As a young physician in the 1950s, Paul Marks was fascinated by blood cells. This curiosity led him to a successful research career and to a number of “firsts.” He was the first to show that hemolytic anemia is caused by a genetic defect in the enzyme glucose-6-phosphate dehydrogenase. In the 1960s, he identified a genetic defect in globin synthesis as the basis of thalassemias — a sometimes fatal group of anemias.
It was while studying blood cells that he learned of a colleague’s curious laboratory finding: Soaking cancerous white blood cells in a common laboratory reagent called DMSO caused them to turn pink. The white blood cells had apparently begun making hemoglobin, which is normally the role of red blood cells (hemoglobin being what makes them red).
Not only that, but DMSO had also curbed the cancer cells’ rapid division. As Dr. Marks recalled in his 2014 memoir, DMSO had “coaxed the monster back into a benign state.”
Thirty years later, these fledgling observations would result in the 2006 US Food and Drug Administration approval of vorinostat (Zolinza®), a drug used to treat certain types of lymphoma. Vorinostat is one of the first so-called epigenetic therapies for cancer: Rather than kill cancer cells, it helps to steer them back onto a normal course. The active component in vorinostat, suberoylanilide hydroxamic acid, is similar in chemical structure to DMSO.
Building Cancer Science from the Ground Up
Inspired by these early discoveries about blood cells, Dr. Marks came to believe that more-effective cancer treatments would come from scientists gaining a deeper knowledge of fundamental biological processes, particularly at the molecular level.
He began looking for ways to transform oncology into a research-driven science.
In 1980, he got his chance. At the request of Memorial Sloan Kettering Board Chairman Laurance Rockefeller, Dr. Marks assumed the reins of MSK’s presidency. He held that position until his retirement in 1999.
One of Dr. Marks’s first actions as president was to recruit some of the most promising young scientists of the time to the Sloan Kettering Institute. Among them were James Rothman, Nikola Pavletich, Dinshaw Patel, Jerard Hurwitz, Ora Rosen, Ken Marians, Joan Massagué, Maria Jasin, Kathryn Anderson, and Mark Ptashne.
This cast of rising stars had the skills, in Dr. Marks’s eyes, to investigate the problem of cancer in the way that was most likely to yield results: from the inside out. “Most of the answers to cancer lie down on the level of the genes, in our understanding of how cells differentiate and divide,” he said in a 1987 New York Times interview.
Dr. Marks’s views on cancer research were shaped in part by his own introduction to basic science, through the time he spent in the Pasteur Institute lab of the Nobel Laureate Jacques Monod in the 1960s. He wanted to bring that perspective to MSK.
“He definitely saw the importance in having a very strong basic science component to this institution,” says Thomas Kelly, a former Director of SKI and now a professor in its molecular biology program. “His vision was to foster the development of SKI by bringing in leaders in their fields. It was a small group of investigators, but the impact on science was very high.”
Through his efforts, Dr. Marks helped to set MSK — and by extension the wider field of oncology — on a more scientific course. The particular field of epigenetics, which Dr. Marks helped to establish through his work on vorinostat, continues to thrive at MSK.
Throughout his life, Dr. Marks’s expertise and leadership were sought and honored widely. He served as a member of US presidential panels on cancer and biomedical research. He was a member of the National Academy of Sciences, the National Academy of Medicine, and the American Philosophical Society, and was a Fellow of the American Academy of Arts and Sciences. To honor his contributions to science, President George H. W. Bush awarded him the National Medal of Science in 1991. Over his long career, Dr. Marks published more than 350 scientific articles in scholarly journals and served as Editor-in-Chief of the Journal of Clinical Investigation.
Dr. Marks influenced the cancer establishment in yet another way: as a teacher. For many years he taught the clinical pathology course to medical students at Columbia University College of Physicians and Surgeons. One of his students was Harold Varmus, who would later win, along with J. Michael Bishop, a Nobel Prize for discovering the cellular origin of cancer-causing genes, or oncogenes.
“Paul Marks made a special impression on me in his lectures,” Dr. Varmus recalled in his memoir. “As Dr. Marks’s lectures made clear, such changes in DNA (mutations) could cause disease when they affected physiologically important proteins.”
Dr. Varmus would succeed Dr. Marks as president of MSK, taking the helm in 2000. True to the influence of his mentor, Dr. Varmus continued the legacy of supporting innovative basic science.
In recognition of Dr. Marks’s many contributions, including his support for young scientists, MSK established the Paul Marks Prize for Cancer Research in 2001. The prize is given every other year to investigators who have made important contributions to cancer research early in their careers. It is a fitting tribute to a man who cared so deeply about nurturing the next generation of scientists.
In a letter sent to the MSK community, President and CEO Craig Thompson and Dr. Massagué lauded Dr. Marks’s contributions to science and MSK’s leadership.
“We will be forever grateful for his extraordinary devotion, exceptional wisdom, remarkable talent, and keen foresight,” they wrote.