The Manhattan Project
for Biomedicine

Timothy Lenoir and Marguerite Hays
Controlling Our Destinies: Historical, Philosophical, Ethical, and Theological Perspectives on the Human Genome Project, Edited by Phillip R. Sloan (South Bend Indiana, University of Notre Dame Press, 2000), pp. 19-46

A topic of central concern to policy makers since the close of the Cold War has been assessing the importance of federal investment in scientific research. With economic competitiveness replacing concerns about military security as a rationale for national funding priorities, there have been calls for a new contract between science and society establishing a closer working relationship between academe, industry and the national laboratories, and creating a supportive environment for the commercialization of innovative technologies generated through public research funds. A model for the new contract between science and society has been the Human Genome Initiative. Indeed the HGI has been heralded as a potential Manhattan Project for biology through the possibilities it affords of stimulating collaborative work among physicists, engineers, computer scientists and geneticists in the national labs which may prime the pump for commercially viable biomedical and information technologies analogously to the way in which the World War II Manhattan Project was the technological incubator for important Cold War electronics, computer science, military, and aerospace technologies (DeLisi 1988, 489; Kotz 1995).

While the call for launching a Manhattan Project for biomedicine may have the rhetorical ring of newness about it -- and its formulation in terms of mapping the human genome certainly is new -- the fact is that since the days immediately following the Hiroshima and Nagasaki bombings there always has been a Manhattan Project for biology and medicine. Our aim in this paper is to show how, well before the end of the War, the chief medical officers for the Manhattan Project began to contemplate plans for adapting the work they had done under extremely close security conditions to the postwar world. They not only contemplated how to continue the promising paths of research they had opened during the war but also how to carry their research outside the confines of military classification into the civilian world. We discuss their plans to establish academic and medical disciplines in health physics, biophysics, and nuclear medicine; we also explore programs they initiated to train medical personnel in the use of radioactive materials, as well as a strategic program to subsidize the development of radioisotopes, radiopharmaceuticals, and biomedical instrumentation as part of an effort to create the infrastructure of a self-sustaining biomedical nuclear industry. We argue that within roughly a decade, by 1960, this program of discipline building was essentially complete, and with it perhaps the most successful example of government technology transfer in the history of American industry.

Atomic Medicine

Initial efforts to use radionuclides for physiological studies and the first glimmerings of a medical research program into the effectiveness of using selectively localizing radioactive isotopes to destroy cancer cells preceded the Manhattan Project. In 1923 George Hevesy, working with Hans Geiger and Ernest Rutherford in Manchester, experimented with thorium-B to study the absorption and localization of lead in plants. He continued this line of exploration with naturally radioactive elements, but these early tracer studies were limited to heavy elements and very slow sampling techniques. In order to examine physiological function, radioisotopes of the lighter biologically active elements were needed. The first of these, heavy water, was made by Harold Urey in 1932, and a number of other radioactive isotopes followed in rapid succession. Ernest O. Lawrence's construction of the Berkeley cyclotron in 1931 and subsequent production of radiosodium obtained by bombarding sodium with deuterons in 1934 opened the path to physiologic tracers (Lawrence 1934). Cyclotron-produced radioactive phosphorus, P-32, was used in a number of pathbreaking investigations of phosphorous metabolism by Hevesy, Otto Chiewitz, Hardin Jones, Waldo Cohn, and John Lawrence. John Lawrence seized upon the preferential absorption of inorganic phosphorous in hematopoietic tissues and rapidly multiplying cells, such as malignancies, and used P-32 to treat leukemia. This first therapeutic use of artificially produced radioisotopes occurred on Christmas Eve 1936 (Lawrence et al. 1939; 1940). Also about the same time, beginning in 1936, first investigations with radioactive iodine, I-128, were undertaken by Robley Evans, Arthur Roberts, and Saul Hertz in the thyroid clinic at Massachusetts General Hospital, but its 25-minute half-life rendered it difficult to use (Hertz et al. 1938; Evans 1969, 105). Stimulated by their Berkeley colleague Joseph Hamilton to construct an isotope of iodine with a longer half-life, Glenn Seaborg and J. J. Livingood devised a method of manipulating the cyclotron to produce a mixture of 12 hour and eight-day isotopes of iodine, I-130 and I-131 (Livingood and Seaborg 1938). This development not only suggested that radioisotopes might be tailor-made for specific needs, but also, given the specificity of iodine for thyroid tissue, a number of researchers, including Saul Hertz, Arthur Roberts, Robley Evans, Earle Chapman, John Lawrence and Joseph Hamilton, pursued the localized therapeutic use of radioiodine in hyperthyroidism. In November of 1940 MIT physicists produced their first sample of the I-130--I-131 mixture in their new cyclotron, using the Berkeley methodology. And in January 1941 Saul Hertz at the Massachusetts General Hospital and Roberts at MIT gave a patient the first therapeutic dose of I-130--I-131 mixture, and started a program of study with thirty patients. In late 1941, the Berkeley group also began treating patients with hyperthyroidism with I-130--I-131, and, before the end of the war, several other groups were using this treatment. Marinelli, and Oshry proved the therapeutic value of I-130--I-131between 1943-46 in their treatment of a patient with thyroid cancer (Seidlin et al 1946). Thus, by 1943 when the Manhattan Project got fully underway--the first nuclear pile went critical in Chicago on December 2, 1942--there were already a number of major successes and several well demarcated lines of research and therapy had been opened up by a small core group of biophysicist-physician teams in nuclear medicine. [1]

From its inception the Manhattan Project incorporated a substantial medical research program (Oak Ridge n.d.). Beyond the need for medical care for project workers at Hanford, Washington, and Oak Ridge, Tennessee, appropriate programs of industrial hygiene had to be instituted in Manhattan District laboratories and plants working with the unusual chemicals required for processing uranium. It was already well understood that the materials involved in these facilities were hazardous and that determining how to protect workers would require a considerable research effort. [2] Investigation was required to determine what effect absorbed uranium and plutonium compounds would have on the human body; what effect absorbed products of uranium (fission products from the pile process) and radioactive products produced in the actual explosion of the uranium and plutonium bomb would have; and what hazards might be encountered from absorption of other chemicals developed for use by the District. In addition, although the dangers of work with radium were fairly well known, it was discovered that the knowledge concerning the maximum safe exposures to various radiations was not well-founded, and that considerable research would be required to establish safe levels with certainty(Lawrence 1938, 1.1-1.2). [3] A natural corollary to these investigations was the need for an intensive research program designed to establish early signs of toxic effects from these chemicals or from radiation, and to develop specific measures useful for treating over-exposures.

From 1942-1945 the work of the Medical Division of the Manhattan Project was conducted at laboratories at the universities of Chicago, Rochester, U.C. Berkeley, Columbia, and Washington, at the Los Alamos laboratory and at Clinton Laboratories in Oak Ridge (Brundage 1946a, 1946b). The research programs conducted at these sites were extensive and wide-ranging, aimed at "the diagnosis and control of effects produced by exposure to radiations emitted by radioactive materials during experimenal or processing operations as well as the chemical toxicity or localized radiation from such materials deposited within the body."(Warren 1946). Among the programs organized and begun during the three-year Manhattan Project were studies of methods for the physical measurement of radiations of various types with an aim toward standardizing dosages of radiation to be used in biological experimentation and in measurement of radiation which might be found in a plant area (ibid., 4). Among the types of biological effects investigated were survival times or percentages that a given radiation dose will reduce the life span of different animal species, studies of genetic effects of radiation as manifested in the development of abnormal individual types from changes in the hereditary mechanism, histopathological changes in the makeup of various body tissues, physiological changes produced by the alteration of normal function of animal tissues following radiation, biochemical and enzymatic disturbances presumed to be the potential source of these physiological abnormalities. Studies were also undertaken of the hazards due to handling the specific toxic materials used in processing uranium, plutonium, and a variety of fission products. Given the pre-war record of research in leukemia and polycythemia, efforts to understand the mechanisms by which radiation suppresses the hematopoetic system received priority, and investigations were made of therapeutic measures for treating acute radiation damage, including possibilities of replacement of hematopoetic elements destroyed by severe radiation damage (ibid., 5-6). Research and development of precautionary methods to be taken in the handling of special materials, the removal of hazardous dusts, reduction of skin contact, prevention of ingestion, and studies of methods for shielding against radioactive materials, ventilating and exhaust systems, and the development of remote control methods for processing radioactive materials received primary attention by the Medical Division.

The members of the medical division of the Manhattan Project were convinced by their wartime experiences that a continuation and expansion of their work would be essential to public health, and to worker health and safety in the nuclear age. Whatever the future military prospects of nuclear energy--and they seemed considerable-- the potential of nuclear power and the application of other aspects of nuclear science for civilian industry seemed unlimited. Manhattan Project medical personnel were also convinced that their work in the Manhattan Project was the harbinger of a revolution in biology and medicine. Since the great discoveries in bacteriology and the introduction of instrumentation into medicine in the late nineteenth century, medicine had taken on the ideology and aura of "science," but medical practice remained very much art- and craft-driven. Of course, the war effort had resulted in the production and widespread use of the "miracle drug," penicillin, but the Manhattan Project opened up more expansive vistas for creating science-based medicine and for basing medicine on its own foundations of research and experiment than anyone had previously contemplated. In his address to the American Association for the Advancement of Science in 1948 Stafford Warren gave a sense of the excitement and sense of the opportunities he envisioned awaiting the implementation of the lessons learned from the Manhattan Project in a peacetime civilian setting:
It was biological research at an entirely different tempo than we had ever experienced before: generous financial support, an organized program with men working in teams, a specific narrow goal for each group, pressure for speed, immediate application of results. ...Even though discoveries in fundamental science were not pursued in any program, those discoveries were either made or were tantalizingly visualized for peacetime research. (Warren 1950, 143)
* * *
...Before the war, and even during the early part of the war, one occasionally heard the statement in research committees that "biological research ideas could not be bought with money," or that , "even with money, medical research was a sterile field in certain areas." It is evident from the war experience that the previous opinion was the result of frustration and isolation, for such statements are not heard any longer. ...The best minds were not directed into research channels because there was no possibility of making a living in a research career. Medical and biological research was tolerated only as an offshoot of teaching.
In summary then modern developments in nuclear energy have influenced public health problems by showing the benefits and accomplishments that can be achieved by team work in correlated, large-scale biological and medical research; by devising new techniques and new instruments, and furnishing a copious supply of radioactive isotopes for general research purposes; by training many young men in new research fields; by aiding in bringing about a rejuvenation of biological and medical research; by creating a new field in industrial hygiene called radiological saftey and a new profession, the health physicist (or biophysicist); by creating the greatest public health hazard of all time; i.e., the possible fantastic contamination that would result from an all-out atomic war, and by posing the problem of how to combat mass fear and how to prevent another war. In every phase of this development there is an obvious lack of trained men, not excluding the fields of social and political sciences. If war can be prevented there is no doubt that we can look forward to the solving of world-wide problems in health and welfare in both the strictest and the broadest terms. We all know the goals and we have the tools. (ibid. 148-149)

