Chapter 9: The Oregon and Washington Experiments In 1963 Carl Heller was an internationally renowned medical scientist, a winner of the important Ciba Prize. In the field of endocrinology, he was a preeminent researcher, so it is not surprising that when the AEC decided to fund work on how radiation affects male reproductive function, they would turn to him. He designed a study to test the effects of radiation on the somatic and germinal cells of the testes, the doses of radiation that would produce changes or induce damage in spermatogenic cells, the amount of time it would take for cell production to recover, and the effects of radiation on hormone excretion.[7] To accomplish this he had a machine designed and built that would give a carefully calibrated, uniform dose of radiation from two sides. The subject lay face down with his scrotum in a small plastic box filled with warm water to encourage the testes to descend. On either side of the box were a matched set of x-ray tubes. The alignment of the x-ray beams could be checked through a system of peepholes and mirrors. Subjects were required to agree to be vasectomized because of a perceived small risk of chromosomal damage that could lead to their fathering genetically damaged children. To carry out this work Dr. Heller was to receive grants totaling $1.12 million over ten years. Mavis Rowley, Dr. Heller's former laboratory assistant, who was interviewed by Advisory Committee staff in 1994, said that the AEC "was looking for a mechanism to measure the effect of ionizing radiation on the human body. . . ." She said testicular irradiation was promising because the testes have "a cell cycle and physiology which allows you to make objective measurements of dosimetry and effect without having to expose the whole body to radiation."[8] Although official documentation is fragmentary, it is clear from other evidence such as interviews and contemporary newspaper articles that the concerns cited above--worker exposures, potential exposures of the general population as a result of accidents or bomb blasts, and exposures of astronauts in space--were of interest to the AEC. In the case of the astronauts, the National Aeronautics and Space Administration has been able to find no evidence of direct involvement in Dr. Heller's project. Yet Ms. Rowley remembers with clarity that NASA representatives, even astronauts themselves, attended meetings with their research team. In her 1994 interview, she said, "NASA was also very interested in this. . . . There was a section of activity which was devoted to what effect would the sun flares and so forth, which give out significant radiation have on the astronauts. And so there were meetings that went on which actually included some of the astronauts attending them. . . ." Rowley explained that the astronauts were concerned that reduced testosterone production might make them lose muscle function, which could compromise their mission, but, belying the comment of the colonel in the 1949 nuclear-powered airplane meeting who said that crewmen were concerned about anything physically harmful, she said they seemed altogether unconcerned "about their own health."[9] During his 1976 deposition, Dr. Heller remarked: "What we would like to supply the medical community with is what happens when you give continual very small doses such as might be given to an astronaut."[10] Moreover, in 1965, Dr. Heller served as a consultant to a Space Radiation Panel of the National Academy of Sciences-National Research Council. And finally, Harold Bibeau, an Oregon subject, recalls that Dr. Heller told him when he signed up for the program that NASA was interested in the results.[11] At the time the Oregon experiment got under way, using prisoners as research subjects was an accepted practice in the United States. And in this particular study Oregon law was interpreted by state officials as permitting an inmate to give his consent to a vasectomy, which they appear to have seen as analogous to consenting to becoming an experimental subject. However, important ethical concerns of today such as balancing risks and benefits, the quality of informed consent, and subject-selection criteria appear, on the whole, not to have been carefully addressed or not addressed at all by the investigators or those responsible for oversight. With respect to the health risks associated with the testicular irradiations, there was very little reliable "human" information at the time about the long-term effects of organ-specific testicular exposure to radiation. Hiroshima and Nagasaki bomb data, however, which of course were not organ specific, suggested that the likelihood of inducing cancers with the amount of radiation Dr. Heller planned to use was small. By way of comparison, today's standard radiotherapy of the pelvis, for prostate cancer for example, often results in doses to the testicles in the ranges encountered in these experiments. So what did Dr. Heller tell subjects about the chronic risk? The answer appears to have been nothing in the early years and, later on, perhaps a vague reference to the possibility of "tumors" but not cancer. In a deposition taken in 1976 a subject named John Henry Atkinson said he was never told there was a possibility of getting cancer or any kind of tumors as a result of the testicular irradiation experiments. Other subjects deposed in 1976 also said they had not been warned of cancer risk, and when asked by one subject about the potential for "bad effects," Dr. Heller was reported to have said, "one chance in a million."