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Harold Varmus Provides Vision While Venting at ASCO Meeting

Rosenthal, Eric T.

doi: 10.1097/01.COT.0000292600.96718.1a

When Harold Varmus, MD, presented his Science of Oncology Award Lecture at the this year's American Society of Clinical Oncology Annual meeting, he used the occasion to promote his open-access Public Library of Science (PLoS) project—and to criticize the American Association for Cancer Research for obstructing the flow of peer-reviewed information to PubMed Central, the National Institutes of Health's free digital archive of biomedical and life sciences journal literature.

What wasn't revealed during his “Oncogenes Come of Age” speech—which primarily addressed changing the culture of cancer research through what Dr. Varmus referred to as the merging of the two concentric circles of molecular biology and medical oncology—was that AACR's publication policy regarding posting to the NIH site was the same as host society ASCO's, as well as some 60 other not-for-profit publishers of scientific, medical, and academic journals.

Dr. Varmus, Nobel Laureate, former NIH Director, and current President of Memorial Sloan-Kettering Cancer Center, was the first recipient of ASCO's Science of Oncology Award, created to recognize outstanding contributions to basic or translational cancer research.

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World of Molecular Genetics, World of Clinical Oncology

His lecture opened with the observation that during the early years of his 35-year career in cancer research, the world of molecular genetics of cancer, to which he belonged, and the world of clinical oncology seemed nearly entirely separate.

“Different language, different culture, different tools for doing research, different people,” he said. “You could almost imagine these as being as separate as the spheres of religion and science. Probably each sphere thought the other was religion.

“Another way to think about this is that one world was perceived as potentially irrational and the other as potentially irrelevant.”

Dr. Varmus said that these two worlds began to overlap in about 1990, the year following his receiving the 1989 Nobel Prize in Physiology or Medicine with J. Michael Bishop, MD, when both were at the University of California, San Francisco.

Evidence of the overlap included DNA-based testing of chronic myelogenous leukemia cells in patients, introducing antibodies against oncogenic proteins, and early ventures into risk assessment by looking for inherited mutations in tumor suppressor genes.



Noting that it is only now that cancer research is “actually entering its most interesting phase,” he said that over the last six years, things have become much more interactive, with the appearance of gene-expression profiling that has been widely employed in research in looking at indicators of diagnostic, prognostic, and therapeutic approaches—“perhaps more invested than has actually become clinical practice, but, nevertheless, bringing these two worlds together.”

Dr. Varmus then offered his four-part prescription for completing the integration and overlapping of clinical oncology and molecular genetics of cancer:

  • ▪ Understand and apply the many things we know.
  • ▪ Move to a position of defining the complete genotype of all cancers.
  • ▪ Develop new strategies for prevention and treatment.
  • ▪ And, “finally, change the culture of what we do, find better ways to disseminate new knowledge to all and to change the basic culture by which we train people to practice the oncological sciences.”
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Follow-up Interview

During a subsequent telephone interview, Dr. Varmus, whose own laboratory has been engaged in translational research, as has the MSKCC Lung Cancer Oncogenome Group, discussed how Memorial Sloan-Kettering is putting its money where its mouth is regarding that final point, and explained why he singled out AACR for “obstructing” the move to contributing articles to the NIH library.

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New MSK Graduate School of Biomedical Science

In July 2006, MSK will admit its first class of 10 to 12 students to the Louis V. Gerstner Jr. Graduate School of Biomedical Sciences.

“We're looking for quality over quantity—only students who are extremely talented,” Dr. Varmus said. “I think there's increasing interest among young people, especially college students, in doing disease-oriented research.

“I think it's useful to think about graduate programs that are tailored to their specific interests in joining basic molecular biology and genetics and other fundamental sciences with understanding of disease and that doesn't necessarily require them to get MDs and PhDs.

“In a sense that's the motivating factor in our new five-year graduate program,” he continued. “You'll do a thesis and get all the basic sciences, but everything you learn about in the basic sciences will be filtered through the prism of understanding cancer.”

He added that the idea for a cancer biology doctoral program is not new, and that other institutions including Stanford and Duke have them, but that the MSK curriculum will include opportunities for clinical activities in the outpatient clinic and hospital, and meeting with clinicians as well as scientists.

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‘Chiding’ AACR

As for criticizing the AACR, or “chiding” the Association as mentioned on Sloan-Kettering's Center News Web site (, what was that all about?

Before speaking with Dr. Varmus, I contacted Kathleen Case, Publisher for AACR, who has been actively involved in a the Washington DC Principles for Free Access to Science, a group of about 60 not-for-profit scientific, technical, and medical publishers who share similar publishing principles and practices.

Ms. Case said AACR's publishing policy is the same as that of ASCO, the American Society of Hematology, and other members of the group.