These statements were an early public expression of the transformation of medicine Warren and his colleagues envisioned following in the wake of the Manhattan Project, a vision already acquiring institutional momentum required for its growth. A new era of biological and medical research populated by an entirely new breed of medical professionals, the biophysicists, health physicists, and practitioners of nuclear medicine, could be inaugurated by implementing the Project's organizational structure in the civilian biomedical sector. The new research medicine would be multidisciplinary, involving close working relationships among physicians, physicists, engineers, physiologists, and other biomedical specialties working in teams at newly minted medical research centers with well-equipped research laboratories. It was necessary to create the conditions for retaining the medical personnel gathered during the war and to establish programs of training and recruitment suited to reproduce the medical profile of this new breed of medical scientist. To nurture the new field of medical research, it was necessary to maintain the atmosphere of emergency that had enabled its wartime success, to retain and recruit academically trained medical and scientific personnel, and to remove secrec surrounding the medical projects and publish useful wartime research results. Warren and his colleagues envisioned a hybrid setting, fulfilling the necessary security requirements of the military with respect to nuclear technology but facilitating a cooperative structure of research and training facilities in government, industry and academe.

Steps toward realizing this vision were taken through the founding of the Atomic Energy Commission, charged specifically with the responsibility to conduct research and development activities relating to, among others, utilization of fissionable and radioactive materials for medical, biological, health or military purposes, and the protection of health during research and production activities. (U.S. Congress, 1946, Section 3a). An interim Advisory Committee to the Medical Division of the Manhattan District which first met on September 5-6, 1946 in the Manhattan District offices in New York City, was established with Warren as chairman. It was continued as a permanent committee under the new AEC. At meetings of this committee in 1946 and 1947, Warren urged a general strategic plan for transforming the work of the medical division of the Manhattan Project into a launching pad for a wide-ranging program of medical discipline-building. A key element of Warren's vision for attracting and retaining appropriately trained scientific personnel was the creation of faculty and research appointments at universities with provisions for tenure(Warren 1946, 10). [4] Believing that men with scientific aspirations would only be attracted by an open community, a second element of Warren's plan was to declassify all Manhattan Project reports in the medical, biological, and health-physics fields, and organize a national meeting at an easily accessible central location open to scientific researchers from all parts of the country, at which Manhattan Project researchers would present information on medical aspects of nuclear energy. [5] In connection with such a meeting, the third element of Warren's vision included creation of a new society for radiobiology as related to medical problems. A fourth, crucial element of Warren's proposal was that in connection with declassifying Manhattan Project research reports encouragement be provided to manufacturers of instrumentation for radiation measurement(Warren, 1947a).

In the AEC's reply Carroll Wilson explicitly acknowedged the importance of fostering the disciplinary aims Warren had outlined by situating the proposed medical research units in universities and creating conditions for them to pursue independent research. Warren's proposed budget for continuing the interim work of the medical division was approved, and it reflected the commitment to locating the main research effort in universities. [6] Below is a breakdown of the approximate current 1 July 1945-30 June 1946 budget. These funds were for fundamental, applied medical and biological research over a one-year period :

 
1945-46

1946-47

University of Chicago

$2,500,000

$1,000,000

University of Rochester

1,700,000

1,200,000

University of California

250,000

250,000

Biochemical Research Foundation

120,000

25,000

Columbia University

80,000

75,000

University of Washington

60,000

30,000

Los Alamos

100,000

100,000

Clinton Laboratories

 
200,000

Other Installations for Miscellaneous

Problems as Appropriate

100,000

1,000,000

Total

$4,910,000

$3,880,000

Although the budget reflected a twenty-percent reduction to remain consistent with the postwar downsizing of military expenditures, Warren concluded that "It is believed that approximately $5,000,000 per annum is an appropriate budget for a program as difficult and broad as this must be."(Warren 1946)--a figure several times less than what Warren thought was actually needed [7]--and in his summary statement Warren went on to recommend a sustained commitment to continuing the research effort of the medical division well beyond the transition period for at least 10 years.(Warren 1946, 10).

Warren and his colleagues made use of the resources of the Manhattan District, and after January 1947 the AEC, to achieve this full-scale disciplinary program. A first step in this direction was the issuing of AEC contracts to universities for projects in nuclear medicine and areas related to civil defense. One of the contracts authorized was AEC contract GEN-12 to UCLA. This project, funded initially at $250,000 annually, was the nucleus of major developments in the fields of biophysics, radiology, and nuclear medicine at UCLA, and also the core of a cancer research institute at UCLA. Warren's assignment after the war had been to head up the collection of data from the Bikini tests as part of Operation Crossroads. While preparing to launch this effort he was approached by Robert Sproul, President of the University of California, to consider the deanship of the new medical school being considered by the Governor and the California legislature for siting in Southern California.Upon his return from the Bikini tests Warren agreed to move to UCLA, "because this was an opportunity to really organize a medical school from scratch....to put the clinical and the basic science departments together.. on a bigger scale."(S. L. Warren 1983, 994-95).

The Manhattan Project was a crucial resource for these developments. Three of the original five founder faculty members of the UCLA Medical School--Warren, John S. Lawrence and Andrew Dowdy--were all colleagues and had worked closely together in building the Manhattan District facilities at Rochester. The new AEC projects were also a key resource for building up his new faculty:

But now the chief problem was to get some faculty, hopefully who would be able to start their research in the Atomic Energy Project. I couldn't think of a field, except maybe psychiatry, where this couldn't be done, because the effect of fallout and radiation was so catholic. It entered every field and every discipline. For instance, Dr. John Lawrence worked in Rochester on the effects of radiation on the blood and had Dr. William Valentine as his assistant. Dr. Valentine had just finished his residency at that time. It was quite simple, when I picked Dr. Lawrence to be the chairman of medicine, to have him bring Dr. Valentine and later Dr. William Adams, both of whom were working in this same field in Rochester during the war on Manhattan money. All three could be cleared top secret, no problms, and I got one of the best clinicians in the country. I could set them down in the lab right away. So this made it easy for them to come, too; no hiatus--their work could go right on. (Ibid., 1075-76)
Consistent with Warren's strategy of maximizing available government and university resources, recruitment of Valentine and Adams also illustrate the importance to the new school of the nearby Wadsworth VA Hospital. Adams received his salary from the VA for several years, and both Adams and Valentine worked in research laboratories at the VA.The AEC project was crucial to building the research facilities Warren envisioned and for recruiting physicists, engineers, and other scientists without medical degrees into a medical environment. Contract, GEN-12, provided a valuable source of contracts needed to train personnel and develop instrumentation for biomedical research (S.L. Warren 1983, 777-79; 1066-75).

Rapidly growing from a small group in 1947 funded at $250,000 to a roster of 145 persons in 1949, [8] the AEC project was from the very beginning a large support organization for Warren's design of a new research-based medicine fusing basic and clinical sciences modelled after the Manhattan Project. In square footage of its facilities alone, the AEC Project occupied 33,600 square feet, whereas the space allocated initially to medicine and surgery totalled 31,000 square feet. [9] While the AEC Project was housed in facilities separated a short distance from the university medical center, projects such as the summer course "The Application of Nuclear Physics to the Biological and Medical Sciences," [10] taught by Staff Warren, Andrew Dowdy, and Robert Buettner were typical of the integration sought between the AEC Project and the new medical school. The budget for the AEC Project incorporated separate line items for support of work in various basic science departments of the medical school. Numerous forms of collaboration developed within different sections of the AEC project and University clinical investigators. Typical was an important early project to develop scintillation counters and radiation flourimeters. Ben Cassen and Fred Bryan reported to Warren in 1948 that:

Sufficient progress has been made recently by the Medical Physics section of this [the AEC] project in collaboration with the Industrial Hygiene division on development of prototype instrumentation for the measurement of roentgen rays, alpha particles, and beta activity in tissue in vivo, that it is now becoming desirable to make arrangements for the future clinical application and testing of these devices.
These instruments are called tissue radiation fluorimeters and essentially consist of a small diameter light pipe in or insertable in a hypodermic needle. Any fluorescence or scintillation of a small amount of screen material placed on the end of the light pipe is transmitted to a photomultiplier tube outside the body. They can be used for measuring roentgen ray intensity in tissue or counting scintillation produced by the presence of radioisotopes or alpha emitters in the tissues. (Cassen and Bryan to S.L. Warren, 2 December, 1948)

To carry their project forward Cassen and Bryan sought permission from Warren and the AEC to engage in clinical trials with investigators at the Birmingham Veterans Hospital affiliated with the UCLA medical school teaching program (more on this below). Stating his view that such research did not appear to fall under the AEC ban against human experimentation which was directed primarily toward the use of toxic materials in the human body, Warren urged pushing forward on this project at the earliest possible moment (Warren to Cassen and Bryan, 31 December, 1948b). Such success in integrating the research projects of the AEC group with the clinical and basic science faculties led Warren to appoint a committee in 1950 to work out the formal integration of the AEC Project with the UCLA Medical School (Warren to Bryan et al., 11 August, 1950). Both parties, the AEC and the UCLA Medical School, were pleased with these arrangements, and in 1953 when reporting to Warren on the approval of plans by the AEC to expand the facilities to twice the size (63,200 square feet) of the original building, Robert Buettner noted that the AEC was extremely pleased with the graduate research training program Warren had constructed at UCLA, particularly the academic influence on the program. The new AEC resources were to be used to expand the graduate training program in the Division of Biology and Medicine from 12 to 24 (Buettner to Warren, 8 December, 1953, esp. p.2, point (7) ).

