject ỊWhat he says is exactly what

assess-he thinks,Ĩ Brown comments

If Alberts was not the academyÕs Þrstchoice, then neither was the academyhis Alberts was, he says, Ịvery happywith what I was doing,Ĩ leading a labo-ratory ỊMy image of management wasnegative,Ĩ he explains, still looking, inhis open-necked shirt, like a bench sci-entist even as he sits in his high-ceilinged presidential suite Whateverthe high marks he had received, he hadnot enjoyed his stint as chairman ofhis department, and he thought theacademy would be more of the same.But friends persuaded him toreconsider He capitulated, heremarks, when he realized that

if he had the institutionÕs topjob there were Ịfour or Þvethings I might be able to do that

I couldnÕt doĨ otherwise Most

of those things turn out to bevariations on AlbertsÕs principalpreoccupation: education.Alberts is a man with a mis-sion His research career hadgotten oÝ to a ßying start when

he made an important ery about the structure of ri-bonucleic acid as he worked onhis undergraduate thesis at Har-vard College in the 1950s Theearly success persuaded him tobecome a scientist rather than aphysician, and after a spell atPrinceton University he foundhis way to California

discov-It was there that he oped his consuming interest inimproving scientiÞc literacy, apassion he says was inspired

devel-PROFILE : BRUCE M ALBERTS

BRUCE M ALBERTS holds forth in the National Academy of SciencesÕs Great Hall Can a

hip lip-shooter find his way through the corridors of power?

Laid-Back Leader Rattles the Academy

Trang 17

mostly by his wife BettyÕs leadership of

the Parent-Teacher Association in San

Francisco Alberts is the principal

au-thor of a noted textbook on molecular

biology, but he prefers to talk now

about another of his achievements,

co-founding the University of California at

San Francisco Science/Health

Educa-tion Partnership The program is a

col-laboration in which university

scien-tists and public school teachers work

to implement fresh approaches to

sci-ence instruction

Now Alberts would like to launch a

similar scheme on a national level ỊA

strong motivation for me in taking this

job was to see if the academy could Þll

a real void in leadership nationallyĨ in

science education, he states AlbertsÕs

vision is breathtaking in its audacity

He wants to harness not just the

acade-my but much of the countryÕs scientiÞc

workforce to his campaign ỊIÕm not

talking about nudging the system; IÕm

talking about very dramatic change,Ĩ

he declares ỊWe can use science

educa-tion as a wedge to change the system,

to empower teachers to change the

na-ture of the public school experience.Ĩ

Heady stuÝ But Alberts is conÞdent

that scientists will rally to his cause

and devote their Ịtremendous amount

of energy and focus and skillĨ to

en-hancing education Within a couple of

months of taking oÛce last July, after

an uncontested election in February,

Alberts had met with the

superinten-dent of schools in Washington with an

eye to setting up a demonstration

proj-ect in the city And in November he

summoned reporters to hear about the

launch of Project RISE ( Regional

Initia-tives in Science Education) RISE is a

pi-lot project in which the National

Re-search Council will support regional

collaborations between scientists and

elementary teachers to promote

hands-on science

The academy is also developing

for-mal national standards for science

edu-cation Alberts has talked to Richard W

Riley, the Clinton administrationÕs

sec-retary of education, about initiating

leg-islation to give school districts

incen-tives for adopting them But there is no

shortage of science curricula, Alberts

notes, at least in the elementary grades:

ỊItÕs just a question of having the

ex-pertise to do it and the will to do it.Ĩ

He hopes to persuade biotechnology

companies, in particular, to follow the

lead of other industries by providing

challenge grants for schools and

dis-tricts that adopt new approaches

ỊIÕm not going to have any problem

Þnding enough scientists and doctors,Ĩ

Alberts asserts Still, he acknowledges

that not everyone is cut out for

teach-ing partnerships ỊThere are some entists who alienate me,Ĩ he concedes

sci-And Alberts says he is aware of thedangers of letting well-meaning re-searchers loose to lecture teachers orstudents about scientiÞc specialities

He recalls a soil scientist who insistedthere were Ịeight facts everyone shouldknow about soil science.Ĩ ỊWell,Ĩ Al-berts chortles, ỊI didnÕt know them my-self, and IÕm president of the academy!ĨThe jest is typical of AlbertsÕs style

He is also famous for being minded in true professorial tradition

absent-He once startled his staÝ by wonderingout loud how he was going to run theacademy when he is too disorganized

to Þnd his glasses On another sion he managed to lock himself insidehis oÛce and had to be rescued

occa-Whether such endearing foibles willserve him well in a hostile congression-

al hearing room is a question yet to beanswered

Despite his relaxed attitude, Albertsdoes not pull many punches The acad-emy and the research council, togetherwith the academyÕs sister institutions,the National Academy of Engineeringand the Institute of Medicine, employmore than 1,000 policy analysts inWashington ỊItÕs grown to be very large,which is a problem,Ĩ Alberts statesbluntly In doing so, he echoes rumorsthat the academy may have to lose largenumbers of staÝ But Alberts will notconÞrm suggestions that cuts of morethan 20 percent over the next Þve yearsare in prospect

Like any institutional leader, Albertsmust address the problem of revenues

Although Press built up the academyÕsendowment substantially during his 12years in oÛce, it is still, at $120 million,small for an organization of the acade-myÕs size, Alberts points out The en-dowment is important because only byusing its own funds can the academyinitiate studies in areas where the gov-ernment may not want to hear advice(the academy was founded to supplyadvice to the government, but demandfor studies is down) The complex pro-duced more than 200 reports last year,most, though not all, commissioned byfederal departments and agencies

On another front, the new presidenthas also taken action in his Þrst sixmonths to address concerns about theimpartiality and independence of theresearch councilÕs studies Because thereports are independently produced,government agencies like to have theacademyÕs Ịblessing.Ĩ But academymembers have complained, Alberts con-Þdes, that research council staÝ havesometimes allowed government oÛ-cials to inßuence reports, which runs

counter to the rules of the academy

A congressional source gives the ample of a research council study ofthe Earth Observing System, a federalsatellite remote-sensing program Criti-cisms of the system in a research coun-cil study were muted after governmentoÛcials who saw prepublication draftsobjected Studies for the Coast Guardand the Department of the Navy andstudies on agricultural policy are alsosaid to have been inßuenced throughcozy relations with external parties Alberts has undertaken Ịan exten-sive review of the proposal review pro-cessĨ to strengthen high-level delibera-tions about the rationales for studiesand to underscore the responsibilities

ex-of research council oÛcials Finally, hehas inaugurated eÝorts to make the re-search council more collegial and eÛ-cient by breaking down Ịinstitutionalbarriers that prevent people from work-ing with one another.Ĩ

In his role as a statesman of science,Alberts expounds on a theme initiated

by Press: that scientists must realizethat their demands for more fundsmay have made them vulnerable onCapitol Hill to accusations of selÞsh-ness To deal with the problem, Alberts

is trying to build bridges with bers of Congress and their staÝs

mem-He has also consulted with the WhiteHouse on its recently announced planfor a National Science and TechnologyCouncil, the administrationÕs initiative

to get a Þrmer grip on federally ported research ỊWe have to be moreadept at disposing students to a widerrangeĨ of scientiÞc careers, Alberts says.Otherwise, Ịwe should not be trainingthe number of Ph.D.Õs in physics andchemistry that we are turning out.Ĩ

sup-A major challenge, he observes, is toremove the barriers that prevent peo-ple with scientiÞc skillsĐincluding un-employed defense workersĐfrom en-tering new Þelds, such as teaching, thetopic that most of AlbertsÕs thoughtscome back to ỊWe have got to try, atleast, to make it an attractive pathway,Ĩ

he declares One approach he favors isthe development of speciÞc courses forteaching science pedagogy

Alberts is sympathetic to the dens of teaching He has a daughterwho teaches science, and like many ofher colleagues she has to buy suppliesfor classes out of her own salary.ỊWeÕve made teaching a profession inwhich it is impossible to do well unlessyouÕre some kind of martyr,Ĩ he says If

bur-he gets his way, that trend could start

to change Educators, as well as searchers, might yet be beneÞciaries ofthe new irreverence in the sanctuary of

Trang 18

In October 1981 President Ronald

Reagan announced the beginning

of the biggest military buildup ever

undertaken by a nation in peacetime

Over the next decade the U.S spent

more than $3 trillion (three quarters of

the current national debt) on its

mili-tary Fully 60 percent of those costs

were devoted to countering the threat

of communism That tremendous

ex-penditure marked the culmination of

the 50-year competition with the Soviet

Union, a period during which tion on one side provoked reciprocalmoves on the other, even after both na-tions had long passed the point of bothmutual intimidation and overkill

escala-When the Soviet Union imploded in

1991, the U.S was still spending morethan $300 billion a year for a militarythat included 530 ships, 16 active armydivisions, more than 3,000 planes andmore than 25,000 nuclear warheads

Such massive forces place an able burden on the American economyand saddle the nation with a militarybuilt around an unrealistic scenario ofvast global conßict American forcestherefore require prompt reduction andreform

unaccept-Prudence implies that such changes

in U.S forces cannot be too sudden, norshould they go beyond the possibili-

ty of reversal Nevertheless, judiciousAmerican military cutbacks could savehalf a trillion dollars by the end of the1990s That money could be far moreproductively targeted toward rebuild-ing infrastructure, expanding healthcare, upgrading education or otherwiseimproving the nationÕs economic andsocial well-being

Such reductions should not be severeenough to threaten the ability of theU.S to maintain a strong nuclear deter-rent or to Þeld conventional forces largeenough to prevail against any foe thenation might plausibly face in the nearfuture At the same time, the nationmust continue along new paths to en-

courage the just resolution of tional conßicts through multilateral se-curity arrangements

interna-In 1990 President George Bush madetentative moves in the direction ofstreamlining the excessive U.S militarycapability The Pentagon presented aÞve-year plan to create a downsizedỊbase forceĨ 25 percent smaller thanthe one that existed at the end of theReagan years Despite much talk aboutadditional military cuts under the ad-ministration of President Bill Clinton,similar thinking appears so far to guideU.S policy

That approach is unsatisfactory fortwo reasons First, the proposed forcesare in many ways as oversized as theywould be if they were still structuredaround containment of the Soviet Union,

a powerful adversary that no longer ists Second, the plans do not yet fullyaddress the need for restructuring ourmilitary to reßect the changed world.The 1990 Ịtwo-warĨ strategy remains:the U.S needs to retain the capability

ex-to fight two major regional wars at thesame time without signiÞcant aid fromallies That strategy seems more a jus-tiÞcation for a large American militarythan a plausible scenario for futureconßicts We expect to see the two-warguideline fade quietly away under theClinton administration

To arrive at an adequate yet able scale for AmericaÕs armed forces,

afford-we attempted to ansafford-wer two basic tions: Who are our most probable ad-

ques-38 SCIENTIFIC AMERICAN February 1994

PHILIP MORRISON, KOSTA TSIPIS and

JEROME WIESNER have been

long-stand-ing advocates of arms control Morrison

is an emeritus professor of physics at

the Massachusetts Institute of

Technolo-gy He has spoken and written on

mili-tary strategy and nuclear disarmament

ever since he completed four wartime

years working on the American atomic

bomb project Tsipis is the director of

the Program in Science and Technology

for International Security at M.I.T His

background lies in experimental particle

physics; he has also written extensively

on the physics and technology of

nucle-ar weapons and nuclenucle-ar wnucle-ar Wiesner is

president emeritus of M.I.T He has

served as science adviser to presidents

John F Kennedy and Lyndon B Johnson

Wiesner helped to establish the Arms

Control and Disarmament Agency and

played a pivotal role in achieving a

par-tial nuclear test-ban treaty and in

limit-ing the deployment of antiballistic

mis-sile systems

The Future

of American Defense

U.S forces were shaped for conflict with a superpower

The emerging multilateral world calls for a smaller, more flexible and far less expensive military

by Philip Morrison, Kosta Tsipis and Jerome Wiesner

Trang 19

GULF WAR brought together a remarkable international

coali-tion dedicated to neutralizing IraqÕs military occupacoali-tion of

Kuwait Such multilateral collaboration is likely to become

more common in the postÐcold war world The U.S can nowdrastically cut its military spending yet remain strongenough to face down any likely aggressor

Trang 20

versaries in the next two decades and

beyond, and what missions and

func-tions do we expect our military to

per-form in that time?

