Attachment 4 NEXT MEETING: WEDNESDAY, JUNE 25, 1952 CANCER BOARD MEETING Wednesday, May 21, 1952 Members Present: D. H.G. Bell Dr. R. Benson (for Dr. Traut) Dr. E.B. Boldrey Dr. W.L. Bostick (for Dr. Rinehart) Dr. D.M. Greenberg Dr. B.V.A. Low-Beer Dr. M.B. Shimkin Dr. R.S. Stone (Chairman) Dr. D.A. Wood Members Absent: Dr. H.B. Jones Dr. F.S. Smyth Dr. W.M. Stanley 1) Approval of Minutes: It was moved by Dr. Bell, seconded by Dr. Greenberg, and carried by the Board that the minutes of the meeting of Wednesday, April 23 be approved as circulated. 2) Reconsideration of Protocol for Experimental Procedure at Laboratory of Experimental Oncology. The Chairman requested that a member who had voted for tabling of these requests now place a motion before the board that they be reconsidered. It was so moved by Dr. Bell, seconded by Dr. Bostick, and carried. The Board agreed that Dr. Bierman be called to discuss his request for reconsideration of these procedures. a) Transplantation of Malignant Melanoma: Dr. Bierman: It is known that any given carcinoma throws off many more emboli than ever grow. Autopsy shows that cancer cells metastasize and are held in abeyance in many instances. The question arises as to the minimum number of cells necessary for growth and the conditions which may alter rate of growth. The rate of growth, rate of increase in size of transplanted tumors, and environmental conditions which affect growth are not known. This experimental procedure is aimed at finding an answer to these questions. I want to emphasize that only terminal patients will be used. Dr. Greenberg: Regardless of how this experiment might be conducted, a large variability would be expected, and to get any meaningful results would require a large series of patients, not a selected handful. Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 2 Dr. Bostick: The number of variables would be infinite. Do you expect to gain any information from this study that could not be gained from animal experimentation? Dr. Bierman: Melanomas in animals are not the same as melanomas in humans. Dr. Greenberg: Do you feel that the anticipated results are of sufficiently great value to warrant the research on humans? Dr. Bierman: Yes. Dr. Stone: Have you read the ethics of the use of human subjects in medical experiments as set up for the War Crimes Tribunal at Nuremberg? Dr. Bierman: Yes, I have. Dr. Stone: And you still feel that you want to do this? Dr. Bierman: I certainly do. I do not think this compares with Nuremberg. These patients are doomed to die of their disease and nothing known can be done for them. Perhaps this study will not do any good for the patients, but the accumulation of knowledge will eventually help people. Dr. Stone: In a study of the large number of breast cases seen at this hospital, there were found to be so many variables that only general conclusions could be drawn. I think you would have to be around here a hundred years to gain any valuable information on melanomas. Dr. Low-Beer: The questions asked haven't really been settled in animals. Why not study the spread of tumors, not just melanomas, and conditions affecting growth, in a sufficient number of animals to gain some data. Dr. Bierman: If we were to find that by changing conditions of growth we could change the number of cells necessary for growth, we would have a means for stopping early spread of lesions. Dr. Stone: Referring to point 9 in the decisions of the War Crimes Tribunal, could you bring the experiment to an end? Dr. Bierman: Yes, you could cut out the lesion. Dr. Stone: You couldn't stop the metastases. Dr. Bierman: The patient already has metastases. He is already terminal. Dr. Stone: That doesn't matter. I can't see where in any sense the experiment could fit in under the War Crimes Tribunal's or the A.M.A.'s Code of Ethics. Dr. Wood: I wonder if a somewhat comparable study couldn't be done with the Brown-Pearce carcinoma in rabbits. I would like to see something like that done before getting into anything like this, as I am not convinced that the number of cells is important in melanoma. There are well-known cases of melanoma where with a small primary, either excised or non-excised, following an apparent latent period of variable time, a shower of myriad of metastases will suddenly appear. This would imply that factors other than number of cells may be of much greater importance. Dr. Bierman: That's what I mean. You don't know the number of cells necessary of the conditions for growth. Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 3 Dr. Ball: Experiments are done every day in surgery. A surgeon is faced with a situation and does something that has not been done before. Some are successful and some not. Dr. Greenberg: But you are doing something for patients when something has to be done. There is a definite intention of helping that given patient. Dr. Stone: If there is no further discussion on this proposed experiment, we will go on the second. b) Temporary Destruction of Hematopoietic Productivity: Dr. Bierman: Many hematologists feel that leukemia resides in the hematopoietic system and is curable if the patient can be given enough x-ray to destroy the hematopoietic system. Of course that also destroys the individual. In animals it has been found that some lethal doses can be overcome by use of antibiotics and cross-transfusions, and a fair percentage will survive. It is proposed to take patients in the terminal phases of leukemia and give the first ones sublethal doses, then to others increasing doses of radiation with full doses of antibiotics, platelet transfusions, cross-transfusion if necessary - to ablate the hematopoietic system but save the individual. This is an ablation experiment. We could find out. 1) does leukemia reside in the hematopoietic system; 2) does leukemia reside in the bone marrow; 3) survival of transfused series; 4) information of radiological interest, although that does not seem to be of interest here; 5) can cross-transfusion do in man what it