Chapter 5: IntroductionIn August 1944, at the secret Los Alamos Laboratory in New Mexico, a twenty-three-year-old chemist was trying to learn what he could about the properties of a radioactive metal. One year later, the new "product"--one of several code words for this three-year-old element with a classified name--would power the bomb dropped on Nagasaki. That day the young scientist, Don Mastick, was working with the entire Los Alamos supply of the material, 10 milligrams. It was sealed in a glass vial several inches long and about a quarter inch in diameter. Unknown to Mastick, a chemical reaction was causing pressure to build up inside the vial. Suddenly it burst, firing an acidic solution against the wall from where it splattered into Mastick's face, some of it entering his mouth.
Realizing the importance to the war effort of the plutonium he had just ingested, Mastick hurried directly to the office of Louis Hempelmann, the health director at Los Alamos. Hempelmann pumped Mastick's stomach and instructed the young scientist to retrieve the plutonium from the expelled contents. Hempelmann expressed a concern related to worker safety: there was no way available to determine how much plutonium remained in Mastick's body. He immediately pressed the lab's director, J. Robert Oppenheimer, for authorization to conduct studies to develop ways of detecting plutonium in the lungs, and in urine and feces, and of estimating the level of plutonium in the body from the amount found in excreta.
Looming over Mastick's accident was the well-known tragedy of the radium dial workers more than a decade earlier. Like Mastick, they had ingested radioactive material through their mouths, as they licked the brushes they used to apply radium paint to watch dials. As time passed, many suffered from a gruesome bone disease localized in the jaw, and some bone cancers developed. Could plutonium cause a similar tragedy? If so, how much plutonium needed to be ingested before harmful effects might arise? How could one tell how much plutonium a person had already ingested? The answers to these questions were crucial, not only in the case of accidents such as Mastick's, but also, in the long run, to establish occupational health standards for the hundreds of workers who would soon be mass-producing plutonium for atomic bombs. Several pounds of radium, handled without recognition of the dangers, had led to dozens of deaths; what might plutonium cause?
A starting point was to examine the available data on radium poisoning, compare the characteristics of the radiation emitted by radium and plutonium, and try to extrapolate from radium to plutonium. However, plutonium had already revealed unexpected physical properties, which were posing problems for the bomb designers. Could plutonium also have unexpected biochemical properties? Extrapolation from radium was a good starting point, but could never be as reliable as data on plutonium itself.
Oppenheimer agreed that this research was critical. In an August 16, 1944, memorandum to Hempelmann, Oppenheimer authorized separate programs to develop methods to detect plutonium in the excreta and in the lung. With respect to biological studies, which Oppenheimer speculated might involve human experimentation, he wrote: "I feel that it is desirable if these can in any way be handled elsewhere not to undertake them here." The reason Oppenheimer did not want these experiments conducted at Los Alamos remains obscure. Nine days later, Hempelmann met with Colonel Stafford L. Warren, medical director of the Manhattan Project, and others. They agreed to conduct a research program using both animal and human subjects.
Mastick, who reported no ill effects from the accident when Advisory Committee staff interviewed him in 1995, was not the first alert to the potential hazards of plutonium. Human experiments to study the metabolism and retention of plutonium in the body had been contemplated from the earliest days of the Manhattan Project. On January 5, 1944, Glenn Seaborg, who in 1941 was the first to recognize that plutonium had been created in the cyclotron at the University of California at Berkeley, wrote to Dr. Robert Stone, health director of the Metallurgical Laboratory in Chicago (a Manhattan Project contractor) and a central figure in efforts to understand the health effects of plutonium:
It has occurred to me that the physiological hazards of working with plutonium and its compounds may be very great. Due to its alpha radiation and long life it may be that the permanent location in the body of even very small amounts, say one milligram or less, may be very harmful. The ingestion of such extraordinarily small amounts as some few tens of micrograms might be unpleasant, if it locates itself in a permanent position.
