NCI Director Harold Varmus Steps Down

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This article is part of The Cancer Letter's MD Anderson Tenure Dispute series.

NCI Director Harold Varmus announced that he will be stepping down at the end of this month.

Douglas Lowy, the current deputy director, will serve as acting director for NCI beginning April 1. Lowy, a long-time NCI intramural researcher, received the National Medal of Technology and Innovation from President Barack Obama in 2014 for his research that led to the development of the human papillomavirus vaccine.

In a letter to colleagues March 4, Varmus, 75, reflected on his five years at the institute, saying that he is leaving with a “mixture of regret and anticipation.”

Varmus was appointed by President Obama May 18, 2010, and started work July 12, 2010. He previously served as director of the NIH under President Bill Clinton from 1993 to 1999, and as president of Memorial Sloan Kettering Cancer Center from 2000 to 2010.

“The nearly five years in which I have served as NCI Director have not been easy ones for managing this large enterprise-one that offers so much hope for so many,” Varmus wrote. “We have endured losses in real as well as adjusted dollars; survived the threats and reality of government shutdowns; and have not yet recovered all the funds that sequestration has taken away.

“This experience has been especially vivid to those of us who have lived in better times, when NIH was the beneficiary of strong budgetary growth. As Mae West famously said, ‘I’ve been rich and I’ve been poor, and rich is better.’”

Varmus will join Weill Cornell Medical College’s faculty as the Lewis Thomas University Professor of Medicine, and team up with the New York Genome Center as a senior associate core member to promote the use of cancer genomics.

“When I return to New York City full time on April 1st, I will establish a modestly sized research laboratory in the Meyer Cancer Center at the Weill-Cornell Medical College and serve as a senior advisor to the Dean,” Varmus wrote. “In addition, I plan to assist the recently founded New York Genome Center as it develops its research and service functions and helps regional institutions introduce genomics into cancer care.”

Varmus’s laboratory, which will be housed in the Belfer Research Building, will continue to focus on lung adenocarcinoma and the cancer-driving mutations found in that disease. Those mutations affect cell signaling, cell growth and processing of RNA.

Varmus will also serve as a senior advisor to Laurie Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell and provost for medical affairs for Cornell University, and will have an appointment in the Weill Cornell Graduate School of Medical Sciences.

During his tenure at NCI, Varmus instituted the Provocative Questions initiative, created NCI’s new Center for Global Health, revitalized the cooperative clinical trials system, launched an initiative to find drugs that target the cell signaling pathway controlled by the RAS oncogene, led the cancer component of the Precision Medicine Initiative, and contributed many other important ideas to biomedical research.

Varmus is the recipient of the 1989 Nobel Prize in Physiology or Medicine, the 2001 National Medal of Science, and the 2001 Vannevar Bush Award. He was also elected to the U.S. National Academy of Sciences in 1984 and in the Institute of Medicine in 1991.

NIH was fortunate to have one of the world’s best minds in cancer research, said NIH Director Francis Collins.

“Who better than Harold Varmus, who won the Nobel prize for discovering oncogenes, to lead the charge as we leap forward in our knowledge about the disease? And it’s not just about cancer,” Collins said in an email. “Few people in history have had as much influence and impact as Harold in shaping the course of modern biomedical science. Harold, indisputably, is a true giant, and we have been lucky to have him here not once, but twice, to help lead this great agency.

“I ask you to join me in congratulating Harold on a job extraordinarily well done, and wishing him the best for the next chapter of his distinguished scientific career.”

Varmus established valuable initiatives that will help transform cancer research for the 21st century and improve cancer care on a global level, said Richard Schilsky, chief medical officer of the American Society of Clinical Oncology.

“He accomplished these tasks during a period when the NCI faced unprecedented financial instability,” Schilsky said.

“As NCI director, Dr. Varmus drew on his deep knowledge of cancer biology and the nation’s biomedical research enterprise to focus the efforts of the cancer community on identifying and tackling the most vexing problems in cancer research and care. ASCO is grateful for his service to the cancer community and the country.”