[12] When asked in his own deposition what the potential risks were, Dr. Heller said, "The possibility of tumors of the testes." In response to the question "Are you talking about cancer?" Dr. Heller responded, "I didn't want to frighten them so I said tumor; I may have on occasion said cancer."[13] The acute risks of the exposures included skin burns, pain from the biopsies, orchitis (testicular inflammation) induced by repeated biopsies, and bleeding into the scrotum from the biopsies. Using consent forms and depositions as a basis for determining what the subjects were told, it appears that they were adequately informed about the possibility of skin burns; sometimes informed, but perhaps inadequately, about the possibility of pain; informed about the possibility of bleeding only from 1970 on; and never informed of the possibility of orchitis. As far as the quality of consent is concerned, the evidence suggests that many if not most of the subjects might not have appreciated that some small risk of testicular cancer was involved. It is also not clear that all subjects understood that there could be significant pain associated with the biopsies and possible long-term effects. In selecting subjects, Dr. Heller appears to have relied on the prison grapevine to get out the word about a project he apparently believed the Atomic Energy Commission did not want publicized. In a 1964 memorandum he was paraphrased as saying "at Oregon State Penitentiary, the existence of the project is practically unknown."[14] In a 1966 letter to the National Institutes of Health describing the review process at the Pacific Northwest Research Foundation, a respected, free-standing research center, Dr. Heller and two colleagues wrote that "the inmates are well informed by fellow inmates regarding the general procedures concerned (i.e., collecting seminal samples, collecting urines for hormone studies, submitting to testicular biopsies, receiving medication orally or by injection, and having vasectomies . . . )."[15] If the volunteers were healthy and normal they were accepted for a trial period during which they donated semen samples. If all went well, in a matter of weeks they were accepted into the radiation program, as long as the prison's Roman Catholic chaplain certified that they were not Roman Catholics--because of the church's objection to their providing masturbated semen samples--and they could pass what appears to have been a cursory psychological screening designed to ensure they had no underlying objections to the required vasectomy. A copy of a form titled "Psychiatric Examination" provided by Harold Bibeau and signed with the initials of the examining psychiatrist, WHC for William Harold Cloyd, says in full: 11-4-64 Seen for Dr. Heller ---- Never married, quite vague about future. Feels he doesn't want children ---- shouldn't have any. I agree. No contraindication to sterilization. As far as potential health benefits to the subjects are concerned, there were none, and the inmates who volunteered for the research were told so. The benefits were in the form of financial incentives. A review of applications for Dr. Heller's program, and depositions of prisoners who sued Dr. Heller, various other individuals, and the state and federal governments for violation of their rights, clearly indicates that money was in most cases the most important consideration in deciding to volunteer. In prison industry inmates were typically paid 25 cents a day. For participating in the Heller program they received $25 for each testicular biopsy, of which most inmates had five or more, plus a bonus when they were vasectomized at the end of the program, which appears to have been an additional $25. Some inmates indicated that they were grateful for an opportunity to perform a service to society. An obvious ethical question is whether the money constituted a coercive offer to prisoners.[16] During the course of his study between 1963 and 1973 Dr. Heller irradiated sixty-seven inmates of the Oregon State Prison. Nominally, three institutions had some oversight responsibility for Dr. Heller's work--the Oregon Department of Corrections, the Atomic Energy Commission, and the Pacific Northwest Research Foundation, where Dr. Heller was employed. Practically speaking, however, it appears that Dr. Heller conducted his research independently. As an example of his independence, as recounted by Ms. Rowley, the AEC requested that Dr. Heller begin irradiating subjects at 600 rad and work upward, but he refused and in the end set 600 rad as an upper limit.[17] (It is not clear whether Dr. Heller was concerned about risk to the subjects' health or other research criteria.) Dr. Heller also was a member of the committee at Pacific Northwest Research Foundation that had responsibility for overseeing his research, giving him a voice in the oversight process. This committee was authorized under a foundation regulation titled "Policy and Procedures of the Pacific Northwest Research Foundation With Regard to Investigations Involving Human Subjects." In a section on ethical policy, the document says: "Since 1958 the investigators of this Foundation have conducted all research under the ethical provisions of the Nuremburg [sic] Code, modified to permit consent by parents or legal guardians."