• Ancel Keys  • Seven Countries  • A Half Century of     Research  • MN Starvation Study  • A History of    Cardiovascular    Disease Epidemiology

A Half Century of Epidemiological Research

At a recent international conference, a Soviet cardiologist told an Epidemiology staff member, "Oh, I know where you work! It's a famous place – some little offices under a big stadium. I was there many years ago to meet with you Dr. Keys!"

Those "little offices" under the bleachers of the University's Memorial Stadium were the home until 1991 of the Laboratory of Physiological Hygiene (LPH) and the laboratory's successor, the Division of Epidemiology.

Today Stadium Gate 27 is gone, supplanted by our main offices at the West Bank Office Building and several sites on and off campus. Collectively, they house nearly 600 faculty, staff, and graduate students engaged in research projects in areas ranging from human biology to public policy.

Professor Ancel Keys and "The Lab," as it became known, both gained national recognition during World War II. Keys assembled a multi-disciplinary team of physiologists, physicians, biologists, psychologists, and chemists who carried out diet and stress studies in the laboratories of the Stadium South Tower. The Lab organizers were veterans of classical training in physiology and biochemistry.

After years of research on body composition and function, Keys and his colleagues were well prepared to address the urgent questions raised by World War II, such as the effects on men of heat, cold, and semi-starvation. The Lab developed a practical field survival ration for fighting troops, later called the K Ration (K for Keys) which became the official combat ration of World War II.

Then, forecasting that starvation would be the most serious physiological problem resulting from the war, the Lab staff began its well-known research on the physiological effects of famine. A group of conscientious objector and army volunteers housed in the Stadium were assigned to long-term deficient diets.

The Human Starvation Study

The Minnesota Human Starvation Study is now recognized as a classic. This wartime research led to a series of fundamental studies of the effect of systematic changes in physical activity and diet on human physiology.

After the war, the Lab became a part of the School of Public Health and began studies on the rapidly emerging health problem of peacetime: cardiovascular disease. The Minnesota Business and Professional Men Study, conceived and initiated in the late 1940s, followed men for more than 30 years, with a goal of examining the aging process and the causes and development of coronary heart disease. From this and studies done elsewhere, the risk factor concept for cardiovascular diseases emerged.

At the same time, Lab researchers felt that many of the answers they sought were being held up by inadequate methods. As a result, they developed a number of basic measures for characterizing human structure and function, along with objective measurements of disease for uses in population studies, allowing the new field of cardiovascular disease epidemiology to move forward. The Minnesota methods include:

• indirect measurement of body fat by underwater weighing and skinfold thickness measurements
• quantitative assessment of maximal work capacity by measures of oxygen consumption and heart rate during work
• standardized methods for measuring blood lipids and their fractions
• objective measurement and classification of the electrocardiac manifestations of heart disease (the Minnesota Code)
• standardization of blood pressure measurement in the field
• standardization of cardiovascular disease survey methods (for the World Health Organization), including methods of population sampling and recruitment, and
• a practical tool for predicting the effects on blood cholesterol of a specific change in dietary fat or cholesterol (the Keys Equation).

These methods were applied to the study of diet, physical activity, and heart disease risk in the late 1950s, when the Laboratory, under Keys' direction, began long-term projects that were international in scope. The roles of diet and occupational activity were studied in U.S. rail workers by a team led by physiologist Henry L. Taylor, operating on the rails in a fully equipped Pullman railroad car laboratory.

Ancel Keys and I supervised locally trained teams who conducted field surveys of heart disease and risk factors in Japanese, Italian, Yugoslavian and Dutch villages, in Finnish forests and on Greek islands. These surveys - the Seven Countries Study - clearly established that populations differ vastly in their rates of coronary heart disease, and that the differences are significantly related to the nature of the habitual diet and its effects on average serum cholesterol levels.

The Lab's small-scale experiments and large-scale population observations, taken together, produced firm evidence of the powerful influence of lifestyle on disease; the time had come to test experimentally the effects of making lifestyle changes. The first test was the collaborative pilot Diet-Heart Study in the 1960s, which demonstrated that blood cholesterol levels could be predictably changed in large numbers of people by modifying their diets, by either preparing or prescribing the food they purchased and ate.

When a government panel decided in the late 1960s that "the definitive diet-heart experiment" was not feasible, the Lab helped devise tests of broader public health strategies, and a generation of national preventive trials followed.

• The Hypertension Detection and Follow-up Program demonstrated that a systematic community-based approach to identification and treatment of hypertension markedly reduced cardiovascular disease risk.
• The Multiple Risk Factor Intervention Trial (MRFIT) showed that systematic strategies lower risk factors of middle-aged high-risk men.
• The Coronary Drug Project showed that risk could be reduced following a heart attack.

The most recent of these trials, the Minnesota Heart Health Program (MHHP), demonstrated that entire communities would organize themselves effectively to promote health through lifestyle change. During five-year intervention periods in each community, this project promoted a "heart-healthy lifestyle" in three Minnesota cities through a variety of local organizations, events, and programs.

The community model, developed and tested by MHHP, is being used widely throughout the United States. Its educational and promotional strategies now are applied not only to cardiovascular disease prevention but to other major public health issues, as well. These pioneering efforts introduced new methods for health promotion in schools, work sites, community organizations, and government.

With the spread of health promotion, the changes in social mores, and the greater value given to health, the U.S. population is changing now almost more rapidly than we can influence it. A major Division surveillance project, the Minnesota Heart Survey, has found that deaths have declined as much as 50 percent for heart attacks and 60 percent for strokes in the last two decades, due to improved lifestyle and to better cardiac care.

Consequently, the Division is turning to new challenges in testing and improving strategies of health promotion. Community projects are studying the proposition that direct and mass media education strategies, combined with community organization, are more effective than a single strategy.

Division investigators are applying what they have learned in cardiovascular disease prevention to helping communities organize preventive approaches to cancer, injury, adolescent substance abuse, sexually transmitted diseases, and health issues of childhood and adolescence.

Basic research also thrives. A tradition of bridging biology and public health with epidemiology and behavioral science continues with the most recent major program development of the Division, the Cancer Prevention Research Unit.

Six decades of Minnesota studies have firmly established that populations and individuals differ greatly in their risk of chronic diseases and that these differences are strongly related to lifestyle, which, in turn, is culturally determined. These findings, and this thesis, have become the core of much epidemiological research on the prevention of chronic disease; they now provide a sound basis for public health policy and preventive practice.