Seaborg urged that a safety program be set up. In addition, "I would like to suggest that a program to trace the course of plutonium in the body be initiated as soon as possible. In my opinion such a program should have the very highest priority." Stone reassured Seaborg that human tracer studies "have long since been planned. . . . although never mentioned in official descriptions of the program." The work began at Berkeley with studies on rats conducted by Dr. Joseph Hamilton.
Even as these studies on the biological effects of plutonium were beginning, the amount of plutonium being produced was dramatically increasing. Most of the effort at Oak Ridge was devoted to the separation of isotopes of uranium. However, the X-10 plant at Oak Ridge was a larger version of the very small plutonium-producing reactor developed at the University of Chicago. The X-10 plant began operating on November 4, 1943, and by the summer of 1944 was sending small amounts of plutonium to Los Alamos. By December 1944 large-scale production of plutonium began at the Hanford, Washington, reactor complex.
By late 1944, in the wake of the Mastick accident, the need to devise a means of estimating the amount of plutonium in the body became acute. It seemed that the only way to estimate how much plutonium remained in a worker's body would be to measure over time the amount excreted after a known dose and, from this, estimate the relationship between the amount excreted and the amount retained in the body.
Maximum Permissible Body Burden (MPBB) for PlutoniumThe plutonium injections were part of a larger research project intended to provide data for an occupational safety program riddled with uncertainty. Not only was there a need for ways to monitor the exposure of personnel--the driving force behind the plutonium injections--but the maximum permissible body burden (MPBB) for plutonium, the maximum amount of plutonium that would be permitted in the bodies of workers, was still under debate.
The concept of "maximum permissible body burden" had begun to develop before the war in light of the known hazards of radium. Just prior to the war, primarily at the request of the Navy, a committee of experts was formed to establish occupational health standards for the factories producing dials illuminated by radium paint. After examining the data on radium dial painters, this committee agreed that 0.1 microgram fixed in the body should be the "tolerance level" for radium: an amount that, in the words of the committee chairman, Robley Evans, would be "at such a level that we would feel comfortable if our own wife or daughter were the subject."[a] After the war the term maximum permissible body burden was adopted and defined more precisely as the amount of a radioisotope that, when continuously present inside the body, would produce a dose equivalent to the allowable occupational exposure (the maximum permissible dose). For radioisotopes that, like radium, primarily reside in bone, biological data and mathematical models were used to determine how much of another bone seeker would produce the same dose as the original 0.1-microgram radium standard.
Between 1943 and the spring of 1945, based on the body burden for radium and preliminary results of animal experiments, a tentative MPBB for plutonium of 5 micrograms was adopted by the Manhattan District.[b] This level was derived by direct comparison of the relative energies of plutonium and radium.
By the spring of 1945, differences between the deposition of radium and plutonium in the body were becoming clearer. Animal data indicated that plutonium deposited in what was called at the time the "organic matrix" of the bone--the part of the bone most associated with bone growth. This was different from radium, which seemed to deposit instead in the mineralized bone. Wright Langham wrote to Hymer Friedell supporting the choice of 1 microgram as an operating limit in lieu of a more formal policy. Langham wrote that with the adoption of this lower limit "the medico-legal aspect will have been taken care of and of still greater importance, we will have taken a relatively small chance of poisoning someone in case the material proves to be more toxic than one would normally expect."[c] This level was adopted and held until the Tripartite Permissible Dose Conference at Chalk River, Canada, in September 1949.
At this conference, representatives from the United States, United Kingdom, and Canada agreed on tolerance doses for many radioactive isotopes, including a maximum body burden of 0.1 microgram for plutonium. This reduced by a factor of 10 the value under which Los Alamos production had been operating. This reduction was based on the results of acute toxicological experiments with animals, which indicated that plutonium was as much as fifteen times more toxic than radium.
On January 20, 1950, Wright Langham wrote to Shields Warren, then the director of the AEC's Division of Biology and Medicine, alerting him to the problems caused by the Chalk River Conference's new "extremely conservative tolerances [which] may have a drastic effect on the efficiency and productivity of the Los Alamos Laboratory. Their official adoption will undoubtedly force major alteration in both present and future laboratory facilities and may add millions of dollars to the cost of construction of the permanent building program now in the planning phases."[d] Langham continued with reasons for regarding the Chalk River value of 0.1 micrograms of plutonium as "unnecessarily low." He cited, among other things, differences between acute and chronic toxicity and new analysis of data from the radium watch dial painters.
