Attachment 3 Washington 25, D.C. DEPARTMENT OF July 29, 1949 ILLEGIBLE AND SURGERY YOUR FILE REFERENCE IN REPLY REFER TO: 10P Dr. Stafford L. Warren, Dean University of California School of Medicine Los Angeles, California Dear Dr. Warren: Enclosed is a copy of the "proceedings" of the March 17-18 meeting of representatives of the Radioisotope Units, which was held in Chicago. This is an abstract which was reduced from a rather voluminous set of material obtained by wire-recording. We are hoping to have another such meeting and a tentative date of October 6 has been set, with a tentative selection of Los Angeles as the place. Since this meeting will follow the Central Advisory Committee meeting in September, any recommendations or suggestions arising from this meeting may be presented to the representatives of the Units. Sincerely yours, A. GRAHAM MOSELEY, JR. Asst. Chief, Radioisotope Section Research and Education Service enc. Present at the meeting of Representatives of the Radioisotope Units, U.S. Veterans Administration, Chicago, Illinois, on March 17 and 18, 1949, were: Julian H. Acker, M.D. Dallas Herbert C. Allen, Jr., M.D. Van Nuys P.M. Denson, D. Sc. Central Office Susan Fleischman, PhD. Fort Howard H.G. Goldner, M.D. Fort Logan Howard Horns, M.D. Minneapolis Edward D. Hudack, M.D. Cleveland Alfred H. Lawton, M.D., PhD. Central Office George V. LeRoy, M.D. Hines Raymond L. Libby, PhD. Los Angeles George M. Lyon, M.D. Central Office George R. ILLEGIBLE, M.D. Nashville A.G. Moseley, Jr. Central Office (Atomic Energy Commission) Chas. H. Perry, PhD. Energy Commission J.F. Ross, M.D. Farmingham B. Roswit, M.D. Bronx William W. Saunders, M.D. San Francisco Wilbur R. Tweedy, PhD. Hines Harold F. Woiler Central Office * * * * * * * * generally agreed that it seemed preferable to adopt the National Bureau of Standards values and methods, and to hope that these would become generally available in the very near future. A number of problems were then discussed relation to appropriate doses of radioisotopes in diagnostic studies. There was no unanimity of opinion, but it appeared that the lowest practicable dose should be sought and adhered to in every case. AFTERNOON MEETING: Dr. Lyon reviewed the legal liability of physicians in the VA using radioisotopes, and pointed out that the individual physician bears the same moral and legal responsibility for the things he does to his VA patients, as he would if they were patients seen in private practice. Dr. Ross had been asked to prepare a discussion of the legal and insurance aspects of the use of radioisotopes. He reported as follows: "There are three aspects to this problem, and I think we should mention their existence: The first is the legal liability of the employer to the employee. The second is the legal liability of the physician to the subject to whom he administer radioactive material. The third is the legal liability of the institution to the public pubic or to the citizens in the environment." "We are only concerned with the first two of these today, and what I have been able to learn about them has been summarized here. In discussing this subject, I thought it might be of interest to learn the situation in on-Government institutions as well as in Government Institutions, and I confess that I could find out more about the situation in the non-Government institutions. First, to say something about the legal liability of the employer for the employee. The ordinary Workmen Compensation Laws generally apply to individuals who handle radioactive materials and who are exposed to radiation such as x-ray. There is no special provision to take into consideration the fact that such workers may be exposed to undue hazards. In most places work with radioactive material and radiation is not considered a hazardous occupation, whether it presents any more dangers than are presented to men in industry in general. There is a marked variation from one state to another as to the coverage of the Workmen Compensation Laws. I think that it is important to point out this variation, since it will alter to a considerable extent the liability of the institutions using radioactive materials. In many states non-profit or charitable institutions -2- do not necessarily have Workmen Compensation Laws applied to them. In many, if not most, states, if a charitable institution does not wish to participate in a Workmen Compensation scheme for employees, they do not have to do so according to the law. This does not, however, absolve them from a basic legal responsibility. Since most universities, colleges and hospitals are nonprofit, or charitable institutions, in many states the Workmen Compensation Laws do not apply to the individuals employed in these institutions. However, many such places have assumed that they do not have some liability to their employees, but they usually assume liability only for technical and laboring types of employees. Few institutions assume liability for professorial staffs, for staffs of instruction, or for investigations or research