EXCERPTS FROM TRANSCRIPTS OF MEETINGS OF COMMITTEE ON MEDICAL SCIENCES OF RESEARCH AND DEVELOPMENT BOARD, DEPARTMENT OF DEFENSE, 1950 DEPARTMENT OF DEFENSE Research and Development Board Washington, D.C. Committee on Medical Sciences 31 January 1 February 1950 at 9:30 a.m. in Room 3-1065 Pentagon, Washington, D.C. Conference Reporting Section Reported By: Martin, Selby, & Gasdor Extension 73252 Room 3D-1051 up how, and of course, the big block is determining how much, if any, human experimentation can be included to get these answers and that is going pretty high in certain levels to find that out. It has been discussed a lot in my groups, this same problem. DR. BLAKE: Two paragraphs in this report bear on this question. One is on Page 6 down at the bottom, 2.1 talks abut deficiencies at present. 2.1: "Lack of data to permit evaluation of sublethal radiation dosages and affects in human." And then on Page 10 in their Recommendations, 4.1.3: "The most essential aspect of research in the individual and collective protection should be emphasized. This will entail an intensification of efforts toward assessing the severity of radiation effects as against dose for critical biological responses including the initiation of human studies." COL. BOWER: Well, I have asked what should we do about it from a military standpoint. You can do it the human, or should you do it, the other research. DR. BLAKE: Of course, this does not exclude animal studies as expressed, does it? It says "including the initiation of human studies." You will recall that at our last meeting as recorded in the minutes, we took this action: endorsed the action of the Joint Panel on Medical Aspects of Atomic Warfare at its second meeting 7 October 1949, in approving the recommendations of the ILLEGIBLE Medical Advisory Committee with regard to human experimentation, both in principle and according to 60 suggested protocol for human studies through the stipulation that other phases in the medical aspects of atomic warfare should not receive any less emphasis because of the Committee action on this matter." And you are asking, really, should more emphasis be put on animal or human experimentation or should they both go on simultaneously and what is the most rapid way of getting the answer? DR. FENN: Mr. Chairman, I'd like to say a word about human experimentation because I have a feeling that is a very dangerous route to get started on and that we shouldn't sanction human experimentation without careful consideration. I think we passed it over too lightly once before. I think we will get the information that is required from animals, animal experimentation and accidental exposure and shouldn't approve routine experimentation on volunteers. I'd like to hear some discussion about it. GEN. ARMSTRONG: I don't believe we can adopt that stand because if we do it for that we should do it for all areas of research, and certainly, many of our valuable findings in the past have been based on volunteer human experimentation. I think that the actual research should be evaluated in each individual case and certainly given every possible safeguard but if we go on record as being opposed to human research experimentation in this field we should apply it, I believe, to all fields. DR. FENN: I wouldn't make it quite as broad as that. I'd qualify that a little. GEN. ARMSTRONG: I don't see there is any great differences in principal in undertaking a hazardous procedures. It seems to me it doesn't make such difference whether it's an atomic energy 61 or using an ejection set at ILLEGIBLE miles an hour. They are both likely to kill you, and I don't see any particular reason why we should include any area, or if you include one you must include them all. I don't see where you should make any distinction. DR. BLAKE: In individual cases it comes down to assessment of risk, doesn't it? GEN. ARMSTRONG: That right. I certainly don't think we should advocate wide-spread and superficial plunging into this thing by any means, but I don't think we can solve that by simply saying we are not in favor of any human experimentation. DR. FENN: I wouldn't say that, but in most cases where you engage in human experimentation the experimenter volunteers to be a subject and that is a totally different thing. If it is an experiment where you volunteer yourself and have served a subject like ejection seat or even decompression sickness or exposure, the experimenter always serves as a subject himself to my knowledge. Now this, as I understand it, you are proposing to use people who perhaps are prisoners, or holding out some sort of reward to them, and it is a type of experiment in which the experimenter would not expose himself. What makes it just a little bit different from my point of view. I certainly wouldn't make that a blanket rule against human experimentation but it is using somebody who is a volunteer because he is a prisoner and because he expects to get something out of it. The experimenter knows that we wouldn't volunteer himself. I think that is quite a different picture. 