Conclusion

Chapter 5: The Manhattan District Experiments

The First Injection

Mr. Cade had been hospitalized since his accident, but the plutonium injection did not take place until April 10. On this date, "HP-12" (the code name HP--"human product"[26]--was later assigned to this patient and to patients at the University of Rochester) was reportedly injected with 4.7 micrograms of plutonium. (It is important here to distinguish between administered dose and retained dose; not all of the injected dose would remain fixed in the body. It was not known with certainty, however, how much of the 4.7 micrograms of plutonium would remain in his body.)

The small amount of material injected into Mr. Cade would not be expected to produce any acute effects, and there is no indication that any were experienced. However, except for his fractures, Mr. Cade was apparently in good health and at age fifty-three could reasonably have been expected to live for another ten to twenty years. Thus, in Mr. Cade's case, the risk of a plutonium-induced cancer could not be ruled out.

Dr. Joseph Howland, an Army doctor stationed at Oak Ridge, told AEC investigators in 1974 that he had administered the injection. There was, he recalled, no consent from the patient. He acted, he testified, only after his objections were met with a written order to proceed from his superior, Dr. Friedell.[27] Dr. Friedell told Advisory Committee staff in an interview that he did not order the injection and that it was administered by a physician named Dwight Clark, not Dr. Howland.[28] The Committee has not been able to resolve this contradiction.

Measurements were to be taken from samples of Mr. Cade's blood after four hours, his bone tissue after ninety-six hours, and his bodily excretions for forty to sixty days thereafter.[29] His broken bones were not set until April 15--five days after the injection--when bone samples were taken in a biopsy.[30] Although this was several weeks after his injury, during this era when antibiotics were only beginning to become available, it was common practice to delay surgery if there was any sign of possible infection. One document records that Mr. Cade had "marked" tooth decay and gum inflammation,[31] and fifteen of his teeth were extracted and sampled for plutonium. The Committee has not been able to determine whether the teeth were extracted primarily for medical reasons or for the purpose of sampling for plutonium. In a September 1945 letter, Captain David Goldring at Oak Ridge informed Langham that "more bone specimens and extracted teeth will be shipped to you very soon for analysis."[32] It remains unclear whether these additional bone specimens were extracted at the time of the April 15 operation or later.

According to one account, Mr. Cade departed suddenly from the hospital on his own initiative; one morning the nurse opened his door, and he was gone.[33] Later it was learned that he moved out of state and died of heart failure on April 13, 1953, in Greensboro, North Carolina.[34]

The experiment at Oak Ridge did not proceed as planned. "Before" and "after" urine samples were mistakenly commingled, so no baseline data on kidney function was available.[35] Thus, the subject's kidney function would be difficult to assess. In May 1945,[36] Dr. Stone convened a "Conference on Plutonium" in Chicago to discuss health issues related to plutonium, including the relationship between dose and excretion rate, the permissible body burden, and potential therapy and protective measures.[37] Wright Langham spoke about the Oak Ridge injection at the conference, carefully qualifying the reliability of the excretion data obtained from Mr. Cade. Langham observed that "the patient might not have been an ideal subject in that his kidney function may not have been completely normal at the time of injection"[38] as indicated by protein tests of his urine.

The Chicago Experiments

Subsequently, between late April and late December of 1945, three cancer patients, code-named CHI-1, 2, and 3, were injected with plutonium. At least two and possibly all three were injected at the Billings Hospital of the University of Chicago. The doses to subjects CHI-2 and CHI-3 were the highest doses administered to any of the eighteen injection subjects--approximately 95 micrograms.[41] However, the amount of material injected was still below what would be expected to produce acute effects. Moreover, unlike Mr. Cade, all three of these patients were seriously ill and at least two of them died within ten months of receiving the injection. That the selection of seriously ill patients was an intentional strategy to contain risk is indicated in a 1946 report on CHI-1 and CHI-2: "Some human studies were needed to see how to apply the animal data to the human problems. Hence, two people were selected whose life expectancy was such that they could not be endangered by injections of plutonium."[42] It remains a mystery why CHI-3 was not included in this report.

