RELATIVE TOXICITY OF PLUTONIUM majority of the patients were at Strong Memorial Hospital in Rochester, New York, where there was not only an active biomedical project under the Manhattan District, but an active and well-managed Metabolism Unit in the Department of Medicine. The four others were at California and Chicago with one individual at Oak Ridge. The experiment was done entirely to study metabolism, not effects, and involved primarily excretion. The results became available fairly soon in the classified literature and indicated sufficient agreement between the excretory patterns of man and the laboratory animals to reassure those concerned with standard setting that there was not a huge species difference. But the data obtained on tissue distribution were meager and the highly classified nature of the effort prevented any general dissemination of the information for a considerable period. As a sidelight on how some of these things had to be done, most of the plutonium analyses on the Rochester patients were done at Los Alamos and only the heroic trundling back and forth of the late Wright Langham between Los Alamos and Rochester, by train arriving at Rochester in the inevitable snowstorm, enabled completion of the project. The report (Langham et al., 1950) contains the names of those who assisted at Rochester, but it was a Los Alamos report and essentially no identification of the laboratories was discernable. Because of the sensitive nature of the subject, including the fact that some of the vatients defied their prognoses and have lived well into their eighties, that report remained classified at various levels down finally to "Official Use Only" until very recently. Fortunately, Pat Durbin has gone back over all of these data recently and reanalyzed them in the light of current knowledge. Thus, you can read a modern interpretation of the meaning of these pioneer efforts. Short reports of distribution and excretion studies in man at the California and Chicago laboratories appeared as "CH" reports (Crowley, et al., 1946, and Russell and Nickson, 1946). I do not know how long these data remained sequestered. The other primary source of early data on the metabolism of plutonium in man was the group of workers at Los Alamos. As you know, some of these have remained available for the long-term study--a facet beyond the scope of this presentation. But there were many more than these and all were subject to routine collection of excreta as a means of bioassay, (Remember that the crystal counters we now employ to detect the low energy photons from plutonium by external measurement had not yet been invented.) These studies of excretion in workers and correlation with animal studies led to the formulation of the so-called Langham (1957) equation for expressing excretion as a function of time. Used for many years before publication, it has served health physicists faithfully, if not always precisely, for many years. We now have modifications of the equations and methodology and computer programs to check the fit of the data. But I submit that the construction and use of the original concept and technique was remarkable when one considers how little plutonium is excreted except in feces soon after inhalation. The fact that the microdistribution of plutonium in bone was found early not to be similar at all to that of radium has already been emphasized. This led to some speculation that its toxicity--or more specifically, its effects in bone--might not be proportional to its energy and half-life relative to radium. But first it needed to be known if plutonium would be carcinogenic in the same sense as radium and to what degree. The answer came primarily, or at least first, from the Chicago group. Among the first of the postwar open literature publications which revealed what had been going on in "The Plutonium Project" was a special issue of Radiology (Anon., 1947) entitled "The Plutonium Project."' The title page and table of contents of this now classical document are reproduced here as Figures 1 and 2. Note first that much of the work concerns external radiation and aspects of the project other than plutonium itself. But note also the presence of a summary paper on the metabolism of the fission products and the heavy elements by Joseph G. Hamilton and, especially for our purpose here, the paper on carcinogenic properties of radioactive fission products and of plutonium by Hermann Lisco, Miriam P. Finkel, and Austin M. Brues. This paper established for the first time in the open literature the carcinogenic potency of plutonium. The paper by Bloom in the same issue summarized other effects and touched upon carcinogenicity (see Section E. also), but it was the Finkel, Brues, et al. team which followed through in determining the relative effectiveness of different nuclides in producing bone cancer, as will be described presently. Although the work at Rochester was under way at about the same time, it was not officially part of "The Plutonium Project" and reached the open literature somewhat later. Besides the metabolic studies in animals and in humans referenced earlier, the Rochester group carried out two laborious studies, one quite large, comparing the toxicity of polonium-210, plutonium-239, and radium-226 in rats. The doses were given intravenously, were relatively large, and the endpoint was lethality. Although published later, it is clear that these experiments established at the time of their performance the fact that plutontum-239 was more toxic even as measured by lethality in a relatively short time than radium-226 (Fink, 1950). Because of the isolation of the various projects for security purposes, it is hard to say that these experiments confirmed the surmises of others based upon the autoradiographic evidence that since plutonium deposited and remained nearer to living cells in bone, it might be more toxic than per unit of dose than its prototype radium-226, But from the vantage point of our present knowledge, the facts are quite consistent with such a view. Full confirmation of the difference in carcinogenicity in bone between plutonium and radium came in 1953 in a now classic paper by Miriam P. Finkel (1953). She compared the average probability of the CFl female mouse dying with a malignant bone tumor as a function of isotope dose. And she studied not only