a vital legacy (1997)€¦ · opportunities of atomic energy—and acknowledging, too, an...

VITAL

A

S e p t e m b e r 1 9 9 7

Biological and

Environmental

Research in the

Atomic Age

LEGACY

To the tens of thousands of scien-

tists, engineers, technicians, postdoctoral research associates, and grad-

uate students who produced the rich record of achievement from which

this account was drawn. And to the nearly one thousand principal

scientists addressing current Biological and Environmental Research

program priorities at more than 200 universities, government lab-

oratories, and private facilities.

I N T H E BE G I N N I N G : An Introduction 6

SAFETY FIRST: In the Shadow of a New Technology

The Proper Study of Mankind 9Enter the Animals 11

Constant Vigilance 13

Radiation Effects: A Closer Look 14

A Logical Consequence: The Human Genome Project 15

A Heritage of Genetics Research 18

A HEALTHY CITIZENRY: Gifts of the New Era

Atoms for Health 21

Slices of Life: Medical Imaging 23

High-Tech Treatments: Isotopes and Particle Beams 26

ENVIRONMENTAL CONCERNS: From Meteorology to Ecology

An Eye on the Weather 31

A Changing Climate 32

The Dynamic Ocean 35

The Outdoor Laboratory 36

Reclaiming the Past 41

AN EN D U R I N G MA N D AT E : Looking to the Future 44

C O N T E N T S

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20

30

4

In 1946 the Congress passed the Atomic En-

ergy Act and with it created the Atomic Energy Commission. For the ensuing half-

century, the AEC and its successors have pursued biological and environmental research

(BER) with an unwavering mandate to exploit the use of fissionable and radioactive

material for medical purposes and, at the same time, to ensure the health of the public

and the environment during energy technology development and use. The following

pages are testimony to the success of this undeviating vision. But more than a clear and

consistent charge underlies this success, and it is important, I think, not to lose sight of

these other ingredients of achievement—especially as we seek to extend our record of

accomplishment into the next millennium.

■ In pursuing its charge, the BER program

has consistently emphasized basic research. It has addressed long-term generic issues, rather

than the near-term questions that are the focus of the regulatory community and industry.

This consistency of focus has been essential to the program’s half-century of success.

■ Equally important has been the scientific

diversity of the energy agencies’ biomedical and environment program. Cooperation

among physicists and physicians, ecologists and engineers has been one of the program’s

hallmarks. In the future, cross-fertilization will become even more important, as science

advances at the interfaces between such disciplines as biology and information science.

■ From the early days of the AEC, coopera-

tion has also linked researchers from the national laboratories, the academic community,

and the private sector. Coordinating these diverse performers has been crucial to the unique

teaming that has made many of the BER successes possible. And this teaming will continue

to be a paramount objective of BER management, as we pursue both our stewardship of

the national laboratories and our commitment to academic research and education.

■ The success of the BER program has often

been shared with other federal agencies. The future will demand even stronger and more

substantive intraagency, interagency, and international collaborations. The BER program

is thus committed to the continuation and enhancement of the interagency collaborations

that have been integral to the success of such programs as the Human Genome Project

and the U.S. Global Change Research Program. The BER program is also committed to

strengthening collaborations with other offices within the Office of Energy Research, such

as Basic Energy Sciences and Computational and Technology Research.

The year 1997 marks the fiftieth anniversary

of biological and environmental research within the DOE and its predecessor agencies.

F O R E W O R D

5

To mark the occasion, and to look ahead to the future, the DOE and the National

Research Council of the National Academy of Sciences cosponsored a symposium in

May. Entitled “Serving Science and Society into the New Millennium: The Legacy and

the Promise of DOE’s Biological and Environmental Program,” it both celebrated the

past and looked optimistically to the future. This booklet likewise commemorates five

decades of contributions to science and society—and concludes with a view to the years

ahead. But the following pages merely hint at the wealth of achievements that have

emerged from the BER program. An exhaustive chronicle of those achievements would,

in fact, exhaust any reader. Therefore, despite the lurking risk of omitting even some of

the most important accomplishments, our intent has been to offer a representative selec-

tion, telling in the process a coherent story of evolution and progress.

At the doorstep of the 21st century, the BER

program is now poised to continue this tradition of scientific advancement. We invite you

to follow our progress at www.er.doe.gov/production/ober/.

Ari Patrinos

Associate Director of Energy Research

for the Office of Biological and

Environmental Research

6

Even during the war years, biologicalresearch was a priority. A MedicalAdvisory Committee chaired by StaffordWarren developed health and safety policyfor the Manhattan Project and inauguratedresearch programs to assure adequate pro-tection for Project workers. Teams ofphysicians, biologists, chemists, and physi-cists worked to learn how radiationaffected the body, what protective mea-sures were most effective, and in the eventof mishap, what methods of diagnosis andtreatment were best.

At the war’s conclusion, recognizing theopportunities of atomic energy—andacknowledging, too, an obligation for pub-lic safety—the Congress passed the AtomicEnergy Act of 1946, which would transferresponsibility for atomic energy researchand development from the War Depart-ment to an independent civilian agency, theAtomic Energy Commission. On January 1,1947, the AEC thus took charge ofresearch programs in health measures and

radiation biology conducted in governmentfacilities at the Clinton Laboratories (nowOak Ridge National Laboratory), Han-ford, and Los Alamos; at theMetallurgical Laboratory atthe University of Chicago(now Argonne NationalLaboratory); and atmany university labo-ratories, large andsmall. Among theongoing efforts werehealth physics researchfor “improving ourknowledge of the poten-tial dangers presented byfissionable materials, reac-tors, and fission products and forproposing methods of elucidating or cir-cumscribing such dangers”; research aimedat extending our “fundamental knowledgeof the interaction of nuclear radiation andliving matter”; and radioisotope distribu-tion programs to “provide indirect aid to

he earliest glimmering of radioactiv-

ity’s promise long predated any sense that ours would be the Atomic Age. By the

time of the Manhattan Project, physicists had almost a half-century of experience

with radioactive elements and their radiation, and several such elements, most

notably radium, had been used since the turn of the century in efforts to treat

human disease. By the 1930s, radioactive isotopes were being produced artificially

in Berkeley’s cyclotrons, and the pace of medical use and biological experimenta-

tion increased dramatically. At the same time, even the earliest pioneers saw that

radioactivity was not a benign blessing; protection standards, albeit far from ade-

quate, were published as early as 1915. Nonetheless, it was World War II that

firmly thrust the nuclear genie onto the public stage. At first, the spotlight was on

the awesome power of the atom, then on the emerging promise of nuclear energy,

but splitting the atom would also herald a vital new era for biology, medicine, and

environmental research.

T

I N T H E B E G I N N I N G

A n I n t r o d u c t i o n

7

research in many fields of biological andmedical research.” The Commission bud-get for fiscal 1947 was $342 million.

Early in its first year, the AEC moved toprovide a solid foundation for its biomed-ical research and education efforts by ask-ing the President of the National Academy

of Sciences to nominate a panelof experts as a Medical

Board of Review to advisethe Commission. TheBoard was promptlyestablished, and byJune it had issued itsinitial recommenda-tions, broadly support-

ing biomedical researchand training efforts and

proposing a permanentAdvisory Committee for

Biology and Medicine (ACBM).In September 1947, the chairman of theAEC appointed seven distinguished physi-cians and biologists to the ACBM.

Immediately upon its creation, theACBM recommended that a Division ofBiology and Medicine be established to“coordinate medical, biological, and bio-physical (health physics) research pro-grams related to atomic energy” and to“direct for the Commission its healthphysics works and industrial hygiene activ-ities.” The recommendation was quicklyadopted. Thus was forged a commitmentthat has endured for a half-century—acommitment to vigorous research aimedboth at nurturing the fruitful use of a newtechnology in the life sciences and at ensur-ing public health and safety in the face ofthat technology’s perils.

Almost thirty years later, the mandatebroadened. On the heels of the 1973 oilembargo, the nation’s awareness of energyissues took a new turn: An unlimited flowof oil was no longer a given. Other optionsmust be explored. And nuclear energy wasonly one of several alternatives whoseprospects and consequences called forthoughtful examination. Accordingly, theEnergy Reorganization Act of 1974 createdthe Energy Research and DevelopmentAdministration, which assumed, and

greatly enlarged on, the AEC’s researchresponsibilities. In the words of theCongress, ERDA was to engage in and sup-port “environmental, physical, and safetyresearch related to the development ofenergy sources and utilization technolo-gies.” The new agency’s Division ofBiomedical and Environmental Researchthus launched significant new programs ofresearch, widening its scope beyond theenvironmental and health consequences ofnuclear energy to encompass conventionaland synthetic fossil fuels and renewableenergy sources.

Three years later, with the creation ofthe Department of Energy, energy concernsachieved Cabinet rank. Today, the DOE’sOffice of Biological and EnvironmentalResearch carries forward the mandate ofits predecessors. Born in the shadow of theatomic bomb, biomedical and environmen-tal research continues to shed light on theconsequences of energy technologies—andto exploit their boundless promise. TheHuman Genome Project, for example, is asurprising but logical offspring of long-standing research on health issues andgenetic effects, research that isthe underpinning of today’sradiation protection stan-dards. Medical researchthat has produced life-saving radiopharma-ceuticals and diagnos-tic technologies nowpursues molecular-levelinsights into humanphysiology and disease.And studies of global cli-mate change continue a tradi-tion of environmental researchthat includes ground-breaking work inmodern ecology, pioneering studies ofoceanic processes, and one of the nation’sfirst environmental impact assessments.

The concerns and aspirations thatlaunched the AEC’s Division of Biology andMedicine gave rise to a continuing traditionof research that is as logical—but, in itsdetails, just as unpredictable—as the courseof progress itself. The following pageschronicle only a few of the highlights.

SAFETY FIRSTIn the Shadow of a New Technology

TH E PR O P E R ST U D Y O F MA N K I N D

One of the giant steps on this road was cre-ation of the Atomic Bomb CasualtyCommission, established in 1946 to followthe long-term consequences of radiation onthe survivors of the Hiroshima andNagasaki bombs. Today, the work contin-ues within the renamed Radiation EffectsResearch Foundation, jointly funded by theU.S. and Japan. This definitive effort has,for a half-century, traced the medical histo-ries of more than 86,000 survivors andtens of thousands of their descendants. Itremains the most ambitious study ever car-ried out on the effects of a toxic agent onhuman beings. From it we have learnedthat the major long-term effect of radiationis an increased risk of leukemia and solidcancers. Between 1950 and 1990, bombsurvivors suffered 7827 cancer deaths,about 420 more than would be expected inan unexposed population. Attempts havealso been made to identify genetic effects inthe survivors’ children, so far without suc-

cess—an outcome that prompted earlythinking about today’s Human GenomeProject (see page 15).

Other early epidemiological studieswere likewise products of circumstance, ina time of routine above-ground nuclearweapons tests. South Pacific Islandersexposed to fallout from a 1954 atmos-pheric test and, decades later, residentsreturning to face residual radioactivity onBikini and Eniwetok were carefully moni-tored for many years, both to provide fortheir own health and to enhance what weknow about radiation and its effects.

Today, with atmospheric nuclear testslargely a relic of the past, concerns aboutradiation have different sources—but theconcerns endure. Furthermore, such stud-ies as that of the atomic bomb survivorscan tell us little about the potential effectsof prolonged exposure to very low doses.For more than thirty years, then, OHERand its predecessors continued long-termhealth studies of naval shipyard workers,

9

or the freshly chartered AEC, perhaps

the most fundamental health research issue was the risk posed by the newly

unleashed power of the atom. World War II had added tragic testimony to the

short-term effects of intense radiation. But a more abiding concern was the less vis-

ible, long-term consequences of much lower radiation doses. Leukemia had already

claimed the life of Marie Curie, and in the twenties, working with fruit flies,

Hermann Joseph Muller had shown x-rays to be powerful agents of mutation. A

new era of radioactive isotopes, nuclear reactors, and atomic bombs demanded the

most thoroughgoing stewardship. Today, rigorous standards born of research

launched by the AEC safeguard radiation workers and the common citizen alike:

Regulations guide the medical use of x-rays and radionuclides, set limits on

radioactivity in consumer products, and define permissible doses for everyone

touched by radiation. But the road to such regulations has been a long one; it

stretches back to the early days of the century, and it is sure to take us even further

in the quest to fully understand the health effects of radiation.

F

A GLOWING ACHIEVEMENT Flowcytometry was developed atLos Alamos in the late six-ties as a means of sortingsingle cells according tosome selected criterion. Thetechnology is now found inthousands of clinical labora-tories, and as shown here, isbeing explored as a way ofsequencing DNA. By attach-ing a distinctive fluorescentdye to each of DNA’s fourkinds of nucleotides, thendetaching them one by one,it might be possible to readthe DNA sequence simply bylooking for the nucleotides’telltale “colors.” The yellowspot in the center of the pho-tograph is the laser-excitedfluorescence from about athousand molecules of onesuch dye.

employees at weapons design and produc-tion sites, uranium miners, and soldierspresent during weapons tests in Nevada.Another effort, stretching from 1947 to

1993, extended prewarstudies of instrument-dialpainters exposed since1912 to radium-lacedpaint. Taken together,these and other epidemio-logical studies form thecore of what we knowtoday of radiation expo-sure risks—both the risksof long-term, low-levelexposure and the dangersof a single high dose. Theyare likewise the founda-tion of the laws and stan-dards that protect thosewho work with radiationevery day, as well as the

citizen on the street.Public perception of the risks of radia-

tion continues to cloud the future ofnuclear energy in the U.S., but we know

A V I T A L L E G A C Y

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ANNUAL CHECKUPS For several decades, doctors and health physi-cists made annual trips to the Marshall Islands to check the healthof islanders accidentally exposed to radioactive fallout during a1954 U.S. bomb test in the Pacific.

A S U B J E C T O F C O N C E R N

■ Using human beings as experimental sub-jects in radiation research is no longer coun-tenanced by the federal government. But thishas not always been the case. In years past,humans were the subjects of therapeuticstudies and of inquiries into how radionu-clides get processed and distributed in thebody. In fact, rudimentary studies date back atleast to 1926, and after the invention of thecyclotron, the pace of such experimentationquickened considerably. In the late thirties, forexample, Joseph Hamilton, at the Universityof California’s Radiation Laboratory, con-ducted a series of human metabolism studieswith sodium-24, in hopes of developing ashort-lived replacement for the long-livedradium isotopes then used to treat leukemiaand other diseases.Then, between 1945 and1947, in four hospitals around the country,eighteen subjects were injected with pluto-nium. The aim was to develop a diagnostictool, based on the amount of the elementexcreted, that could be used to quantifyindustrial exposures to plutonium. Despitethe studies’ laudable goals—namely, to estab-lish protective standards for industrial work-ers—these experiments were recently thefocus of a national controversy. None of the

subjects suffered any apparent harm from theplutonium injections, but neither had theybeen fully informed of what was being done.And many of the scientific results were keptsecret for years. ■ When details of theseexperiments were revealed in 1993, the publicwas indignant at the appearance of scientificarrogance. Fortunately, times—and ethicalstandards—have changed. Well before thisstory hit the press, strong federal regulatorymeasures were in place to protect subjects ofresearch. Since 1976 DOE regulations haveprotected human research subjects, and in1991 the DOE was the first agency to signthe Federal Policy on Protection of HumanResearch Subjects. Further, following thedeliberations of the White House AdvisoryCommittee on Human Radiation Experi-ments, even greater federal attention is nowfocused on the need for subjects to be fullyinformed regarding experimental proceduresor treatments. Research using human sub-jects, including clinical trials to assure thesafety and efficacy of new pharmaceuticals, isan important part of modern biology andmedicine, but today it is performed openlyand in strict accordance with ethical andhumanitarian principles. ■

1895 German physicistWilhelm Conrad Röntgendiscovered an invisibleform of radiation, whichhe called “x-rays.”Röntgen would win thefirst Nobel Prize forPhysics in 1901.

1896 French physicistAntoine-Henri Becquerelfound that uranium saltsemit an invisible pene-trating radiation—thefirst observation ofradioactivity.

