A tribute to Paul A. Marks, MD, 1926–2020
James E. Rothman
J Clin Invest. 2020. https://doi.org/10.1172/JCI140020.
Obituary
On April 28, 2020, the world lost a giant of medicine: Dr. Paul Alan Marks, a pioneer in human genetics, the architect of the modern cancer center, and a former editor of this Journal (1967–1971) (Figure 1). Marks had humble beginnings in a coal town in rural Pennsylvania, born to Russian Jewish immigrants employed in the clothing industry. Raised by his grandparents in Brooklyn, Paul was taken under the wing of a high school teacher who had recently lost his physician son in the ongoing World War II; this teacher helped inspire Paul to a career in medicine. While at Columbia, Paul’s fate was sealed, when — as chance would have it — his roommate was the future Nobel laureate Joshua Lederberg, who was already doing research on genetics and who “literally dragged [him] into the lab,” as Paul told the JCI (1). Now permanently hooked, Marks completed his MD degree and medical residency at Columbia before embarking on his research career, which began at the NIH as a postdoctoral fellow in the laboratory led by enzymologist and later Nobel laureate Arthur Kornberg. Returning to Columbia in 1955, Marks artfully combined enzymology and genetics with his clinical interest in hematology using the relatively simple red blood cell as a model. In what is now considered classic work, he soon discovered […]
Find the latest version: https://jci.me/140020/pdf The Journal of Clinical Investigation OBITUARY
A tribute to Paul A. Marks, MD, 1926–2020
On April 28, 2020, the world lost in academia and in the biopharma- a giant of medicine: Dr. Paul Alan ceutical industry. Marks, a pioneer in human genet- Paul’s early scientific contribu- ics, the architect of the modern tions were recognized by his elec- cancer center, and a former editor tion to the US National Academy of of this Journal (1967–1971) (Figure Sciences in 1973, and his later and 1). Marks had humble beginnings broader contributions were rec- in a coal town in rural Pennsylva- ognized by the National Medal of nia, born to Russian Jewish immi- Science, presented to him by Presi- grants employed in the clothing dent George H.W. Bush in 1991. industry. Raised by his grandpar- Paul Marks was a man of great ents in Brooklyn, Paul was taken energy, ambition, and charisma; he under the wing of a high school was tall, with the gift of stunningly teacher who had recently lost brilliant blue eyes and an infec- his physician son in the ongoing tious smile. He had an uncanny World War II; this teacher helped ability to spot and cultivate talent, inspire Paul to a career in medi- and he was a remarkable and quick cine. While at Columbia, Paul’s judge of character. While given to fate was sealed, when — as chance wry humor and radiating a natural would have it — his roommate was warmth, he could also be formida- Figure 1. Paul A. Marks, MD, led Memorial Sloan Kettering Cancer ble, pursuing important goals sin- the future Nobel laureate Joshua Center from 1980-1999, during a period of dramatic transforma- Lederberg, who was already doing tion for the institution. gle-mindedly and practically, but research on genetics and who “lit- ultimately unselfishly. For Paul, it erally dragged [him] into the lab,” was always about the institution, as Paul told the JCI (1). Marks brilliantly seized on this seren- not the individual. This extraordinary Now permanently hooked, Marks dipitous finding to found a new field. He combination made him a natural leader. completed his MD degree and medical surmised that the cancer phenotype could People from all walks of life were drawn to residency at Columbia before embarking potentially be reversed — even when the him, pulled in by the vortex resulting from on his research career, which began at the cancer was caused by permeant mutation- his larger-than-life persona. NIH as a postdoctoral fellow in the labora- al changes in the DNA sequences — by a Thus, Paul did not go unnoticed. In tory led by enzymologist and later Nobel totally novel kind of differentiation ther- the wake of the student disruptions of the laureate Arthur Kornberg. Returning to apy that would epigenetically reset the late 1960s, famously begun at Berkeley Columbia in 1955, Marks artfully com- developmental program to that of the nor- and Columbia, the latter’s medical school bined enzymology and genetics with his mal cell. With his colleague and long-term turned to Marks, then 44 years old, to be clinical interest in hematology using the research partner, the late Richard Rifkind, its next Dean, despite his young age and relatively simple red blood cell as a mod- and the late Columbia chemist Ronald limited administrative experience. Marks el. In what is now considered classic work, Breslow, Marks systematically and force- attracted major talents to Columbia, he soon discovered a genetic defect in the fully tested his idea, developing ever more including the future Nobel laureates Eric enzyme glucose-6-phosphate dehydroge- potent analogues of DMSO, ultimately Kandel and Richard Axel, and provid- nase (G6PD) as a cause of hemolytic ane- resulting in the 2006 FDA approval of the ed strong leadership to its cancer center. mia. He went on, in the 1960s, to make the drug SAHA (vorinostat) for treatment of When Axel (and Michael Wigler) discov- pivotal observation that defective messen- cutaneous T cell lymphoma. SAHA alters ered how to introduce DNA into cultured ger RNA for one of the subunits of hemo- the pattern of gene transcription by acting animal cells, broadly enabling molecular globin is a cause of thalassemia. Then, in on key enzymes that chemically remove biology, Marks recognized the commer- 1971, Charlotte Friend made the acciden- acetyl groups from the histones that pack- cial potential in an era when it was not yet tal and unexplained discovery that the age DNA. This landmark body of work the custom to patent basic methodologies, simple solvent dimethyl sulfoxide (DMSO) provided the proof of principle that drugs ultimately fueling Columbia’s growth with caused an erythroleukemic cancer cell line can successfully target epigenetic modifi- royalty streams exceeding $100 million to produce hemoglobin. cations to treat cancer, now a major goal annually. Increasingly visible outside of the academy, Paul served on presidential panels for cancer and biomedical research.