On April 26, 1945, CHI-1, a sixty-eight-year-old man who had been admitted to Billings Hospital in March, was injected with 6.5 micrograms of plutonium. At the time of injection he was suffering from cancer of the mouth and lung. The patient reportedly "remained in fair condition until August 1945, when he complained of pain in the chest."[43] His lung cancer had apparently spread, and he died on October 3, 1945.[44]

The next injection took place eight months later. CHI-2 was a fifty-five-year-old woman with breast cancer who had been admitted to Billings Hospital in December 1945 after the cancer had already spread throughout her body. The 1946 report recorded that "the patient's general condition was poor at the time of admission and deteriorated steadily throughout the period of hospitalization."[45] She was injected with 95 micrograms of plutonium on December 27 and died on January 13, 1946.[46]

There is little known about the condition of CHI-3, the other subject who was injected with approximately 95 micrograms. He was a young man suffering from Hodgkin's disease, reportedly injected on the same date as CHI-2.[47] His condition at the time of injection remains unknown, as does his date of death. There is some question whether he was injected at Billings hospital or at another hospital in the Chicago area.[48]

There was no discussion of consent in the original reports on the Chicago experiments. However, a draft report on an interview conducted with E. R. Russell for the 1974 AEC investigation into the experiments (Russell was coauthor of the 1946 report on the Chicago experiments) summarized Russell's description of consent as follows: "[H]e prepared the plutonium solutions for injection and acted together with a nurse as witness to the fact that the patient was or had been informed that a radioactive substance was going to be injected. The administration of this substance, according to what was said in obtaining consent, was not necessarily for the benefit of the patients but might help other people."[49] To say that the injection was "not necessarily" for the benefit of the patient implies that there was some chance these patients might benefit; in fact, there was no expectation that this would occur.

Russell's account was obtained in the context of an official inquiry into his conduct and the conduct of the other investigators and officials involved in the plutonium injections, an inquiry that focused on whether consent was obtained from the subjects. We have no way of corroborating this account or of assessing what Dr. Russell's motivations were in explaining the plutonium injections to the subjects in the way claimed.

The Rochester Experiments

The university's metabolism ward, at what is now the Strong Memorial Hospital, became the central Manhattan District site for the administration of isotopes to human subjects. The two-bed ward, headed by Dr. Samuel Bassett, was part of the Manhattan District's "Special Problems Division," which worked on the health monitoring of production plants, the development of monitoring instruments, and research on the metabolism and toxicology of long-lived radioactive elements.[51] An experimental plan called for fifty subjects altogether, in five groups of ten subjects each. Each group would receive plutonium, radium, polonium, uranium, or lead.[52] Although the exact number of subjects remains unknown, at least twenty-two patients were administered long-lived isotopes in experiments with plutonium (eleven subjects), polonium (five subjects), and uranium (six subjects).

At the time the experiment was being designed, the main selection criterion for the subjects chosen at Rochester for the plutonium experiment was that they have a metabolism similar to healthy Manhattan Engineer District workers. In a work plan for the plutonium study based on a September 1945 meeting with a representative of Colonel Warren's office and the Rochester doctors, Langham wrote:

The selection of subjects is entirely up to the Rochester group. At the meeting it seemed to be more or less agreed that the subjects might be chronic arthritics [patients with serious collagen vascular diseases, such as scleroderma] or carcinoma patients without primary involvement of bone, liver, blood or kidneys.

It is of primary importance that the subjects have relatively normal kidney and liver function, as it is desirable to obtain a metabolic picture comparable to that of an active worker.

