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P&S Journal

P&S Journal: Fall 1995, Vol.15, No.3
Alumni News and Notes
Profile: Paul Marks '49

Alumni News Writer:

PETER WORTSMAN

Paul Marks: At the Cancer Command

Paul Marks '49
His piercing blue eyes encased in steel-rimmed glasses flash the message: MIND AT WORK! His powerful frame (once used effectively to plow through the opposition in his days as right tackle on Columbia's junior varsity football team) is no less daunting now at age 70. For close to half a century, as physician, research scientist, teacher, medical administrator, and national health policy adviser, Paul Marks'49 has been a leading player and tactician in the war against cancer.

As president and CEO of Memorial Sloan-Kettering Cancer Center, the nation's oldest and largest private institution devoted to cancer prevention, patient care, research, and education, Dr. Marks' influence in the field of cancer research reaches around the country and the world. Dr. Marks has applied his combined talents as a world-class scientist and a strong administrator to stimulate research at the molecular level and refocus clinical care to encompass non-invasive alternatives to surgery.

A man accustomed to being at the top, who graduated first in his class at P&S in 1949 and 21 years later rose to the rank of dean, Dr. Marks is uncharacteristically humble when it comes to talking about the rigors of biomedical science. "In research, you've got to learn that the number of really exciting, satisfying experiments you do will be few and far between," he admits. "But hopefully, if you're working on something that's important, and you

keep at it, its impact will be broad."

An abiding passion for the intellectual challenge of biomedical science dispels any doubts. "There is no answer which doesn't raise more questions," Dr. Marks reflects. "My life is a continuing love affair, if you will, with the whole potential of exploring the unknown."

The seeds of such passion were evident early on. "There is no doubt in my mind," he wrote in his student application to P&S, "that my greatest happiness lies in the pursuit and practice of medical knowledge to the best of my ability." Inspired by a high school English teacher to pursue medicine, he took his B.A. degree at Columbia College and enrolled in P&S on a Navy scholarship as part of the V12 program.

At P&S, the biochemistry bug bit him and he has never been the same since. A student research project with DeWitt Stetten (known to his colleagues as Hans), on the blood-brain barrier whet his appetite for more. And though in the course of an elective in biochemistry with another P&S legend, Erwin Chargaff, Dr. Marks failed to accomplish his ambitious goal of solving the problem of the biochemical defect of Gaucher's disease, "the experience was thrilling. I got hooked on research."

After graduation, Dr. Marks spent a year as a research fellow at Cornell, where he worked under Ephraim Shorr on the biochemistry of cartilage and bone formation. He returned to Presbyterian Hospital to pursue his housestaff training under Robert Loeb and a medical fellowship on problems related to the physiology of blood volume under Stan Bradley, himself a veteran associate of Nobel laureates André Cournand and Dickinson Richards'23.

Dr. Marks remembers with a smile Dr. Loeb's famous "Sunrise Serenades," those often-grueling but always enlightening early morning consultations with housestaff and fellows six days a week-seven if you were on call. In the course of one such consult, Dr. Loeb, who had just returned from a visit to the NIH, discussed the exciting work being done there on the synthesis of nucleotides by Arthur Kornberg (later to win the Nobel Prize for his discoveries related to DNA synthesis). At Dr. Loeb's urging, his promising young protégé successfully applied for a position in Dr. Kornberg's lab. Dr. Marks' experience at the NIH, where he also worked with Bernard Horecker at the National Institute of Arthritis and Metabolic Diseases, gave him "a real insight into and a taste for rigorous biochemistry at its best."

Recruited back to Columbia as an instructor in medicine in 1955, Dr. Marks sought to apply his newly acquired biochemical expertise to a clinical problem. Setting up a laboratory in the basement of the old Delafield Hospital, he began to study the pathway by which blood cells metabolize sugar. Delafield was a cancer hospital and, consequently, the blood samples Dr. Marks studied came from cancer patients. He noticed a curious phenomenon: All cancer patients proved to have an elevated level of the enzyme G-6-P dehydrogenase and a slight hemolytic anemia, destroying their red blood cells faster than normal. This led to Dr. Marks' trailblazing discovery in genetic blood disorders. He was among the first to demonstrate that the inherited thalassemias result from diminished globin chain synthesis.

For the next two decades Dr. Marks pursued his research at Columbia-with the exception of a sabbatical leave from 1961 to 1962 as a visiting scientist at the Pasteur Institute in Paris, where he worked

with Drs. Jacques Monod and François Gros at the time they discovered messenger RNA. He went on to study the mechanism of protein synthesis in cells and did seminal work on a class of cytodifferentiation agents, chemicals that have the capacity to induce cancer cells to resume normal growth and development.