Staff Warren's visionary efforts to create a multidisciplinary medical center integrating clinical and basic science research by utilizing the resources made available to him through his connections with the Manhattan Project and his leading role on the Medical Advisory Board to the AEC was perhaps the most spectacular but by no means the only effort to recreate the institutional infrastructure of the Manhattan Project after the war. A similar vision was pursued by John Lawrence at Berkeley. Prior to the war in 1941, William H. Donner, president of the International Cancer Research Foundation, later named the Donner Foundation, donated $165,000 for the construction of a laboratory for medical physics. The Donner Lab became one of the sites after the war for the continuation of AEC support for nuclear medicine and biophysics. But well before the end of the Manhattan Project, Berkeley pioneers in nuclear medicine and medical biophysics were working to establish the institutional arrangements necessary for continuing their work after the war. In August of 1944 the Regents of the University of California approved the appointment of four faculty members, John Lawrence, Joseph Hamilton, Cornelius Tobias, and Hardin Jones to the Physics Department, where they formed the Division of Medical Physics, the rationale being that "no distinction was made, at first, between the two types of work--physical and biological" (Westwick 1996, 7). The official approval granted by the Regents of the University of California on July 1, 1945 explicitly acknowledged the desirability of linking the appointments of these new physicists with the Medical School:
There should be a nucleus of men including Drs. John Lawrence, Joseph Hamilton, [Paul] Aebersold and [Cornelius] Tobias who would hold joint appointments in the Medical School and in the Department of Physics, and then a second group of people who would play important parts in the development of medical physics such as Doctors Miller, Chaikoff, Hamilton, Anderson, Robert Aird, Strait, Low-Beer, Althausen, David Greenberg, C.L.A. Schitt and Soley. This second group would be carrying out experimental studies and therapeutic studies through the Medical School. (In Budinger, 1987, 9-10)
In addition to the links between Donner Lab medical physicists and clinical personnel in the University Medical School, the guidelines for the new appointments also stipulated that the Donner Lab have direct control of its own clinical research facility, effectively rendering it an outpatient department of the university hospital:
...there should be no limitation or "ham-stringing" of the freedom of the members of the subdivision of Medical Physics or others in the medical school to carry on treatment or investigations at Berkeley if research were the prime interest. (Ibid., 10)
Building the Industrial Infrastructure: The Isotope Distribution Program

The most important of the components necessary for the nascent medical field was the support it received from the Atomic Energy Commission's program for distributing radioisotopes. Paul Aebersold who had completed his Ph.D. with Ernest Lawrence at the Berkeley cylclotron with a dissertation on the collimation of fast neutrons, became the director of the isotope program, transferring from Los Alamos Lab to Oak Ridge in January of 1946. Aebersold successfully headed the program for twenty years, until his retirement in 1965. The program for distributing reactor-produced radioisotopes was formulated between January and August of 1946 by a committee appointed by the National Academy of Sciences (Atomic Energy Commission 1946). The enactment of the Atomic Energy Act on August 1, 1946 provided for the distribution of radioactive byproduct materials from nuclear reactors. The first shipment was on August 2, 1946 (Atomic Energy Commission 1946a, 1). Among the milestones of the early isotope distribution program, the following are most significant for our purposes:

Isotope Program Milestones [11]

January 1, 1947

Jurisdiction of the program turned over to civilian Atomic Energy Commission

March 1, 1947

Inititation of service whereby the radioisotope user may submit own sample for irradiation or neutron bombardment in the nuclear reactor

July 1947

First compound labeled with radiocarbon (methyl alcohol) available from the Commission

January 25, 1948

Enactment of regulation by the Interstate Commerce Commission for shipment of radioisotopes by common carrier (rail and truck).

April 1, 1948

Initiation of a program available free of production costs three isotopes -- radiosodium, radiophosphorus, and radioiodine -- for research, diagnosis, and therapy of cancer and allied diseases.

June 1948

Opening of first Commission-sponsored training course in radioisotope techniques by Oak Ridge Institute of Nuclear Studies

July 1948

Production and distribution of radioisotope labeled compounds by commercial firms.

February 25, 1949

Extension of Commission's support of cancer research program to include the availability of all normally distributed radioisotopes free of production costs for use in cancer research.

June 1949

Initiation of a program for commission support of commercial development and synthesis of selected radioisotope labeled compounds

June 1949

Initiation of a program for cyclotron production and distibuion of certain long-lived radioisotopes not producible in the nuclear reactor.

July 20, 1949

Enactment of regulations by Civil Aeronautics Board for shipment of radioisotopes by commercial aircraft.

As authorized by the Atomic Energy Act, the directors of the Isotopes Division interpreted their mission in its broadest terms as: improving the public welfare, increasing the standard of living, strengthening free competition in private enterprise, and promoting world peace (Aebersold 1949, 1). This mission could best be accomplished by assisting and fostering private research and development to encourage maximum scientific progress (ibid., 2). How best to transition the facilities at Oak Ridge, which had operated under maximum security conditions throughout its brief existence, raised challenging scientific, technical and managerial issues. [12] In the post-war effort to downsize and consolidate the nation's military research enterprise, consideration was given to transferring the basic research programs at Oak Ridge to Chicago. Such a move would have resulted in Oak Ridge losing its status as a national laboratory under the AEC's newly forming guidelines on national labs, and this loss of lab status was bitterly protested through a letter writing campagn to President Truman and AEC officials by the directors of the Oak Ridge facility, who feared their facility was being demoted to a chemical processing factory. [13] David Lillienthal, the Chairman of the Atomic Energy Commission, intended to achieve this objective of uniting government sponsored academic research and industrial prototype development through the establishment of the Oak Ridge Institute of Nuclear Studies.

From the earliest phases of its establishment the isotope division at Oak Ridge was chartered with the explicit aim of performing research and development that would stimulate industrial and medical uses of atomic energy. [14] In an era when American Science and the free enterprize system had won the war, the projects generated under the aegis of the Atomic Energy Commission could not interfere or compete with American industrial interests. The goal of the Isotope Division was to promote the use of radioisotopes as widely as possible through dissemination of information, through training programs, and through the distribution of radioisotopes to researchers, and at the same time the Division was to encourage private commercial interests to develop the industry. The projects generated by the AEC were to be handed off to private commercial interests as quickly as possible. It was decided that a reasonable policy for the Commission to follow in the synthesis and distribution of isotope-labelled compounds would be that the Commission only distribute materials which commercial firms were not prepared to produce and distribute in the foreseeable future and that the Commission withdraw from production as soon as a commercial firm demonstrated a satisfactory synthesis. Syntheses developed in Commission laboratories should be made freely available, and isotope-labelled compounds which were not of interest to commercial firms but which were of significance to scientific research should be made by Commission labs (Anon. AEC 1947. Minutes, p., 9).

While Aebersold and the Isotopes Division were eager to put the entire industrial production of radioisotopes in the hands of commercial vendors, including reactor production as soon as feasible, they repeatedly argued that the cost of building the reactors and other facilities would make radioisotopes prohibitively expensive. Thus from the beginning they followed the policy established within the Manhattan Project of government ownership of the reactor and operation by management contractors from private industry. Citing separate studies by Bendix Aviation and Tracerlab on the feasibility of private radioisotope production in 1951, Aebersold urged, "It is obvious that the Commission must supply radioisotopes until private industry is ready and willing to produce them,"(Aebersold 1951, 13-14) and he doubted that reactor production of radioisotopes would become a truly comptetitive enterprise in the near future. One of the approaches taken to commercialize production of radioisotopes was to encourage the entry of intermediate producers of isotope-labeled compounds. Early entrants into this field were Tracerlab of Boston and Abbott Laboratories of North Chicago. Tracerlab submitted a proposal to synthesize 14-C labeled compounds for medical research use.(Tracerlab, 1947) According to the conditions of the arrangement worked out in December 1947, Tracerlab received 100 millicurie allocations of 14-C from Clinton Laboratories in Oak Ridge which it could stockpile and process into a variety of synthesized intermediates. Abbott worked under a similar arrangement but quickly pursued the lease of a site in Oak Ridge for a radiopharmaceuticals processing plant. By 1952 Abbott had built a plant in Oak Ridge adjacent to one of the main reactors, and by 1955 announced plans to double the floor-space and triple the capacity of its radiopharmaceutical processing plant (Aebersold, 1951, 9).

Although firms like Abbott and Tracerlab were beginning to get into the isotope processing business, in the early stages of the isotope program they could not meet all the needs of the scientific and medical researchers Aebersold was attempting to stimulate, nor could they generate a synthesis program on a scale adequate to the needs of the experienced research groups already within the AEC labs. Considerable delay in the research programs at these facilities (by as much as 6 months according to one Commission estimate--memo 3 September 1947--of delays caused for Memorial Hospital, New York, Western Reserve Medical School and others in medical and cancer research) would have been caused by enforced dependence on commercial producers. Moreover commercial producers were not in a position to handle very large quantities of radioactive material (in the hundreds of millicuries) safely.