workers. This is particularly true in Massachusetts in several of the large university hospitals where compensation can be paid to a technician but, if a professor becomes injured, the institution does not assume responsibility for his injury. In contrast to this. other institutions make an attempt to carry liability for their research or academic staffs. As a rule this is carried through commercial insurance companies and it is usually a blanket policy which covers everything. So far as I know nothing has been said specifically in those policies bout about radiation hazard. In talking this over with insurance companies who at the present time are much concerned and are doing a considerable amount of think about it, it was ascertained that probably in the not too distant future certain policies would be set up to cover people who deal with radioactive materials, and in all probability such policies would greatly increase the premiums which such individuals may have to pay. Universities and research institutions who are contractors for Government agencies --- for example, the Atomic Energy Commission, and the Office of Naval Research --- frequently have allotments by these Government agencies which allow them to carry insurance on their employees. This was the case, for example, at Los Alamos, which is operated under contract by the University of California. The University of California has received a considerable sum of money from the Government to provide the necessary insurance against radiation hazard for the workers at this laboratory. The coverage of workers exposed to radioactive materials ordinarily is a Workmen Compensations Insurance. The compensation is relatively slight, and there is considerable difficulty arising from the fact that the effects produced by radioactive materials may not be demonstrable until a considerable period of time has elapsed. Many radioactive materials exert their effects at a very remote period. So it will depend to a large extent on the Workmen Compensation Laws in a state whenever late injuries may or may not be compensable. As regards the commercial companies at the present time, it isn't clear whether a commercial policy will cover radiation injury, which does not appear until a much later -3- time. It appears that an effort is being made to clarify the situation with respect to this sort of hazard and perhaps in the course of the next few years suitable policies will be in force. At the present time the ordinary insurance company has not realized there hazards and has not set up any special method for handling them. I think we can summarize this aspect of our problem by saying that the occupational disease related to exposure to radioactive agents is covered at present only by routine Workmen Compensation Laws, and that such laws are frequently inadequate from the standpoint that they do not cover all personnel who may be exposed to radiation hazards. "We consider now the legal liability in regard to employees who are handing radioactive materials in Government institutions. Apparently only the general Civil Service Workmen Liability Compensations apply to those people. It certainly does not apply to all Government employees who are not on Civil Service. In other words, the Chief of Medicine, the Chief of the radioisotope Unit, and the technicians who clean up the laboratories do not necessarily get the same degree of compensation. In any case, the benefits are extremely limited. People who work for Government agencies, even though they may have marked exposure or large hazard of exposure, have no special insurance and the Government has not provided them with any special insurance as far as can be ascertained. Dr. Shield Warren of the Atomic Energy Commission is of the opinion that no additional provision could e be made for any Governmental employees, no matter how hazardous his occupation, unless some special act was passed by Congress enabling the Government to assume liability. It apparently is the policy of the Government at the present time not to assume such liability and in the Veterans Administration, there apparently can be no way of increasing it or expanding it unless a law is passed. "We consider now the responsibility of the physician who administers radioactive materials. This responsibility can be divided into two categories. First of all, whether claims against the physician shall be considered as malpractice or whether they shall be considered assault and battery. Procedures which a direct relationship to the treatment of disease and which become the basis for a suit are tried as malpractice, whereas procedures which are done without direct relationship to the treatment of disease, such as diagnostic studies, et., if they form the basis of a suit, may be considered an infringement on the rights of the individual and are then tried as cases of assault and battery. It would seem, therefore, that if you are to sued because of an unfavorable result in the treatment of the patient with leukemia, you would be sued for malpractice. However, if