During the height of the cold war,

potential enemiesĐprimarily the Soviet

Union, Eastern Europe and

ChinaĐin-cluded some highly industrial countries

that wielded nuclear weapons Those

nations contained about 1.5 billion

people, about one third of the worldÕs

population; they could collectively Þeld

armies seven million strong In

con-trast, the nations that might

conceiv-ably confront the U.S in the

foresee-able future (Iran, Iraq, North Korea and

Libya) all lack strong industrial bases

Together these hostile countries have a

population of just 110 million, from

which they draw armies totaling no

more than two million men and

wom-en Even after a substantial reduction

in American forces, the U.S and its

al-lies would outspend the rest of the

world in defense

Large-scale aggression against

Cen-tral Europe is a fading vision If the

huge, powerful and militarily honed

So-viet Union did not attempt it, its

im-poverished, fragmented successors,

many of which are seeking aid from the

West, surely will not Regional conßicts

in Eastern Europe or the former Soviet

states might make necessary

interna-tional peacekeeping missions, but they

would not occasion a frontal assault by

American forces In the postÐcold war

world, it seems equally unlikely that

American armies will be sent to Þght in

Asia against China or India The U.S

cer-tainly will not be warring against other

countries in North or South America

The most demanding military tasks

the U.S might plausibly face in the

next decade or two would be

counter-ing aggression in the Middle East or on

the Korean Peninsula Congressman Les

Aspin of Wisconsin, later the U.S

secre-tary of defense, selected Iraq as an

ex-ample of the mightiest military force

the U.S is likely to face in the near ture It is a good choice None of theother plausible U.S opponents are amatch for the land and air capabilitiesIraq had when it invaded Kuwait in

fu-1990 Even Iran, whose population isnearly three times that of Iraq, has nosuch military assets today

Past conßicts oÝer another way to ibrate AmericaÕs future military needs

cal-At present, the U.S uses about 50 craft to monitor Iraq, and maybe twice

air-as many planes (not all of them fromthe U.S.) monitor the airspace overBosnia During Operation Desert Storm,nearly 1,700 aircraft of all types ßew100,000 sorties in 45 days The U.S

used a total of about 1,000 planes ing both the Vietnam and Korean wars

dur-Humanitarian assistance and keeping eÝorts in Bangladesh, Lebanonand Somalia have engaged mainly Ma-rine Expeditionary Units containing up

peace-to a peace-total of 20,000 men and women

During the next 10 or 20 years, theU.S is far more likely to Þnd itself en-gaged in multinational humanitarian,peacekeeping and counterterrorism ac-tivities than in a major armed conßictwithout allies The U.S should prepare

to contribute to future common

securi-ty forces assembled by the United tions or other groupings of nations foroperations such as the Gulf War or So-malia For that responsibility, our coun-try will need the means to keep sea-lanes open and to impose blockades aspart of collective sanctions against na-tions that have taken up arms We notethat any force powerful enough to pre-vail in a large-scale battle will be morethan suÛcient for international polic-ing missions

Na-In developing our proposal, we havetried to look beyond the present divi-sion of U.S forces along service lines Acomplex military establishment seemsmore amenable to timely and logicalrestructuring when it is deÞned by mis-sion rather than along service lines We

have grouped our recommendationsaround the six distinct functions of theAmerican military: nuclear deterrence,air-land battle, control of the seas, land-sea operations, intelligence gathering,and research and development.AmericaÕs long experience with jointoperations oÝers a blueprint for such arevised military structure For example,

in the 1970s the U.S developed an land battle doctrine for the defense ofEurope During the Gulf War, the U.S.eÝectively combined its land, air, navaland space-borne weapons and systems.The success of that venture suggeststhat it may be to AmericaÕs advantage

air-to reorganize its forces under six mands corresponding to the functions

com-we have described

One of the most dramatic and

welcome results of the end ofthe cold war is the virtual dis-appearance of the possibility of nuclearconßict with the former Soviet states

As long as nuclear weapons continue

to exist, however, they pose a risk toU.S and world security We set as aclear requirement that the U.S preserveunquestioned deterrence against anynuclear threat Nuclear war betweentwo nations that possess substantialnuclear arsenals will almost surely re-sult in mirror devastation of both com-batants A few hundred or a few dozenassuredly deliverable nuclear weaponswill ensure symmetrical obliteration ofbases, cities and industry even in largecountries such as Russia or the U.S

U.S.: 9,860 warheads, including 2,370 on intercontinental ballistic

missiles (ICBMs) START II will reduce the total number to 3,500

by the year 2002

Former Soviet Union: 10,920 warheads, including 6,630 on

ICBMs, located in Russia, Ukraine, Belarus and Kazakhstan

START II will limit the total to 3,000 by the year 2002

U.K.: Approximately 300 warheads, none of them on ICBMs.

France: 426 warheads, 18 of them on ICBMs.

China: About 270 warheads, roughly 100 of them on ICBMs.

Declared Nuclear Nations

Trang 21

Such modest nuclear holdings

there-fore can suÛce to dissuade an

aggres-sor from a nuclear attack But

super-power nuclear forces long ago grew

be-yond that size

In 1990 the U.S held more than

12,000 strategic nuclear warheads

The Soviet Union had 11,000 Under

the Strategic Arms Reduction Treaty

( START ), signed by the two nations in

1991, the U.S reduced its arsenal to

8,500 and the U.S.S.R to 6,000 In June

1992 Bush and President Boris Yeltsin

agreed to additional nuclear arms cuts:

by the year 2003 the U.S would have

3,500 warheads and Russia 3,000 At

that time, China, France and Britain will,

we expect, hold a few hundred nuclear

weapons apiece The newer undeclared

nuclear powers may collectively

pos-sess an additional 200 or so warheads

We recommend instead that by the

year 2000 the U.S possess a deterrent

force of approximately 800 assuredly

deliverable warheads Present U.S

nu-clear forces wield such immense

de-structive power that even after drastic

cutbacks, the country will be able

eÝec-tively to face down threats from any

present or imminent nuclear nation

American holdings of nuclear warheads

should be cut further as the nation

strives to bring about a nuclear-free

world We would advocate even faster

reductions in nuclear arms but for our

awareness that more profound change

will come only slowly as long as

cau-tion guides nacau-tional leaders

Tactical nuclear weaponsÑusually

small-yield weapons meant for useagainst engaged forces on the battle-Þeld or against airÞelds, bases and for-ward transportÑseem to be of littlemilitary use In September 1991 Bushwisely ordered the elimination of allsea-based tactical nukes but spared afew hundred bombs located on somecarrier aircraft This lingering ability toinitiate nuclear attack on nonnuclearstates is intolerable and dangerous; thecomplete end of all shipboard nuclearweapons by the year 2000 is a wiserstance We also recommend eliminat-ing the nearly 1,000 U.S tactical nucle-

ar weapons deployed on aircraft inwestern Europe, Þrst by negotiatingwith Britain and France to end their de-ployment of such weapons That initia-tive could set a splendid tone for the

1995 Review Conference on the

Nucle-ar Non-Proliferation Treaty

Nuclear weapons development, ing and manufacture are unnecessaryand in fact are ending, both in the U.S

test-and in Russia Clinton has initiated lomatic eÝorts aimed at a formal ban

dip-of nuclear testing The $8 billion ournation spends annually at some 16specialized plants dedicated to the pro-duction of U.S nuclear weapons cannow be devoted entirely to the disas-sembly, safe storage and eventual dis-posal of nuclear cores and for thecleanup of radioactive pollution left in

a dozen states

The biggest nuclear threat to the curity of the U.S and to the rest of theworld now comes from the prolifera-

se-tion of nuclear weapons and relatedtechnology Attempts to combat prolif-eration only by stanching the ßow ofmaterials, equipment and know-howcannot prevent the appearance of newnuclear powers Even the most thor-ough systems for safeguarding nuclearknowledge eventually leak

To reduce the risk of proliferation,the nations of the world must lowerthe demand for, as well as the supply

of, nuclear weapons Wider

internation-al sharing of economic progress andpolitical decision making could helpease tensions between nations andlessen the demand for nuclear prestige

or protection

Crucial though the nuclear

cut-backs will be, most of the eÝort

at military restructuring will volve conventional forces, which ac-count for 80 percent of the U.S defensebudget We turn our attention Þrst tothe portion of the military dedicated toair-land battle: ground forces and theaircraft that both precede and supportthose forces in battle The strength of

in-an army is often measured in terms ofdivisions of troops A division is thestandard unit large enough to includeall the elements of ground war : infan-try, armored vehicles, artillery, antiair-craft and engineers During wartime,

a U.S Army division contains about17,000 men and women

The present base force plan pates only a modest reduction in Amer-ican ground forces, from the 16 army

antici-SCIENTIFIC AMERICAN February 1994 41

Israel is believed to have 50 to 100 nearly ready warheads.

India has 20 to 50 unassembled warheads.

Pakistan may have up to 10 unassembled warheads, possibly of

foreign design

South Africa says it will dismantle its six Hiroshima-type bombs.

North Korea is reported to be in the final stages of warhead

fabrication

Iraq was well along in development of warheads before the

Gulf War

Libya and Syria and perhaps Iran and Algeria have long been

interested in acquiring nuclear weapons

Germany, Italy, Japan and Switzerland could produce nuclear

weapons within a year of deciding to do so

Argentina, Brazil and Sweden have abandoned their nuclear

Trang 22

divisions that existed in 1991 to 12

di-visions by 1995 We see no productive

use for such extensive standing ground

forces Only China, India, Russia,

Viet-nam and North Korea have bigger

armies, and they lack AmericaÕs

mod-ern equipment and Þrst-rate air and

sea support Moreover, the U.S

Depart-ment of Defense (and some defense

analysts) continue to calculate

Ameri-can needs on the assumption that we

will be Þghting alone But America has

fought with allies in the past and

al-most certainly will do so in the future

The massive, modern forces of

west-ern Europe and Japan are far more

like-ly to Þght beside those of the U.S than

against them Nevertheless, there is the

remote possibility that one nation with

modern forces might change from ally

to adversary U.S conventional forces

that equal but do not exceed the

over-all strength of any two of the nationÕs

strong allies seem a reasonable

stan-dard in a world moving toward

com-mon security

That gauge leads us to suggest that

by the year 2000 the U.S should keep

the equivalent of about Þve active army

division equivalents, including heavy

armor, airborne, helicopter-borne and

light infantry units This ßexible,

mo-bile force would retain a core of almost

two full-armored divisions The army

would comprise about 180,000

full-time members, augmented by

signiÞ-cant army reserves

How many modern main battle tanks

ought the U.S to possess as the decadeends? German preparations for theirdefense against the Red Army (andnow its still unformed successors) inCentral Europe oÝer a guide to appro-priate American tank strength Ger-many deploys almost 4,000 top-of-the-line tanks, which are as good or betterthan the Þnest American tanks Franceand the U.K., two of GermanyÕs NATOpartners, have another 2,500 goodmodern tanks between them The U.S

Army has placed 6,500 of its most vanced tanks in Europe

ad-Because of geographic, economic andhistorical factors, however, U.S inter-ests extend beyond Europe We there-fore need to consider the tanks andother armored forces elsewhere aroundthe world In the Middle East, Iraq hadthe most extensive array of up-to-datetanks before the Gulf War dramaticallyreduced its intact weaponry Today thestrongest Middle Eastern tank forcesare those of Israel (more than 3,000main battle tanks) and of Syria (close

to 4,000 tanks, many of them of olderdesign) Iran has fewer than 500 tanks,just one tenth of the pre-war Iraqi force

China has a force of 8,000 tanks, andIndia holds about 3,000 older tanks

Both countries have substantial armiesand vast territories, but it is highly un-likely that either will engage Americanground forces in the next decade ortwo Aside from a few American allies( Germany, France, the U.K and possi-bly Israel and South Korea ), no countrynow possesses a tank force that couldmatch 500 of the newer U.S tanks

