IN MEMORIAM -- DEAN BURK (1904-1988), FLUORIDE, 22:3, 1989 July
by H.L. McKinney, University of Kansas; Lawrence, Kansas
 

Both science and the humanities have lost a major intellect with the recent death of Dean Burk, October 6, 1988, at the age of 84, Burk was born March 21, 1904, in Oakland, California, the son of Frederic Burk, who was President of what is now San Francisco State University. He entered the University of California Farm School at Davis at the age of 15 and studied agriculture. A year later, he transferred to the University of California at Berkeley, where he received his B.S. in Entomology in 1923. Four years later at the age of 23, he earned a Ph.D., in Plant Nutrition and Chemistry (1).

He continued his advanced studies as a fellow, National Research Council/International Education Board (1927-1929), successively at University College, University of London (with A.V. Hill, a Nobel laureate), the Kaiser Wilhelm Institute for Biology in Berlin, and Harvard University. In Germany he had investigated nitrogen fixation with Otto Meyerhof and also befriended Otto Warburg, both Nobel Prize winners, and their students.

He maintained a forty-year friendship with Warburg, "my greatest mentor," and perhaps the world's greatest biochemist, who worked with him in Bethesda, Maryland, on photosynthesis in 1949. From 1950 up until 1969, the year before Warburg's death, Burk spent most summers in Berlin and translated many of Warburg's "most important contributions on cancer and photosynthesis...." (2). In 1953, he became a Foreign Member of Warburg's Institute.

In 1935 Burk also had the opportunity to study in the U.S.S.R. at the Academy of Sciences (Biochemistry Institute) as a Guest Research Worker, and he returned to study in the summer of 1937 under the famous biochemists A.N. Bach and V.I. Englehardt. During the period of his government service, he spent parts of many years in England, Germany and the U.S.S.R. He also travelled throughout the world ranging from Europe to Africa and Australia, where he toured extensively in 1977. He attended countless international meetings. Linguistically, he was proficient in German and French and knew some Russian.

Burk's professional career began in 1929 as an Associate Physical Chemist, at the Fixed Nitrogen Research Laboratory, Bureau of Chemistry and Soils, Department of Agriculture in Washington, D.C. (3). In 1939 he left that job to join the National Cancer Institute (NCI) of the National Institutes of health, with which he was associated until 1974, when he reached the mandatory retirement age of 70. His government career, therefore, spanned 45 years. With the NCI, he was Senior Chemist (1939-1948), Principal Chemist (1948-1951), Head Chemist (1951-1958) and Chief Chemist (1958-1974). He was also simultaneously a faculty member, Associate Professor of Biochemistry, at the Cornell University Medical College during 1939-1941. From 1947 until his death he held the honorary post of Research Master, Graduate Faculty, George Washington University, and during 1974-1976, he was Guest Scientist at the U.S. Naval Research Institute.

His impressive list of memberships and honors is too numerous to cite completely here (4). A few examples of some of these are: Fellow, American Association for the Advancement of Science (and organizer of cancer research conferences, 1942-1945); American Association of Cancer Research; Foreign Scientific Member, Max Planck Institute of Biochemistry, Munich, Germany and also the Institute for Cell Physiology, Berlin; Society of Experimental Biology and Medicine; Honorary President, German Society of Medical Tumorotherapy; and the Royal Society of Medicine, London. He was a member of the prestigious Cosmos Club in Washington, D.C. and the Commonwealth Club of California.

Aside from his major contribution to scientific literature of more than 250 articles, Dr. Burk was also recognized as a leading American authority on photosynthesis by receiving the American Chemical Society Hillebrand Prize in 1953 "For the experimental discovery of a photosynthetic energy cycle of high quantum efficiency, with demonstration of the applicability of the Einstein law of photochemical equivalence and studies of related biochemical energy transformations in cancer metabolism" (5). According to the American Chemical Society (which he joined in 1931), the stimulus for "Burk, and the principal reason for his receiving the award," was "his discovery with Otto Warburg of one quantum reaction in photosynthesis at 90% utilization efficiency of incident light" (6). Dr. Burk achieved singular honor for his distinguished cancer research in 1965 with the Gerhard Domagk Prize "for the development of procedures for distinguishing the differences between a normal cell and one damaged by cancer" (7) normally reserved for native-born German, Swiss or Austrian citizens (8).

