Harold Varmus: A Decade of Leadership at MSK

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Harold Varmus former CEO of MSK

Harold Varmus became President and Chief Executive Officer of Memorial Sloan Kettering Cancer Center on January 1, 2000. He ended his decade-long tenure on July 1, 2010. And on July 12, 2010, Dr. Varmus took up a new role as Director of the National Cancer Institute. In the following article, we feature some of the many accomplishments of his more than ten years of leadership.

Growing the Center

Focusing on the intersection of research and disease — working to enrich the connections between science and the clinical control of cancer — has been the overarching theme of my years at Memorial Sloan Kettering.

Dr. Varmus made key new appointments of institutional leaders who have helped to create and guide clinical and scientific programs. Among his early recruits were Robert E. Wittes, as Physician-in-Chief, and Thomas J. Kelly, as Director of the Sloan Kettering Institute. They both joined Memorial Sloan Kettering on March 1, 2002. “From my perspective, this was a pivotal moment in my history here,” he says. “Getting these two people to run the two major components of the institution dramatically simplified my job and made it much more enjoyable. They are wonderful people with vision, skill, and experience.” Another “significant recruitment beyond Bob and Tom was Charles Sawyers,” says Dr. Varmus. Dr. Sawyers played a key role in the development of imatinib (Gleevec®), one of the first targeted therapies for cancer, and was appointed the inaugural Chair of the Human Oncology and Pathogenesis Program in 2006.

Thomas Kelly, Douglas Warner, Harold Varmus, and Robert Wittes

(From left) Thomas Kelly, Chairman of the Boards of Overseers and Managers Douglas Warner, Harold Varmus, and Robert Wittes.

“Harold Varmus has provided visionary leadership during a critical period in the history of Memorial Sloan Kettering. He presided over an extraordinarily ambitious expansion of our research programs that resulted in the recruitment of an exceptional group of scientists and the development of new ways to bridge basic and clinical science. This investment in cancer research occurred at just the right time, as the next decade will see profound advances in our understanding of cancer and our ability to apply that understanding to the prevention, diagnosis, and treatment of cancer. Because of Harold, Memorial Sloan Kettering is poised to make major contributions to this effort. I think that Harold has also left his mark on Memorial Sloan Kettering in less obvious ways. His infectious enthusiasm for science and his supportive leadership style have fostered a collaborative and vigorously interactive research environment that contributes directly to our success and will be one of his most important legacies.”

—Thomas J. Kelly, Director, Sloan Kettering Institute

Expanding Basic and Translational Research Programs

In the early years of his tenure, as Dr. Varmus expanded and refocused the Center’s research enterprise, new programs were created within the Sloan Kettering Institute — the basic science research arm of Memorial Sloan Kettering. These programs included computational biology, developmental biology, structural biology, and cancer biology and genetics; they joined already existing programs in cell biology, molecular biology, immunology, and molecular pharmacology and chemistry. Later, to increase institutional research strength in areas crucial to contemporary translational research (translational research seeks to move molecular insights about cancer into patient care), the Memorial Hospital-based Human Oncology and Pathogenesis Program (HOPP) was established.

Facilities

I don't think of my time at Memorial Sloan Kettering as being about bricks and mortar, but in order to expand old programs and build new ones — and bring in new people — you have to build new facilities.

Chief among those facilities is the Mortimer B. Zuckerman Research Center (ZRC), a 23-story state-of-the-art tower that opened in May 2006. There were, in addition, several major construction projects planned or underway to support Memorial Sloan Kettering’s clinical operation when Dr. Varmus assumed the presidency, and he became an ardent supporter. These included the Claire Tow Pediatric Pavilion, which opened in 2004, and construction of 21 new surgical suites, which opened in 2006. “Part of my support was just saying, ’Let’s go full-bore and finish these projects,’ and part of it was saying that we had to have a capital campaign to raise the money to pay for them — as well as for other projects and initiatives,” Dr. Varmus remarks. The Campaign for Memorial Sloan Kettering, launched in 2003 with an original goal of raising $1 billion over five years, was extended in 2006 and a new goal was announced — to raise $2 billion by the end of 2011. The Campaign, co-chaired by Chairman of the Boards of Overseers and Managers Douglas A. Warner III and Vice Chairman Louis V. Gerstner, Jr., exceeded that goal in 2009, well in advance of schedule.

