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Chapter I BAC KGROUN D THE present monograph is designed as a de- tailed report on certain efforts made during the period 1946-1955 to provide answers to the following two questions: 1. Can there be observed, during the first year of life, any differences between the children born to parents, one or both of whom were exposed to the effects of the atomic bombings of Hiroshima and Nagasaki, and the children born to suitable control parents, and 2. If differences do exist, how are these to be interpreted ? 1.1 The general administrative framework of the study. The study to be described was undertaken as one facet of a comprehensive at- tempt to obtain detailed information concern- ing the various possible late or delayed biologi- cal effects of exposure to an atomic bombing. Certain information pertinent to the develop- ment of the over-all program is essential to an understanding of the manner in which the effort to provide answers to the two questions listed above evolved. The background of this program begins shortly after Japan's surrender, when a Joint Army-Navy Commission made extensive obser- vations in Hiroshima and Nagasaki on the sur- vivors of the bombings. At the conclusion of the Commission's work its chairman, Cot. A. W. Oughterson, M.C., AUS, recommended to the Surgeon General of the Army that the National Academy of Sciences National Research Council be requested to undertake a long-range study of the medical and biological effects of the atomic bomb. This recommendation was transmitted by Surgeon Gen. Norman T. Kirk to Lewis H. Weed, chairman of the Division of Medical Sciences of the National Research Council. As a result, in June of 1946, a con- ference group was convened by the Council, and in November, following its recommenda 1 hon. a tve-man commission composed of repre- sentatives of the Council, the Army, and the Navy left for Japan for the purposes of (1) determining the current status of Japanese work on atomic bomb casualties, (2) evaluating the feasibility of American participation in con- tinued research on these casualties, and (3) indicating the lines along which such studies should proceed. This commission, composed of Austin Brues, Paul S. Henshaw, Lt. Melvin Block, M.C., AUS, Lt. James N1. Neel, M.C., AUS, and Lt. (j.g.) Frederick Ullrich, (MC) USNR, submitted a report of its findings to the Council in January, 1947. The June, 1946 conference group had recom- mended that appropriate action be taken to obtain a Presidential Directive authorizing the National Research Council to initiate a long- range study of atomic bomb effects. This Di- rective was issued at the request of the Secretary of the Navy, James T. Forrestal, in November, 1946, and on its authority the Council, in Janu- ary, 1947, established a Committee on Atomic Casualties, composed of Thomas M. Rivers (chairman), George W. Beadle, Detlev W. Bronk, Austin Brues, George M. Lyon, C. P. Rhoads, Shields Warren, Stafford L. Warren, George H. Whipple, and Raymond E. Zirkle. At its first meeting, on March 25, 1947, the Committee on Atomic Casualties went on record to the effect that a large-scale program should be organized towards the end of learning as much as possible of medical significance from the Japanese experience. Financial support for the program was sought from the U.S. Atomic Energy Commission, which, during the fall of 1947, formally signified its intention of financ- ing the program in Japan. Ever since November of 1946, i.e., beginning with the visit of the five-man commission re- ferred to earlier, there has been resident in Japan a group of investigators and supporting

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Genetic Efects of Atomic Bombs personnel concerned with various phases of the over-all program. This group has been known as the Atomic Bomb Casualty Commission (ABCC) . Starting with a scant handful, it grew until at its peak strength it consisted of 143 "allied" personnel (Americans, English, Aus- tralians, etc.) and 918 Japanese Nationals. At the time that the ABCC began its opera- tions in Japan, that country was of course under U.S. Military Occupation. It was Occupation policy that groups such as the Atomic Bomb Casualty Commission, having to do primarily with the Japanese people, should work with and through some existing Japanese agency. In early 1947, the Japanese Ministry of Welfare, at the instigation of the Public Health and Welfare Section of GHQ, SCAP, established a National Institute of Health, designed to oc- cupy roughly the place in Japanese medicine which the National Institutes of Health then occupied in the United States. Several months later, in June of 1947, Brig. Gen. C. F. Sams, then Chief of the Public Health and Welfare Section, suggested that it would be appropriate for the ABCC to develop its program in co- operation with the Japanese National Institute of Health. Eventually there was established an Atomic Bomb Casualty Section of the Japanese National Institute of Health. The personnel of this Section have been closely integrated with ABCC personnel, in such a manner as to make the program truly a combined Japanese-Ameri- can effort. 