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Part II

Chapter 8


What is TBI?

Early Use of TBI for Radioresistant Tumors: The Manhattan Project Experiments on Patients and the Subsequent AEC Review

Renewed Interest in Total-Body Irradiation

Postwar TBI-Effects Experimentation: Continued Reliance on Sick Patients in Place of Healthy "Normals"

AEC-Sponsored TBI at Oak Ridge


Chapter 8: Introduction

In the fall of 1971, a public controversy erupted about the ethics of a research project at the University of Cincinnati College of Medicine funded for more than a decade by the Department of Defense (DOD). In this research, the subjects were cancer patients who underwent external total-body irradiation (TBI); the DOD was funding postirradiation research on the biological effects of this type of exposure to radiation. Critics of the research charged that the physician-investigators were exposing unknowing patients to potentially lethal doses of TBI--not to treat their cancer, but to collect data on the effects of nuclear war for the military--and that numerous patients had died or seriously suffered from the radiation. Defenders asserted that the TBI was reasonable medical treatment for people with incurable cancer and that this treatment was performed in accordance with contemporary professional ethics. Over the next four months, the research was reviewed favorably by ad hoc committees of physicians appointed by the American College of Radiology (ACR), the preeminent professional organization of radiologists, and by University of Cincinnati officials, but critically by an ad hoc committee of junior nonmedical faculty members at the university. Following these reports, the university president rejected further Defense Department funding for the posttreatment data-collection program, and the use of TBI was suspended.

When news reports about human radiation experiments appeared in late 1993, journalists and investigators again focused on this Cincinnati project. Critics charged that the reviews commissioned by the university and the ACR were biased and had been "whitewashes"; supporters countered that the Cincinnati research had been conducted in the open, had been thoroughly and favorably reviewed by the medical community, and was old news. In addition, patients were identified publicly for the first time, leading a number of their family members to file a lawsuit against the university, the physicians, and other parties in federal court.[1] The family members also formed an advocacy group called the Cincinnati Families of Radiation Victims Organization.

The University of Cincinnati was only the last in a line of institutions that received funds to provide data to the government on the effects of total-body irradiation on humans. In this chapter we review thirty years of research supported by the Manhattan Project, the Department of Defense, and the AEC aimed at gathering data on the effects of radiation on hospitalized patients who were medically exposed to total-body irradiation. Much of the record is incomplete, and some of it is contradictory. We cannot and do not resolve all the inconsistencies and uncertainties in the record. We do, however, focus on the ethical issues that emerged in this research, some of which are still with us today.

The history of TBI research is important to the Committee for several reasons. First, in the other case studies conducted by the Committee, there was never any expectation or any claim that subjects, even if they were patients, would benefit medically from their being involved in experiments. By contrast, in the TBI research, the TBI itself was recommended as treatment for incurable cancer, for which the expectation of benefit was low, although possible; chemotherapy, which would be considered "standard" today, was not well established until the mid- to late 1960s. (The postradiation effects studies sponsored by the DOD, however, were not intended to benefit the patients.) As we noted in chapter 4, the presence of an intent to benefit, if that intent is both genuine and reasonable, alters the ethics of the situation. An intent to benefit the patient-subject does not, however, ensure that an experiment is ethically acceptable. Many perplexing questions about the ethics of research involving human subjects that we face today occur at the bedside with patient-subjects who may or may not benefit medically by their participation. The TBI story thus foreshadows important issues we discuss in part III of this report when we focus on contemporary research involving human subjects, much of which involves patient-subjects and the prospect of medical benefit. The core of the ethical problem is straightforward. Whenever the treatment of a patient is intertwined with the conduct of research, the potential emerges for conflict between the interests of science and the interests of the patient. The patient may, for example, be exposed to additional risk or discomfort as a consequence. At the same time, for some patients, participation in research may offer the only chance, or the best chance, of improving their medical condition.