In light of such concerns another strategy developed by the Isotopes Division was to encourage AEC labs to develop the production and distribution stages of processes for synthesizing radioisotope-labeled intermediates they might use for their own research purposes. It was argued to be more cost-effective to add the additional capcity required to increase the batch size of isotopes beyond the needs for immediate experimental work and distribute them to off-commission researchers than it would be for commercial producers to enter the market. An effective example of this strategy was implemented in the Berkeley Radiation Laboratory, where Dr. Melvin Calvin had developed numerous effective, high-yield syntheses of 14-C labelled compounds. Concerns were raised about the advisability of entering the business of providing intermediate compounds by Carroll L. Wilson, the General Manager of the Oak Ridge Laboratory, urging that "the making of compounds may well represent the basis for a useful business in the manufacture of chemical intermediates or final products. Unless the Commission considers very carefully the various steps in this direction, it may seriously prejudice the possibility of building a small but useful industry in the production and sale of compounds containing radioisotopes." Such concerns were countered by the view that:
The program will actually improve the opportunity for such entrance by immediately helping to build up the market and by accumulating data on synthesis procedures and costs as well as on degree of demand. This should enable the Commission within 12 to 18 months to offer private concerns a definite industry and market. It will save private firms a considerable inititial investment in C-14, in facilities and development costs without their having even an approximate knowledge of the market. It will allow the Commission time to perfect the techniques employed in the syntheses and to aid in the training or dissemination of information that will be required for larger scale off-Commission operations with C-14.(Williams, 1947, 6)
As a guarantee to industry that the Isotope Distribution Program was intended to promote scientific research and facilitate rather than compete with private industry in promoting the commercial use of nuclear isotopes the agreements reached in the October 30, 1947 meeting between AEC officials and industry representatives specified that syntheis processes which had been developed in Commission laboratories should be made freely available, and that the Commission would make isotope-labeled compounds which were not of interest or profit to commercial firms but were important for scientific research.( Anon. AEC, Minutes, 1947, 6)

In addition to contracting within AEC laboratories for the development of economical syntheses and their initial scale-up to production level, the Isotope Division also operated a program for purchasing on open bids from private laboratories special compounds of special interest for biological or medical research in cases where the synthesis was difficult and the demand uncertain. Examples of compounds developed in this manner were labeled folic acid, thiouracil and hormones needed for cancer research, labeled vitamins, and labeled DDT.(Aebersold, 1951, 12) These programs for research and development of syntheses as encouragement to the commercial production of medically relevant isotopes succeeded in generating more than 225 compounds by June of 1952.(Ibid., 13)

In the 1949 formal review of the distribution program Paul Aebersold reported that Oak Ridge distributed radioisotopes for cancer research free of production costs. The total expenditure for production and free distribution of radioisotopes for medical research in 1949 was $300,000. Aebersold projected that the cost of this free distribution program for 1950 would be $450,000.(Aebersold, 1949, 8-9). In addition the AEC budgeted $100,000 in 1949 for the production of isotope-labeled compounds, including $25,000 for research on new synthesis methods, and provided an additional $100,000 for cyclotron-produced radioisotopes. In his general address to the AEC for the March 4, 1949 meeting, Aebersold defended the level of promotional effort as essential, and he urged even larger future government support for these programs:
The Government can go further than above and even distribute the irradiated materials and basic products at less than the already inherently low production costs. This is because of the expectation of great returns to the general national health and welfare from the wide scale use of the materials in medicine, science, agriculture and industry. Although the cost to the govenment of the isotope distribution program is not over one million dollars a year each for radioactive and stable isotopes, the benefits resulting from this investment, through all the investigations and applications made possbible by the progam, could in not too many years hence easily be worth 10 to 100 times the original investment.(Ibid., 3)
Aebersold assured his AEC colleagues that such Government promotion of isotope usage would not interfere with private enterprise, "but actually encourages new areas of enterprise for industry as well as profitable improvements in existing industry."(Aebersold, 1949, 6). The early success of this program in launching the medical and industrial uses of radioisotopes was considerable, and every indication suggested it would continue to grow. Thus in a "Memorandum of Information" on the program filed in 1951 Aebersold projected the total sales volume would double within the next five years, and he reported that radioisotopes had become so widely adopted in medical research that their use would continue despite removal of government subsidy, although at a retarded rate.(Aebersold, 1951, 30). Industry interest in radioisotopes, while initially small, was increasing rapidly after the first three years of the program (commercial distribution was authorized by AEC-108, June 2, 1948, see Table above). Aebersold noted that 183 of the 800 institutions receiving radioisotopes in 1951, or approximately 23%, were industrial organizations. This figure represented a 50% increase over the previous year. Industrial use of cobalt 60 was especially strong, growing by 552%, due principally to its importance in radiographic testing in several industries. But the importance of government subsidy for the new field was undeniable. As Aebersold reported, while Union Carbide projected "sales" of radioisotopes exceeded $1-million for 1952, the $450,000 AEC subsidy for the free distribution of medical isotopes, combined with the approximately $200,000 per year of the Oak Ridge National Laboratory's "sales" of isotopes to other AEC installations meant that approximately 65% of the costs for producing and distributing isotopes were subsidized by the AEC. Furthermore, when it was considered that many of the institutions purchasing isotopes did so with funding supplied by contracts through a variety of AEC divisions, the subsidy was considerably higher.(Ibid., 31)

The Oak Ridge Radioisotope Training Program

From the beginning of Paul Aebersold's career as director of the Isotope Distribution Program it was clear that the major obstacle to overcome in creating conditions for greater commercial participation in production and distribution as well as the utilization of radioisotopes in industry was the lack of personnel trained in radioactivity techniques. The lack of training was considered far more of a problem for industry than either the fields of medical or scientific research. Aebersold and the Isotopes Division were the primary forces in setting up training courses in radioisotope techniques by the Oak Ridge Institute of Nuclear Studies beginning in June of 1948. Through publication in scientific and technical journals, and by distribution of fliers sent to universities and medical schools and companies encouragement to attend these courses was given to a wide range of potential candidates in medicine and industry.(Oak Ridge Institute, 1947, 1)

In its first year the training school accepted 48 students at a time into one-month training courses. The courses were intended primarily for technicians in university and industrial laboratories, agricultural experiment stations, medical schools and other organizations who might desire to employ radioactive isotopes in their research programs but did not have the appropriate personnel or equipment for such work. The goal of the course was to develop familiarity with the uses of radioactive isotopes as a technique and research tool in tracer studies. Trainees were selected on the basis of previous training and experience of the individual applicant, but also on the basis of evidence presented that the institution they represented intended to establish a laboratory for isotope tracer work. Selection was also made to ensure wide geographical participation and diversity of the type of institution and research activity.(Brucer 1951) Trainees paid a $25 fee for the course and had to defray their own travel and living expenses.

The instructional program was divided equally between laboratory and lecture courses from 9-12 noon Monday through Friday. Monday and Friday afternoons were reserved for seminars. Occasional afternoon demonstrations of equipment by commercial manufacturers and conferences were also part of the program. The laboratory was partly done by demonstration and partly direct experiments performed by trainees. A demonstration lab was scheduled on Wednesdays from 1:30 to 4 PM. Individual lab work was done in smaller groups of 12 trainees. The lecture topics included basic nuclear physics, instruments (such as ionization chambers, Geiger-Mueller counter tubes, preamplifiers, electroscopes and photographic detection, and analysis by mass spectrometry), design of tracer experiments, radiochemistry, design of small radioisotope tracer laboratories, health physics and precautions, production of isotopes, and sources and procurement of isotopes and equipment. There were "special lectures on radiation effects on gene mutations, chromosome breaks, and mitosis; nature of radiation burns, radiation induced cancers, electron microscope techniques and general biophysics."(Brucer, 1951).

The isotope tracer technique school was extremely important for the development of nuclear medicine and for the nuclear industry generally. In the first formal review of the Isotope Distribution Program in 1949, Paul Aebersold reported that practical considerations related to the recruitment of qualified teaching staff in the program had limited the number of students that could be accepted and trained in the program to 200 per year, but that more than three times that number of applications was received from qualified applicants.(AEC 1949, 7) In response to this demand the Navy opened a training course similar to the Oak Ridge school at Bethesda, Maryland. The contributions of both the Bethesda and Oak Ridge schools to the growth of the field was impressive; in its second annual report to the AEC on the progress of the school, the Oak Ridge Institute of Nuclear Studies reported that the total number of participants who had attended the basic course to date was 963. Another 120 persons had attended the advanced biochemical research sessions (Brucer, 1952). But in spite of the apparent success in attracting trainees to the isotope tracer technique program, Aebersold reported that while medical interest in isotopes was strong, "Industry has been slow in utilizing radioisotopes in research, in process control and in new products....Industrial uses will not increase rapidly until it can be demonstrated that the overall costs of procurement, shielding, instrumentation, and special handling will permit economic advantage to the user."(AEC 1949, 8-9) There seemed to be no shortcut to alleviating the problem other than to continue and possibly intensify the promotional programs.

Building a Clinical Infrastructure for Nuclear Medicine: The Veterans Administration (VA) Hospitals

A crucial component evident in the discussion of the programs at Berkeley and at UCLA discussed above was establishment of links from the AEC projects both to academic science disciplines and to clinical facilities for medical training and research. The Donner Lab group worked persistently at increasing its immediate access to patients for clinical research, unrestricted by the necessity of having their research initiated and approved by the Medical School. [15] The problem was resolved eventually by construction of the Donner Pavilion, a special two-floor wing costing $191,000 added to the Cowell Hospital student health center in 1954 for research in radiobiology under supervision of the Donner Laboratory. At UCLA Staff Warren faced the difficulty that no hospital facilities yet existed and building completely new ones required financial resources exceeding funds available to him from the allocation of the state legislature. The solution for this problem confronting efforts to transition the work of the Medical Division of the Manhattan Project to the postwar civilian medical enviroment was provided by the Veterans Administration (VA) hospitals.

A set of developments with direct implications for the clinical infrastructure of nuclear medicine within the VA began with the atomic bomb tests at Bikini in 1946. After Japanese forces had been driven from the Marshall Islands in 1944, the islands and atolls, Bikini among them, came under the administration of the US Navy. In 1946 Bikini was selected as the site of Operation Crossroads, a vast military-scientific experiment to determine the impact of atomic bombs on naval vessels (Weisgall 1994). The world's first peacetime atomic-weapons test was conducted at Bikini on July 1, 1946. A twenty-kiloton atomic bomb was dropped from an airplane and exploded in the air over a fleet of about eighty obsolete World War II naval vessels, among them battleships and aircraft carriers, all of them unmanned. The second test, on July 25, was the world's first underwater atomic explosion; it raised an enormous column of radioactive water that sank nine ships. Stafford L. Warren at that time still in his position as Medical Director for the Manhattan Engineering District had been assigned in April 1946 to serve the Joint Task Force One for the Operation, charged by Leslie Groves with setting up a radiological civil and military defense to protect the troops and then to create the information which would enable a force to occupy an area whether it was military or civilian (S. L. Warren, 1983, 821-22). Dr. George M. Lyon, a pediatrician from Huntington, West Virginia, was Warren's chief medical officer on Operation Crossroads. Lyon, who had also served during the Manhattan Project as an observer at the Alamogordo test, assisted in designing the gathering of data on fallout and related exposure effects of the Bikini detonations. Lyon's next assignment was as Special Assistant for Atomic Medicine in the Office of the Chief Medical Director of the Veterans Administration.

