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Why Japan?

Ancel Keys and colleagues hypothesized that the Japanese, at the lower pole of fat diets, would hinge the correlation between saturated-fatty- acid intake and coronary disease risk.

In the 1950s, a few things were clear about Japan's traditional diet even before the Seven Countries Study or modern nutritional surveys. It was extremely low in animal fats, modest in protein, relatively high in fish, and high in complex carbohydrates. The Japanese diet also contained several times more salt than most other traditional diets.

The early hypotheses of our Japanese colleagues about the causal role for hemorrhagic stroke of low-fat, low-protein diets, with attendant low blood cholesterol levels, were hopelessly confounded by the high-salt, high-blood pressure picture.

Even now, in the 1990s, Japanese investigators attribute, without the evidence needed, the decline in deaths from cerebral hemorrhage as much to the rising average cholesterol levels as to the lowered average blood pressure in Japan. The finding of excess risk of cerebral hemorrhage among individuals with low blood cholesterol values in other cultures where diets are not high in salt has, however, provided strength to their views.

At any rate, the very low-fat diet set the stage for Keys to include Japan in the Seven Countries Studies, thanks to early studies by Noboru Kimura, and independently, by Yoshio Komachi, a distinguished epidemiological colleague.

A pilot study by Keys and Kimura showed differences in blood cholesterol level among miners, clerical workers, and executives within Japan. It also found striking differences in beta-lipoprotein cholesterol levels between Japanese on the mainland and in southern California, while alpha-lipoprotein levels were comparable.

Kimura, mainly interested in the internal differences in Japan, chose the farming village of Tanushimaru to contrast with the predominantly fishing village of Ushibuka because of theories about fish and protein intake being protective against cerebrovascular disease.

Tanushimaru, Third Round, March, 1968

As in the farming villages of the Mediterranean regions, surveys in Tanushimaru required that we arrive in the field immediately before planting or after the harvest, to be assured of local cooperation. So, the Tanushimaru survey was geared up in March, with one drizzly, somber day strung out after another. It was particularly damp in the Kurume hotel where I was preparing for the field by reviewing forms, schedules, and procedures with Toshima.

In Tanushimaru, we had the full program of automated exercise electrocardiograms, chest recordings, respirograms, and pulmonary flow curves recorded by Rautaharju's team, and a marvelous local team of smiling, industrious, young Japanese physicians and nurses, somehow liberated from their regular jobs for several weeks.

We examined all farmers of the Tanushimaru region, with close to a hundred percent response rate. The major logistic problem was the damp cold. I did a lot of talking, encouraging, and walking about the center to ensure that the coal grates and the kerosene stoves were appropriately distributed so that men awaiting physical examinations and blood pressure measurement weren't exposed to cold stress. I probably needn't have worried. Those hardy, wiry men were well-adapted to the climate.

The only other hazard I knew of in Tanushimaru was the catered team lunches that arrived in festive, lacquered boxes containing bamboo trays of sundry unidentifiable squares, rounds, and triangles; colored fish paste; cold clots of rice wrapped in dark, paper-thin seaweed; briny pickled fruits and vegetables; and semi-cooked mussels and shrimp. I chose to eat the rice only, using chop sticks, much to the amusement of our Japanese colleagues, washing it down with Kirin beer. This allowed me to survive until dinner, when I could have bland dishes of tempura or sukiyaki.

Another hazard I had heard about but not experienced: Japanese earthquakes. That was quick to change. The team was hard at work one morning in the frame elementary school-house of Tanushimaru, counting pulses and taking blood pressures, while I supervised exercise tests. Suddenly, I felt as if something were disturbing my balance. Looking out the window at a stone memorial to the founder of the school, three stones, one on top of the other, were dancing, undulating but not falling. The school's flimsy wood and bamboo floors and walls were creaking wildly.

The survey activity paused, the Westerners looking at one other in consternation, the Japanese poised calmly at their posts. The undulations continued for a good ten seconds, subsided, started again slightly for a couple of seconds, and then disappeared. I understood then the reasons for the light architecture. A masonry building would have crumbled and fallen on us. Afterwards came the "rush," typical when one has escaped danger.

Relationships were particularly cordial with Yasume Egami, the family practitioner of Tanushimaru. One of our sample cohort, he visited the survey center daily to chat with the participants. He knew all of them, as well as their families and family histories. His blessing raised our credibility above that of the distant academics we might otherwise have been considered. I chatted with this kind man on his visits, enough to learn of his sensitivity, intelligence, and understanding of what we were doing. His devotion to his community was clear.

