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Obituary: Marvin Zelen

1 January 2015 265 views No Comment
Karen Feldscher

    Marvin Zelen of the department of biostatistics at the Harvard School of Public Health (HSPH) passed away November 15, 2014, at age 87 after a battle with cancer.

    Marvin-Zelen-photo

    Zelen was Lemuel Shattuck Research Professor of Statistical Science, as well as a member of the faculty of arts and sciences (emeritus) at Harvard University. He served for a decade in the 1980s as chair of the school’s department of biostatistics. He was known as a giant in the field of biostatistics, as well as a man of vision, generosity, and warmth. He is credited with transforming HSPH’s biostatistics department into a best in the country.

    Zelen was known for developing the statistical methods and study designs used in clinical cancer trials, in which experimental drugs are tested for toxicity, effectiveness, and proper dosage. He also introduced measures to ensure data from the trials are as free as possible of errors and biases—measures that are now standard practice. Zelen helped transform clinical trial research into a well-managed and statistically sophisticated branch of medical science. His work in this area has led to significant medical advances, such as improved treatments for several forms of cancer. His research also focused on improved early detection of cancer; on modeling the progression of cancer and its response to treatment; and on using statistical models to help determine optimal screening strategies for various common cancers, especially breast cancer.

    Born and raised in New York City, Zelen attended New York’s City College, where he became interested in statistics and probability. After college and a master’s degree in mathematical statistics from The University of North Carolina at Chapel Hill, he worked for 10 years at the mathematics lab of the National Bureau of Standards in Washington, DC. He was the only one working in the lab without a doctorate—which he remedied by earning one at American University in 1957.

    In the early 1960s, Zelen spent two years as a visiting professor at the University of Wisconsin Mathematics Research Center, where he first worked with cancer researchers, helping them address problems with study design. After that, beginning in 1963, he led the National Cancer Institute’s applied mathematics and statistics section for four years, where he delved further into cancer and clinical research. He spent a year in London as a Fulbright Scholar, after which he joined the biostatistics department at the State University of New York in Buffalo.

    During his decade in Buffalo, Zelen helped the Eastern Cooperative Oncology Group (ECOG)—one of several regional organizations established by the National Cancer Institute (NCI) to test experimental cancer therapies—with their studies. In an American University alumni magazine article in 2008, Zelen said those early studies were “terrible.” He said the studies were “poorly thought out; the data was wrong; they had poor quality control, not enough patients—everything you can think of that was antiscientific.” He suggested to the physicians in charge of the studies that they basically start again from scratch. The physicians agreed and Zelen, along with his longtime collaborator Paul Carbone, established the standards and practice now used in clinical trials of many diseases. Along the way, Zelen formed the statistical laboratory at the University of Buffalo, which was dedicated to overseeing and improving the statistical aspects of large, complex drug trials. ECOG would go on to become one of the largest programs in the world for testing various cancer treatments.

    “Marvin had a lot of guts and a vision for what was important,” said Mitchell Gail, senior investigator in the biostatistics branch of NCI’s Division of Cancer Epidemiology & Genetics. “He finagled NCI into supporting the use of DEC-10 computers in clinical trials, long before the study-section supported it. He inspired the clinical trials community of statisticians.”

    Zelen also played a key role in President Nixon’s “war on cancer” in the early 1970s, serving as chair of a committee responsible for drafting the new program. His involvement in this endeavor was “tremendous and lasting,” according to Lee-Jen Wei, professor of biostatistics at HSPH.

    In the mid-1970s, Zelen’s pioneering work in Buffalo brought him to the attention of HSPH’s then-biostatistics chair, Frederick Mosteller, who was working to strengthen the biostatistics department. Zelen insisted he would only come to Harvard if he could bring with him the team he’d built in Buffalo. In the end, 27 faculty, researchers, and staff moved from Buffalo to Boston in 1977, bringing with them a huge DEC-20 computer and the ECOG trials—150 cancer trials involving several thousand patients. Zelen’s lab was established at the Dana-Farber Cancer Institute (DFCI), where, simultaneously with his tenure at HSPH, he built the cancer institute’s department of biostatistics and computational biology.

    Zelen’s colleague, biostatistics professor Nan Laird of HSPH, recalled that “those first few years of integrating 12 new faculty members from Buffalo with half as many from Harvard were part of Marvin’s grand plan to make Harvard the number-one biostatistics department in the country—which it is and has been for quite some time. It was an enormously exciting time when we were united in working toward a common goal. Marvin’s genius was that he got all of us involved, then stepped back and gave us all the credit.”