The Atomic Medicine Division of the Veterans Administration was initiated out of concerns raised about potential future legal claims arising from Operation Crossroads, similar future atomic tests, and from human exposure to ionizing radiation in laboratories and processing plants. In a summary history of the program dated December 8, 1952 Lyon states that at the meeting convened with General Leslie Groves and others by General Hawley in August of 1947, it was agreed that a Central Advisory Committee be formed consisting of Stafford Warren, Hymer Friedell, Shields Warren, Hugh Morgan, and Perrin Long, all of whom had participated in either the Manhattan Project or Operation Crossroads, to advise on steps to be taken for dealing with potential alleged service-connected disability claims associated with atomic energy. The Central Advisory Committee held its first meeting on September 5, 1947. According to Lyon, no one on the Committee was interested in drawing public scrutiny to problems with nuclear energy, and they were concerned that creating alarm by drawing attention to suspected grounds for disability claims might jeopardize the positive development of nuclear medicine. It was decided to downplay the negative concerns behind the formation of the program by characterizing it primarily in terms of research aimed at bringing veterans the benefits of medical breakthroughs connected with the use of radioisotopes carried on during the War. Lyon wrote:
At this time (September 5, 1947) the objectives of the Atomic Medicine Program were formulated and the broad aspects of a scheme for establishing a radioisotope program to support the more inclusive Atomic Medicine Program were drafted. The advisory committee was given the name, "Central Advisory Committee on Radioisotopes", as it was not desired at this time to publicize the fact that the Veterans Administration might have any problems in connection with atomic medicine especially the fact that there might be problems in connection with alleged service-connected disability claims. The committee recommended, (a) the establishment of an Atomic Medicine Division within the Department of Medicine and Surgery and the appointment of a Special Assistant for Atomic Medicine to head up the Division and to represent the Chief Medical Director in the handling of atomic medicine matters, and (b) the establishment of a Radioisotope Section to implement a Radioisotope Program. It further recommended that, for the time being, the existence of an Atomic Medicine Division be classified as "confidential" and that publicity be given instead to the existence of a Radioisotope Program administered through the Radioisotope Section. General Hawley took affirmative actions on these recommendations and it was in the manner described that the Radioisotope Program was initiated in the Fall of 1947. (Lyon 1952, 554)
A related mission of the Division was to prepare for the possible role of the Veteran's Administration in connection with civil defense. Specifically the VA was charged with developing a program of training and education in civil defense:

A major objective of the Radioisotope Program was, from the very beginning, to provide the Veterans Administration with qualified professional, scientific, and technical personnel, as well as the specialized facilities required, (a) to meet the varied and unique problems of atomic energy that might be of concern to the Veterans Administration, particularly in respect to problems associated with the study and analysis of alleged service-connected disability claims, and (b) in connection with certain responsibilities that the Veterans Administration may have in civil defense (ibid., 554-55).

Thus, it was decided to emphasize the VA Radioisotope Program in the public eye, describing it primarily in terms of its contribution as research in support of civil defense programs and in terms of the potential of research with radioisotopes for improving clinical medicine affecting veterans, particularly through the development of diagnostic aids. The Division's original mission to collect data and conduct research for evaluating potential disability claims became a minor effort.(United States. Advisory Committee on Human Radiation Experiments. 1995 pp. 477-79.)

The emphasis on the basic biological and clinical research character of the radioisotope program was the principal message in the letters inviting Stafford Warren, Hymer Friedell, Shields Warren, Hugh Morgan, and Perrin Long to serve on the Central Advisory Committee sent by E.H. Cushing, the Assistant Chief Medical Director for Research and Education of the Veterans Administration.(Cushing to S. L. Warren, 15 August, 1947). Cushing also emphasized that benefits the contemplated program would offer the larger medical research community:
Within the hospitals of the Veterans Administration there is an important reservoir of valuable clinical material. The administrative facilities and the professional organization of the Veterans Administration in large measure tend to favor the harvesting of valuable information through the conduct of investigations of an approved nature within these hospitals. The close association of the staff of many of these hospitals with outstanding teaching and research centers through the Dean's Committees favors the conduct of investigations and the appropriate utilization of radioisotopes within certain hospitals of the Veterans Administration on a high plane of medical acceptance.(Ibid., 2)

Pointing to the use of 32-P in the treatment of patients with chronic leukemia and with Hodgkin's disease as an example, Cushing observed that the VA offered controlled conditions permitting statistical evaluation on a larger scale than anywhere else. "As time goes on," he noted, "there will be continuous opportunity for similar contributions" (ibid.)

Summarizing these developments we can observe that the "research ethos" in the immediate postwar period nurtured a fruitful convergence of interests among the Veterans Administration and discipline-building physicians, such as Warren. For their part physicians like Warren seeking to transform clinical medicine into a science-based experimental research field required new hospital training and research facilities to accommodate their plans of expansion. In the immediate postwar era, traditional academic positions were scarce and did not always fit the profile of the emerging new biomedical researcher. The construction of the radioisotope research units established within VA hospitals provided crucial enabling components for this program in terms of positions, facilities, and "clinical material." For its own part, through the creation of research facilities in its hospitals for radioisotope work as well as other research, the Veterans Administration benefitted by establishing close working relations with academic medical programs that could aid in solving its desparate shortage of qualified medical staff, intensified by the increasing numbers of veterans requiring medical care.

At the end of the first year of the program eight Veterans Administration hospitals had been equipped with Radioisotope Units. [16] Each of these units was established in close association with local medical schools having active radioisotope programs. The five year history of the program demonstrates a steadfast effort to expand the number of radioisotope facilities: in 1949 there were twelve VA Radioisotope Units, fourteen in 1951; and by the end of 1953 there were thirty-three units employing 202 full-time staff (Committee on Veteran's Medical Problems 1954, 622.). These labs occupied spaces between 1,200-3,000 square feet in their hospital units (Central Advisory Committee 1949, 8). [17] During the first four years of its existence, the VA Radioisotope Program was funded at roughly $500,000 annually:

 

Equipment and Supplies [18]

Personnel

FY 1948

$220,500

$ 31,604

FY 1949

157,970

290,260

FY 1950

216,052

299,838

FY 1951

225,480

183,978

Total

$820,002

$805,680

The progress reports of the Radioisotope Units filed annually for the meetings of the Central Advisory Committee provide evidence of the sophisticated assembly of equipment and experimental research being undertaken in these labs. [19] Typical VA-Radioisotope Units consisted of an administrative office, separate biochemical and biophysical laboratories with specially constructed hoods, chemical benches, etc., and a clinical room or rooms where patients were brought for diagnostic studies involving administration of radioisotope materials. The staff of a radioisotope laboratory consisted initially of 5-8 full-time individual professional, scientific, and technical personnel. In addition usually two or more faculty members or laboratory staff persons from a local university medical school served on a part-time basis in the unit. University faculty also served as consultants (Lyon 1950,1). [20] Oversight of the Radioisotope Program in an individual hospital was administered by a Director of the unit, usually an MD in internal medicine, or on occasion a radiologist. The Director of the radioisotope unit was directly responsible to the Chief of Medical Service of the hospital.

The salient feature of the VA radioisotope units was their close relationship to a local medical school or university. In fact,VA radioisotope laboratories were established only in VA hospitals having affiliation with medical schools (Lyon 1952, 555). Thus, the radioisotope units of the VA hospitals were crucial enabling structures for nuclear medicine and for efforts to place clinical medicine on experimental foundations in the post-War era. The VA radioisotope units played at least two essential roles: first they were crucial sites for developing therapies, instrumentation, training programs, and the production of basic biomedical research conducted in close connection with both the AEC labs and with university departments of basic science. Secondly, by designing and implementing practical laboratory spaces and clinical wards integrated seamlessly within the structure of the normal hospital, the architects of these radioisotope units--George Lyon and his staff--not only created structures that were implemented throughout the large number of VA hospitals (by 1965 there were 86 VA hospitals licenced by the AEC to use isotopes). These clinical laboratory facilities were the prototypes of all such clinical-laboratory facilities in the U.S. and as such were major sources of transformation in the American hospital system.

An excellent example of the manner in which the radioisotope units served as major research centers in the nascent field of nuclear medicine is suggested by the work of the VA Center (VA Wadsworth) in Los Angeles. As we have indicated above, this center developed in close association with Staff Warren's program for building the UCLA Medical Center. He saw the unit as a means for creating positions for physicists, radiologists, and physicians working with radioisotopes that he could not get appointed on the regular faculty at UCLA. In addition, the VA provided the crucial clinical wards needed for his fledgling medical school, and it served as an important training center for potential residents in nuclear medicine. By 1955, when the formative stages of the VA radioisotope program can be considered to have been completed, the radioisotope unit of the VA Wadsworth had a staff of 19 persons including three consulting physicians and radiologists, and a budget of $66,000, of which $59,000 went for salaries of support staff and consultant fees (Bauer l956). Members of the radioisotope unit made twenty presentations of work at scientific meetings and produced fourteen publications in 1955 on a range of topics including studies of skin collagen with the electron microscope (Linden, et al. 1955), use of radioactive phosphorus in the diagnosis of skin tumors (Bauer and Steffen 1955), and uses of radioisotopes in studying neuromuscular diseases. (Blahd et al. 1955). Members of the unit were working on eight different long-term research projects, particularly in areas of muscular distrophy, the use of rubidium-86, potassium-42, and sodium-22 in electrolyte disorders, peripheral clearance of radioisotopes in patients with heart disease, and several projects involving electron microscopy. In addition to projects initiated and directed by members of the radioisotope unit, six different research projects directed by UCLA medical faculty were being carried out with collaboration of the Radioisotope Service. A similar record of high-level research achievement would be documentable at most of the other thirty-three radioisotope units. No less significant was the clinical work being done in the unit. Seventy-five patients received a variety of radioisotope treatments and 1100 patients received radioisotopes in diagnostic procedures in 1955. Two residents on the Medical Service and one resident in Radiology were assigned to the Radioisotope Service on a 3-month rotations. [21]

Conclusion

The trademark of today's clinical nuclear medicine services, the "scan", or image of the distribution of radioactivity in a patient's body, is the product of work begun at the Wadsworth VA Hospital in the late 1940s. Herbert Allen, who assumed direction of the VA Radioisotope Service at Wadsworth in 1950 after having set up the first six radioisotope units under George Lyon, was seeking a way to localize radioactivity precisely in the patient's body. He used a gamma radiation detector which Benedict Cassen and his colleagues at the UCLA AEC laboratories had developed.(Cassen, et al. 1950) This detector was collimated so that when it was placed directly over an anatomic area, it could measure the activity present in that area without much interference from surrounding areas. Allen used this device to map out the pattern of radioactivity in patients' thyroid glands, laboriously counting the activity at each point as the detector was manually moved through a grid pattern.(Allen, et al. 1951) Cassen and Raymond Libby together with engineers Clifton Reed and Lawrence Curtis, extended this concept to develop an electrically driven device which would move the collimated detector back and forth to "scan" the anatomic area of interest and so to map out the pattern of its radioactivity.(Cassen, et al., 1951) This device was first demonstrated at a national meeting of VA radioisotope unit personnel in 1950. (Lyon 1951) Its earliest use was in imaging the normal and diseased thyroid gland, taking advantage of the fact that the thyroid gland concentrates radioiodine in its simple iodide form.