The one time I visited Egami's home and commented on its beauty, he must have seen my eyes rest momentarily on a particularly handsome lacquer. Imagine my chagrin when, on the train north to Tokyo, I opened the package he had placed in my arms at the station. There was the lacquer, a deep Chinese red, emblazoned with a gilt lion.

Twenty-five years later, that lacquer decorates a Japanese corner of my home. Imagine my greater embarrassment when I learned indirectly some time later that the lacquer had been handed down to him from his great grandparents. I, the visiting Westerner, have his precious family heirloom.

I have not yet learned - and expect will never learn - how to deal with such generosity, or with the social debt that it incurs. But I have learned to avoid expressing any admiration of the belongings of the Japanese!

Collaborators
	Noboru Kimura Noboru Kimura was one of the first clinical scientists anywhere to highlight the rarity of coronary disease and frequency of hemorrhagic stroke in Japan and to pose hypotheses about their causes. He was also one of the first clinicians anywhere to look beyond the clinic to the general population for the causes and prevention of common cardiovascular diseases. He sought out Ancel Keys in the early 1950s to encourage him to come with Paul Dudley White to Japan and make both internal and external comparisons of ardiovascular disease rates. And he sat as one of the pioneers, with Paul White, Gunnar Bjšrk of Sweden, and Ancel Keys, on the platform of the first major symposium on cardiovascular disease epidemiology and prevention at the World Congress of Cardiology in Washington, in 1954. Our friend and colleague, Kimura, embodied all the strong traits we think of in traditional Japanese culture. "Nobe," as his American friends called him, was blessed with a remarkable serenity and good humor, a quiet sense of values promoted by example rather than pedantry, a prodigious industry disguised by calm efficiency, an effective authority without authoritarianism, and a lifetime loyalty to friends. Not only innovative on his own, but sensitive to innovations elsewhere, he came for a six-month period in our laboratory in 1952, at the very time that Ancel Keys was beginning to formulate ideas about the importance of lifestyle in population disease differences. In further meetings with Keys, at the World Congress in Washington in 1954 and at the WHO Expert Committee Meeting in Geneva in 1955, their discussions about collaboration continued. Both recognized that Japan held a key to understanding the mechanisms of mass atherosclerosis. Kimura sponsored the formal meeting with Keys and White in Fukuoka in 1956, when they set up the first study to demonstrate occupational differences in cardiovascular disease risk in Japan. Kimura became a regular fixture in all Seven Countries Study activities, present at the pilot studies in Italy and Crete in 1957, and at the first survey in Makarska in 1958. After Makarska, he immediately launched the Japanese surveys in Tanushimaru and Ushibuka. He became principal investigator and field director for all Japanese Seven Countries activities thereafter. The solid collaboration and collegiality of Noboru Kimura, and the findings of the Japanese surveys, have contributed to the useful outcomes and understandings of the Seven Countries Study and to the scientific, professional, and personal satisfactions of his study colleagues.
	Hironori Toshima In the early 1950s, "Hiro" Toshima trained with Kimura and then in the early 1960s took a post-doctoral fellowship at the Laboratory of Physiological Hygiene in Minnesota. At Minnesota, he worked primarily in electrocardiography, but was exposed to the epidemiological pursuits going on there. He later took on the study leadership in Japan after the retirement of Kimura. Toshima reinvigorated the Japanese Seven Countries Study by recommencing surveys in 1977-78 with a newly established cohort representative of that period, twenty years following the baseline survey. He broadened the age range and included men and women in this survey, as well as adding new risk measurements. In addition to carrying on the professional and personal traditions of Kimura, Toshima has been innovative in cardiovascular medicine in Japan and internationally. For example, he helped introduce modern cardiac rehabilitation strategies in Japan. Toshima is now Director of the Kimura Memorial Heart Foundation, which is concerned with primary prevention and health promotion. Closest to the hearts of his international colleagues was the great personal effort, and the immense contribution Toshima made in bringing together all the Seven Countries principal investigators to celebrate the thirty-fifth anniversary of the study, along with the ninetieth birthday of its founder, Ancel Keys. This took place in a superb professional meeting and social occasion in Fukuoka on October 30, 1993, documented in a publication, "Lessons for Science from the Seven Countries Study."