ATTACHMENT B Letter dated October 20, 1948 from Dr. Alan Gregg, Chairman of the AEC Advisory Committee on Biology and Medicine to Dr. Robert S. Stone at the University of California Hospital; Letter dated November 4, 1948 from Dr. Stone to Dr. Gregg. [We apologize for the quality of the copies; these are the best available.] October 20, 1948 Dear Doctor Stone: The secrecy with which some of the work of the Atomic Energy Commission has to be conducted creates special conditions for the clinical aspects of its work in that the public is aware of this necessity for secrecy and of the consequent difficulty of probing into it. This situation makes the Advisory Committee on Medicine and Biology concerned to a unique degree with the measure of confidence it can place in the judgment of the clinicians and medical scientists who carry on treatment of patients by means of any substances or facilities provided by the A. E. C. I think that I do not misinterpret the opinion of the Advisory Committee in saying that we agree with those who believe the x-ray treatment of arthritic patients you have been giving patients is not justified, and that they do not wish to collaborate in clinical investigations with physicians in whose considered judgment they do not have confidence. When you explain as in your letter to Dr. Harmon of July 26 that the selection of patients, the administration of the treatment, and the responsibility for it are not a part of the Atomic Energy Commission's activities, but are activities of the staff members of the University of California Hospital, acting in their capacity as individual doctors, you apparently miss a point to which I would like to draw your attention. The point is that you misunderstood the reasons for our concern. Our view is that we have no right to compromise with fears you have not allayed. This is a matter serious enough in my opinion to justify some further comment. In the first place past experience shows that unfavorable views of new forms of treatment have not always been right merely because they have been conservative. Granted. But on the other hand, there is plenty of experience that shows that some forms of therapy attract enthusiastic supporters only to be discarded later as unsafe or unjustified. Neither of these facts relieve the Advisory Committee from the duty of forming an opinion of a procedure that you consider to be the responsibility of the staff members of the University of California Hospital. Very obviously the Advisory Committee on Medicine and Biology has no obligation to do more than decide what persons it considers to have good clinical judgment as a basis for its recommendations to the A. E. C. If this letter seems to you to go beyond that obligation, please charge it against me personally as unnecessary candor for I would prefer that charge to many other causes for resentment. If you are not quite aware of the fact that your letter of July 26 has put you a long way toward losing the Committee's confidence I would not feel that I had treated you as I would want to be treated, if I did not tell you so. If that loss seems to you of minor importance relative to your own freedom to treat patients as you and your colleagues think best, then there is an honest difference of opinion. The Committee would feel, I think, that it is a difference that will prevent such further developments under your direction as depend upon our confidence in your clinical judgment. Under such circumstances you and I could report the situation to Dean Smyth since the University of California Hospital deserves an equally free and informed choice of its course of action. I hope that conclusions on our side as well as yours will be arrived at patiently and carefully with full comprehension of the other's sense of responsibility and of the special circumstances in which this responsibility takes on unusual importance. Yours sincerely, Alan Gregg, M.D., Chairman Advisory Committee on Biology and Medicine U. S. Atomic Energy Commission November 4, 1948 Alan Gregg, M.D., Chairman Advisory Committee on Biology and Medicine U. S. Atomic Energy Commission Room 5500 49 West 49th Street New York 20, N. Y. Dear Doctor Gregg: The candor of your letter of October 20th is much appreciated. I assume that you want the same candor from me. Let me assure you that I am writing this reply with a full comprehension of the sense of responsibility that we must all share. The solution of the biological problems created by the use of nuclear energy in peace and war, is a national - if not a universal - responsibility. While that responsibility is in one sense focussed on you and your Committee, none of us should attempt to evade it. Your letter appears to me to contain such serious implications to science and to make such direct charges against my colleagues and myself that I believe it is not a matter to be discussed solely between the two of us. I am therefore sending copies of my letter of July 26 to Doctor Warren, of your letter of October 20 to me and of this reply, to each member of your Committee, to Drs. Shields Warren and Carroll Wilson and to Dean Smyth. The discussions in these letters can be summarized for convenience. After your visit to our hospital last spring, Doctor Warren wrote that your Committee and he himself did not approve of treating patients afflicted with rheumatoid arthritis with total body irradiation and therefore requested me to discontinue those "experiments" so far as the Atomic Energy Commission's support was concerned. I replied that: the treatments were not being given by or for the Atomic Energy Commission; they were given by radiologists at the request of the attending physicians; they were given with a reasonable hope of helping the patient. I should have explained that the contract with the Atomic Energy Commission provided only the means of making and analyzing the blood studies on these patients. You (apparently acting for the Committee) now write to the effect that even though the selecting, treating and clinical care of these patients is not done under the Atomic Energy Commission's sponsorship "they do not wish to collaborate in clinical investigation with physicians in whose considered judgment they do not have confidence". You further state that even if "there is an honest difference of opinion ..........it is a difference that will prevent such further developments under your direction as depend upon our confidence in your clinical judgement". The implication of your letter to scientific freedom in this country is one of very serious import. When any national governmental committee dictates the way medicine shall be practiced, it is a matter of major importance. I feel sure that your Committee does not want to set any pattern of dictatorial control over science. Wittingly or otherwise you have dictated how I should treat patients even outside of the Atomic Energy Commission's supported activities. That you will employ similar against younger and long established men and by the power of your control of substances, facilities and money, will attempt to control the practice of medicine in this country, is the foremost issue. A second important point is that because of a difference of opinion on one subject - a difference which you admit may be an honest one - you threaten to stop all collaboration dealing with any subject. If the scientific workers learn that every time they have ideas with which those in power disagree, they are subject to