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Why The Railroad Study?

The study of U.S. railroad men was the "baby" of Henry Longstreet Taylor. He had the idea to compare coronary heart disease rates among rail occupations to get at the role of habitual physical activity. Taylor realized that there would likely never be a "definitive experiment," due to feasibility and cost, in which physical activity would be modified and the effect on heart attack rates measured.

The U.S. Railway Workers Study was originally designed to be independent from the Seven Countries Study and to make only internal comparisons among rail occupations having different levels of habitual physical activity. It was only later incorporated by Keys and Taylor into Seven Countries analyses to provide representation of the homogeneously high-fat, high-saturated-fat eating pattern of North America. It was not a part of the initial Keys' hypotheses about differences in coronary disease rates according to habitual diet among contrasting, stable, rural populations.

Lewis Thomas once defined epidemiology as "thumbing through death certificates," an insensitive and incomplete depiction, at best. But it was such a "thumbing," done early on and systematically, that revealed to Henry Taylor and those of us who had become his colleagues, that coronary heart disease death rate differences among classes of railworkers were in the direction of the hypothesis that physical activity causes lower rates. Taylor was also the first to criticize his own brainchild, pointing out problems of misclassification of physical activity in the Railroad Retirement Board list of occupations, and of selection bias, which might tend to concentrate workers who were ill, or who were becoming ill, among the less active railroad professions.

This refreshingly candid criticism of one's own offspring is rarely found in science today. Taylor's basic integrity was accompanied by a skeptical and dispassionate "Old School Physiology," which put him in good stead for epidemiological pursuits. So it was that the novel idea was proposed to the National Institutes of Health to examine the active and less active rail workers at their work sites, measuring coronary disease incidence in the railway cohort while accounting for measured confounders and coexisting morbidity. To his surprise, and certainly to the surprise of some of his Minnesota colleagues, the proposal was approved by peer review in the National Heart Institute. Thus began the U.S. Railway Workers Study.

Fall, 1957 - Riding the Rails

The Railroad Study operation was "first class" from the beginning, and I was happy to be involved. I had a few pangs of regret when I was unable to accompany Ancel Keys in the fall of 1957 to conduct pilot surveys in Finland, Crete, and Southern Italy, but my services were needed to get the Railroad Study on track. This we did, with procedures, forms, and the beginnings of cardiovascular disease classifications that would eventually become The Minnesota Code and the WHO book: Cardiovascular Survey Methods.

In those exciting early days, I particularly enjoyed working with Taylor to design a unique traveling laboratory. He proved extremely skillful in face-to-face negotiations with railway managers and union brotherhoods, obtaining, among other things, the long-term loan of a Pullman car for the study. With the new National Heart Institute grant, he proceeded to have that car renovated in the old Great Northern maintenance yards off Como Avenue in St. Paul, where we spent countless hours supervising and kibitzing. The laboratory car was well laid out, with a reception area; a series of examining rooms for anthropometric measurements, medical history, physical exam, and blood pressure; and a large work area for the resting and exercise electrocardiogram. Toward the end, there was a booth for the chest x-ray and then a wet lab. area for blood and urine sample processing.

After a trial run in the old St. Paul Depot, we moved out on the rails, hooking up to the power, water, and steam in stations or rail yards across the line, northwest to the cities of Spokane, Pasco, Seattle, then down to Portland and San Francisco, and back again.

Taylor had carefully negotiated two essential elements for the success of the study: Clerks could be examined at their work site during working hours without their pay being docked, and, at my insistence, information we collected on all employees would be held confidential and not provided to railway physicians or companies. These guarantees clinched the enlistment of the rail brotherhoods. The first-round survey involved comparing the risk factors and medical findings of rail executives and clerks with switchmen and right-of-way personnel, among whom Taylor's pilot work had validated different levels of habitual activity and on-the-job oxygen consumption.

The railmen were a jovial bunch, and our crew, too, was congenial, working together effectively and examining up to forty men a day. Our team developed in this first-round survey many of the field strategies that became trademarks of Minnesota population studies over the years: careful planning and pre-negotiations; field testing and pilot studies; clear definition of the population with a census; intensive recruitment; thoughtful scheduling; and central data-editing, processing, and analysis. In our working and traveling together, we also elaborated - by plan and by trial and error - much of the general field procedure that the Laboratory of Physiological Hygiene, and then the Division of Epidemiology, utilized in subsequent operations.

We learned, for example, that staff, after six straight days of work, need a break in order to remain effective. And after three weeks straight, they need a brief home leave. We also found it impossible to use a converted 1895 Rock Island Line presidential sleeping car as a dormitory. So we were housed in quiet motels and ate dinner in attractive restaurants. This helped relieve the heavy work routine and maintain morale over the long haul. We also learned to avoid over-booking, particularly the first day at a new location.

