A True Measure of Exposure 234 Los Alamos Science Number 23 1995 A True Measure of Exposure A TRUE MEASURE OF EXPOSURE the human tissue analysis program at Los Alamos by James F. McInroy he human tissue analysis pro- postmortem analysis of tissues from oc- physics measures that are meant to gram, a 35-year-long research cupationally exposed individuals. Be- keep plutonium contamination to a Tprogram at Los Alamos, has cause the risk of cancer is highly de- minimum. been scrutinized by the local and na- pendent on not only the amount of tional news media and, more recently, plutonium retained in the body, but also The author (now retired from the Labo- by the President's Advisory Committee the fraction that goes to specific organs, ratory) hopes that the tissue results pre- on Human Radiation Experiments. Al- our discoveries on plutonium distribu- sented here, some of which are relative- though this program does not technical- tion have helped to clear away uncer- ly recent, will inspire rejuvenation of an ly fall under the description of "human tainties about the human metabolism effort that can continue to help elimi- experimentation," as defined by Secre- and potential health effects of this ra- nate the remaining uncertainties charac- tary of Energy Hazel O'Leary, charges dioactive substance. terizing plutonium dosimetry. by the news media of DOE's "body snatching," unethical procurement of The plutonium excretion models, which human tissues and organs, and hiding were the main product of the plutonium or withholding resulting data from the injection studies, provided an indirect Early Studies of Plutonium next-of-kin and their lawyers mandated means for estimating the amount of Metabolism that this program be included in the plutonium retained in the body of a liv- Advisory Committee's investigation ing person from the amount excreted in Bill Moss's article, "The Human Pluto- and that all documents and other infor- the urine. Those models were crucial nium Injection Experiments," reviews mation about the program be made because they were the most commonly the fact that, in 1944, when plutonium available. used means for estimating the body began to be produced in large quanti- burden and the ultimate risk from acci- ties, nothing was known about human As the leader of the Los Alamos tissue dental plutonium exposures, but they metabolism, retention, distribution, and project for 21 years, I will take this op- gave no information about the distribu- excretion of this manmade element. portunity to review the motivations, the tion of plutonium in the body, nor were The leading scientists and medical doc- manner of obtaining tissue samples, and there any independent means to check tors in the Manhattan Project, however, the most important findings of what the on their accuracy. The painstaking col- were well aware that working with plu- general public, including my wife, sees lection and analysis of tissues from de- tonium might pose a serious health haz- as a very ghoulish activity. Work on ceased individuals over the last 35 ard. They had done research on using cadavers has been at the heart of med- years has provided at least some of the radionuclides for medical diagnostics in ical discovery and medical education missing information, and that informa- the 1930s, and they knew that long- for hundreds if not thousands of years. tion now serves as a cornerstone of the lived radionuclides such as radium are This work is no exception—our pro- present models for determining the dangerous if they are retained inside the gram enabled us to quantify the pluto- doses and the risks from plutonium ex- body because they become a constant nium distribution in the body through posure. The early biokinetic models internal source of radiation. Biomed- used to estimate body burdens were ically, plutonium was assumed to be The image at left is an autoradiograph of based primarily on indirect measure- much like radium. Internal deposits of a tracheobronchial lymph node from a ments such as urinalysis, fecal analysis, radium had produced fatal anemias and former worker at the Laboratory. It external lung counting, and/or whole bone cancers in the radium dial painters shows alpha tracks radiating in a typical body counting. In contrast, the tissue of the 1920s, and there was great con- star pattern from tiny alpha-active data are direct and definitive. The tis- cern that internal exposure to plutonium clumps of matierial. Chemical analyses sue program has also provided an accu- and its compounds might be at least as of the radioisotopes in this individual’s rate measure of the general level of plu- dangerous. lungs and lymph nodes indicated that tonium exposure of Laboratory those clumps most likely consisted of an employees and thus a check on the effi- By January 29, 1944, 11 milligrams of aggregate of plutonium particles. cacy of industrial hygiene and health plutonium (a fair share of the world's Number 23 1995 Los Alamos Science 235 A True Measure of Exposure total supply at that time) had been allo- Lawrence of Los