62 DR. TOPPING: Mr. Chairman, I'd like to hear Dr. Coggeshall's opinion. He's an old hand at working with human volunteers in various ways. DR. COGGESHALL: Well, as Dr. Fenn pointed out, whenever you say the word "volunteer" if you read on two or more sentences you see the work "prisoners at such and such a prison", etc., and I'd share Dr. Fenn's point of view. For example, in malaria research programs a great many human volunteers are used. Now as an example of what Dr. Fenn pointed out, again, the young Army doctor there not only gives himself malaria but he took the new drug and it was calculated risk, and I think that is all right, but it seems to me there are two points in this that are the unknowns, the using of human subjects for investigation. I'd prefer to change the word "investigation" to "experiment", although I think that this correction "experiment" is a little more descriptive, that calculated risks are such that I doubt if you are justified. How the second point is, it seems to me that the Military, the Departments of the Army, Navy and Air Force, are in the weakest position in that connection because you are prohibited from doing certain things that we on the outside can do; that there is a vast amount of human investigation going on in the Military Services but all of it, I think can be shown to be of some value to the man. That could not be under any stretch of the imagination, and I certainly would not be opposed to human investigation, but I think in this connection I would have many reservations about it because the risk is not a calculated one, especially for diagnosis, and I don't think you would ever use military subjects for this or justify it by any argument that you could present. 63 DR. BLAKE: One can see there are plenty of examples in which human experimentation could not in any sense have been correct and of value to the individual. To quote you, I think the man who get the malaria might have been considered to obtain any value from having malaria. The same thing is true of the work on infectious hepatitis. You can see that the results might be of value to the human race in general. DR. COGGESHALL: No, I am taking exception to that because in the Services only the men, the investigators, as far as malaria was concerned, were given the drugs, new drugs admittedly that they were shown to be of benefit to them. DR. BLAKE: That doesn't apply to prisoners. DR. COGGESHALL: That doesn't apply to prisoners because there is a difference between prisoners and military and civilians. You do not given malaria to any subject in the Armed Forces. You couldn't get away with that. I want to make that distinction between the two. COL. WOOD: Mr. Chairman, I think one other distinction could be made here. We face this problem all the time in experimentation with chemical warfare. We do not feel that you can ever justify human experimentation where you can reasonably expect irreversible injury, life-long lasting injury. We more or less hesitate to undertake any part of human experimentation of any short duration. In other words, we are ready to take considerable risk with acute short-lived experimentation, but not willing to undertake essentially 64 any risks where we think there will be amazing injury the rest of a man's life. Now in this radiation field, we simply don't now where irreversible injury begins. It might be an injury that cuts off the last years of a man's life and that simply isn't know whether we will investigate a remote ILLEGIBLE or shorten his life at the distal end, and until we know a little more about that it seems to me we are quite unsafe in recommending human experimentation. COL. BOWER: Colonel Wood expressed the opinion of many people who have spoken on this, that there is the problem of damaging the lower grade tolerances, but for the military aspects to tell the staff what they want to know within the next five years, the answers perhaps would best come from animal work, and transferred to the human. How you might only be able to tell the Commander: "Well, your casualties will be between 15 and 30%, but you can't get down and say between 15 and ILLEGIBLE, but that is the whole principle they operate on, relative crude estimates of what they are going into, just so they know approximately. That is what they seem to have been asking of us. DR. LOCKWOOD: What is the attitude of this question in the Medical Biological Division of the ILLEGIBLE? DR. COGGESHALL: I think it is just like we are discussing right now. COL. WOOD: Up to now they