DOE Openness: Human Radiation Experiments: Roadmap to the Project
Early Use of TBI for Radioresistant Tumors: The Manhattan Project Experiments on Patients and the Subsequent AEC Review
Chapter 8: Early Use of TBI for Radioresistant Tumors: The Manhattan Project Experiments on Patients and the Subsequent AEC ReviewIn the early 1930s, researchers at Memorial Hospital in New York, a major cancer research center (now known as the Memorial Sloan-Kettering Cancer Research Institute) engaged in an extensive study on the medical effects of total-body irradiation. As part of this study, the researchers attempted to treat a few radioresistant carcinomas. When they published their results in 1942, they noted that "[e]xcept for transient relief of pain in a few cases, the results in generalized carcinoma cases were discouraging. The reason for this is quickly apparent. Carcinomas are much more radioresistant than the lymphomatoid tumors, and by total body irradiation the dose cannot be nearly large enough to alter these tumors appreciably." They cautioned that a cancer-killing dose "will produce deleterious reactions in the bone marrow and general metabolism which may prove lethal to the patient." The equipment used to deliver the TBI during this time was suboptimal because most of the radiation was deposited in superficial structures such as the skin and other soft tissues.
During World War II, Memorial Hospital was one of three medical institutions chosen by the Health Division of the Manhattan Project's "Metallurgical Project" to conduct TBI experiments in order to help understand the effects of radiation; the other two were the Chicago Tumor Institute and the University of California Hospital. All three studies focused on individuals with radioresistant diseases. From the limited records that are currently available, it appears that these three studies achieved little, if any, medical benefit to subjects. In addition, the interest of the military in these studies was classified and kept secret from the patients in order not to reveal the ongoing atomic bomb project.
The first experiment was carried out from 1942 to 1946 at the University of California Hospital in San Francisco to "study the effects of total-body irradiation with x-rays of varying energy on hematologically normal individuals." Twenty-nine patients were treated with total dosages ranging from 100 to 300 R (using a 250-KV machine). The investigators noted that the "treatments were administered as part of the normal therapy of these patients" and reported that "advantage was taken of the fact that patients were receiving such treatment by making numerous blood studies for the Manhattan Project." Little is known, for this and the other two studies, about the treatment of the patients or the issue of patient consent. A number of the patients in the University of California study had rheumatoid arthritis, and the use of TBI for that disease was severely criticized after the war by the Advisory Committee for Biology and Medicine of the newly formed Atomic Energy Commission (see below). In 1948 Dr. Robert Stone, chief of the Manhattan Project's Metallurgical Laboratory Health Division, noted that although "no signed consent was received from the patient . . . the treatment was explained to them by the physicians and they, in full knowledge of the facts, accepted the treatments." At the same time, however, it was admitted that "the fact that Manhattan District was interested in the effects of total body irradiation was kept a secret."
A second Manhattan Project experiment was performed from December 1942 to August 1944 at Memorial Hospital in New York by one of the researchers who had previously written that they were "discouraged" by the use of TBI for radioresistant cancers--Dr. L. F. Craver. Despite his earlier negative results, eight patients were given a total of 300 R (using a 250-KV machine), at various dose rates, in order "to yield some detectable effects on the blood count and to serve as a guide to the clinical tolerance for whole-body irradiation." The patients had to have
metastatic cancer of such an extent and distribution as to render their cases totally unsuitable for any accepted method of surgical or radiological treatment, yet . . . be in good enough general condition so that they might be expected not only to tolerate the exposure to 300 R of total-body irradiation in a period of ten to thirty days, but also to survive the combined effects of their disease and the irradiation for at least six months in order that some conclusions might be drawn as to the later effects of the irradiation.
The report on this experiment makes clear that the primary purpose of this TBI was to obtain data for the military. Dr. Craver essentially acknowledged that there was little prospect of actual medical benefit to the patients in light of the previous failure using the same procedure.
A third TBI study involving fourteen people was performed at the Chicago Tumor Clinic from March 1943 to November 1944; doses up to 120 R were given with a 250-KV machine. None of these individuals had radiosensitive cancers. The use of TBI was justified by the investigators because there were no known treatments for their illnesses, and therefore, "x-ray exposures that were given were as likely to benefit the patient as any other known type of treatment, or perhaps even more likely than any other." This study appears to be the only TBI study that included healthy subjects: three "normals" were each given three doses of 7 R.
After the war, Dr. Stone took on the task of editing an official history of the experiments done for the plutonium project. At one point, he complained to Dr. Shields Warren, chief of the AEC's Division of Biology and Medicine (DBM), that declassifiers were withholding the report of the Chicago TBI experiment on grounds that its release would cause "adverse publicity and even encourage litigation." Stone proposed to solve the problems by carefully rewording the report. The report would make clear that the patients were suffering from incurable illnesses for which radiation was as good, if not better than, any other known treatment. Stone then proposed to deflect the likelihood of adverse publicity or litigation by deleting identifying information so that the patients could never "connect themselves up with the report." The study was declassified and published in the form that Stone proposed.
At about the same time in the fall of 1948, Dr. Alan Gregg, chairman of the AECs Advisory Committee for Biology and Medicine (ACBM), engaged Stone in an exchange regarding the Manhattan Project TBI experiment on the arthritic patients at the University of California Hospital. Stone, who by this time had returned to the staff of the UC Hospital, had requested funding to monitor these arthritic patients. Gregg told Stone that "I think that I do not misrepresent the opinion of the Advisory Committee [for Biology and Medicine] in saying that we agree with those who believe the x-ray treatment of arthritic patients you have been giving patients is not justified." (Despite Dr. Gregg's concerns, the role of TBI in the treatment of benign autoimmune diseases such as rheumatoid arthritis continues to be explored today.) Gregg stated that the AEC had an obligation to provide a check on overly enthusiastic researchers. While admitting that a conservative consensus against certain treatments is not always correct, Gregg cautioned that "there is plenty of experience that shows that some forms of therapy attract enthusiastic supporters only to be discarded later as unsafe or unjustified."
In response, Stone acknowledged that the military's need for worker safety information during the war was a primary motivation for choosing patients with nonradiosensitive carcinomas and some benign disorders such as arthritis. "At that time I was confronted with the problem of building up the morale of the workers on the new atomic bomb project, many of whom were seriously worried about the effects of prolonged whole body irradiation." But he countered that he and the other researchers did believe that the total-body irradiation would be therapeutic. Moreover, Stone retorted, Gregg's statements threatened researcher and doctor freedom: "Wittingly or otherwise you have dictated how I should treat patients even outside of the Atomic Energy Commission's supported activities." Stone's declaration marked a boundary that government officials (including Stone's fellow medical researchers) would not be eager to cross.