[18] In January 1973, in a rapidly changing research ethics environment, the Oregon irradiations were terminated when Amos Reed, administrator of the Corrections Division, ordered all medical experimentation programs shut down essentially because he concluded that prisoners could not consent freely to participate as subjects. It is not known exactly what was behind the timing of Reed's decision, but according to Oregon Times Magazine, he had recently read Jessica Mitford's article in the Atlantic Monthly titled "Experiments Behind Bars" and an article in The (Portland) Oregonian headlined "Medical Research Provides Source of Income for Prisoners."[19] In 1976, a number of subjects filed lawsuits effectively alleging poorly supervised research and lack of informed consent. In their depositions they alleged among other things that prisoners had sometimes controlled the radiation dose to which they were exposed, that an inmate with a grudge against a subject filled a syringe with water instead of Novocain, resulting in a vasectomy performed without anesthetic, and that the experimental procedures resulted in considerable pain and discomfort for which they were not prepared.[20] These suits were settled out of court in 1979. Nine plaintiffs shared $2,215 in damages.[21] For the last twenty years all efforts to put in place a medical follow-up program for the Oregon subjects have been unsuccessful. Dr. Heller and Ms. Rowley explicitly favored regular medical follow-up. During the period between 1976 and 1979, the pending lawsuits might have been the reason for the state's reluctance to initiate a follow-up program, but it is less clear why during other periods such efforts have also failed. Two possible reasons suggested by state officials are the cost of such a program and the difficulty of finding released convicts. Other possible reasons are that a follow-up program would not provide a significant health benefit to former subjects and that it would not provide significant new scientific knowledge. According to Tom Toombs, administrator of the Corrections Division of the State of Oregon at the time of the lawsuits, the Corrections Division wrote to the AEC's successor (the Energy Research and Development Administration) in early 1976 recommending medical follow-up for the subjects. Mr. Toombs said there was no record of a response to this request.[22] In 1990, James Ruttenber, an epidemiologist at the Centers for Disease Control, designed a follow-up program for Oregon, but it has not been implemented. In an interview with Advisory Committee staff, Dr. Ruttenber said state officials told him that Oregon does not have sufficient funds to carry out his plan.[23] Washington C. Alvin Paulsen was a student of Carl Heller at the University of Oregon in the late 1940s, and in the early 1950s he was a fellow in Heller's lab. But by 1963 he was ready to direct a substantial research program on his own. His chance came when he was called to Hanford to consult on an accidental radiation exposure of three workers. The upshot of this experience was a $505,000 grant from the Atomic Energy Commission to study the effects of ionizing radiation on testicular function. Dr. Paulsen remarked in the 1994 interview with Advisory Committee staff that the main research questions he was trying to answer were what would constitute "a reasonably safe dose" of ionizing radiation to the testes as well as what dose "would cause some change in sperm production and secondly, to determine the scenario of recovery."[24] He recalled a 1962 letter to the Washington State Department of Institutions in which he wrote that he would like to find out "the maximum dose of radiation that would not alter spermatogenesis" and "the maximum dose of radiation that affects spermatogenesis, but only temporarily."[25] Dr. Paulsen said in a 1995 telephone interview, however, that for reasons he can no longer remember, he limited dosage to 400 rad, not enough to test a maximum-dose thesis.[26] In the 1994 interview, Dr. Paulsen said: When I recognized a tremendous void of information relative to human exposure, and space travel had started and there was the question of solar explosions and ionizing radiation exposure in space, the nuclear power plants were going in then, a few men throughout the world were exposed . . . I then contacted the Atomic Energy Commission to determine . . . whether they would entertain receiving an application.[27] Obviously, Dr. Paulsen too was interested in the space applications of his research. In 1972 he and a colleague published their work titled "Effects of X-Ray Irradiation on Human Spermatogenesis" in the proceedings of the National Symposium on Natural and Manmade Radiation, a NASA-sponsored symposium. And Dr. Paulsen said that when he explained his research to potential subjects, one of the things he referred to was concern about exposures in space.[28] An August 1, 1963, article in the Oregonian about the Washington experiments said, "Although one of the primary benefits of the research will be in space exploration, the findings are also expected to be of value to an atomic industry where an occupational hazard might exist."