1901 Becquerelobserved one of the bio-logical effects of radio-activity when he carriedsome radium in a vestpocket, reddening theskin beneath. In 1903Becquerel and hisFrench colleagues Pierreand Marie Curie (pic-tured) would receive theNobel Prize for Physics.Both Marie Curie and herdaughter Irène Joliot-Curie would later die ofleukemia, probablycaused by their long-term exposure to radio-activity in the laboratory.

now that no energy source is entirely freeof untoward consequences. Since the sev-enties, the DOE has thus extended its epi-demiological studies to gauge the healtheffects of the energy choices we must make.Subjects have included turn-of-the-centurylaborers in coal-gasification plants in Japanand England, present-day workers exposedto diesel bus exhaust, and even residentsliving near high-voltage power lines.

EN T E R T H E AN I M A L S

Notwithstanding their undeniable value,retrospective epidemiological studiesamount to unintended experiments—experiments that often emerge from histor-ical naiveté, thetragedy of waror accident, ornatural forces.Better to knowthe likely effectsof toxic agentsbefore humanssuffer the con-sequences. Toget at a deeperunderstandingof radiation’seffects, there-fore, the AECsupported ani-mal studies inits very firstyears—studiesthat were, in fact, a logical continuation ofresearch carried out during the ManhattanProject to protect workers confronting anutterly unexplored frontier of science.

Perhaps the most comprehensive ofthese investigations was the “internal emit-ters” program. Using beagles as their sub-jects, scientists at many universities andnational labs sought to understand thehealth effects of ingested or inhaledradioactive fallout and of radioactivityassociated with nuclear power generationand weapons production. For a variety ofelements, in a variety of chemical forms,researchers asked, Where does the radioac-tivity go? How long does it persist in thebody? What organs are affected? Whatare the health consequences? The answers

became a landmark database for the estab-lishment of national and internationalsafety standards.

Another tack was taken by William andLiane Russell at the Clinton Laboratories(now Oak Ridge National Laboratory),where they established a mammaliangenetics program in 1947. It was there inthe early fifties that Liane Russell observedthe exquisite vulnerability of the mam-malian embryo to radiation, leading to newradiation safety guidelines for women ofchild-bearing age, and especially for preg-nant women. In the sixties and seventies,the Oak Ridge mice were pioneers again, asmouse genetics studies were extended to

the chemicals in our daily lives: the com-ponents of pharmaceuticals and pesticides,fuels, airborne pollutants, and cigarettesmoke. In 1991, in a commemorative vol-ume, the international journal MutationResearch lauded William Russell by sayingthat “no single person has contributed moreto the field of mammalian mutagenesis, andthus to genetic risk assessment in man.”

S A F E T Y F I R S T

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A FAMILY AFFAIR At the Clinton Laboratories in1947, Liane and William Russell established aprogram that would make notable contribu-tions to mammalian genetics for the next half-century. An assay they developed for quantify-ing heritable gene mutations in mice remainsa standard today for assessing the humanrisks posed by radiation and toxic chemicals.

1915 Protection stan-dards describing “safepractices” for handlingradium and x-raymachines were pub-lished in Germany andSweden.

1927 American geneti-cist Hermann JosephMuller found that x-raysgreatly increase muta-tion rates in fruit flies.His work would berewarded in 1946 withthe Nobel Prize forPhysiology or Medicine.

1928 An internationalcongress adopted thefirst widely accepted x-ray protection standard,a monthly dose limitequal to 1/100 of theamount that burns skin.

1946 President Trumandirected the NationalAcademy of Sciences tostudy the long-termeffects of radiation onsurvivors of the atomicbombs. The AtomicBomb Casualty Commis-sion was created to pur-sue this effort, supportedby funds from the AEC’sDivision of Biology andMedicine; its workwould continue after1975 within theRadiation EffectsResearch Foundation.

Other animal studies, many with a her-itage that predated the AEC, focused onthe risks of ingested strontium andtransuranics, inhaled plutonium, inhaledfission products, inhaled radon, and later,diesel exhaust and other products of fossilfuel combustion and conversion. AtHanford, site of the nation’s first majorreactor complex, some early experimentswere part exposure study and part ecologi-cal research. In both field and laboratorystudies, University of Washington scientistslooked at the effects of waste effluents on

Columbia River biota and cooperated insimilar early studies on the fisheries of thePacific Northwest. Such efforts were “ani-mal studies” in a broader sense and pointedto a whole suite of ecosystem studies thatwill be one of the subjects of this booklet’sthird chapter.

Later, between 1975 and 1985, chemistsand biologists from Argonne, Oak Ridge,Pacific Northwest, and the InhalationToxicology Research Institute (now theLovelace Respiratory Research Institute)extended their studies to other energy tech-


12

■ In 1984 an employee of a nuclear power plant triggered the facility’s radiation detectors whenhe arrived at work. The cause was a level of radioactive radon gas in the worker’s home muchhigher than allowed in a uranium mine.This incident rekindled smoldering concern about radon inhomes and led to a Congressional mandate to study the extent of the risk. Epidemiological datawere available for uranium miners exposed to radon, so the key challenge was to define the dis-tribution of radon in American homes and then to relate household exposures to workplaceexperience. Over the next twelve years, the DOE played a central role in providing the data neededto rationally assess this household risk.The map above, for example, shows median indoor radonconcentrations across the country, as estimated by a predictive model based on available moni-toring data, together with information on soil types, climatology, and home construction standards.■ In addition, animal studies at Pacific Northwest uncovered a synergy between radon and ciga-rette smoke in heightening the risk of lung cancer. The bottom line? We now know that undersome circumstances household exposure to radon and its decay products can be a significanthealth risk, but we also have guidelines that suggest when consumers should take action to reduceexposures—and that point to effective actions they can take. ■

I N S I D E T H R E A T : R A D O N I N T H E H O M E

1947 Argonne under-took a long-term studyof instrument-dialpainters to assess theeffects of occupationalexposure to radium. Asa group, the paintershad high rates of bonedisease and anemia;below a threshold dose,however, no ill-effectswere observed.

1947 AlexanderHollaender created theBiology Division at theClinton Laboratories. In1983 Hollaender wouldreceive the DOE’s presti-gious Enrico FermiAward, and in 1986OHER would establishthe Alexander HollaenderDistinguished Postdoc-toral Fellowships. Todate, some eighty-fiveyoung investigators ofoutstanding promisehave received fellow-ships to conductresearch in BER-supported programs.

nologies. Together with industrial engi-neers, and using model systems such as lab-oratory animals, cultured cells, and bacte-ria, they worked to define the health risksposed by the manufacture of synfuels fromoil shale and coal, and by several advancedfossil fuel combustion technologies. Theresulting database remains one of the mostextensive bodies of information availableon the short- and long-term toxicity of thecomplex chemical mixtures that emergefrom the production and use of fossil fuels.

The aim of all this, of course, the epi-demiological studies, the controlled animalexperiments, and the toxicological studies,is to understand the nature of the risksposed by our society’s activities. This kindof “risk assessment,” born of AEC, ERDA,and DOE research, led to guidelines for theuse of diagnostic x-rays, to confidence inthe safety of countless radiopharmaceuti-cals, and to safety standards for the pres-ence of radionuclides in the air, in food,and in drinking water. It is also one of theunderpinnings of our ability to assess thelikely consequences of such incidents as thereactor accidents at Three Mile Island andChernobyl.

CO N S TA N T V I G I L A N C E

Well before the years of the AEC, stan-dards prescribing safe practices in dealingwith radiation had grown increasinglystrict. But safety would become a preoccu-pation with theenergy agencies.Among the earliestapostles of radia-tion safety wasHerbert Parker, aBritish-born med-ical physicist whobecame chief healthphysicist and even-tually director atHanford. Amonghis contributions,Parker’s concept ofthe rem, still a stan-dard measure ofbiological dose, isperhaps the mostobvious. But more

than that, the vigilance of the earliest pio-neers and those who followed them hasbeen a driving force behind today’s safetyconsciousness. In that same postwar era,increasing attention to radiation healthprotection led the AEC’s Division ofBiology and Medicine to establish gradu-ate-level programs at the University ofRochester, the University of Washington,and Vanderbilt, all linked to field trainingprograms at nearby national laboratories.Fifteen other universities added similarprograms later. All told, these programshave produced about a thousand profes-sionals with postgraduate degrees in healthphysics, industrial hygiene, and radiationbiology.

Support also extended to the develop-ment of techniques to assess individualradiation exposure. Film-badge dosimetrywas the early standard, followed in the six-ties by thermoluminescence dosimetry,developed largely at the University ofWisconsin. This is the method now used byradiation workers worldwide. Researchalso took an entirely new turn in the six-ties, focusing on ways to quantify the dose


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ONE ATOM AT A TIME Samuel Hurst at Oak Ridgedeveloped resonance ionization spectroscopy,a laser-based technique that succeeded forthe first time in counting individual atoms. Theearliest success was the detection of a singlecesium atom among 1019 argon atoms.

1951 Using an ion-exchange techniqueoriginally developed toseparate fission prod-ucts, Oak Ridgeresearchers devised asimple method for isolat-ing the components ofDNA and RNA, a discov-ery that would signifi-cantly accelerate bio-chemical studies ofthese materials aroundthe world.

1956 At Oak RidgeLarry Astrachan andElliot Volkin (pictured)discovered a previouslyunrecognized form ofRNA, which they called“DNA-like RNA.” Fouryears later, this specieswould become known asmessenger RNA, theessential courier ofgenetic instructions tothe sites of protein syn-thesis in the cell.

1956 At Brookhaven W. L. (Pete) Hughes syn-thesized a radiolabeledversion of thymidine,whose uptake by cellssignals the synthesis ofDNA.

of potentially toxic agents—chemicals aswell as radiation—and to reckon theireffects by looking for biological change inhuman tissues. New cell-culture techniquesand sensitive methods for assessing chro-mosome damage in cultured human cellsled Oak Ridge researchers to the concept ofbiological dosimetry or biomarkers. In oneextension of this concept, Richard Albertiniat the University of Vermont quantifiedmutations to a specific “reporter” gene,known as HPRT, as a means for gauginghuman exposures to radiation and to haz-ardous materials. Since their introduction,biomarkers have been used successfully toestimate radiation doses to astronauts,radiotherapy patients, and radiation acci-dent victims. They were widely used, forexample, in the wake of the reactor acci-dent at Chernobyl.

Along similar lines, engineers and physi-cists have directed consistent effort sincethe forties toward improving instrumenta-tion for measuring radioactivity in medical,biological, and environmental samples.Early research centered around photomulti-plier tubes and scintillation detectors, but acrucial breakthrough came in the sixtieswith the development of solid-state siliconand germanium detectors. Properly pre-pared, these materials produced electricalsignals precisely matched to the energy ofthe detected x-rays—and thus pinned downthe identity of the radioactive isotopes pres-ent. Now successfully commercialized byseveral manufacturers, many of the under-lying practical discoveries arose from AEC-supported research, especially by FredGoulding and his colleagues at Berkeley.

Then, in the seventies, with the broaden-ing scope of ERDA, and then the DOE,concern extended to the chemical by-prod-ucts of all energy production and use.Techniques have thus been developed tomonitor known cancer-causing chemicals,to measure skin contamination, and todetect trace amounts of environmental con-taminants. An especially notable tool is res-onance ionization spectroscopy (RIS), anOak Ridge–developed technique so sensi-tive that in 1977 it allowed single atoms tobe detected for the first time. Spin-offs haveincluded several RIS-based analytical tech-

niques for studying trace materials in theenvironment. And in 1990, at Los Alamos,similar concepts led to another milestone,the first detection of a single molecule.

RA D I AT I O N EF F E C T S : A CL O S E R LO O K

A shortcoming of epidemiological stud-ies—and most animal studies, too, for thatmatter—is that they offer little insight intoWhy. Why does radiation cause mutations?Why are low levels of radiation often

harmless? Why do the consequences ofmore severe exposures often appear as can-cers decades later? These and similar ques-tions fall within the province of radiationbiology, which looks beyond mice and fruitflies, to uncover the underlying effects ofradiation on cells and their components.One of the ground-breaking discoveriescame at Oak Ridge in the early sixties,when Richard Setlow pinpointed the dam-age caused by ultraviolet light in thegenetic material of bacterial cells, and fur-


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DAMAGE CONTROL In the early sixties at OakRidge, Richard Setlow elucidated the mecha-nism of DNA repair, thus opening the door to afield of inquiry that is at the center of cancerresearch today. Now at Brookhaven, he isshown here with fish used to study the induc-tion of melanoma by ultraviolet light.

1959 At ColumbiaUniversity, Harald Rossiintroduced the conceptof measuring energydeposition by ionizingradiation in small vol-umes, thus launchingthe field of microdosime-try. This concept wouldlead to significantadvances in our under-standing of the risks ofexposure to low-levelradiation.

1961 In a joint effortwith the NIH, a teamheaded by NormanAnderson developed ahigh-speed zonal cen-trifuge at Oak Ridge. Bythe late sixties, com-mercial descendants ofthis machine were pro-ducing highly purifiedvaccines for humans andanimals.

1962 Richard Setlow atOak Ridge pinpointedthe damage caused inbacteria by ultravioletlight. Two years later,he would discover therole of genetic repairmechanisms in mendingsuch damage.

ther discovered that the bacteriasurvive the insult by repairing thedamage—snipping the damagedregions from one strand of theirdouble-stranded DNA. Then, in1968 at the University ofCalifornia, San Francisco, JamesCleaver found that a geneticallyimpaired DNA repair apparatusunderlies xeroderma pigmento-sum, a human disease that predis-poses affected individuals to skincancer. A link was thus solidlyforged between unrepaired DNAdamage and human cancer.

The legacy of these landmarkdiscoveries is striking. The roleplayed in hereditary cancers bydefective repair genes—the genesthat direct the production of theenzymes responsible for the actualrepair work—is now a focus ofresearch around the world. AndOBER-supported scientists con-tinue to be leading players. AtLivermore and Los Alamos, forexample, researchers have iso-lated and cloned several repairgenes, including the very one whose defectslead to xeroderma pigmentosum. But theclear picture that unrepaired DNA damagewas the insidious culprit in the long-termconsequences of radiation exposure had fardeeper ramifications. It was now seen thatx-rays, ultraviolet light, and cancer-causingchemicals worked in similar ways, subvert-ing or overwhelming the natural DNArepair mechanisms that our health reliesupon. So central is the role of DNA repair,and so active is today’s research communityin seeking to understand it better, that in1994 the prestigious journal Science desig-nated the entire class of DNA repairenzymes as its “Molecule of the Year.”

Another upshot of the earliest researchon DNA repair was the development ofnew screening tests for possible cancer-causing chemicals. If unrepaired DNA dam-age was at the source of most cancer, thendetectable cellular mutations were dangersigns to be heeded. In short order, then, theseventies produced a number of new testsfor cancer-causing potential, the best

known of which is the Ames test, devel-oped with AEC support in 1973 by BruceAmes at the University of California,Berkeley. Some strains of bacteria, hobbledby an inability to produce an essential mo-lecular building block, can reproduce onlyif something alters them genetically. Thus,any chemical that produces a flourishingcolony of these bacteria is a potentialhuman mutagen. Today, around the world,the Ames test is one of the first hurdles a new chemical or pharmaceutical mustclear on its way to regulatory and publicacceptance.