have not said. DR. COGGESHALL: They have not said. It is still under consideration. DR. FENN: I talked with Dr. Warren and he agreed with me. 65 DEPARTMENT OF DEFENSE Research and Development Board Washington, D.C. Committee on Medical Sciences Transcript of Meeting Held on 23 May 1950 in Room 3E1065, The Pentagon Washington, D.C. Reporters: Marjorie R. Martin Pages 1-99, Inclusive Mary Selby - Pages 100-193, Inclusive Conference Reporting Section Reported By: Martin & Selby Extension 73252 Room 3E-115 take a large number of prisoners and say that is sufficient. You have to get a sufficient level and follow them over a period of 20 years and particularly where you have this repeated business on small dosage, and not get into a lot of trouble. I think we will get into a lot of trouble, anyway, but why ask for it by way of experiment? DR. BLAKE: I take it the Panel, if I read their report here correctly, is thinking in terms of acute single doses and not in terms of multiple doses. I mean, our Panel, not the NEEPA panel, and I am not sure that we are expected or concerned with approving all the details of the experiment by NEEPA, but the general principles as set forth in this recommendation adopted by NEEPA Advisory Committee April 3, 1949, which has not specified any of the details. COL. STONE: Well, I think we'd be perfectly safe if we passed a resolution saying that we did need this information, but I think it would be unsound to refer to the NEEPA recommendations as such, because they do contain a lot of them. I think they could be certainly used in setting up the experiment, but that should be very carefully gone into before action has been decided. ADM. GREAVES: Is the proposition to reach some decision so that Dr. Meiling's office will know what action to take? Is that the proposition? 8 DR. BLAKE: Well, as I understand it, Dr. Meiling's office want to know the position of this Committee with respect to human, the principal of human experimentation. COL. STONE: [Off the Record] ADM. GREAVES: I agree with Colonel Stone in that there certainly is a need for this type of information, particularly in view of the fact that we are going to be confronted with the problem of protecting personnel, not only in airplanes, but also in submarines, of this type of thing. It is information that is virtually needed, for future advances in those two fields. Whether this information can be acquired through studying of records in patients who are being treated with evacuary (?) therapy in one form or another for one pathological condition or another. I am not sure that we get that information because we are starting off with an individual who is not, probably not well, anyhow, and there is that question. But this is a long- range thing, and people who have types of diseases in which it is necessary to give them x-ray therapy may not be with us long enough to make the information we get valid. COL. STONE: Admiral Greaves, I'd like to point out from the Army's viewpoint, at least, the levels that we are particularly interested in are those of relatively short duration. 9 In other words, a many may develop a cancer 20 years later but if he is in the middle of combat we don't think that would deter from actually something, so that what we are interested in is what level is going to make this man sick or noneffective within a period of 30 days, in all probability. Now we are very much interested in long-term effects but when you start thinking militarily of this, if men are going out on these missions anyway, a high percentage is not coming back, the fact that you may get cancer 20 years later is just of no significance to us. DR. COGGESHALL: What about the other way around? Do you believe you can get answers from people subjected to radiation therapy usually by reason of neoplastic disorders. COL. STONE: I think it would have to be a selective study. For instance, take any of our big centers where we have quite a lot of cases of carcinomas; (you can't pick lymphomas, but carcinomous types of metastesis) a number of those individuals will live in varied states of health from a period of six to eight months and x-ray therapy was indicated in epilating measures, and I think when we study our material on the population in Japan, plus our combined animal work, then we might logically 10 draw up a series of bracketing experiments in which you probably get 30 to 50 such cases in a hospital like Memorial Hospital, for instance, in New York or certain hospitals in other cities, by carefully selecting the cases and getting the amount of radiation for that bracket we might be able to get a very satisfactory answer. ADM. GREAVES: I agree with that absolutely. We could use information from whatever source, but I am wondering if we are not being a little too skiddish