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N14®22900S7 ! v /A Z7,7- i ~ FROM ATOM TO EVE J ) by LEON O. JACOBSON Reprioted From: Perspectlvo In Biobgy aod Mcdkine Vdnme 2A Namber 2 Wioter 1981

NK12290038 FROM ATOM TO EYE* LEON 0 fACOBSONt In the Beginning In January of 10421 was an assistant in the Department of Medicine at the University of Chicago. One afternoon I was helping an intern catheterize a patient with a "watering pot perineum." This descriptive phrase applies to an individual who has active tuberculosis of the bladder with multiple fistulae that lead from the bladder through to the skin in the perineum and lower buttocks. No antibiotics were available for the treatment of tuberculosis, and since such patients were highly infectious, the nurse, the intern, and I were all properly gowned, masked, and rubber-gloved to protect otdrselves as well as the patient. During this medical protedure. I heard my name being called re- peatedly over the t.elepage, indicating an emergency. Since we had now completed our catheterization. I hurriedly removed my gown, scrubbed my hands, and went to the nursing station. The message from telepage' had been taken-it was simply, "Repon to the dean immediately." As a medical student and later as a house officer, I had never had any contact with the dean g office, but I knew that William Taliaferro was the dean, for his face graced the center of every medical class picture on the walls of Billings Hospital corridors. At that moment in my mind's eye I saw him with a stern and sinister look. , As I hurried to the dean's office, I wondered if I had done something wr7ng. Was I behind in summarizing the patients' charts at discharge or death? Was there a complaint from a patient or patients I might some- how have failed to please? Was my chief of medicine dissatisfied with my performance? There were other thoughts darting in and out of my mind since. For the life of me, I could not imagine why Dean Taliaferro would want to see me. I arrived at the dean's office and told the secretary who I was. She knocked on the dean's rbsed door and ushered me in. There sat Itean *Read in part to a private interdisciplinary social club (Stochastics) at the University of Chicago. February 1979., tEmeritus profesmr, Ilepartment of Medikine, Joseph Regenstein pmfessor, Biological and Medical Sciences. University of Chicago. ® 1981 by The Univetsity of Chicago. OOs 1-598281/2402-04Y9S01.00 Pmpertivrs in Biology snd Medkine ' Wint.r 1981 I 195 i

NK12290039 Taliaferro, Dr. George Dick (Chairman of Medicine), Dr. Arthur Bachmeyer (Director of Hospitals and Clinics), Dr. Paul Hodges (Chief of Radi'olugy). and two men I had never laid eyes on before. By now my respiratory rate had doubled, my heart was racing at least 125 beats per rninute: and my mind was muddled up with vague fears and conjectures. "Hcllo, Leon. You know Dr. Dick, Dr. Bachmeyer, and Dr. Hodges, of course; meet Professor Wollah and Professor Hilberry. Please have a chair. Leon," he said after we were all seated, "Mr. Hilberry and Mr. Wollan are from the Physics Department. Dean Arthur Compton has talked with Dr. Dick, Dr. Robertson, Dr. Hodges. Dr. Bachmeyer; and me, and we have decided that ~ou are the one they need to help them with a special problem they are having in their research." How could I help C:ompton and his physics group? I thought. Taliaferro continued. "They are doing research with penetrating radiations produced by the cyclotron, as well as with radioactive substances. They need someone who is aphysician aud who knows the blood•forming tissue as you do. to keep careful tabs on those who are or may be exposed to these hazards." George Dick and O. H. Robertson were aware of my research on estrogen effects on the bone anarnow, the clinical use of radiophos- phorus' for treatment of the leukcmias, research on pernicioas anemia, and the like. Perhaps, I thought, they can't find anyone else, so they have decided I'm it--sounds like routine stuff to me. George Dick looked at me through his penetrating eyes and said, "Your suiroeillance of these scientists will be an exciting adventure in prevenu4e medicine and closely related to your snecial interests in blood and blood-form:ng tissue. Professors Wollan and Hilberry will give you the background. but I assure you that the work they are doing is essential to the war effort and yourgartieipation in their program is essential to its progreas." What could I say?. I'm sure I had been signed, sealed, and delivered before I even got to the dean's ofl'ice. So I came up with -the dich "e-- "Thank you, I71 be glad to hear more details and will try to do my best." The cotiversation' continued, with Wollan and Hilberry saying a few words about the human hazards involved in their work. Bachmeyer stating that a laboratory and clinic space would be made available, and Taliaferro mentioning the relationship of radiation injury to immune suppression=and everyone stood up. I mumbled something like, "Thanks, it all sounds interesting." Wollan and Hilberry and I left the dean's office together and walked up to the third floor of $illings, where I shared an office with four cages of mice on which I was conducting an 'I did this r!esearch in collaboration with Louis Slopn, who provided the radiophos• phwus'sp produced m the cyclotron. Dr. Slotin. who lefl the htetallurgical laboratory to join the t.os Alamos staff, was the second individual to succumb to a nuclear accident: this accident occurired 'ni late 1945 atter the Nagasaki and Hiroshima detonations. 196 1 Lron t). faroDn.on Frrom .imom to E:w