Burk will probably be best remembered to biochemists as the co-author, with Hans Lineweaver, of the most frequently cited paper in biochemistry, "The Determination of Enzyme Dissociation Constants," in the Journal of the American Chemical Society, published in 1934 (9). With 20-20 vision of hindsight, we now view the lack of enthusiasm by the six referees of this classic article with amusement -- they recommended rejection of the article, but editor Arthur B. Lamb overruled them! -- because we see that "the double reciprocal plot usually provides, automatically and conveniently, a considerably improved weighting for linear graphics of most enzyme velocity data as a function of concentration" (10). The consequences, as one recent review of biochemistry stated: "One can hardly find any enzymological publication in which kinetic data are presented in a way other than the double reciprocal plot according to Lineweaver and Burk. The results here confirm the opinion of Dowd and Riggs (1965) [J.E. Dowd and D.E. Riggs, J. Biol. Chem., 240:863, 1965] that the popularity of the Lineweaver-Burk method is based upon the ability to provide what seems to be a good fit even wen the experimental data are poor...." (11). But, as Burk himself commented, "It is much more importantly used to test the general qualitative correctness of an assigned mechanism formulation before ascertaining the numerical values of the parameter constants involved" (12).

Burk himself has summarized his other major laboratory projects in an interview: "thermodynamics of nitrogen fixation, biochemistry, and cancer; photosynthesis with and without green plants; biology and biochemistry of nitrogen fixation by bacteria; ... trace mineral elements; B vitamins (co-discoverer of biotin); optical activities of various biochemical racemates; cancer metabolism in all kinds of cancers and leukemia in animals and humans' poloragraphic analysis of cancer and normal blood; antibiotics; cobalt models of hemoglobin-oxygen systems; cell-tissue cultures; mitochondrial control of metabolism; iron-binding compounds in blood; chromatographic separations; manometric techniques for measurement of gases; efficiency of photosynthesis in green plants; origin of cancer cells; conventional anticancer agents' mode of action; cytotoxic actions of human sera; insulin; correlation between cancer growth rate and magnitude of metabolism (Domagk Prize, 1965); purification of tobacco smoke; effects of amygdalin (Vitamin B-17, Laetrile) on cancer cells" (13). The period from 1975-1988 was sharply focused on fluoridation and cancer.

On November 18, 1974, after his retirement, Burk founded the Dean Burk Foundation "devoted to research on health, nutrition, and chronic and degenerative diseases including cancer." Two major reports (called "Briefs") were published. One focused on vitamin B-17 and also alluded briefly to vitamin B-15 and vitamin B-13 (14). Burk carefully analyzed the federal food, Drug and Cosmetic Act (as amended August 1972), Title 21 USC, Chapter 11 (Definitions), Sec. 201 (321) (f), and demonstrated conclusively that amygdalin (vitamin B-17/Laetrile) is by definition, and long-standing scientific knowledge -- to which he had personally contributed -- "scientifically to be regarded as a food, a vitamin...." (15). Unfortunately, he caustically added, irresponsible human nature appeared certain to reject such an axiom in the same way the flat earth advocates reject the view of a round earth. What was true about vitamin B-17 was equally true of vitamin B-15 and vitamin B-13. (16)

The other major focus during his retirement years was on the link between fluoridation and cancer. As a result of Dr. Burk's expert views on conventional as well as nonconventional cancer therapies, he became a sought-after speaker before nonmainstream health groups during the late 1960s and an embarrassment to his superiors at the National Cancer Institute (NCI), who advocated only the traditional medical cancer therapies of surgery, chemotherapy, and radiation treatments. The NCI therefore attempted to muzzle Burk when he was invited to speak to many groups on nonorthodox treatments he was acquainted with that had shown promise. Clinton R. Miller, legislative advocate in Washington, D.C. for the National Health Federation (NHF), knew that Burk was being harassed by the NCI -- the notoriety of the maverick head of Cytochemistry was very well known -- and lobbied the NCI through Congress to release Burk to speak to health groups. The NCI refused to approve Burk's talks, but they did not **positively** disapprove his appearances, a distinction bureaucrats might be expected to make. On Sunday, July 16, 1969, during his weekend, for example, Burk delivered a talk on "Healthier Cigarettes and Cancer Prevention," to the International Association of Cancer Victims and Friends, Inc. in Los Angeles. The NCI frowned with disapproval; the IACVF groups clamored for more (17)!