More recently, in the fall of 2009, Memorial Sloan Kettering opened a new 16-story Breast and Imaging Center housing the Evelyn H. Lauder Breast Center and the Memorial Sloan Kettering Imaging Center; and, in the spring of 2010, the Center for Image-Guided Intervention, a new Surgical Day Hospital, and a new endoscopy suite opened on the second floor of Memorial Hospital (see full story).

Collaborations

Nearly all great ideas come from individual minds … But validation and acceptance of new information requires communication, convening, and consensus building — activities that involve a community. Science is an inherently paradoxical activity.

His Memorial Sloan Kettering legacy has been enhanced by collaborations between the Center and its neighbors on Manhattan’s Upper East Side — Weill Cornell Medical College and The Rockefeller University — neighbors that had worked with Memorial Sloan Kettering previously to build training programs. In an effort to advance basic biological research, the three institutions were brought together again in 2000 to form the Tri-Institutional Research Program, supported by the Atlantic Philanthropies. The partnership includes joint faculty appointments, shared graduate education programs, and shared core-resource facilities. Two PhD programs emerged from the Tri-Institutional Research Program, one in chemical biology and the other in computational biology and medicine. In 2005, the Tri-Institutional Stem Cell Initiative was established, funded by a $50 million grant from the Starr Foundation. It built on the existing research ties among the institutions “and was one of a series of events that’s helped me strengthen relationships with our neighbors,” says Dr. Varmus.

Another significant collaborative research initiative created under his leadership was the Starr Cancer Consortium, an ambitious $100 million undertaking designed to coordinate cancer research efforts at Memorial Sloan Kettering, The Rockefeller University, and Weill Cornell Medical College, along with the Broad Institute of MIT and Harvard, and Cold Spring Harbor Laboratory.

“It’s not just the sharing of resources, it’s the ambience of having a bigger community that works well together. The connections that extend outside Memorial Sloan Kettering have allowed us to maintain our independent institution with its unique qualities, while gaining access to new technologies and encouraging the personal interactions that influence everyone’s research in favorable ways.”

— Harold Varmus

“What Harold accomplished at Memorial Sloan Kettering over the last ten years is absolutely extraordinary. He grew and focused our research, recruited outstanding people throughout the organization, developed programs and processes to stimulate translational initiatives, began our graduate school, expanded facilities, and raised over $2 billion in new capital. He leaves Memorial Sloan Kettering better and stronger than he found it — and it was strong when he got here — and for that the entire Memorial Sloan Kettering community is grateful.”

— Douglas A. Warner III, Chairman, Boards of Overseers and Managers

Lung Cancer Oncogenome Group

Dr. Varmus’ own research exemplifies his determination that “the medical treatment of cancer and efforts to understand cancer at the molecular level should be pursued concurrently.” As part of his work at Meorial Sloan Kettering on lung cancer, he has marshaled a multidisciplinary team — the Lung Cancer Oncogenome Group (LCOG) — to study a range of genetic abnormalities found in that disease.

Created in 2003, LCOG is an alliance of oncologists, surgeons, radiologists, pathologists, molecular biologists, and others. The group was originally established to investigate the molecular underpinnings of two targeted therapies, gefitinib (Iressa®) and erlotinib (Tarceva®). These medications inhibit a normal signaling protein called the epidermal growth factor receptor (EGFR), which is mutated in about 10 percent of cases of the most common form of lung cancer.

In his own laboratory, Dr. Varmus is looking for ways to improve these therapies — which include avoiding the secondary drug resistance that he and his colleagues have shown is the result of an additional mutation in the EGFR gene. “We’re encouraged that we can study the resistance and efforts to overcome it in mouse models, and also seek explanations for the 30 to 40 percent of lung tumors in humans that don’t have either of the two known resistance-conferring mutations,” he says.