the unfavorable result had occurred in the course of a study of blood volume, using radioactive -4- cells, the suit might be brought against the physician on the basis of assault and batter. This is likely to vary somewhat from state to state. In either case, the suit could be brought regardless of whether or not the subject had signed a prior consent enabling the physician to make such a study. It appears then that the ordinary malpractice insurance, such as is cold by the commercial companies, is of relatively little use to people working in medical research. There are certain types of policy which are written as blanket policies for liability policies which offer liability protection for limits between $100,000 and $300,000. They are not extremely expensive and they can be written to cover the individual from the standpoint of suits on the basis of assault and battery, such as may result from the use of radioisotopes in diagnostic studies. It is customary to insert in the policy a statement such as follows: It is agreed that such insurance as is afforded by the policy applies solely to activities of the insured in his capacity as a medical research worker conducting research, including supervision and the use of radioactive materials. It is further agreed that the word "accident" wherever used with respect to body injury is changed to "occurrence of" or to "occurrence," it appears that such a policy can cover a person working with radioactive materials from almost every sort of claim which might be brought against him. Such policies can be issued only to M.D.'s licensed to practice medicine. No comparable protection can be provided for other than licensed M.D.'s. "We consider now the responsibility of the United States Government for suits arising from the administration of radioactive materials. The Government does not assure any responsibility for suits arising from malpractice, assault and battery or deceit of any employ, and the Federal Court Claims Act, Title IV, Public laws 601, of the 79th Congress states this specifically, saying that the individual's responsibility is his own. It is not the Government's, and this means that if you get sued for what you do in the Veterans Administration, that it is your misfortune, and the Government apparently will not be able to do anything to help you about it. "In summary, it would appear that individuals engaged in the use of isotopes for investigation and therapy should assume the responsibility of the liability insurance themselves, since the Federal Government will assume no such liability. Furthermore, it should be emphasized that coverage for claims arising from the use of radioactive materials may have to be insured under a general liability policy as well asunder the ordinary -5- malpractice insurance." There was a general discussion of this report which was of great interest to all concerned. Dr. Lyon introduced the subject of the safety plans in operation in the Radioisotope Units in the various VA hospitals. This was followed by a general discussion, including such subjects as Methods of Storage'; Construction of Hoods; Stippable Paint; Laboratory Furniture; and Plumbing. No definite conclusions were reached on any of these subjects, and it was the sense of the meeting that each of the Radioisotope Units was making an effort to solve the problems presented by the use of hazardous material in a number which was suited to the facilities and the equipment which was on hand. It was the general opinion that the time was not proper for the establishment of an overall regulation for the safe handling of radioactive material. Dr. Roswit then presented a paper on Human Applications of Radioisotopes as related to Safety Plans. He discussed potential carcinogenicies in the skin of persons exposed to betaomitting radioisotopes; routine blood examinations; monitoring devices; hazard to other organs than those specifically treated; hazards to other patients close to the patient receiving radioisotopes treatment; and general features of the use of radioisotopes in therapy. Following his paper, there was a general discussion of the points that he presented. No conclusions or recommendation were made at this time, and all agreed that his presentation was stimulating. Dr. D.E. Tabern, Director of Special Research at the Abbott laboratories, North Chicago, discussed briefly his interest in the preparation and supply of radioisotopes. At the present time his laboratory is equipped to process and supply radiogold, radiofluorescein, radioiodine, and radiophosphorus. Dr. Tabern reviewed the necessary formalities which had to be undertaken to obtain these materials from Abbot's . he also discussed the types of containers in which they were provided, and the cost of these agents. The first day's session adjourned at 4:30 p.m. THE SECOND DAY. Morning Session: Dr. LeRoy distributed copies of he Procedure Book and Safety Regulations which are followed at Hines Hospital. There was a general discussion of safety regulations in force at the various