HK12290040 experiment. There the briefing began, but it lasted only 15 minutes. I had many questions, and they gave evasive answers to some of them. Finally, they said ihey had to leave because of experiments in p'rogrrss, but I'm quite sure that it was the essence of mice in the room that shortened the briefirdg time. S'oon thereafter, I met them for further information in Eckhart Hall in Wollan's office. The office had a musty smell and I added another ingredient, the smell of mice. I had taken physics, and advanced math in college. The former I shall never forget; I missed the first semester of the physics sequence because of a ruptured appendbx. I enrolled with the engineering students for the second sequence in physics, green as green. As far as I can remember, it is the only course that ever drove rne up a wall. I just didn't get the pitch. After the final ex~m, my professor called me in. He wore a long face, and the mofirtent I saw him, my physiognomy resembled his. He told me I had done poorly on the exam. But as we talked, his face softened. In fact, the more we talked, the more enthusiastic and frien*lly he became. I soon found out why-=-he would give me a passing grade in physics if I agreed to become a niedical missionary. I never went to Africa, as I'm sure he had in mii{d, but I've kept the promise and preached medicine and meflical sciench every day of my life since that interview. By the way. I had no probiem with the next semester course in physics. While I.+as in med~al school, Dr. Paul Hodges selected me to do the radiography for variotts scientists who were using experimental animals to study diseases like pneumonia and tuberculosis. I developed the films and reported the results as well. In the same room under the supervision of Dr. Jane Hamilkon from the Department of Physics was an X-ray therapy machine for dudies on the biological effects of radiation; with Dr. Hamilton's tutoring, much additional reading, and patient iristruc- tion fr9m Do•. Hodges, I learned a great deal about penetrating radia-/ tions. Perhaos it was this background that had led Hodges, Dick, and Rrbertson to suggest that I handle the health hazard problems in the Office of Scientific Research and Development Project in the physics department. Conferences with Wollan and Hilberry and others continued. Fanally, since it was not clear to me just what their research project was all about and I felt I needed to know more if I were to be effective. I asked for more specific information. Hilberry administered the oath of seerecy, and after I had taken ia, he said, "Suppose you read this paragraph in this physics text:": He handed me the book, arid there, in esseti.ce, it stated: "If some morning you should awaken and find half the world blown away, you will know that a nuclear fission chain reaction has been accomplished " Realizing the possibility that a devastating instrument of war-an atomic bomb--was the objective of this project was an over- PersJrwrn-es rn Beolagi and .Nrdutn. • WinUr 1981 I 197 I

Hlc12290041 whelming experience. 1 know I blanched; I know I had a bump in my throat, and for a frtoment at least I was speechless and at the point of tears. To find mysi'lf involved in the effort to split the atom in an atomic pile, and in the awesome codsequences were it to succeed, hit me with my hands down. I realized that by now I was inextricably involved, and I already felt 5 years older. The secret remained with me until one day in August 1945, when, early in the morning, I called my wife and said, "You've been wondering what I've been up to these several years. Turn on the radio-get a newspaper." That was the day of Hiroshima with its dreadful consequences-dedth and morbidity, sickness, destruction, and a lasting question of morality. Health C,onsideratiores for th,e ScientiJu Personnel More briefing .4as forthcoming from Hilberry, Wollan, Edward Creutz, and others, and at each briefing the magnitude and the serious- ness of the health hazards to all scientific personnel from penetrating radiations and from the many radioactive atoms produced in fission became more obvious and more alarming. I It was clear that 2s a physician I first had the duty of arranging space to examine all employees of the Met Lab. No one escaped a thorough physical examination, a urine test, and complete blood counts. I recall personally examining many of the great experimental and theoretical physicists and chemists, including Fermi, Teller, Franck, Hogness, Zachariasen, Szilard, Zinn, and Seaborg. 1 found out which of them had a wooden leg by simple inspection, not by failing to feel an anterior or posterior tibial pulse. I found that there was only one woman physicist among all these intellectual giants. She was Leona Woods, a young, brilliant. and beautiful person who has recently written an account of her experience on ihe Manhattan Engineer Project. [See book review in this issue. Eotrott.) Local professional help was mobilized for exami- nations because scientists, technicians, guards, and secretaries came to Chicago by the hundreds. We had to set up individual schedules for inieial and repeat exams for each individual, depending on his or her work area, and on the potential exposure to penetrating radiations, radioisotopes, and toxic chemicals each might receive. To facilitate all this, we had a.special area set aside for physical exams, with specific appointment times that we adhered to rigidly. Could you imagine ha:ing Enrico Fetmi, and especially Ixo Szilard [1), wait for an hour in the clinic? The same procedure was used for the laboratory exams. Mrs. Edna K. Afarks, a nurse and superb lab technician whom I hireda was in charge, and we gathered many more experienced technicians. ' Why did we doo so many repeat histories, physical exams, and lab 198 1' Lron O. farnAcon • From Atom to Eve

