The Seven Countries Study: Japan

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 schoolhouse 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!

Ushibuka, Third Round, October, 1970

Ushibuka, the southernmost village on Kyushu, which is the southernmost island of Japan, was chosen by our Japanese colleagues as representative of a stable, rural culture predominantly of fisherman. It would serve as contrast to Tanushimaru, the farming community in the interior.

The fishermen of Ushibuka are a hardy lot, often at sea for as many as nine months of the year, their catch bought on the high seas by following fish tenders. We were advised that in October, a blustery cold month in the China Sea, most fishermen were home on leave with their families.

Arriving at Ushibuka by boat from Minimata across the bay, we were met by the local physician, Toseio Fukomoto, who spoke no English. His gestures and wonderfully kind face nevertheless helped us feel at home. He explained to me through a pleasant translator, his hospital nurse, that I would be living in the hospital and eating at his house.

I felt grand, as do all Westerners, in the presence of such kindness. It only proves unfortunate when we come to accept this hospitality as our due. The translator told me, aside, “I think I’ve heard, Professor Blackburn, that in addition to Dr. Fukomoto’s usual household chef, he has laid on two assistant chefs for your visit!”

This concerned me. I had neglected to ask my Japanese academic colleagues, Toshima and Kimura, to prepare the way for me, as other colleagues in the Seven Countries around the world had figured out how to do long ago. I was neither “culinarily curious” nor “gregariously gourmet.” I realized that I was trapped. For the successful conduct of our study in Japan, I would have to submit to Ushibuka hospitality in every regard.

Prior to arriving at the good doctor’s home for our first dinner together, I took a stroll around the bay to look at the fishing boats tied up at the wharf and to see the cargos they had brought home for local markets. Exotic scenes and tantalizing aromas ranged from fishes to hawsers to the straw that packs the ice in the ships’ holds, to tea, spices, and seaweed.

Stronger than these delights was the sickening odor of sewage. Nevertheless, the waters of the harbor were clear. I could see echinoderms, starfish and spiny sea urchins, fixed to the rocks below. But I knew the clarity of the water was misleading.

Far across the bay, we could see the peninsula of Minimata. Life magazine had just a few years earlier depicted on its cover a young woman victim of Minimata Disease – chronic mercury poisoning. Industrial toxins drained into the bay, built up in the food chain, and concentrated in the fish and seafood consumed so prominently by the Japanese. The taught skin around the victim’s face; the drooling mouth; the scrawny, contracted limbs and distorted posture, forever fixed, worldwide, the image of industrial pollution.

West of Ushibuka Harbor, one could see the tiny island where the Portuguese established a trading foothold in 1600, built a church, and converted many islanders to Christianity. The church still stands as a memorial to the courage of those Japanese who, later, when the Portuguese were driven away, were challenged by their Samurai leader to stand on the symbol of Christ and swear they were not Christians. None of these devout new converts, according to legend, could desecrate the symbol. They all admitted their religious conviction and were carried off to their deaths.

Beyond the island, I watched the sun set over the Japan Sea, with red, purple, and lavender-scalloped clouds radiating in long tendrils, like some huge sea animal. The cries of sea birds, the beauty, and the centuries of tradition – all were inconsistent with my image of Minimata Disease and with the pervasive stench of Ushibuka Bay.

New Hazards in the Field: Sashimi

One hour later, a parboiled, pink, Western creature emerged from the 120-degree waters of Fukomoto’s Japanese bath, clad in a lightly starched yukata (lounging robe), and feeling every bit the honored visiting American. We sat down together – Kimura, Toshima, Fukomoto and I – and the dinner service began. Fortunately for me, Fukomoto had a dining area allowing our feet to be placed comfortably on wooden racks below the table, so I didn’t have to sit cross-legged. From the racks, a soft heat radiated, to take away the chill of a wintry day in the otherwise unheated house.

With fanfare, the rice-paper partitions opened and three impeccably clad chefs entered and laid before us the first course – purple, spiny sea urchins like those I had seen a short time before at the bottom of smelly Ushibuka Bay. Their tentacles were still moving. I was instructed to use a tiny spoon to dip into the shell of the living urchin and extract an orange granular substance, presumably the roe, and to transfer this mass to a small enamelware dish. This I was to mix with a spiced, highly salted seasoning, and eat. The delicacy was meant to prepare the palate for later courses.

Down it went. The first wave of nausea and apprehension swept over me. I tried to convince myself that my discomfort was psychological – that the chances of becoming ill, from an allergic or toxic reaction to the seafood or later from contaminants – were extremely remote. I should simply face the odds and take it like a man!

The second course arrived, presumably from the same foul bay. It was the largest lobster I have ever seen, resembling the Florida species without major claws but antennae well over a foot long. The head chef, in a deft motion with an incredibly sharp blade, sliced open the cartilaginous carapace and, with a simple gesture, pried and propped it open, exposing the jelly-like, translucent, uncooked flesh.

I assumed that lobster process sewage actively, not like oysters and clams, and that its meat was not likely to contain the source of pollution I had smelled. But having avoided sashimi so far, and having never before eaten a piece of raw fish or seafood, I felt overwhelmingly threatened. At the first bite, I broke out in a sweat, convinced that I was having a reaction. The lovely pink glow from the hot bath merged into a ghastly pallor.