In Europe, Germany is well preparedfor land defense We propose that, inaddition, the U.S should deploy about1,200 of its best heavy tanks in Europe

Half of those tanks could be kept instorage, the other half on active duty

Another 800 U.S tanks should be tained for rapid deployment in any bat-tles that might erupt in other theatersaround the world AmericaÕs powerfulcombat helicopters will remain an im-

main-portant antiarmor weapons system thatenhances the eÛcacy of the nationÕstanks

A reduction in tactical air strengthshould accompany the deep cut inground forces The Bush base force planprovided 56 combat squadrons of Þght-

er and ground-attack, Þxed-wing craft in 1993, which adds up to nearly1,200 primary airplanes; spares, train-ing craft and the like nearly double thatnumber We recommend a diminution

air-of tactical air strength, roughly in portion to the cuts in ground forces, toabout one third the 1993 number ThereconÞgured aerial forces will consist

pro-of 18 squadrons armed with the newestaircraft types: the F-117 Stealth Þght-ers, F-15s and F-16sĐAmericaÕs top-of-the-line ÞghtersĐand the sturdy A-10ground-attack airplane Marine and navyaviation units will augment this total

Control of the seas has long been

a central function of Americanarmed forces; this historical em-phasis is sure to continue Such capa-bility will support both American andmultilateral interventions in overseascrises of any kind Among the armedservices, the U.S Navy now receives thelargest share of the military budget.Aircraft carriers account for a heftyportion of that expenditure The De-partment of Defense still intends tomaintain an amazing 12 carrier battlegroups in 1995, even though Soviet na-val forces are no longer a threat U.S Navy attack carriers are the big-gest, most costly, complex warshipsever invented A ship of the nuclear-powered Nimitz class stretches 1,000feet long It carries its crew of 5,000men and women anywhere in the world

at a cruising speed of 35 miles per hour.One Nimitz-class carrier can transport

to any coast an aerial strike force parable to the entire air power of coun-tries such as Canada, Denmark or Iran.Navy carriers make it possible toproject American air power a few hun-

com-42 SCIENTIFIC AMERICAN February 1994

HOSTILE NATIONS still abound, but

they present more localized challenges

than did the Soviet Union or China Iraq

(left ) has repeatedly defied the United

Nations and is attempting to rebuild its

forces North Korea continues to

pur-sue nuclear weapons In Libya (center ),

a repressive regime sponsors terrorism

And IranÕs brand of Islamic

fundamen-talism (right ) may threaten Middle

East-ern nations, including U.S allies

Trang 23

dred miles inland, a considerable

ad-vantage when there are no friendly

air-bases onshore The carriers also retain

an old function: to Òshow the ßagÓ

spec-tacularly, giving warning of impending

U.S hostile action and taking control of

straits and ports from the sea

In the world we hope to enter, there

is no great reason for the U.S to act so

determinedly alone If Americans can

accept a more cooperative view of

secu-rity, this country will not need so much

power against distant states Five active

carriers seem plenty; they would remain

an unmatched force for the projection

of American power Two carriers might

normally be devoted to nonviolent

mis-sions, for instance, to rescue, relief

supply and evacuation duties, carried

out under international sponsorship or

even unilaterally The navy might

bene-Þt from building several smaller

carri-ers as cheaper, more vcarri-ersatile

replace-ments for the current behemoths

While at sea, each carrier currently

receives support from six warships As

the number of carriers dwindles, so

would this support Twelve antiair and

antiship missile cruisers, along with 18

of the most up-to-date antisubmarine

ships, would furnish ample surface

es-corts for the remaining carriers Two

nuclear-powered attack submarines for

each battle group would add undersea

protection

The 1992 report of the secretary of

defense calls for 145 combat ships in

1995 We recommend instead a stiÝ

drawdown in the navy comparable in

magnitude to that we found reasonable

for the army Once again, we base our

recommendation on the principle that

the U.S military resources contributing

to the collective security of our allies

should constitute a force second to

none but no greater than any other two

combined That principle allows for a

generous U.S ßeet containing more

than 30 destroyers and frigates, over

and above the 18 assigned to the

carri-er battle groups The total U.S surface

naval strength (12 cruisers, 50 ers and frigates and Þve big carriers)would continue to be the biggest navalforce at sea

destroy-Naval air strength might be kept at alevel somewhat higher than the num-ber of aircraft that can be delivered bythe reduced ßeet of carriers Such air-planes can operate from runways onland in addition to those at sea The

present 620 active carrier-borne navalÞghters, bombers and attack aircraftcan be pared to about 210 planes Land-based, long-range maritime patrol air-craft can perform a wide variety ofsurveillance tasks on the high seas In aworld full of surprises, we recommendretaining nearly the full present num-ber of these craft About 250 Orion P-3turboprop patrol airplanes can surveythe most important ocean areas in con-junction with the aircraft capable ofperforming the same missions that be-long to American maritime allies.The U.S Marines, by origin and bytradition, operate at the interface be-tween sea and land They are the mostversatile component of the Americanarmed forces One Marine Expedition-ary Unit numbers about 2,500 men andwomen, along with 10 tanks and ar-tillery batteries, half a dozen vertical-takeoÝ attack aircraft and 30 helicop-ters and their crews The marines nowhave a dozen or more helicopter carri-ers that are able to land an expedition-ary unit and its armor on any beach

Declines in Military Threats to the U.S.

Plummeting world military expenditures offer an opportunity for

commen-surate cuts in U.S defense spending (top ) Some changes seen here

re-flect shifts in the value of currencies and a reclassification of former WarsawPact nations into the “rest of the world” category Our projection assumesthat by the year 2000 the U.S and its allies will account for 60 percent ofworld military spending, a higher percentage than in 1987 American militarycutbacks will be steep but no more so than during postwar transitions earlier

in this century (bottom )

1990 DOLLARS (BILLIONS)400

0 100 200 300 500 600 700 800 900

198719922000*

*projected, including authors’ proposal

SOURCE: International Institute for Strategic Studies

SOVIET BLOC AND CHINA

UNION AND CHINA

U.S ANNUAL EXPENDITURES

1990 DOLLARS (BILLIONS)

19301940195019601970198019902000

400

0 100 200 300 500 600 700 800 900

KOREAN WARVIETNAM WARBUILDUP IN 1980S

AUTHORS’

GOAL

WORLDWAR II

WORLDWIDE ANNUAL EXPENDITURES

Trang 24

These units allow the ßexible, speedy,

small-scale response that is likely to be

necessary for future missions, whether

sent across a beach for an

interven-tionary attack or for less belligerent

missions, such as the U.S entry into

Somalia

The unique capabilities of the

ma-rines seem crucial to preserve Even if

forcible entry onto foreign soil becomes

as rare as it should, many

humanitari-an humanitari-and peacekeeping missions will

con-tinue to demand quick action, often

through inadequate seaports But the

existing marine forces could be

sub-stantially trimmed We propose that the

U.S sustain a dozen distinct

expedition-ary units, which would be grouped as

needed This change would bring about

an overdue reduction in marine forcesfrom almost 200,000 persons to oneaugmented division and its air support,

or about 50,000 persons

The marines would retain about 25

of the present 65 amphibious warfareships, mainly the newer ones Thetrimmed marine forces would receiveair support comparable to that of one

of the present Marine Air Wings: 150Þxed-wing combat aircraft ( including

40 of the unique vertical-takeoÝ ers) and a similar number of gunshipsand transport helicopters

Harri-Two very important components ofthe U.S militaryÑintelligence and mili-tary R&DÑlie outside the boundaries

of either conventional or nuclear

forc-es We envision these two sectors tually falling under their own, separatecommands Only some of their func-tions can be reduced in proportion withthe deep cuts outlined so far The U.S.mostly keeps secret the costs of its information gathering, including thatconducted from spy satellites Defenseanalysts have made informal estimates,however, which are becoming increas-ingly credible We use those estimates

even-in our proposal

The largest single ering item in the U.S defense budget($11 billion in 1990 dollars) pays fordecentralized tactical intelligence: re-connaissance aircraft, radio monitoring

information-gath-44 SCIENTIFIC AMERICAN February 1994

The military reorganization outlined in this article would

maintain U.S security while leading to enormous cost

reductions A breakdown of our proposal (below, right )

shows the size and cost of the restructured forces for the

year 2000 The “base force” plan developed under dent George Bush still reflects the Pentagon’s spendinggoals through 1995 Our approach would save $670 billion

Presi-in current dollars by the end of the decade (below, left ).

A Strategy for U.S Arms Reductions

COST (BILLIONS OF CURRENT DOLLARS)

NONNUCLEAR FORCES

AIR-LAND BATTLE

5 ACTIVE ARMY DIVISIONS

5 RESERVE ARMY DIVISIONS

400 ACTIVE AIRCRAFT

400 RESERVE AIRCRAFT

10 SHIPS AND 20 PREPOSITIONED SEALIFT FORCES

LAND-SEA INTERFACE

1 ACTIVE MARINE DIVISION

1 RESERVE MARINE DIVISION

150 AIRCRAFT AND 30 ASSAULT SHIPS

500 AIRLIFT PLANES

SEA CONTROL

5 CARRIER GROUPS

47 CRUISERS, FRIGATES AND DESTROYERS

15 MINE WARFARE SHIPS

“BASE FORCE” PLAN AUTHORS’ PROPOSAL

Trang 25

and a dozen or more other activities

that deliver short-term battleÞeld

infor-mation to combat forces wherever they

are Reductions in the size of AmericaÕs

armed forces decrease the need for

such intelligence These activities can

be pared to $3.5 billion, a somewhat

smaller cut than those we suggest in

the combat forces themselves

AmericaÕs diverse military satellites

and its signal-decrypting organization,

the National Security Agency, provide a

valuable stream of hard information on

global aÝairs We would retain this

use-ful ßow nearly in use-full at $9 billion per

year, a slight drop from the current $11

billion The Central Intelligence

Agen-cyĐestimated to cost $3 billion a year,

about one tenth of the intelligence

to-talĐcan sustain a 50 percent funding

cut, in part to curtail covert operations

of dubious value all over the globe The

total costs of intelligence can decline

from the surmised 1992 sum of $29

bil-lion to $18 bilbil-lion in current dollars by

the year 2000 The U.S should

serious-ly consider sharing substantial chunks

of the costs and results of its

intelli-gence activities with American allies

and with the U.N

Research and development of new

nuclear and conventional weapons has

provided the American military with an

unsurpassed technological edge on the

battleÞeld and a redoubtable

deter-rence to nuclear aggression from afar

In Þscal 1993 weapons research, at

slightly more than $42 billion, took 59

percent of all federal R&D funds for

the year Of that total, nearly $38

bil-lion was spent on the development,

testing and evaluation of new weapons

Forty years of such investments have

paid oÝ In many cases, U.S arms are

now technologically superior to those

that an opponent could deploy even a

decade from now Moreover, defense

R&D spending in the former Soviet

Union has plummeted since its

dissolu-tion in 1991 The race to stay ahead

can now slow down

Even at $15 billion a year, the U.S

would spend nearly 10 times as much

on military R&D as Germany and Japan

combined Key savings will result from

canceling further work on inessential

projects such as tilt-rotor aircraft and

new attack submarines and from

end-ing other big R&D programs aimed at

the nonexistent Soviet threat Such

sav-ings will allow full funding for the

com-munications, electronic

countermea-sures and surveillance-and-attack

sys-tems needed to safeguard the qualitative

superiority of many American weapons

systems Basic and applied, dual-use

military research can stay at the present

$4 billion a year while leaving ample

funds for preserving the defense nology base and for pressing forwardwith advanced technology programs

tech-Recent American military

engage-ments oÝer a glimpse of a ture deÞned not by massivepreparations for a superpower war but

fu-by a versatile mix of forces suited to aworld in transition Television hasbrought the American public vivid im-ages of air deliveries to besieged towns

in Bosnia, helicopters rocketing points in Mogadishu and Iraqi radarsites knocked out by missiles fromAmerican ships speeding at sea far-away What those powerful but piece-meal images cannot show is how pre-posterously disproportionate U.S mili-tary forces have become in comparisonwith the challenges they face

strong-The military restructuring that wepropose attempts to respond realisti-cally to the historical changes in thegeopolitical map that have taken place

in the past few years It is a cautiousplan that anticipates a welcome em-brace of the notion of peace throughcooperation while remaining alert tonew risks of war The reduced forces

we advocate should be adequate to dertake six to eight simultaneous So-malia-like operations or to mount aforce somewhat larger than the Ameri-can component of Desert Storm By theyear 2000 U.S forces would remainmore capable and more versatile thanany other in the world, at a cost of

un-$164 billion per year in current dollars,

a 60 percent reduction from real penditures in 1992

ex-Such cutbacks will place a deÞnite,though localized, burden on the Ameri-can economy ; indeed, the apprehen-

sion of that stress has slowed the evitable reduction in military spending.But the U.S has weathered similar tran-sitions in the past Moreover, each bil-lion dollars of military savings, if spent

in-in the civilian economy, can createmore than twice as many jobs as thoselost in the weapons industry