On January 24, 1950, Shields Warren, Austin Brues of Argonne National Laboratory, Robley Evans, Karl Morgan, and Wright Langham met in Washington. Langham wrote later: "As a result of this meeting, Dr. Shields Warren of the Division of Biology and Medicine authorized 0.5 ug (0.033 uc) of Pu239 as the AEC's official operating maximum permissible body burden."[e] There were no minutes or transcripts taken of this meeting. The calculation of this level was again based on the body burden for radium, this time modified by the 1/15 toxicity factor (since experiments had indicated that plutonium was up to fifteen times more toxic than radium), by the relative retention of plutonium and radium in rodents, and by the energy ratios modified by radon retention.
Thus far, the entire debate had occurred behind the closed doors of the AEC. Consideration of all the complex issues applied in setting a permissible body burden had been within a small circle of scientists and administrators. While the MPBB for plutonium accepted at the January 1950 meeting has held until today, its derivation has changed over the years.
a. Robley Evans, "Inception of Standards for Internal Emitters, Radon and Radium," Health Physics 41 (September 1981): 437-448.
b. W. H. Langham et al., "The Los Alamos Scientific Laboratory's Experience with Plutonium in Man," Health Physics 8 (1962): 753.
c. Wright Langham, Los Alamos Scientific Laboratory Health Division, to Hymer Friedell, 21 May 1945 ("Since the Chicago Meeting, I am somewhat lost as to what our program should be in the future . . .") (ACHRE No. DOE-113094-B-7), 1.
d. The letter went on to say that "operations of the Los Alamos Laboratory would be curtailed or stopped if such action were necessary to the reasonable and sensible protection of the personnel. The seriousness of this action, however, seems to be adequate reason for requesting that official adoption of the tolerances by the AEC be postponed until they have been carefully reviewed in order to make certain that the values are not unnecessarily conservative." Wright Langham, Los Alamos Laboratory Health Division, to Shields Warren, Director of AEC Division of Biology and Medicine, 20 January 1950 ("Radiation Tolerances Proposed by the Chalk River Permissible Dose Conference of September 29-30, 1949") (ACHRE No. DOE-020795-D-6), 1.
e. W. H. Langham et al., "The Los Alamos Scientific Laboratory's Experience with Plutonium in Man," Health Physics 8 (1962): 754.
By March 1945, there was disturbing news that urine samples from Los Alamos workers were indicating, based on models developed from animal experimentation, that some might be approaching or had exceeded a body burden of 1 microgram. A March 25 meeting led to Hempelmann's recommendation that the Project "help make arrangements for a human tracer experiment to determine the percentage of plutonium excreted daily in the urine and feces. It is suggested that a hospital patient at either Rochester or Chicago be chosen for injection of from one to ten micrograms of material and that the excreta be sent to the laboratory for analysis." The overall program, as it was envisioned by Dr. Hymer Friedell, deputy medical director of the Manhattan Engineer District, Oppenheimer, and Hempelmann, consisted of three parts: improvement of methods to protect personnel from exposure to plutonium; development of methods for diagnosing overexposure of personnel; and study of methods of treatment for overexposed personnel. On March 29, Oppenheimer forwarded the recommendation to Stafford Warren, with his "personal endorsement."
The accident at Los Alamos was part of the prelude to experiments conducted between 1945 and 1947 in which eighteen hospital patients were injected with plutonium to determine how excreta (urine and feces) could be used to estimate the amount of plutonium that remained in an exposed worker's body. One patient was injected at Oak Ridge Hospital in Oak Ridge, Tennessee; eleven were injected at the University of Rochester, three at the University of Chicago, and three at the University of California.