Undoubtedly the selection of subjects will be greatly influenced by what is available. The above points, however, should be kept in mind.[53]

Although this protocol specifies cancer patients as potential subjects, evidently the deliberate choice was made later by the experimenters to select patients without malignant diseases in the hope of ensuring normal metabolism.[54] Thus no cancer patients were included among the plutonium subjects at Rochester. Preference appears to have been given to patients the doctors believed would benefit from additional time in the hospital.[55]

An additional perspective on the selection of subjects for the plutonium experiments is provided in three retrospective reports written by Wright Langham. In a 1950 report on the plutonium project, including the experiments conducted at Rochester, Langham wrote that "as a rule, the subjects chosen were past forty-five years of age and suffering from chronic disorders such that survival for ten years was highly improbable."[56] In subsequent reports, Langham refers to the plutonium subjects as having been "hopelessly sick"[57] and "terminal."[58]

Documents retrieved for the Advisory Committee show that all but one of the plutonium subjects at Rochester suffered from chronic disorders such as severe hemorrhaging secondary to duodenal ulcers, heart disease, Addison's disease, cirrhosis, and scleroderma.[59] One subject, Eda Schultz Charlton, did not have any such condition. According to the draft of the 1950 report, she was misdiagnosed: "a woman aged 49 years may have a greater life expectancy than originally anticipated due to an error in the provisional diagnosis."[60]

Most of the subjects at Rochester were not terminally ill, and at least some of them had the potential to live more than ten years. Three of the Rochester subjects were known to still be living at the time of the 1974 AEC investigation into the plutonium experiments. Whether the inclusion of subjects at Rochester with the potential to live more than ten years is an indication that the investigators were not using Langham's criterion to select subjects or that they erred in their predictions is unclear. Judgments about the life expectancy of the chronically ill are difficult to make and often in error, even today.

The likelihood that long-term risks can be altogether eliminated does exist, however, if the subject is in the terminal stages of an illness and death is imminent. This was recognized by the plutonium investigators, and it led to the observation that the use of a terminal patient permitted a larger dose, which would make analysis easier. The first terminal patient at Rochester was injected toward the end of that series, and the possibility of further injections into terminal patients was discussed explicitly. In a March 1946 letter, Wright Langham wrote to Dr. Bassett, the primary physician-investigator at Rochester:

In case you should decide to do another terminal case, I suggest you do 50 micrograms instead of 5. This would permit the analysis of much smaller samples and would make my work considerably easier. . . . I feel reasonably certain there would be no harm in using larger amounts of material if you are sure the case is a terminal one [as was done in two of the three Chicago injections].[61]

As was the case at Oak Ridge and Chicago, there was no expectation that the patient-subjects at Rochester would benefit medically from the plutonium injections. The Advisory Committee found no documents that bear directly on what, if anything, the subjects were told about the injections and whether they consented. The recollections of at least some of those intimately involved have survived, however, and these recollections all suggest that the patients did not know they had been injected with radioactive material or even that they were subjects of an experiment.

Milton Stadt, the son of a Rochester subject, told the Advisory Committee the following at a meeting in Santa Fe, New Mexico, on January 30, 1995:

My mother, Jan Stadt, had a number, HP-8. She was injected with plutonium on March 9th, 1946. She was forty-one years old, and I was eleven years old at the time. My mother and father were never told or asked for any kind of consent to have this done to them.

My mother went in [to the hospital] for scleroderma . . . and a duodenal ulcer, and somehow she got pushed over into this lab where these monsters were.

Dr. Hempelmann, in an interview for the 1974 AEC investigation, said he believed that the patients injected with plutonium were deliberately not informed about the contents of the injections.[62] Dr. Patricia Durbin, a University of California researcher who in 1968 undertook a scientific reanalysis of the experiments, reported on a visit with Dr. Christine Waterhouse in 1971. Dr. Waterhouse was a medical resident at Rochester at the time of the plutonium injections. Durbin wrote the following regarding the Rochester subjects who were still alive:

She [Dr. Waterhouse] believes that all three persons would be agreeable to providing excretion samples and perhaps blood samples, but they are all quite old--in their middle or late 70's and cannot travel far. More important, they do not know that they received any radioactive material.[63]

In notes on a 1971 telephone conversation with Wright Langham, Dr. Durbin wrote: "He is, I believe, distressed by . . . the fact that the injected people in the HP series were unaware that they were the subjects of an experiment."[64] This recollection is even more troubling than the recollections of Drs. Waterhouse and Hempelmann, as it indicates not only that the subjects did not know that they were being injected with plutonium or a radioactive substance, but also that they did not know even that they were subjects of an experiment.