about this. We have a problem on our hands and I think we should consider it very seriously, but whether it is enough of a problem to go ahead and take a chance..... COL. STONE: Well, we think it is a problem, all right, and certainly willing to take a chance on this thing. It is a question about where you are going to get the best information in the most scientific manner. For instance, on long-term effects of cancer, we are sponsoring some two and a half million dollars a year. I am speaking Governmental-wise in Japan, just following up those people from the bombings. So we actually have a bracket, there, of individuals who had an epilating dose of radiation from the atomic bomb so that I think that we are not completely at a loss to determine what the long-term effects would be. 11 DR. COGGESHALL: Well, I was exposed to the risk made on that human experimentation, human investigation, on the basis of the information we had at that time. I must say that if these people that wish to do this are willing to subject themselves to the same type of experimentation I am less hopeful than I was before. I think there will always be a gap in methods of obtaining information between the Nagasaki skin cancer therapy and animal work, I think there is that gap that you just can't bridge, just can't decide by Committee action. DR. FENN: Mr. Chairman, is it really contemplated that the experimenters will subject themselves to the same experiments or will they...... DR. BLAKE: That was inferred in the NEEPA proposal, but it the last sentence in our Panel report, then..... DR. FENN: I think that is certainly very important to know the precise threshold that you are going to do, and find out the number of experiments, and all that you are going to find out is there is no precise threshold. It may get a few volunteers and you get a certain threshold, but it won't be a precise one. I question, myself, whether the end is going to justify the means. We certainly ought to do every other method until we are absolutely certain it can't give us any information. I think the 17 important thing is whether you take the decision to go down this road of human experimentation and work on prisoners, even though they are volunteers, and start the idea that as long as they are prisoners it really doesn't matter very much what you do to them, and it is no great loss to society, which I think it isn't, but it is a bad decision. DR. COGGESHALL: I's say, in comment on this, they are already down this road. There is quite of bit of human utilization of prisoners, of one type or another. It seems to me it differs only in the type of work they propose to do, not in the opinions of the thing. That doesn't make it right, necessarily, but..... ADM. GREAVES: I think that the reasoning behind the proposal to use prisoners was that they are long-term prisoners and that they would be available for observation and study. I don't think the reason for the proposal to use prisoners is because they were prisoners to society, or little use to society. The reason was that they would be there and you can put your finger on them and observe them for a long period of time. That isn't true of volunteers from the rest of the world, either Armed Forces or otherwise. They are here maybe this year and gone next. You lose track of them. This is a long-term thing. 18 DEPARTMENT OF DEFENSE Research and Development Board Washington, D.C. Committee on Medical Sciences Transcript of Thirteenth Meeting Held on 28-29 November 1950 in Room 3E 1060, The Pentagon Washington, D.C. Reported by: Lloyd Haynes Mary Selby Marjorie Martin Josephine Felton Conference Reporting Section Reported By: __________________ Extension 73252 Room 3E-115 1,2,3 1 3 OCRD 43343 2 3 A&A (R&D) Lt Col C. W. Cook Beta Hazard Experiment Using Volun- CRD/N teer Military Personnel PURPOSE To obtain the approval of the Secretary of the Army to use volunteer subjects in research involving nuclear radiation. DISCUSSION 1. Army Regulations 70-25 require the consent of the Secretary of the Army for research wherein volunteer subjects will be deliberately exposed to nuclear radiation. These regulations further provide that Chief of Research and Development will submit the research proposal together with the review and recommendations of The Surgeon General to the Secretary of the Army for approval. 2. The U.S. Army Nuclear Defense Laboratory has requested approval of an experiment to determine the military significance of the beta radiation hazard under field clothing contaminated with radioactivity. (Incl 1) In spite of the theoretical studies made of this problem and the large amount of data obtained from nuclear testing, insufficient data is available to make a definitive determination of the hazard. There is wide disagreement among authorities on the subject. Opinions range from the belief that no hazard exists to the belief that a serious risk to health is involved. 