Alamos had modified baugh, who was also a research scien- cated for animal metabolic studies. The the Langham model to take into account tist at the Laboratory, decided to send results indicated that the skeleton was long-time excretion data from a selected several of the organs and bones to the the major deposition site, the retention group of Los Alamos workers who had Laboratory for radiochemical analysis time was long, and the liver had the experienced accidental intakes during to determine the plutonium content. highest concentration among the soft the Manhattan Project and who had tissues, followed by the kidneys and the been followed as part of an epidemio- Kelley had worked with plutonium for spleen. How appropriate were those logical study (some of those men tell a number of years prior to his death animal data for quantifying the distribu- their stories in the roundtable "On the and was carrying in his body a measur- tion and retention of plutonium in hu- Front Lines"). But many uncertainties able plutonium "burden," which pre- mans—and thus for determining the remained. Most worker exposures were sumably had been obtained mostly doses and the risks of plutonium the result of inhaling tiny airborne parti- through inhalation of moderate routine exposure? cles of plutonium into the lung. How airborne contamination. The estimated did that mode of exposure compare to whole-body content, based on urine ex- The human injection experiments were, the injection of plutonium directly into cretion data and the application of Jim in part, an effort to answer that ques- the bloodstream? It was suspected that Lawrence's PUQFUA (Plutonium Body tion. Excretion data were collected the patterns of retention, distribution, Burden (Q) From Urine Assays) code, from all subjects following injection of and excretion, and thus the dose to the was 18 nanocuries, a little less than half plutonium into the bloodstream, and body, would change depending on the maximum permissible body burden small tissue specimens from those sub- whether the intake was by inhalation, of 40 nanocuries. The tissue samples jects who were terminally ill were ana- ingestion, or a cut or puncture wound, represented the first opportunity to de- lyzed for plutonium following their but no human data were available to termine directly the plutonium burden death. A number of important observa- check the conjectures. It was also ex- carried in an individual who had been tions followed: 1) there were no major pected that the dose and the ultimate analyzed for plutonium content prior to differences between humans and the risk of exposure would be affected by death and thus to check the predictive common laboratory animals in the dis- the particular chemical form and particle power of the urine excretion models tribution in tissues with the exception of size of the material taken in, the time against real data. It was also an oppor- liver; 2) the liver of humans contained since exposure, the duration of expo- tunity to measure the real efficacy of 20 to 40 per cent of the total amount re- sure, and the effects of individual bio- the industrial hygiene and health tained versus 10 per cent or less for rats logical variation. physics measures that had been taken to when both received the same plutoni- reduce airborne plutonium contamina- um-citrate complex; 3) the retention tion in the work environment. Those half-time in liver was greater in hu- The Beginnings and the Philosophy responsible for industrial hygiene at mans; 4) the retention half-time for of the Los Alamos Tissue Program Los Alamos, including Wright Lang- whole body in humans was much longer ham, Donald Petersen, and Dr. Lush- than in laboratory animals; and 5) the Our human tissue analysis began spon- baugh, felt it was incumbent on them to excretion pattern in humans was differ- taneously following the accidental death take advantage of the availability of ent, especially that a much lower frac- of Cecil Kelley, a plutonium worker that information, even though it result- tion was eliminated in human feces here in Los Alamos. Kelley was expo- ed from the untimely and tragic death compared to animal feces. sure to a lethal dose of gamma and of a colleague. neutron radiation on December 30, Wright Langham, a radiobiologist in the 1958 and died 35 hours later. The radi- The Kelley data offered some surprises. Health Group at Los Alamos who had ation source was a plutonium collection Although the whole-body content was planned the analytical protocols for the vessel at DP Site that suddenly and un- found to be 19 nanocuries, in close human injection experiments, used the expectedly went critical during the agreement with the excretion model, excretion data to create a model relating year-end inventory (see "The Cecil Kel- that result was considered by Wright the amount of plutonium injected into ley Criticality Accident: The Origin of Langham to be "undoubtedly fortu- the bloodstream to the amount excreted the Los Alamos Human Tissue Analy- itous" because the fraction in the lung in the urine.