Varmus demonstrated exemplary leadership and vision in cancer research, prevention and treatment, said Chris Hansen, president of the American Cancer Society Cancer Action Network.

“Dr. Varmus achieved major accomplishments during nearly five years at the helm of NCI, despite the enormously challenging budget environment,” Hansen said. “He initiated the creation of two new centers within NCI, one focusing on global health and another on cancer genomics, that address critical areas in the fight against cancer. He significantly improved the efficiency and breadth of the National Clinical Trials Network and the Community Oncology Research Program to ensure that NCI’s clinical trials programs reflect new approaches to cancer treatment. He also spearheaded the innovative Provocative Questions Initiative to identify potentially promising approaches to cancer research.

“On behalf of millions of people in this country and around the world who have battled cancer or supported a loved one in their fight, ACS CAN thanks Dr. Varmus for his unshakable commitment to public service and his unwavering leadership of the National Cancer Institute.”

Varmus guided NCI with a steady and sure hand in an era of exceptional fiscal challenges, said Louis Weiner, director of the Georgetown Lombardi Comprehensive Cancer Center.

“His focus on promoting the NCI’s scientific mission has led to a set of initiatives that position the national cancer effort for ongoing success,” said Weiner, chair of the Board of Scientific Counselors for Clinical Sciences and Epidemiology for NCI.

The full text of Varmus’s letter follows:

To NCI staff, grantees, and advisors:

I am writing to let you know that I sent a letter today to President Obama, informing him that I plan to leave the Directorship of the National Cancer Institute at the end of this month.

I take this step with a mixture of regret and anticipation. Regret, because I will miss this job and my working relationships with so many dedicated and talented people. Anticipation, because I look forward to new opportunities to pursue scientific work in the city, New York, that I continue to call home.

The nearly five years in which I have served as NCI Director have not been easy ones for managing this large enterprise—one that offers so much hope for so many. We have endured losses in real as well as adjusted dollars; survived the threats and reality of government shutdowns; and have not yet recovered all the funds that sequestration has taken away. This experience has been especially vivid to those of us who have lived in better times, when NIH was the beneficiary of strong budgetary growth. As Mae West famously said, “I’ve been rich and I’ve been poor, and rich is better.”

While penury is never a good thing, I have sought its silver linings. My efforts to cope with budgetary limits have been guided by Lord Rutherford’s appeal to his British laboratory group during a period of fiscal restraint a century ago: “…we’ve run out of money, it is time to start thinking.” Rather than simply hold on to survive our financial crisis without significant change, I have tried—with essential help from my senior colleagues—to reshape some of our many parts and functions. In this way, I have tried to take advantage of some amazing new opportunities to improve the understanding, prevention, diagnosis, and treatment of cancers, despite fiscal duress.

This is not the place for a detailed account of what we have achieved over the past five years. But a brief list of some satisfying accomplishments serves as a reminder that good things can be done despite the financial shortfalls that have kept us from doing more:

  • The NCI has established two new Centers: one for Global Health, to organize and expand a long tradition of studying cancer in many other countries; and another, for Cancer Genomics, to realize the promise of understanding and controlling cancer as a disorder of the genome.
  • Our clinical trials programs (now called the National Clinical Trials Network and the NCI Community Oncology Research Program) have been reconfigured to achieve greater efficiencies, adapt to the advent of targeted drugs and immunotherapies, and enhance the contributions of community cancer centers.
  • Research under a large NCI contract program in Frederick, Maryland, has been redefined as the Frederick National Laboratory for Cancer Research (FNLCR), with more external advice, a large new initiative to study tumors driven by mutant RAS genes, and greater clarity about FNLCR’s role as a supporter of biomedical research.
  • In efforts to provide greater stability for investigators in these difficult times, we have established a new seven year Outstanding Investigator Award; are discussing new awards to accelerate graduate and post-doctoral training; and are planning to provide individual support for so-called “staff scientists” at extramural institutions.
  • To strengthen the NCI-designated cancer centers, we are awarding more supplements to the centers’ budgets to encourage work in high priority areas; helping centers to share resources; and working with the center directors to develop more equitable funding plans.
  • The NCI has attempted to improve the grant-making process in various ways at a time when success rates for applicants have reached all-time lows:

— We have engaged our scientists to identify inadequately studied but important questions about cancer—so-called Provocative Questions—and have provided funds for many well-regarded applications to address them.