This radioisotope scanner greatly expanded nuclear medicine. Soon radioactive compounds were developed to image many organs of medical importance. The clinical usefulness and commercial profitability of scanning and the agents which made it possible led to commercial interest, and to rapid expansion of clinical nuclear medicine applications, not only in university and veterans' hospitals but in community hospitals as well. Within a few years, by the mid-1960s the Anger scintillation camera, developed in the AEC Donner Lab at Berkeley, began to come into use. The Anger Camera, which provides a simultaneous image of all parts of the field of view, gradually supplanted the scanner, though the term "scan" persists to this day. Modern tomographic methods use principles inherent to both the camera and the scanner.

We have described the first Manhattan Project for biomedicine as the efforts to build the infrastructure of research facilities in the basic and clinical sciences as well as the industrial base needed to transition the work of the Medical Division of the Manhattan Project to the commercial sector. These efforts were successful beyond anyone's wildest imagining. In 1976, thirty years after the legislation establishing the Atomic Energy Act an ad hoc committee headed by James Potchen of Michigan could report to the Energy Research and Development Agency (ERDA):

The effect that nuclear medicine has had on the practice of medicine can be demonstrated in at least two ways. The first relates to the use of nuclear medicine procedures in the clinical practice of medicine. For example, in 1973, some 7.5 million Americans received in vivo nuclear medicine procedures. This represents approximately one procedure for every 4.4 hospital admissions. These procedures were performed in some 3,000 hospitals and 2,000 independent clinical laboratories. The related nuclear medicine industry is now growing between 20 percent and 25 percent per year according to recent market research analyses.
The second area of major impact relates to the effect of nuclear medicine as a scientific discipline with regard to careers in health care. The Society of Nuclear Medicine now has some 8,000 members and the American Board of Nuclear Medicine has certified 2,070 physicians as specialists in nuclear medicine since its inception on July 28, 1971. These numbers represent individuals who spend a major portion of their careers in nuclear medicine, and do not include the large number of other users of nuclear medicine techniques in fields such as endocrinology. Careers range from the physician-practitioner to the research radiopharmaceutical chemist. That this field is well recognized as a medical discipline is shown by the establishment of the American Board of Nuclear Medicine and the recent formation of a Section on Nuclear Medicine in the American Medical Association. Additional testimony can be gleaned from the 1975 Report of the Joint Congressional Committee on Atomic Energy which concludes that "nuclear medicine represents one of the most successful applications of the peaceful use of atomic energy."(ERDA 1976, 10)

Modern nuclear medicine, carried out by physicians, scientists and technicians certified after formal training in the field, is now a requirement for hospital certification. It depends upon commercial availability of radioactive tracers tailored to the needs of the patient, on highly sophisticated equipment and on modern knowledge of the principles of radiation safety. We have told in this paper how all of these elements began in the programs of the AEC and the VA, programs which were the direct descendents of the Manhattan Project.


ENDNOTES

[1] See Hertz et al., 1938; Hamilton and Soley 1939; Lawrence, 1940; Hamilton 1942.
[2] John Lawrence called attention to the potential hazards for laboratory workers following his early work on isotope production following neutron bombardment with brother Ernest's accelerator: ...At the present time physicists rather than biologists are exposed to this potentially dangerous form of radiation; and it is imperative that those workers become familiar with the changes which take place in tissues of the body after sufficient doses.
We have as yet no knowledge of the possible delayed effects of exposure to small doses over a long period of time. However, the changes that occur after relatively large doses make it imperative that workers in laboratories where neutrons are generated protect themselves, by screening, from exposure. ...The daily dose to those working with neutrons should not exceed one-fourth that accepted as the tolerance dose for x-rays. Whether daily doses of this magnitude over a long period of time will result in damage is not known, nor is information as yet available concerning the effects of neutrons on the skin." (Lawrence 1938).
[3] In his 1948 address to the Pharmaceutical Association, Stafford L. Warren, the Chief Medical Officer for the Manhattan Project, later provided a revealing sense of the uncertainties regarding exposure levels:
Warren stated that for years dosage exposure to x-rays had been set at one-tenth of a roentgen by the Bureau of Standards. When Warren checked into the accuracy of this he found that the standard had been set out of ‘thin air.' It was set a hundred times lower than the Bureau thought hospitals could achieve at the time:
"In order to qualify this tenth of a roentgen as a reasonable figure and supply some experimental data against the time in the postwar period when the Project would be disbanded and we would have these thousands of employees who might claim compensation, we set up a dog, rat, monkey, mouse experimental program in which these animals had blood counts....It has shown up the fact that a tenth of a roentgen is not safe."
[4] In Warren's view the desirability of this proposal from the AEC's perspective was that:
"teaching institutions may be utilized and work stimulated in all parts of the US; these men and their laboratories also offer facilities of use to the Manhattan District in emergencies and for medico-legal consultation." (Warren 1946, 9)
[5] On the issue of declassification of medical documents the AEC was more guarded in its cooperation. A memorandum dated April 17, 1947, from Colonel O.G. Haywood, Jr., of the Atomic Engergy Commission to Dr. Fidler, US Atomic Energy Commission, Oak Ridge addressed the subject of medical experiments on humans as follows:
1. It is desired that no document be released which refers to experiments with humans and might have adverse effect on public opinion or result in legal suits. Documents covering such work should be classified "secret". Further work in this field in the future has been prohibited by the General Manager. It is understood that three documents in this field have been submitted for declassification and are now classified "restricted". It is desired that these documents be reclassified "secret" and that a check be made to insure that no distribution has inadvertently been made to the Department of Commerce, or other off-Project personnel or agencies.

2. These instructions do not pertain to documents regarding clinical or therapeutic uses of radioisotopes and similar materials beneficial to human disorders and diseases." (Haywood to Fidler 1947)