A LO G I C A L CO N S E Q U E N C E : TH E

HU M A N GE N O M E PR O J E C T

A surprising but cogent thread links theatomic bombs that ended World War IIwith today’s most ambitious healthresearch effort, the Human GenomeProject. One of the unanswered questionsof radiation research is the extent to whichthe descendants of bomb survivors harborDNA mutations as a legacy of their par-


15

D N A S N A P S H O T S

■ Another window into theworkings of the cell opened in1956 at Brookhaven, when W. L.(Pete) Hughes synthesized tri-tium-labeled thymidine, a highlyspecific precursor of DNA.(Tritium is a radioactive isotopeof hydrogen.) Cells take upthymidine in preparation for celldivision, build it into their DNA,

and then hand it down to their daughter cells.The triti-ated version emits low-energy electrons, which can bemade to expose photographic film and thus to producemicroscopic pictures showing where DNA synthesishas taken place. By observing the fate of tritiated thymi-dine in living cells, Brookhaven scientists were able toconfirm the Watson-Crick hypothesis for DNA replica-tion at the chromosomal level—and to “watch” chro-mosomes exchange genetic material during the processof cell division. Their careful experiments also eluci-dated many of the details of the cell cycle, the sequenceof observable stages a cell passes through between celldivisions. Today, tritiated thymidine is a standard toolaround the world in studies of how cells proliferate andhow cancer develops and responds to treatment. ■

1966 Argonne radiationbiologist Miriam Finkelisolated the murineosteosarcoma virus, thesource of a gene thatwould be widely used insubsequent research.The fos gene plays aprominent role in theregulation of cell prolif-eration.

1967 At Los AlamosMack Fulwyler andMarvin Van Dilla devel-oped the fluorescence-activated flow cytometer.

1968 James Cleaver atthe University ofCalifornia, SanFrancisco, showed forthe first time that ahuman disease (xeroder-ma pigmentosum) asso-ciated with a suscepti-bility to cancer iscaused by a geneticallyimpaired ability to repairdamaged DNA.

ents’ exposure to radiation. Indeed, theRadiation Effects Research Foundationmaintains a precious resource of frozenwhite-blood cells from almost a thousandfamilies of survivors and children, awaitingthe day when their DNA can be analyzedfor telltale mutations. But that day awaitsnew tools for genetic analysis and a farmore detailed knowledge of the humangenetic makeup. Thus the tie to the genomeproject.

In 1986 the DOE boldly announced itsHuman Genome Initiative, both to developthese needed tools and, far more broadly, toprovide a comprehensive picture of thehuman genetic script. For the genome proj-ect is no less than this, to read in detail thesequence of three billion letters (or basepairs) that makes up the genetic recipe ofour species. The ultimate payoffs stretch theimagination: Molecular medicine will turnfrom treating symptoms to addressing thedeepest causes of disease; new pharmaceuti-cals will attack diseases at their molecularfoundations. More sensitive diagnostic testswill uncover ailments in their earliest stages.New preventive therapies targeting individ-uals with genetic susceptibilities—either toheritable disease or to environmental car-cinogens—will thwart some diseases alto-gether. Even gene therapy will become pos-sible, actually “fixing” genetic errors.

By the mid-eighties, the foundations forthis formidable project were already firmlyestablished. GenBank, a DNA sequencerepository, was in place at Los Alamos,backed up by DOE computer and data-management expertise. Chromosome-sort-ing capabilities, essential to the genome ini-tiative, existed at both Livermore and LosAlamos. And these same labs had recentlylaunched the National Laboratory GeneLibrary Project. Nonetheless, the idea ofsequencing the entire genome was greetedat first by skepticism. Today, though, theDOE’s prescient initiative has beenembraced nationally and internationally,and the genome project is making steadyprogress toward reaching its goal in theyear 2005.

Together with investigators supportedby the National Institutes of Health, DOE-funded laboratories and university scien-

16


MAPPING THE TERRAIN A much-simplified mapcovering some 20 million base pairs of chromo-some 16 hints at the complexity of chromoso-mal mapping. Most of the different symbolsindicate a different kind of well-characterizedchromosomal fragment or marker; collectively,these genomic signposts provide a sound basisfor detailed sequencing efforts.

1972 Peter Mazur andStanley Leibo pioneeredcryopreservation ofmammalian embryos.At Oak Ridge they suc-ceeded in freezing,thawing, and implantingmouse embryos, thusspurring a revolution inthe livestock industry.

1973 Bruce Ames atthe University ofCalifornia, Berkeley,devised a screeningtest, now known as theAmes test, for identify-ing potential cancer-causing chemicals andpharmaceuticals.

1974 Brookhaven biol-ogists demonstratedthat ultraviolet-producedpyrimidine dimers incells induce the forma-tion of tumors. Theywould later succeed forthe first time in usingUV light to transformnormal human cells inculture to premalignantcells.

tists continue to lead the U.S. effort.Although “production sequencing” of thehuman genome is just beginning aroundthe world, the project has already pro-duced newsworthy results. Los Alamos andLivermore have published high-resolutionmaps of chromosomes 16 and 19, the firstefforts to provide a sufficient number ofchromosomal signposts to support large-scale sequencing projects. In the process ofthis and later work, mappers uncoveredgenes implicated in many human ailments,including adult-onset diabetes, pathologi-cally high cholesterol levels, the most com-mon form of muscular dystrophy (a successshared by an international team ofresearchers), and very recently, Down’ssyndrome. Livermore also shares credit forfounding the I.M.A.G.E. (IntegratedMolecular Analysis of Genomes and theirExpression) Consortium, which coordi-nates the world’s largestpublic collection of clonedgene fragments, an invalu-able resource for the inter-national biological commu-nity. Berkeley, meantime,has focused on automatinga large-scale sequencingtechnology, which has beenadopted by private compa-nies and by two major NIHsequencing efforts.

Another part of the taskis genome “informatics,”the full range of computa-tional support the projectdemands. At Oak Ridge,for example, researchers in1991 developed GRAIL(Gene Recognition andAnalysis Internet Link), anon-line computer programthat uses the principles ofartificial intelligence to sortout genes from the muchlonger stretches of noncod-ing DNA in the genome. In1995 alone, the interna-tional community usedGRAIL to search for genesamong 180 million basepairs of human DNA—a

volume of DNA equal to six percent of theentire genome. OBER also manages theworld’s central repository of mappinginformation, the Genome Data Base at theJohns Hopkins University.

The OBER genome program alsobroaches ethical, legal, and social issues.For example, one effort has led to highschool curriculum units on human geneticsand on the ethical management of genomicinformation. In addition, a model privacyact developed at Boston University’s Schoolof Public Health has become the basis forpending state and federal legislation aimedat safeguarding individual rights. And yetanother effort, headed by the nonprofitEinstein Institute for Science, Health andthe Courts, led to educational workshopsfor state and federal judges who must dealwith increasingly sophisticated genetic evidence.


17

1979 High levels ofnaturally occurringradon were observed byArgonne researchers inhomes in the Midwest, aconsequence of soilporosity beneath thehouses, rather than theconcentration of radium(the parent of radon) inthe soil. Public aware-ness of radon would beheightened in the mid-eighties, leading to anintensive nationalresearch program.

1982 Brookhaven sci-entists William Studierand John Dunn completedthe first DNA sequenceof a double-strandedvirus, the bacteriophageT7. At 39,936 basepairs, it was the longestsequence then known.

1984 The NationalLaboratory Gene LibraryProject was establishedjointly betweenLivermore and LosAlamos to create chro-mosome-specific genelibraries from each ofthe human chromo-somes and to distributethem to the worldwidescientific community.

■ In the fifties and sixties, the details of the genetic apparatuswere still being filled in: the double helix discovered, thegenetic code deciphered, and the intricate process of proteinsynthesis sorted out. In 1956 Oak Ridge scientists LarryAstrachan and Elliot Volkin isolated a form of RNA that theycalled “DNA-like RNA.” Four years later, this molecule wouldbecome known as messenger RNA (mRNA), the molecularcourier that carries the instructions contained in DNA to siteswhere the encoded information is used to produce enzymes,antibodies, and the rest of the body’s proteins. Among thevisual landmarks of this period were early images fromBrookhaven showing RNA to be made in the nucleus of theanimal cell and then the first photo (below) of mRNA actuallybeing transcribed from chromosomal DNA. This picture, ahigh-resolution electron microscope image, was produced atOak Ridge in 1970. ■

T H E T H R E A D S O F L I F E

A HE R I TA G E O F GE N E T I C S RE S E A R C H

But DOE’s interest in genetics research isboth older and broader than today’sgenome project. One of the historic efforts,for example, was two decades of researchat Brookhaven, culminating in 1982 withthe longest DNA sequence then known,the complete genome for the “bacte-ria-eating” virus T7. Furthermore,the work produced more than justsequence; it provided a profoundinsight into how the genetic pro-gram is translated into action—themolecular mechanisms by which T7

takes over and exploits thereproductive machinery of itshost bacterium. As a directconsequence, T7 has nowbeen genetically engineeredby the biotechnology indus-try to serve as cellular “facto-ries” for producing selectedproteins.

Oak Ridge scientists alsoplayed an early role, owing inlarge part to their celebrated“mouse house.” Years ofmutagenesis studies therehelped shape the foundationfor today’s molecular genet-ics research. Mutant strainsof Oak Ridge mice expressheritable disorders thatmodel human birth defects,metabolic maladies such asobesity and diabetes, andhuman cancer. Over the pastdecade, many of the genesresponsible for these disor-ders have been identified,and often the correspondinghuman genes have been char-acterized as well. Further,whereas many of thesestrains arose from randomgenetic alterations, modern

biotechnology has now largely supplantedsuch reliance on chance. Today, at OakRidge, Berkeley, Livermore, and manyother labs around the world, transgenicmice carry “designer mutations” that allowscientists to study specific genetic defects


18

1984 OHER and theInternational Commissionon Protection againstEnvironmental Mutagensand Carcinogens co-sponsored a conferencein Alta, Utah, highlight-ing the growing role ofrecombinant DNA tech-nologies. The Congres-sional Office ofTechnology Assessmentwould subsequentlyincorporate the Alta pro-ceedings into a reportacknowledging the valueof a human genome ref-erence sequence. Thefollowing year, CharlesDeLisi and David Smithwould outline plans for aDOE Human GenomeInitiative.

1986 OHER announcedits Human GenomeInitiative after organiz-ing a meeting in SantaFe to explore the proj-ect’s feasibility.

1988 The DOE and theNIH sign a memorandumof understanding forcoordination of the U.S.Human Genome Project.Two years later, theagencies would jointlyannounce the project’sfirst set of five-yeargoals.

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

■ Often unsung in the march of scientific progress are theachievements in instrumentation that make modernresearch possible. One such instrumental foundation stonewas laid between 1965 and 1972 when Mack Fulwyler andMarvin Van Dilla developed the flow cytometer at LosAlamos. For the first time, this device made it possible torapidly sort single cells and subcellular components accord-ing to some chosen criterion (the amount of DNA in a cell,for example, or the size of a chromosome). An entire indus-try subsequently arose to put this device to clinical use—most routinely for performing blood counts—and it nowplays a leading role in a host of research areas, from AIDS totoxicology. Adapted for chromosome sorting and purifica-tion, it is a staple of the Human Genome Project. ■

A COLOR-CODED GENE The different coat colorsof these Oak Ridge mice arise from mutationsin the "agouti" gene, which affects a numberof functions, including pigmentation. Themouse in the rear has the normal grizzledagouti coat.

that mimic those found in human patients,thus paving the way to new diagnostic andtherapeutic techniques. Diseases beingstudied in such mice include sickle-cell dis-ease, polycystic kidney disease, andleukemia.

Also recent are breakthroughs in a fieldcalled molecular cytogenetics. In 1986, aspart of the biodosimetry effort at Liver-more, Joe Gray developed a technique for“chromosome painting” whereby the dif-ferent human chromosomes can be uni-formly tagged with fluorescent dyes ofdiagnostic colors. Major genetic changes—the swapping of pieces of chromosome, forexample—are thus easily seen, whether theproduct of natural mutational events orexposure to mutagenic agents. Thus theobvious application to biodosimetry (seepage 14). Chromosome painting has alsobeen used to illuminate the incrementalgenetic changes that accompany the trans-

formation of normal to malignant cells in anumber of human cancers, including thoseof the breast, colon, and prostate.

Efforts launched in the immediate post-

war years to ensure the public safety thus

produced not only today’s radiation

safety standards, short-term assays such

as the Ames test, and advances in dosime-

try, but also the bright prospects of the

Human Genome Project. Another thrust,

though, had medical advances as its goal

from the start—not the protection of

human health, but its dramatic enhance-

ment through nuclear medicine—the

theme of the next chapter in the history

of biological research in the Atomic Age.

19


MIX AND MATCH Developed at Livermore in 1986, chromosome painting allows many genetic events,natural and otherwise, to be readily observed. In this image, human chromosomes 1, 2, and 4 (twoof each) have been stained orange, chromosomes 3, 5, and 6 green. Along with the normal chro-mosomes, two can be seen that are part orange, part green, a result of chromosomal exchange.

1989 Los Alamos scien-tists isolated and char-acterized the ends (ortelomeres) of humanchromosomes. Thetelomeres are involvedin cell maintenance andlongevity, since they areshortened during normalcell replication.“Immortal” cancer cellssomehow escape therestraint of telomericshortening.

1992 The gene formyotonic dystrophy wasdiscovered by a consor-tium that includedLivermore scientists,leading to a diagnostictool for a late-onset dis-ease that affects oneout of every eight thou-sand people.

1993 Using hybrid fishas their model systems,Brookhaven scientistsshowed that UVA wave-lengths are more impor-tant than UVB wave-lengths in the inductionof malignant melanoma.

1994 Livermore and LosAlamos announced high-resolution physical mapsof human chromosomes19 and 16, respectively.

1997 OBER formed the Joint GenomeInstitute to integratethe high-throughput pro-duction efforts of thegenome centers atBerkeley, Livermore, andLos Alamos.

❧

A HEALTHYCITIZENRY

SPECIAL DELIVERY In August 1946, Clinton Laboratoriesresearch director Eugene Wigner (in dark suit) handed acontainer of carbon-14 to the director of the BarnardFree Skin and Cancer Hospital of St. Louis. This was thefirst delivery of a radioisotope acknowledged to be theproduct of the formerly top-secret wartime reactor.

Gifts of the New Era

AT O M S F O R HE A LT H

The AEC thus inherited a field not yetmature, but brimming with potential. In1946 the veil of wartime secrecy was liftedfrom the nuclear reactor at the ClintonLaboratories, which had for three yearsbeen the clandestine origin of phosphorus-32 being produced for medical purposes. Aprolific new source of radioisotopes wasthus revealed, and before production ceasedin 1963 at the original reactor, Oak Ridgehad filled over a half-million orders forradioactive tracers and pharmaceuticals.

Nor did the AEC limit itself to supplyingthe biomedical community with isotopesalready well characterized. In the late six-ties, for example, under AEC sponsorship,Paul Harper, at the University of Chicago’sFranklin McLean Memorial ResearchInstitute, developed radioactive thallium asan imaging agent and proposed it as a

potassium analog for visualizing the livingheart. Subsequently, in the mid-seventies,Brookhaven scientists developed the firstpractical techniques for producing thal-lium-201 and then used the isotope suc-cessfully in obtaining cardiac images fromgoats. Today, thallium-201 exercise testingis among the standard noninvasive meth-ods of scanning for reduced blood flow ortissue damage to the heart. In 1995 aboutone million thallium-201 scans were per-formed in the U.S. alone, most of themheart scans. The underlying idea is com-mon to the use of all diagnostic radioiso-topes. The isotopes themselves, or bio-chemicals containing them, are taken uppreferentially by one organ or another,whereby the emitted radiation can be mea-sured or used to produce pictures notunlike conventional x-ray images. Theresults reveal not so much the structure of

21

odern nuclear medicine has

a pedigree that stretches almost a hundred years. As early as the first years of the

twentieth century, radium was used in several hopeful experiments to treat condi-

tions for which no effective therapies were known: tuberculous skin lesions, goiter,

tumors, and chronic infections. Two decades later, George de Hevesy was the first

to explore the use of radioactive tracers, following the course of radioactive lead in

plants. Over the next few years, minute quantities of radioactive elements were

injected into humans and animals to study metabolic processes and to trace the cir-

culation of blood. Then, in the thirties, at the University of California’s Radiation

Laboratory in Berkeley, Ernest O. Lawrence produced radioactive isotopes under

controlled conditions for the first time. In a few short years, Lawrence’s cyclotrons

produced iodine-131, technetium-99m, carbon-14, thallium-201, and gallium-67,

all of which would play pivotal roles in the future of nuclear medicine and biology.

At the same time, the therapeutic use of radionuclides and their application to

physiological studies increased in proportion to the sudden availability of these

new “artificial” substances.