dismissal, scientific progress will cease in that project and the useful investigators will move to another. Of course if the actions of an individual, even on one subject, are at such variance with all others that no one can trust his judgement on any subject, his participation in a project is undesirable. I maintain however, that no group of responsible people should level such accusations against any person with an established reputation without a full investigation of the facts. In the face of these larger issues the Committee's opinion of me as an individual and of my colleagues as a group is relatively unimportant. I fully recognize the sense of responsibility that you and your Committee must have when dealing with matters that must be kept secret. I wonder however, if you and your Committee are working under some misunderstanding with regard to the secrecy surrounding the treatment of patients having rheumatoid arthritis with total body irradiation. There is not now nor has there ever been any secrecy concerning those treatments. Prior to the bombing of Hiroshima, the fact that the Manhattan District was interested in the effects of total body irradiation was kept a secret, but the fact that patients were receiving total body irradiation and were having continued blood counts was never a secret from anyone in the Medical School. Those responsible for the medical care of patients with rheumatoid arthritis were continuously aware of what was being done. Some satisfactory results encouraged them to continue to send patients to us for those treatments. This is not the place to enter into a discussion of the value of x-ray therapy for arthritis, but I believe I should clarify the circumstances surrounding the of this particular type of therapy at our institution. Here, as in a great many places in this country and abroad, spondylitis, rheumatoid arthritis and related conditions have been treated with to local areas. The patients are referred to the radiologists only when their attending physicians believe that radiation therapy is the treatment of choice. To accept them for such therapy when we believe that we have a reasonable chance of alleviating their symptoms. The results of localized therapy are often so good that many patients are referred to us. Many patients have such wide-spread disease that the general effects of the multiple local treatments are quite pronounced. Consequently, we are always looking for better methods of treatment. In two books and several articles, Doctor Gilbert Scott published a method of treatment which he calls "wide field therapy", a method that stimulates total body irradiation. He started using this treatment in and used it until his death in the forties and claimed that he was able to achieve excellent results. While we were skeptical of his claims and were never "enthusiastic /decided to try this method on a selected group of patients who were to non- radiological methods of treatment. I felt then and still feel that we had sufficient grounds for trying this type of treatment on a group of patients with a very incapacitating painful, disease. I freely admit that in 1948 when we started this work I was influenced by the fact that we needed to learn as much as we possibly could concerning the effects of total body irradiation on people with relatively normal blood pressure. At that time I was confronted with the problem of building up the morale of the on the new atomic bomb project, many of whom were worried about the effects of prolonged whole body irradiation. In the treatment of patients with arthritis (and others with cancer) by means of whole body irradiation we felt that there was a reasonable expectation that the method utilized might be of value to the subject, and as a by-product we could study the effects on the blood. To expect the from the patient, but the patient, but the treatment was explained to them by the physicians and they, in full knowledge of the facts, accepted the treatments. The clinical results of these treatments were not considered as belonging to the province of the Manhattan District or the Atomic Energy Commission and therefore have not been reported, but the changes have been reported at regular intervals. Between 1942 and 1946 thirty-two patients were treated by this method. SOME HAVE BEEN SINCE 1946. During the war years Dr. , and internist specializing in the study of arthritis and Dr. , a radiologist had many discussions about how to treat patients with rheumatoid arthritis. They reasoned that since the patients had a diffuse inflammatory reaction, and since inflammatory tissue took up more than normal tissue, it might be possible to effectively radiate the diseased tissues by giving the patient radiophosphorus. They tried this cautiously on some of Dr. private patients and obtained some satisfactory results. The members of the Arthritis Clinic were sufficiently impressed to want to give the method a wider trial. Here again we saw a chance to study the blood of patients who were being irradiated by a beta ray omitting isotope deposited throughout the body. Between December 1946 and May 1948, thirty-three patients were so treated and studied. We stopped this method before Dr. Warren's letter arrived because we had noted that the lobe indices of the patients who had been treated with x-ray and with P32 seemed to be too low. This trend I pointed out to you and your Committee at the time of your visit. We now know that the changes in the lobe indices are a function of time and technical procedures and are probably of no statistical significance. We wish that our budget had been increased enough to employ a hematologist to make a more comprehensive study of the data we have accumulated. Thus we have treated no patients with whole body x-ray irradiation since 1946 and none with P32 since May 1948. We believe that valuable information can be obtained by continuing to follow the blood pictures of the patients previously treated for as long a time as we can persuade them to return to us and therefore request your permission to do so. So much for the past, now let us look to the future. You have recommended and the business offices have transferred certain funds for the expansion of the facilities for studying the effects of radiation, including volt radiations at the University of California Hospital under my direction. In so far as I personally am concerned this will add increased responsibilities to an already heavy load. If it were not for my own feeling of responsibility to science and my country I would not have suggested this expansion. However if you and your Committee now intend to advise the Committee that I and my colleagues are not to be trusted or if you are to be swayed in your feelings of confidence in my judgement as easily in the future as you appear to have been, and if the Commission intends to accept your advice, there is no use in proceeding with the project until such time as those who may trust my judgment or that of some colleagues, are in a position to advise the Commission. I hope that I have misunderstood your letter as completely as you appear to have misunderstood my position. You and your Committee have been given positions of great responsibility in this country of ours, much the same as I hold during the crucial war years. I find it hard to believe that you would lightly challenge that which every physician values most highly - confidence in his considered judgment. Yours sincerely, Robert S. Stone, M.D.