does in animals; 6) transfusion of splenic tissue might be of some interest from a national security point of view. Dr. Stone: I haven't changed my point of view. So long as I have control of x-ray therapy at the University of California, this will not be done. Dr. Low-Beer: I agree. Dr. Stone: I has been proven that transfusions do little good in radiation cases. So much can be done on animals that to even consider doing in on human beings is entirely beyond the sphere of common sense. Dr. Bostick: I can see one point in favor of this - philosophically - as against your melanoma proposal. The patient might possibly benefit from this, whereas in the melanoma experiment there would be no benefit, even if it worked. Has this been done on mouse leukemia? Dr. Bierman: No. Dr. Wood: I think philosophically this type of problem is acceptable, providing you can control the after effects. One is going out to destroy the hematopoietic system, which apparently is the one in the production of leukemia. I think this might have considerable merit and we might learn a lot. In view of the risks from radiation, agents such as nitrogen mustard would be preferable. I would hazard a guess that an reappearance Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 4 of hematopoietic activity would be associated with reappearance of leukemia, but that is only a guess. Dr. Bierman: Since Dr. Stone will not change his position, it doesn't matter. That settles it. Dr. Stone: Well, you could use something other than x-ray - nitrogen mustard as Dr. Wood has suggested. Dr. Bierman left the meeting. After brief discussion, it was moved by Dr. Greenberg that permission for the proposed transplantation of malignant melanoma be denied. This was seconded by Dr. Low-Beer, and carried by the Board, Dr. Shimkin not voting. Dr. Low-Beer moved that permission for temporary destruction of the hematopoietic system be denied. This was seconded by Dr. Bell and put to vote. It was decided the question put to the Board for vote was ambiguous, and the motion was declared out of order due to ambiguity. Dr. Bostick and Dr. Low-Beer commented that there was a lack of knowledge regarding animal experimentation, and suggested that recommendation be made to Dr. Bierman that a systematic study be undertaken with animals. It was also pointed out that there is no proof that cross- transfusion or other efforts are successful in saving the lives of animals exposed to lethal doses of radiation, and Dr. Stone reported that no means were found to save the scientists who were accidentally exposed to lethal doses of radiation at Los Alamos. Dr. Bell suggested that the proposal be set aside until adequate proof was available on the effects in animals. Dr. Greenberg called the attention of the Board to the ethics of the proposal, that there must be proof of effectiveness in animals before an experimentation can be tried on humans. Dr. Boldrey quoted from the minutes of the April meeting, when Dr. Jones reported that experiments on animals were not adequate to justify experiments on humans in this regard. Dr. Low-Beer moved that permission for this experiment be denied as sufficient animals data are not available to the Board. This was seconded by Dr. Bostick and carried by the Board, Dr. Shimkin not voting. 3) Review and Reconsideration of Cytology Program: Dr. Wood explained that Cytology has been a program of Dr. Traut's, supported by two grants from the U.S. Public Health Service and one from the State of California Department of Public Health. The program has interlocked with that of Dr. Farber at the County Hospital. At the present time the U.S. Public Health Service has approved one Trainee in Cytology for Dr. Farber for the coming year, and two grant applications for Dr. Traut. In addition, one grant from the California Department of Public Health has been approved. Dr. Wood reported that at the present time it is mutually agreeable with Dr. Rinehart and Dr. Traut that the Cancer Research Institute should be responsible for the program administratively rather than the Division of Obstetrics and Gynecology, as in past years, at least until such time Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 5 as it might be decided to transfer the program to Pathology, if such time ever arrives. Dr. Wood asked the Board for authority to be responsible for this program, with Dr. Traut's full approval. Dr. Benson commented that Dr. Wood had expressed Dr. Traut's opinion - that he wants to see training and research continued but feels the program is no longer a function of Gynecology and should have interest for everyone at the Medical Center. Dr. Benson asked if Dr. Moon, who will participate in the program for the coming year, would have sufficient time to accept both teaching responsibilities and the final screening of slides. Dr. Bostick commented that of all the men in the Division of Pathology, Dr. Moon would be his choice for this responsibility. It was moved by Dr. Bostick that approval be given, with Dr. Traut's permission, for transfer of the administrative responsibility for the Cytology Program to the Director of the Cancer Research Institute. This was seconded by Dr. Benson and carried by the Board. Dr. Shimkin stated that Cytology should be part of the School of Medicine program, and asked if it would be possible to have a full time appointment with tenure for Dr. Moon. An application for a senior Damon Runyon Fellowship is pending for Dr. Moon, and Dr. Shimkin commented that the physician in charge of such an important program should not be at the level of Fellow. The problem of this activity will become progressively more acute in the years immediately ahead, and an attempt should be made now to outline permanent plans. Dr. Shimkin suggested that a resolution be formulated for approval by the Cancer Board providing that: Whereas the Cytology activity is a continuing function both as to teaching and diagnosis as well as research, all proper steps be taken to set up the program on a permanent basis as a regular University function. Such would entail the development of a proper University budget for the main part of the program, to which various grants could be added as warranted by expansion of its research activities. The Board agreed to such a resolution, the wording to be clarified by Dr. Wood and Dr. Shimkin, to be submitted to the Cancer Board at its June meeting. 