[29] One major difference between the Heller and Paulsen projects was that from the outset Dr. Paulsen planned to eventually move from x rays to neutron irradiation, which, among other things, is more analogous than x rays with the radiation encountered in space.[30] A neutron generator was purchased, calibrated, and shielding was developed. However, the work took years to complete, and this part of the research was never carried out. Dr. Paulsen has expressed the belief on a number of occasions that one reason his project was terminated by the state of Washington in 1970 was concern about the possibly greater risks of exposing subjects to neutrons. Another difference was that Dr. Paulsen used a standard General Electric x-ray machine, which he says he believed would deliver as precise and well-targeted a dose of radiation as Dr. Heller's specially designed machine.[31] Still another difference was that at a certain stage of the Washington study, Dr. Paulsen used the prison bulletin board to advertise for volunteers. Under the headline "Subject: Additional Volunteers for Radiation Research Project," a notice said in part: The project concerns effects of radiation on human testicular function and the results of the project will be utilized in the safety of personnel working around atomic steam plants, etc. . . . It is possible that those men receiving the higher dosages may be temporarily, or even permanently, sterilized. It should be understood that when sterilized in this manner, a man still has the same desires and can still perform as he always has. . . . Submit to surgical biopsy. (This is a simple procedure performed under local anesthesia. It is not a very painful procedure.)[32] According to a March 9, 1976, report prepared for then-Governor Daniel J. Evans by Harold B. Bradley, director of Washington state's Adult Corrections Division, neither Dr. Paulsen's 1963 outline of his research project nor the November 1964 announcement to inmates mentioned a requirement to undergo a vasectomy at the end of the experiment to ensure that subjects would not father genetically damaged children.[33] Dr. Paulsen said he did not recall precisely when in the recruitment process the vasectomy requirement was conveyed to subjects, but he pointed out that once it was they had the option of dropping out of the project without penalty.[34] Dr. Paulsen's review process and consent procedures are less well documented than Dr. Heller's, but he says his research application, including provisions for subject selection and consent, was approved by what he described as a "human experimentation committee" at the University of Washington. He said the process was "very informal," noting that it was done over the phone. Paulsen added that "somewhat later" his work was also reviewed by a "radiation safety committee."[35] His recollection of both processes is vague. The minutes of a December 10, 1969, meeting of a University of Washington Research and Clinical Investigations Committee at the U.S. Public Health Service Hospital in Seattle includes a recommendation that Dr. Paulsen's consent form be modified to indicate that "a risk of carcinoma of the testes exists although it is extremely small."[36] According to Mr. Bradley's report, his department's records show that Dr. Paulsen's project was reviewed and approved on two occasions--March 1963 and June 1966--by the University Hospital Clinical Investigation Committee. The report shows no state Department of Institutions review until mid-1969.[37] The Bradley report and related correspondence from 1970 show that at that time some state officials had a sharp concern for research ethics. In mid-1969 a review of all experimentation in the prison system was undertaken by Dr. Audrey R. Holliday, chief of research for the Department of Institutions. At this time Dr. Holliday took steps to temporarily halt the irradiation phase of the project. After investigating the origins of Dr. Paulsen's research, Dr. Holliday asked the University of Washington to conduct a new review of the study, emphasizing her concern about the state's responsibility to safeguard human rights. The university stood by its initial findings allowing the research to continue, although at about the same time it turned down Dr. Paulsen's request to move into the neutron-irradiation phase of his project.[38] Dr. Holliday then debated the issue with Dr. William Conte, director of the Department of Institutions, who was disposed to allow the project to continue. On March 18, 1970, she wrote a letter to Dr. Conte noting, . . .There is no question but what the Federal Government has made considerable investment in this project. The Federal Government, however, as a reading of any newspaper will show, has supported a number of projects over which there have been many moral-ethical questions (both large and small) raised, e.g., nerve gasses, toxins, etc. I remind you that the Federal Government is not responsible for the care, safety and safeguarding of human rights of populations under the purview of the Department of Institutions. This is a responsibility we must discharge, regardless of the amount of money that the Federal Government is willing to