M

KEYS TO THE PLANT KINGDOM

Melvin Calvin’s early use ofcarbon-14 tracers uncoveredmany of the mysteries of pho-tosynthesis and led to the1961 Nobel Prize for Chemistry.The central metabolic cycle bywhich plants transform carbondioxide and water to sugar isnow known as the Calvin cycle.

the body, but rather thedetails of function and dys-function.

Even more widespreadthan thallium heart scans isthe use of technetium-99mfor diagnosing diseases of thethyroid, kidney, liver, heart,brain, and bones. Aboutthirteen million patients per year, roughlyone-quarter of all U.S. inpatients, receivetechnetium-99m scans as one of their diag-nostic tests. As a radiotracer, its propertiesare nearly ideal: It exposes the patient tominimal radiation, while sending out aclear beacon to the camera. And its activitythen diminishes in a matter of hours. Onthe other hand, owing to its short, six-hourhalf-life (the period during which half of

the material undergoes radioactive decay),technetium-99m was long overlooked as apractical tool for widespread use; in effect,it had no “shelf life.” But in the late fifties,Walter Tucker, Powell Richards, and othersat Brookhaven discovered a way by whichhospitals and research institutes could“milk” technetium-99m as needed from itslonger-lived parent isotope. And in theyears following, the next necessary stepwas also taken—the incorporation of theradioisotope into biologically active mole-cules, much of the work being done at theArgonne Cancer Research Hospital and atBrookhaven.

In medical diagnostics, radioisotopesserve as tiny sources of invisible butdetectable light, revealing their presence asthey accumulate in organs or tumors, orcourse through veins and arteries.Moreover, as long as a tracer’s activity per-sists, its movements can be traced even as it


22

1903 AlexanderGraham Bell proposedusing radium to treattumors.

1923 Hungarianchemist George deHevesy used a naturalradioisotope of lead toinvestigate the metabo-lism of lead in plants.His realization thatradioactivity had noeffect on the biochemi-cal properties of thelead laid the groundworkfor all subsequent bio-logical uses of radiotrac-ers. Hevesy wouldreceive the Nobel Prizefor Chemistry in 1943.

1929 Ernest O.Lawrence invented thecyclotron, which wouldbecome a major tool forthe production ofradionuclides. Lawrencewould win the NobelPrize for Physics in1939.

1936 At Berkeley’sRadiation Laboratory,John H. Lawrence madethe first clinical use ofan “artificial” radionu-clide, treating aleukemia patient withphosphorus-32.

MILKING MOLYBDENUM Technetium-99m, ashort-lived decay product of molybdenum-99and the most widely used tracer in modernnuclear medicine, is a practical tool onlybecause of a Brookhaven discovery in the latefifties. A chemical means, embodied in theearly “generator” shown here, was found forseparating the technetium from the molybde-num, thus providing hospitals a way to obtainthe tracer on demand.

shuttles along metabolic pathways—evenas it is incorporated into different bio-chemical compounds. Naturally enough,then, many of the earliest uses of radio-tracers were in explorations of life’s intri-cate biochemistry. During the AEC era,both carbon-14 and tritium (hydrogen-3)were used in notable experiments to tracemetabolic pathways in animals and plants,and the utility of these isotopes as researchtools continues today. Carbon and hydro-gen are ubiquitous constituents of biomol-ecules, and the radioactive versions of theseatoms do not alter the chemistry of life.Among the most celebrated of such meta-bolic studies was the unraveling of the

complex cycles of photosynthesis, theprocess by which green plants convertatmospheric carbon dioxide and water intosugar. For this AEC-sponsored work,Berkeley chemist Melvin Calvin receivedthe 1961 Nobel Prize for Chemistry.

More recently, studies with metabolictracers have turned especially to the humanheart and brain. But to make such studiespossible, better ways were needed to “see”just where the tracers were.

SL I C E S O F L I F E : ME D I C A L IM A G I N G

All that has been said about radioisotopesas tools for medical diagnosis and as keysto the mysteries of plant metabolism and

A H E A L T H Y C I T I Z E N R Y

23

1938 Also in Berkeley,Glenn Seaborg (a futurechairman of the AEC)and Emilio Segrè discov-ered technetium-99m.Berkeley’s cyclotronswould also produce thefirst iodine-131, carbon-14, thallium-201, andgallium-67. Seaborg andSegrè would both winNobel prizes for laterachievements.

1946 Nuclear medi-cine’s modern era beganwith the announcementin the June 14, 1946,issue of Science thatradioactive isotopesfrom the Oak Ridgenuclear reactor, a secretwartime facility, wereavailable to qualifiedresearchers.

1947 Benedict Cassenat UCLA used radio-iodine to determinewhether a thyroid noduleaccumulated iodine, akey to differentiatingbenign from malignantnodules.

1948 John Gofman andhis colleagues at theUniversity of California’sRadiation Laboratorybegan ultracentrifugestudies that would allowthem to identify themacromoleculesinvolved in the develop-ment of atherosclerosis.This work would belargely responsible forfocusing the world’sattention on the role ofcholesterol and lipopro-tein patterns in coro-nary artery disease.

M E D I C A L S E R E N D I P I T Y

■ It is a truism of scientific research thatsome of the greatest discoveries emerge assurprising revelations of research with itssights set elsewhere. Examples abound inthe biological research supported by theDOE and its predecessors. Sodium’s role incontributing to high blood pressure, forexample, was revealed at Brookhaven in theearly sixties during studiesthat were focused onanother metabolic issue alto-gether—the retention ofradioactively labeled salt inrats. Also at Brookhaven inthe late sixties, the successfulapplication of L-dopa as amedication for the treatmentof Parkinson’s disease was atangential product of brainfunction studies using radio-active manganese. Followingearly clinical trials, a NewEngland Journal of Medicineeditorial in 1969 described this discovery byGeorge Cotzias (pictured) as “the mostimportant contribution to medical therapyof a neurological disease in the past fiftyyears.” Today, second-generation drugsbased on this research are the treatment ofchoice for tens of thousands of Parkinson’ssufferers in the U.S. alone. ■ Anotherexample of unexpected, though not entirelyserendipitous, ramifications is the emer-

gence of organ transplantation as a main-stream medical procedure from earlyresearch on irradiated mice. In the fifties, itwas known that mice exposed to usuallylethal doses of radiation survived if the dam-aged blood-forming cells of their bone mar-row were replaced with healthy marrow. In1954, however, Oak Ridge researchers

showed that rat marrowcould be used to save themice as well. Contrary toconventional wisdom, thealien donor cells were notrejected by the host. Thisdemonstration of immuno-suppression, in this caseinduced by radiation, trig-gered a renaissance of think-ing about tissue and organtransplantation. Further devel-opment of immunosuppres-sive techniques led to suc-cessful bone marrow trans-

plantation for the treatment of leukemia andother diseases—and eventually to the prac-ticality of kidney, heart, liver, and other organtransplants in humans. The ground-breakingwork at Oak Ridge was one of the startingpoints for these striking developments,which would culminate in 1990 with theNobel Prize for Physiology or Medicine,awarded jointly to Joseph Murray andDonnall Thomas. ■

human physiology presupposes a way ofobserving the invisible emanations of theradioactive tracers. In the experiments ofthe thirties and forties, primitive by today’sstandards, the flow of a radionuclidethrough the body could only be monitoredby Geiger counters or similar devices. Atrue image of the tracer’s distribution wasonly a dream.

In the fifties, however, a new era wasushered in, first by the development of therectilinear scanner by Benedict Cassen atUCLA, and then by Hal Anger’s inventionof the stationary scintillation camera at theRadiation Laboratory in Berkeley. Both ofthese instruments not only detected thegamma-rays (high-energy x-rays) emittedby radioactive tracers, but also preciselyidentified their origins in the body. Cassen’sinnovation was the mechanization of theearliest, point-by-point manual scanningtechniques. Using his motorized raster-stylescanner, Cassen and his UCLA colleaguesperformed diagnostic imaging studies ofthe thyroid using iodine-131, as well assome of the earliest scans to look for brain

tumors. Anger’s more revolutionary stepwas to build a stationary, cameralike sys-tem to do the same job much more quickly.Many of the most commonly used radio-tracers, including thallium-201 and tech-netium-99m, owe their current utility totoday’s generation of Anger cameras;roughly a quarter of all patients in U.S.hospitals undergo tests using these devices.

The next step was an extension to threedimensions—a step that demanded a prac-tical way of visually reconstructing“slices,” or transverse sections, of thebody, which might then be “stacked”together to produce a 3-D picture of inter-nal structures. In the end, several contribu-tions, in both instrumentation and compu-tation, converged in what we now know ascomputed tomography, or CT. One of theearliest contributors was David Kuhl,working in part with AEC and ERDA sup-port at the University of Pennsylvania. In1959 Kuhl constructed a device thatembodied many of the principles of today’ssingle-photon emission computed tomog-raphy, or SPECT, instruments. With it,


24

1951 Benedict Cassenand his colleaguesdeveloped an automated“rectilinear scanner” toimage the distribution ofradioiodine in the thyroidgland. This followed onCassen’s constructionof the first medical scin-tillation detector in1949. The rectilinearscanner would becomethe workhorse of nuclearmedicine for more thantwo decades.

1951 Iodine-131became the first radio-pharmaceuticalapproved by the Foodand Drug Administrationfor routine human use.

1951 Frank R. Wrenn,Jr., an AEC Fellow atDuke University, pub-lished the results of apositron-counting studythat used copper-64placed within a brainpreserved inside itsskull—the first studysuggesting the medicalpossibilities of positronemitters.

1952 John H. Lawrenceand Cornelius Tobiasused a helium-ion beamfrom Berkeley’s 184-inch cyclotron to treathuman patients suffer-ing from pituitarytumors. Using particlebeams for medical ther-apy had first been pro-posed by Robert Wilsonin 1946.

GETTING THE INSIDE STORY Benedict Cassen (left) at UCLA and Hal Anger at Berkeley’s RadiationLaboratory took major strides in diagnostic imaging by providing practical means for visualizing thedistribution of radioactive tracers in the body. Descendants of Anger’s camera remain the standardimaging tool of nuclear medicine around the world.

despite the lack of sophisticated mathemat-ical algorithms for doing tomographicreconstructions, he produced the firsttransverse section images ever obtained bysingle-photon imaging. As did Kuhl’s pro-totype, today’s SPECT scanners—main-stays of present-day nuclear medicine—detect a radiotracer’s gamma-ray emissionsby rotating detectors around the body. Intoday’s machines, a computational algo-rithm then reconstructs the distribution ofthe tracer that gave rise to the detected sig-nals. This reconstructed slice is then com-bined with others to produce a 3-D image.Six years later, Kuhl performed the firsttransmission transverse section scan of apatient’s chest, this time producing imagesby detecting gamma-rays transmittedthrough the body from source to detector.This concept is similar to that now embod-ied in commercial x-ray CT scanners.

Yet another stride in medical imagingexploited a peculiar property of someradioactive isotopes: As they decay, theyemit a positron, an elementary particle ofantimatter that promptly undergoesmutual annihilation with a nearby elec-tron. The product of this annihilation istwo gamma-rays traveling in exactly oppo-site directions. Detecting this pair ofgamma-rays thus fixes their origin along astraight line between the two opposingdetectors. Detecting many such pairs canpin down the point of origin to within a few millimeters—aprocess called positronemission tomography.PET emerged as animportant medical toolonly in the seventies, itspractical developmentsupported by both theNIH and the AEC. Thebreakthrough was aseries of machines con-structed by MichaelPhelps, Edward Hoff-man, and Michel Ter-Pogossian at Washing-ton University in St.Louis. But much of thegroundwork had beenlaid earlier. In 1953, at

MIT, Gordon Brownell fabricated the firstdetectors designed to take advantage of thepositron-annihilation process, and in 1961James Robertson at Brookhaven built aring-shaped detector system that foreshad-owed later instruments. One element miss-ing from Robertson’s prophetic device,however, was again an efficient mathemati-cal algorithm for computing the three-dimensional tomographic images.

Today, more than 260 centers around theworld make use of PET scanners, amongthem one at Berkeley with the world’s high-est resolution. PET scanning technology hasbeen the key to a whole generation of meta-bolic studies, as well as clinical diagnostictests. An organ of especially keen interest isthe brain. Mapping its activity usuallymeans following the uptake and metabo-lism of glucose, the brain’s dominant sourceof energy. In the early seventies, a collabo-ration among Brookhaven researchers,


25

1953 Gordon Brownellat MIT constructed thefirst device to exploitpositron-electron annihi-lations as an imagingtool, another precursorof today’s PET scanners.

1954 Oak Ridgeresearchers successfullytransplanted functionalbone marrow from a ratto an irradiated recipi-ent mouse, thus demon-strating the immunosup-pressive effects of radia-tion, a key to futureorgan transplantation.

1955 At UCLA GeorgeTaplin used rose bengallabeled with iodine-131to image the liver andsimilarly labeled hippu-ran to image kidneyfunction.

1958 Walter Tuckerand his coworkers atBrookhaven invented ameans of making theshort-lived nuclide tech-netium-99m available tosites far removed fromresearch reactors. Thisisotope is now the mostwidely used radionuclidein medicine.

1958 Hal Anger atBerkeley developed the“scintillation camera,”which would makedynamic studies withradionuclides practicalfor the first time. Thisupdated instrumentsuperseded Anger’s first“gamma camera,” whichhe developed in 1952.Anger cameras are nowin use around the world.

IN-DEPTH ANALYSIS Beginning in the late fifties,supported by the AEC and other agencies,David Kuhl at the University of Pennsylvaniaconstructed some of the earliest forerunnersof today’s SPECT and CT scanners. The MarkIII scanner shown here detected photons froman injected tracer and applied interactivereconstruction techniques using a built-incomputer. The first quantitative three-dimen-sional measures of brain function were per-formed with this machine

workers at the University of Pennsylvania,and scientists at the NIH produced thepositron-emitting compound that made thispractical—a compound known by its short-hand name 18FDG. In 1976, at Pennsyl-vania, the same team used PET and 18FDGto obtain the first images of glucose metab-olism in the human body. Among subse-quent studies, work at UCLA provided thefirst “brain mapping” of normal functionand illuminated how the brain developsfrom childhood to adolescence. And atBrookhaven studies have revealed meta-bolic changes in the brain associ-ated with smoking and drug use.Over the past two decades, BER-supported research has also used18FDG and other tracers labeledwith positron emitters to studyepilepsy, Alzheimer’s disease,Parkinson’s disease, schizophre-nia, depression, and a host ofother ailments. Some of thesesame compounds are equally use-ful as PET tracers in the diagnosisof heart disease and in searchingfor the sites of primary andmetastatic cancers.

HI G H -TE C H TR E AT M E N T S :I S O T O P E S A N D PA R T I C L E

BE A M S

Beyond diagnosis lies treatment,and here, too, radioisotopes have

had enormous impact. One isotope, iodine-131, is still the most widely used radioac-tive substance for the treatment of diseasessuch as toxic goiter and thyroid cancer. Asa result of its use, no other metastatic can-cer is more effectively treated than thyroidcancer. Cancer treatment with radioactiveiodine-130 was first tried at MIT and atBerkeley’s Radiation Laboratory in 1941,and in 1946 iodine-131 was first used in an“atomic cocktail” for thyroid cancer ther-apy. After iodine-131 became availablefrom the Oak Ridge reactor, it was widely


26

1959 David Kuhl at theUniversity of Pennsyl-vania made the firsttransverse section scanof the body with adevice that was theforerunner of today’ssingle-photon emissioncomputed tomography(SPECT) scanners.

1960 While studyingsalt retention in differ-ent strains of rats,Lewis Dahl at Brook-haven discovered thelink between salt con-sumption and high bloodpressure.

1961 James Robertsonand his colleagues atBrookhaven built a 32-crystal positron camera,the “head-shrinker,” thefirst single-plane PETinstrument.