Even the doctors in charge of some of the injections at Rochester may not have known what they were injecting into patients. In 1974, Dr. Hempelmann suggested that the physician who actually injected the solution quite possibly did not know of its contents.[65]

Further evidence suggesting that the patient-subjects were never told what was done to them comes from 1950 correspondence between Langham and the physicians at Rochester. These physician-investigators were looking for signs of long-term skeletal effects in follow-up studies with two of the subjects at Rochester. Langham wrote to Rochester that he was "very glad to hear that you will manage to get follow-ups on the two subjects. The x-rays seem to be the all-important thing, but please get them in a completely routine manner. Do not make the examination look unusual in any way."[66]

Moreover, a letter from Langham to Dr. Bassett discussed the undesirability of recording plutonium data in the Rochester subjects' hospital records:

I talked to Col. [Stafford] Warren on the phone yesterday and he recommended that I send copies of all my data to Dr. [Andrew] Dowdy where it would be available to you and Dr. [Robert M.] Fink to observe. He thought it best that I not send it to you because he wanted it to remain in the Manhattan Project files, instead of taking a chance on it finding its way into the hospital records. I think this is probably a sensible suggestion.[67]

Uranium Injections at Rochester

The subjects of this experiment, like some of the plutonium-injection subjects, were not at risk of imminent death, but did suffer from chronic medical conditions such as rheumatoid arthritis, alcoholism, malnutrition, cirrhosis, and tuberculosis. According to Dr. Bassett, again the primary investigator, the subjects "were chosen from a large group of hospital patients. Criteria of importance in making the selection were reasonably good kidney function with urine free from protein and with a normal sediment on clinical examination. The probability that the patient would benefit from continued hospitalization and medical care was also a factor in the choice."[68]

The 1948 report on the experiment did not discuss the question of consent. We were not able to locate any documents that bear on what, if anything, the subjects were told about the uranium injections, nor have any relevant recollections about the experiment survived. Two 1946 documents, however, discussing whether Dr. Bassett should be permitted to give a departmental seminar on the excretion rate of uranium in humans, illustrate the secrecy that surrounded these injections and suggest that the subjects were not informed of the experiment. By the time of this correspondence, the uranium research with animals at Rochester had been declassified. The first document, a letter written by Andrew Dowdy, the director of the Manhattan Department at the University of Rochester, to a Manhattan District Area engineer requesting permission for Bassett to give the seminar, included the following: "I feel that there is no reason why he should not discuss this matter, and I believe that the fact that this information was actually obtained on his own patients is of more concern to himself than to the District."[69] In the second document, an intraoffice memorandum, the area engineer discussed this point, and more:

Dr. Dowdy states that the patients were Dr. Bassett's, but it should be borne in mind that all the work performed by Dr. Bassett was performed at the request of the Manhattan District Medical Section. This seminar is to be conducted for persons who are all Doctors of Medicine and it is doubtful if this information would get out to any of the families of the patients or the patients on whom the experiments were performed. . . .

At the time these experiments were started, this office was given strict orders that the information should not be released to any but authorized persons. Almost all the correspondence and result of experiments were exchanged between Dr. Wright Langham at Santa Fe and Dr. Bassett of the University of Rochester. This rule is still in effect on some of the material that Dr. Bassett is using and knowledge of the experiments is kept from personnel at the Rochester Area.[70]

Polonium Injections at Rochester

The final report, unlike other reports on the Manhattan District metabolism studies, briefly discusses the question of consent: "the general problem was outlined to a number of hospital patients with no previous or probable future contact with polonium. Of the group that volunteered as subjects, four men and one woman were selected for the excretion studies outlined below."[73] This statement leaves no clear impression of what the subjects actually were told; like the experiments with plutonium and uranium, the human polonium experiment was a classified component of the metabolism program. Still, this report provides a contrast to the contemporaneous reports on the Manhattan District plutonium and uranium experiments, which make no mention of consent and which do not refer to the patient-subjects as "volunteers."