In fact, the letter she wrote to AACR's 21,000 members—about the NIH's new policy requesting that “authors of papers reporting NIH-funded research deposit the full text of those articles, immediately upon acceptance by a peer-reviewed journal, in the National Library of Medicine's PubMed Central database”—was identical to the letter that ASH had sent to its members.

The AACR letter was co-signed by AACR CEO Margaret Foti, PhD, and written on behalf of the AACR Publications Committee and the AACR Board of Directors.

That letter stated: “The NIH policy is a request; it is NOT a requirement [highlighted like that in the original]. It is a policy, not a rule, and because NIH does not own the intellectual property of its grantees, it cannot force compliance. Further, the NIH has clearly stated that it will honor copyright agreements authors make with publishers and will not monitor whether grantees have deposited articles with PubMed Central.”

Three paragraphs down, the AACR letter reads, “PubMed Central will require that you adhere to their technical standards to deposit articles. The standards are different from those of AACR journals; thus, AACR will not be able to assist you in depositing articles.”

In Dr. Varmus' ASCO speech, he said that dissemination of knowledge is critical to changing the culture of cancer research. He then talked about how that dissemination is being hindered by “the grossly for-profit entrepreneurs, like those at Elsevier,” as well as not-for-profit scientific societies that publish journals.

“We need to face the question of whether we are going to behave like a community that believes in the public library, or like monks who believe in squirreling away documents,” he said. “Are we going to make the best use of the Internet and the powers of information technology?

“Why are scientific societies, even scientific societies that are disease-oriented and immensely interesting to the public, even cancer-oriented societies, obstructing this move, with letters to their members which discourage participation?”

Dr. Varmus then cited and paraphrased the AACR letter, and said, “For example, look at this letter received by members of the American Association for Cancer Research saying, ‘The NIH policy is a request; it is NOT a requirement. NIH…cannot force compliance…there would be two versions of your article online…AACR will not be able to assist you in depositing articles…AACR authors will be required to stipulate that their article can be made public on PMC one year after journal publication, but not sooner….’

“What is gained by doing this?,” he asked. Who benefits from this? In my view, this is going to hurt everyone in the long run. Do we need to rethink how some of our societies are behaving?”

Ms. Case explained that when AACR wrote that it will not be able to assist authors in depositing articles to PubMed Central, it was because the different technical standards at the NIH made it impossible for AACR and many other societies to comply.

“We didn't say we would not help authors, we said we will not be able to assist them until compatible standards are in place,” she said.

She also noted that the one-year guideline was similar to many other medical and scientific societies' publishing policies, and said the AACR had previously opposed the NIH policy, but adapted to it once it was put in place.

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Why Not Fuller Context?

When asked why he did not provide fuller context during his speech regarding similar publishing policies by other societies, Dr. Varmus said, “I singled them out only because I had seen their letter and they're a big organization politically, and there were no doubt thousands in that audience who had seen that letter, which I found frankly offensive.

“It goes beyond whether one believes in making the scientific literature more accessible,” he continued.

“The NIH public-access policy is partially a manifestation fueled by Congressional interest in seeing the work taxpayers pay for made more accessible to the public.

You know the public isn't as stupid as some scientific societies seem to think. It includes doctors, teachers, patients, advocates, patients' families, and reporters. They want access to this information, and to have a scientific society throw out pretty clear signs that they're hostile to the policy is not going to do us any good in relation to Congress. “Let's distinguish between publishing policies and a letter that's as ‘in your face’ as that letter was. I'm fully aware of publishers who send out their principles of free access to science, which is part of the point, but it's not true open access; it's laughable.

“But forget about that, the issue is: who's in charge of these societies anyway? Is it the rank and file for whom the society was created, or the staff members?”

Dr. Varmus went on to say that if ASCO had sent him a letter he could have used, he would have used ASCO's letter. “I know ASH sent a letter out, but I didn't see that one. I used what I had, and if I didn't quote every word, I think I pretty much fairly conveyed the sense of the letter.”

He added that it “was politically stupid too, because Congress cares about this, and, of course, people are bringing this letter to the attention of the people in Congress who want the NIH to provide the content of the work that NIH performs for the public. It doesn't help when it appears that scientific societies in cancer research appear to be opposing those policies.”

In his ASCO lecture, Dr. Varmus concluded with the comment, “Notwithstanding the enthusiasm of The Economist [which had featured a cover story in October on “Beating Cancer—The New Frontier of Molecular Medicine”] or the enthusiasm of Dr. von Eschenbach, we have a long way to go before we beat cancer. We're not going to do so before 2015.”

After all, that will only be four years after the first class at the Gerstner Graduate School of Biomedical Sciences graduates, and the concentric circles come full circle into a fully overlapping one.

© 2005 Lippincott Williams & Wilkins, Inc.
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