There were many delightful adventures "on the rails," both intellectual and social. As we traversed the land, we on the team held long conversations about the colorful railmen we met, and about the burgeoning new field in which we were involved - cardiovascular disease epidemiology. On the second round of exams, starting in 1962, I had my soprano saxophone along. I'd serenade the countryside from the rear of the lab. car, which usually served as the caboose for the train to which we were attached. We acquired many friends along the line as we made contacts to hire and train short-term medical examiners. Several Twin Cities colleagues, Robert Rothenberg, Dennis Kane, James Dahl, "Mack" Richards, and William Moore, participated in two survey rounds over six years, '57-'58 and '62-'63. We were joined by a series of overseas visitors who came to train at the new "epidemiological Mecca" at the University of Minnesota, Stadium Gate 27.

The staffing was quite exceptional as we began the first-round survey, with such Minnesota experts as Francisco (Paco) Grande helping with the initial dietary interviews, and Joseph (Jaschka) Brozek doing the anthropometric measurements. I, along with technicians Walt Carlson and John Vilandre, and later, biophysicist Pentti Rautaharju, carried out the exercise electrocardiographic monitoring. Nedra Foster and Gail Dolliff handled the blood, urine, and x-ray technical duties, while I conducted the clinical exams, along with drop-in colleagues. In all it was a happy, disciplined, and effective operation.

We chose to study U.S. Railroad employees because they were largely stable in their specific occupations and in their lifetime employment, and had measured differences in the physical activity required at work. Moreover, all rail employees are covered by a pension plan which maintains detailed employee records of employment, disability, retirement, and death. Permission was required of the rail companies, of the Railroad Retirement Board, and of the various labor unions involved, including each local railroad brotherhood official. All twenty rail companies that operated in the northwestern quadrant of the United States - circumscribed by Chicago, St. Louis, San Francisco, and the Canadian border - were involved. Selection of thirty sampling units ensured proportional representation in each geographical area and each size of urban area. Our staff, usually Taylor or me, recruited and scheduled participants at union meetings. The laboratory car visited each location at least twice during each survey round. Unfortunately, I kept no written or photographic record of the details of these railroad expeditions.

Conclusions

We learned from the Railroad Study that it is difficult to make valid occupational comparisons of cardiovascular disease rates when so much depends on the characteristics at entry and reasons for going into the occupation. Subsequently, there is selection tending to concentrate coronary events among the less active jobs. We also learned "the hard way," that the numbers of men sampled were inadequate for a valid comparison of active and inactive populations, and that 10,000 to 15,000 men would have been required in each activity class, based on five-year coronary heart disease incidence in the sedentary group, to demonstrate any real differences related to job activity.

The Railroad Study was among the first major longitudinal studies in which an independent relationship was not found between relative body weight or skinfold obesity and risk of coronary heart disease. On the other hand, the study did confirm very early the universality of the "standard" coronary heart disease risk factors, thus contributing to the strong inference of their causal role. Data from the study were entered into the American Heart Association Pooling Project, the first statistical summary carried out in cardiovascular disease epidemiology.

We also studied the occupational differences in reported mortality rates for the entire railway population. The relative risk of death from coronary heart disease for sedentary versus active railroad populations nationwide was 1.18. We may conclude that the relative risk ratio of 1.18 for deaths between clerks and switchmen is perhaps the best estimate available of the true difference in coronary heart disease incidence between sedentary and more active rail occupations (which have an average 600 kilocalories difference in physical activity per day). This can be compared to risk ratios of 2.2 for high blood cholesterol level, 2.1 for systolic blood pressure, 0.95 for relative weight, 1.2 for skin fold thickness, and 1.3 for height.

The Railroad Study, along with the experience in Finland, has led us to conclude that, within high-risk cultures, skinfold obesity, relative weight, and physical inactivity are coronary heart disease risk factors for the individual of "a second order of magnitude."

Finally, it should be recalled that the Railroad Study was developed by Henry Taylor independently of the Seven Countries Study and was only much later co-opted into the larger organization and analyses. Despite the industrial nature of the railroad population, the Railroad Study strengthened the comparative framework of Seven Countries by adding an affluent industrial culture. And what was learned on the rails about field methods, data handling, and disease classifications was directly applied to the overseas and general operation of the Seven Countries Study, beginning in the fall of 1958.