Radioisotope Units, and there was agreement that a procedure book was a useful technic. -6- Dr. LeRoy then presented the experience of the Radioisotope Unit at Hines Hospital for the use of radiophosphorus in the treatment of leukemia. Essentially the technic followed at Hines Hospital is as follows: An attempt is made to maintain the amount of radioactive material inside the patient at a fairly constant level on a weekly basis. This is accomplished by keeping track of the excretion of radiophosphorus, and by replacing each week the amount of radioactive material which has decayed and which has been excreted. Following this technic it has been possible to maintain the patients on a constant level of exposure to radioactivity. The results in the treatment of chronic myclogenous leukemia were presented and have been fairly successful. There was a general discussion of the plan of treatment of chronic leukemia with radiophosphorus. It was the sense of this discussion that approximately 10 t0 20 cc. per course of treatment are required over a period varying from 10 to perhaps 35-days. It was also the general opinion that oral therapy was not advantageous. In the course of the discussion, it developed that certain remote, unfavorable results may follow the use of radiophosphorus over a prolonged period time. These include marrow fibrosis, aplonomegaly, and questionably the appearance of acute leukemia. It was the sense of the group that such results were not sufficiently certain or invariable to justify withholding this form of therapy. Dr. Horns discussed the treatment of polycythemia with radiophosphorus. He considered the dosage, the problems of diagnosis, and the other forms of treatment which are necessarily undertaken at the same time that radiophosphorus is used. It seemed to be the general opinion that rather small doses on the order of 3 to 5 cc. are likely to produce a satisfactory remission. His presentation was followed by a general discussion of the diagnostic criteria, and of the various treatment regimes. No general conclusions were reached by the group. Dr. Allen then discussed the use of radioiodine in the diagnosis and treatment of diseases of the thyroid gland. The work at Van Nuys hospital has been concerned primarily with an investigation of the physiology of the thyroid gland, and relatively little effort has been directed to the establishment of regimes of treatment. It is the opinion of most workers in this field that approximately 5 mc. of radioiodine will cause a satisfactory remission of hyperthyroidism over a period of 30- days. Dr. Allen's paper was followed by a rather general discussion of the philosophy of the use of radioiodine in the treatment of hyperthyroidism. At the time of this meeting who problems presented by the patient with cancer of the thyroid gland were not discussed because most of the participants in -7- the discussion had had too little experience with the treatment of such patients. THE AFTERNOON SESSION. March 18: Dr. Denson, Statistician from the VA Central Office, presented a very interesting discussion of Statistical Methodology. He discussed the complications of large scale studies of the evaluation of drug treatment of disease. He went into considerable detail on the problems that arose in the course of the streptomycin evaluation program which was conducted jointly by the United States VA, and the National Military Establishment. He also described the problems that were presented in the recent study of anticoagulants in the treatment of heart disease under the auspices of the American Heart Association. His presentation was followed by a general discussion of the advisability of an evaluation program within the Veterans Administration. The various discussants pointed out that at the present time the physical standards for assay have become firmed and are generally accepted, it is then proper to consider evaluations. Another objection to evaluations programs at the present time. After such physical standards at the present time is the wide variability in the dosage technics, whether the various diseases suitable for treatment with radioisotopes should be managed by single dose or fractional dose methods. An additional difficulty in an evaluation program is the problem of the proper criteria for the diagnosis of the various diseases to be studied. In the case of leukemia this is not so critical as in other diseases, but it is definitely a problem. Dr. Ross was asked to summarize the various views, and to present the sense of the discussion so that it could be passed along to the Central Office. Dr. Ross spoke in effect as follows: First of all, it seems to me that classification of hematological diseases is not so difficult as perhaps has been emphasized here today. I grant that there are different types of leukemia, that there are different types of polycythemia, but they can be recognized, and they can be categorized, so that this is not an insurmountable obstacle. In the second place, we are dealing with groups of diseases in which