In collaboration with Richard Rifkind'55, now chairman of the Sloan-Kettering Institute, and Dr. Arthur Bank, now P&S professor of medicine and of genetics and development and chief of hematology in the Department of Medicine, Dr. Marks studied the effect of hexamethylene bisacetamide (HMBA) on murine erythroleukemia cells in the mouse. Rather than destroy cancerous cells, as do classical chemotherapeutic agents, treatment with HMBA, they found, altered the expression of certain genes, causing the cells to cease malignant growth and assume more normal characteristics. Clinical studies demonstrated the ability of such agents to induce remission in patients with certain cancers. Dr. Marks and his colleagues are still working with a variety of agents in an attempt to optimize the results of cytodifferentiation therapy.

Rapidly rising in the academic ranks at P&S, Dr. Marks proved as superb a teacher and administrator as he was a scientist. Named director of the hematology training program and director of clinical hematology at Presbyterian Hospital in 1960, he was instrumental in rethinking pedagogical methods in those areas, which later served as a precedent for the important curricular reforms of 1968-70. In 1967 he was appointed professor of medicine and in 1969 professor and chairman of the newly created Department of Human Genetics and Development. In 1970 he became dean of the Faculty of Medicine and vice president in charge of medical affairs. Dr. Marks reorganized the administrative structure at P&S, bolstered funding, and embarked on an ambitious recruitment of scientific talent from around the country.

In 1973, Columbia decided to separate the deanship and the vice presidency. Dr. Marks was appointed to the new title of vice president for health sciences and also assumed the responsibilities as director of the Cancer Research Institute, which he helped found. In 1974 he was named Frode Jensen Professor of Medicine.

In 1980, Sloan-Kettering wooed him crosstown. Parallel to his research and administrative careers, Dr. Marks has answered repeated calls to public service at the highest levels. A member of the President's Biomedical Research Panel in

1975-76, the President's Cancer Panel from 1976-79, and the President's Commission on the Accident at Three Mile Island in 1979, he more recently served on an advisory committee to the director of the NIH to help overhaul its intramural research program.

At the international level, he has served in various capacities as a kind of biomedical diplomat, helping to foster a cooperative atmosphere of scientific interchange of knowledge. While dean of P&S, he helped open a scientific dialogue with China, and P&S was among the first American medical schools to welcome a group of Chinese physicians and scientists. In 1980, with the financial support and sponsorship of fellow P&S alumnus, the late Armand Hammer'23, Dr. Marks organized at P&S the first bilateral Conference on Cancer Research in the People's Republic of China and the United States.
He was also a member of the organizing committee of the International School of Developmental Biology and a founding member of the Committee on the Radiation Effects Research Foundation in Japan.

He is author or co-author of more than 300 hundred scientific articles, nine book chapters, and some 60 articles on medical subjects of general interest. His editorial contributions include tenures as editor-in-chief of The Journal of Clinical Investigation from 1967 to 1971 and of Blood from 1978 to 1982.

Such prodigious achievements have earned him a garland of laurels, including honorary degrees from the University of Urbino in Italy, Hebrew University in Jerusalem, and the University of Tel Aviv; the Centenary Medal of the Institut Pasteur, the President's National Medal of Science, the P&S Alumni Association's Gold Medal for Distinguished Achievements in Medicine, and, at the P&S graduation ceremonies this May, the Joseph Mather Smith Prize. He is a member of the American Academy of Arts and Sciences and the Institute of Medicine of the National Academy of Sciences.

Testifying over the years before various government organs, including, most recently, the Senate Finance Committee on Health Care Reform, Dr. Marks has been an eloquent spokesman on behalf of America's great academic medical centers. "I believe that institutions such as Columbia and Memorial Sloan-Kettering are vital to the health of our society," he asserts. Acknowledging the current crisis in funding for biomedical research, he argues against the dangers of short-sighted budget cuts. In cancer research, he insists, "the public's investment has paid off marvelously. Twenty years ago, about a third of all cancers were curable. Today, well over 50 percent are curable, and for those that aren't, we can control the disease for much longer periods of time, permitting even the afflicted a useful and valuable life experience."

The most exciting area of progress in current cancer research, according to Dr. Marks, is taking place at the genetic level. "The detection of genes that place individuals at increased risk," he points out, "gives rise to a whole new concept: pre-symptomatic diagnosis. The Human Genome Project has markedly accelerated the identification of these genes and the development of practical probes to detect them." Major challenges remain, however, notably "just how to intervene once you diagnose a pre-symptomatic cancer stage."

While the battle against cancer is by no means won, the disease is no longer the invincible bogeyman of old. "Yet we still have a ways to go," he insists, "for while 50 percent of all cancers may be curable, 50 percent are not, and that's simply not acceptable!"

At a time of life when most people begin to consider retirement, Dr. Marks continues to put in 13-hour days at his desk and lunch hours in the lab. (His only other avowed ambition: "To be able to play tennis till I'm 85!") "Biomedical research and health care is what I'm good at," he shrugs. "I'll be at it as long as I'm productive."

From all appearances, that is likely to be a good many years to come.


copyright ©, Columbia-Presbyterian Medical Center

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