A Man For All Seasons, Part II

GUEST: Dr. Harold Varmus
VTR: 04/21/2005

I’m Richard Heffner, your host on The Open Mind. And this is the second of two programs that I’ve titled, “A Man For All Seasons”. For my guest again today is just exactly that.

Dr. Harold Varmus is President of the world renowned Memorial Sloan Kettering Cancer Center here in New York. Has shared a Nobel Prize with a colleague for studies of the genetic basis of cancer. Has won many other distinguished scientific and medical awards, writes beautifully, researched and taught for two decades at the University of California Medical Center in San Francisco. And for the greater part of the Clinton-Gore Administration presided brilliantly over the National Institutes of Health in Washington.

Dr. Varmus has quite intrigued many of us with his recent criticism in The New York Times of medical science geared entertainments in film and on television. And we talked about them last time and about print journalism’s portrayal of health and serious science matters. My guest sees great opportunities here. But ones not always seized, to put the matter gently.

Well, Dr. Varmus and I also talked a bit last time about cabbages and kings; he mentioned the importance of a proper relationship between the scientific community and government; suggested that in scientific as well as public policy matters, generally, faith-based, rather than fact-based thinking is not the way to go; offered DNA research as a source of hope for those of us who are cancer patients and then, just as I was getting the “No time” left signal here in our studio, Dr. Varmus just mentioned the enormous promise of computerized and open access publishing as an incomparable clue to the rapid dissemination and meaningful use of scientific information. And that’s where I’d like to pick up today, asking my guest to describe and to elaborate a bit on the importance of open access publishing. What gives there?

VARMUS: Well, we have an opportunity created by the Internet, just as the … just as Gutenberg made it possible for scientists to create scientific journals and books and distribute information that way, the Internet has made it possible to store and retrieve and search information that scientists generate with public money … in the most part. They generate without the hope of making profits from their writings. Indeed, scientists write only for fame … they want to be known, they want their work to be known and used.

And there is no real limitation on the capacity of, of the society of scientists who make their work fully available … not just because it becomes free on the Internet, but because it’s stored in a digital library and can be searched by anyone.

The cost of publication of the work we do is roughly less than one percent of the cost of doing the research itself. Most of us do our research with money provided by national … federal agencies like the National Institutes of Health, or by other funding agencies, or by philanthropy and everybody who gives money to support research wants the fruits of that research to be available. So, what’s the problem? Why not just create a, a means of freely distributing research? Well, there’s … there are …

HEFFNER: Yeah, what are … is … the problem?

VARMUS: There are … Yeah, what is the problem? The problem is … first of all we have an existing set of journals that, that scientists respect and have used for many years. Scientists although they appeared to be free thinkers are often very conservative in their habits. The reason for that is that, that academic institutions in particular … others as well, have used the existing hierarchy of journals as a means by which to evaluate how well a scientist’s work is viewed. So if you publish in somebody’s existing journals, you immediately have credibility and most of those journals are profit making and are not easily changed into an open access venue where … while there is the potential for profit, the likelihood is that they’ll be closer to “break-even”.

And it’s important to know that most scientific journals … and there are over 6,000 in the bio-medical sciences … many of them are actually profit making and they are profit making because large publishers … Elsevier is the most well known … have been marking up those prices, charging very, very high fees with thirty to forty percent profit margins because there is a sort of fixed audience. Publishing is a monopoly-creating business. You publish your article in one place, it doesn’t appear anywhere else. If scientists want to read it, they’ve got to … currently they’ve got to buy the journal … or libraries have to buy the journals and the prices are extraordinarily high.

The approach we’re advocating is an approach in which the authors, or more realistically, the funders of the authors pay the cost of publication and then information is freely distributed. And that is a … definitely a workable objective and few of us found that a couple of years ago, an organization called The Public Library of Science, entitled or aims to reflect our interest in building a public library, just like the New York Public Library that all scientists and any interested parties, whether they’re patients or patients’ relatives or school kids or teachers or science writers … anyone can tap into it and get to the, the articles they want and see the entire articles freely.

The Public Library of Science publishes journals and we publish journals in the manner that I’ve described. We have an author’s fee; the author’s fee is paid usually by the funding agency and the article is then immediately placed on the web and placed in a digital library that was created in my final days at the NIH called “Pub Med Central”. So if you have an article published there you search “Pub Med” in “Pub Med Central” and people see your article, they click, your article is on the screen, they can download it. We operate under a licensing agreement was created by the so-called Creative Commons, an organization headed by, founded by Larry Lesig the law professor at Stanford who is a great believer and cheerleader for …

HEFFNER: Dissemination.