THE BIRTH OF PET The “head-shrinker” (at left),developed by James Robertson at Brookhavenin 1961, was a direct forerunner of today’spositron emission tomographs. The first prac-tical PET camera built for human studies isshown above, with one of its developers,Michael Phelps. Called PETT III (the extra Twas for “transaxial”), it was developed atWashington University in 1974. Unlike theBrookhaven prototype, the WashingtonUniversity instruments embodied advancedmathematical algorithms for computing three-dimensional images.

used in both treatment and diagnosis;indeed, until the advent of technetium-99m, it was the most commonly usedradioisotope for medical diagnosis. In1951 it became the first radiopharmaceuti-cal approved by the FDA for human use.

Many of the early radiopharmaceuticalswere first produced at Berkeley’scyclotrons, which propelled atomic parti-cles—protons and the nuclei of light ele-ments, for example—into awaiting targets,thereby producing trace amounts of mate-rials never before seen, many with medicalapplications. But as the cyclotrons grew insize, another enticing possibility emerged.In 1946 Robert Wilson, then in Berkeleyand later director of the Fermi NationalAccelerator Laboratory, suggested that theracing beams themselves might be directedat deep-seated tumors. X-rays were already

used for such purposes, but they are indis-criminate beams, depositing their poten-tially destructive energy all along theirpaths. Charged particles, on the otherhand, behave more like explosive depthcharges, doing most of their damage justbefore they stop. The trick would be to tai-lor a beam of such particles to stop exactlywhere a tumor was known to be.

With this vision in mind, researchers ledby John Lawrence and Cornelius Tobiasbegan to lay the groundwork for medicaltreatments with charged particles. Then,between 1954 and 1993, with the DOE(and its predecessors) and the NIH provid-ing support, beams from two Berkeleyaccelerators were used to treat more than2000 patients whose conditions werejudged inoperable or surgically risky. Inthese clinical trials, striking successes were


27

THE BRAIN AT WORK These classic PET images, obtained at UCLA’s Laboratory of Structural Biologyand Molecular Medicine, depict brain activity during five typical tasks. The highest level of activity,meaning the highest rate of glucose metabolism, is indicated by the red areas. The five tasks were“looking” at a visual scene, “listening” to a mystery story that included both language and music,counting backwards from 100 by 7’s (“thinking”), “remembering” previously memorized objects,and touching the thumb consecutively to the four fingers (“working”).

1961 Melvin Calvin, aBerkeley chemist,received the Nobel prizefor his elucidation ofphotosynthesis, theprocess by which plantsconvert carbon dioxide,water, and sunlight intochemical energy. Hiswork was a landmarkapplication of radiotrac-ers to the study of meta-bolic pathways.

1966 The scanningtransmission electronmicroscope (STEM)arose out of AEC-fundedbasic research under thedirection of AlbertCrewe, at Argonne andat the University ofChicago. In the eighties,Brookhaven scientistswould develop heavy-atom-conjugated labels(yellow in the imageabove) for pinpointingspecific molecules orsites in biological struc-tures.

1968 George Cotzias atBrookhaven publishedthe first report of long-term L-dopa treatmentfor Parkinson’s disease.L-dopa analogs remainthe medications ofchoice today.

L O O K I N G L I S T E N I N G T H I N K I N G

R E M E M B E R I N G W O R K I N G

achieved in treating pituitary tumors, can-cer of the eye, and a life-threatening mal-formation of cerebral blood vessels. Today,the legacy of these early experiments andclinical trials includes several proton accel-erators around the world—including oneat the Loma Linda University MedicalSchool, designed and built by Berkeley and

Fermilab physicists—and a heavy-ionaccelerator in Japan dedicated to patienttreatment.

An approach that is potentially evenmore effective in treating brain tumors thatresist conventional therapies is beingexplored at several DOE and universitylaboratories. In boron neutron capture


28

1968 Brookhaven sci-entists developed thetechnique of neutron dif-fraction for the struc-tural analysis of proteinmolecules. In the imageabove, neutron-scatter-ing data were used toproduce a picture of abacterial ribosome sub-unit comprising twenty-one proteins.

1968 Researchers atthe Oak Ridge Institutefor Nuclear Studies(now the Oak RidgeInstitute for Scienceand Education) discov-ered the affinity of galli-um-67 for soft-tissuetumors, leading to itswidespread medical usein imaging lymphomas,lung cancer, and braintumors.

1974 Following workwith several prototypes,a Washington Universityteam partially funded bythe AEC developed thefirst practical PET scan-ner (PETT III) designedfor human use. The firststudies of human brainand liver tumors andcardiovascular diseasewere carried out withthis system

B I G M A C H I N E B I O L O G Y

■ Biomedical scientists continue to do someof their most notable research at the bench,using the tools and techniques of the smalllaboratory. But an increasing fraction of theirresearch demands the involvement of physi-cists, chemists, and engineers. Indeed,throughout this account of biological andmedical progress, the instrumental con-trivances of science and medicine haveshared the spotlight with biological insight.Not surprisingly, then, the resources of biol-ogy extend even to some of the nation’slargest scientific facilities, national user facili-ties built and supported for the use of allqualified individuals and research groups.The DOE plays the preeminent role in con-structing and operating these facilities.■ Studying biological function, for instance,increasingly relies on uncovering the detailed

structure of biological macromolecules. Thisis now commonly done by using the intensex-ray beams produced at synchrotron radia-tion facilities—machines often costing hun-dreds of millions of dollars to construct.X-rays are focused on a tiny protein crystal,producing a diffraction pattern that canreveal the protein’s intricate structure. Today,almost half of the new structures of biologi-cal macromolecules reported in the leadingjournals have been refined using synchrotrondata.The busy floor of Brookhaven’s NationalSynchrotron Light Source, shown above,reflects this intense current interest in syn-chrotron radiation. Users of these and othermajor DOE facilities include scientists frommany universities, medical schools, govern-ment laboratories, and pharmaceutical com-panies. ■

therapy, or BNCT, a nonra-dioactive boron-labeled com-pound is administered thataccumulates predominantly inthe tumor, which is then irra-diated with neutrons. Theneutrons cause the boronatoms to fission, releasingenergy that destroys thetumor cells. This kind ofhighly localized cell surgerywas conceived in the thirtiesand tried clinically in thefifties, with inconsistentresults. Following furtherrefinements, however, clinicaltrials resumed in 1994 atBrookhaven and at MIT, in associationwith nearby medical schools and hospitals.

Human health has always been at the

heart of biological research within the

energy agencies, and it has thus been the

central subject of the last two chapters.

But from the earliest days of the AEC, at

a time dominated by anxiety about

radioactive fallout, environmental and

ecological studies, too, have been a nat-

ural part of the picture. Next, then, a

short history of environmental research

—research born of worries about the fate

of wind-blown products of nuclear blasts

and sustained today by a much wider

concern about the global effects, and last-

ing impact, of energy production and use.


29

RAYS OF HOPE A patient is pre-pared for treatment with a beamof charged particles tailored todeposit most of its destructiveenergy within a malignanttumor. The tumor’s proximity tocritical neurological structuresmakes this form of therapyespecially suitable.

❧

1976 Scientists fromBrookhaven, led byAlfred Wolf, synthesized2-deoxy-2-fluoro-D-glu-cose (FDG) labeled withthe positron emitter fluo-rine-18. This tracer wasthen used by a teamfrom the University ofPennsylvania and theNIH to obtain the firstimages of energymetabolism in thehuman brain, an earlystep in a revolution inbrain imaging using PET.

1987 At UCLA patientscarrying the Hunting-ton’s disease gene wereidentified with PETabout five years beforedamage from this abnor-mal gene could be iden-tified by symptoms,behavior tests, CT, orMRI.

1994 Phase I clinicaltrials using boron neutroncapture therapy to treatglioblastoma multiformebegan at Brookhaven, incollaboration with theBeth-Israel MedicalCenter, New York.

1997 The RegionalNeuroimaging Centerwas launched at Brook-haven, jointly funded by OBER and theNational Institute onDrug Abuse. It will usestate-of-the-art medicalimaging technologiessuch as PET, SPECT,and MRI to study thebiochemical roots ofdrug abuse and addic-tion in an effort todevelop more effectivetreatments.

ENVIRONMENTALCONCERNS From

Meteorology to Ecology

AN EY E O N T H E WE AT H E R

In the postwar years, responsibility for fall-out monitoring was spread among severallaboratories. Chief among them was theHealth and Safety Laboratory (now theEnvironmental Measurements Laboratory)in New York City, which established theearliest and most authoritative monitoringnetwork in the world—and ultimately pro-duced an integrated history of the distribu-tion of nuclear weapons debris in the air,on land, and in water, as well as in plantsand animals, especially the human foodchain. As part of the High-AltitudeSampling Program, for example, instru-mented balloons and aircraft were sentaloft to sample the stratosphere and toassess the exchanges of material betweenthe stratosphere and the lower atmosphere.The resulting data contributed in a con-crete way to the international moratoriumon above-ground testing in 1963.

Beyond measurement, however, lay themore daunting challenge of prediction—achallenge that would naturally breed threedistinct research thrusts: inquiries into thetransport of radioactive materials releasednear the ground (a situation that mightarise following, say, an accident at a

weapons production facility), research intohow clouds scavenge radionuclides andthen deposit them in rain, and efforts tounderstand the global transport of materi-als released during atmospheric weaponstests.

In pursuit of answers to the near-surfacequestion, several of the national laborato-ries installed meteorological facilities,including several Air Resources Laboratory(ARL) facilities operated by the U.S.Weather Bureau for the AEC. There inves-tigators sought scientific methods to pre-dict how airborne materials are trans-ported in the lower atmosphere and howtheir eventual deposition depends on thenature of the material and on atmosphericand topographic variables, including thepresence of complex mountainous terrain.Using the collective results of these efforts,Frank Gifford and his colleagues at the ARLAtmospheric Turbulence and DiffusionLaboratory in Oak Ridge then developed aset of curves for calculating the spread ofpollution from a “point source.” In a timewhen the slide rule was the dominant com-putational tool, these dispersion modelswon international acceptance as tools forpredicting the fate of nuclear reactor emis-

31

n matters of the environment, public

awareness lagged far behind the activities of the energy agencies. As early as the

forties and fifties, in an era when most people had never even heard the word “ecol-

ogy,” the AEC was forging an enviable record of environmental and ecological

research. The initial catalyst was again the development of nuclear weapons and

the two decades of atmospheric testing that followed. Estimating the health effects

of released radioactivity depended not only on epidemiology and radiation biol-

ogy, but also on knowing the fates of the airborne radioisotopes in the first place.

Meteorology and oceanography were no less important than biology—as was

research into the ecological processes that cycled materials through plants and ani-

mals to human beings. Atmospheric and environmental studies thus fell naturally

within the purview of biomedical research.

IILL WINDS The AtmosphericStudies in Complex Terrainprogram, carried out atseveral of the national labsbeginning in 1978, pursuedimprovements in the mod-eling of wind flows in hillyor mountainous areas. Inthis Livermore computersimulation, the white dotsrepresent a pollutantentrained in the nocturnalair flow within a Coloradomountain canyon.

sions and industrial pollutants.A natural part of the effort to under-

stand atmospheric dynamics was the use oftracers to track the movement of materials,both locally and around the globe—not

unlike the use of radionuclides to followdynamic processes in the human body.Early “tracers of opportunity” includedsuch natural constituents of the atmos-phere as spores and ozone, as well aspower plant emissions and debris fromweapons tests. In at least one case, anuclear weapon was even “salted” withtungsten, which could be convenientlytraced around the world. Today’s experi-

ments in the outdoor laboratory are morebenign. In the seventies, inert chemicaltracers were developed at the ARL facilityin Idaho Falls, at the EnvironmentalMeasurements Laboratory, at Brookhaven,

and at Los Alamos. Together withultrasensitive detectors, these tracersare now used in dispersion experi-ments extending up to 2500 kilome-ters.

Early AEC studies of cloud chem-istry evolved no less dramatically.The initial studies focused on thescavenging and deposition of air-borne radionuclides, but by the sev-enties, concerns had shifted toindustrial pollutants. In this new eraof environmental awareness, aciddeposition—more popularly, acidrain—promptly blossomed into aninternational issue, blamed for thedecline of forests, damage to aquaticecosystems, and human respiratoryillness. In the mid-seventies, buildingon the earlier AEC studies, ERDAscientists were among the first in theU.S. to tackle this problem. In 1976ERDA established the MultistateAtmospheric Pollution Power Pro-duction Study, a program of atmos-pheric experimentation and model-ing that focused on the regionaltransport and chemical transforma-

tion of emissions from oil- and coal-firedpower plants. Working with the Environ-mental Protection Agency and the ElectricPower Research Institute, this programprovided part of the justification for subse-quent controls on sulfur emissions frompower plants. Then, in 1980, as part of theten-year, multiagency National Acid Pre-cipitation Assessment Program, OHERestablished the Processing of Emissions byClouds and Precipitation program, whichfocused three decades of research experi-ence on the acid rain issue.

A CH A N G I N G CL I M AT E

In the area of atmospheric studies, thelegacy of the fifties and sixties has thusbeen especially fertile. But perhaps the rich-est payoff has been a heightened awarenessof our atmosphere’s complexity and, in


32

1949 Brookhaven sci-entists began a thirty-year program aimed atassessing the effect ofradiation on livingplants. Much of thework would take placeat the cultivated GammaField, established in1951. Results here andat Oak Ridge would con-firm Brookhaven predic-tions that relativeradiosensitivity amongplant species varies withnuclear volume andchromosome size.

1950 Using phospho-rus-32 in a Connecticutlake, Evelyn Hutchinsonat Yale documented thequantitative cycling ofthe element—an essen-tial and often limitingnutrient—within a lakeecosystem.

1951 The AEC sup-ported the establishmentof the Laboratory ofRadiation Ecology atSavannah River, directedby Eugene Odum of theUniversity of Georgia.

THE WAY THE WIND BLOWS Early research aimedat improving models to predict the near-sur-face dispersion of pollutants relied in part onspecial meteorological facilities such as thisone at Brookhaven. On this particular day, asshown by the three plumes, the wind wasblowing in different directions at three heightsabove the ground—a worst-case scenario forthe spread of airborne materials.

turn, a keener appreciation of its sensitivityto human activity. The third of the AEC’smajor research thrusts—atmosphericdynamics on a global scale—contributed inan especially important way to this growingenvironmental awareness.

In the early sixties, the AEC’s interestwas the global transport of weapons testdebris. Accordingly, at Livermore, mathe-matical physicist CecilLeith was one of only ahandful of researchers inthe world using theemerging power of scien-tific computing to simu-late global atmosphericdynamics. Later, hewould move on to thenew National Center forAtmospheric Research(NCAR) in Boulder,where he established itsreputation as one of theworld’s leaders in devel-oping atmospheric gen-eral circulation models(GCMs)—advanced cli-mate models that providenot short-term meteoro-logical forecasts, but

rather long-range prognosesof global climate. In theearly seventies, with AECsupport, NCAR’s WarrenWashington was the first touse their GCM to study thepossible climatic effects ofthe heat generated by energyproduction.

Looming even larger,however, was growing evi-dence that human activitieswere tilting the worldwidebalance of atmosphericgases: By the late seventies,the burning of fossil fuelswas recognized as a principalculprit in a steadily risinglevel of atmospheric carbondioxide (CO2), a trend dra-matically illustrated by themeasurements of C. DavidKeeling at the Mauna Loa

Observatory in Hawaii. A direct relationshipbetween atmospheric CO2 concentrationsand air temperatures had been known sincethe turn of the century, so it was natural tobe alarmed about the possibility of globalwarming if the trend continued unchecked.In 1977 ERDA was the first federal agencyto outline a comprehensive research pro-gram on the CO2-climate connection.

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

33

1955 Early efforts tounderstand atmospherictransport and dispersionled to the publication ofMeteorology and AtomicEnergy, which quicklybecame a basic meteo-rological reference. Asecond edition, pub-lished in 1968, wouldfor years remain thedefinitive reference forsmall-scale meteorology.By 1984 it had evolvedinto the thousand-pagevolume, AtmosphericScience and PowerProduction.