The second reason the history of TBI research is important to the Committee is that although the research was conducted on cancer patients, the government's interest in the research was not to advance the treatment of cancer but to find answers to problems facing the military in the development and use of atomic weapons and nuclear-powered aircraft. It is this disparity that raised questions, both in 1971 and today, about the motivations behind treatment of these patient-subjects with TBI. Whether it matters morally that the government pursued its interests in the effects of TBI on patient-subjects depends in large measure on whether the government's objectives in supporting this research inappropriately compromised the medical care the patient-subjects received. We have just noted that the conjoining of research with medical care necessarily creates a potential for conflict between the interests of the research and the interests of the patient. This is true even where the objective of the research is to find a treatment for the condition from which the patient suffers. A central issue in the case of the TBI research is whether this conflict was exacerbated by the nature of the gap between the interests of the patient and the objectives of the research. A complicating feature of the TBI story is that the DOD did not pay directly for the patients to be administered TBI; the funding by these agencies was restricted to the costs associated with the physiological and psychological measurements taken in conjunction with the TBI, rather than the costs of the TBI itself.

The Committee was also struck with how well the history of TBI research illustrates two very contemporary problems--how to draw boundaries between medical care and medical research, and how to draw boundaries between research with patient-subjects that is "therapeutic" and research that is "nontherapeutic." Was the administration of TBI always an instance of medical research, was it ever standard care, or was it sometimes administered as a departure from standard care outside of research? When TBI was administered in the context of research, was there a basis for believing that there was a reasonable prospect that patients could benefit, or was it the kind of research from which patients could not benefit medically? Because of conflicting and incomplete evidence, these were questions that we could not always answer but that guided our inquiry.

The Committee began our review by seeking to track down TBI research identified in a "Retrospective Study" of TBI exposures conducted in the mid-1960s by the Oak Ridge Associated Universities on behalf of the National Aeronautics and Space Administration (NASA), which collected records on more than 2,000 TBI exposures on both radiosensitive and radioresistant cancers from forty-five U.S. and Canadian institutions.[2] The Committee then focused on approximately twenty research studies that were published between 1940 and 1974 on the use of TBI in the United States. Nine of these twenty studies involved at least some patients with "radioresistant" cancers. Eight of the nine institutions that conducted the studies received funding from either the Manhattan Project or the DOD;[3] the Atomic Energy Commission sponsored one of the studies involving "radiosensitive" cancers at the Oak Ridge Institute of Nuclear Studies (ORINS).[4] In addition, the Committee found only one instance in which nongovernment-funded TBI research involved patients with radioresistant cancers.[5]

In this chapter, we begin with a definition of TBI, including a discussion of the then-contemporary distinction between the use of TBI to treat radiosensitive and radioresistant tumors. The distinction is important to what follows, because patients with radiosensitive cancers (for which TBI was considered most promising medically) were less useful subjects for obtaining the type of information that the military sought--information on the acute effects of radiation on healthy soldiers or citizens during the course of atomic warfare-related activities. In these patients, it would be less clear whether signs such as nausea, vomiting, or other acute effects were due to rapid destruction of cancer cells by the radiation or due to the radiation acting on normal tissue, such as normal blood cells. Similarly, patients with radiosensitive cancers were less useful for research intended to find biological measures of radiation doses ("biological dosimeters"), because this research depended on measuring various cell products in the blood or urine that could also be released by tumor cells that were destroyed. Patients with radioresistant tumors were more desirable because it was more likely that the effects seen were related to radiation effects on normal tissue rather than rapid destruction of their tumor cells.

Following a discussion of TBI itself, we turn to a chronological history of government sponsorship of research related to the effects of TBI with radioresistant tumors. This research began during the Manhattan Project. In 1949 and 1950, as we next discuss, DOD and AEC experts and officials met to consider the need for further TBI human experiments in order to gain information needed in the development of the nuclear-powered airplane. When the decision was made not to proceed with human experiments involving healthy subjects, the military began to fund research on the effects of TBI on patients undergoing treatment for cancer. As we discuss, this program began in 1950 at the M. D. Anderson Hospital for Cancer Research in Houston and continued through the end of the Cincinnati research, in the early 1970s. We conclude our review with a discussion of the AEC-funded TBI research conducted at Oak Ridge between 1957 and 1974, which focused on patients with radiosensitive cancers.

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