standard forms of evaluation from one clinic to another for a large group of cases is the only way in which proper evaluation therapy can be obtained. If you sit down and try to go through the literature and to attempt to understand how one patient treated in one clinic corresponds to another patient in anther clinic, you would be impressed with the fact that, if they had at least just a single, very simple form as to what kind of response they got, the evaluation of therapy would be more satisfactory. It is -8- only by making such a study for large numbers of patients that we can tell very much how successful therapy is. I have been treating leukemia now for 7 years, and by a great amount of hard work in my small hospital have gotten 50 cases, which is not very many in terms of evaluation of the treatment of leukemia in Veterans Administration hospitals, we have an opportunity to study a significant number of patients with these diseases. Probably we have a better opportunity for doing this on a coordinated basis than any other organization in the country. It certainly would provide definite information concerning certain specific things. Granted it may be just the relationship of dosage to response of the white cell count, but that in itself would certainly be a valuable bit of information to obtain. Furthermore, the fact that we might have a specific form which was sent in for central evaluation would not preclude anyone keeping all the additional records or making additional studies as he might wish to. Also, it probably might preclude him from varying his technic of therapy from time to time. I also think that a general study of this sort would be very highly educational for the various participating groups. I am certain I should like very much to know the type of approach of other groups, and this seems to me to be a very valid form of investigation which, of course, I am not competent to do myself. So I would say that I would favor very much at least preliminary studies regarding radioactive phosphorus in the two conditions leukemia and polycythemia. Maybe initially as an educational process limited to one of these conditions, and maybe limiting the type of information which we expect to get from such a study to a very narrow or a very few categories which would help, we would try to tabulate. Maybe if we did this for a matter of a few months we would learn a number of things about it, and then later on, when the other VA Radioisotope Units are in operation and are administering such treatment, we would then be able to set up a more extensive study. "As far as radioiodine is concerned, the people here who are using it have expressed the viewpoint that they do not feel at the present time that they are quite willing to go ahead with a general, overall evaluation program. It would seem to me that it would do better to maybe start in a small scale and then expand than to try to start on too large a scale and have a failure in one or two elements. Following Dr. Ross's remarks there was a general discussion of the desirability of an overall evaluation program. -9- ABSTRACT OF PROGRESS REPORT FARMINGHAM Period of September 1948 to September 1949; Dr. Jos. F. Ross, Director PHYSICAL FACILITIES: During the past year structural alterations and laboratory furniture installation was completed, giving excellent facilities of ILLEGIBLE square feet. This space is adjacent to the General Medical Research Laboratory and consists of four well equipped laboratories, office, storeroom, counter room, and a treatment and conference room. Laboratory equipment and supplies have been procured, set up, calibrated and put into operation. PERSONNEL: Miss Adams has been reclassified from a consultant basis to Radioisotope Scientist (Biochemistry) Dr. Arthur Hagelstein, Resident in Medicine is assigned to the Unit full time and Dr. Robert Chodes, Resident in Medicine, is assigned part-time. A secretary has been added. Authority for a technician has been received, but the position is still unfilled due to difficulty in finding a qualified applicant. Dr. Margaret Lewis has been added as a Consultant in Physics. WORK COMPLETED AND IN PROGRESS: a. Therapy. Twelve cases of leukemia and one case of Hodgkin's Disease have been treated with p32. Results have been tabulated and a plan will be formulated for evaluation of the therapeutic effect in these cases. Two cases of hyperthyroidism and one case of recurrent adenocarcinoma of the thyroid have been treated with I131 with good results. b. Diagnosis. Nine cases of suspected thyroid abnormality have been studied with the use of tracer doses of I131. Three of these subsequently received therapeutic doses, after demonstration of iodine uptake. c. Research. The technique for tagging erythrocytes with p32 for blood volume terminations has been perfected and applied to a study of blood volume in cardiac cases and in a series of patients in whom it was desirable to evaluate the blood volume response to therapeutic administration of mercurial diuretics. Results indicate that blood volume in patients with frank congestive heart failure is not as greatly increased as had been believed. Dr. Bernard Silverstone is currently working in this hospital and is employing p32 as an aid to localization and demarcation of brain tumors. 