invest in a project. . . . There is no doubt but what the prison setting is an ideal setting for this type of research. . . . I suppose concentration camps provided ideal settings for the research conducted in them. . . . If , in fact, non-inmates were to volunteer in the substantial numbers of persons Dr. Paulsen needs, then I would have less qualms about offering up a captive population for this research, i.e., I would have some evidence, assuming the volunteers were, in fact, normal, that non-captive populations might make the same decision as a captive population. . . . I am not against high risk research. I have engaged in some myself. I am not against federally sponsored research. I have engaged in some myself. However, the risk should be commensurate with the probable benefits to be received by the population or others like it to follow. I don't think we can argue that in this case. Neither am I opposed to use of a prison population on a volunteer basis for research projects that may not be of direct benefit to the population, but which are of clear benefit to society or mankind. I don't think we can argue that in this case either.[39] Dr. Holliday also argued that the study should have been done on "lower order primates" and that if the state allowed Dr. Paulsen's study to continue it would forfeit its right to speak out on behalf of human rights relating to future research proposals.[40] While favoring continuation of Dr. Paulsen's research, Dr. Conte authorized a review by the Department of Institutions's Human Rights Review Committee. The committee recommended that the study be shut down, noting that the Paulsen project "seems clearly inconsistent with the standards laid down by the Nuremberg Code" for the protection of human subjects with respect to freedom of choice and consent. The recommendation went on to say that "within the context of Dr. Paulsen's project, it is largely irrelevant whether or not a volunteer declares his 'desire to undergo vasectomy' since there is no assurance that his real reasons would be ethically-morally acceptable or that his reasons (whatever they may be) will stand the test of reality after release." It specified that the money paid for participation and the expectation of privileges, "real or imagined," could constitute undue inducements.[41] This review, according to the report, "recommended that Dr. Paulsen's request for continuation of his study be rejected as it was found to be inconsistent with standards for the protection of the individual as a research subject. The essential issue raised by departmental personnel was that of informed consent." On March 23, 1970, Dr. Holliday wrote to Dr. Paulsen to inform him that his project was over.[42] The Bradley report added that "so far as is known to departmental personnel, no ill effects have been reported by subjects of the experiments."[43] In 1994, however, a former Washington state inmate named Martin Smith told Karen Dorn Steele of the Spokane Spokesman-Review that ever since participating in the experiment he has suffered testicular pain.[44] Dr. Paulsen notes, however, that Smith was a control and therefore not actually irradiated, although he did have one testicular biopsy.[45] There has been less debate than in Oregon on the subject of medical follow-up. This may be in part because Dr. Paulsen has taken the position, based on his conversations with inmates, that the subjects of the Washington experiments want their privacy protected, and he has refused to disclose their names. A December 1975 AEC memorandum from Nell W. Fraser, a government contract administrator, to Oscar J. Bennett, director of the Contracts and Procurement Division, paraphrases Dr. Paulsen as saying that a follow-up program was not medically indicated and "a follow-up program would be harmful because most of the prisoners wish to disassociate themselves with the prison experience."[46] According to the memorandum, Dr. Paulsen also noted that his medical malpractice insurance would apply in the event that litigation resulted from his radiation study.[47] In recent years, however, a handful of former subjects have told reporters such as Karen Dorn Steele that they would like to be followed up.[48] In late 1994 state officials said they would seek federal funds to carry out a follow-up program or ask the Department of Health and Human Services to mount such a program. The Advisory Committee conducted its own analysis of the risks incurred by the Oregon and Washington testicular irradiation subjects based on a 600-rem dose, which was the maximum testicular exposure of any subject in either state. For purposes of this analysis we assumed that the testicles have average radiation sensitivity; that there is a linear relationship between cancer incidence and dose, and that there is a linear relationship between the risk of cancer and the amount of tissue exposed. Using these assumptions, we calculated that it would take more than double the dose received by any prisoner-subject to yield an effective dose of 1 rem. This means that the predicted increase over the expected cancer rate for the individuals who received the greatest exposure would be less that four-hundreths of 1 percent. For those who received smaller doses of radiation, the risk would, of course, be smaller, too.[49]