The Very Early Years of the ABCC Genetics Program, 1946-1954
The Very Early Years of the ABCC Genetics Program, 1946-1954
by James V Neel,
Professor Emeritus of Human Genetics and Internal Medicine,
University of Michigan Medical School
In a previous article (RERF Update 1(4):7-8, 1989), I have described the beginnings of the ABCC, and also the origins of its genetics program. The reader may recall how in the summer of 1947, after having spent some seven months in Japan attempting to develop a plan for a genetics program, I returned to Washington, DC, to present a protocol for a genetics study to an advisory committee of the National Academy of Sciences. Having received its endorsement and having recruited a team of three American associates for the program, I returned to Japan in the fall of 1947 to initiate the study under the auspices of the fledgling ABCC. Our task was to learn as much as possible about the children being born in Hiroshima and Nagasaki. As I have related earlier, the key to this was the special ration system for pregnant women which was in effect in Hiroshima and Nagasaki during the immediate postwar years. We developed a questionnaire to be administered when for ration purposes the women registered their pregnancies at the completion of the fifth lunar month of pregnancy. Registration occurred at the various city health centers. The plan was to obtain identifying information and radiation histories when the women registered, then information on the children at birth. We began to register pregnant women in Hiroshima in February 1948 and in Nagasaki in July of the same year. The information to be collected following the birth of a child included the sex of the child, viability at birth, presence of congenital malformation, birth weight, and survival through the neonatal period.
In postwar Japan, midwives were present at more than 90% of births, and thus in Hiroshima and Nagasaki they were able to notify ABCC of most births occurring in the two cities from 1948-1953. Above, the ABCC genetics staff is shown meeting with a small portion of the several hundred midwives upon whom the collection of data depended. At left, Dr Yasumitsu Tachino and Head Nurse Kiyoko Minato are shown making a postnatal house call, as a follow-up to information provided by the attending midwife. Of the more than 76,000 children seen up through 1953, ABCC pediatricians were able to reexamine about 30% at the age of about nine months. A subsequent drastic drop in the live birth rate led to discontinuation of the physical exams in 1954, although data on sex ratio and survival of newborns were still collected.
Early scientific expectations
It seems important at this point to describe the scientific expectations with which this study was approached.
In the early postwar years, the chief information concerning the genetic effects of radiation was based on the fruit fly, Drosophila. Data on the genetic effects of radiation on the mouse (which would have been more appropriate when thinking about human risks) were limited, consisting primarily of the results of studies by Dr Donald Charles at the Rochester, NY branch of the Manhattan Engineering District (the military’s cryptic term for the US atomic bomb project). From these data and what was known about the amounts of radiation received by survivors and the numbers of children they would probably have, we really did not expect to observe a statistically significant increase in malformed children in the offspring of irradiated survivors. On the other hand, there were some scientists who did have that expectation, and the popular presses of both the US and Japan carried many wild speculations. The level of these rumors was such as to create serious problems when a survivor exposed as a child reached marriageable age. The NAS advisory committee mentioned earlier agreed with our assessment, but felt there was no choice but to proceed with a study, despite the fact that statistically significant effects of radiation would probably not be observed.
One thing was clear: the study had to be as complete as possible, i.e., we had to obtain data on all the babies, not just some of the babies.
Posts of importance
Four jobs were critical to the program in those early days. First, there were young Japanese physicians–many just out of medical school and internship–working with the ABCC while they were establishing a practice. Many of these have gone on to be important members of the medical communities of Hiroshima and Nagasaki. The second very critical type of personnel was the midwives of the two cities. They were requested after a woman’s delivery to complete the questionnaire which had been initiated when the mother-to-be had registered her pregnancy. Finally, there were clerks and nurses–the clerks to administer the questionnaires at the various city health centers and to process the data from the questionnaires, and the nurses to assist the doctors in their home visits and clinic examinations. Ultimately, in the two cities, about 15 clerks were employed. Many of the readers will remember Mrs Jean Okumoto, who so skillfully supervised the clerical operation during those early days, and Kiyoko Minato, Chiyoko Watanabe, and Setsuko Hanazono, “genetics” nurses who, like Mrs Okumoto, stayed on with ABCC (and RERF) for many years after the clinical genetics program was terminated.