VARMUS: For dissemination and … you know, determining that the public really owns cultural goods and that cultural goods should be re-used. The only thing we require is that the people who use the information give proper, proper attribution because that’s all scientists care about. We want attribution. We want someone to read … we want more people than ever to read our papers, to talk about what we’ve done and to say, you know, “the following people did this work”.

But otherwise, the more use our work gets, the better we feel because our whole point in generating new knowledge is to use it.

HEFFNER: But there is opposition to what you’re saying.

VARMUS: Of course there is. Because …

HEFFNER: Okay.

VARMUS: … the publishers and … the private publishers and … unfortunately some scientific societies that have built a business plan that’s dependent upon revenue from a society’s journals are reluctant to make the change because they think they will make less money. There is …

HEFFNER: Won’t they?

VARMUS: … they may make less money. And that’s all right. But, you know, it’s easy for me to say that.

HEFFNER: It certainly is easy for YOU to say that.

VARMUS: But … but the fact is that scientific societies are guilds … they are created for the well-being of their constituents. And they should operate in that way and not to protect income that supports staff. There are other ways to, to keep scientific societies going.

HEFFNER: Dr. Varmus you sound very much as though you’re in battle mode. Obviously this is a battle going on right now.

VARMUS: Oh, it’s a big battle. And it’s an interesting one. It’s one that I think we’re … we are actually winning. There are more and more journals that are either becoming open access journals, or allowing authors to pay an extra fee to publish their articles in a free, or open access, mode.

Congress has taken up the charge here. They see this as a taxpayer access issue. They view their constituents as taxpayers who support the research effort … in my years as the Director of NIH I became very familiar with the Congressional battle-cry …you know we want to know what you guys in NIH are doing with our money. We want to be sure that all of our, all of our constituents have access to what you’ve done. What is your communication policy? How do you let people know what you’ve done?

And we say, “We publish articles”. Well, if a constituent then goes to his computer or her computer and attempts to get an article that might be important for understanding a new development in the treatment of a disease that one of his relatives has and then meets with a, a sign that says, “you can see this if you pay $10 or $15 or $20, or, or subscribe to our journal”. That doesn’t speak well, in my view, for what the NIH or other federal agencies are trying to do.

HEFFNER: It’s just so interesting to me that you’re doing this, right now, and obviously are associated with a number of other major scientists … at the same time that in other areas, when you talked about cultural matters … the public owns cultural matters … at the same time, there’s a battle going on, on the other side for protection of copyrights; protection of authors’ creations … and you …

VARMUS: Well, that’s a …

HEFFNER: … must be running into …

VARMUS: We argue that authors should retain their copyright.

HEFFNER: MmmHmm.

VARMUS: … and that copyright shouldn’t be ceded to journals.

HEFFNER: But … ceded to this thing called the computer?

VARMUS: No, it’s not … you’re not ceding anything, you’re holding … you hold the copyright, but you’ve basically said, when you’ve published in an open access journal that anybody who gets hold of this is free to download it, to use it for teaching, to take parts of it and incorporate it into, into another article, all you have to do is give the proper attribution to the source of the information.

HEFFNER: And you feel that scientists, generally, if not universally …

VARMUS: Scientists are concerned about the, about their careers, about being published in journals that, that have high impact and, and are widely credited because when they come up for promotion people do pay attention to where their articles have been published and that’s understandable.

I know very few scientists who care … who are happy about ceding their copyrights to journals. They do it because they want to be published in those prestigious journals.

We’re offering them prestigious journals published by a public library of science that have very strict peer review, reject a very high percentage of articles that are sent in, that have a high degree of credibility because are our articles are … a) they are very accessible, so everybody sees them; secondly they are accompanied by, by summaries in layman’s language so they’re more likely to be read by even layman and certainly by science writers and picked up in, in newspapers. And we try to provide an alternative to the existing system.

We’re not trying to … we don’t want to see existing journals destroyed. We want to see existing journals convert to an open access mode.

HEFFNER: Do you feel you’re winning this battle?

VARMUS: We are because we’ve had some help from a number of important agencies. The Howard Hughes Medical Institute has been very supportive. The Welcome Trust in England, the biggest supporter of medical research, these organizations are urging their, their investigators to publish in an open access way because of what I said earlier, namely that funders of research want the information that their money generates to be widely used and widely seen.

There is a recent policy from the NIH itself asking that all investigators who, who publish provide a digital version of their article before they transfer the copyright, before the paper’s published to Pub Med Central at the NIH so that they will have, in digital form, a fully, fully searchable form … all of the work that the NIH has distributed. This is something that has been done, in part in response to the, the Congress’ interest in dissemination and in part because the NIH Director, Elias Zerhouni has seen the, the importance of having the work the NIH has achieved made fully accessible.

HEFFNER: What’s your vision, Dr. Varmus, of this sort of Gutenberg outreach …

VARMUS: Well, ultimately …

HEFFNER: … explosion.

