Ancel Benjamin Keys

http://en.wikipedia.org/wiki/Ancel_Keys

Ancel Benjamin Keys (January 26, 1904 – November 20, 2004) was an American scientist who studied the influence of diet on health. In particular, he hypothesized that different kinds of dietary fat had different effects on health.

He examined the epidemiology of cardiovascular disease (CVD) and was responsible for two famous diets: K-rations formulated as balanced meals for combat soldiers in World War II and the Mediterranean diet, which, with his wife Margaret, he popularized. Science, diet, and health were central themes in his professional and private lives.

Early life

Ancel Keys was born in Colorado Springs in 1904 to teenage parents and in 1906, they moved to San Francisco before the 1906 San Francisco Earthquake struck. Shortly after the disaster, his family relocated to Berkeley where he grew up. His intellect was well-known ever since a young age as Lewis Terman, noted psychologist, prominent eugenicist, and inventor of the Stanford-Binet IQ Test identified Keys as one of the 1528 intellectually "gifted" students that he studied at Stanford. During his youth, he left high school to pursue odd jobs such as shoveling bat guano in Arizona, working as a powder monkey in a Colorado mine, working in a lumber camp and even working as a crewmember on a ship to China. He eventually finished his secondary education and was admitted to the University of California at Berkeley in 1922.

Higher Education

Keys attended the University of California, Berkeley, where he initially studied chemistry, but was dissatisfied and took some time off to work as an oiler aboard the S.S. President Wilson (1st) which traveled to China. He then returned to Berkeley, switched majors and graduated with a B.A. in economics and political science (1925), an M.S. in zoology (1928). For a brief time, he took up a job as a management trainee at Woolworth's, but returned to his studies at Scripps Institution of Oceanography in La Jolla on a fellowship and in 1930, received his Ph.D. in oceanography and biology. He was then awarded a National Research Council fellowship that took him to Copenhagen, Denmark to study under August Krogh at the Zoophysiological Laboratory for two years. During his studies with Krogh, he studied fish physiology and contributed numerous papers on the subject. Once his fellowship ended, he went to Cambridge but took some time off to teach at Harvard University, after which he returned to Cambridge and earned a second Ph.D. in physiology (1936).

Professional

Early Physiology Studies

While doing fish research at Scripps, Keys would use regressions to determine the weight of fish from their length, a pioneering use of biostatistics at the time. Once in Copenhagen (1931), he would continue to study fish physiology and developed techniques for gill perfusion that provided evidence that fish regulated their sodium by controlling chloride excretion through their gills. He would also use this perfusion method to study the effects of adrenaline and pitressin on gill fluid flow and osmotic regulation in fishes. He also designed an improved Kjeldahl apparatus which improved upon Krogh's earlier design and allowed for more rapid determination of nitrogen content in biological samples. This would prove useful for activities as diverse as determining the protein content in grasshopper eggs and anemia in humans.

While at Harvard's Fatigue Laboratory, he was inspired by his Cambridge mentor John Barcroft's ascent to the top of Tenerife's highest peak and his subsequent reports. Keys wrote up a proposal for an expedition to the Andes suggesting the study could have practical value for Chilean miners that worked at high altitudes. He was given the go-ahead and in 1935, assembled a team to study the effects of high altitude on the body such as how it affects blood pressure. He spent a couple of months at 9,500 feet and then 5 weeks at altitudes of 15,000 to 20,000 feet. He noted that there was no good way of predicting how well humans might adapt to high altitude, even if they adapted well to medium altitudes, which would be a problem for potential pilots in a time before pressure control. It was from these studies that he outlined the phenomenon of human physiological adaptation to environmental changes as a predictable event; a novel idea in a time when such things as blood pressure and resting heart rate were considered immutable.

Development of K Rations

Main article: K-ration

http://en.wikipedia.org/wiki/K-ration

In 1936, Keys was offered a position at the University of Minnesota's Mayo Foundation in Rochester where he would continue to carry out his studies in physiology. He only lasted a year there, citing an intellectually stifling environment where research was secondary to clinical "doc business" and playing bridge. In 1937, he would leave the Mayo Foundation for the University of Minnesota to teach physiology and eventually found the Laboratory of Physiological Hygiene. His earlier research on human physiology eventually led to an assignment with the Army Quartermaster Corps where they worked to develop a more portable and nonperishable ration that would provide enough calories to sustain soldiers (such as paratroopers) in the field for up to two weeks. This development did not begin without some turbulence: his colleague Dr. Elsworth Buskirk notes:

“When it appeared that the U.S. would be in World War II, Keys went to the Quartermaster Food and Container Institute in Chicago to inquire about emergency rations. The story goes that he was told to go home and leave such things to the professionals. Undissuaded, he went to William Wrigley's office and secured $10,000 for the development of an emergency ration. Then, he went to the Cracker Jacks Company. They couldn't supply money, but did provide the water-tight small box concept. The result was the K-ration in sealed Cracker jacks boxes.”