American leadership will be vital inbringing about a more peaceful, lessmilitarized world At the beginning ofthe 1990s, nations squandered nearly atrillion dollars a year in military pro-grams worldwide In the near future,

we hope much of the resources so directed can be used to tackle environ-mental and human problems in theU.S and around the globe

mis-SCIENTIFIC AMERICAN February 1994 45

SOMALIA MISSION heralds the international humanitarian actions that may come an increasingly important function of the U.S military in the future Despitesome missteps, the mission brought food and supplies to a devastated population

be-FURTHER READINGCUTTING CONVENTIONAL FORCES: AN

ANALYSIS OF THE OFFICIAL MANDATE,STATISTICS AND PROPOSALS IN THENATO-WTO TALKS ON REDUCING CON-VENTIONAL FORCES IN EUROPE East-West Conventional Force Study Insti-tute for Defense and DisarmamentStudies, July 1989

DECISIONS FOR DEFENSE: PROSPECTS FOR

A NEW ORDER William W Kaufmannand John Steinbruner Brookings Insti-tution, 1991

DEFENSE CUTS AND COOPERATIVE RITY IN THE POSTÐCOLD WAR WORLD

SECU-Randall Forsberg in Boston Review, Vol.

17, Nos 3Ð4, pages 5Ð9; May/July 1992( reprinted by the Institute for Defenseand Disarmament Studies )

FACING REALITY: THE FUTURE OF THE U.S

NUCLEAR WEAPONS COMPLEX Edited byPeter Gray Tides Foundation, 1992

THE MILITARY BALANCE 1992Ð1993 Col.Andrew Duncan et al International In-stitute for Strategic Studies, 1992

Trang 26

The greenhouse eÝect is a

geo-physical fact of life Atmospheric

gases such as carbon dioxide and

methane trap and hold heat, enabling

the earthÕs biota to survive Such gases

warm the surface of this planet by

about 33 degrees Celsius, from below

freezing to a current average of about

17 degrees C Models and analyses of

global warming generally agree that

most of the long-lived gases that

hu-man economic activity adds to the

at-mosphere make the earth warmer than

it would otherwise be Yet

discrepan-cies between theory and observation

persist The predicted warming based

on recent increases in concentrations

of greenhouse gases is slightly more

than the observed warming of the

at-mosphere In addition, the warming

trend in North America does not

ap-pear to follow the global pattern What

might account for these and other

de-viations of fact from theory?

The answer is ironic In all

probabili-ty, aerosols primarily composed of

sul-fates, themselves the result of

commer-cial activity, enhance the ability of the

atmosphere to reßect sunlight back into

space before it can reach the planetÕs

surface and participate in the warming

process The sulfate particles, about

0.1 to one micron in diameter, are

par-ticularly concentrated over the

indus-trial areas of the Northern Hemisphere

Their roles as contributors to acid rain,

as irritants and as obscurers of such

splendid vistas as the Grand Canyon

have been known for years But theircapacity to cool by scattering sunlighthas become a recognized force in cli-matic change only recently Clearly, boththe cooling eÝects of aerosols and thewarming caused by greenhouse gases

must be taken into account if we are toattain accurate climate models and ef-fective industrial policies

In theory, industrial aerosols are notthe only particles that can contribute tocooling Several kinds of aerosols exist

48

Sulfate Aerosol and Climatic Change

Industrial emissions of sulfur form particles that may be reflecting solar radiation back into space, thereby

masking the greenhouse effect over some parts of the earth

by Robert J Charlson and Tom M L Wigley

SULFUR FROM INDUSTRY and, to a

less-er extent, phytoplankton exless-erts many

environmental influences It cools the

earth by forming minute particles that

scatter sunlight back into space,

offset-ting the greenhouse effect in part

Sul-fate compounds also help to cause

hazi-ness, acid rain and ozone depletion

1 The main source of sulfur dioxide is industry Marine phytoplankton also

contributes sulfur in the form of dimethyl sulfide, which reacts with chemicals

in the air to form sulfur dioxide Precipitation and the circulation of air remove about half the sulfur dioxide

2 In the clear-sky process the sulfur dioxide forms sulfate

aerosol directly via chemical reactions with compounds

in the atmosphere

3 In the cloud process the sulfur dioxide is

oxi-dized by hydrogen peroxide in cloud droplets

Sulfuric acid in solution forms The droplets evaporate, leaving behind sulfate particles

Trang 27

4 Residing mostly in the lower troposphere, sulfate aerosol directly cools the earth

by reflecting sunlight The particles may also act as seeds for cloud condensation

and increase the reflectivity, or albedo, of clouds

5 When injected into the stratosphere by large volcanic eruptions, the sulfate

com-pounds can help destroy the ozone layer

6 The sulfate particles acidify rainwater, damaging lakes and plant life.

SULFATE HAZE

WASHOUT BY RAIN

DAMAGE BY ACID RAIN

INDUSTRIAL EMISSIONSEVAPORATING DROPLET

Trang 28

naturally They do not, however, seem

to be major factors causing change

Natural aerosolsÑmostly continental

dust, sea salt and marine sulfate

com-poundsÑhave probably remained

roughly constant in their

concentra-tion, distribution and properties for at

least a century Thus, they would not

have contributed to any observable

al-terations in climate Volcanic aerosols

have probably not added to long-term

eÝects The cooling trends precipitated

by the gigantic eruptions of Tambora

in 1815, Krakatoa in 1883 and

Pina-tubo in 1991 lasted only a few years

In stark contrast, man-made aerosolcompounds in the atmosphere have in-creased dramatically, primarily duringthe course of industrialization andmost rapidly since about 1950 Of allthe particulate pollutants humans cre-ate, climatologists have thus far fo-cused much of their attention on sul-fate compounds That is because alarge body of data, gathered in studies

of acid rain, makes sulfates the understood aerosol Other aerosol sub-stancesÑsoot from oil combustion, soildust from desertiÞcation and smokefrom slash-and-burn agricultureÑmay

best-have an impact approaching the nitude of that caused by industrial sul-fur Limited research Þndings, howev-

mag-er, render the uncertainties in ing those eÝects much greater

calculat-As one might expect for complexsystems such as the climate, determin-ing the amount of cooling by sulfateaerosol is not a straightforward task.Many variables complicate the eÝortÑamong them, the amount of sulfur inthe atmosphere, its distribution overthe globe, the mechanism of aerosolformation, the degree of reßectivity ofthe particles and their eÝect on clouds

An accurate prediction also depends

on making correct assumptions Someearly studies exploring the role of aero-sols on climate did not do so For ex-ample, one common and unsubstanti-ated supposition was that most of thehaze outside cities was a Ònatural back-groundÓ aerosol

Another early, implicit assumptionwas that processes at the earthÕs sur-face make most aerosol particles Butthat conclusion is valid for only twokinds of aerosols: those introduced into

CLIMATIC FORCING by human activity is evident in

calcula-tions of global heat gain during the Northern summer Every

July greenhouse gases warm the earth by about 2.2 watts per

square meter (left ); the effect is most pronounced over the

warm areas of the subtropics When the cooling by sulfateaerosol is included, however, the forcing drops to about 1.7

watts per square meter (right ) In fact, the cooling dominates

over industrial regions in the Northern Hemisphere

ROBERT J CHARLSON and TOM M L WIGLEY have combined their respective

exper-tise in atmospheric chemistry and the interpretation of temperature records to study

how sulfate aerosol aÝects the earth Charlson is professor of atmospheric sciences at

the University of Washington, where he received his Ph.D He earned B.S and M.S

de-grees in chemistry at Stanford University He holds six patents on instruments for

at-mospheric measurements and has served on numerous committees of the National

Academy of Sciences Wigley, the former director of the Climatic Research Unit at the

University of East Anglia in Norwich, England, now heads the Office for Interdisciplinary

Earth Studies at the University Corporation for Atmospheric Research ( UCAR ) in

Boul-der, Colo He received his Ph.D from the University of Adelaide in Australia

Trang 29

the atmosphere by wind (such as sea

salt and soil dust) and those arising

di-rectly from combustion ( for example,

industrial smoke or smoke particles

from forest and grass Þres) Studies

during the past decade indicate that

most sulfate aerosol originates from

chemical reactions of sulfur gases

dis-charged into the air These reactions

take place in the troposphere, that part

of the atmosphere extending from the

surface of the earth to an altitude of

about 10 kilometers

To calculate the increases of sulfur in

the troposphere, climatologists rely on

industrial emission rates These rates

act as excellent guides for estimating

changes in the average concentration

of atmospheric sulfate aerosol over

time Sulfur gases and the sulfate they

make last only a few days in the

tropo-sphere, so that the average

concentra-tion in the atmosphere is directly

pro-portional to the product of the emission

rate and the lifetime of the substances

Consequently, the primary effects

must mirror the geographic

distribu-tion of the sources of sulfur

More than two thirds of the sphereÕs supply of sulfur gases, mostlyemitted in the form of sulfur dioxide ( SO2), is man-made About 90 percent

tropo-of that amount arises in the NorthernHemisphere There human activity in-jects about Þve times the amount ofsulfur gases emitted naturally In theSouthern Hemisphere, man-made emis-sions currently equal only about onethird of natural emissions The mainnatural carrier of reactive sulfur is di-methyl sulÞde ((CH3)2S ), or DMS, whichoriginates from marine phytoplankton

In the absence of anthropogenic

sourc-es, DMS is thought to be the dominantsource of submicron particles A smallamount of sulfur (as hydrogen sulÞde

or sulfur dioxide, or both) comes fromvolcanoes and from swamps and bogs

The sulfur dioxide generally remains

in the hemisphere in which it was duced The thermal and chemical mix-ing of the two halves of the earthÕs at-mosphere requires about a yearÑfarlonger than the average lifetime of sul-fur dioxide or the sulfate aerosol itproduces Although the hemispheres

pro-are essentially decoupled regions as far

as aerosol distributions are concerned,the aerosols in the Northern Hemi-sphere may nonetheless inßuence theclimate worldwide, just as regionalcloud cover controls the average albe-

do, or reßectivity, of the earth

About half the amount of sulfur

gas-es is lost directly from the atmosphere;

it is either washed out by rain or reactschemically with plants, soil or seawa-ter The remainder goes on to oxidizewith compounds in the troposphereand hence to produce aerosol particles.Indeed, almost all types of sulfur-con-taining gases are chemically reactive inthe presence of oxidizing agents Themost important such agent is the hy-droxyl ( OH ) radical

The reactions that create sulfate

aerosol can loosely be dividedinto clear-sky and in-cloud pro-cesses In clear-sky processes, sulfurdioxide and DMS in the presence of wa-ter vapor react via a complex series ofsteps to produce gaseous sulfuric acid( H2SO4) The compound forms parti-

AVERAGE HEAT GAIN, JULY 1993 (WATTS PER SQUARE METER)