    On a more personal level, Laird said Zelen was “a tremendous force in my personal and professional life. He was always in and out of my office, asking how things were going. Even as he was trying to convince me to do something I absolutely did not want to do, I always felt his intentions for me were the best. Marvin was always honest and unpretentious.”

    Zelen succeeded Mosteller as biostatistics chair in 1981. He continued working on the ECOG trials, helped lay the groundwork for the department’s pre-eminence in AIDS clinical trials, and improved the biostatistics curriculum. As chair, he was the driving force that propelled the department to its position as a leading center for biostatistical research.

    Zelen also achieved another level of fame in the early 1980s, when he and his late colleague in the biostatistics department, Stephen Lagakos, launched a study of a possible connection between a cluster of childhood leukemia cases in Woburn and the town’s water supply. Known as the Harvard Health Study, the investigation showed, for the first time, a connection between Woburn’s contaminated water and a variety of adverse health effects, including leukemia. The matter made headlines, wound up in court, and was chronicled in the book A Civil Action, which was later made into a movie. As the book notes, when Zelen announced the study’s results in the basement of a Woburn church in February 1984, someone in the audience called out, “Thank God for Marvin Zelen,” and the crowd burst into applause.

    Another of Zelen’s achievements was his establishment, in 1975, of the Frontier Science and Technology Research Foundation, a nonprofit devoted to advancing the use of statistical science and practice and data management techniques in science, health care, and education. Zelen served as president, and his wife, Thelma, was chief administrative officer. Richard Gelber, professor of biostatistics of HSPH and DFCI, said, “This is another excellent example of how Marvin established an environment within which others could flourish. Thelma’s contributions to Marvin’s success cannot be overlooked. Their partnership is a role model of working together, and she has been a major force in the formation and administrative leadership of Frontier Science as its chief operating officer for almost 40 years.”

    Last but not least, Zelen has been widely praised for his mentorship and generosity. Gelber said, “During the past 39 years, Marvin taught me much about the importance of collaborative research and how progress is fueled by statistical and clinical scientists working together as partners.”

    Fellow biostatisticians from around the country—people like Jack Kalbfleisch from the University of Michigan, Ross Prentice from the Fred Hutchinson Cancer Research Center, and Norman Breslow from the University of Washington—have all spoken of Zelen’s huge influence. “Marvin was a tremendous force in the profession and a great mentor to so many of his colleagues and students,” said Kalbfleisch. Prentice said Zelen “did much to define the biostatistical profession.” Breslow said he was “greatly influenced by Marvin and his work.” Mitchell Gail of NCI put it this way: “So many people were helped by Marvin, whether they needed assistance with starting a company, with a personal matter, or with ideas and guidance in academic statistics. That is truly a legacy to be proud of.”

    Current biostatistics chair of HSPH, Victor DeGruttola, said, “Scientists from around the world have benefited from Zelen’s innovative ideas and transformative effect on biomedical research, but those of us associated with the Harvard Department of Biostatistics are particularly grateful for Marvin’s commitment to educating students and advancing the careers of junior scientists.”

    Zelen’s work has been recognized around the world through awards and other accolades. In 1997, in honor of his 70th birthday, the school established the annual Marvin Zelen Leadership Award in Statistical Science, which has become one of the most prestigious awards in the field and is meant to reflect Zelen’s contributions to quantitative science and beyond. In 2009, Zelen was awarded the American Cancer Society’s highest honor—a Medal of Honor. He received the Samuel S. Wilks Memorial Award, one of the most prestigious awards from the American Statistical Association, in 2006, and the Fisher Lecturer Award from the Committee of Presidents of Statistical Societies (COPSS) in 2007 in recognition of his outstanding contributions to statistical science. A special issue of the journal Lifetime Data Analysis was dedicated to him in 2004. Three symposia have been held around the world in his honor. And he received an honorary doctoral degree from the Universite Victor Segalon in France.

    Zelen is survived by his wife, Thelma; two daughters, Deborah and Sandy Zelen; and two grandsons, Matthew and Toby Mues.

    Contributions may be made in Zelen’s memory to the Marvin Zelen Education and Leadership Fund, Department of Biostatistics, Harvard School of Public Health, c/o HSPH Office of External Relations, 90 Smith St., Boston, MA 02120. They also may be given online. Please designate in the comment field that your contribution is for the Marvin Zelen Education and Leadership Fund.

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