Once the basic design had been completed, The Navy, through the National Research Council, funded the testing of the K-rations on its soldiers to determine its feasibility as a temporary and mobile foodsource. The initial ingredients of the K-ration were procured at a local Minneapolis grocery store: hard biscuits, dry sausage, hard candy, and chocolate. The final product was different from Keys' original ingredients, but most of Keys initial suggestions made it to the final product. The rations weighed only 28 oz (790 g), but provided 3200 calories per day and though a few sources claim the name was unrelated to Keys, many historical references support the claim that the K-ration was indeed named after him. The K-ration became such a success that it was often used for more than temporary sustenance, becoming a major staple of military nutrition.

Starvation Studies

Main article: Minnesota Starvation Experiment

http://en.wikipedia.org/wiki/Minnesota_Starvation_Experiment

During World War II, Keys produced various studies related to human physical performance that were of interest to the military such as studying the effects of testosterone on muscle work, and vitamin supplementation as a performance enhancer on adequately fed soldiers among many other similar studies. It was during the war that Keys and fellow researchers recognized the importance of knowing how to properly treat the widespread starvation since simple overfeeding for so many would be imprecise and there was a potential that the refeeding would fail. To gain insight into the physiology of starvation, in 1944, Keys carried out a starvation study with 36 conscientious objectors from Civilian Public Service as test subjects in the Minnesota Starvation Experiment. At the time, conscientious objectors were being placed in virtual concentration camps with a few functioning like the Civilian Public Service so that recruiting them would prove easier than seeking out volunteers in the general population. The original pool of 400 responders was reduced to 36 selectees, of whom 32 would go on to complete the study. The main focus of the study was threefold: set a metabolic baseline for 3 months, study the physical and mental effects of starvation on the volunteers for 6 months and then study the physical and mental effects of different refeeding protocols on them for 3 months. The participants would first be placed on the 3 month baseline diet of 3200 calories after which their calories were reduced to 1800 calories/day while expending 3009 calories in activities such as walking. The final 3 months were a refeeding period where the volunteers were divided into 4 different groups. The war came to an end before the final results of the study could be published, but Keys sent his findings to various international relief agencies throughout Europe and by 1950, he completed publication of his two-volume 1385-page Biology of Human Starvation.

Seven Countries Study

Main article: Seven Countries Study

http://en.wikipedia.org/wiki/Seven_Countries_Study

His interest in diet and cardio-vascular disease (CVD) was prompted, in part, by seemingly counterintuitive data: American business executives, presumably among the best-fed persons, had high rates of heart disease, while in post-war Europe, CVD rates had decreased sharply in the wake of reduced food supplies. Keys postulated a correlation between cholesterol levels and CVD and initiated a study of Minnesota businessmen (the first prospective study of CVD), culminating in what came to be known as the Seven Countries Study.

Keys hypothesized that a Mediterranean-style diet low in animal fat protected against heart disease and that a diet high in animal fats led to heart disease. In order to do this, Keys collected data on deaths from coronary heart disease and fat consumption from 22 countries, but chose to analyze the data from only 7 of these countries, a decision which has since, in recent years, resulted in criticism.[26] The results of what later became known as the “Seven Countries Study” appeared to show that serum cholesterol was strongly related to coronary heart disease mortality both at the population and at the individual level. As a result, in 1956 representatives of the American Heart Association appeared on television to inform people that a diet which included large amounts of butter, lard, eggs and beef would lead to coronary heart disease. This resulted in the American government recommending that people adopt a low fat diet in order to prevent heart disease.