w KM2290042 exams? Simply because, at that time, there was no way of mass- monitoring radiation exposure, except by observing changes in the skin and in the blood count. A fall in the white counts, and especially a reduction in lymphocytes, was the most sensitive and reliable biologic evidence of exposure. However, this problem was tackled promptly by a group of the old cosmic-ray physicists, including Drs. Volney Wilson, Wollan, Jesse, and Shonka, all of whom were experts at radiation detection work. With the machine shop's production efforts, badges with sensitive photographic film, pocket electrometer dosimeters, and a variety of radiation detection meters became available. With the availabifity of monitoring equipment it became possible to recruit radiological physicists, such as Rose, Mor- gan, and Parker. under whose leadership an effective health physics monitoring system was established. Feasibility Studies At this point you tqight well ask, "Why did the decision to involve medicine and. biology not come long before 1942? Why weren't in- formed physicians and biologists consulted during the period when feasibility studies and the many committee meetings of physicists, chemists, and engineers were going on?" Perhaps I can best answer this question by stating that it took in- numerable experiments to determine whether a sustained controlled atomic reaction could, in fact, be achieved. Could natbral uranium be produced in a pure form and in a sufficient quantity so that a pile could be built? What material would be used to slow down the fast neutrons and to enhance their capture by uranium-235? As we now know, graphite was found to have acceptable characteristics for this purpose. By the end of 1941, small amounts of money (in the tens of thousands of dollars) had been authorized and used for various studies related to the ultimate goal of an atomic bomb. It was not until December of 1941 and January and February of' 1942 that decisions emerged, one after another, involving the president of the United States and his advisors. These advisors included many individuals, some of whom were on the University of Chicago faculty: Fermi, Compton, Szilard, Allison, Bush, Conant, Sachs, Einstein, and many others. The decision was made to proceed with all haste, with not just one approach but several, to the production and separation of' fissionable material [2J. There was the uraniurn-235 gaseous diffusion separation work being done at the Uni- versity of Californi.a~ Berkeley. And there was the plutonium production work at the Univetsity of Chicago. The isotope separation projects ended up with production plants at Oak Ridge. The plutonium work moved from the natural uranium graphite pile under the stands at Stagg Persqrciaes in Biotogy and Medinru • Wintrr 1981 1 199