Trang 30

cles a fraction of a micron in size It

does so by condensing on existing

par-ticles or by interacting with water

va-por or other sulfuric acid molecules

This transformation is called

gas-to-particle conversion The sulfuric acid

then reacts with minute quantities of

ammonia to form varying hydrated

forms of ammonium sulfate (( NH4)2

SO4) salts In addition, DMS can react

to form another condensable species,

methane sulfonic acid ( CH3SO3H ), or

MSA Although MSA is an important

at-mospheric constituent and tracer

com-pound ( it has been measured in fossil

form in ice cores), the latest research

indicates that its aerosol has only a

small impact

Sulfate aerosol is also produced in

clouds This pathway begins when

sul-fur dioxide dissolves into existing cloud

droplets There it may be oxidized by

the small concentrations of aqueous

hydrogen peroxide ( H2O2) that formwhen two hydroxyl molecules combine

The oxidation reaction then forms furic acid and its ammonium salts insolution In the droplet the acid sulfateexists as a strongly hydrated form, inwhich water molecules are bonded tothe sulfate Evaporation removes some

sul-of the moisture Because the sulfatescling to water, the product of evapora-tion is a highly concentrated sulfate so-lution The result is a submicron aero-sol droplet that is chemically indistin-guishable from the aerosol produced

by gas-to-particle conversion

The strong chemical aÛnity that furic acid and its ammonium salts havefor water is highly signiÞcant in terms

sul-of the aerosolÕs ability to scatter light

When the tiny solution droplets mixwith humid air (such as over moist land

or oceans), they absorb moisture andgrow Larger particles scatter more vis-

ible light, thus explaining the increase

in haze when humidity is high At a ative humidity of 80 percent (the globalaverage value for air near the ground ),

rel-a given rel-amount of sulfrel-ate producesabout twice as much apparent haziness

as it does during a low-humidity day.Once formed through chemical reac-tions, the sulfate particles in the tropo-sphere can cool the climate in twoways: either directly, under clear skies,

by reßecting away some incoming solarradiation, or indirectly, by increasingthe reßectivity of clouds

In the direct, or clear-sky, eÝect thesulfate aerosol particles scatter sun-light out of the atmosphere and intospace; as a result, less solar radiationreaches the ground There are two ways

to estimate the fraction of incomingenergy lost to space One technique is

to conduct detailed optical calculationsbased on particle sizes and refractiveindices An alternative and currentlymore reliable approximation is simply

to make use of the observed tion between the amount of aerosol inthe atmosphere and the energy loss

correla-caused by scattering [see box on page

57 ] These analyses indicate that at

to-dayÕs levels man-made sulfate scattersabout 3 percent of the direct solarbeam About 15 to 20 percent of thisamount goes back into space, for a to-tal loss of about 0.5 percent The aver-age reduction of sunlight, however, isactually about half this amount, be-cause clouds cover about half the earth

at any given time On the ground, thedeprivation of sunlight is calculated to

be roughly about 0.2 to 0.3 percent

Is this loss at all signiÞcant? The

solar radiation reaching the layer

of sulfate haze near the groundamounts to roughly 200 watts persquare meter, so the implied lossamounts to about 0.4 to 0.6 watt persquare meter Because the NorthernHemisphere contains more aerosols,the average forcing there must begreater, probably around one watt persquare meter ( Climatologists use theterm ỊforcingĨ to refer to the eÝect offactors external to the atmosphere andoceans on the changes in the planetaryenergy balance.)

Such a loss of incoming energy mayseem small, but it is not inconsequen-tial The present-day increases of car-bon dioxide resulting from human ac-tivity amount to a gain of 1.5 watts persquare meter in the planetÕs heat bal-ance ( When other greenhouse gasessuch as methane and nitrous oxide areconsidered, the increase is about two

to 2.5 watts per square meter.) Hence,the cooling caused by sulfate aerosol is

Sulfur compounds in the air do more than just cool the earth

Investiga-tors have known for many years that sulfur contributes to the acidity of

rainwater and to the depletion of ozone in the stratosphere Acid rain comes

about in large part because of the oxidation of sulfur dioxide in the

atmo-sphere The oxidation process forms sulfuric acid, which creates aerosol

particles In the troposphere, these submicron-size particles attract water

Hence, they can act as nuclei for cloud condensation when the relative

hu-midity exceeds 100 percent The cloud droplets incorporate the acidic

in-gredient, which will be deposited on the earth’s surface as rain or snow

In-dustrial acidity can spread over perhaps 1,000 kilometers (about 600 miles)

from its source before the particles precipitate out

Sulfate particles help to deplete ozone when they reside in the

strato-sphere, that part of the mosphere above the tropo-sphere Deposited thereprimarily by enormous vol-canic eruptions, the sulfurparticles can provide sur-faces on which ozone-de-stroying compounds act[see “Polar StratosphericClouds and Ozone Deple-tion,” by Owen B Toon andRichard P Turco; SCIENTIFIC

at-AMERICAN, June 1991] cally, the effects of ozonedepletion in the strato-sphere are countered tosome degree by sulfateaerosol in the lower atmo-sphere The aerosol therereduces the amount of so-lar ultraviolet radiation thatreaches the ground and off-sets some of the increasesexpected from stratospher-

Ironi-ic ozone loss ( but of courseonly in those areas wheresulfate particles abound)

BRONZE MEMORIAL in Gettysburg National

Military Park shows discoloring by acid rain

Sulfur, Acid Rain and the Ozone Layer

Trang 31

comparable in magnitude to the

heat-ing caused by carbon dioxide, at least

in the patches of haze concentrated

over industrial regions

Needless to say, these calculations

are crude To quantify more precisely

the aerosol eÝect and to describe its

geographic distribution, researchers at

Stockholm University and the

Universi-ty of Washington used a meteorologic

model developed at the Max Planck

In-stitute for Chemistry in Mainz The

de-scription, which details the chemical

production and wind-driven transport

of particles generated from

anthropo-genic sulfur dioxide, enabled the

work-ers to produce a map of the change in

heat balance caused only by the direct

eÝect of anthropogenic sulfate This

model showed three large masses of

haze in the Northern Hemisphere One

mass, over the eastern U.S., creates

losses of solar radiation of more than

two watts per square meter The two

others, over Europe and the Middle

East, reßect up to four watts per square

meter The average over the Northern

Hemisphere, based on sulfur dioxide

emissions recorded in 1980, is 1.1

watts per square meter, happily close

to the crude calculation above

The second, indirect way sulfate

aero-sol cools the earth is by inßuencing the

albedo of clouds When in clouds, some

of the sulfate particles act as nuclei for

condensation The density of

cloud-condensation nuclei determines the

number and the size of cloud droplets

For a given amount of condensed

wa-ter, the number density in turn aÝects

the albedo of the cloud A 30 percent

rise in cloud albedo only over the

worldÕs oceans would be suÛcient to

counteract the average warming by

an-thropogenic carbon dioxide increases

during this century

Unfortunately, this indirect eÝect of

the sulfate particles has thus far

resist-ed reliable quantiÞcation Although

ob-servations show that

cloud-condensa-tion nuclei are greatly enhanced over

industrial regions, investigators do not

know how diÝerences in the number of

nuclei relate to the changes in the

amount or mass of anthropogenic

aero-sols As a result, estimating the

magni-tude of the indirect aerosol forcing is

not yet possible Satellite observations

suggest that the eÝect is not huge,

al-though theoretical analyses permit it to

be comparable to direct forcing

In view of the fact that the ability to

model completely the meteorologic

ef-fects of aerosols is limited, one may

wonder whether aerosol cooling is real

In particular, one may ask whether the

aerosol cooling is evident in the

obser-vational record The most

straightfor-ward way to answer this question is tocompare the changes in the NorthernHemisphere with those in the SouthernHemisphere As a whole, the globe haswarmed by about 0.5 degree C duringthe past 100 years [see ÒGlobal Warm-ing Trends,Ó by Philip D Jones and Tom

M L Wigley; SCIENTIFIC AMERICAN, gust 1990] If the enhanced greenhouseeÝect (that is, the additional warmingcaused by human activity) is the solemechanism for climatic forcing, thenthe Northern Hemisphere should warm

Au-a bit more quickly thAu-an the SouthernHemisphere The Southern Hemisphereholds most of the worldÕs oceans andhence has more inertia with respect tothermal changes

Yet the observations show

other-wise: since 1940 the NorthernHemisphere has warmed moreslowly In fact, the strong warmingtrend that occurred earlier this century

in the Northern Hemisphere ceasedaround 1940 and was not renewed un-til the mid-1970s, even though indus-trial emissions of greenhouse gasescontinued to rise over the entire peri-

od This reprieve in warming may haveresulted from the counteracting prop-erties of sulfate aerosol, at least to someextent Although the changes broadlyparallel the hypothesized aerosol cool-ing, they are not enough to prove acausal relation ( Indeed, the lack of amarked diÝerence between the warm-ing trends in the two hemispheresthroughout the 20th century imposes

an upper bound on the total tude of the aerosol forcing, which im-plies that the cloud albedo contribu-tion has been small.)

magni-Another piece of circumstantial dence comes from an analysis conduct-

evi-ed by the Unitevi-ed Nations mental Panel on Climate Change (IPCC)

Intergovern-In 1990 the panel pointed out a crepancy between the observed globalmean temperature changes and thepredictions made by climate models.The models suggested that the worldshould have warmed somewhat fasterthan the record indicates Sulfate aero-sol may help explain the discrepancy

dis-To see why, we need to introduce theconcept of Òclimate sensitivity.Ó In com-puter simulations of the climate, inves-tigators double the atmospheric carbondioxide concentration and then allowthe climate system to adjust to the new(warmer ) steady state The change inglobal mean temperature is a measure

of the sensitivity of the global averagetemperature to external forcing TheIPCC has given a Òbest guessÓ value of2.5 degrees C for this quantity, althoughthe sensitivity may in fact range from1.5 to 4.5 degrees C When observationsare compared with the results from cli-mate models designed to estimate spe-ciÞcally the time-dependent response

to observed changes in greenhouse-gasforcing, the implied climate sensitivity

is found to be a little less than 1.5 grees C In other words, the empiricalestimate of the climate sensitivity gives

de-a vde-alue more thde-an de-a full degree below

SULFATE AEROSOL sampled from the atmosphere was photographed through anelectron microscope The particles are about 0.1 micron in diameter

Trang 32

the IPCCÕs best guess and slightly

be-low the expected range

These numbers suggest that the

cur-rent global warming induced by

green-house gases may have exceeded the

observed 0.5 degree C rise and been

oÝset by some kind of cooling process

Natural variability of the climate could

account for the cooling Alternatively,

external factors may be responsible

The aerosol eÝect is an obvious

candi-date Indeed, factoring aerosol cooling

into models yields a value for climate

sensitivity that is a little above the

IPCCÕs best guess but well within the

expected range Unfortunately, none of

the conclusions is suÛciently

convinc-ing to allow us to jump out of the

bath-tub crying, ÒEureka!Ó

Although subject to considerable

quantitative uncertainty, the evidence

clearly indicates that aerosols have a

signiÞcant inßuence on the climate,

comparable to that produced by

green-house gases In fact, from 1880 to 1970,

aerosol cooling may more or less have

canceled out the enhanced greenhouse

eÝect in the Northern Hemisphere

( Since 1970 emissions of greenhouse

gases have increased more rapidly than

have those of aerosol particles.) The

cooling caused by aerosols may even

dominate in some areas Recent work

by JeÝrey T Kiehl and Bruce P Briegleb

of the National Center for

Atmospher-ic Research in Boulder, Colo., suggeststhat aerosols produce a net cooling inlocal regions of the eastern U.S., southcentral Europe and eastern China

A crucial complication, however, ishidden in the use of the words Òcancelout.Ó The term is deceptive Aerosolcooling and the greenhouse eÝect havecharacteristics that prevent them fromneatly oÝsetting each other First, thecooling and warming occur mostly overdiÝerent parts of the world As we men-tioned, sulfate cooling happens primar-ily over industrial zones in the North-ern Hemisphere Although carbon diox-ide spreads throughout the atmosphere,greenhouse forcing is more potent overthe subtropical oceans and deserts

Both types of forcing also diÝer porally The heat-trapping property ofcarbon dioxide varies only moderatelyduring the course of a day and through-out the year In contrast, the aerosoleÝect has a distinctive diurnal and sea-sonal character It acts more vigorously

tem-in the summer and, of course, operatesonly during daylight hours Thomas R

Karl of the National Climatic Data ter and his co-workers have shown thatthe U.S., the former Soviet Union andChina all have displayed increases inannual average minimum temperaturesbut no increases in the maximum tem-