The California Experiments

Under the Manhattan District contract, Hamilton's studies originally had involved exposing rats to plutonium in an effort to determine its metabolic fate and thereby project the risk to workers at atomic plants. Toward the end of the war, Hamilton began to conduct plutonium studies on humans for the government.[75] Experiments with humans could be handled expeditiously, Hamilton wrote, because of the close relationship between the Rad Lab and the medical school at the University of California at San Francisco.[76] In January 1945, Hamilton confirmed to the Manhattan District that he planned "to undertake, on a limited scale, a series of metabolic studies with [plutonium] using human subjects."[77] The purpose of this work, Hamilton wrote, "was to evaluate the possible hazards . . . to humans who might be exposed to them, either in the course of the operation of the [Chicago] pile, or in the event of possible enemy action against the military and civilian population."[78]

Subsequently, three subjects, two adults and one child (known as CAL-1, 2, and 3), were injected with plutonium. In addition, in April 1947 a teenage boy (CAL-A) was injected with americium, and in January 1948 a fifty-five-year-old female cancer patient (CAL-Z) was injected with zirconium.[79]

On May 10, 1945, Hamilton reported he was awaiting "a suitable patient" for the plutonium experiment.[80] Four days later, fifty-eight-year-old Albert Stevens, designated CAL-1, was injected with plutonium, becoming the first human subject in the California portion of the project.[81] Albert Stevens was chosen in the belief that he was suffering from advanced stomach cancer.[82] Shortly after the injection, however, a biopsy revealed a benign gastric ulcer instead of the suspected cancer. The researchers collected excreta daily for almost one year, analyzing them for plutonium content.[83] Evidently, by two months after the injection, Mr. Stevens was considering moving out of the Berkeley area; this would have prevented further collection of excretion specimens. Dr. Hamilton proposed to Drs. Stone and Stafford Warren that he be permitted to "pay the man fifty dollars per month" in order to keep Mr. Stevens in the area. Hamilton recognized, however, that there were "possible legal and security situations which may present insurmountable obstacles."[84] In response to this request, Dr. Joe Howland (who was reportedly involved with the Oak Ridge plutonium injection) wrote the following to the California area engineer:

Possible solutions to this problem could be:

a. Pay for his care in a hospital or nursing home as a service.

b. Place this individual on Dr. Hamilton's payroll in some minor capacity without release of any classified information.

It is not recommended that he be paid as an experimental subject only.[85]

According to a 1979 oral history of Kenneth Scott, an investigator at Berkeley who evidently was responsible for the analysis of Mr. Stevens's excretion specimens, the patient was paid some amount each month to keep him in the area. However, Dr. Scott also recalled that he never told Mr. Stevens what had happened to him: "His sister was a nurse and she was very suspicious of me. But to my knowledge he never found out."[86]

In addition, an April 1946 report on the experiment records that "several highly important tissue samples were secured including bone."[87] It appears that these tissue specimens, which included specimens of rib and spleen, were removed four days after the injection in an operation for the patient's suspected stomach cancer.[88]

Four months after Mr. Stevens was injected, Dr. Hamilton told the Manhattan District that the next subject would be injected "along with Pu238 [plutonium], small quantities of radio-yttrium, radio-strontium, and radio-cerium." The purpose of this experiment was to "compare in man the behavior of these three representative long-lived Fission Products with their metabolic properties in the rat, and second, a comparison can be made of the differences in their behavior from that of Plutonium."[89] This research would provide data to improve extrapolation from higher-dose animal experiments.