— We have pioneered the use of a descriptive account of an applicant’s past accomplishments, moving away from mere listings of publications, to allow a fairer appraisal of past contributions to science.

— Our program leaders now make more nuanced decisions about funding many individual grants, considering a wide range of highly rated applications, not simply those with scores above an arbitrary pay-line.

— And we have maintained NCI’s numbers of research project grants, despite the limits on our budget, while continuing to emphasize the importance of balancing unsolicited applications to do basic cancer research against an increasing call for targeted programs to deliver practical applications.

Of course, it is still too early to judge the long-term consequences of most of these actions. But we do know that many good things have happened in cancer research over the past five years as a result of existing investments:

  • Our understanding of cancer biology has matured dramatically with the near-completion of The Cancer Genome Atlas and with results from other programs that depend on genomics and basic science, including work with model systems.
  • Many new targeted therapies have been tested in clinical trials, and several have been approved for general use.
  • Remarkable clinical successes against several kinds of cancers have been reported with immunological tools—natural and synthetic antibodies, checkpoint inhibitors, and chimeric T cell receptors.
  • More widespread use of a highly effective vaccine against human papilloma viruses (HPV) and the several cancers they cause has been encouraged by further studies and by an important report from the President’s Cancer Panel.
  • Radiographic screening for lung cancers in heavy smokers—validated by a large-scale trial just after I arrived at the NCI—has now been endorsed for wide-spread use and for reimbursement by Medicare and other insurers.
  • New computational methods, such as cloud computing and improved inter-operability, are advancing the dream of integrating vast amounts of molecular data on many cancers into the daily care of such cancers.

Some of these advances are now essential features of the President’s recently announced Precision Medicine initiative that will focus initially on cancer.

Such accomplishments have been possible only because the NCI has been able to recruit and retain exceptional people during my years here; I am grateful to all of you. I am also grateful to the many selfless individuals who have made our advisory groups stronger than ever and to the cancer research advocates who regularly remind me—as well as Congress and the public—about the importance of our work to human welfare.

So what is next?

In my remaining few weeks in this position, I will continue to do the NCI Director’s job with customary energy, despite my inevitable status as a “lame duck.” I will also schedule a Town Hall meeting to review some of the things that have happened during my tenure here—revisiting the ambitions I announced when I accepted the job and answering questions.

As I just learned today, the White House has approved the appointment of my chief deputy and close friend, Doug Lowy, to serve as Acting Director of the NCI, beginning on April 1st. This gives me enormous pleasure, because Doug—along with Jim Doroshow, the NCI’s Deputy Director for Clinical and Translational Research—made many of NCI’s recent accomplishments possible; is a distinguished scientist, who was recently honored by the President with a National Medal for Technology and Innovation for his work on human papilloma virus vaccines; and is a remarkably congenial person to work with. The NCI will be in excellent hands.

Finally, when I return to New York City full time on April 1st, I will establish a modestly sized research laboratory in the Meyer Cancer Center at the Weill-Cornell Medical College and serve as a senior advisor to the Dean. In addition, I plan to assist the recently founded New York Genome Center as it develops its research and service functions and helps regional institutions introduce genomics into cancer care.

While I look forward to these new adventures and to leading a life concentrated in one place, I know I will miss many of the people, authorities, and ideas that make the NCI Directorship such a stimulating and rewarding position.

With deep respect and gratitude to the entire NCI community,
Harold Varmus

Matthew Bin Han Ong
Senior Editor

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