VARMUS: … well, ultimately, we, we hope that all legitimate journals in the bio-medical sciences will be publishing in an open access way, or at least providing all their content to Pub Med Central within, say, six months of publication.

The goal, from my perspective is, of course, to encourage open access publishing, but a short term goal that I think is achievable is to create what we, we set out to create in the first place, a public library of science that anyone can go to just as you can walk into the public library in New York City and, and ask for a book and not have to pay a fee. The Internet and its wonderful search tools make that transformation not only possible, but … it just seems to me to be a, an abrogation of our responsibility as scientists who are supported by public money not to create this, this tremendous basket of knowledge.

HEFFNER: This question of credibility … it has great meaning to me because I’m aware of the fact that in the area of so-called journalism, news reporting … anyone can put anything on …

VARMUS: Sure.

HEFFNER: … what we used to call “the air” and there’s no sense any longer of the distinction that’s provided … the guarantee that some one has edited …

VARMUS: Right.

HEFFNER: … this material.

VARMUS: Well, it’s interesting …

HEFFNER: … what do you think about that?

VARMUS: It’s interesting that people think that whenever I talk about open access publication and digital storage and the kinds of operations of publishing that we’ve just been discussing, that I’m saying that we’re going to throw away the quality screening.

That’s not the case at all. We have, as I’ve mentioned before very, very strict peer review. We reject, for our two flagship journals, Public Library of Science Medicine and Public Library of Science Biology, roughly 80% of the papers that are submitted and we do a very careful job editing. We’ve hired … we’re an expensive operation at the moment. We’ve hired editors from the leading journals … Nature, Science, Cell, Lancet … and other places …

HEFFNER: What do you mean “at the moment”? Won’t you always be?

VARMUS: Ah, no because we … the cost that we, we allocate to each article will become less and less over time. Right now we’re focused on two flagship journals that compete with the very best in the market. But with time we will be creating many more journals that accept higher numbers of articles. We’ll require, of course, a high degree of scientific competence, but we won’t be aiming solely for articles with tremendous impact on the growth of science. After all, a lot of the science that every lab, including mine does, is science which is confirmatory, makes small incremental steps … none of us can claim that, that a high percentage of their papers have dramatic impact. So we … there’s a tremendous need for a, a facile way to distribute the knowledge that’s incremental and confirmatory.

I mean we’re in the process at Public Library of Science … which by the way your viewers should look at by going to www.plos.org. But at our organization we’re creating what we call community journals, that are discipline specific … don’t cover topics that … as broad as all of biology or all of medicine, but will be specific for certain areas of science.

And then we’re creating a larger vehicle called PLOS Reports which will encompass basically anything in biology and medicine in, in one large basket. We’ll be reviewing for, for competence and scientific credibility, but we won’t be looking at those articles for dramatic impact.

HEFFNER: Well I know, I can take it from looking at your face when you’re talking about this …

VARMUS: MmmHmm.

HEFFNER: … and from hearing the tone of your voice ….

VARMUS: MmmHmm.

HEFFNER: … that in your fondest imaginings you see something explosive happening in this area through the dissemination in the general field of science and medicine.

VARMUS: Well, there’s no doubt that everyone has the sense of living in a, in a tremendous knowledge flow that’s so rapid, that all of us have to depend heavily on the computer to sort out what we think about. That is actually exemplified by the human genome project which everyone is probably familiar with at this point. That, that the rise of new technologies that allow us to map and determine the nucleotide sequence of every gene in the genomes of not just humans, but virtually every living thing has created an amount of data that you can’t use in the way in which we traditionally have used biological information.

You can’t simply go to a simple text and look at pictures of all the species, you have to, to look at, at the genetic blueprint of any organism gene by gene and even nucleotide by nucleotide and that has to be done using computational methods. The same is now true of the entire literature in biology and medicine. But it is possible to take advantage of existing tools that are based on computer science and try to manage an unbelievable torrent of information.

If we don’t get that information into a way that is reasonably searchable and create access to the information, most scientists can’t subscribe to more than a few journals. But why should they be unable to look at everything, when almost all of literature is generated by, by money that is intended to lead to new knowledge that people can, can have access to.

HEFFNER: So the computer plays a larger and large role?

VARMUS: If … if it’s an illness, yes, of course.

HEFFNER: And what do you think …

VARMUS: This is not novel to scientists. I mean every, everybody I know is heavily dependent upon new, the new tools of information technology for living their daily lives.

HEFFNER: But a heck of a lot more important in the area of science and particularly medicine.

VARMUS: Well, perhaps. I think that’s arguable. I mean you could argue that it’s very important to us, but it’s also very important to people doing business of any kind and people engaged in virtually every realm of activity.