1956 The EnvironmentalResearch Branch wascreated within theAEC’s Division ofBiology and Medicine,for “research pertainingto man and his environ-ment, including disci-plines such as ecology,oceanography, marinebiology, geophysics, andmeteorology.”

1955

310

320

330

340

350

360

370

CO

2 co

ncen

trat

ion

(ppm

v)

Year1970 1985 2000

A DANGEROUS TREND? The forty-year record of atmospheric CO2concentrations on Mauna Loa in Hawaii depicts an undeviatingupward trend, as well as predictable seasonal variations. Sinceatmospheric CO2 concentrations have long been correlated withglobal temperature, these measurements by C. David Keeling ofthe Scripps Institution of Oceanography, supported in part by theenergy agencies, were an important catalyst in stimulatingtoday’s research on global climate change.

A CHANCE OF RAIN Global climate models aim at predicting the world-wide consequences of certain input assumptions—a rising concen-tration of atmospheric CO2, for example. Here, a Livermore simulationpredicts the changes in rainfall patterns during an El Niño event, aperiod of surface water warming in the tropical Pacific. Precipitationincreases (compared with normal) are foreseen in areas shown inblue, whereas decreases are predicted for areas shown in red.

Over the past two decades, the DOE hastackled some of the central tasks in globalclimate research. One has been to examinethe global carbon cycle, quantifying byway of modeling and measurement all sig-nificant natural sources and sinks of CO2,as well as those attributable to humanactivity. One of the key figures in this areawas Oak Ridge’s Jerry Olson, who wasamong the first researchers to identify theimportance of carbon exchange betweenterrestrial ecosystems and the atmosphere.A second task has been the continuousrefinement of GCMs as tools for simulat-ing climate dynamics and for predicting cli-mate change. Using one such model,Warren Washington estimated in 1984 thata doubling of atmospheric CO2 levelswould produce a global temperature rise of4 degrees Celsius. This remarkable earlyprediction has been revised only slightly, to1.5–3.0 degrees Celsius, despite the avail-

ability today of far moreelaborate models.

Yet another task wasthe continuing challengeof measurement. In 1989the government launchedthe U.S. Global ChangeResearch Program, anambitious multiagencyeffort to focus on globalenvironmental changeand its impacts. TheDOE responded by estab-lishing the largest sur-face-based research pro-gram among the U.S. cli-mate research efforts, theAtmospheric RadiationMeasurement (ARM)program. This multi-institutional effort strivesto quantify the fate ofsolar radiation interact-ing with clouds andfalling on the earth andto capture that knowl-edge in improved atmos-pheric models. Some fun-damental questions drivethe effort: How muchsolar energy is reflected

or absorbed by clouds and atmosphericaerosols? How much is reflected orabsorbed at the earth’s surface? And howmuch is returned to space as heat? Only byunderstanding these processes can we hopeto further refine models of the earth’s cli-mate and thus reconstruct the past and moreconfidently predict the future. Accordingly,the ARM sites represent the most inten-sively measured volumes of the atmosphereever maintained for an extended period.

Today, global climate change researchcontinues as a vigorous multiagency prior-ity, propelled by the issue’s overarchingimportance and challenged by the profoundcomplexity of atmospheric and biologicalprocesses. The DOE is now one of severalfederal agencies, notably NASA, the NationalScience Foundation, and the NationalOceanic and Atmospheric Administration,working as partners to predict future con-centrations of greenhouse gases, to assess


34

1959 Wallace Broeckerat Columbia Universityused natural radiocarbonin the ocean to quantifyocean circulationprocesses.

1960 In advance of theproposed use of nuclearexplosions to excavate a harbor near CapeThompson, Alaska, AEC-sponsored scientistsbegan an exhaustiveecological survey of thearea. This “environmentalassessment” predated byalmost a decade therequirements of theNational EnvironmentalPolicy Act of 1969.

1960 University ofWisconsin scientistsused radiosodium andradioiodine to documentthe physical and biologi-cal mechanisms of mate-rial mixing and transportin a chemically stratifiedlake.

1961 Researchers atOak Ridge developed aspecific-activity method-ology to estimate thebioaccumulation of radio-nuclides in terrestrialand aquatic organisms.The following year theywould introduce the firstanalog models to simu-late the distribution,cycling, and fate of radio-nuclides in ecosystems.

ARM’S REACH OBER’s Atmospheric Radiation Measurement programwill provide a firmer foundation for computer models used for atmos-pheric research and climate predictions. Data are being acquired fromthree Cloud and Radiation Testbed (CART) sites, located in the south-ern Great Plains, on the North Slope of Alaska, and in the westernPacific. Each CART site consists of a central facility and smaller clus-ters of instruments deployed over an area of 22,500 square kilometers.

their likely effects on the climate, and toevaluate the resulting biological and eco-nomic impacts.

TH E DY N A M I C OC E A N

Perhaps even more deeply mysterious thanatmospheric dynamics are the workings ofthe oceans. From the earliest days of atmos-pheric testing, the AEC sought to under-stand the fate of radioactive fallout overPacific waters. But the agency’s interest wasgreatly heightened in 1954, when aJapanese fishing boat and its cargo of fishwere contaminated following a PacificOcean nuclear test. Suddenly, the sea andits denizens were subjects of intense inquiry.Ensuing AEC support for oceanic researchreaped unexpected rewards.

One of the pioneers was WallaceBroecker, of Columbia University’sLamont-Doherty Geological Observatory(now the Lamont-Doherty Earth Obser-vatory). Soon after the 1954 incident, hebegan using natural and bomb-generatedradionuclides as “clocks” to study oceandynamics. By measuring the ratios of car-bon isotopes, for example, he found that,

whereas the average CO2 molecule remainsin the atmosphere for seven years, bottomwater in the Pacific Ocean turns over onlyonce every thousand years. His analyses ofCO2 absorption by the oceans also pro-vided new data on the fate of atmosphericCO2 more than a decade before it wouldbecome an important climate change issue.Broecker’s methods were seminal: Distri-butions of stable and radioactive isotopeswere subsequently used to measure theaccumulation rates of deep-sea sedimentsand to develop the first records of climatechange in the past. Broecker also turned toradionuclides as tracers. Using strontium-90 from fallout, for example, he was ableto define the Atlantic Ocean “conveyorbelt” that operates between Greenland andthe equatorial tropics. In 1996, in part forwork supported by the AEC, he wasawarded the Presidential Medal of Science.

In the seventies, increasing attentionturned to the ocean margins. Fallout frompast decades was washing into lakes andrivers, then moving downstream intocoastal waters. Toxic chemicals followed asimilar path. At the same time, nuclear

35


Sea-to-Air Transfer

Warm Shallow Curre

nt

Cold and Salty Deep Current

A GLOBAL CONVEYOR BELT The connectedness of the world’s oceans is suggested by this schematicdepiction of the “great ocean conveyor.” Evaporation in the North Atlantic and transfer of the vaporto the Pacific leaves behind saltier water, which then sinks and drives the cold deep current. Thewarm surface current has a direct impact on world weather, accounting, for example, for NorthernEurope’s relatively mild winters. Many of the details of this global conveyor were revealed by earlyAEC-sponsored research.

1962 Radiotracerswere used by OregonState scientists to showthat fecal pellets pro-duced by marine organ-isms are the major vec-tor for transporting sub-stances from the oceansurface to deep water.

1963 Cecil Leith atLivermore developed oneof the first atmosphericgeneral circulation mod-els, providing the foun-dation for future globalchange calculations andglobal weather predic-tions.

1967 Oak Ridge begana major effort to under-stand the thermaleffects of nuclear powerplants. Aquatic ecologyprograms at Oak Ridge,Hanford, and SavannahRiver would expand dra-matically in the seven-ties, in response to theNational EnvironmentalPolicy Act. The researchwould reveal fewadverse effects of ther-mal discharges intoaquatic ecosystems.

1968 Two permanentsites were set aside forlong-term ecologicalresearch: 120 squaremiles of sagebrushdesert near Richland,Washington, and 100acres of prairie forestborder at Argonne. Fieldwork was inaugurated at both sites.

facilities were being developed on majorriver systems throughout the U.S., and oilexploration and waste disposal were beingproposed for offshore waters. The resultinginterdisciplinary studies led to freshinsights into continental shelf dynamics—and ultimately to confident predictions ofthe consequences of oil spills, to standardsfor the release of hazardous substances atsea, and even to scientific fishing forecasts.

Impelling the earliest of this oceano-graphic work was concern about ocean-borne transport of radioisotopes awayfrom the sites of atmospheric weapons testsin the South Pacific. But an equally vitalhuman health issue was the accumulationof radioactivity in seafood. Accordingly,AEC-supported researchers founded thefield of marine radioecology by studyingthe bioaccumulation of radionuclides inmarine organisms and assessing the conse-quent ecological risks. One of theresearchers, Roger Revelle, of the ScrippsInstitution of Oceanography, received thePresidential Medal of Science in 1990, inpart for his pioneering work in this area.As part of this effort, the first applicationof carbon-14 as an ecological tracer was tomeasure photosynthetic rates inthe world’s oceans. For twentyyears, AEC research provided fun-damental insights into marine foodchains and produced most of theworld’s information on the rate ofCO2 fixation and on its fate in theoceans—information that wouldfeed naturally into later work onglobal climate change.

TH E OU T D O O R LA B O R AT O RY

This prescient work on oceanecosystems points, in fact, to yetanother strand of environmentalresearch, one intricately entwinedwith studies of atmospheric andoceanic dynamics and the disper-sion of air- and waterborne conta-minants. Its early theme was thefate and effects of radioactivityreleased into terrestrial and fresh-water ecosystems. In concert withresearch on human health effects,these strands of environmental

exploration thus sought a complete pictureof the impacts of nuclear technology: Whatis the fate of the radioactive materials werelease? What are their direct effects onhumans? And what are their effects on thebiosphere of which we are a part? The sev-enties would again broaden the charge toencompass all energy-related emissions,but the larger question would remain thesame: What are the consequences of theenergy choices we make?

In approaching such questions, theAEC’s most pervasive contribution fol-lowed the theme of its efforts in nuclearmedicine and atmospheric studies, namely,the use of radioactive tracers. Beginningwith modest efforts at several universitiesand national laboratories, radioecologygrew to encompass studies of materialpathways and flow rates through terrestrialand aquatic ecosystems of every descrip-tion. The research involved nearly all of theAEC national laboratories, in part becauseof their locations in different environmentsof the country.

At first, radiotracer studies dealt mainlywith iodine-131, a short-lived fission prod-uct deposited on the landscape from


36

■ In light of their research activities, it is not surprisingthat the energy agencies have also played a significantrole in developing instrumentation for oceanography.Examples include acoustic sounders to measure themass and movement of plankton, modified flow cytome-ters that have isolated new species of organisms, andexpendable microcomputer-controlled sensors that canbe dropped from airplanes or ships. Another was a fast-repetition-rate fluorimeter,developed by Paul Falkow-ski at Brookhaven, thatmeasures real-time photo-synthesis in seawater. Nota-bly, this instrument playeda central role in recent,highly publicized experi-ments that produced ashort-lived phytoplanktonbloom in the South Pacificby “fertilizing” the oceanwith iron. ■

M E A S U R E M E N T S A T S E A

1971 The first terrestrialcarbon cycle modelswere developed fromdata obtained by theInternational BiosphereProgram, jointly sup-ported by the AEC, theNational ScienceFoundation, the U.S.Forest Service, andother agencies.

1972 Oak Ridge andColumbia University sci-entists used carbon-14and the inorganic chemi-cal properties of sea-water to quantify theocean carbon cycle andto determine the fate ofCO2 produced by fossilfuel combustion.

1972 The AEC desig-nated Savannah River as the first NationalEnvironmental ResearchPark.

1973 The AtmosphericRelease AdvisoryCapability was estab-lished at Livermore totrack and predict thetransport of potentiallydangerous atmosphericreleases, both naturaland anthropogenic.

weapons-material pro-duction plants, and withradioactive productsreleased into theColumbia River fromthe reactors at Hanford.Later, nuclear testing ledto the spread of radioac-tive cesium and stron-tium isotopes, whichprompted research pro-jects on soil migration,root uptake, uptake bygrazing and browsinganimals, and transfer tofood products. A majorpart of the aquaticresearch was conductedat Oak Ridge, Hanford,and Savannah River,whereas much of thework on soils, plantuptake, and the dairypathway was done at agricultural schoolswithin major universities. Together, theseresearch efforts pioneered the quantitativestudy of environmental processes and pro-vided not only the mechanistic understand-ing, but also the historical databases thatsupported the DOE’s early environmentalrestoration program, and that underlietoday’s ongoing cleanup of contaminateddefense sites.

But the first ecological research linked tothe nuclear era focused on radioactivity’sdirect effects—work that predated even theAEC. Already mentioned on page 12 werestudies by fisheries scientists from theUniversity of Washington, aimed at assess-ing the possible effects of effluents fromHanford’s wartime reactors. And by 1946the region’s sheep and cattle were beingmonitored for radioactive iodine uptake.Nor was the plant kingdom ignored. Forthirty years, starting in 1949, Brookhavenscientists studied the effects of radioactivityon plants, first on introduced species andplants of economic importance and later onnative species. An important result of thiswork was the discovery that the volume ofthe cell nucleus in different plant specieswas an important factor in determining thespecies’ relative sensitivity to radiation.

Then, in 1951, the AEC took a majorstep toward the systematic study of ecol-ogy: The agency granted $10,000 each tothe University of South Carolina and theUniversity of Georgia to conduct a biologi-cal inventory of the Savannah River site, inpreparation for constructing a facility thereto produce materials for nuclear weapons.Eugene Odum led the Georgia effort, intime putting together a research center ofinternational repute, first called theLaboratory of Radiation Ecology, then theSavannah River Ecology Laboratory. Earlystudies of plant succession and pioneeringapplications of radiotracers to the study offood chains and food webs led to studies ofwetlands ecology, endangered species of theSoutheast, regional biodiversity, and theenvironmental chemistry of trace metals.

Also in the fifties, the AEC created itsEnvironmental Sciences Branch to supportstudies of terrestrial, freshwater, andmarine systems, with the emphasis on thelong-term fate and effects of radionuclides.In this encouraging environment, StanleyAuerbach at Oak Ridge shifted his empha-sis from laboratory experiments to fieldwork focused on how radionuclides mightmigrate through the food chain, from waterand soil to plants, animals, and humans. A


37

EXPLORING NEW FIELDS Eugene Odum, a young University of Georgia pro-fessor, pioneered the use of radionuclides as ecological tracers in thefifties at the Savannah River reservation. In recognition of his contri-butions to ecological research, Odum shared the 1987 Crafoord Prize,awarded by the Royal Swedish Academy of Sciences in areas not cov-ered by the Nobel prizes.

1975 ERDA establishedthe first integrated pro-gram dedicated tounderstanding the move-ment of contaminantsand other materials incoastal waters.

1975 Research at OakRidge documented theimportance of dry depo-sition as a contributorto total acid precipita-tion in a forested water-shed.

1976 Global carboncycle models predictedthe future doubling ofatmospheric CO2 fromthe combustion of fossilfuels. The followingyear, ERDA wouldlaunch the first system-atic federally fundedprogram to study globalclimate change as apossible consequence ofthis rising atmosphericCO2 level.

1976 Edward Goldbergat the Scripps Institutionof Oceanography usedradionuclide profiles inmarine and lake sedi-ment cores to quantifythe historical effects ofhuman activities onaquatic environmentalquality.

particular public worry, for example, wasstrontium-90, which can reach humans viacattle fodder and cow’s milk and then accu-mulate at dangerous levels in bones. As aresult of his pioneering field work,Auerbach would establish a reputation asone of the country’s leading ecologists.

Auerbach and his colleagues pursuedsome of their first studies in the dry bed ofWhite Oak Lake, where Oak Ridge onceflushed low-level radioactive wastes. In theprocess of their studies, Oak Ridge ecolo-gists introduced computer simulations toecological science, a striking innovation in1958. Products of this and other AECresearch on radionuclide transport andbioaccumulation still provide the basis formodels used to assess the impact ofradioactive emissions on living organisms,including humans.