1.2 The beginnings of the Genetics Program. -So well known are the genetic effects of the irradiation of a variety of plant and animal ma- terial that inevitably one of the foremost ques- tions in the minds of those considering the possible late consequences of the atomic bomb- ings had to do with the characteristics of the children of exposed parents. As a member of the five-man survey commission which went to Japan in the late fall of 1946, the senior author was especially responsible for an evaluation of the lines along which the study of this question could best proceed. The results of this evalua- tion were laid before an ad hoc Genetics Con- ference convened by the National Research Council in the summer of 1947, composed of G. W. Beadle (chairman), D. R. Charles, C. H. Danforth, H. ]. Muller, L. H. Snyder, and Lt. I. V. Neel. It was clearly recognized by the members of this Conference that the demonstra Chapter I tion of the potential genetic effects of the ir- radiation of the human species presented many difficulties not encountered in laboratory ma- terial. It was further recognized that post-war conditions in Japan were by no means the most favorable for a study of this type. In finally recommending that a rather large- scale effort be undertaken in Japan, the Confer- ence felt constrained to make the following statement: "Although there is every reason to infer that genetic effects can be produced and have been produced in man by atomic radiation, neverthe- less the conference wishes to make it clear that it cannot guarantee significant results from this or any other study on the Japanese material. In contrast to laboratory data, this material is too much influenced by extraneous variables and too little adapted to disclosing genetic effects. In spite of these facts, the conference feels that this unique possibility for demonstrating genetic effects caused by atomic radiation should not be lost." (Genetics Conference, 1947.) Although the study which was undertaken will for purposes of convenience be termed the "Genetics Program," because of its obvious implications, it must be emphasized that those concerned in its organization and conduct have always regarded it first and foremost as an effort to collect data on the characteristics of the children born to the irradiated survivors of the atomic bombings, data which, if indicating that the bombs had had some effect, were then subject to several possible interpretations, ge- netic and otherwise. 1.3 The early f~pa'~ese efforts along these lines.- The U.S. Army-Navy Joint Commis- sion which studied the medical effects of the atomic bombs in Japan as soon as possible after the surrender worked in close cooperation with the Medical Section of a special Committee for the Investigation of the Effects of the Atomic Bombs, appointed by the Japanese National Re- search Council. The members of this group also recognized clearly the desirability of long-range studies on the medical effects of the bombs, but in the organization of such studies were greatly handicapped by post-war conditions in Japan. The administrative reorganization of the Japa- nese National Research Council and other aspects of Japanese science which the Occupa- tion sponsored also unavoidably created uncer- tainties which delayed the work of this group.

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Background Despite these many difficulties, at the time that the U.S. National Research Council's survey group visited Hiroshima in December of 1946 they found the Japanese planning to obtain data on the characteristics of the children then be- ing born. This program, under the immediate supervision of Dr. I. Matsubayashi, was care- fully reviewed. It was felt to be inadequate in several respects. Nevertheless, it is certainly a favorable commentary on Japanese interest in the problem and desire to carry on research that plans for even a small program had been set up under the circumstances then prevailing. This program was in effect very briefly and then merged with the program of the ABCC; Dr. Matsubayashi became a member of the ABCC staff. I.4 Scientific arid administrative considera- tions shaping the r;at?'re of the program ire fapan. The lines along which the Genetics Program in Japan was laid out in 194661947 were dictated not only by purely scientific con- siderations but also by certain practicalities of the situation. The more important scientific considerations were as follows: 1.4.! The possible observable genetic ef- fects of irradiation upon the first generation born after an atomic bombing are many and varied. These include changes in the sex ratio, an increase in the frequency of stillbirths, an increase in the frequency of congenital mal- formation, an increase in infant mortality, etc. Each of these possible indicator of genetic damage is also influenced by a number of other factor; there are no knows' antique yardsticks of genetic damage. Under these circumstances, the crux of any program of study was the feasi- bility of establishing control material which in- sofar as possible differed from the irradiated only with respect to the radiation factor. 1.4.2 At the time this program was organ- ized, although there was available a mass of data concerned with spontaneous mutation rates and the genetic effects of irradiation on Drosophila, little was known concerning spontaneous muta- tion rates in mammals, including man, and, with the exception of the work of Charles (1950), still less concerning the mutagenic effects of the irradiation of mammalian ma- terial. Largely by extrapolation from the Dro- sophila material, it could be anticipated that in the light of the probable irradiation dosages sus- tained by the survivors of Hiroshima and Naga 3 saki, only very slight genetic effects should be detected in the first generation. In particular, it is worth pointing out that although the atomic bombs were dropped in August of 1945, be- cause of the various time-consuming administra- tive developments recounted above, involving policy decisions and their means of implementa- tion for the National 'Research Council, the U.S. Atomic Energy Commission, the U.S. Army of Occupation in Japan, and the Japanese Govern- ment, it was March of 1948 before the Genetics Program as it will be described presently was actually in action. The first children to come under the scrutiny of the program were con- ceived in October of 1947. There was thus a loss of information for the two years following the bombing. For a variety of reasons, some to be discussed below, it was felt that no attempt to reconstruct the frequency of malformations, stillbirths, or neonatal death during'these first two post-bomb years could succeed. The practi- cal corollary of these considerations was the necessity, once the program got under way, of a large-scale effort which would utilize as much of the available material as possible. 