Despite Hamilton's hope to have a second patient by the fall, CAL-2 was not selected until April 1946. Simeon Shaw was a four-year-old Australian boy suffering from osteogenic sarcoma, a rare form of bone cancer, who was flown from Australia to the University of California for treatment. According to newspaper articles at the time, Simeon's family had been advised by an Australian physician to seek treatment at the University of California.[90] Arrangements then were made by the Red Cross and the U.S. Army for Simeon and his mother to fly by Army aircraft to San Francisco. Within days, he had been injected with a solution containing plutonium, yttrium, and cerium by physicians at the university.[91]

Following his discharge on May 25, about a month after his injection, the boy returned to Australia, and no follow-up was conducted. He died in January 1947. In February 1995 an ad hoc committee at the University of California at San Francisco (UCSF) concluded that probably at least part of the motivation for this experiment was to gather scientific data on the disposition of bone-seeking radionuclides with bone cancers.[92]

One piece of evidence indicating that there was a secondary research purpose for the injection of CAL-2 was a handwritten note in the boy's medical record saying that the surgeons removed a section of the bone tumor for pathology and for "studies to determine the rate of uptake of radioactive materials that had been injected prior to surgery, in comparison to normal tissues."[93]

It is likely that the CAL-2 experiment was designed both to acquire data for the Manhattan District and also to further the physicians' own search for radioisotopes that might treat cancer in future patients. The California researchers themselves noted the dual purpose of their research at the time. Hamilton wrote in a report to the Army in the fall of 1945 that there were "military considerations which can be significantly aided by the results of properly planned tracer research."[94]

As the February 1995 UCSF report on the experiments concluded, however, the "injections of plutonium were not expected to be, nor were they, therapeutic or of medical benefit to the patients."[95] This corresponds with the evidence of a letter, written by Hamilton in July 1946, three months after the injection of CAL-2, to the author of an article on the peacetime implications of wartime medical discoveries:

To date no fission products, aside from radioactive iodine, have been employed for any therapeutic purposes. There is a possibility that one or more of the long list of radioactive elements produced by uranium fission may be of practical therapeutic value. At the present time, however, we can do no more than speculate.[96]

Documentary evidence suggests that consent for the injections likely was not obtained from at least some of the subjects at the University of California. A 1946 letter from T. S. Chapman, with the Manhattan District's Research Division, said the following regarding preparations for injections:

. . . preparations were being made for injection in humans by Drs. [Robert] Stone and [Earl] Miller. These doctors state that the injections would probably be made without the knowledge of the patient and that the physicians assumed full responsibility. Such injections were not divergent from the normal experimental method in the hospital and the patient signed no release. A release was held to be invalid.

The Medical Division of the District Office has referred "P" reports for project 48A to Colonel Cooney for review and approval is withheld pending his opinion.[97]

Chapman does not specify whether the "injections" referred to in this letter were injections of plutonium or of some other substance. It is unclear whether "'P' reports" refers to Hamilton's overall progress reports on his tracer research, which had reported mostly on research with plutonium (but also on research with cerium and yttrium), or whether "P" referred specifically to reports on work with plutonium. As we noted at the outset of this chapter, Chapman's claim that it was commonplace at the time to use patients in experiments without their knowledge and without asking them to sign a "release" is correct.

In the case of Albert Stevens (CAL-1), no documentary evidence that bears on disclosure or consent has been found. Simeon Shaw's (CAL-2's) medical file contains a standard form "Consent for Operation and/or Administration of Anaesthetic." This form, however, was signed by a witness attesting to consent of Simeon's mother one week after the injection and therefore probably applies to a biopsy done a week after the injection, not to the injection itself.[98]

On December 24, 1946, at the prompting of Major Birchard M. Brundage, who was chief of the Manhattan District's Medical Division, Colonel K. D. Nichols, commander of the Manhattan District, ordered a halt to injections of "certain radioactive substances" into human subjects at the University of California.[99] "Such work," Nichols wrote, "does not come under the scope of the Manhattan District Programs and should not be made a part of its research plan. It is therefore deemed advisable by this office not only to recommend against work on human subjects but also to deny authority for such work under the terms of the Manhattan contract." The following week, the civilian AEC took over responsibility for all Manhattan District research and temporarily reaffirmed the Manhattan District's suspension of human experimentation at the University of California.[100] It is unclear why this action was taken.