In the early sixties, attention at OakRidge shifted to the “cesium forest,” astand of radiolabeled tulip poplars, whichproduced some of the first research to doc-ument the extent to which an element isrecycled within a forested ecosystem.Efforts then expanded in 1966 to include

38


A TOWERING SUCCESS Oak Ridge’s WalkerBranch Watershed project is one of the twolongest-running forest ecosystem studies inthe U.S. The aerial photo on this Sciencecover shows a meteorological tower above theforest canopy. Information on weather andatmospheric deposition is among the baselinedata being used in an effort to understand thedynamics of forest ecosystems.

E L V E R D E : E C O L O G Y O F A T R O P I C A L R A I N F O R E S T

■ Based on experimental evidence that plant resistanceto radiation is a function of cell nuclear volume (see page37), it appeared likely that some tree species would behighly sensitive to gamma and neutron radiation.To assessthe potential effects of nuclear warfare or a major reactoraccident on forest ecosystems, the AEC thus began abroad program of forest radioecology. Beginning in 1963and continuing into the seventies, the AEC funded a com-prehensive study of the effects of gamma-rays (high-energyx-rays) on a tropical forest at El Verde in the LuquilloMountains of Puerto Rico. Howard Odum, who wouldshare the Crafoord Prize with his brother Eugene, headedthe study. A 10-kilocurie cesium-137 gamma source wasplaced by helicopter at the center of a selected site. At theend of three months, it was removed and a large team ofscientists began detailed comparative studies of the irradi-ated site and two nearly identical control sites. The studyrepresented one of the most comprehensive and detailedexperimental investigations of a terrestrial ecosystem everconducted.The disordering stress of the radiation servedas an especially illuminating experimental tool for studyingthe mechanisms that maintain order in ecosystems. ■

1977 An ERDA confer-ence on CO2 and cli-mate change defined a multidisciplinaryresearch agenda thatwould later be pursuedby the multiagency U.S.Global Change ResearchProgram.

1980 The DOE desig-nated six additionalNational EnvironmentalResearch Parks atFermilab, Hanford, theIdaho National Engi-neering Laboratory, LosAlamos, the NevadaTest Site, and Oak Ridge.

1980 A decade ofresearch at theUniversity of Texas onscrewworm genetics,ecology, and radiationsensitivity, jointly spon-sored by the DOE andthe U.S. Department ofAgriculture, concludedwith the development ofsuccessful measures tocontrol screwworminfestation in the U.S.

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ecosystem metabolism, thus forming thebasis for the DOE’s later terrestrial carboncycling research and becoming the center-piece for the International BiologicalProgram’s global woodlands research effortin 1968. Still later, ecologists launched theWalker Branch Watershed project, whichcontinues today, one of the two longest-running studies of a forest ecosystem in theU.S. Over the years, it has afforded deepinsights into the flow of nutrients, water,and contaminants through a forestedwatershed and on the physical, chemical,and biological processes that control thisflow. More broadly, it has provided newtools for evaluating the effects of humanactivities on natural environments.

The AEC was no less committed to sup-porting ecological research in universities,where ecologists and limnologists used trac-ers to study the transport of materials inlakes and rivers, sometimes using entiresmall lakes as experimental ecosystems. In1951, for example, Arthur Hasler at the

University of Wisconsin took a whole-ecosystem approach in testing a way tomanipulate algal and fish production. Heseparated the two halves of an hourglass-shaped lake in northern Wisconsin with anearthen barrier, thus creating two separatelakes. One was then treated with lime toreduce the acidity and thus the concentra-tion of dark organic matter in the water,while the other remained untreated as acontrol. Early efforts such as this paved theway for much of modern limnology byoffering key insights into how lake ecosys-tems work and how they might be man-aged to enhance their intrinsic and utilitar-ian values.

On another ecological front, the latesixties saw growing environmental concernover the nonradioactive thermal dischargesfrom nuclear power plants (which typicallyused river water as a coolant, heating it inthe process). The lack of information onthe sensitivity of aquatic organisms toheated discharges was highlighted in envi-


39

C A P E T H O M P S O N : B A L A N C I N G

T E C H N O L O G Y A N D T H E E N V I R O N M E N T

1980 The Congressestablished the ten-yearNational Acid Precipita-tion Assessment Pro-gram, involving severalDOE national laboratoriesas major participants.Four years earlier, ERDAhad responded to acidrain concerns by launch-ing the MultistateAtmospheric PollutionPower Production Study.

1981 Tomas Hirschfeldat Livermore developedthe remote fiber fluo-rimeter, an early appli-cation of fiber optictechnology. Such instru-ments are now widelyused for remote monitor-ing of environmentalcontamination.

1984 With OHER sup-port, Warren Washingtonat the National Center forAtmospheric Researchused a coupled atmos-phere-ocean general circulation model to pre-dict that a 4 degreeCelsius global tempera-ture increase wouldaccompany a doublingof the atmospheric CO2concentration.

■ By the late fifties, thoughtful scientists had become deeply aware of the intricacy andsensitivity of the ecological web.At the same time, proponents of the Plowshare programwere proposing to use nuclear detonations to excavate harbors and construct canals.Topave the way for such projects, an experimental harbor excavation, dubbed ProjectChariot, was proposed for Cape Thompson in northwest Alaska. In a landmark effort, theAEC sent a team of scientists to survey the area beforehand—the first major ecologicalsurvey ever done in advance of proposed development. Among the goals were to gatherenough information to allow credible estimates of the biological cost of the harbor proj-ect and to establish a baseline for assessing future change, natural and otherwise. In the

end, the study contributed morebasic ecological information aboutthe Arctic than all previous investiga-

tions combined. Further, itsuggested that Project Chariotwould entail unacceptable

ecological and public health risks,and, perhaps most important, itpresaged a new era of ecologicalawareness, almost a decadebefore the National Environmen-tal Policy Act of 1969 woulddemand such environmentalimpact assessments. ■

ronmental impact statements prepared byAEC scientists in response to the require-ments of the National EnvironmentalPolicy Act. As a result, in the early seven-ties, the AEC expanded its aquatic ecologyefforts to include programs at Oak Ridge,Hanford, Argonne, and Savannah River.The products would include data thatunderlie today’s national water qualitystandards for the protection of fisheriesand aquatic ecosystems from heated dis-charges.

But perhaps the most visible symbol ofan early commitment to ecological researchis a system of seven National Environmen-tal Research Parks, each representative ofan important ecoregion in the U.S. TheAEC established the concept of these parksin 1972, underscoring its leadership amongfederal agencies in environmental research.This farsighted step led eventually to moreextensive ecological research and assess-ment programs in other agencies, especiallythe National Science Foundation and the

Environmental Protection Agency. Todaythe parks continue to serve as outdoor lab-oratories, where resident scientists and vis-iting researchers study ecosystem responsesto a whole gamut of environmentalchanges.

Taken together, ecology programswithin the energy agencies have had a pro-found effect. AEC biologists pioneeredand, for years, dominated ecosystem stud-ies, touching every facet of ecologicalresearch, from the cellular to the global.Collectively, they created the new field ofradioecology and in so doing were largelyresponsible for changing ecology from amainly descriptive discipline to a fully ana-lytical and quantitative science. AEC biolo-gists were among the first using tracers totrack the pathways of chemicals throughanimals and food chains, to follow themovements of animals, and to study thenatural cycling of materials. They also pio-neered the use of a systems analysisapproach to model the fate and effects of


40

HanfordResearch Park

NevadaResearch Park

Shrub-Steppe

Los AlamosResearch Park

Savannah RiverResearch Park

Oak RidgeResearch Park

IdahoResearch Park

FermilabResearch Park

Desert Shrub

Juniper-Pinyon and Grasslands

S Rockies Conifers

Tallgrass Prairie

E Deciduous Forest

SE Mixed Forest

NATIONAL PARKS Seven DOE National Environmental Research Parks represent major ecoregions cov-ering more than half of the lower 48 states. The parks are open to researchers for ecological stud-ies and to the general public for environmental education.

1985 Pacific North-west published in bookform the first energy-usemodel of CO2 emis-sions; it would subse-quently be adoptedinternationally to pre-dict global emissions asa function of futureenergy and economicdevelopment.

1988 OHER initiatedthe first theoreticalecology research pro-gram devoted entirely todeveloping a theoreticalbasis for understandingand predicting thebehavior of complexecological systems.

1990 Oak Ridge’sCarbon Dioxide Informa-tion Analysis Center pro-duced a report entitled“Trends: A Compendiumof Data on GlobalChange.” It wouldbecome the globalchange data most oftenrequested by govern-ment, academic, andprivate customers.

1991 Successful reme-diation of contaminatedsediments began atSavannah River, basedon stimulating the activ-ity of native subsurfacemicroorganisms capableof degrading the con-taminants.

environmental contaminants, and theywere early leaders in the study of largeecosystems. The spirit of these efforts con-tinues today in studying global climatechange and its environmental effects.

RE C L A I M I N G T H E PA S T

A half-century ago, environmental researchemerged in response to concerns about fall-out and the effects of atmospheric weaponstests. Following the 1963 ban on above-ground tests, and in concert with a growingenvironmental movement, attention shiftedto a much broader set of issues—ecosystemmodification, acid rain, even the possibilityof global climate change. Over the pastdecade, OHER and OBER have widenedthe scope of their environmental researchstill further, impelled by a commitment toclean up the contamination left by pastgenerations.

From the dawn of the Atomic Age,workers were well aware of the potentialfor harm harbored by the radioactive wastethey produced; much of the researchdescribed in the preceding pages testifies totheir concern. But treatment and storagetechnologies were relatively primitive, andthe needs for weapons research and nuclearpower production were compelling. The

result was a legacy of contamination. In thesame era, nonnuclear wastes were alsohandled carelessly: Organic solvents werediscarded with little thought to the conse-quences, and toxic materials were oftensimply buried and forgotten. Today, we areless tolerant of environmental insults andmore confident of our ability to avoidthem—even to remedy those of the past.Among the means available to us are thetools of modern molecular biology.

The first forays into bioremediation, theuse of biological processes to address theproblems of waste management, came inthe late sixties, when Oak Ridge sought toharness microbes to clean up wastes fromcoal conversion reactions and nuclearmaterials processing. More recently,Brookhaven patented a process that relieson naturally occurring citric acid to treat


41

NOTES FROM UNDERGROUND Once con-sidered a lifeless place, theearth’s deep subsurface has nowbeen shown to be home for a hostof microorganisms. Using innova-tive aseptic techniques, scientistssupported by OHER’s subsurfacescience program isolated microbessuch as the red bacterial cellsshown in this confocal microscopeimage. Associated with basalticrock several kilometers beneaththe sur face in the state ofWashington, these organismsobtain their energy and nutritionexclusively from the rock. Suchmicrobial systems as this may bemodels for early life on earth andperhaps on other planets.

1992 Pacific North-west developed tech-niques for asepticdrilling and microbiologi-cal sample-handling tocollect and preservemicrobial populationsfrom the subsurface forpotential application tobioremediation and phar-maceuticals.

1993 OHER GlobalChange Research (con-ducted by scientists atthe National Oceanicand Atmospheric Admin-istration, Columbia Uni-versity, and East AngliaUniversity) produced ahistorical climate data-base revealing a globaltrend of increasingnighttime temperaturesover the past fifty years,a finding consistent withthe greenhouse gaswarming theory.

1994 OHER launchedthe Microbial GenomeInitiative to understandthe workings of the sim-plest life forms. Withinthree years, CraigVenter at The Institutefor Genomic Researchwould sequence thecomplete genomes offour microorganisms.

waste contaminated by toxic metals. Themetals, even uranium, form water-solublecomplexes with the citric acid, allowingthem to be precipitated by bacteria or, inthe case of uranium, by light. The usualproducts are a relatively small volume ofrecoverable metal and clean, reusable soil.Apart from its use at contaminated DOEsites, this process has been used successfullyto remove cadmium and lead from munici-pal incinerator ash.

Two other recent thrusts likewise under-score the likely value of microorganisms.First was a careful look underground. Inthe mid-eighties, a program was inaugu-rated to explore the deep subsurface envi-ronment for microorganisms that might beuseful in new bioremediation strategies.Microbiologists, geohydrologists, and geo-chemists from about thirty universities andnational laboratories took part, probingdeep beneath the surface at Savannah River,Hanford, and the Idaho National Engi-

neering Laboratory, as well as non-DOEsites. As a result, previously unknownmicrobes and microbial ecosystems havecome to light, including ecosystems thathave been isolated for hundreds of millionsof years, microbes that thrive at 60 degreesCelsius (140 degrees Fahrenheit) in brinetwice as salty as the sea, and nonphotosyn-thetic bacteria whose only energy sourceappears to be the hydrogen produced inreactions between water and rock. Theresulting Subsurface Microbial CultureCollection, housed at Florida State Univer-sity, has attracted wide scientific attention—including the interest of pharmaceuticalcompanies, for whom the collection has sig-nificant potential market value as an aid todrug screening and discovery.

Direct descendants of this program haveincluded highly successful bioremediationschemes. During demonstrations in the earlynineties, underground organic contaminantsat Savannah River were effectively eliminated


42

D E E P S E C R E T S

■ In 1996 scientistssupported by the DOE’sMicrobial Genome Pro-gram reported the com-plete genome sequenceof Methanococcus jan-naschii, a methane-producing microor-ganism that dwells around “white smok-ers” on the seafloor. The details ofthe genome confirm the exis-tence of a third kingdom ofliving organisms, theArchaea (from theGreek word for“ancient”), distinctfrom other mi-crobes lacking acell nucleus, aswell as higherplants and animals.Details of thegenome and the pro-teins it codes for mightwell lead to heat-stableenzymes for the textile,

paper, and chemicalindustries; to systemsthat produce methanefor chemical feedstockand renewable power;and even to tailor-made

proteins that rid living cells of toxic con-taminants. Shown above is a photomi-

crograph of the microbe itself; at lefta depiction of its circular

chromosome. The twoouter rings of colored

lines show the pre-dicted protein-cod-ing regions. Thesequencing of M.jannaschii wasp r o m i n e n t l ydescribed in theNew York Times

and was chosen byDiscover magazine

as one of the two mostimportant scientific dis-

coveries of the year. ■

1995 Research atPacific Northwest led tothe development of anin situ redox manipula-tion technique to immo-bilize or destroy selectedcontaminants in groundwater. The techniquewould be promptlyapplied at DOE sites toclean up ground watercontaminated withchromium.

1995 OHER conceivedthe Natural and Acceler-ated BioremediationResearch program, amultidisciplinary programdesigned to enhancethe potential of bioreme-diation as a useful, reli-able, and cost-effectivetechnique for cleaningup contaminated environ-ments.

1995 Livermoreresearchers contributeda news-making analysisto the second Intergov-ernmental Panel onClimate Change Scien-tific Assessment: The“balance of evidencesuggests a discerniblehuman influence on cli-mate.”

1995 Field experimentsat Oak Ridge, KansasState University, andthe Smithsonian Insti-tution on plant responsesto elevated CO2 demon-strated enhanced plantgrowth and productivityand increased carbonsequestration by eco-systems.

by injecting air and methane to enhance theactivity of bacteria already present in thesubsurface. This remediation technology isnow in use around the world. Meanwhile,at Hanford, researchers developed aprocess that exploits natural chemistry inthe subsurface to form a barrier permeableto ground water that efficiently removescontaminants as the water passes through.

A second BER research thrust, focusingthe technologies of the Human GenomeProject on remediation needs, is even morefundamental. If the genetic details of keymicrobes could be obtained, they wouldafford profound insights into the workingsof these “minimal” forms of life, some ofwhich inhabit environments notable forextremes of temperature, pressure, acidity,and salinity, as well as high concentrationsof toxic chemicals and even high fluxes ofradiation. In addition to enhancing ourunderstanding of evolution and the originof life, the benefits would extend to medi-cine, agriculture, industrial processes, and,not least, environmental bioremediation.Such were the incentives for the MicrobialGenome Program, launched by OHER in1994. Among the program’s early successeswere the complete genomic sequences ofMycoplasma genitalium, the smallest-known free-living organism—and a key tounderstanding the minimum requirementsfor life—and Methanococcus jannaschii,an evolutionary throwback that survivesentirely on inorganic nutrients near hot

43


1996 Pacific North-west scientists providedthe first scientific evi-dence of active, anaero-bic microbial ecosystemsin the deep subsurfacethat derive metabolicenergy from geochemi-cally produced hydrogen.Their discovery wouldoffer opportunities forlow-cost bioremediationof ground water and forimproved methods ofmicrobially enhanced oilrecovery.