HEFFNER: What’s the impact, do you see, what impact do you see in terms of your own hospital.

VARMUS: Well, there are …

HEFFNER: What’s the future?

VARMUS: I mean as you, you know, our place is not just a hospital, it’s a research and teaching and patient care center. It’s a cancer center. So we use computational methods for a very wide variety of things. When you walk into our hospital, one of the first things you notice is that we have a computerized medical record … a doctor sitting at 53rd Street at our outpatient clinic who wants to view the x-ray images of, of a patient who had x-rays done some months ago at another insti … at another part of our, of our campus … simply goes to the computer screen, types in the name and sees all the old x-ray images. They just flash right up.

Now I was … I was trained in a day when, when you wanted to see an old x-ray or even a new x-ray … meant that some, some messenger had to go down and sort through films that were packaged in large envelopes and stored in a, a radiology storage room.

This is a new world in which the retrieval of information that’s relevant to patient care is instantaneously available. In the world of cancer, one of the most important developments that I see coming in the next few years is the recategorization of cancers based on the nature of the genetic mutation, the genetic changes that have occurred in the cells that ultimately are destined to become cancer cells. That’s going to require the analysis of large numbers of cancers of every kind and the linkage of that information to … what we call our clinical database … that is … tends to correlate the genetic changes that cause a cancer with the likely outcome, the kinds of drugs that are likely to work, the various habits of patients that may lead to the generation of such cancers. This sort of information overload has to be sorted through by, by bio-informative specialists and that’s going to be a place where the clinical experience is recorded in our patient database … is linked to genetic information about tumors that will lead to a different kind of characterization of, of cancers.

In lung cancer, a field in which I’m currently quite active, it’s clear that the old way of, of diagnosing lung cancer simply by looking under the microscope and saying “this is one kind of cancer or another” is going to be superceded in the near future by an analysis that says, “this lung cancer is, is primarily caused by mutation in gene x and this one by mutation in gene y. They may look the same under the microscope, but they are profoundly different kinds of cancer because the underlying cause is different.

It’s like looking at pneumonia, and saying “this is pneumonia, as opposed to looking at pneumonia and saying, with appropriate bacteriological tools, “this is pneumonia caused by the pneumococcus and this is, this is pneumonia caused by clebcella or tuberculosis, or some other organism”. So, we’re trying to get at root causes and those root causes are going to dictate the kinds of cancer therapies we use, just as, as microbiology changed the way in which we approached the treatment of infectious diseases by choosing the right antibiotic or trying to prevent them with the right vaccine.

HEFFNER: And then what? Life ever-lasting?

VARMUS: No, no. Of course not.

HEFFNER: Tell me what, then.

VARMUS: Well, the whole point here is to, is to reduce the likelihood of suffering or death from, from treatable illnesses. You know, human beings are machines, biological machines and they’re going to wear down, nobody’s going to live forever. But when, when I see a friend dying of breast cancer at the age of 50. I said, “This is wrong,” we should be able to treat these cancers effectively and reduce the number of cancer cells to a minimum so there are no symptoms and keep those cells from growing. We’re not going to prevent cancers of all kinds. We can reduce the numbers of cancers by understanding causes. By controlling tobacco use, we can reduce many types of cancer, especially lung cancer, but we know that there are people who never smoked who get lung cancer. And there are people who … we’ll probably never reduce smoking to zero, either. But we have a responsibility as fellow citizens to try to reduce the, the pain and death that come from cancers that can be controlled.

HEFFNER: We have 30 seconds left, which I can’t believe.

VARMUS: I can’t either.

HEFFNER: Do you think Lew Thomas here at this table …

VARMUS: MmmHmm.

HEFFNER: … was willing to say he thought there was a natural limit to life, a certain number of years. Do you?

VARMUS: I don’t know what that number is. I think we can extend the number and there are examples from studies of fruit flies and worms and even mice that suggest it’s possible to manipulate the, the length of time that we have. I think none of us wants the situation … out of control so that we have many people alive with no mental function. So, I think there is an opportunity to extend life … more importantly useful, happy life. But we’re not going to go beyond, beyond a termination time.

HEFFNER: Promise me you’ll come back.

VARMUS: [Laughter]

HEFFNER: Okay?

VARMUS: You bet, yeah.

HEFFNER: Thanks so much for joining me, Dr. Varmus.

VARMUS: My pleasure.

HEFFNER: And thanks, too, to you in the audience. I hope you join us again next time, and if you would like a transcript of today’s program, please send $4.00 in check or money order to The Open Mind, P. O. Box 7977, FDR Station, New York, New York 10150.

Meanwhile, as an old friend used to say, “Good night and good luck.”

N.B. Every effort has been made to ensure the accuracy of this transcript. It may not, however, be a verbatim copy of the program.