Just at that moment, the nurse serving as my translator entered the dining room with effusive apologies and numerous curtsies, and knelt between my host and me. She explained to me, systematically, the dishes served and those coming up. Fortunately, subsequent dishes were baked or boiled. I made it through the meal without embarrassing myself, eventually retiring to my room in the hospital, where I did as much as I could to lose the exotic meal I had consumed.

The next morning, summoning the translator, I started with the long story of how, years before in Yugoslavia, I had become ill with Shigellosis, a form of typhoid, and had lost both good digestion and all lactose tolerance as a result of the severe dysentery.

I indicated that for survival I had been forced, over subsequent years, to bring much of my own food on field studies. I pleaded that I could eat only well-cooked, lightly seasoned fish, meat, and vegetables, with a little of the local beer or wine, and lots of rice. I explained earnestly that I understood the remarkable sacrifice my host had made to provide this hospitality. But I explained to her, as I could not explain to him directly, that unless he wanted me as a long-term patient in his hospital, a radical shift in the menu was indicated. I needed simple fare – vegetable or seafood tempura, or sukiyaki, boiled meats and vegetables.

The good doctor, whether or not he ever really understood, “got the message.” He fired the two extra chefs and put on alternating meals of tempura and sukiyaki, along with desserts of canned Bartlett pears. This change allowed me a hard-working and delightful sojourn of several weeks on the southern island of Japan.

The Ushibuka survey concluded, the entire survey team stood in a row at the quai, waving to me at the rail of the ship. Long confetti streamers led from my heavy pink hands down to the delicate olive hands of our hosts on the wharf. I flirted with them by tugging various lines of confetti until the connected one giggled. Later I found in my stateroom the ultimate gift from Fukomoto: a new Seiko quartz watch!

Thirty-fifth Anniversary Conference of the Seven Countries Study, Fukuoka, October, 30, 1993

The Seven Countries Anniversary celebration arranged by Toshima and Koga was professionally and socially delightful, particularly the renewal of old friendships. Flaminio Fidanza refound his old “moniker” for me: “Enrico Il Nero,” in contrast to Henry Taylor whom he called “Enrico Il Grande.”

The scientific part of this celebration dealt mainly with the changes observed by the Seven Countries investigators in the lifestyles and disease experience of their regions over the decades since the original surveys. These changes are touched on in the several conclusions throughout this presentation and are treated in detail in a companion volume, Lessons for Science from the Seven Countries Study (Eds. H. Toshima, H. Koga, and H. Blackburn, Springer Verlag, Tokyo, 1995).

The social part of the conference honored Ancel Keys, approaching his ninetieth birthday. It included numerous post-prandial reminiscences by the Seven Countries colleagues. A few of these are reproduced here.

Srejko Nedeljkovic tells of life in Belgrade these days – many burglaries, and a large black market run by thugs. The whole of society is in upheaval in the former Yugoslavia. He felt fortunate to have made the trip, “escaping” through Budapest.

Alessandro Menotti reminisces about one of the Italian surveys: “In the mornings between 9:30 and 10:30 the electrocardiograms were terrible because of AC interference. After three days of this, we discovered that in the basement of our building was a kitchen. At that moment each day, the cook started an enormous potato-peeling machine, and the electrical fields created were disturbing the ECG recording. We had to call back the men who had been seen during those hours, because their records weren’t readable at all by the Minnesota Code!”

“Another story started at the survey in Rome for the Italian Railroad Study. Our major consultant was Henry Taylor. In my family, he was called, “the American cowboy,” because of his kind of casual fooling around. He stayed in a small pension. Every morning, I went to pick him up by car to take him to the hospital where the work was going on. During this period his wife was traveling in Denmark. She bought a new Volvo to take to the States, and drove it down to Rome. There the car was available to Henry Taylor, so one day I didn’t have to go to take him to the hospital.

On that day, he didn’t arrive for several hours. I called the pension to find out what happened. At the first bend, a curve to the right, he had crashed into the first car parked on the street. He had a lot of problems with insurance, and he didn’t speak Italian. But the Volvo resisted very well; they are very strong cars. The next day, again, he didn’t arrive. Again, he had crashed into another car at the same curve, at exactly the same place! The telephone calls for the insurance posed all kinds of problems. The third day, the same story. So I started picking him up again.

At the end of the survey, together with his wife (she drove), they took the Volvo to Rotterdam. They put the car on a ship and took a plane back to Minneapolis. There they waited for the ship to arrive in New York so they could pick up the car. Unfortunately, the ship sank in mid-Atlantic!”

Andy Dontas also reminisces. “In 1956, at a meeting of the American Heart Association in Chicago, Ancel Keys was already expounding his ideas about diet and heart disease. I approached him afterwards as I was about ready to return to Greece, and we had a long talk about possibilities for field research.”

“You can’t imagine the problems we had to face in the Crete pilot survey in 1957. It was just like going today to Nigeria or maybe to Nepal to do a study. Electricity was a big problem. No electricity anywhere on Crete except in Iraklion. There was no running water. There were no paved roads anyplace except in Iraklion.

In Corfu the next year the difficulties were more personal than physical because no participant could be convinced to be examined unless he got some kind of reward. So we had to examine his family as well, and do their electrocardiograms and everything, free of charge.

I think the best story of the Crete survey was when we walked down to the dock area where all the nice grapes were packed. Flaminio Fidanza was worrying all day how to pack the grapes he had bought, and so finally put them in his bathtub.

He was rooming with Kimura, who complained bitterly. One wanted to eat, the other to bathe! The prototypical Italian and Japanese.”