Cen-peratures It is possible, therefore, thataerosols may now be canceling outgreenhouse warming during the day(when temperatures are highest) butnot at night (when temperatures areusually lowest)

How should one regard the

evi-dence garnered to date foraerosol cooling? A good way

to judge is to compare it with the hanced greenhouse eÝect Although theIPCC recommends large-scale cuts inemissions of carbon dioxide, it has not been able to say conclusively thatchanges in greenhouse-gas concentra-tions have caused the observed globalwarming A deÞnitive verdict is diÛcultbecause the magnitude of the eÝect todate is roughly comparable to the natu-ral variability of the climate In otherwords, the signal is about the samestrength as the background noise.Precisely the same situation applies

en-to aerosol forcing of the climate tologists have not yet found the Òsmok-ing gunÓ that would prove beyonddoubt the existence of sulfate cooling.Yet the strong theoretical basis of theaerosol eÝect, the consistency of thedata with expectations and the lack ofany counterevidence give us consider-able conÞdence in its reality Still, twolarge areas of uncertainty limit our pre-dictive capability : understanding thefundamental physics of global climaticchange and forecasting the levels of fu-ture emissions of sulfur dioxide Rightnow the estimated uncertainty in forc-ing caused by the best-understood an-thropogenic aerosolÑsulfatesÑis muchgreater than the uncertainty in forcingcreated by greenhouse gases For sul-fates, the amount of cooling ranges by

Clima-a fClima-actor of two; for greenhouse gClima-ases,the degree of warming is known towithin roughly one tenth to one Þfth.Nevertheless, we can make a few gen-eral predictions Because anthropogen-

ic sulfate aerosol is conÞned for themost part to speciÞc parts of the North-ern Hemisphere, greenhouse warmingshould proceed relatively unabated inthe Southern Hemisphere (and in morerural parts of the Northern Hemi-sphere) The IPCC forecast of a sea-lev-

el rise of a few tens of centimeters overthe next 50 years therefore remainsreasonable A substantial fraction of thisrise is associated with the global-scalethermal expansion of the warming wa-ter Other repercussions are somewhatharder to predict, because they depend

on the regional details of the combinedaerosol and greenhouse forcing.Reducing the emissions of carbondioxide and sulfur dioxide would havetwo contrasting outcomes Because the

ANTHROPOGENIC SULFUR EMISSIONS now far outstrip those from natural

sourc-es, such as marine phytoplankton It is estimated that humans currently release

be-tween 65 billion to 90 trillion grams, or teragrams, of sulfur every year

Trang 33

carbon cycle and the climate system

are slow to respond to changes, carbon

dioxideÐinduced warming would

con-tinue for decades In contrast, reduced

sulfur dioxide emissions would rapidly

result in a cessation of the cooling

be-cause of sulfate aerosolÕs short

atmo-spheric lifetime Thus, the ironic result

of curtailing fossil fuel use may initially

be a warming, particularly in industrial

areas

Of course, many issues about

cli-matic forcing and sulfur remain

open Do other sources of

aero-sol, such as extensive biomass

com-bustion in the tropics, have a more

substantial impact than has commonly

been assumed? Even more important,

how do meteorologic processes

re-spond to forcing that does not act

uni-formly over the earth?

One might be tempted to conclude

that the uncertainty leaves the issue of

human-induced climatic change

unre-solved Therefore, one might reason, no

changes in policy should be plated That line of thinking, we believe,

contem-is a serious mcontem-istake Obviously, no acea presents itself that would cure theproblem of global change For instance,decreasing emissions of sulfur dioxide

pan-to reduce acid rain might accelerateglobal warming What does seem clear

is that a better and more complete derstanding is needed and that a cau-tious path be taken Many good argu-

un-ments can be made for conserving sil fuels and reducing emissions of bothcarbon dioxide and sulfur dioxide Do-ing so sooner would be less disruptive

fos-to the climate than waiting, becausethese industrial gases humans are re-leasing at this moment are having animpact on the weather that will persistfor decades The longer the world de-lays implementing reductions, the moresevere will be the consequences

THE CHANGING ATMOSPHERE Thomas E

Graedel and Paul J Crutzen in Scientific American, Vol 261, No 3, pages 58Ð68;

September 1989

CLIMATE FORCING BY ANTHROPOGENIC

AEROSOLS R J Charlson, S E Schwartz,

J M Hales, R D Cess, J A Coakley, Jr.,

J E Hansen and D J Hofmann in ence, Vol 255, pages 423Ð430; January

Sci-24, 1992

CLIMATE CHANGE: THE IPCC SCIENTIFIC

ASSESSMENT Edited by J T Houghton,

et al Published for the tal Panel on Climate Change by Cam-bridge University Press, 1990 And: CLI-MATE CHANGE 1992: THE SUPPLEMEN-TARY REPORT TO THE IPCC SCIENTIFIC

Intergovernmen-ASSESSMENT Edited by J T Houghton et

al Cambridge University Press, 1992

THE RELATIVE ROLES OF SULFATE SOLS AND GREENHOUSE GASES IN CLI-MATE FORCING J T Kiehl and B P Brie-

AERO-gleb in Science, Vol 260, pages 311Ð314;

April 16, 1993

Atmospheric sulfate aerosol scatters light in all

direc-tions About 15 to 20 percent of the light is scattered

back into space The backscattering constitutes the direct

effect of atmospheric aerosol on incoming radiation The

light-scattering efficiency of aerosol, represented by the

Greek letter alpha (α), is high, even at low humidity: each

gram represents an area of about five square meters

Moisture increases the scattering by making the aerosol

expand At the global average relative humidity, the

effi-ciency doubles, to almost 10 square meters per gram

One can use this value to estimate the magnitude of the

direct effect of anthropogenic sulfate

The rate at which light is lost from the solar beam is

de-fined by the scattering coefficient, represented by the

Greek letter sigma (σ, expressed in units of per meter)

This value is determined by the amount of aerosol mass,

M ( in grams per cubic meter), multiplied by the

light-scat-tering efficiency: σ=αM When both sides of this

equa-tion are integrated over altitude, z, a dimensionless

quan-tity called the aerosol optical depth and represented by

the Greek letter delta (δ), results:

Here B is the world average burden of anthropogenic

sulfate aerosol in a column of air, in grams per cubic

me-ter The optical depth is then used in the Beer Law (which

describes the transmission of light through the entire

ver-tical column of the atmosphere) The law yields I/Io= e–δ,

where I is the intensity of transmitted radiation, Io is the

incident intensity outside the atmosphere and e is the

base of natural logarithms In the simplest case, where

the optical depth is much less than 1, δis the fraction of

light lost from the solar beam because of scattering The

question, then, is just how large δis or, more properly,that part of it that results from man-made sulfate

This global average burden of anthropogenic sulfateaerosol can be estimated by considering the entire atmo-spheric volume as a box Because the lifetime of sulfate

aerosol is short, the sum of all sulfate sources, Q, and its lifetime in the box, t, along with the area of the earth, determine B:

About half the man-made emissions of sulfur dioxidebecome sulfate aerosol That implies that currently 35 tera-grams (35×1012

grams) per year of sulfur in sulfur ide is converted chemically to sulfate Because the molec-ular weight of sulfate is three times that of the elemental

diox-sulfur, Q is about (3)(35×1012

) or 1.1×1014

grams peryear Studies of sulfate in acid rain have shown that sul-fates persist in the air for about five days, or 0.014 year.The area of the earth is 5.1×1014

square meters

Substi-tuting these values into the equation for B yields about

2.8×10–3

gram per square meter for the burden

This apparently meager amount of material produces asmall but significant value for the aerosol optical depth.Using the value of scattering efficiency (α) of five squaremeters per gram and a factor of two for the increase inscattering coefficient because of relative humidity, the es-timated anthropogenic optical depth becomes δ≈5×2

×(2.8 ×10–3

)≈0.028 This value means that about 3 cent of the direct solar beam fails to reach the earth’s sur-face because of man-made sulfate A smaller amount—perhaps (0.15)(3 percent), or about 0.5 percent—is thuslost to space This scattering operates over the noncloudyparts of the earth About half the earth is cloudy at anygiven time, so that globally 0.2 to 0.3 percent is lost.How Much Light Do Aerosols Reflect Away?

area of the earth

Trang 34

All animals develop from a single

fertilized egg cell that goes

through many rounds of

divi-sion, often yielding millions of

embry-onic cells In a dazzling and still

myste-rious feat of self-organization, these

cells arrange themselves into a

com-plete organism, in which bone, muscle,

brain and skin integrate into a

harmo-nious whole The fundamental process

is constant, but the results are not :

hu-mans, mice, ßies and worms represent

a wide range of body designs

Noting that variation, biologists have

often supposed that the molecular

ar-chitects of body formĐthe genetic

pro-cesses that control embryonic

develop-ment in diÝerent speciesĐwould also

be quite diverse There is compelling

evidence, however, that an interrelated

group of genes, called HOM genes in

invertebrates and Hox genes in

verte-brates, governs similar aspects of body

design in all animal embryos

In at least some of the molecular

sys-tems that mold our form, we humansmay be much more similar to our fardistant worm and insect relatives than

we might like to think So similar, infact, thatĐas our work has shownĐcu-rious experimenters can use some hu-

man and mouse Hox genes to guide the

development of fruit-ßy embryos

The story of these universal lar architects actually begins with thepioneering genetic studies of Edward

molecu-B Lewis of the California Institute ofTechnology Lewis has spent much of

the past 40 years studying the bithorax

complex, a small cluster of homeotic

genes in the fruit ßy Drosophila nogaster The Greek word homeo means

mela-Ịalike,Ĩ and the ßy homeotic genes are

so named because of their ability, whenmutated, to transform one body seg-ment of the fruit ßy into the likeness of

another Mutations in bithorax complex

genes usually cause such tal defects in the posterior half of the

developmen-ßy body plan Thomas C Kaufman ofIndiana University and his colleagueshave discovered and studied a second

cluster of ßy homeotic genes, the tennapedia complex (named for the founder gene of the complex, Antenna- pedia) Mutations in these genes usual-

An-ly cause homeotic defects in the

anteri-or half of the ßy body plan

It is often the case in biology thatbizarre defects in odd organisms con-tain the clues to solving importantproblems, and few biological phenome-

na are more bizarre than the tions in body design caused by home-otic mutations For example, some mu-

disrup-tations in the Antennapedia gene can

cause the antennae on the head of thefruit ßy to be transformed into an ex-tra pair of thoracic legs Surprisingly,some of the animals that develop theextra legs survive, feed and even matewith normal ßies

Antennapedia adults are rare

excep-tions, because most mutations in meotic genes cause fatal birth defects

ho-in Drosophila Nevertheless, even those

dying embryos can be quite instructive.For instance, Ernesto Sanchez-Herreroand Gines Morata of the IndependentUniversity of Madrid found that elimi-

nation of three genes in the bithorax complexĐUltrabithorax, abdominal-A and Abdominal-BĐis lethal Yet such

mutant embryos survive long enough

to develop specialized structures thatindicate all eight abdominal segmentsare replaced by thoracic segments.Most people would be unnerved byanalogous birth defects in mammals,but these grotesque defects in ßies can

be observed with equanimity

From his original genetic studies

of the bithorax complex genes,

Lewis derived two key insights.The Þrst was that the normal function

of these homeotic genes is to assigndistinct spatial (or positional ) identities

to cells in diÝerent regions along theßyÕs anterior-posterior axis That is,they ỊtellĨ cells that they are part ofthe ßyÕs head or thorax or abdomen.These identities are to some extent ab-stract, in that the positional coordinatesassigned by homeotic genes are inter-preted in dissimilar ways in diÝerent

developmental settings Antennapedia

assigns thoracic identity during boththe embryonic and pupal stages of theßyÕs life cycle, even though the struc-tures (sense organs, legs, wings and soon) that develop along the thorax diÝer

in larvae and adults

LewisÕs second important insight was

that the linear order of the bithorax

complex genes on the fruit ßyÕs mosome exactly paralleled the order ofthe body regions they speciÞed alongthe embryoÕs anterior-posterior axis

chro-58 SCIENTIFIC AMERICAN February 1994

WILLIAM MCGINNIS and MICHAEL

KUZIORA investigate the eÝects of the

homeobox supergene family on animal

development McGinnis is professor of

molecular biophysics and biochemistry,

with an appointment in biology, at Yale

University After earning his bachelorÕs

degree in biology from San Jose State

University in 1978, he continued his

studies in molecular biology at the

Uni-versity of California, Berkeley While

working at the University of Basel

dur-ing the mid-1980s, McGinnis and

Mi-chael Levine discovered the homeobox

sequence motif in genes of Drosophila

fruit flies Kuziora has been assistant

professor of biology at the University of

Pittsburgh since 1991 He received his

Ph.D from the Baylor College of

Medi-cine and worked with McGinnis for five

years at Yale as a postdoctoral fellow

The Molecular Architects

of Body Design

Putting a human gene into a fly may sound like the basis

for a science fiction film, but it demonstrates that nearly

identical molecular mechanisms define body shapes in all animals

by William McGinnis and Michael Kuziora

Trang 35

EMBRYOS of vertebrate animals as diverse as Þsh, manders, birds, rabbits and humans show great similar-

sala-ities early in their development Drosophila fruit ßies

and other invertebrates develop along a very diÝerentpath, yet at the earliest stages they and the vertebratesshare a common pattern of expression of the so-calledhomeobox genes That discovery reveals that despitethe diÝerences in the Þnal appearance of the animals,they use closely related genes to specify parts of thebody along the anterior-posterior (or head-tail ) axis.ANTERIOR

Trang 36

The same relation also holds for the

genes of the Antennapedia complex.