The undertaking required a major training program for physicians and clerks. And how many times we met with the midwives to explain the study and to discuss the types of findings we expected them to report (see the accompanying article by Dr Schull)! We planned that all newborns would be examined by a physician. If the midwife had observed some abnormality in the child, she was to notify us at once, and one of the doctors would make an immediate house call. If the child appeared normal, the midwife still notified us of the birth but on a more leisurely schedule–and the doctor still made a house call, accompanied by a nurse. All this required a small fleet of jeeps plus their drivers. In one way or another, when the program was in full swing, at least 200 persons were involved in the genetics program in the two cities. When this clinical program was terminated, these people were all reassigned if they wished to stay with ABCC. Two former “genetics drivers” who were with ABCC and RERF for many years were Masaru Nakagawa and Minao Kurisu.
Observing Japanese custom: a key goal
It was a great stroke of good fortune during the early survey stages of the study to make contact with Hawaiian-born Dr Koji Takeshima, then a young surgeon at the Hiroshima Red Cross Hospital (see RERF Update 2(1):7, 1990). During the very early days, when the genetics program was housed in the Red Cross Hospital, Dr Takeshima was the right-hand man, first of myself and then of successive directors of the genetics program. In 1948, after he became associate director and chief Japanese National Institute of Health (JNIH) representative, Dr Hiroshi Maki was to assume this same role. Needless to say, the developing genetics program was also closely scrutinized by the appropriate JNIH personnel.
In this study, we were determined to observe Japanese custom as far as possible; Dr Takeshima was our principal advisor. Our deep commitment to the question of congenital defect forced us to intrude upon people in times of sorrow and, since we needed to know if there was a pertinent family background, we had to ask very personal questions. It was necessary that we be both very professional and very sympathetic. I would like to believe that if we occasionally caused embarrassment, it can be excused on the grounds that our failure to demonstrate a striking increase in congenital defects removed a great barrier to the prospects of a good marriage for many of the younger survivors–and even their children.
I also need to remind the reader that although this study was initiated during the US occupation of postwar Japan, and of course required the concurrence of General Headquarters, it was in no way official “policy.” Its success depended on the voluntary cooperation of the Japanese people, just as the program of RERF does today. It is to me a tribute to the intelligence of the Japanese people and to the tact of the ABCC staff that cooperation was so high.
Largest early ABCC program
The genetics clerical staff administered questionnaires at the city health centers and later processed the data collected. In1950, clerk Mariko Tai and her co-worker were busy converting parents’ stated positions at the time of the bombing to distance from hypocenter.
On the US side, there was also a need for additional and continuing personnel. I was in and out of Japan during those early years, but there were others who came for periods of two or more years. The original team of three Americans consisted of Dr Ray Anderson, a pediatrician-geneticist; Dr Masuo Kodani, a cytogeneticist; and Richard Brewer, the data processor. Ray, then in the army, returned to the US as soon as his tour of duty ended (and subsequently became a pediatric cardiologist). The other two stayed on, but replacing Ray was urgent, especially since we had not been able to recruit a Japanese geneticist.
At this juncture (1949), I was fortunate enough to attract Dr WJ Schull to the program. He had just completed his doctorate in genetics at Ohio State University. When he completed his two-year ABCC contract, I was delighted to recruit him for the University of Michigan human genetics program, from which base, like myself, he continued his involvement in the follow-up studies. At ABCC, Dr Schull was replaced by Duncan McDonald and Newton Morton.
On the pediatric side, ABCC was by now interested in building up strength in this area, and during this early period we had a string of very able associates: Drs John Wood, James Yamazaki (see RERF Update 1(4):4, 1989), Wayne and Jane Borges, Frank Poole, Robert Kurata, Stanley and Phyllis Wright, and George Plummer. This pediatric strength enabled us to reexamine about 30% of all live-born infants registered in the genetics program when they were 8-10 months old. To obtain the most accurate information possible on congenital defects, an autopsy program was initiated under the direction of William Wedemeyer in Hiroshima and Naomasa Okamoto in Nagasaki.
Associated professional and support personnel swelled the ranks devoted directly or indirectly to genetics studies to undoubtedly the largest of the early ABCC programs.
Demographic changes cause end of program
The ABCC genetics department staff meeting with the Hiroshima Midwives Association in the early 1950s. Standing are Genetics Department Chief Duncan McDonald (left) with Dr Koji Takeshima, whose services as interpreter and advisor to the American staff were indispensable. At McDonald’s right is Midwives Association President Setsuko Yamamoto.