1 ABSTRACT OF PROGRESS REPORT We will attempt to develop a radioautographic technique for evaluating localization of radioiron in precursors of ILLEGIBLE, by the nuclear tracking technique. Development of scintillation counters will be continued by Dr. Margaret Lewis. SPECIAL ACTIVITIES: A series of lectures and demonstrations dealing with radioisotope techniques will be arranged by the staff and consultants, for the hospital staff. An excellent exhibit on production, use and measurement of radioisotopes was arranged by Dr. Engelstein and Miss Adams for Hospital Day. Excellent press coverage was given this exhibit. Dr. Hagelstein gave a lecture on Medical Applications of Radioisotopes to Kivanis International on July 14, 1949. A popular description of the work of the unit has been prepared by a feature writer for a Boston paper and will appear in the near future. 3 ************************ ABSTRACT OF PROGRESS REPORT BRONX Period of September 1948 to September 1949; Dr. Bernard Roswit, Director PHYSICAL FACILITIES: The unit has operated ILLEGIBLE into ILLEGIBLE inadequate space in the preliminary wind of the hospital. Two ILLEGIBLE have been authorized for the near future by the Bureau of the Budget. One of these will profile alterations in the radiotherapy wing to provide four additional small laboratories, which will provide the Unit with approximately ILLEGIBLE square feet. Laboratory furniture to equip these rooms is on order from section funds. The second authorized project is a $200,000 addition to the radiotherapy wind, which will provide space for a thoroughly shielded 1,000 kv-x-ray, and also several rooms and offices for the Radioisotope Unit. Adequate apparatus and supplies are on hand for current operation. PERSONNEL: During this period great progress has been made in respect to personnel. One person has been reclassified as chemist under Civil Service, while a physicist and a biological aid have been added. Also added are two physicians, one an associate radiologist and one an associate hematologist. These, with the Director, the Consultant physicist and a secretary compose the personnel of the Unit. WORK COMPLETED AND IN PROGRESS: a. Therapy. During the year the Medical Service has shown growing interest in radioiodine therapy for ILLEGIBLE hyperthyroidism. Five such patients were successfully treated in collaboration with medical internists. Five, patients with metastatic carcinoma of the thyroid were examined for radioiodine uptake by the metastatic feed, ILLEGIBLE I131 ILLation of existing normal thyroid tissue. One of these patients ILLEGIBLE ILLEGIBLE of nearly 1000 mc of radioiodine in fractionated doses and received a ILLEGIBLE remarkable degree of clinical improvement, (this ILLEGIBLE the "ILLEGIBLE Magazine" case). A second patient gives promise of similar response. Radiophosphorus was employed in the management of 10- patients with malignant ILLEGIBLE. One case of ILLEGIBLE fungoides showed no response. Two patients with polycythemia ILLEGIBLE received treatment. Qualifications of p32 therapy by various fractionation techniques have been introduced and will continue. b. Diagnosis. A large percentage of time has been spent on perfection of the radioiodine ILLcer technique for the precise determination of dynamic thyroid function. A total of 75- patients was referred to the 4. for radiocardiography, particularly in the study of circulation time, various heart diseases and determination of amputation site. Radiosodium is also expected to assist in better understanding of the mechanism and evaluation of therapy in such problems as progressive heart failure. Addison's disease, renal disorder and hypertension. Of general interest will be the application of radioiodine as a tracer to study the circulation of the teeth, employing radioautographic and other techniques. SPECIAL ACTIVITIES: Through a continuous series of lectures, seminars and personnel talks an excellent rapport has been established with hospital personnel resulting in whole hearted cooperation and understanding of the functions of the Unit. Papers are in preparation on "The Diagnostic Role of Radioactive Isotopes" and "Recent Advances in Nutrition through Radioactive Isotopes." A paper on "Diagnosis of Testicular Tumors by Radioactive Phosphorus" had been accepted by the Journal of Urology. An exhibit entitled "Radioactive Phosphorous in Medicine" was prepared for the Golden Anniversary Exposition of New York City, and by request is now a permanent exhibit in the Museum of Atomic Energy. Oak Ridge Tennessee. An exhibit on "The Diagnostic Role of Radioactive Isotopes" is now in preparation for the Annual Graduate Fortnight, "New York Academy of Medicine, and will also be shown at the Radiological Society of North America meeting in Cleveland December 1949.