1996 After receivingEPA approval, Oak Ridgeconducted the first fieldtrial of a geneticallyengineered microorgan-ism in the U.S., a firststep toward developinga process to degradepolycyclic aromatichydrocarbons in contam-inated soils.

1997 The William R.Wiley EnvironmentalMolecular SciencesLaboratory at PacificNorthwest began fulloperation as a state-of-the-art research facility.Using advanced analyticand computational capa-bilities, scientists therefocus on forefrontresearch in environmen-tal chemistry and onenvironmental cleanup.

❧

Environmental remediation thus com-

pletes a research picture that encompasses

a lasting emphasis on public health and

safety, a noble record of medical break-

throughs, and a deep concern for the envi-

ronment. But in fact, this canvas of

achievement is no more complete than

any other description of scientific

advance. It is more like a mural in

progress than a completed portrait. The

only proper conclusion must be a glimpse

of the future, a look to the promise of the

genome project, to the latest advances in

medical imaging, and toward an era of

swift environmental cleanup. In closing,

then, a brief forecast for the coming years.

vents on the ocean floor. Of particular cur-rent interest is the microorganismDeinococcus radiodurans, which prosperseven when exposed to doses of radiationthat would kill the typical microbe manytimes over. The secret is not avoidance ofdamage, but rather a remarkably efficientDNA repair mechanism—one that mightbe engineered to allow bioremediation ofdangerously radioactive wastes.

44

he DOE’s Office of Biological and

Environmental Research (OBER) currently supports research at more than 200

institutions around the country—a research portfolio that, for all its diversity,

reflects a direct lineage from the earliest charge to the AEC: to exploit the promise

of a new age and to safeguard the public health in the face of its uncertainties.

And yet, this constancy of purpose has demanded inevitable change, as new ideas

have emerged, as tools have evolved, and as the foundation of knowledge has

grown. Underscoring this truth is the example of the Human Genome Project,

unthinkable little more than a decade ago and yet a direct descendant of the AEC’s

earliest concerns about radiation’s unseen effects. Seen in this light, the birth of the

genome project within the Biological and Environmental Research (BER) program

is no surprise.

T

Often characterized as the Holy Grail orthe Rosetta Stone of biology, the genomeproject is more aptly compared to thechemists’ periodic table. Just as the peri-odic table transformed chemistry into a rig-orous and quantitative science, so willsequencing the human genome pave theway for a systematic study of biologicalfunction and dysfunction—at the same timeanswering some of the AEC’s oldest ques-tions about radiation and genetic damage.

The genome project links past andfuture in another way, as well. It points toan enduring strength of today’s OBER thatis again a legacy of the AEC and thenational laboratories that were born of thewar years: a tradition of multidisciplinaryteamwork, historically grounded in daunt-ing scientific challenges. Taking advantageof this unique asset, the BER program iscontributing significantly to the nation’sgenome sequencing effort.

The BER program also pioneered theMicrobial Genome Initiative, which, in afew short years, has already deliverednews-making discoveries holding greatpromise for the Department’s missions.Deciphering, then perhaps reengineering,the genetic organization of microorganisms

opens exciting new prospects for environ-mental bioremediation and sustainableenergy production. The future promiseseven more exciting developments as thefruits of this Initiative mature.

Two other forward-looking disciplinesare structural and computational biology,where advances rely in large part on long-standing BER commitments to synchrotronlight sources and neutron sources at ournational laboratories—and on the labs’advanced computational resources. Indeed,structural biology is the linchpin in one ofmodern biology’s central research para-digms: sequence to structure to function.Using a variety of techniques, most promi-nently x-ray crystallography, structuralbiology seeks to determine the structures ofkey biological macromolecules as clues tobiological function. If we can now onlylearn to deduce the three-dimensionalstructure of proteins from genomicsequence—a challenge for computationalbiology—the product of the HumanGenome Project will be not just sequence,but insights into countless biologicalprocesses pertinent to the future environ-mental and energy needs of the DOE andthe nation.

A N E N D U R I N G M A N D A T E

L o o k i n g t o t h e F u t u r e

45

To take but one example, understandingthe genome-structure-function connectionwill reveal the genetic and functional rea-sons behind individual susceptibilities tovarious environmental insults—and maylead ultimately to reliable screening tests forsusceptible populations. Such break-throughs will protect DOE workersinvolved in environmental cleanup, as wellas the population at large.

In reaching to the genome for an under-standing of biological function, the newresearch paradigm extends to nuclear med-icine as well—thus the nascent field of mo-lecular nuclear medicine. The BER program

has been the principal steward of nuclearmedicine for fifty years, touching millionsof lives with epochal developments. Nomore than enticing novelties in the forties,radiotracers, radiopharmaceuticals, andadvanced medical imaging systems are nowstaples of medical practice and biologicalresearch. Today, molecular nuclear medi-cine offers prospects no less bright. Thepromise of directly imaging gene functionin living tissue, already realized in recentresearch, dramatically enhances the prog-nosis for treating diseases such as cancer,since it would allow genetic dysfunction tobe detected long before the resulting ail-

UNLOCKING AN ANTIBODY’S SECRET One of the body’s mysteries is how the immune system responds tothe virtually unlimited variety of foreign molecules it must combat. However, insights are emergingfrom images such as these, produced from data obtained at the DOE-supported StanfordSynchrotron Radiation Laboratory. X-ray crystallography reveals the detailed molecular structuresof a “naive” antibody in both its free form (blue) and with an antigen bound to it (purple), as wellas a “mature” antibody (green and red). The binding of the antigen (yellow) to the naive antibodyleads to structural changes in the antibody that establish a more secure lock-and-key interactionwith the antigen. This effort by Berkeley scientists working at SSRL was supported by the DOE, theNIH, and the Howard Hughes Medical Institute.

46

ments become clinically manifest.The BER program will also press ahead

with the basic environmental research thatmust undergird the Department’s cleanupcommitments, particularly the stubborn,long-term restoration problems that arebeyond the reach of today’s remediationtechnologies. The Microbial GenomeInitiative is one part of this continuingresearch. Another is a coordinated effort atthe William R. Wiley Environmental Mo-lecular Sciences Laboratory (EMSL),whose operational start-up correspondswith the 50th anniversary of the AEC’sDivision of Biology and Medicine. EMSL isthe first major facility for which the BERprogram assumed principal stewardshipand represents an important transition to“big science.” This facility will open newvistas on the chemistry of our environment,including insights into how chemical wastestreams and contaminated environmentscan be cleaned up, as well as clues to thelong-term fate of chemicals released intothe ground, air, and surface waters. In theyears ahead, 200 staff scientists will workhere at the forefront of such fields as waste

processing, bioremediation, and atmos-pheric chemistry. OBER is also committedto seeing EMSL become an internationallyrecognized user facility, where visiting sci-entists can study environmental processesat the molecular level, with applications toenvironmental cleanup and sustainabledevelopment.

Yet a third facet of the BER program’senvironmental commitment is the Naturaland Accelerated Bioremediation Research(NABIR) program, conceived in 1995.NABIR is building on the foundation laidby the subsurface science program, bringingtogether geologists, chemists, biochemists,molecular and cellular biologists, microbi-ologists, and ecologists to focus on impor-tant bioremediation questions. The goal isto combine laboratory studies, field studiesat contaminated sites, and theoreticalresearch to enhance the scientific basis forusing bioremediation to restore and protectthe environment.

Also part of the environmental picture isglobal environmental change, an under-standing of which must be a critical ingredi-ent in our technological choices. The sub-

REPORTING FROM THE SCENE Positron emission tomography has now been used to detect the detailsof genetic activity. In these two images, a living mouse has been injected with a reporter probe thatdiscloses itself to PET imaging, as well as an adenovirus (which accumulates in the liver) carryingboth a gene-therapy gene and a PET “reporter gene.” In the left-hand image, neither gene is active,so the probe has diffused through the bloodstream and passed through the kidneys to the bladder.In the right-hand image, both genes have been activated by a genetic promoter carried by the ade-novirus. The reporter gene produces a protein that binds the reporter probe, which thus reveals thesimultaneous activity of the therapeutic gene in the liver. Experiments such as this, performed atUCLA, are hopeful harbingers of an age of molecular nuclear medicine.

B L A D D E RB L A D D E R

L I V E R

47

tlety of global systems continues to chal-lenge DOE scientists today, just as it didtheir AEC forebears. Global environmentalchange is sure to remain a major issue foryears to come, and efforts to understand thecauses and ramifications of this change willcontinue to receive the highest priority. Oneof the central global issues is the impact ofgreenhouse gas emissions. Internationalagreements on such emissions, aimed atpreventing dangerous climatic change, willdemand increasing attention to the ecologi-cal impacts of environmental change, andthe concept of sustainable development willdominate many research and developmentagendas in the coming years. The BER pro-gram will thus expand its research on envi-ronmental impact to address the Depart-ment’s objective of sustainable energydevelopment.

THE LEGACY AND THE PROMISE To look at both the past and the future of the BER program, the DOEand the National Research Council (NRC) of the National Academy of Sciences cosponsored a sym-posium in May 1997, entitled “Serving Science and Society into the New Millennium: The Legacyand the Promise of DOE’s Biological and Environmental Research Program.” The symposium cele-brated five decades of achievement by the DOE and its predecessor agencies, often in partnershipwith the NRC, and explored the promise of its current programs at the threshold of the next cen-tury. Speakers reflected on the implications of changing paradigms, enabling research, and sciencepolicy on biotechnology, medicine, and the environment, and discussed the BER program directionsthat could best serve the needs of the Department and society. The symposium was held at theNational Academy of Sciences, Washington, D.C.

❧

The pioneers of biological and environ-

mental research within the AEC could

hardly have predicted the course BER

research would take. Efforts focused on

the fate of radioactive fallout would

evolve into today’s global climate

research. Exploratory studies of human

metabolism using radiotracers would

lead to high-resolution PET and molecu-

lar nuclear medicine. And questions

raised by early epidemiological studies

would ultimately give rise to the Human

Genome Project. The next fifty years are

equally unpredictable. The future, as

usual, promises unknown challenges—

and unexpected opportunities. It is cer-

tain only that as technology evolves, so

will our responsibilities for understand-

ing the impact of our decisions on human

health and the health of our environ-

ment. And as long as our well-being

depends on the wisdom of our choices,

the enduring mandate of the AEC will

continue to inform the research of the

DOE scientists charged with its legacy.

48

This booklet was prepared at the request of the U.S. Department of Energy, Office of Biological andEnvironmental Research, to commemorate the legacy and to explore the promise of the Biological andEnvironmental Research (BER) program on the fiftieth anniversary of its formation, September 24, 1947, withinthe U.S. Atomic Energy Commission. The boundaries of the BER program are, however, sometimes indistinct.The goals of separate offices or agencies frequently converge, and the facilities of one are commonly used by sci-entists supported by another. In some cases, therefore, credit for the achievements we cite is properly shared withother offices within the DOE and with other federal agencies. We have sought to identify these instances of con-fluent research effort by mentioning other sponsoring agencies in the text. For our oversights, we apologize.

Though this account was edited and produced at the Ernest Orlando Lawrence Berkeley National Laboratory,it aims to provide the general reader with a broad but brief overview of the entire BER program: its role, itscontributions to science and society during five decades of research, and its exciting prospects for the future. Fortheir help in this effort, many deserve our thanks for elucidating historical highlights, tracking down illustra-tions, and offering their advice and criticism: At DOE, David Bader, James Beall, Michelle Broido, Pat Crowley,Roger Dahlman, Jerry Elwood, Ludwig Feinendegen, Marvin Frazier, Roland Hirsch, Peter Lunn, Curtis Olsen,Rick Petty, Michael Riches, Susan Rose, Prem Srivastava, Marvin Stodolsky, David Thomassen, Matesh Varma,and Frank Wobber, and former staffers Gerald Goldstein, Joshua Holland, Helen McCammon, William Osburn,Charles Osterberg, David Slade, Joop Thiessen, Robert Thomas, and Robert Wood; at Argonne NationalLaboratory, Jeff Gaffney, Douglas Grahn (retired), Karen Haugen, Eliezer Huberman, David Nadziejka, ChrisReilly, and Marv Wesley; at Brookhaven National Laboratory, Paul Falkowski, Kathy Folkers, Joanna Fowler,A. J. Francis, Dawn Mosoff, Richard Setlow, Suresh Srivastava, Jack Van’t Hof, Nora Volkow, and Alfred Wolf;at Columbia University, Eric Hall; at the Environmental Measurements Laboratory, Phillip Krey (retired); at theHanford Site, Michele Gerber; at the Harvard Medical School, James Adelstein; at Johns Hopkins University,Henry Wagner, Jr.; at Lawrence Berkeley National Laboratory, David Gilbert and Sylvia Spengler; at LawrenceLivermore National Laboratory, Linda Ashworth, Anthony Carrano, Kenneth Sperber, and Gordon Yano; atLos Alamos National Laboratory, Scott Cram and James Jett; at the Lovelace Respiratory Research Institute,Charles Hobbs and Joe Mauderly; at Oak Ridge National Laboratory, Murray Browne, Donald Hunsaker, Jr.,Sheryl Martin, David Reichle, and Barbara Walton; at Pacific Northwest National Laboratory, Nancy Burleigh,Ted Cress, Jake Hales (retired), Ray Stults, and Ray Wildung; at Savannah River Ecology Laboratory, MarieFulmer; at Savannah River Technology Center, Robert Addis; at Stanford Synchrotron Radiation Laboratory,Peter Kuhn; at the University of California, Berkeley, Bruce Ames; at the University of California, Los Angeles,School of Medicine, Michael Phelps; at the University of California, San Francisco, Sheldon Wolff; at theUniversity of Florida, Howard Odum; and at the University of Michigan Hospital, David Kuhl.

In addition, we owe special gratitude to those who made exceptional efforts in providing first-hand perspectiveson past program achievements: Stanley Auerbach, Oak Ridge (retired); William Bair, Pacific North-west(retired); Antone Brooks, Washington State University; Todd Crawford, Savannah River Technology Center(retired); Charles DeLisi, Boston University College of Engineering; Michael Fry, Oak Ridge (retired); SamuelHurst, Oak Ridge (retired); Merle Loken, University of Minnesota Medical School; Michael MacCracken, U.S.Global Change Research Program; Charles Meinhold, National Council on Radiation Protection andMeasurements; Mortimer Mendelsohn, Livermore; Dennis Patton, University of Arizona Health SciencesCenter; and Cornelius Tobias, Berkeley (retired).

And finally, we must acknowledge the inevitable omissions in this list. This has been a complex, sometimes try-ing effort, probably involving more people than we realize. But to all who helped, we are sincerely grateful.

A C K N O W L E D G M E N T S

This document was prepared as an account of work sponsored by the United States Government. While this document isbelieved to contain correct information, neither the United States Government nor any agency thereof, nor The Regents of theUniversity of California, nor any of their employees, makes any warranty, express or implied, or assumes any legal responsi-bility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or representsthat its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or serviceby its trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recom-mendation, or favoring by the United States Government or any agency thereof, or The Regents of the University of California.The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Governmentor any agency thereof, or The Regents of the University of California.

Ernest Orlando Lawrence Berkeley National Laboratory is an equal opportunity employer.

Prepared for the U.S. Department of Energy under Contract No. DE-AC03-76SF00098. PUB-800/September 1997.

PRINTED ON RECYCLED PAPER

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DOUGLAS VAUGHAN, Editor

BENJAMIN J. BARNHART, DOE, BER50 Project Manager

MURRAY SCHULMAN, DOE Technical Consultant

Design: NIZA HANANY

a vital legacy (1997)€¦ · opportunities of atomic energy—and acknowledging, too, an...

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