Because so little was known about the radiation histories of the people then living in Hiroshima and Nagasaki in those early days, our first plan included two comparison or “control” cities–Kure for Hiroshima and Sasebo for Nagasaki. In fact, we began registering pregnancies in Kure in March 1948.
Later, however, it became apparent that many residents of Hiroshima and Nagaski had either not been in the cities at the time of the bombings (ATB) or, if present, had been well beyond the zone of radiation. So, we decided we had sufficient “internal” controls for our studies. Accordingly, in September 1950, after data had been collected on some 8,391 pregnancy terminations, work was discontinued in Kure. No corresponding operation was ever attempted in Sasebo.
A few years after the genetics program was initiated, the Japanese government, in response to the burgeoning population which had resulted from the extensive repatriation of Japanese from such areas as Manchuria, Korea, and Formosa, greatly relaxed the indications for induced abortion, in part at least as a means of reducing the live birth rate. Thereafter, Japan sustained the sharpest drop in live birth rate per 1,000 persons ever observed since nations had instituted a system of vital statistics.
Confronted with these developments, Dr Schull and I began to wonder how much longer it would be scientifically justifiable to continue the program in its present form. We had been carrying out annual analyses of the accumulated data, and now seemed to be the time for a summary analysis. This analysis, conducted with the assistance of Drs McDonald and Morton, revealed very little difference indeed between the children of parents presumed to have received significant amounts of radiation ATB and the children of parents who had not been radiation-exposed.
Knowing trends in birth rates and knowing in general how the population of exposed parents would decline year by year, we could in the early 1950s look ahead and ask, “How much will the statistical precision of the results be increased by another 5 or even 10 years of data like these?” We tentatively concluded that there was very little likelihood that statistically significant differences would be obtained with another 5 or even 10 years of this large and expensive program. Under the circumstances, should the program be continued in its present form? We thought not, but the decision to discontinue a program with this momentum was almost as major as the original decision to initiate the program. We consulted with the NAS Committee on Atomic Casualties–then the supervisory body on the American side–and were encouraged (in keeping with our own wishes) to submit the question to a very senior committee of geneticists.
This committee, meeting in 1953 at the University of Michigan in Ann Arbor, concurred and recommended that the program be greatly reduced. (Members of the committee were: Drs GW Beadle, DR Charles, CC Craig, LH Snyder, and Curt Stern, chairman.) The physical examinations would be discontinued in early 1954, but we would continue to collect data on the sex ratio and survival of newly born infants. These two observations were continued because, on the one hand, a sex ratio effect of borderline significance had been observed and, on the other hand, it could not be precluded that an effect of parental exposure on a child’s survival might become apparent during childhood. But there was another reason to continue to accumulate a record of newborns (now through birth registrations): it would provide a continuing roster of children born to survivors, so that if future genetic developments provided new approaches to the genetic effects of A-bomb radiation exposure, the children for study would already be identified.
With this decision, Dr Schull and I then embarked on the definitive analysis of the results of these six years of study. A total of 76,626 infants had been seen during the course of the program. The results of the preliminary analyses were all confirmed, and the program and its findings then written as a book entitled, The effect of exposure to the atomic bombs on pregnancy termination in Hiroshima and Nagasaki, published in 1956 by the National Academy of Sciences-National Research Council.
In those days, it seemed that the most important and appropriate use of the data was to set limits, at specified probability levels, on the effects of the exposure on sex ratio, congenital defects, stillbirths, or neonatal deaths. This we did in the final chapter of the book. It was to be more than 34 years before these same data, combined with the data resulting from later innovations in the genetics program and dramatically revised dosimetry procedures, plus advancing understanding of human genetics, would permit an estimate of that most important of radiation parameters for humans, the genetic doubling dose. (See Neel et al., Am J Hum Genet 46:1053-72, 1990.)
Acknowledgment The author is indebted to Dr WJ Schull for refreshing his memory about a number of details.
Role of Japanese Midwives Critical to Birth of Genetic Program
by William J Schull
Director, Genetics Centers, University of Texas Health Science Center
During the 40-odd years that studies of the atomic-bomb survivors and their offspring have been underway, many local contributors have gone largely unrecognized. This is the story of two such individuals–Setsuko Yamamoto and Tei Murakami.
To understand their importance and contributions, one must bear in mind the design of the early genetics studies and the nature of the obstetrical practices of the time.