3. The proposed experiment to be conducted at the U.S. Army Nuclear Defense Laboratory Field Facility, ILLEGIBLE McCoy, Wisconsin, beginning on 22 april 1963, will involve 12 volunteer enlisted men. They will be exposed to a whole body radiation dose not to exceed 3 ILLEGIBLE during a period of five days. This does not exceed that permitted by Code of Federal Regulations, Title 10, Chapter 20, "Standards for Protection Against Ionizing Radiation." The project officer will be Mr. John L. Meredity, MDL, and the attending physician will be Colonel Louise E. Browning, MC, CTSG. 4. The Surgeon General has reviewed the research proposal and recommends approval (1st Ind of Incl 1). RECOMMENDATION: That the Secretary of the Army give his consent to conduct the subject research and sign the attached memorandum (Incl 2). COORDINATION: None required. 2 Incl 1. 1st Inc. 15 Apr 63 fr OTSG, w/incl 2. Memo for sig of S/A crash injury project, two crash injury projects. Those, I think, are the only comments I have concerning implementation of action, and the minutes have been circulated. Do I hear a motion of approval? DR. MCLEAN: I so move. DR. BLAKE: It has been moved and seconded that the minutes of the 12th meeting be approved. All those in favor say "Aye." Opposed? Carried. The second item is "Report on Panel Activities." The panels have met during the last month and a half, their reports of their meetings and recommendations have been provided for you. I regret that time did not permit mailing out two of the panel reports, but it was impossible to schedule them in time. There are certain items in these panel reports that need to be noted, or require some action by the Committee apart from the program guidance recommendations and the supplemental FY 1951 budget review to be taken under items 4 and 5, so will pass over these panel reports at the present moment. We come to the panel report on Medical Aspects of Atomic Warfare. You will note on page 6, paragraph "f", the item dealing with human experimentation which is still in the stage of negotiation, and I'd like to ask Dr. McLean as representing that panel to bring us up to date on the situation. DR. MCLEAN: I understand that this question has been before this Committee twice before and the second time received 3 approval of this Committee and was passed on up to the Department of Defense. The Department of Defense referred it back to the Division of Biology of Medicine of the Atomic Energy Commission for opinion, and the opinion that was given was unfavorable. As a result, the proposal for these observations on man did not re- ceive approval, but was referred back to the Panel on Medical Aspects of Atomic Warfare. It was following this that the action recorded on page 6 was taken. Those actions were, first: "The panel approved by majority vote a motion expressing its desire to continue efforts to secure approval for human experimentation; and (2) appointed a working group consisting of representatives of the three Services to devise ways and means of presenting the views of the panel to proper authorities in order to secure approval for initiation of the program." I understand informally that this group led by General Cooney has done a good deal of work on this subject: they have been to Dr. Meiling, and they have also, I think consulted the Surgeons General; and finally, I believe that they have gone to--General Cooney went before the Advisory Committee on Biology and Medicine of the Atomic Energy Commission in order to attempt to get the concurrence of that group. The result of that I believe is that the Medical Advisory Committee is now taking this matter under advisement and they will report back to General Cooney some time later as to what their position will be with respect to the matter. In the meantime, no work is under way. It might be 4 said also that in addition to the military services, the United States Public Health Service has indicated a desire to, and willingness to undertake this work, but that has not yet received approval; and apparently it is necessary and desirable that all the Services, the Department of Defense and the Division of Biology and Medicine of th Atomic Energy Commission agree before any work is to be undertaken. They have already spent a great many man-hours in...in discussing this question, I take it you do not want to get in any medical discussion in this meeting. DR. BLAKE: No, I think the action of the panel and the indorsement of the Committee in its vote at the last meeting express our current views; and as I understand it from your report it is now really resting in the hands of the Medical Advisory Committee of the AEC, to