1.4.3 It was apparent from the outset that the Genetics Program could not and would not operate independently of the various other facets of the activities of the ABCC, but as one of a collection of integrated units. However, the or- ganization of the Genetics Program proceeded somewhat more rapidly than the organization of other segments of the ABCC. Furthermore, there was for some time uncertainty as to the scale of operations in Japan. Under these cir- cumstances, it was necessary to design a program with a basic, irreducible framework to which additions could be made later if circumstances permitted, but the additions had to be of such a nature that they would not invalidate a com- parison of the early and later data. It was fur- ther necessary that the observations selected as possible indicators of genetic damage be rela- tively simple, as devoid as possible of the sub- jective element, and capable of being carried out under the conditions in Japan to be de- scribed below. 1.5 Local considerations shaping the nature of the program in fapar'. Among the condi- tions in Japan which were determining elements in the program, the following deserve special mention: 1.5.1 In Japan, the practice of obstetrics

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4 Genetic Effects of Atomic Bombs Chapter I is still largely in the hands of midwives. They attend approximately 96 per cent of the deliv- eries. Thus, in 1948, out of a total of 2,681,624 deliveries in Japan, 2,468,821 were attended by midwives, 102,627, by physicians, and 110,176 by unlicensed attendants. The deliveries for which midwives and unlicensed attendan* are responsible usually occur at home. The prerequisites for licensure as a midwife were revised upwards during the Occupation. However, the great majority of midwives now in practice were of course licensed under the pre~ri- ous system. This required that a candidate for admission to a school of midwifery had com- pleted a kotoshogakko education (about eight years, corresponding to grammar school). A1- though not required, some candidates had also completed chu~gaku (middle school, about four years, corresponding to high school). The course in midwifery covered two years. One could either spend all two years in a school, or spend one year in school and the last year obtaining experience either in the obstetrics- gynecology department of a hospital or in asso- ciation with a senior midwife. One had then to pass a prefectural examination for licensure. The legal minimum age was 20 years. Not un- commonly a licensed midwife married soon after completing school and did not return to the practice of midwifery for some years. It is apparent that whatever the midwife's qualifications for the practice of obstetrics may be, her training had not prepared her for the detection and careful description of congenital malformations. This made it necessary with respect to the Genetics Program to develop a system whereby each newborn infant was seen by a physician as soon as possible after birth. 1.5.2 The Japanese economy during the immediate post-war years, when this study was instituted, was marginal. There was strict ra- tioning of food and articles of clothing. Since official rations were inadequate to meet caloric needs, there was a widespread "black market" in food. One of the features of the ration sys- tem was special provision for pregnant women. Such women (or their designated representa- tive) upon certification of pregnancy by a mid- wife or physician could register at any time after the fifth lunar month of pregnancy and thereby obtain access to certain items of value to them and their future children. Registration was re- vealed by a preliminary study to be in excess of 95 per cent complete. There was thus available a system whereby very nearly all pregnant women could be contacted at mid-pregnancy. 1.5.3 Finally, mention must be made of the psychological and sociological pitfalls in- volved in a study of this type. This is scarcely the place for a detailed analysis of the psycho- logical problems inherent in the operations of the ABCC in Hiroshima and Nagasaki. Some of the inevitable problems in Japanese-American relationships are apparent. Others were unex- pected (Matsumoto, 1954~. Each step in the program had to be planned and taken cautiously, after every effort had been made to explore the possible repercussions. In retrospect, the first year of activity in Japan may be characterized as an apparently interminable series of confer- ences punctuated by weekly crises which, al- though often inconsequential in retrospect, at the time threatened to stall the entire operation until met. Lacking any semblance of authority in Japan, the ABCC was wholly dependent upon the voluntary cooperation of the Japanese peo- ple. The good will of the city officials, local physicians, and above all-of the midwives, was, if not indispensable, highly desirable. It should particularly be mentioned that in Japan the social stigma attached to the birth of a mal- formed child is rather considerable. Every effort had to be made to develop a program which would not antagonize the mothers of malformed children by exposing them to what they con- sidered undue publicity. In this effort, the mid- wives were the key. Although the destruction and desolation which were the aftermath of the atomic bomb- ings have been many times described, neither photographs nor words are adequate to the occasion. In addition to the post-war stresses and strains to which all the inhabitants of Japan were subject, the citizens of Hiroshima and Nagasaki were confronted with a more formi- cable job of reconstruction than the inhabitants of most Japanese cities, badly bombed though these had been. These are not the circumstances in which research or even cooperation in the re- search of others flourishes.