In memoriam: Prof. Marvin Zelen, a ‘tremendous force’ in biostatistics

Marvin Zelen

November 18, 2014

The Harvard School of Public Health community was saddened to learn that Professor Marvin Zelen—a driving force behind both the Department of Biostatistics at Harvard School of Public Health (HSPH) and the Department of Biostatistics and Computational Biology at Dana-Farber Cancer Institute (DFCI)—died on November 15, 2014, at age 87 after a battle with cancer.

Prof. Zelen was known as a giant in the field of biostatistics, as well as a man of vision, generosity, and warmth who served as a mentor to two generations of researchers.

At HSPH, Prof. 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 as chair of HSPH’s Department of Biostatistics from 1981-1990, and at Dana-Farber in the 1970s he helped create (and chaired through 1999) the Department of Biostatistics and Computational Biology. In both cases he led the growth of these programs to worldwide prominence and impact.

“He was an unstoppable positive force whose influence will be felt for as long as there will be cancer research,” said Giovanni Parmigiani, current chair of Dana-Farber’s Department of Biostatistics and Computational Biology and professor of biostatistics at HSPH. “He was a pioneer and a tireless advocate in establishing rigorous quantitative approaches as an integral part of clinical cancer research across the U.S. and internationally. He contributed by innovating across the board: from trial design and analysis to data quality assurance; from academic administration to the establishment of nonprofit models for clinical research organizations; from mentorship to philanthropy.”

“Scientists from around the world have benefited from Dr. Zelen’s innovative ideas and transformative effect on biomedical research,” said current HSPH biostatistics chair Victor De Gruttola.

Prof. Zelen was known for developing the statistical methods and study designs that are used in clinical cancer trials, in which experimental drugs are tested for toxicity, effectiveness, and proper dosage. He also introduced measures to ensure that data from the trials is as free as possible of errors and biases—measures that are now standard practice. Prof. Zelen helped transform clinical trial research into a well-managed and statistically sophisticated branch of medical science, leading to significant medical advances such as improved treatments for several different 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, Prof. Zelen graduated from New York’s City College, where he became interested in statistics and probability. After 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, D.C. 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 Prof. Zelen spent two years as a visiting professor at the University of Wisconsin’s Mathematics Research Center, where he first worked with cancer researchers. Beginning in 1963, he led the applied mathematics and statistics section of the National Cancer Institute (NCI) for four years, where he delved further into cancer and clinical research. He spent a year in London as a Fulbright Scholar, and then joined the biostatistics department at the State University of New York in Buffalo.

During his decade in Buffalo, Prof. Zelen helped the Eastern Cooperative Oncology Group (ECOG)—one of several regional organizations established by the NCI to test experimental cancer therapies—with their studies. In an American University alumni magazine article in 2008, Prof. Zelen said those early studies were “terrible” and “poorly thought out,” with faulty data, poor quality control, and not enough patients—“everything you can think of that was antiscientific.” He suggested the physicians in charge basically start again from scratch. They agreed, and Prof. Zelen, along with his longtime collaborator Paul Carbone, established the standards and practice now used in clinical trials of many diseases. Along the way, Prof. 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.

Prof. 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, Prof. Zelen’s pioneering work in Buffalo brought him to the attention of HSPH’s then-biostatistics chair, Frederick Mosteller, as well as to then-Dana-Farber Physician-in-Chief Emil “Tom” Frei III. Frei recruited Prof. Zelen to come to Boston—but Prof. Zelen insisted that he would only do so 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. Prof. Zelen took appointments both at HSPH and at DFCI.

At Dana-Farber, Prof. Zelen’s arrival had an almost instant impact on the way research was conducted. Prof. Zelen and his ever-growing team developed a database-management system—one of the first anywhere—to create a formal system for processing clinical information. And they built a database for collecting and organizing research results that Prof. Zelen later said “put us half a decade ahead of everybody else.”

“The team he built at Dana-Farber helped move the field of cancer research with important studies in breast cancer, lymphoma, and pediatric cancer,” said David Harrington, former DCFI biostatistics chair and professor of biostatistics at HSPH. “Marvin’s work in clinical trials set the standard that many groups now adhere to. If you were a young statistician in the late 1970s and early 1980s, there was no better place than DFCI to learn the craft of clinical trials and to contribute to the fight against cancer.”

At HSPH, according to biostatistics professor Nan Laird, “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. It was an enormously exciting time when we were united in working towards 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 that Prof. Zelen was “a tremendous force in my personal and professional life. 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.”

Richard Gelber—one of Prof. Zelen’s young SUNY Buffalo staff to make the move to Boston in 1977 and a current member of both the DFCI and HSPH biostatistics departments—agreed. “For me, the hallmark of Prof. Zelen’s exceptional talent was his ability to establish a working environment in which others could flourish,” he said.

Prof. Zelen achieved another level of fame in the early 1980s when he and his late colleague in the HSPH biostatistics department, Stephen Lagakos, launched a study of a possible connection between a cluster of childhood leukemia cases in Woburn, Mass. 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 Prof. 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 Prof. 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. Prof. Zelen served as president, and his wife Thelma was and remains chief administrative officer and board secretary. Said Gelber, “Their partnership is a role model of working together, and Thelma has been a major force in the formation and administrative leadership of Frontier Science as its chief operating officer for almost 40 years.”

Throughout his long career, Prof. Zelen has been widely praised for his mentorship and generosity. DFCI colleague Paul Catalano called him “a tireless advocate for students and mentor to generations of young biostatisticians, and also an amazing teacher, positively influencing countless trainees both in and out of the classroom.” Fellow biostatisticians from around the country—people like Jack Kalbfleisch from the University of Michigan, Ross Prentice from the Fred Hutchinson Cancer Research Center, Norman Breslow from the University of Washington, and Mitchell Gail, senior investigator in the biostatistics branch of NCI’s Division of Cancer Epidemiology & Genetics—have all spoken of Prof. Zelen’s huge influence. Prentice said Prof. Zelen “did much to define the biostatistical profession.” Said Gail, “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.”

Prof. 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 honors in the field, meant to reflect Prof. Zelen’s contributions to quantitative science and beyond. In 2009, Prof. Zelen was awarded the American Cancer Society’s highest distinction—a Medal of Honor. 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. He received an honorary doctoral degree from the Universite Victor Segalon in France, 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 the Presidents of the Statistical Society (COPSS) in 2007 in recognition of his outstanding contributions to statistical science.

“Marvin was a transformative leader of his field, a wonderful teacher and mentor, ‎and a fabulous colleague,” said Dana-Farber President Edward J. Benz Jr. “We will all miss him.”

Prof. Zelen is survived by his wife Thelma, two daughters, Deborah and Sandy Zelen, and two grandsons, Matthew and Toby Mues. A memorial service will be held Friday, May 22, 2015; details will be forthcoming. Contributions may be made in Prof. 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 Street, Boston, MA 02120. They may also be given online. Please designate in the comment field that your contribution is for the Marvin Zelen Education and Leadership Fund.

photo: Shaina Andelman

Note: This article was updated on January 7, 2015