Other documents suggest that managing the image problem related to human experimentation continued, as suggested in the correspondence of Shields Warren with Albert Holland, Director of the Oak Ridge facility:
Reference is made to your memorandum dated January 28, 1948, which requested reconsideration of the classification on the following documents:
CH-3592, entitled, "Uranium Excretion Studies."
CH-3607, entitled, "Distribution and Excretion of Plutonium in Two Human Subjects."
CH-3696, entitled "An Introduction to the Toxicology of Uranium."
MUC-ERR-209, entitled, "Distribution and Excretion of Plutonium."
It is the feeling of the Division of Biology and Medicine, the Advisory Committee for Biology and Medicine and the Technical Information Office of the Atomic Energy Commission that these documents should not be declassified (Sheilds Warren to Holland, 1948).
[6] Wilson to Warren, 30 April, 1947:
....The Commission also hopes to strengthen the position of the Universities to attract personnel of high calibre to the medical research work, by authorizing them, with the approval of the commission to enter into contracts of employment with key personnel for periods up to three years.
The Commission is entirely sympathetic with the view of your Committee that research personnel engaged in medical projects should be encouraged to exercise their own initiative and should be given an opportunity to devote part of their time to pursuing lines of research which appear fruitful to them, even though not immediately related to specific items in the approved program for the particular project. Accordingly, the Commission is authorizing its Area Managers to approve such research, up to twenty percent of the time of the research personnel engaged on such medical projects. When such approval is given, the Director of the medical project will be required to certify to the Commission (1) that the research is useful and is not outside the general scope of the Commission's research interests, and (2) that the research will not unduly interfere with the progress of the work on the approved program at the project. The director also will be required to indicate separately in his reports to the Commission what research has been done under this authorization.
The memo went on to discuss guidelines for obtaining medical data:
"It is understood that your committee has recommended a program for obtaining medical data of interest to the commission in the course of treatment of patients, which may involve clinical testing. The Commission wishes to make clear to your Committee its understanding of the program which is being approved. The Commission understands that in the course of the approved program:
a. treatment (which may involve clinical testing) will be administered to a patient only when there is expectation that it may have therapeutic effect;
b. the decision as to the advisability of the treatment will be made by the doctor concerned.
[7] In his oral history interviews with Adelaide Tusler Warren later recalled:
Well, when the committee and I resigned during this interim preiod late in 1947, we recommended that a budget of $28 million be given to the division each year because there was so much needed for the instruments and for the full support of the programs at Oak Ridge, Brookhaven, Argonne, Rochester,Berkeley, Los Alamos, and the new one at Los Angeles. We felt it was warranted. Shields Warren didn't believe this was so. Anyway, the recommendations on his side, I think, were only $6 million or so. Fortunately this did not cut either Rochester or Los Angeles, but it didn't do much for Oak Ridge" (Warren, 1983, 1074).
[8] Due to security arrangements there was no official listing of persons employed in the AEC project. An internal phone directory dated October 15, 1949 shows a roster of 145 persons (S. L. Warren, 1949).
[9] Arthur 1992, p. 92 reports as space allocations: 15,500 for medicine, 15,500 for surgery, physiological chemistry 18,000, physiology 17,000, pharmacology 5,400, obstetrics 9,000, pediatrics 9,000, and infectious disease 22,795 square feet. Building plans and space allocation for the AEC Project are discussed in (Buettner and Warren, 8 December, 1948).
[10] Taught August 2-20, 1948, see AEC Project annual report for 1948, Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 600, Box 30, Fldr. "AEC Project UCLA."
[11] Source: Oak Ridge National Laboratory, 1949, Appendix 1-A, 30-31.
[12] See (Johnson and Schaffer 1994, 50-55) for a thorough discussion of the relationship of Monsanto to Clinton Laboratories and the transfer of plant operations from Monsanto to Union Carbide in 1947.
[13] The AEC did not release a precise definition of a national laboratory. It granted the title, however, only to laboratories engaged in broad programs of fundamental scientific research, that had facilities open to scientists outside the laboratories and cooperated with regional universities in extensive science education efforts.
[14] These concerns are clearly evident in the early memos of Paul Aebersold. See Aebersold 1946.
[15] See Lawrence to Deutsch, 23 April, 1947. Lawrence urged Deutsch to expand clinical access of the Donner group:
The suggested revision of paragraph one would result in interference with academic freedom to initiate research, which would be a very dangerous situation in the University. Furthermore, this revised paragraph would prevent members of the Division of Medical Physics who are not licensed physicians and indeed others in the University, (such as Doctor Hardin Jones, Doctor Cornelius Tobias, Professor C.F. Cook and numerous others on this campus) from carrying out any study on a human being unless it were initiated and approved by the chairman of a division of the Medical School, even though the particular investigation were a safe one." Lawrence went on to suggest: "With reference to the revised paragraph five...we would suggest the following revision: It is recognized that in order to have a continuing supply of patients who need the types of investigation that will be proposed, contact with the hosptial and out-patient department with large clinical facilities is advantageous. It is to be recommended therefore that the University of California Out-Patient Department and Hospital can be used for obtaining certain specific patients for study. The Medical Physics work can be considered an Out-Patient Unit of the University of California Hospital.
[16] These were VA hospitals in Framingham, Mass.; Bronx, New York; Cleveland, Ohio; Hines, Illinois; Minneapolis, Minnesota; Van Nuys, California; Los Angeles, California; and Dallas, Texas. Two additional Radioisotope Units were authorized for San Francisco, California and Fort Howard, Maryland at the end of the first year (VA Information Service, 1948).
[17] In its preliminary recommendation of 15 September, 1948, the Central Advisory Committee recommended that at least 2,000 square feet be allocated in new hospital constructions for the radioisotope labs (Central Advisory Committee 1948, 2).
[18] Exclusive of construction and alterations
[19] We are relying here on the reports filed on equipment and facilities at the Meeting of Representatives of VA Radioisotope Units, November 21-22, 1948, Washington, D.C. The early reports are quite extensive, since they sought to elaborate the full range of equipment being installed in the labs and the programs contemplated. Typical equipment in the VA Radioisotope units included Geiger-Mueller Scaling Units (usually two) such as those produced by Technical Associates and accessory equipment such as lead shields, all glass G.M. tubes for beta and gamma ray counting, an oscillograph, preamplifiers and a counting rate meter. Each lab had a range of monitoring equipment, including Victoreen miometors, Potter decade scalers, an Autoscaler, and a Berkeley decade scaler. Also on hand were Tracerlab sample changers (both manual and automatic), Lauritsen Quartz Fiber Electroscopes and a variety of radiation reference sources. Physical instruments included specal equiment such as Beckman photoelectric spectrophotometers, mass spectrometers (particularly at the Van Nuys unit). The Wadsworth VA in Los Angeles had a number of state-of-the-art instruments, including a mass spectrometer, an infrared spectrometer, an electron microscope, and a visible spectrometer with ultra violet range attachment ( see Raymond Libby in Central Advisory Committee 1949, 22). Isotope units also had chemical instrumentation useful in immunological work such as Beckman pH meters, analytical balances, drying ovens, a centrifuge, a bacteriological bench, autoclave, 370 degree incubator, and a refrigerator. Apparatus for ultramicrochemical studies included an electrophoresis apparatus, a Chambers micromanipulator, an air-driven microcentrifuge, and a mercury microburet. A Spencer research microscope and a circular Barcroft-Warburg apparatus for work with the micromaniplator was also a standard lab component. VA labs were also equipped with a high vacuum line glass apparatus for C-14 studies.
[20] By 1955, however, the staff of these facilities had greatly expanded. See below.
[21]This emphasis on training was a key part of the VA radioisotope effort. In 1967 the VA established a formal two year training program for physicians in nuclear medicine which became a residency program after the Board of Nuclear Medicine was founded in 1972.

REFERENCES

Aebersold, Paul C. 1946. Memorandum to Members of the Interim Advisory Committee on Isotope Distribution Policy. Agenda and Discussion Material for Meeting April 20, 1946 , April 20, 1946. Memorandum and Appendices. Oak Ridge National Laboratories, Public Reading Room, ORF 00799, Folder 91.
Aebersold, Paul C. 1946a. "Availability of Radioactive Isotopes." Science, 103 (No. 2685)(June 14) : 697-705.
Aebersold, Paul C. 1949. "Present and Future Scope of Isotope Distribution Program." Document for Meeting with the General Manager, March 4, DOE Human Radiation Experiments, ORF02250, Folder.1627.
Aebersold, Paul C. 1951."Atomic Energy Commission: A Memorandum for Information. Isotope Distribution," June 29, 1951. Memorandum, Oak Ridge Operations, Records and Holding Area, Doc 1944-94, Box H-122-2, Bldg 2714-44, Box 19 of 49, Chief Counsel HRE 67.
Allen, Herbert. Raymond Libby, and Benedict Cassen. 1951. "The Scintillation Counter in Clinical Studies of Human Thyroid Physiology Using 131I," Journal of Clinical Endocrinology and Metabolism . 11: p. 492-511.
Anon. AEC 1947. Conference on Commercial Distribution of Isotope-Labeled Compounds . Minutes of Conference Meeting, Oak Ridge, Tennessee, October 30, 1947, Oak Ridge National Laboratories, Public Reading Room, ORF00774, Folder. 70.
Arthur, Ransom. 1992. By the Old Pacific's Rolling Water: Birth of the UCLA School of Medicine . Los Angeles: University of California Press.
Atomic Energy Commission 1946. "Availability of Radioactive Isotopes," Science, 103(No. 2685)(June 14) pp. 697-705.
Atomic Energy Commission. 1946a. "Isotope Distribution--First Year: July 1, 1946-June 30, 1947." Isotope Division Circular E-10, page 1. D.O.E. Human Radiation Experiments, Oak Ridge Reading Room, ORF 00821.
Atomic Energy Commission 1949. "Summary of a Special Staff Conference," Minutes of Meeting, Oak Ridge National Laboratory, Public Reading Room, ORF 02250, Folder 1627.
Atomic Energy Commission.1954. The Contribution of Atomic Energy to Medicine . Washington, D.C.: U. S. Government Printing Office.

Bauer F.K. and C.G. Steffen. 1955. "Radioactive Phosphorus in the Diagnosis of Skin Tumors. Differentiation of Nevi, Malignant Melanomas, and other Skin Tumors," Journal of the American Medical Association. 158(June): pp. 563-565.
Bauer, Franz K. 1956. "Annual Progress Report, Radioisotope Service, VAC," Los Angeles, January 31, 1956, Warren Papers, UCLA Special Collections, 987, Box 112.
Blahd, W. H., F.K. Bauer, R.L. Libby, and A.S. Rose. 1955. "Radioisotope Studies in Neuromuscular Disease. 2. Studies in Muscular Dystrophy and Myotonia Dystrophica with Sodium 22 and Potassium 42," Neurology, 5(March): pp. 201-207.
Brucer, Marshall 1951. Progress Report of the Medical Division, June 1 1950-June 1, 1951. Oak Ridge Institute of Nuclear Studies 1951.
Brucer, Marshall 1952 Progress Report of the Medical Division, June 1, 1951-June 1952. Oak Ridge Institute of Nuclear Studies 1952.
Brundage, Birchard M. 1946a. "Present Research Program, 1946." Letter Memorandum, February 26, 1946. Warren Papers, UCLA Special Collections, 987, Box 112, Folder. "Medical Advisory Committee to AEC 1946-47."
Brundage, Birchard M. 1946b. "Summary of Present Medical Research Program, November 7, 1946." Department of Energy Human Radiation Experiments, ORF-00735, Folder. 34.
Budinger, Thomas F. 1987. Fifty Years of Progress 1937-1987: Donner Laboratory Division of Biology and Medicine of the Lawrence Berkeley Laboratory, University of California Berkeley, CA , Berkeley: U.S. Department of Energy PUB-628, 1987. Pp. 45-46.
Buettner, Robert J. 1953. Letter of Robert J. Buettner to Stafford L. Warren, December 8, 1953, Letter Memorandum. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 600, Box 30, Folder "AEC Project UCLA General 1950."

Cassen, Benedict. 1948. Letter of Benedict Cassen and Fred Bryan to Stafford L. Warren, Memorandum, December 2, 1948. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 400, Box 25, Folder "Atomic Energy Medical 1948."
Cassen, Benedict, Lawrence Curtis, and Clifton Reed. 1950. "A Sensitive Directional Gamma-Ray Detector." Nucleonics, 5(6): p. 78-80.
Cassen, Benedict, Lawrence Curtis, Clifton Reed, and Raymond Libby. 1951. "Instrumentation for I 131 Use in Medical Studies," Nucleonics, . 9(2): pp. 46-50.
Central Advisory Committee. 1948. "Report on Radioisotopes, Summary and Specific Recommendations," 15 September 1948. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 300, Box 88, Fldr. Veterans Administration, 1948.
Central Advisory Committee. 1949. "Progress Reports, Minutes Third Annual Meeting of the Central Advisory Committee." Washington D.C. September 15, 1949. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 300, Box 88, Fldr. Veterans Administration, 1949.
Committee on Veteran's Medical Problems. 1954. "Tabulated Summary from Annual Progress Reports of Radioisotope Units," Bulletin of the Committee on Veteran's Medical Problems , April 20. Appendix VII.
Cushing, E. H. 1947. Letter of E. H. Cushing to Stafford L. Warren. "Invitation to Serve on VA Radioisotope Committee," August 15, 1947. ACHRE, Briefing Book, VA Research Activities, TAB I, pp. 1-2.

