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James Buchanan Brady
(Diamond Jim)

Donald S. Coffey, Ph.D.
DIRECTOR OF RESEARCH

1974-2004



Donald S. Coffey was born in Bristol, Virginia, on October 10, 1932. The town of Bristol straddles the border of Virginia and Tennessee, and in 1951 when he entered King College it was in Bristol, Tennessee. His first two years at King gave no indication of the academic direction he would follow later but were good preparation for the business of living. Aside from basketball and track, he read philosophy, wondered about religion and war, participated in political action, and met his future wife, Eula Cosby. In 1953, after a separation from King College, he married Eula and entered the University of East Tennessee. In 1955, the Coffeys had their first child, and it became necessary for him to earn more money. He was hired by the North American Rayon Company in Elizabethton, Tennessee, as a chemist during his last two years of college. After graduation in 1957, he was hired by the Westinghouse Electronic Corporation in Baltimore, as an associate chemical engineer.

Meanwhile, his desire was to do research in cancer at Hopkins. He had been encouraged in this direction by his former boss at North American Rayon, Dr. Lee R. Herndon, an alumnus of Johns Hopkins. His academic credits were not sufficient to get into graduate school (he had already been rejected by 23 schools) but he was able to attend evening classes at McCoy College, the Hopkins night school. While there, he found out about an opening in the medical school at the Brady Research Laboratory and was hired to work at night.

Early in 1959, Scott learned that Tesar, then director of the Brady lab, had been awarded a prestigious Fulbright Fellowship for the year beginning July 1, 1959, to work with Dr. Albert Claude in the Laboratory of Cytology and Experimental Cancer in Brussels, Belgium. (The details of this association are given under Tesar's biography). Consequently, someone was needed to direct the laboratory in Brady for a year. Fortunately, Coffey applied for the job and became acting director of the Brady Urological Research Laboratory for the year 1959-1960. He left his position at Westinghouse, at quite a financial sacrifice, but made an excellent impression in the laboratory. Dr. Scott realized his potential as a research investigator and director, and thought his horizon might well be expanded with further study. With Scott's encouragement, Coffey applied for the graduate program in the medical school's Department of Physiological Chemistry. The tale of his acceptance, as related by Scott, is worth retelling.

A few years before Coffey came on the scene, the Brady Research Laboratory had succeeded in purchasing a Perkin-Elmer recording infrared spectro- photometer for studying urinary steroids. This magnificent 'Cadillac' of instruments was made possible by a gift of some $10,000 from the late Morris Macht. Dr. Roy Finney, spending his year in the laboratory while in training, was the first to work with the instrument, to be followed by the late Dr. Frederick B. Burt who had elected to spend two years in the lab instead of one. With Burt, Coffey had mastered the intricacies of infrared spectrophotometry.

I was convinced that Coffey should obtain further training in the basic sciences and introduced him to my friend, Dr. Albert L. Lehninger, DeLamar Professor of Biological Chemistry at Johns Hopkins. Interviews for Coffey were scheduled with members of the Lehninger's staff, one with Dr. Thomas Bruce who had considerable interest in infrared spectrophotometry. Dr. Bruce was amazed at Coffey's knowledge of infrared analysis, and, even more so on learning that a clinical specialty such as urology had a magnificent Perkin-Elmer recording infrared spectrophotometer. Don tells us that this helped with the interview, but knowing Don he required very little help.

What Coffey did need help with, in order to become a student again, was money. He didn't mind lowering his standard of living but he had a family to feed. It wasn't until this past year he found out that Scott had contributed to the medical school's stipend of $2,000 to make a total of $5,000. That income, plus Eula Coffey's working as a lab technician, kept the family going for the next four years.

Coffey began his graduate studies in physiological chemistry under Dr. Leslie Hellerman in Dr. Lehninger's department in 1960. He received his Ph.D. in 1964 and continued his association with Hellerman for several years resulting in some seven papers dealing with sulfhydryl groups and the enzymology of flavoprotein catalysis.

During the late sixties, Coffey once again became involved in research with the Brady Institute during Dr. Guy Williams-Ashman's tenure as Director of the Brady Laboratory for Reproductive Biology. Upon Williams-Ashman's resignation and return to Chicago in 1969, Coffey became director of that laboratory, holding that position until 1974, when it merged with the Brady Research Laboratory, after the retirement of Tesar, and Coffey was made director of the merged laboratories.

Coffey's versatility had attracted notice in other Hopkins departments and he was appointed assistant professor in the Department of Pharmacology and Experimental Therapeutics in 1966 by Dr. Paul Talalay. Coffey was promoted to Associate Professor in 1970 and became Acting Chairman of the Department in 1973-1974 while the chairman, Paul Talalay, was taking a sabbatical leave to conduct research in England. The Department of Oncology made Coffey an associate professor in 1973 and he was promoted to full professor in the Department of Pharmacology and Experimental Therapeutics and the Oncology Center in 1974. In 1975, he was made professor in urology.

Dr. Coffey's reputation as a man with warm personal qualities as well as tremendous creative abilities has led many people to want his services. For the Johns Hopkins School of Medicine he has been a member of the President's Committee on Governance, member and first faculty-elected vice-chairman of the Medical School Council, the Advisory Board, the Committee on Educational Policy and Curriculum, the Professional Promotions Committee, the Medical Scientist Training Program, and the Committee on Cultural and Social Affairs.