Collaborators
	Louise Dalderup and FSP van Buchem From Ancel Keys' early contacts with distinguished Dutch nutritionists, M.J.L. Dols, P. Muntendam, and C. den Hartog, they were keen to be a part of the Seven Countries Study and named young academic nutritionist Louise Dalderup as the point person. Competent and well-organized, Dalderup joined the activity with enthusiasm, participating in the Nicotera pilot survey in 1957. But when the Medical Research Council was finally considering the cost and commitment of joining the Seven Countries Study, they decided that a prestigious senior medical person should be in charge. Professor Van Buchem, recently retired from his position as Chief of Medicine, under a cloud that is not relevant to this story, took over the Zutphen Project with a vengeance. He was resistant to ideas about standardization or to any true collaboration. He allowed no "interference" in the surveys by visitors from Minnesota or elsewhere. Though he frequently created diversions at meetings of the international investigators, we thought that he had eventually signed on to the common study protocol, minus direct quality control or supervision of the field team. Imagine our surprise, months later in Minnesota, when we received at Stadium Gate 27, the data from the first round Zutphen survey consisting of poor carbon copies of the medical histories and physical forms, and no electrocardiograms. In response to our written and then telegraphic communications, we were informed that the electrocardiograms would not leave Dutch premises, being "too valuable to risk their loss in surface transportation." Air transportation in those days was too costly to be considered. The proposed solution to this stand-off: send Blackburn to Holland to read and code the Zutphen electrocardiograms. Already scheduled for a trip to Venice for the Research Committee of the International Society of Cardiology, plus a follow-up visit to Geneva to complete the Rose-Blackburn WHO survey manual, I made it a family affair. Wife and kids went to Nelly's parents in Geneva, and I jaunted about the continent on Seven Countries Study business. Van Buchem's solicitous care of the Zutphen electrocardiograms was so intense that he insisted they be read and coded only in his own study, which in summer was in his beach cottage at Noordwyk. He maintained, furthermore, that I should stay in that somber bourgeois home with him and his wife. I opted rather to stay in a local resort hotel, spending a pleasant eight days there. I read cardiograms for several hours every morning chez van Buchem, to the limit of my concentration, and every afternoon took tennis lessons at the resort's clay courts, and then ran the beach. The Nordic shore was eerie. My youth on the bright beaches of Florida did not prepare me for the monochrome North Sea beaches, gray sands, puny dunes, chill, steely surf, and scudding dark clouds. The natives bask under an occasional pallid sun behind brightly colored windbreaks, the only color to be seen. Dogs and horses cavort on the sand along with bathers, joggers, and kite flyers. In the end, all standard requirements of the study, and all eccentricities on both sides, were satisfactorily accommodated and no lasting harm done to the Minnesota-Dutch collaboration. As documented in the companion volume to this, "The Seven Countries Study. An Adventure in Cardiovascular Disease Epidemiology," Daan Kromhout and company - innovative and delightful colleagues - became a central force in the study following van Buchem's retirement.
	Daan Kromhout Kromhout single-handedly instigated a renaissance in the nutritional studies of the Seven Countries Study, bringing to bear his education in nutrition at Wageningen and in epidemiology at Minnesota. He was named principal investigator of the Zutphen Study by Netherlands authorities in 1978, and began participating in the rebirth of Seven Countries Study activities that dated from the Iraklion meeting of investigators in 1979. Quietly and industriously, Kromhout has effectively exploited the rich data from Zutphen in pioneer investigations of the individual and population correlations of nutrients - particularly fishes, fish oils, and anti-oxidants - with chronic disease mortality. Representing the second generation of investigators in the Seven Countries Study, he is most appreciated for his innovative concepts and for maintaining excellent collaboration with the original principal investigators. He has renewed, refined, and extended the dietary hypotheses of the study; set into motion effective new investigations and editorial processes; and shared with others a vigorous new leadership throughout the study. Just as the efforts of Hironori Toshima stimulated the study with the remarkable scientific and social conference of 1993 in Fukuoka, so did Kromhout's efforts boost the study with his editorship of the publication, "The Seven Countries Study. A Scientific Adventure in Cardiovascular Disease Epidemiology." Kromhout was the one who initiated the book, obtained funds for its support, and pushed it through to publication in the Netherlands in 1994. He and the Dutch also sponsored a delightful scientific meeting of Seven Countries investigators and others at the 30th anniversary of the Zutphen Study in 1990. Kromhout remains an active investigator in the Seven Countries Study and of other issues in nutrition. His stature and work have been recognized by his being named Director of Public Health in the National Institute of Health and Environmental Protection in Bilthoven, and by his participation in other international collaborative studies, including MONICA and INTERSALT. The energy, quiet efficiency, and collegiality of Daan Kromhout is centrally involved in this international study of human characteristics and disease risk.