Copyright: © 2020, American Society for Clinical Investigation. In 1979, President Carter called on Marks Reference information: J Clin Invest. https://doi.org/10.1172/JCI140020. to provide expert advice as part of the
jci.org 1 OBITUARY The Journal of Clinical Investigation
President’s Commission on the [Nuclear] became the acknowledged world leader in and Elizabeth Ostrer — as well as six grand- Accident at Three Mile Island. cancer research, training, and treatment. children and two great grandchildren. Marks’ success at Columbia was Paul Marks’ impactful career at the I had the privilege of working with Paul noticed across town. In 1974, the Sloan- intersection of science, medicine, busi- at MSKCC from 1991 to late 1999, when he Kettering Institute was torn by a very ness, and government occurred in the retired as President as the century ended. public research fraud scandal, caus- global epicenter of culture, New York City, During that time, our family became part ing a frank structural appraisal by its where he touched many people from many of his family, and it remains so. There are Board, which included the venture capi- walks of life. It seemed that everyone knew few, very few, people with whom virtual- tal pioneer Benno Schmidt and Laurance Paul Marks — and that he knew everyone. ly every encounter is etched in memory Rockefeller, the Chair of the Board and And not just scientists. In a typical visit to because it was somehow remarkable. I was long-time patron of Memorial Sloan- his office, our meeting would be interrupt- privileged to have many singular moments Kettering (MSK). They knew that funda- ed by a call from the Clinton White House with this great man. When he was recruit- mental changes would be needed, and in and, a few minutes later, from a US Sena- ing me, I was offered a standard faculty 1980, Marks agreed to lead the rebuild- tor. Then, a board member or family friend office, about a third the size of my office ing effort as President. Marks found an seeking medical advice. Later, a banker at Princeton, and I balked. He paused and, inbred culture, which he set about fixing wanting Paul’s opinion on a biotech prod- only when the tension had peaked, said, by insisting on a uniform and high stan- uct. Once, the Israeli Prime Minister called “Okay Jim. We can do that. But from now dard of excellence, whether for basic or to say he was in town. All of this made Paul on, you and I are going to have a relation- clinical researchers, relying on external memorable, made his own life interesting, ship.” He really meant it. peer review by stars in the field. There had and also provided a springboard for the been no tenure system. Installing one pro- prodigious fund-raising that helped him James E. Rothman vided Marks the catalyst and the means to build the world’s greatest cancer center. to effect systemic changes. This dramatic Paul and his wife, Joan, a major figure Address correspondence to: James E. reshaping resulted in the globally influen- in the field of genetic counseling, conduct- Rothman, Department of Cell Biology, tial concept of what a cancer center should ed MSKCC as an elegant extended family. Yale University School of Medicine, 333 be. However, getting there was not with- They made us all feel a part of their home Cedar Street, New Haven, Connecticut, out controversy, as famously captured in a and life, and they shared their many and USA. Phone: 203.737.5293; Email: james. contemporaneous cover story in the New varied interests in music, art, and travel. In [email protected]. York Times Sunday Magazine. Within a addition to Joan, Paul leaves three children 1. Neill US. A conversation with Paul Marks. J Clin decade, MSK Cancer Center (MSKCC) — Andrew Marks, MD; Matthew Marks; Invest. 2012;122(10):3371–3372.
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