HKS2290043 Football Field to a pilot plant operation at Oak Ridge and the final productain facilities at Hanford. Washington. The decision to proceed with an all-out approach was related to the fact that there was reason to believe that Germany was involved in a similar program and might be well ahead of us. During the last half of 1941, these working on the project became reasonably confident. but still were not sure, that a chain-reacting pile could be achieved. The same was true with the other projects involving different approaches that were being tried elsewhere. Experiments done in the late fall of 1941 and early January of 1942 made success appear much tneire likely, and the decision was made in Washington to locate the first experimental pile in Chicago under the direction of Arthur Compton [2]. By early February 1942. Fermi, Szilard, Wigner, ~llison, Wheeler, Breit, Mialliken, Manley, and their co-workers were either in Chicago or on the way. Shortly, this core of physicists was joined by a similar cadre of cheniists-McCoy, Spedding. Franck, Seaborg, Johnson, Boyd, Coryell, and Burton and co-workers--and by thf key engineers, Tom Moore and Miles Leverett. The Metallurgical laborAtory was rapidly assuming at least a semblante of effective organization under such leadership, and its professional and operational staffs wcre growing almost explosively in the early months of 1942. The Metallurg'ual Z.aboradory When I asked Norman Hilberry how and why the Chicago operation got its name, he responded: The decision to name the project the Metallurgical Project and the laboratory operation at the University of Chicago the Metallurgical Laboratory was made as a sec urity measure to cloak its real nature. There !tad been casual talk for years that, since metropolitan Chicago was a center for the metallurgical industry, the University should recognize some sort ofohligation to it establishing a Metals Institute. Here was the chance to fulfill that obligation an effectively hide what was actually going on. No one would have bVlieved in January 1942 that this obvious project in physics and chemistry would, within six months, be hiring metallurgists like mad in order to solve the really crucial problems being faoed in the design of production piles. MEDICAL ASPECTS While my initial assignment to the project came as a result of COmp- ton's long research experience in the field of X-rays and consequent realization of the health hazards involved, the true immensity of the problems was not recognized at the stan. I was the lone physiciam scientist on the project staff in February 1942, and II believe I was the 200 1 l.nm O. Jamb.+on ' From A+om to E-

HN92290044 first to be officially a part of any of the related nuclear weapons projects [3J. (The only possible exception was Joe Hamilton in Berkeley, and I don't think he was in then.) In April of 1942, this situation changed suddenly and dramatically. Norman Hilberry told me that, at that time, pile design had pro- gressL-d to a point where the shielding design group became deeply con- cerned with, the magnitude of the radiatiotrt control problems posed by the core of an operating nuclear chain reaction pile. Not only was the radiation generated enormously greater than anything ever experienced before; bnt hundreds of new radioactive isotopes would be formed which would have to be dealt with in the chemical processes required to recover plutonium from the irradiated uranium. In priorexperience, a 10-gram radium source was about the most intense radiation emitter for which there were valid biological and medical data. The intensities being computed for the, core of an operating production reactor were the equivalent of thousands of tons of radium, some hundred million times greater. Hilberry said that Creuu came into his ofTice one morning in a highly agitated state. He first broke the news about the magnitude of the radia- tion health problem and then pointed out the imperative need, not only to monitor present staff and future operations personnel, but also to gain a far more profound knowledge and understanding of the interac- aon of radiation with living systems and of• the behavior of radioactive isotopes introduced into Gving systems than existed at the time. Hilberry passed the word on.to Contpton. Both had realized that there would be radiation problems, but both were startled at their magnitude. Compton immediately assigned Hilberry the task of getting an active biomedical program under way. It was clear that such a program would have to go far beyond supervi- sion of health surveillance. It would have to undertake the study of the biological effects of fission products-fast and slow neutrons, gamma rays, X-rays, beta •rays--and the even larger problem of many fission product radioisotopes that are the by-products of the fission chain reac- tion which produces plutonium, the element that the whole Metallurgi- cal Project was about. (It had been estimated even in 1941 that, if but a very few kilograms of plutonium were produced and purified and if fission by fast neutrons could be induced, an explosion with a destructive power equivalent to that of some tens of thousands of tons of TNT was possible.) INCREASING THE STAFF As the outlines of the necessary biomedical program became dear. Compton approached the selection of personnel in a rather unusual PPrVlAVPS tn BIDIOgy QMlI AJP1tf7RP ' WMtPI 1981 1 201