United by these shared characteristics,

the genes in the bithorax and

Antenna-pedia groupings are collectively

re-ferred to as the HOM complex.

Apartial understanding of how the

HOM complex genes determine

axial positions in the fruit-ßy

body plan can come from looking at

where those genes are active in

em-bryos The HOM genes are present in

the DNA of all of a ßyÕs cells but are

ac-tive only in some of them When

acti-vated, the HOM complex genes are

cop-ied as molecules of messenger RNA,

which serve as templates for the

syn-thesis of HOM proteins During early

developmental stages, before regions

of the embryo show any signs of their

eventual fates, the diÝerent HOM

com-plex genes are activated in successive

stripes of cells along the

anterior-pos-terior axis Some of these stripes of

ac-tivation overlap, but each HOM

com-plex gene has a unique anterior ary of activation in the body plan

bound-If deletion of a gene or some similarincident interferes with the expression

of a HOM protein, then embryonic cellsthat normally contain high levels ofthat protein often undergo a homeotictransformation That transformation

occurs because of a backup HOM gene

that is already active in the same cellsand that can substitute its own posi-tional information For instance, if the

function of the Ultrabithorax gene is

eliminated from cells within a ßyÕs

an-terior abdominal region, Antennapedia

will take over the development of thatregion As a result, structures normallyassociated only with the thorax (which

Antennapedia helps to specify) also

ap-pear more posteriorly

Homeotic transformations can alsoresult from mutations that cause ahomeotic gene to become active in an

inappropriate position The

Antennape-dia mutations in adult ßies are caused

by activity of Antennapedia in the head,

where that gene is normally turned oÝ

In summary, the genetic evidence

indi-cates that each HOM complex gene is

needed to specify the developmentalfate of cells in a certain position on theanterior-posterior axis: the posteriorhead, anterior thorax and so on Moreimportant (and more instructive abouttheir biological function), the activity of

HOM complex genes is apparently

suÛcient to determine the fate of atleast some cells, even when those cellswould not normally fall under a givengeneÕs inßuence

The genes of the HOM complex

are virtually the only ones in

Drosophila that have those

prop-erties They also share an interestingresemblance at the structural level be-cause all of them are members of thehomeobox gene family Homeoboxesare DNA sequences that carry the de-scriptions for making a related group

of protein regions, all about 60Ðaminoacid residues in size, called homeodo-

mains The homeo- preÞx in the name

of these domains stems from their

ini-tial discovery in Drosophila HOM

pro-teins Since then, however, mains have been found in many otherproteins with varying degrees of simi-

homeodo-larity The homeodomains of the sophila HOM proteins are especially

Dro-similar to one another, which suggeststhey are closely related For that rea-

son, they are often referred to as tennapedia-class homeodomains.

An-What do these HOM proteins do atthe biochemical level? Only a super-Þcial answer can be given at present.They belong to a large group of pro-teins whose function is to bind to DNA

in the regulatory elements of genes.The right combination of these boundproteins on a DNA regulatory elementwill signal the activation or repression

of a geneÑthat is, to start or stop ing that geneÕs encoded protein Inves-tigators have shown that the homeo-domain region of the HOM proteins isthe part that directly interacts with theDNA binding sites

mak-We are fascinated by the contrast tween the structural similarity of theHOM proteins and their varied, speciÞceÝects Here is a family of proteins thatall bind to DNA and are presumablyderived from a single ancestral Anten-napedia-class protein Yet their roles indevelopment are remarkably diverse:one protein assigns cells to becomeparts of the head, another assigns cells

be-to become thorax and so on It seemslikely that HOM proteins designate var-

HOMEOTIC TRANSFORMATIONS, in which body parts develop in the wrong

posi-tions, occur in fruit ßies that have mutations in their homeobox genes Mutations

of the Antennapedia gene, for example, can cause belts of thoracic denticles

(spikes) to appear on the heads of larvae (top right ) Another developmental

con-sequence of the mutation is that the mutant adults have legs growing in place of

antennae (bottom right ) A normal larva and adult are shown at the left.

Trang 37

ious positions along the

anterior-poste-rior axis by regulating the expression

of what may be large groups of

subor-dinate genes The functional speciÞcity

of the HOM proteins can therefore be

deÞned by the diÝerences between

them that allow them selectively to

reg-ulate certain genes in embryos

To learn more about this speciÞcity,

we decided in 1986 to construct

chime-ric HOM proteins that had components

derived from diÝerent sources ( The

chimera, a monster of Greek

mytholo-gy, was part lion, part goat and part

snake.) By testing the function of these

chimeric proteins, we thought it would

be possible to deÞne which subregions

of the HOM proteins determined their

selective regulatory abilities

For the subjects of our Þrst

experi-ments, we chose the HOM proteins

De-formed, Ultrabithorax and

Abdominal-B These proteins have structurally

sim-ilar homeodomains: that of the De-

formed protein is identical to that of

Ultrabithorax protein at 44 of its 66

amino acidsÑbut they share no

exten-sive resemblance in other regions Each

of these proteins also exerts an

inßu-ence on other genes in the HOM family

Thus, the Deformed protein selectively

activates the expression of its own

gene; Ultrabithorax protein represses

the expression of the Antennapedia

gene; and Abdominal-B protein

regu-lates its own gene and those of others

in the HOM complex, including

Anten-napedia, Ultrabithorax and

abdominal-A We knew we could use these

auto-and cross-regulatory relationships in

tests of the speciÞc functions of

chi-meric HOM proteins

The Þrst challenge was to create

genes that would make the chimeric

homeotic proteins we desired

Recom-binant DNA techniques make that feat

possible through the splicing of bits

and pieces of genes at the DNA level If

the gene engineering is done with care,

protein domains can be very precisely

moved from one protein to another

while retaining their functional

charac-teristics We then had to make sure that

the chimeric genes would be active

in all embryonic tissues We therefore

used a method worked out a few years

previously by Gary Struhl, now at

Co-lumbia University, that involves

attach-ing the gene to regulatory DNA

sequenc-es that can be activated by a mild heat

shock Finally, we inserted our

heat-in-ducible HOM gene chimeras into

Dro-sophila chromosomes by a technique

called P-element transformation

The Drosophila ßies that we

trans-formed in this way thereafter carried

the chimeric genes in every cell of their

body, and those genes would producechimeric proteins at any stage of devel-opment if we simply raised the temper-ature of the ßiesÕ growth chamber to

37 degrees Celsius for a brief period

(Drosophila prefer to live at 25 degrees

C but can tolerate 37 degrees C for anhour or two with no ill eÝects.) Usingthese animals, we could assay the abili-

ty of the chimeric proteins to act onthe regulatory elements of target genes

in their normal chromosomal positionsand in their natural embryonic environ-mentÑa demanding test that closelymimics the usual conditions underwhich these proteins operate

Because HOM proteins have

high-ly similar homeodomains, theybind to nearly identical DNA siteswhen tested in the laboratory It there-fore initially seemed likely that the fea-tures giving each protein its functionalspeciÞcity would be found outside thehomeodomainÑin the parts of the pro-teins that were most individual Yet asoften happens when simple deductivereasoning is applied to biological prob-lems, that expectation was wrong

We found that if we removed the tive homeodomain from a Deformed

na-protein and put an Ultrabithorax meodomain in its place, the chimeric

ho-protein lost the ability to regulate formed gene expression in embryos In-

De-stead the new protein acted on the

ex-pression of the Antennapedia geneÑ

much as a normal Ultrabithorax protein would By transferring the Ultra-bithorax homeodomain to Deformed,

we had apparently also transferred itsselective regulatory abilities Anotherhomeodomain swap experiment gave

us similar results A Deformed proteincarrying an Abdominal-B homeodo-main instead of its own mimicked theregulatory speciÞcity of an Abdominal-

B protein

The chimeric proteins did not behaveexactly like the protein from whichtheir homeodomain was derived Boththe Deformed/Ultrabithorax chimeraand the Deformed/Abdominal-B chi-mera activated expression of their tar-get genes, whereas the normal Ultra-bithorax and Abdominal-B proteins re-pressed expression of the same genes.Presumably, regions of the Deformedprotein outside the homeodomain re-gion supply a strong activation func-tion that can work with any of theseHOM homeodomains Consistent with

HOMEOBOX GENE COMPLEXES have been identiÞed in both invertebrates and

ver-tebrates Drosophila have HOM genes, which occupy the same order on the ßy

chro-mosome as the anterior-to-posterior order of body regions whose development

they control Mice and humans have Hox genes, which are closely related to bers of the HOM complex and show the same spatial and functional arrangement.

D4 D3 D1

MOUSE HoxB GENES

MOUSE HoxA GENES

HUMAN HOXD GENES

Trang 38

this notion, Deformed does have a few

regions of protein sequence that are

rich in the types of amino acids

charac-teristic of Òactivation domainsÓ in

oth-er gene regulatory proteins

Similar experiments on the

function-al speciÞcity of HOM proteins have function-also

been carried out by Richard Mann and

David S Hogness of Stanford University

and by Greg Gibson and Walter J

Gehr-ing and their colleagues at the

Univer-sity of Basel Their experiments were

based on evaluations of the homeotic

transformations that mutant and

chi-meric HOM proteins induced in

devel-oping ßies Because they were looking

at the developmental eÝects of the HOM

proteins rather than just at their

ef-fects on gene expression, those

investi-gators were using a more demanding

measure of HOM protein function than

the one we applied Yet their results,

too, support the idea that much (thoughnot all ) of the functional speciÞcity ofthe HOM proteins resides in the smalldiÝerences within or immediately adja-cent to the homeodomain regions

To us, all those Þndings also

suggest-ed that certain long-shot experimentsalready ongoing in our laboratory, forwhich we had only faint hopes of suc-cess, actually had a chance of yieldinginterpretable results Those experimentsinvolved functional assays of mouseand human homeodomain proteins in

Drosophila embryos To convey the

sig-niÞcance of those tests, we need to view what is known about the mam-

re-malian Hox genes.