DeLisi, Charles. 1988. "The Human Genome Project," American Scientist 76, 488-493.

ERDA (Energy Research & Development Administration). 1976. Nuclear Medicine Research: An Evaluation of the ERDA Program , ERDA-76/135, August 1976. Washington, D.C.: U. S. Government Printing Office.
Evans, Robley. 1969. "Early History of Nuclear Medicine at Massachusetts General Hospital ," Medical Physics 2, 105-110.
Gray, Carl R. Jr. 1952. Letter of Carl R. Gray to Herbert Loper, December 2, 1952, ACHRE Document, Briefing Book, Tab I, listed as DNA1.941031.005.

Johnson, Leland and Daniel Schaffer. 1994. Oak Ridge National Laboratory: The First Fifty Years . Knoxville: University of Tennessee Press.

Hamilton, J. G. 1942. " The Use of Radioactive Tracers in Biology and Medicine." Radiology, 39, 541-572.
Hamilton, J. G. and M. H. Soley. 1939. "Studies in Iodine Metabolism by Use of New Radioactive Isotope of Iodine." American Journal of Physiology , 127 (No. 2), 557.
Hamilton, Joseph G. 1946. "Summary: Medical Research Program 1943-46," August 28, 1946. Memorandum, Stafford L. Warren Papers, UCLA Special Collections, 987, Box 112, Folder. "Medical Advisory Committee to AEC 1946-47."
Haywood, O.G. 1947. Letter to Dr. [Harold] Fidler. US Atomic Energy Commission, Oak Ridge , April 17, 1947. Memorandum. Declassification of Documents , Oak Ridge Operations Office, Record Holding Tank Group, Classified Documents 1944-1994, Box 209.
Hertz, S., A. Roberts, and R.D. Evans. 1938."Radioiodine as Indicator in Study of Thyroid Physiology." Proceedings of the Society of Experimental Biology and Medicine , 38, 510-513.

Kotz, Deborah. 1995. "The A-Bomb, 50 Years Later: The Evolution of Nuclear Medicine," Journal of Nuclear Medicine 36(no. 8), 17N-21N.

Lawrence, Ernest O. 1934. "Radioactive Sodium Produced by Deuteron Bombardment," Physical Review 46, 746-47.
Lawrence, John H. 1938. "The Effects of Neutrons on Tissues." Two page memo-circular, Lawrence Papers, Container 1. Bancroft Library.
Lawrence, John H. 1940. "Nuclear Physics and Therapy: Preliminary Report on a New Method for the Treatment of Leukemia and Polycythemia." Radiology, 35, 51-59.
Lawrence, John H., J.G. Scott and L.W. Tuttle. 1939. "Studies on Leukemia with the Aid of Radioactive Phosphorous," New International Clinics 2, 35-58.
Lawrence, John H., L.W. Tuttle, J.G. Scott and C. I. Connor. 1940. "Studies on Neoplasms with the Aid of Radioactive Phosphorus. I. The Total Phosphorus Metabolism of Normal and Leukemic Mice." Journal of Clinical Investigation 19(No.2), 267-271.
Lawrence, John H. 1947. Letter of John Lawrence to Provost Monroe E. Deutsch, April 23, 1947, Life Science Division, R&D Administrative Files, Carton 24/39.
Lilienthal, David E. 1948. Letter of David Lilienthal to Director, Oak Ridge Institute of Nuclear Studies, April 7, 1948, reproduced in Annual Report , Oak Ridge Institute of Nuclear Studies 1948, p. 2.
Linden, I.H. E. Laden, J.O. Erickson, and D. Armen. 1955. "Electron Microscopic Study of Normal Skin Collagen and Elastic Fibers," Journal of Investigative Dermatology, 24(February): pp. 83-88.
Livingood, J. J. and G. T. Seaborg. 1938. "Radioactive Iodine Isotopes." Physical Review , 53, 1015.
Lyon, George M. 1950. "Radioisotope Program of the US Veteran's Administration," Report to the NRC, December 15, 1950. Bulletin of the Committee on Veterans Medical Problems, 1951: Appendix II, pp. 409-413.
Lyon, George M. 1951. "Veterans Administration Radioisotope Conference," Science, 113(No. 2925): p. 71.
Lyon, George M. 1952. "Medical Research Programs of the Veterans Administration," Bulletin of the Committee on Veterans Medical Problems , National Research Council, December 8, 1952, Part II, VA Radioisotope Program Historical, pp. 553-560.

National Research Council. 1946b. Division of Medical Sciences, "Minutes of the Committee On Veterans' Medical Problems," 20 September 1946, in Bulletin of the Committee on Veterans Medical Problems 46, p. 11.
National Science Foundation. 1958. Government-University Relationships in Federally Sponsored Scientific Research and Development , NSF 58-10. Washington, D.C.: U.S. Government Printing Office.
Nichols, K. D. 1946. "Letter to Stafford L. Warren," [n.d.]. Warren Papers, UCLA Special Collections, 987, Box 112, Folder. "Medical Advisory Committee to AEC, 1946-47."

Oak Ridge Institute of Nuclear Studies 1947. "Program for Performance Under Letter Contract No. AT-40-1-GEN-33 and Subsequent Definitive Contract with the United States Atomic Energy Commission.". Manuscript Draft Government Contract.Oak Ridge National Laboratory, Public Reading Room, ORF, Folder 1198.
Oak Ridge National Laboratory. [n.d.] "Non-Technical Record of the History of the Medical Program of the Manhattan Project, 1945." ORF-00752.Oak Ridge National Laboratory, Public Reading Room. Typescript.
Oak Ridge National Laboratory. 1949. Isotopes:A Three-Year Summary of U.S. Distribution . Washington, D.C.: United States Atomic Energy Commission.

Seidlin, S. M., L.D. Marinelli, and E. Oshry. 1946. "Radioactive Iodine Therapy," Journal of the American Medical Association, 132, 838-347.

Tracerlab, Inc. 1947. "Proposal to Atomic Energy Commission Requesting Permission for Tracerlab to Synthesize and Stock Organic Compounds Containing Carbon 14". Memorandum. Oak Ridge National Laboratory, Public Reading Room, ORF00774, Folder 70.

United States. Advisory Committee on Human Radiation Experiments. 1995. Final Report of the Advisory Committee on Human Radiation Experiments. , October 15, 1995. Washington, D.C.: Supt. of Docs., U.S. G.P.O., U.S. Congress. 1946. Atomic Energy Act . Public Law 585. 79th Cong. Washington: U.S. Government Printing Office.

Veterans Administration Information Service. 1948. Press Release, September 15, 1948. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 300, Box 88, Fldr. Veterans Administration, 1948.

Warren, Sheilds. 1948. Letter of Sheilds Warren to Albert H. Holland, Jr., Medical Advisor Office of Oak Ridge Directed Operations. Declassification of Documents , March 2, 1948. Office Memorandum. Oak Ridge National Laboratory, DOE Human Radiation Experiments, ORF-00729, 28.
Warren, Stafford L. 1943. "Radiation as a Weapon." Memorandum and Accompanying Document. July 27, 1943. "Conclusion 16." Warren Papers, UCLA Special Collections 987, Box 58, Folder 14.
Warren, Stafford L. 1946. "Proposed Medical Research Program, 1946-47, 1946." Memorandum, March 5, 1946, Warren Papers, UCLA Special Collections, 987, Box 112, Folder "Medical Advisory Committee to AEC 1946-47."
Warren, Stafford L. 1947a. "Agenda for Medical Advisory Meeting 23-24 January 1947," Memorandum. Warren Papers, UCLA Special Collections, 987, Box 112, Folder. "Medical Advisory Committee to AEC 1946-47." See Item VI.
Warren, Stafford Leake. 1947b. "Possible Expedited Program on Cancer Research," Memorandum, August 27, 1947, Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 600, Box 78, Fldr. "Cancer Research-General-1946-1948."
Warren, Stafford. L. 1948. "The Influence of Modern Developments in Nuclear Energy on Public Health Problems." Centennial: Collected Papers Presented at the Centennial Celebration [American Association for the Advancement of Science] , September 13-17,1948 . Pp. 143-149. Washington: The American Association for the Advancement of Science.
Warren, Stafford L. 1948a. "Address to American Pharmaceutical Association, 1948." Lecture Manuscript, August 12 1948, Warren Papers, UCLA Special Collections, 987, Box 57, Folder 10.
Warren, Stafford Leake. 1948b. to Dr. Ben Cassen and Dr. Fred Bryan, December 31, 1948, Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 400, Box 25, Fldr "Atomic Energy Medical 1948."
Warren, Stafford Leake. 1949. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 600, Box 30, Fldr. "Atomic Energy Commission Project 1947-49."
Warren, Stafford Leake. 1950. Letter of S.L. Warren to F.A. Bryan, B.M. Brundage, R. J. Buettner and C.H. McBain, August 11, 1950. Administrative Papers of Stafford L. Warren, UCLA University Archives, Collection 300, Subseries 600, Box 30, Folder. "AEC Project UCLA 1950 General."
Warren, Stafford Leake. 1983. An Exceptional Man for Exceptional Challenges . 3-Volume University of California Oral History with Tusler. Los Angeles: University of California, 1983, p. 1074.
Weisgall, Jonathan M. 1994. Operation Crossroads : The Atomic Tests at Bikini Atoll , Annapolis, Md. : Naval Institute Press.
Westwick, Peter J. 1996. "Abraded from Several Corners: Medical Physics and Biophysics at Berkeley," Historical Studies in the Physical and Biological Sciences , 27:1-31.
Williams, Walter J. 1947. to Carroll L. Wilson , September 3,1947. Memorandum with multiple appendices. Proposal for Distribution of C 14-Labeled Compounds Synthesized under Berkeley Area Program , Oak Ridge National Laboratories, Public Reading Room, ORF00774, Folder 70.
Wilson, Carroll L. 1947a. Letter of Carroll Wilson to Stafford L. Warren, 30 April, 1947. Letter, two pages. Oak Ridge National Laboratory, Files in Public Reading Room, ORAU-3007.
Wilson, Carroll. 1947b. Letter of Carroll Wilson to Stanford L. Warren, February 6, 1947. Warren Papers, UCLA Special Collections, 987, Box 112, Fldr. "Medical Advisory Committee to AEC 1946-47."