NK®2290045 > I i i . way. He already had me in place, and my show was in operation. It was rumored that Cotnpton had invited, or, shall we say, !rers'uaded, two individuals to join the Met Lab in 1942, each of whom thought he was to be head of the health and biology program. He more or less simulta- neously invited both Dr. Kenneth Cole and Dr. Robert Stone. Hilberry recalls, Creutz and others, as you might well guess, were demanding that a biophysicist head the project to ensure adequate appreciation of the radiation effects. Ken• neth Cole's name came up. He was one class behind me at Oberlin, where his father was dean of men. I knew him tiery well. Compton ok'd the choice: I got Cole on the phone and he came out. He and Compton had a long session, and Compton hired him. Cole had properly stressed that he could not be responsible for the medical aspects. Gompton got to thinking about this and realized that medical credibility was not only going to be essential for the health surveillance activities but would also have to be part and parcel of the whole radiobiological prograni. So he called Stone. Stone came and Compton persuaded him to join up. After Stone left, Compton opened the door from his office to mirle and said. "Norman. I seem to have hired two men for the same job. Will you please straighten it out?" In wartime it worked. Stone, Head of Radiology at the University of California, San Fran- cisco, had collaborated with F.. O. Lawrence in using fast neutrons gen- erated in the Berkeley cyclotroc tp treat a variety of diseases such as cancer and severe arthritis of the spine., Blood counts and other tests had been done on these patients. Later in 1943 and 1944, as these exposures continued, Stone asked me to review the case histories and to see some of the patients, but primarily to examine carefully the effects of the fast- neutron therapy on the blood and blood-forming tissue of the necipients. The damage to some of these patients was severe, and the trial with fast neutrons was discontinued. Only in the past few years has interest in the use of fast neutrons been revived, and several medical centems in this country, including the University of Chicago, are again conducting trials with fast-neutron therapy. Cole, a physicist, had spent years working on nerve conduction and other problems in biology that required a physicist-biologist type. At Columbia, he had collaborated with Ross Golden on calibration of X-ray therapy nta,hittes and related equipment. Here, briefly. is part of Cole s account of his Chicago experience (taken from (4) and a personal communication). I got a call to come to C'.hicago for consultation. Compton and Hilberrjr told me the story of nuclear fission and demanded that I take charge of the biomedical problems. I knew at least how to start after convincing them I could arld would not take the medical responsibility. It was an exciting 4 years; we grew exponen- tially to a biology~ staff of nearly 400 before splitting in part to Site X. Oak Ridg,e. It took 6 months to get our lab in operation in a lysoli7led stable of an extinct tce 202 1 Lro>r 0. fQroGion • from Atom to F.re

HK®229004b f I plant south of the Midway, called site B, and it was expanded twice. We had cyclotron-produced radioisotopes and the availability of 250 kV X-ray machines for radiobiologic studies; but that was it until I got one of the first practical hunks of uranium•2J8 from Spedding just before the Stagg Field pile went critical. Then the Corps of Engineers took over and the battle for survival of a truly biological pn,gram began with General Groves on the one hand and tuPont on the other. I'U never forget the time when fission products became available and George Svikla and I decided to try a radioautograph for fission product dose. An exposed guinea pig was frozen, sawed into thick sections, and reassembled with X-ray him between sections. Svikla watched'as the machinist cut the guinea pig in slices using leaded gloves, etc., and then carefully replaced the band-saw blade. I stole H. J. Curtis from a Hopkins Aviation project, and he later became my counterpifn at Site X, Qitk Ridge. Everything was all tightly programmed, but after Hiroshima and tiagasaki, the Chicago radiobiology program all blew up as the Argonne, National Laboratory came intu being. Everyone had his pet hate that he kept to himself until the war was won. War is so disgusting, so futile. Simeon Cantril, a radiotherapist, was brought here by Stone from Swedish Hospital in Seattle. He recruited Dr. Nickson and Dr. Margaret Nickson to collaborate with him, not only on health effects monitoring, but also on programs he initiated at Sloan-Kettering in New York, at Michael Reese Hospital, and at the University of Chicago on the effects on man of various doses of whole-body X-irradiation. At that time, X-ray therapy was used almost exclusively for treatment of localized areas of the body. Dr. Albert Tannenbaum was asked to and did initiate a com- prehensive program on uranium toxicity in rodents at Michael Reese Hospital. I have made reference to the rumor that Stone and Cole each came to Chicago thinking he would be the director of biology and medicine; but it all turned out well without any obvious friction. Cole became head of all biological investigations: Cantril, after working for a time in Chicago, went to become Head of Industrial Miedicine at the Oak Ridge Labora- tory, and I became Associate Director of Biology and Medicihte under Stone, He and I shared a small suite of offices in Eckhart Hadl, where Compton's office was located. Also invited to join the Met Lab was Ray Zirkle, a radiobiologist from Indiana University in'Bloomington, who brought with him several of his colleagues and graduate students, including Eric Simmons and Charles Hagen, Drs. Zirkle and Simmons. Edna Marks, and I teamed up on many studies, but our principal collaborative study was a project on the comparative biologic, effects of these penetrating radiations. Zirkle and I had rabbits and mice in the uranium pile room before. ,;uring, bnd after the atomic reactor in Stagg Field went ctitical. These animals were mon- itored at ftrquent intervals for blood count changes, just in case physical monitoring failed. Both Zirkle and I have often told this story, partly to indicate that there was biological monitoring, but always adding the Prrsprrtim in Biotogy and Medirme • Winter 1981 1 203