During the past nine years, genes that

contain Antennapedia-class

homeobox-es have been found in the chromosomhomeobox-es

of many animal species besides sophila Such genes have been carefully

Dro-studied in frogs, mice and humans,

where they are called Hox (short for

ÒhomeoboxÓ) genes In both mice and

humans, Hox genes cluster into four

large complexes that reside on ent chromosomes In their organiza-tion and patterns of embryonic expres-

diÝer-sion, the genes of the Hox complexes

share intriguing likenesses to the genes

of the ßy HOM complex For example, one can identify Hox genes that structurally resemble the HOM genes labial, proboscipedia, Deformed, Antennape- dia and Abdominal-B The equivalent Hox and HOM genes are arranged in

the same linear order within their spective complexes

re-A further parallel has been observedboth by Denis Duboule of the Universi-

ty of Geneva and Pascal DollŽ at theCNRS Laboratory of Eukaryotic Molecu-lar Genetics in Strasbourg and by RobbKrumlauf and his colleagues at the Na-tional Institute for Medical Research inLondon They have assembled convinc-ing evidence that the patterns of ex-pression for the two types of genes are

alike That is, the Hox genes are

activat-ed along the head-tail axis of the earlymouse embryo in the same relative

order that the HOM genes are

activat-ed on the anterior-posterior axis of

Drosophila.

Structural similarities between themouse and ßy proteins are mainly lim-ited to the homeodomain regions FlyAntennapedia and mouse HoxB6 arenearly identical in the amino acid se-quence of their respective homeodo-

HOMEODOMAINS are the highly similar60Ðamino acid regions of the proteinsmade by all homeobox genes Each let-ter in the consensus string represents

an amino acid; deviations from thatconsensus are shown for several close-

ly related HOM and Hox proteins

EXPRESSION of the Deformed gene in ßy embryos, as

re-vealed by a brown dye, is normally conÞned to a band of cells

that become posterior head structures (left ) Genetically

en-gineered embryos that carry heat-inducible Deformed genes,

however, will produce the Deformed protein in every cell of

their body after a brief exposure to heat (right ) The

devel-opmental abnormalities found in such embryos can be used

to infer HOM gene function.

H A

Trang 39

mains (they diÝer at only four of 61

positions), which means that these two

proteins resemble each other more

than Antennapedia does any other ßy

HOM protein In an evolutionary sense,

this information argues that HoxB6

and Antennapedia are structural

homo-loguesÑthat is, they descended from a

common ancestral gene diÝerent from

the one that gave rise to, say,

Abdomi-nal-B or Deformed.

By the same reasoning, the similarity

between the entire HOM complex and

the Hox complexes argues that the most

recent common ancestor of Drosophila,

mice and humansÑa wormlike creature

that lived about 700 million years ago,

give or take a few hundred million

yearsÑhad a protocomplex of

Anten-napedia-class homeobox genes The

ex-act type and arrangement of genes in

that complex remain a mystery

Never-theless, we can be conÞdent, using the

modern HOM and Hox complexes as

guides, that the ancient protocomplex

contained structural homologues of

labial, proboscipedia, Deformed,

Anten-napedia and Abdominal-B This overall

view of HOM and Hox gene evolution is

strongly supported by research on

bee-tle homeotic genes by Richard W

Bee-man of the U.S Department of

Agricul-ture and Rob E Denell of Kansas State

University and by recent reports from

many laboratories that the primitive

roundworm Caenorhabditis elegans also

has a HOM complex distantly but

rec-ognizably related to the Drosophila

HOM and vertebrate Hox complexes.

All this structural evidence, though

suggestive, still does not directly

tell us whether HOM and Hox

proteins do serve the same

develop-mental function in embryos After all,

the mouse and ßy gene complexes have

been in diÝerent evolutionary lineages

for hundreds of millions of years, with

plenty of time to evolve new or

diver-gent abilities So the similarities in

struc-ture and expression might be

histori-cal quirks and not trustworthy

indica-tors of functional resemblance between

present-day HOM and Hox proteins

One approach to the problem is to

explore the biological eÝects of Hox

genes in vertebrate embryos and to

compare them with what is known

about the eÝects of HOM genes in

vertebrates For instance, does the

in-appropriate activation or speciÞc

inhi-bition of Hox gene function during

mouse development cause homeotic

transformations? In one eÝort to

an-swer this question, Peter Gruss and his

colleagues at the Max Planck Institute

for Biophysical Chemistry in Gšttingen

created strains of mice whose embryosproduce HoxA7 protein in the headand anterior cervical region Normally,HoxA7 protein (which is similar to theAntennapedia and Ultrabithorax pro-

teins of the HOM complex) is most

abundant in the posterior cervical andanterior thoracic regions and is exclud-

ed from more anterior parts Some mice

in which HoxA7 is expressed

inappro-priately develop deformities of the earand palate and occasionally have ho-meotic transformations of the cervicalvertebrae

The diÛcult converse experimentÑ

knocking out Hox gene functionÑhas been accomplished for HoxA3 by Os-

amu Chisaka and Mario R Capecchi of

the University of Utah and for HoxA1

by Thomas Lufkin and Pierre Chambonand their collaborators at CNRS in

Strasbourg Their work has shown that

some structures in the anterior regions

of mouse embryos do depend on those

genes Mutation of the HoxA3 gene

re-sults in mice that die just after birthwith a complicated set of head andneck deformities, including abnormallyshaped bones in the inner ear and faceand the absence of a thymus

Such deformities are reminiscent of

a human congenital disorder called GeorgeÕs syndrome, raising hopes that

Di-the study of HOM and Hox genes will

be of practical beneÞt in explainingsome human birth defects Much moreresearch needs to be done before biolo-gists have a good understanding of how

Hox genes participate in the

develop-mental design of mice and humans, butthese and other initial experiments cer-

tainly suggest that the Hox and HOM

genes serve comparable purposes

In our own work, we have tried tomake a direct comparison by testing

whether Hox proteins can take theplace of HOM proteins in developing

Drosophila embryos Ideally, one would

accomplish this swap by completely

re-placing the HOM gene of a ßy with its Hox homologue; the Hox gene might

then be expressed only when and

where the HOM gene would be

ordinar-ily Unfortunately, such an experiment

is not yet feasible, because the genes intheir entirety are too big to be manipu-lated by current technology Still, wecould do the next-best possible thing :

by using Hox DNA sequences linked to

heat-inducible regulatory elements, wecould make all the cells of a developing

ßy express a Hox protein

The Þrst protein that we and our

laboratory colleague Nadine Ginnis tested in this way was thehuman HOXD4 protein, the equivalent

Mc-of a mouse HoxD4 ( When referring

speciÞcally to human genes, the HOX

label is capitalized to conform withstandard genetic nomenclature.) Thegene for this human protein, which has

a homeodomain like that of the ßy formed protein, was isolated and char-acterized in 1986 by Fulvio Mavilio andEdoardo Boncinelli and their colleagues

De-at the Institute for Genetics and physics in Naples

Bio-In Drosophila, when the Deformed

gene is expressed outside its normalanterior-posterior limits, the adult ßiessuÝer a variety of head abnormalities,such as the absence of a ventral eye

We were amazed to Þnd that the man HOXD4 protein, when expressed

hu-in develophu-ing ßy cells, caused the samedeformities We could not attributethese changes entirely to the humanprotein, however : our experiments in-dicated that the human protein was

GENETIC TARGETS of homeodomain proteins are largely determined by the meodomain regions of those proteins For example, a chimeric Deformed proteincarrying an Ultrabithorax homeodomain acts on the same genes as does Ultra-bithorax Yet the regulatory eÝect of the chimeraÑactivationÑis more like that ofDeformed because of protein regions outside the homeodomain

ho-CHIMERIC Deformed/ Ultrabithorax PROTEIN

Deformed PROTEIN Ultrabithorax PROTEIN

Deformed GENE Antennapedia GENE

ACTIVATE

Trang 40

promoting the expression of the ßyÕs

Deformed gene as well ( Remember

that one normal eÝect of the Deformed

protein is that it activates its own gene,

in a cycle of positive feedback.) The

hu-man HOXD4 protein was therefore

mimicking the eÝects of inappropriate

Deformed expression becauseÑat least

in partÑit was causing inappropriate

Deformed expression Nevertheless, we

could see that HOXD4 did act like a

weak but speciÞc replica of its

Drosoph-ila homologue.

Encouraged by this result, Jarema

Malicki, a graduate student in our

lab-oratory, tested the function of the

mouse HoxB6 protein in developing

ßies HoxB6, which Klaus Schughart and

Frank H Ruddle identiÞed and

charac-terized a few ßoors away from us at

Yale University, has a homeodomain

that is highly similar to Antennapedia

protein The eÝects of HoxB6 protein

expression in developing ßy cells was

spectacular and unmistakably

homeot-ic In Drosophila larvae the HoxB6

pro-tein caused much of the head region to

develop as if it were thoracic: instead

of a larval head skeleton, the

trans-formed ßies produced denticle belts,

rows of spikes that are usually

ar-ranged on the bellies of Drosophila In

Drosophila adults, HoxB6 caused a

ho-meotic transformation of the antennae

into thoracic legs Both the larval and

adult homeotic transformations weremuch like those caused by the inappro-priate expression of Antennapedia pro-tein throughout the body

What can one make of these

evo-lutionary swap experiments?

First of all, they reinforced ourconclusions that the homeodomainsthemselves determined much of theregulatory speciÞcity of the proteins:

the homologous ßy and vertebrate teins have little in common outside thehomeodomain region In addition, theexperiments suggested that from afunctional standpoint, the homologousproteins are at least somewhat inter-changeable and have similar Òmean-ingsÓ for early embryos The system fordetermining anterior-posterior axial po-sitions has evidently changed little inthe past 700 million years

pro-If one were to imagine the

complicat-ed network of interactions betweengene regulatory proteins inside an or-ganism as a jigsaw puzzle, then the ho-mologous ßy and mammal proteins arepieces that can Þt in the same places

Looking at the HOM/Hox system in this

way also highlights how much we stillhave to learn: the other puzzle piecesthat enable the HOM and Hox proteins

to regulate genes and to have a speciÞcfunction have yet to be identiÞed

In a way, these experiments also

hark back to the classical observations

of Karl Ernst von Baer, who in the1820s concluded that if one examinedearly embryonic morphologies, all ver-tebrate forms seemed to converge to-ward a common design The story,which sounds too good to be true, isthat von Baer came to this epiphany af-ter the labels fell oÝ some of his bot-tled specimens of early embryos, and

he realized with some chagrin that hecould not be sure whether the embryoswere lizards, birds or mammals The

structure and function of the HOM and Hox gene systems suggest that this de-

velopmental convergence embraces theearly development of a great many ani-mal species But only at the level ofmolecular pattern can the developmen-tal convergence of such diÝerent em-bryos be Òseen.Ó

Sometime between 600 million and a

billion years ago, the HOM/Hox system

evolved; it has proved so useful thatmany animals have since relied on itsfundamental abilities to determine axi-

al position during development Is itthe only developmental genetic systemthat has been so conserved? That seemsunlikely Researchers have found hintsthat some other regulatory genes inßies and mice are highly similar instructure and are activated in the same

or homologous tissues Exploring thefunctions of those novel genes, and

how they interact with the HOM/Hox

system, promises to reveal many morefascinating insights into the evolutionand mechanism of the ancient geneticsystems that serve as the molecular ar-chitects of animal body plans

FURTHER READINGHOMEOBOX GENES AND THE VERTEBRATE

BODY PLAN Eddy M De Robertis,Guillermo Oliver and Christopher V E

Wright in Scientific American, Vol 263,

No 1, pages 46Ð52; July 1990

MOUSE H OX -2.2 SPECIFIES THORACIC

SEGMENTAL IDENTITY IN DROSOPHILA

EMBRYOS AND LARVAE Jarema Malicki,Klaus Schughart and William McGinnis

in Cell, Vol 63, No 5, pages 961Ð967;

R A Lazzarini and L Pick in Genes and

Development, Vol 7, No 3, pages 343Ð

354; March 1993

DEFORMED MUTANT FLIES have a variety of head abnormalities, including the

ab-sence of the lower half of the compound eyes The same abnormalities can be

in-duced by making the immature ßies express the human HOXD4 protein This

hu-man protein resembles the Deformed protein and seems to have a similar function

NORMAL FLY Deformed MUTANT FLY

Tiêu đề	Do Aerosols Slow Climatic Warming
Tác giả	Robert J. Charlson, Tom M. L. Wigley
Chuyên ngành	Climatic Change and Aerosols
Thể loại	article
Năm xuất bản	1994

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Số trang	89
Dung lượng	6,18 MB