Attachment 4 Telegram from Dr. Shields Warren to Dr. John Lawrence (dated January 13, 1949) and letter dated January 22, 1949. ROCHESTER NY JAN 13 1949 405P DR JOHN H LAWRENCE RADIATIONA LAB DIV OF MEDICAL PHYSICS UNIV CALIF BERKELEY CALIF REGARDING PROPOSAL, BELIEVE INADVISABLE DUE TO REFUSAL OF SIMILAR REQUESTS IN RELATED FIELDS BY RADIOISOTOPE COMMITTEE, AND INADEQUATE ANIMAL DATA. HAVE DISCUSSED WITH GOFMAN, WHO WILL RELAY INFORMATION TO YOU. REGRET DECISION. DO NOT WISH TO RESTRICT CONTRACTORS BUT MUST APPLY SAME PROCEDURE AND SAFETY CONSIDERATION TO ALL. FURTHER ANIMAL DATA ON THIS DESIRABLE. SHIELDS WAREN MD 155P(XXXX (155P) PLS ACK R WU A 73 RE TNX.... 22 January 1949 Dr. John H. Lawrence University of California Donner Laboratory Berkeley 4, California Dear John: In explanation of my telegram to you on the use of carbon14 in the form of stilbamidine, the Subcommittee on Human Applications has been very reluctant as yet to approve use of carbon14 in humans. They have turned down a number of requests, some involving quantities of carbon14 similar to the amount in your request. I felt it would be unwise in light of this to have them approve your application in spite of the fact that, as you state, there is no danger in this particular instance. Whenever possible, I think it is best for the Subcommittee on Human Applications to operate on the basis of fairly broad principles, and when it is prepared to make an alteration policy to make it all across the board. One factor that influenced me a little also is that the cases with multiple myeloma are fairly frequent and when and if the Subcommittee liberalized its policy with regard to carbon14, it would be not too difficult to get an adequate supply of clinical material. Sincerely yours, Shields Warren, M. D. Director, Division of Biology and Medicine SW:NF I. Review of the minutes of the last meeting, March 22, 23, 1948. A. Consideration of use of radioisotopes in tracer studies in normal adult humans. The following remarks apply to beta and gamma emitters with a biological half-life of 20 days or less. These remarks are for general guidance but the Subcommittee on Human Applications will examine each case on its own merits. Applicants who desire to use radioisotopes in normal adults should submit the results of animal experiments, or adequate references to the literature, concerning the following points. 1. Metabolism and distribution of the radiomaterial in the form administered. 2. The tissue of highest concentration and the relative concentration therein. 3. The relative concentrations in the tissue of interest and particularly radiosensitive tissues such as the gonads and hematopoietic system. 4. The biological half-life of the radioisotope in the tissue of highest concentration, the tissue of interest and the particularly radiosensitive tissues. All tracer studies in normal humans must be approved by the local Radioisotopes Committee before consideration of the Application will be made by the Subcommittee on Human Applications. The above statements apply to both Atomic Energy Commission and other installations. B. Applications for use of radioisotopes in normal children will be given special scrutiny by the Subcommittee on Human Applications. C. Review of Policy with regard to long-lived radioisotopes. 1. In general, for isotopes with a biological half-life greater than 20 days, the dosage in the critical tissues should be such as to conform to the limitations stated by the National Committee on Radiation Protection. In special cases, however, the Subcommittee on Human Applications may permit the use of radioisotopes in higher dosages. 2. The Subcommittee on Human Applications feels that each request for use of a long-lived radioisotope in human subjects must be reviewed separately. 3. In the minutes of the initial meeting of the Interim Advisory Committee on Isotope Distribution Policy, held June 28, 1946, at Oak Ridge, the following statement appears on page 9. "Carbon 14. The Opinion was generally expressed that, even though the scarcity of C 14 is a major factor to be considered, the use of this material in a human being should not be sanctioned until its absorption and elimination properties is clearly demonstrated in animals. The very long half-life of the material makes caution desirable." The Subcommittee on Human Applications feels that, in view of recently accumulated information, it is prepared to consider applications for use of certain C 14 compounds in humans. In arriving at this conclusion, the following papers were considered: