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Why Italy?

Italy presented Ancel Keys and the Seven Countries Study collaborators with the prototypical Mediterranean lifestyle and its apparently healthy diet of grains, pasta, legumes, vegetables, fruits, olive oil, bread, and wine. Italy, in contrast to other Seven Countries areas, also has one of the great traditional cuisines of the world. Moreover, for the Italian investigator concerned with both regional and individual differences, Italy is not just one country or culture. The contrasts of Nicotera in Calabria, Porto San Georgio on the Adriatic coast, Montegiorgio in the Marché hills above the coast, and Crevalcore in the rich delta of the Po River, provide abundant contrasts of northern and southern Italian eating patterns, heavier on meats in the north and on legumes, pasta, and olive oil in the south.

Field adventures in Italian villages began with Crevalcore (which I have loosely translated, Broken Heart), in Reggio Emilia, a region north of Bologna that has unusual Catho-Communist politics and classic Northern Italian cuisine. For medical historians, Crevalcore is the birthplace of anatomist Marcello Malpighi, 17th century "father"of histology and discoverer of glomerular corpuscles, the complex filtration system of the mammalian kidney. His life-sized likeness in bronze decorates the town's main piazza, as well as the cover of the companion volume to this one: "The Seven Countries Study, an Adventure in Cardiovascular Disease Epidemiology." An hour's drive north of Bologna, in the fertile plain of the Po Valley, Crevalcore was inhabited by prosperous, proud, and - incongruously - Communist farmers. The region was chosen by our nutritionist colleague, Fidanza, as representative of the rich northern Italian eating pattern.

March 6 : "Uno Disastro, Enrico" (A Disaster, Henry)

The survey went as swimmingly as the accompanying wet March weather. On its first day, the team examined sixty men. We find in field studies that we must strike a delicate balance between over- and under-scheduling participants, to prevent chaos among the staff and ill-will among the hardworking farmers. Delays occur mainly at the primary interview and diet recall, or at the electrocardiographic and high-tech recording station. At any rate, we did a good job the first day, though it was a long and arduous one for all.

Night fell as we shuttered the Crevalcore survey center at the close of work. With it came a steady cold rain and blustery winds. Dead tired, two Italian medical colleagues and I set off in a tiny Fiat 500 toward the promise of comfort and dinner in the warm restaurant of the Hotel Bologna. In the back seat, I was decidedly uncomfortable as we careened along the slick, wet-black roadways, narrowly avoiding ambulant peasants dressed in somber grey capes and dark hats. We dodged between them and farm carts and bolted down the straightaways. I fantasized about the meal to come in the restaurant under the ancient arches of Bologna: twisted loaves of flaky peasant bread, a tangy radicchio salad, and an immense bolito, the traditional platter of boiled chicken, beef, pork, and lamb, washed down with a solid Lambrusco. Eventually, I dozed off in the back seat.

Some fantasies later, I was awakened suddenly by an awful thud, a shock, and a blast of cold wet spray in my face. Our tiny Fiat was swerving wildly, decelerating, finally coming to a stop in blackest night on the outskirts of a small town. In the front seat, my colleagues were profiled against a weak street lamp through a huge, jagged hole in the windshield. They began to shout hysterically: "Misericordia, Enrico! Accidente! Uno disastro! La bambina. Muerta!" This was followed by an incomprehensible stream of keenings and apparent cursings.

My dulled consciousness slowly awoke to the tragedy around us as my colleagues gestured frantically back up the roadway toward a tiny still figure in a puddle at the side of the road. I forced myself to be calm, if only to contrast with their panic, while they, paralyzed, hung onto each other and onto the steering wheel. I suggested that two of us go back to the form in the road and the third run to summon help. No one moved.

Finally, I pushed by them from the back seat, opened the Fiat's door and stumbled up the street in the dim light in the rain, noting out of the corner of one eye a bright brass plaque reading "Dottore" something or other, on the gatepost of a villa along the way. I then came upon the crumpled bundle, a girl of about ten years. An old peasant lady picked herself up from the side of the road and hobbled toward me, mumbling unintelligibly. Meanwhile, my colleagues remained in the car, transfixed and moaning. Nothing else was happening. No ambulance, no police, nothing!

Against my better judgement, fearing long delays in help, I gathered the unconscious girl in my arms and struggled back toward the bronze plaque which I now could make out: "Dottore Sergio Messina, Medico Practico." I rang the bell insistently until a distinguished, though rumpled, middle-aged man in a bathrobe appeared, also mumbling, at the gate. He took one look at the face of the child in my arms, then he, too, became hysterical, shrieking in Italian, "Horror of horrors, she is the daughter of my housekeeper. Is she dead?" We then moved together toward the villa, where he opened the portal and we entered, he wringing his hands, weeping, casting furtive glances at the still form in my arms.

I placed the little one on the doctor's examining table, repeating over and over, "Prego, ambulance, prego!" He would rush to the phone, then rush away, scurrying ineffectually about his cabinette, wailing "Sono solo, sono solo!" I, too, felt all alone, but proceeded to examine the girl. One pupil was large, but both responded to light. She may have had a head injury, but she wasn't dead! All her extremities were flaccid and the right leg drooped at an exaggerated angle, indicating a major hip or thigh fracture. Unexpectedly, she began to whimper, and then wretch. Not only was she alive, but was regaining consciousness!

My colleagues then appeared in the doctor's villa, still speaking in torrents. Finally one of them took the doctor's telephone and called the police and an ambulance. We all milled about, miserable, until the child was splinted and taken away to a hospital in Bologna. Then, summoned by the police back to the roadside, we underwent an official, if cursory recounting of the "accidente" and detailed measurements on the pavement to indicate the trajectory of the girl and of our car.

These good colleagues, as I have found is customary with all my Italian friends, drive their small Fiat projectiles on the open road with the accelerator floored. If the little cars were able to go 120 kilometers an hour, they were driven at 120. The terrible driving conditions of a dark, windy, wet night, and entering the outskirts of a village, were no deterrent.

The girl had started running across the street from the left, seeking we know not what. She was struck first by the Fiat's left front bumper, hurled upward to hit the windshield, shattering it. Then she was thrown to the top of the car, hurtled off to the opposite side, knocked down the old peasant woman passerby, and finally landed in the roadside puddle. No doubt these progressive decelerations explained her survival.

In the days following this awful event, my otherwise bright and charming colleagues continued to refer to the event as, "uno disastro, Enrico," implying an uncontrollable event, an act of God. The only culpability, it seemed, was the girl's, darting across the street on a rainy night. That we were driving too fast on a dark, wet night through a village, simply never seemed to enter their minds. Nowhere, moreover, were these facts noted by the village policeman who became obsequious when the Professori Dottori introduced themselves. Later, the rationalizations led to an apparent absence of concern. To my knowledge, nothing further was done about the injured girl and her family, other than sad shaking of heads. I hope, however, that my knowledge is incomplete.

At any rate, I often wonder whether that little girl is now a happy Italian matron and mother of beautiful children, or possibly is a professional, perhaps even an especially compassionate orthopedic surgeon. Or, might she be a crippled recluse in a barren institution somewhere?

I will never know.

March 8

Back in Crevalcore, not a word was spoken about this horrible stain on our mission. There was no discernible effect on the community's attitude or level of participation, as far as we could tell. The survey settled into an efficient routine for a full three weeks. The Italian team, certainly less stoical than the U.S., Yugoslav, Dutch, Finnish, or Japanese teams, nevertheless worked together effectively. Team members were quick to identify bottlenecks, and resolve them, and respond to the usual daily confusions. And our evenings at the Hotel Bologna were a delight.

In Crevalcore itself, the long mid-day break became the most pleasant part of the long work day. We would visit Trattoria Julia, little more than a "hole in the wall" with tables for a dozen people and a tiny, narrow kitchen with open gas burners. Julia prepared exquisite dishes, especially a spinach lasagna. Unfortunately, I had three strikes against me as far as Julia was concerned. I was American and non-communist; I spoke little Italian; I was not possessed of the gigantesque appetite of my Italian colleagues. Eventually, however, Julia accepted me, probably because I was such a faithful, if modest, customer. The whole team delighted in the ambiance of her place, the banter, the aromas, and the elegant meals.

Evenings in the team's Bologna hotel were usually productive as we reviewed the day's survey activities and made suggestions for improvements. Northern Italian cuisine, served until late in the brightly lit dining room, included huge plates of fresh pasta lightly scented with butter, olive oil and herbs. This was washed down with a light, red wine, and complemented in texture by the flaky twists of local bread. Lightly broiled fish, skillfully de-boned by our cheerful waiter, was followed by a huge traditional platter of boiled meats.

On evenings when I felt less sociable, I holed up in my room, playing saxophone along with Sydney Bechet records on a boisterous Italian portable record player. It was there that I learned "The Egyptian Fantasy," "Passport to Paradise," "Waiting for the Day," and other expansive Bechet ballads. It was the first year of my romance with an old Conn soprano, still my favorite horn thirty years later. These evenings, accented by a Dewars with San Pelligrino, without ice, provided a marvelous release from the grueling monotony of days in the field. I became known in the Bologna neighborhood as "Il Maestro Musico," receiving a kind, if bemused, tolerance.

March 10

It appears that alternating current interference is with us permanently, with no alternative locations available for the electrocardiographic station. Nevertheless, the station is highly efficient; average time for an electrocardiogram from start of a case to start of the next is only ten minutes. The average time from the moment of stopping exercise to starting the precordial lead record is thirty seconds, and to completion, another fifty seconds.

We have seen two typical old anterior myocardial infarctions in the first hundred participants at Crevalcore, a case of malignant hypertension with fundal papilledema, macular star, and hemorrhages, and one diabetic with capillary aneurysms.

My job of training and early supervision here is nearly done. I will leave behind extensive guidelines for colleagues Mohacek and Tedesco on electrocardiographic recording and trouble-shooting, and on criteria for standard clinical coding.

March 22

We hit case number 600 today in Crevalcore.

continue...

Collaborators
	Flaminio Fidanza Fidanza was the first major Italian collaborator of Ancel Keys. They met during Keys' 1951-52 Oxford Sabbatical, spent partly in Naples where Fidanza was a young academic nutritionist. Through Fidanza's local contacts, they were able to recruit clerical workers and executives of Italian banks and industries to carry out the first informal population comparisons relating diet to blood lipid levels. Fidanza was and is a devoted, passionate Italian academician, harboring strong professional opinions based on a long career of research and field experience in nutrition and in methods of measurement. Bombastic, great-hearted, and warm with his friends, he can be sharply critical of those who fail to meet his high standards. Portly but quick-moving, he is always at the center of attention. But Fidanza is a careful listener and a "quick study," always responding enthusiastically, with only a tinge of Old European intellectual skepticism and a trace of Italian fatalism. Tales abound to illuminate the emotional side of his nature. But professionally, he is immensely informed, with great bench savvy and practical experience in the field. There is no nonsense when Fidanza directs, or is even involved in a survey; he is a fierce cloud one moment, a warm ray of light the next. Fidanza's curiosity led him to explore, incorporate, and elaborate on many of Ancel Keys' ideas. His skepticism led him to question them as well. I suspect that his persistent dogging of Keys with the idea that U.S.-Italian differences in blood cholesterol levels were not entirely explainable by fat composition of the diet contributed to the series of careful metabolic ward explorations of Keys and company. These were carried out in the University of Minnesota Laboratory of Physiological Hygiene through the 1960s, using fruits, nuts, complex carbohydrates, vegetables, and fibers, while holding fat and calories constant. It may also have been Fidanza's persistence about individual differences in blood lipid responses that encouraged Keys' pioneer explorations of the intrinsic level of blood cholesterol and the variability of individual responses to a given dietary change. And it was surely Fidanza's gregariousness and acquaintance with foods, people, and places in Italy that principally determined the choice of Italian villages in which to test the dietary hypotheses. It was a delight to have Fidanza in the Laboratory of Physiological Hygiene for the better part of a year in the late 1950s, when he was a bachelor and life of the party among younger faculty and graduate student gatherings. We were all pleased, of course, when he found his quietly competent Italian bride, Adelberta, who shared his knowledge of the laboratory, complemented his skills, and softened his restless impatience and acerbity. I think of Fidanza mainly as leader, critic, and stimulus. He is always on target with a well-timed welcoming or celebratory toast, a salutatory introduction, a learned dissertation, or a sentimental eulogy. But I also remember him for the beauty of his language. In Fidanza's speech, every vowel is rounded and musical, every word intelligible, every phrase original, every sentence elegantly but simply constructed, and every message sparkling clear. Fidanza was, from the outset, one of the "seminarists"living in the community called Minnelea on the coast south of Salerno. He was one of the originals responsible, along with Vittorio Puddu, for finding the property that they all bought advantageously in the middle 1960s and share so graciously today with colleagues Ancel Keys, Jeremiah Stamler, and Martti Karvonen of Finland. In recent years, Fidanza has become preoccupied with the duties of his chair at Padova. Unfortunately, we see him rarely at international cardiological gatherings. He has reverted to nutritionist type. He remains, however, a leading Italian light, an international figure in his field, and deserving of great credit for the success Ñ conceptually and practically Ñ of the Seven Countries Study and its operations in Italy. The thirty five-year reunion and conference of the Seven Countries Study, arranged by Toshima and Koga in Fukuoka in October, 1993, was graced by Flaminio's and Adelberta's presence. There, he forcefully insisted that the monograph recently prepared by the investigators and edited by Kromhout, Menotti, and me, should not see light without his rigorous edit. When, aside, I remarked to Adelberta: "Flaminio really hasn't changed, has he?," she replied with a resigned but affectionate smile, "Unfortunately, not at all!"
	Vittorio Puddu Professor Puddu, now departed after a long illness, was ever gracious, calm, and dignified, fully as Italian as Fidanza, but in the manner of "il grande padrone." It was he who gave our team access to the hospitals and to the recruitment of young colleagues, Mario Mancini, Alessandro Menotti, Bruno Imbimbo, and Salvatore Panico. And it was he who chaired the Seven Countries Study working conferences in Rome. It was also he who provided quiet and effective leadership to the International Society of Cardiology, without putting himself forward for acclaim or for the presidency. It was he who introduced us Minnesotans to the grandest and to the simplest of Roman restaurants. I recall particularly the deep-fried baby octopus and artichoke, specialties of a tiny restaurant in the Jewish Quarter where he was so admired. And I recall the most elegant Roman restaurants where he presided with grace, regaling us with stories of La Bella Roma, pre-World War II, when, as he said, that magnificent city was just a big town. He helped us to imagine Rome with all its ancient history and beauty, yet with the calm of the 1920's and early 1930's Ñ and a population of only 250,000! That would be as delightful a prospect as, say, living in San Francisco during the same Belle Epoch. Vittorio Puddu, victorious, kind, dignified, and physically grand with his beige suits and bronzed bald head. He was elegant down to his toes, and to his traditional Christmas gift, a special Italian coffee cake.
	Mario Mancini Mario Mancini was the earliest collaborator of the second generation of Seven Countries Study investigators. He is now distinguished Chief, Medical Clinic II, in Naples, editor of a new journal, Chair, International Society and Federation of Cardiology Scientific Councils, and dignitary in cardiovascular and metabolic circles in Europe. In the 1950s, as a young protégé of Puddu and clearly destined for leadership, Mancini was one of the early post-doctoral fellows to arrive at the University of Minnesota Stadium Gate 27, working on projects in hemostasis and lipids. There he was frequently amazed with middle America, the quiet calm of our lives, our confidence in our professional futures, and to him the unexpected richness of our family life. Overwhelmed also with mid-western orderliness and manners, particularly on the streets and roadways, he marveled at how people drove with such courtesy to others; without anger, pride, or showing off. Mancini, no longer active in Seven Countries data or its field work, remains a superb host for gala celebrations in Anacapri for Ancel and Margaret Keys and the Seven Countries collaborators. He remains a steadfast friend of the study, and an international leader in the field.
	Alessandro Menotti Menotti, too, was a fellow in cardiology under Puddu in Rome, and became progressively involved in the Seven Countries Study through an assignment to the Italian Railroad Study, a collaboration between Henry Taylor and Puddu. Solid, calm, hardworking, meticulous, and intellectually curious, Menotti was the ideal person to be responsible for quality control and coordination of the Italian Railroad Study, and later, of the Seven Countries Study. Happily, he was given the field organization, data collecting, and data editing responsibilities after the first series of five-year Seven Countries surveys. At that time, taken up with crucial concerns for new activities at the Minnesota base, I agreed, "carte blanche," that Menotti take over coordination of the data gathering and develop collaboration in analyses with Keys and the Seven Countries investigators, a collaboration that has proved smooth and productive. Menotti, recently retired from his high post in Rome, has currently the position of Visiting Professor at the University of Minnesota, which promises continued productivity and collegiality for the Seven Countries Study.