come back with their report to General Cooney and your working committee and the Surgeons General; so that the matter at least is not dead, and perhaps it is making a little progress. Is there any questions any of you would like to ask? ADM. GREAVES: May I interpose a statement? I attended the meeting of the Medical Sciences group of the AEC at the time General Cooney presented his views, and I think that what--the way I understood it, that they were going to again canvass the leaders in radiology and see if they could come up with some sort of an agreement among them as to what would the be safe exposure dosage. As it stands now, the answers that they get are anyplace 5 from 21R to 600R. DR. BLAKE: There has been no previous agreement on the canvasses of opinion has there? ADM. GREAVES: That's right. DR. BLAKE: And they will probably come out with the same finding that there is no agreement. We might emphasize the fact that we need some scientific data. ADM. GREAVES: That's what they've been trying to do to see if they can't get together on it. DR. BLAKE: Are there any other questions? COL. WOOD: Dr. Blake is there anything that prohibits us from doing it? I don't believe there is. DR. BLAKE: Well, you would have to, I think, get pretty high top level agreement and approval before it could be initiated. Wouldn't you? COL. WOOD: No, I don't think so. I think that is the point in error here. Because actually when you take a subject of this type and put it up for top level agreement on human experimentation, then that throws open the whole problem, particularly at political levels where human experimentation has to be agreed upon. Now we all know that as far as our studies in medicine and the allied sciences that human participation in the experimental work is subjects that has been right straight through; and actually, I think we are in error in bringing the subject up. I think we would go ahead and do the work and not talk about it. Because we have the previous 6 decision, not by this Committee, but in one of the sister committees, that in Biological Warfare the subject was brought up and referred to the Combined Chiefs of Staff finally and the political decision was handed back that you couldn't do it. Now unquestionably if the same subject comes up at a political level you are going to get the same answer every time. No political side of it will ever agree to it. I take the instructions there is nothing that prohibits it. It's done entirely on a voluntary basis and we are very careful to live up the ethical side of the voluntary basis as laid down by the American Medical Association and the Associations of the various scientific fields that have passed upon this subject that there is no real disagreement and it depends on the individual investigator to stay within those bounds. DR. BLAKE: I take it is your view, and Dr. Shilling concurs by bobbing his head, that you would feel, then, in planning your development and research programs, if you so desired your could go ahead with it. COL. WOOD: I think so. DR. BLAKE: A proposal for a project. COL. WOOD: That's right. CAPT. SHILLING: Legally, we have to get it, we have to get the approval of the Secretary of the Navy. ADM. GREAVES: Before we can use... CAPT. SHILLING: Human subjects. ADM. GREAVES: No, Naval personnel. 7 CAPT. SHILLING: Naval personnel--that is correct. But we don't have to do that if we don't use Naval personnel, legally. ADM. GREAVES: Well, I think that is fine; that is a good way to look at it, except it has already been brought up, you see, and Dr. Shields Warren took a very firm stand on the matter in his meeting. I don't know. I don't see any reasons why this experimentation of human beings is radiology should be different than it is when you study typhoid fever, you use human beings for various tests in infectious diseases and everybody gets scared to death of radiology. COL. WOOD: How many of them do you think would agree to heart catheterization if you had put it up to them? CAPT. SHILLING: That's right, at the political level. DR. BLAKE: Well, perhaps, really no action is needed here in this committee at this time. We are glad to have those views. The Committee may see a project some time. There is a second item on page 7, in the report of the panel on the Medical Aspects of Atomic Warfare, with a specific recommendation, it starts on the bottom of page 6, "Utilization of Catastrophes to Study Mass Handling of Casualties", the recom- mendation is, and this is the second time I think it has come before us, "...that there be established several cooperative teams composed of the three military branches, with respect for cooperation of the U.S. Public Health Service, and civilian surgical personnel for long term tenure of at least three years, and that the Department 8