GSK Graduate School of Biomedical Sciences

I think for people who don’t want to be doctors but want to know medicine and something about disease, a cancer biology PhD program is very attractive,” Dr. Varmus says. “Fortunately, we had people on the Board, especially Lou Gerstner, who liked the idea.” The first class of the Gerstner Sloan Kettering Graduate School of Biomedical Sciences matriculated in 2006. Currently, 35 students are enrolled in the school, and eight more will matriculate in July 2010.

There was a demand from young prospective scientists for a graduate training program that allowed them to become knowledgeable about disease without necessarily becoming doctors. I thought we had something special to offer at Memorial Sloan Kettering.

Seeking to bridge basic research and real-life clinical challenges, GSK offers its students an intensive PhD program to study the biological sciences through the lens of cancer. The faculty includes many SKI investigators and Memorial Hospital physician-scientists, with the clinical faculty taking students directly into the clinic. “We expose them not just to research about cancer,” Dr. Varmus explains, “but to the clinical experience of cancer. Most basic scientists who didn’t go to medical school don’t have a clue about what it’s like to take care of a patient.”

Centers Without Walls

A major theme of Dr. Varmus’ tenure was “centers without walls.” The Geoffrey Beene Cancer Research Center, created in 2006, is an internal “virtual” center that builds on MSKCC’s scientific and clinical programs, bringing together investigators from SKI’s Cancer Biology and Genetics Program (CGB), the Human Oncology and Pathogenesis Program (HOPP), and other programs and departments, to explore the biology and genetics of cancer.

Further augmenting the connections between clinical and basic science investigations was the William and Alice Goodwin Experimental Therapeutics Center (ETC), established two years after Dr. Varmus’ arrival. The ETC gathers investigators from around the institution under one “virtual roof” to foster drug discovery from the laboratory through to early-stage clinical trials. The number of shared core facilities that provide services and technical expertise to basic and translational researchers also grew during his years as president.

He observes “in the study of cancers, for example, we have yet to learn the full repertoire of events that drive a normal cell to adopt a malignant behavior or to identify changes in most cancer cells that are optimal targets for intervention.”

Science is inevitably an incomplete process, and our knowledge of nearly all aspects of the natural world remains very far from complete.

Clearly, prodigious work remains to be done in the quest to control and some day cure cancer — and Dr. Varmus’ role in this undertaking is far from over. On July 12, 2010, when he assumed the directorship of the National Cancer Institute, he began a challenging new chapter in his personal and scientific journey. “There are tremendous new opportunities in cancer research,” he said in an interview with the New York Times on the day his appointment was announced by the White House. “Everyone feels a sense of accelerating success. There are amazing prospects.”

“Harold’s immense impact on Memorial Sloan Kettering has affected all the institution’s programs. Over the past decade we have seen major expansion and modernization of the physical plant for clinical and research activities. Many parts of the hospital — pediatrics, pathology, the operating rooms, the intensive care unit — have been replaced by state-of-the-art facilities. Other facilities and programs — the Breast and Imaging Center, the Center for Image-Guided Interventions, and the Human Oncology and Pathogenesis Program — have very recently come into being and are spectacular institutional assets.

Early on in his tenure, he redesigned the configuration of our research programs and reoriented several, so that they might more effectively bridge the gap between laboratory and clinic. As a result, this gap is much narrower now than before his arrival, and, although there is much yet to be done, Memorial Sloan Kettering is well on its way to having the kind of translational research effort that befits one of the world’s premier cancer centers. The creation of the Gerstner Sloan Kettering Graduate School, with its unique emphasis on exposing graduate students to the realities of clinical oncology, is likely to produce a generation of new PhDs with a strong interest in the study of human cancer. And finally Harold has been an indispensible force in our successful recruitment of numerous outstanding research leaders to the Center. It’s been quite a decade!”

— Robert E. Wittes, Physician-in-Chief, Memorial Hospital