The resulting "cholesterol controversy" revealed sharp divisions in post-war scientific culture over whether the statisticians' "strong associations" could provide scientific certainty. In its simplest form, the debate over cholesterol, dietary saturated fat and CVD pitted "interventionists" against those calling for further studies—preferably clinical or laboratory studies. The role of cholesterol in CVD was cemented in the minds of many when huge studies with powerful cholesterol-lowering drugs seemed to show a correlation between lowering LDL cholesterol and reduced risk of cardiovascular disease. (Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. BMJ. 2003 Jun 28;326(7404):1423. www.bmj.com/cgi/content/full/326/7404/1423). However, one of the largest studies in their meta-analysis(Heart Protection Study, Lancet. 2002 Jul 6;360(9326):7-22) used rather questionable methods: all prospective subjects were given the investigative drug (simvastatin) for 6 weeks, and anyone showing signs of abnormal responses to the drug was excluded from the formal study. These exclusions were far stricter than standard management of statin therapy, and resulted in fully two-thirds of the initial pool of subjects being ineligible for the study. This would have grave implications for clinical practice, but was not mentioned in the conclusions or discussion section of the primary research article. Not dissimilar to the dishonesty of which Dr Keys was accused, this has incited far less criticism, but the significance of dietary saturated fat intake for cholesterol and CVD remains an area of heated debate.

However, already in the 1960s Keys was able to convince a sizable part of the US public that replacing saturated by unsaturated fat would reduce blood cholesterol and the incidence of coronary heart disease. The resulting changes in the composition of food fats led to a doubling of the proportion of the unsaturated fatty acid, linoleic acid, in the body fat of Americans between 1960 and 1975 Mortality rate from coronary heart disease in the US began to fall from 1968 onwards, and about half of the decline was ascribed to changes in lifestyle including diet.

Keys had concluded that saturated fats as found in milk and meat have adverse effects opposite to the beneficial effects of the unsaturated fats found in vegetable oils. These same unsaturated fats and oils are however, found in meats and to a larger extent than Dr. Keys ever gave these foods credit for in any of his work. This message was obscured for a 20-year period starting around 1985, when all dietary fats were considered unhealthy. This was driven largely by the hypothesis that all dietary fats cause obesity and cancer (Prentice RL, Sheppard L. Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Causes Control. 1990 Jul;1(1):81-97). The idea began to be called into question in the late 1990s due to research that did not support a link between fat and cancer and an obesity epidemic in the face of reductions in fat intake (Katan MB, Grundy SM, Willett WC. Should a low-fat, high-carbohydrate diet be recommended for everyone? Beyond low-fat diets. N Engl J Med. 1997 Aug 21;337(8):563-6; discussion 566-7).

With the advent of ever-more powerful cholesterol lowering drugs, high cholesterol has ceased to be a major cause of premature heart disease in affluent countries. Its place has been taken by obesity and the subsequent type 2 diabetes, problems for which the diets developed by Keys offer no solution, though he appreciated the connection between obesity and cardiovascular disease (Circulation 1952:5; 115-118).

Keys also popularized the use of the body mass index (BMI) as a measure of body fat, following a 1972 paper.

Keys was always considered an interventionist. He generally shunned food fads and vigorously promoted the benefits of the "reasonably low-fat diets" he contrasted with "the North American habit for making the stomach the garbage disposal unit for a long list of harmful foods." Keys' studies and recommendations have had a substantial impact on changes in the U.S. diet[citation needed] that may have caused a downward trend in CVD. Several recent studies have vindicated Keys' thesis that unsaturated oils are more effective at improving markers of CVD than high-carbohydrate low-fat foods.[citation needed] Because of his influence in dietary science, Keys was featured on the cover of the January 13, 1961 issue of Time magazine.

Ancel Keys died on November 20, 2004, two months before his 101st birthday. A year earlier, he had left Pioppi, his beloved village in Southern Italy where he had spent 28 years of his life.

Criticism

The research of Ancel Keys has been criticized by Uffe Ravnskov amongst others for having selection bias when supporting his conclusions. Ravnskov examined the data that Keys used and found no correlation to back up Keys' findings. A University of Minnesota study in the late 1940s injected 11 public service employee volunteers with malaria, then starved them for five days. Some were also subjected to hard labor, and those men lost an average of 14 pounds. They were treated for malarial fevers with quinine sulfate. One of the authors was Ancel Keys.

Personal life

When Keys was hired at the Mayo Foundation in 1936, he hired Margaret Haney (1909–2006) as a medical technologist. In 1939, they married and had three children: Carrie D'Andrea, Henry Keys, and Martha McLain (deceased, 1991). Together, they coauthored numerous books including Eat Well and Stay Well (Doubleday, 1959) and The Benevolent Bean (Doubleday, 1967). They also traveled the world, traveling to places like Japan and South Africa to record data for Ancel's published works such as the Seven Countries Study.