The results of these experiments contributed to the development of a monitoring method that, with small changes, is still used today. The experimental data were used to develop a model relating body burden to short-term excretion rate. Known as the "Langham model," it was based on short-term excretion data, long-term excretion data that were collected in 1950 from two injection subjects, and worker excretion data. This model has been used almost universally to monitor plutonium workers since 1950, although it has been modified over the years as longer-term and more extensive data were accumulated. While now, fifty years later, not every question concerning the quality of the science or the basis for estimating risk can be answered with precision, there is general agreement among radiation scientists that the experiments were useful.
Although this would be the first time that plutonium would be injected into human beings, the plutonium experiments were not viewed at the time as being extremely risky, and for good reason. Based on experience with other bone-seeking radioisotopes such as radium, the investigators had firm basis for believing, even in the 1940s, that the amount of material to be injected was likely too small to produce any immediate side effects or reactions. No one was expected to feel ill or have any negative reaction to the injection, and apparently no one did. Because acute effects were not expected, the plutonium injections were viewed as posing no short-term risks to human subjects. There was concern, however, about long-term risk. A draft report, written by one of the primary investigators within a few years of the injections, records that "acute toxic effects from the small dose of pu [plutonium] administered were neither expected nor observed." The document also recognized that "with regard to ultimate effects, it is too early to predict what may occur." Based largely on the experience of the radium dial painters, it was recognized that exposure to plutonium could result, perhaps ten or twenty years later, in the development of cancer in a human subject. This was viewed as a significant risk but also as a risk that could be minimized by the use of small doses and wholly avoided if the subjects were expected to die well before a cancer had a chance to materialize.
Even if the plutonium injections had been entirely risk free, an impossibility in human experimentation, they could still be morally problematic. As we discussed in chapter 2, it was not uncommon in the 1940s for physicians to use patients as subjects in experiments without their knowledge or consent. This occurred frequently in research involving potential new therapies, where there was at least a chance that the patient-subjects might benefit medically from being in an experiment. But it also occurred even in experiments--like the plutonium injections--where there was never any expectation and no chance that the experiment might be of benefit to the subjects.
The conduct of the plutonium experiments raises a number of difficult ethics and policy questions: Who should have been the subjects of an experiment designed to protect workers vital to bomb production in wartime? What should the subjects have been told about the risks of the secret substance with which they were being injected? What should they have been told about the purpose of the experiment? What were the subjects told? Did they know they were part of an experiment in which there was no expectation that they would benefit medically?
An inquiry initiated by the AEC commissioners in 1974 investigated some of these questions. That inquiry focused on whether consent was obtained from the subjects, either at the time of the plutonium injections or during 1973 follow-up studies funded by the AEC's Argonne National Laboratory in Chicago, designed to determine the long-term effects of the injections. Sixteen patient charts were examined for evidence of consent at the time of injection; the other two charts had been either lost or destroyed. Of the sixteen charts examined, only one chart--that of the only subject injected after the April 1947 directive of AEC General Manager Carroll Wilson (discussed in chapter 1) that required documented consent--contained evidence of some form of consent. The other fifteen contained no record of consent. According to AEC investigators, oral testimony pointed to failure to obtain consent in the case of the Oak Ridge injection and to some form of disclosure to patients for the California and Chicago experiments. The AEC concluded that testimony was inconclusive for the Rochester experiments. With regard to the follow-up studies conducted with three surviving subjects in 1973, the investigation concluded that two subjects had deliberately not been informed of the purpose of the follow-up and that one subject had actually been misled about the purpose.
As we will see later in this chapter, the AEC's conclusion that consent was not obtained from the surviving subjects for the 1973 follow-up studies was correct. Moreover, additional documentary evidence and testimony suggests that patient-subjects at the Universities of Rochester and California were never told that the injections were part of a medical experiment for which there was no expectation that they would benefit, and they never consented to this use of their bodies.
The rest of this chapter provides a chronological account of the plutonium injection experiments and follow-up studies conducted over the course of many years, assesses the influence of secrecy on the conduct of the experiments, and examines the motivating factors behind the prolonged secrecy of the experiments and the continued deception of surviving subjects. We also consider the conduct of experimentation with uranium and polonium. Finally, we render judgments where we can about the ethical conduct of these experiments.