From the U.S. Public Health Service, Coffey received the Research Career Development Award from 1966 to 1972 and was in the Experimental Therapeutics Study Section from 1971 to 1975. He has been a member of the National Prostatic Cancer Task Force, Working Cadre, National Cancer Institute since 1971 and became National Chairman of that group in 1984.

He has served or is serving on the editorial boards of the Journal of Urology, Advances in Sex Hormone Research, International Union Against Cancer, Prostate, and the World Journal of Urology. He has also been active in the American Cancer Society, Maryland Division; the American Society of Pharmacology and Experimental Therapeutics; the Batelle Human Affairs Research Center Medical Advisory Committee; and the Pasadena Research Foundation.

As if this is not enough to keep him busy, Coffey has given several commencement addresses and is in constant demand for his lecture on "Human Destiny." One popular version of the lecture places man in evolutionary time and cosmic space using visual aids, metaphors, and analogies geared to understanding by the layman.

Coffey's most recent contribution to basic medical research has opened a whole new field on the "nuclear matrix." This is the term he uses for the residual core scaffolding of the nucleus of the cell around which is wound the strands of DNA (deoxyribonucleic acid). He thought there was a cablelike structure within the core and, with a postdoctoral fellow in the Brady Research Laboratories, Ronald Berezney, was able to locate the core. They found not only a structure as Coffey had conceived, but newly synthesized DNA sticking to it. They concluded the structure must in some way be associated with the reproduction of DNA. Up until that time, investigators had hypothesized that DNA was reproduced by a mobile recording device that moved along the strands of DNA. More research was done, and Drew Pardoll, a medical and graduate student, formulated a theoretical model: the DNA strands reel through thousands of fixed sites on the matrix in loops, rather than a mobile recording device passing over them. Another investigator, Bert Vogelstein, did the necessary calculations to show that Pardoll's theoretical model would work. Finally, they were able to illustrate the loops around the nuclear matric with pictures and models.

Coffey now speculates that cancer may be caused by a defect in the nuclear matrix during the reproduction of the DNA and not in the strands themselves. The nuclear matrix is complex, and the fact that it is being studied in many laboratories is Coffey's major achievement.

A talent for bringing together clinicians and research investigators is another of Coffey's accomplishments. Hugh Jewett, a distinguished clinical urologist at Hopkins, had been monitoring cell samples of prostatic cancer patients for more than 15 years but still could not predict with certainty their mortality rate. Although he is somewhat leary of basic research, he took his problem to Coffey. Coincidentally, Coffey and his associates, Joseph Eggleston, David Diamond, and Stephen Berry, had been exploring the role of cell shape in prostatic cancer cells. Since the cancer cells are in constant motion their shapes are distorted, as opposed to normal prostate cells. Working with Jewett's cell samples and patient histories they discovered the more distorted the cell shape, the more serious the cancer. With the use of a computer they were able to trace the cell shapes and predict the outcome for the patient. Although it is not a routine test at present, Coffey predicts it is only a matter of time until technology conquers the problem.

Coffey believes his main accomplishment may be in attracting young students and basic scientists to join the efforts of the Brady laboratories. Mixing the thoughts and efforts of these young scientists with the urology residents in the laboratory year is synergistic for both groups. These young basic scientists are now populating the urological and research field and include Jun Shimazaki, Ronald Berezney, Leland W. K. Chung, Warren D. W. Heston, David G. Brown, Evelyn R. Barrack, and John T. Isaacs. Two of these young scientists, Barrack and Isaacs, have become faculty members at the Brady and they join Coffey and Dr. Thomas Chang to provide four full-time faculty in the Brady Research Laboratory. A new phase of Brady training includes graduate student's doing their doctoral research in the laboratory such as Evelyn Barrack, Stephen Berry, William Isaacs, Gail Cornwall, and William Nelson. In addition, a host of young medical and graduate students have spent their summers and elective quarters in the Brady Laboratory. Another new educational and research program was initiated in the Brady to allow young urologists who had completed their resident training to spend two additional years in full-time postgraduate research. Involved in this program have been Neil de Klerk, Robert Weissman, John Trachtenberg, Charles Brendler, Mitchell Benson, and James Mohler.

Coffey believes he is only carrying on the long-standing heritage of the Brady Laboratory, which is to provide an opportunity for all willing and dedicated young scientists to develop their excellence in the pursuit of medical research. He says,

The Brady and its fantastic leadership and fine faculty have provided me with an opportunity to work in this wonderful department. I must now do my very best to keep doing the same for the next young person coming through the Brady doors. It has been an honor and thrill to be part of this fine team effort.

Donald S. Coffey, as director of the Brady Urological Research Laboratory, has continued in the "heritage of excellence." In a tribute to him Dr. William W. Scott said:

Donald Coffey is one of the most gifted and finest human beings I have had the pleasure of knowing in my entire experience in academic medicine. He has the unusual capacity of being able to get at the heart of the matter whether it involves basic researches on the nuclear matrix or better ways of predicting the biological potential of human prostatic cancer.

He gives freely of his time to students, residents, fellow investigators and clinicians and is indefatigable. Combine this with his delightful sense of humor, his genuine love of people and his sense of fairness and you have a wonderful person which is what he is.

References
  1. Joe Levine, "The Man Who Says Yes," Johns Hopkins Magazine, 36, no. 1 and 2, p. 34. February/April 1985. Baltimore, Maryland, The Johns Hopkins University.






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