In January 1975, shortly after retiring from the NCI, Burk spoke to the National Health Federation about Laetrile. At that time he first met John Yiamouyiannis, a Ph.D. in biochemistry who had joined the NHF as Science Director and who was a formidable combatant in the fight against fluoridation. Burk couldn't understand why Yiamouyiannis was "first wasting his time: pursuing such a dead-end subject (18).

Burk's familiarity with fluoride reached back to the very beginning of his career. As he observed in 1976, "I did my first experiments with fluoride in 1929, and was present in Meyerhof's laboratory in Berlin when Fritz Lipmann was doing his fluoride experiments in 1929" (19). Burk's friendly, but sharp, advice to Yiamouyiannis therefore had deep roots, although Yiamouyiannis doggedly continued to pursue the topic.

In about May 1975, Yiamouyiannis finished an expanded version of his fluoridation efforts comparing cancer mortality rates in some major fluoridated cities without fluoridation. The paper was sent to Clinton R. Miller, who took it to the National Cancer Institute; the reception was negative, and Miller then asked Dean Burk, whom he knew from Burk's Laetrile talks to read the paper,. Burk, again, was typically caustic, and repeated his carefully considered opinion that Yiamouyiannis was wasting his time on a "worthless" enterprise -- if there were a connection it would have been found already. Nevertheless, he agreed as a favor to Miller to read the paper and criticize it. After spending "all night" and several more days minutely analyzing the data, Burk conceded the arguments were sound, convincing, in fact, despite his strong preconceptions, probably correct (20). He then began to view the fluoridation/cancer link in an entirely new light. Miller took Yiamouyiannis to Burk's house, and an important, lengthy collaboration began.

Burk's preliminary statement on the subject was a publication of his Foundation ("Brief" No. 2) discussing the probable link between fluoridation and cancer and the Delany Amendment to federal law, which prohibits the addition of *any* carcinogen to food or water (21). If the fluoridation/cancer link is correct, then by law fluoridation must be discontinued immediately. The NCI, however, repeatedly disclaimed any connection.

Burk's preliminary statement was followed by a detailed collaborative effort between himself and Yiamouyiannis -- Burk's "second most important paper" (22). The authors showed that crude cancer death rates in the 10 largest fluoridated cities in the U.S.A. "were higher and had risen faster than those in the 10 largest nonfluoridated U.S. cities that had essentially the same crude cancer rates during the decade before fluoridation." They found that his increase occurred in persons 45-65 and 65 and over and that corrections for age, race, and sex did not eliminate the difference as suggested by the NCI (23). The bottom line was a 5-15% higher death rate (unweighted) in the fluoridated over the unfluoridated communities compared in the study (24).

Criticism from fluoridation proponents was swift and hostile: the authors had failed to correct for age, sex, race, and cancer site distribution, it was claimed. When proper "adjustments" (i.e., manipulations) were made -- a constant proponent theme -- all was well with fluoridation (25). Another author emphasized that population gains (demography) explained the apparent problems away (26). The battle still continues with great vehemence a decade later.

Burk's final statement on the subject, and indeed his last scientific paper, reiterates his strong scientific conviction that demographic changes of the two groups of central cities do *not* explain away the apparent causal relationship between fluoride and cancer death rate. "It is concluded that artificial fluoridation appears to cause or induce about 20-30 excess cancer deaths for every 100,000 persons exposed per year after about 15-20 years." Burk and his co-authors therefore pleaded: "In light of this conclusion, we urge the governments of civilized countries of the world to bring about a prompt end to artificial fluoridation of public water supplies" (27). Tens of thousands of unnecessary deaths -- at one time he estimated about 40,000 in the U.S.A. alone -- would thereby be averted (28). Saving lives was a primary concern of Burk, and he though his work on fluoridation was the most important he had done during his life (29). There is no doubt that one of his most personally fulfilling moments was experienced when he received the news that he was largely responsible for the termination of fluoridation in the Netherlands (3), despite erroneous claims to the contrary (31), and his impact in Australia was widely reported in the press there (32).

Dr. Dean Burk musician, artist, scientist, sage -- lived a rich and valuable life. he published more than 250 scientific articles. He probed abstruse mysteries; he proposed profound answers. he devoted his life to science and mankind. he made an indelible mark where he has passe. The world is infinitely richer having known such a gentle, brave man of genius, industry, and altruism.