4) Applications for Funds: a) Dr. D.M. Greenberg: It was moved by Dr. Low-Beer, seconded by Dr. Bostick, and carried by the Board that, if funds are available, the sum of $3,500. be granted to Dr. Greenberg for support of the project "Metabolism of C14 and N15 labeled amino acids in normal and cancer-bearing animals". b) Dr. Donald R. Smith: Dr. Shimkin pointed out that the aim of this proposed experiment - "Carcinoma of the Prostate - A clinical and laboratory study" - is too broad and that Dr. Huggins has already progressed beyond the studies proposed. He also commented that bilateral adrenalectomy has been approved by the Board as a surgical procedure to be supported from the Bed Fun of the American Cancer Society Institutional Grant. It was agreed by the Board that this study might be incorporated as part of the Institutional Grant program, but no other funds were to be granted. Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 6 c) Dr. Frances Torrey: The applications of Dr. Torrey for support of the projects "Study of Biochemical Changes in Certain Proliferative Lesions of the Skin", "Study of Skin Tumors in Animals", and "Chemosurgical Therapy of Skin Cancer" were discussed briefly. It was the consensus of opinion that a histo- pathologist would be required to adequately carry out the proposed studies. It was moved by Dr. Wood, seconded by Dr. Bostick, and carried by the Board that these applications be considered at the June meeting, as they were received by the members too late for adequate study. In the meantime, it was requested that Dr. Wood and Dr. Bostick investigate the proposed research. Dr. Shimkin suggested that all applications for Cancer Board funds be considered at the June meeting, rather than whenever received throughout the year. Dr. Stone pointed out that the usefulness of these funds was due to their availability for projects as they develop. 5) New Business: a) Summer Students: Dr. Shimkin reported that he had received two applications from students to study during the summer at the Laboratory of Experimental Oncology, one student having been accepted. He reported that applications had been received from two Stanford students, and asked the Board if they would approve accepting students from other schools. Dr. Boldrey moved that the Board approve the principle of accepting students from schools other than the University of California, providing students are not available from the University of California. This proposal was agreed to the by Board. The meeting was adjourned. Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 ETHICS OF THE USE OF HUMAN SUBJECTS IN MEDICAL EXPERIMENTS as set up for the WAR CRIMES TRIBUNAL AT NUREMBERG* "The great weight of the evidence before us is to the effect that certain types of medical experiments on human beings, when kept within reasonably well-defined bounds, conform to the ethics of the medical profession generally. The protagonists of the practice of human experimentation justify their views on the basis that such experiments yield results for the good of society that are unprocurable by other methods or means of study. All agree, however, that certain basic principles must be observed in order to satisfy moral, ethical and legal concepts: "1. The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, overreaching, or other form of ulterior constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possible come from his participation in the experiment. "The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity. "2 The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature. "3. The experimental should be so designated and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problems under study that the anticipated results will justify the performance of the experiment. *An excerpt from "Doctors of Infamy", by Alexander Mitscherlich, M.D., translated by Heinz Norden. Reproduction from Special Collections, The Library, University of California, San Francisco. No portion of this material may be quoted, copied, or reproduced in any fashion without written permission from the copyright holder. 1 DOCUMENT SOURCE: University of California at San Francisco Special Collections Library, San Francisco CA RECORDS SERIES TITLE: BOLDREY, EDWIN BARKLEY, PAPERS ACCESSION NO: MSS 88-56 FILE CODE NO. CARTON NO.: 6/25 FOLDER NAME: CANCER BOARD 1951-52 NOTES: FOUND BY: ANDY MUGNIETZ 11/9/94 "4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury. "5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects. "6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment. "7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death. "8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stage of the experiment of those who conduct or engage in the experiment. "9. During the course of the experiment, the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him impossible. "10. During the course of the experiment, the scientist in charge must be prepared to terminate the experiment at any stage if he has probable cause to believe, in the exercise of good faith, superior skill, and careful judgment required of him, that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject." Reproduction from Special Colficient knowledge and comprehension of the elements of the subject matter involved as to enable him to make an understanding and enlightened decision. This latter element requires that before the acceptance of an affirmative decision by the experimental subject there should be made known to him the nature, duration, and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person which may possible come from his participation in