TAB C DRAFT FOR DISCUSSION PURPOSES ONLY MEMORANDUM TO: Members of the Knoxville Small Panel FROM: Advisory Committee Staff DATE: May 19, 1995 RE: Gallium Experiments at Atomic Energy Commission (AEC) Facility, Oak Ridge Institute of Nuclear Studies (ORINS) The ORINS research program's response to the public's interest in cancer research centered on "investigating the use of short-lived (that meant [less than] 14 days) radionuclides in cancer therapy." (1) A central part of the radioisotopes research was an inquiry into the potential uses and toxic limits of Gallium-72. Gallium was originally identified as a possible reactor coolant, and in the resulting toxicological studies was found to concentrate where new bone was being formed.(2) As one of the researchers noted afterwards: Ga-72, as a therapeutic agent for osteogenic sarcoma, was the first program that really fit the Medical Division's reason for existence. . . . We chose to study only patients with an osteogenic sarcoma in a leg and metastases to the lung. (In 1950 all such patients died within a few months.(3) The researchers administered gallium in doses they hoped would be therapeutic to a group of twenty-one patients with advanced tumors, for whom prior therapies had failed. Gallium was also given in test doses to thirty-four other patients with various types of cancer. Both the distribution of the element and the absorption patterns of radiation were studied. The researchers identified both chemical and radiological toxic effects and concluded that: "Superimposed in already debilitated tissues, [gallium's chemistry and radioactivity] are sufficient to make supposed therapeutic doses lethal." (4) The choice of words was careful, because these doctors had reported in a companion article (attached), "Clinical Studies with Gallium-72" that: [i]n the 'therapeutic' group, doses which were believed to be moderate were given and gradually increased to a toxic level. In two patients our estimates of safe dosage were in error and the radio-gallium is believed to have hastened death.(5) Preliminary calculations and small animal experiments had left the question of toxic dosage levels open. The patients receiving gallium therapy also suffered from side effects including anorexia, nausea, vomiting, and severe mental depression. "There is uniformly very serious bone marrow depression." (6) No similar side effects on the patients in the tracer group study are reported. This research program was reported in unclassified AEC documents and in open scientific literature. The patient deaths in the gallium experimental program were reported in Radiology. No previously secret aspects of the gallium research program have been identified. However, there is no recorded reaction to the deaths of any of the retrieved surviving documentation from the various bodies responsible for overseeing ORINS research at the Oak Ridge Cancer Hospital. The deaths are not discussed in reports to the AEC, or in documents from the program reviews for ORINS conducted by the Advisory Committee on Biology and Medicine. An ORINS report says that the comprehensive reports (later published as the Radiology articles just discussed) had been provided to the Human Use Subcommittee of the AEC's Isotope Licensing organization, but no reaction from that body has yet been identified.(7) Moreover, the records from this research which have been located do not identify any of the then-known risks from gallium therapy as having been disclosed to ORINS patients. Such patients with advanced cancer may well have consented to the risks of gallium as a last-chance, heroic therapy, had those risks been disclosed to them. But the evidence available does not show whether they were afforded that opportunity. The contrast between the silence surrounding this episode and the strong official reaction to other misadventures leading to radiation injuries is striking. The accidents at Los Alamos helped to shape wartime and post-war research in plutonium and other elements. A later accident at Oak Ridge, without immediate fatalities, nevertheless stimulated both the TBI research subsequently conducted at Oak Ridge, and other work at Oak Ridge and elsewhere. 1. Brucer, Chronology of Nuclear Medicine, p.279. 2. Stannard, Radioactivity and Health: A History (1988), p.1766. 3. Brucer, Chronology, p.280. 4. Vol. 61 Radiology 1953, "A Study of Gallium" 534, 536 5. Vol. 61 Radiology 570, 571 (1953) 6. 1950-51 Progress Report at 17. 7. Sixth Annual Report of the Oak Ridge Institute of Nuclear Studies, June 30, 1952, at 12.