In the immediate postwar period and for some years thereafter, most Japanese infants were born at home. Since less than 10% of these births were attended by a physician, the cooperation of the midwives was essential to a successful ABCC genetics program.
At the outset of the genetics studies in 1948, several hundred women were practicing midwifery in each of the two cities. When a pregnant woman registered her pregnancy with the municipal authorities and with the ABCC, a form was completed in duplicate that identified her and her husband, detailed their exposure experiences and previous reproductive performance, and provided space for a description of the termination and the physical status of the infant. One copy was given to the registrant to give to the attendant at the birth of her child, and the other was retained by the Commission. The midwife completed a portion of this form to notify us of a terminated pregnancy and whether the infant was stillborn or died prematurely, to aid us in obtaining the body for postmortem examination. Each midwife was remunerated for the births she reported to the program, but–beyond weighing the infants with portable scales we provided–the midwives could not be expected to carefully describe congenital malformations. This was the function of our staff physicians who, accompanied by one of the Commission’s public health nurses, would call upon the family after we had been notified of a birth.
As with medical or paramedical groups worldwide, the midwives had organized an association with a president, a vice president, and a council charged with administering the association’s affairs. During the roughly six years of clinically surveying births in Hiroshima and Nagasaki, Mrs Yamamoto and Mrs Murakami served as presidents of the respective associations and through them most of our interactions with the midwives occurred. These periodic meetings with the entire association included explanations of proposed changes in the research program and discussions of problems or findings. Social gatherings, such as the open house and barbecue held in 1950 when the Commission began to operate out of its new facilities on Hijiyama, were usually attended only by the association officers.
Inevitably, in a study of this scope involving countless individuals, misunderstandings arose. Commonly, these took the form of an ill-considered remark by the staff physician to the family while examining a newborn. Such comments were communicated to the attending midwife who understandably took offense. These conflicts were never reported directly to us, but nonetheless we promptly learned of the damaged feelings through Mrs Yamamoto or Mrs Murakami to whom the midwife had complained.
A ritual evolved to resolve these matters, and each of us soon learned our parts in the unwritten script. If the incident occurred in Hiroshima, I or whoever happened to be the resident head of the genetics program, accompanied by Dr Koji Takeshima, would call upon Mrs Yamamoto.
When we reached her home, we were always cordially welcomed and invited to the pleasant second-floor room she used whenever we visited. As soon as we were seated, she served us tea, and after the customary pleasantries and inquiries into health had been exchanged, she began to explain what had happened as it was reported to her by the offended midwife. It was evident that whether the physician had or had not been correct, he had committed a tactical error that we could not ignore–the cooperation of the midwives was too central to our whole program.
I would tell Mrs Yamamoto that the physician was a young man, recently employed, but whom I knew to be considerate and not given to deliberately insensitive statements. I was sure that he meant no slight. These were truthful, if not terribly enlightening, remarks; indeed, they characterized our whole professional staff.
However, if she thought it necessary, we would see that the physician in question apologized to the midwife. Invariably, she would say, with a half-suppressed smile–for she too understood the need to preserve protocol–that she appreciated what we proposed to do, but did not believe so drastic a step was necessary. She would call the midwife and tell her of our visit and concern, and assure her that she, Mrs Yamamoto, was confident that this would not happen again.
Although different in their manner and appearance, both Mrs Yamamoto and Mrs Murakami were obviously respected by the members of their associations for their skill, experience, and diplomacy–particularly concerning the relationship between the associations and the Commission. Mrs Yamamoto, whom I knew better, was a tiny, wizened woman who usually wore the small-patterned, conservatively colored kimonos seemly for her age; she was in her late sixties. Her hair was drawn sharply back from her face. Her skin, etched with age, was swarthy, and she appeared so fragile one was fearful for her with each movement. Soft-spoken, her speech studded with honorifics, she seemed like everyone’s grandmother. But the twinkle lurking in her eye and the vigor with which she managed the midwives and their affairs revealed no frailty.
Mrs Murakami was a more sturdily built, somewhat younger, round-faced woman who was no less cordial than Mrs Yamamoto and administered her association just as effectively.
Both Mrs Yamamoto and Mrs Murakami are now deceased; however, they are survived not only by the many infants they delivered but also by the genetics program to which they contributed so unstintingly.
This article was originally published in RERF Update 2(3):6-9, 1990.