July 18, 2005
Dr. Lee Hartwell, President and Director, Fred Hutchinson Cancer Research Center, June 1, 2005
Dr. David Lemberg: Our first guest is Dr. Lee Hartwell, President and Director of the Fred Hutchinson Cancer Research Center, located in Seattle, WA. Fred Hutchinson, home of two Nobel Laureates, is an independent, non-profit research institution, dedicated to the development and advancement of biomedical research to eliminate cancer and other potentially fatal diseases. Dr. Lee Hartwell is also Professor of Genome Sciences, and Adjunct Professor of Medicine at the University of Washington School of Medicine, and American Cancer Society Research Professor of Genetics.
Dr. Hartwell is the recipient of many national and international scientific awards, including the 2001 Nobel Prize in Physiology or Medicine. Other honors include the Albert Lasker Basic Medical Research Award, and the Alfred P. Sloan Award in cancer research. Dr. Hartwell is a member of the National Academy of Sciences. Welcome, Dr. Lee Hartwell.
Dr. Lee Hartwell: Hello.
Lemberg: Lee, thank you very much for being with us today. I’d like to start with the broad topic of how our knowledge of biology and cancer can be effectively used, more effectively used to cure patients of their disease.
Hartwell:
When cancer is detected early, it’s almost always cured, whereas, once it has metastasized, it’s almost always fatal. And, that’s true for almost all types of cancer. So, about 60% of cancer patients now survive their disease, and they’re almost always those people whose disease has been detected at an early stage.
Lemberg: Lee, did you say that currently, 60% of cancer patients are surviving?
Hartwell: In the U.S., are surviving for five years or more.
Lemberg: OK. And, how does our overall knowledge of biology contribute to this?
Hartwell: Well, we understand a great deal about cancer now, and this has all come about in the last two or three decades, but, you know, just briefly, what we understand about cancer, is that it begins in a single cell, and is the result of the progeny of that cell, that there are changes in a half a dozen or so different cellular pathways and processes, and we understand those pathways in fairly good detail, so that, at the current time, we could probably list many hundreds of genes and proteins that are likely to be playing a role in cancer, in some way.
And, those are currently thought of, primarily, as drug targets, against which pharmaceutical companies can make drugs, but we haven’t given enough thought to the use of this knowledge in diagnostics, and looking for the molecules that can reveal cancer at an early stage.
Lemberg: So, possibly using, just as an example, high-throughput arrays to analyze a person’s proteome, for example.
Hartwell: Yeah, there are various molecules that can be informative, and I feel like we’re, right now, at a very important transition in molecular diagnostics where, during the last five years or so, we’ve become very sophisticated in monitoring DNA and RNA changes. And, these are very useful in cancer, but usually, require that you sample the cancer, itself, to monitor those changes, and that requires knowing that a person has it, of course.
For early detection, you want to use molecules which are circulating in body fluids like blood, and while DNA is found, often, in the blood of cancer patients, and is a potential diagnostics, it’s likely that proteins are going to be much more informative because there are so many different species of protein, and they’re so much more closely related to the functional changes that go on in cancer.
The technology for finding those informative protein markers is not near as good as the technology for finding DNA or RNA markers, and so, while the technology has improved in the last couple of years, and improvements in mass spectrometry, we’re going to need to make a fairly large scale, highly coordinated effort to identify those molecules. It’s not something that can be done in a single laboratory.
Lemberg: Right, Lee, now when you say a large scale, highly coordinated effort, is Fred Hutchinson involved in such an endeavor, or are there other key institutions?
Hartwell: Yeah, we’re trying to lead the effort to do this, and we’re doing it at a variety of levels. One is, we have put together a large team involving seven institutions to discover markers for breast cancer. That project is being funded by the Entertainment Industry Foundation. I’ve been working with the National Cancer Institute to develop a large scale program to discover biomarkers, and that’s nearing its process through the National Cancer Institute that would present grants that various places could apply for.
The National Cancer Institute has, already, funded us to build a database, and informatics platform that’s publicly accessible so that teams can collaborate effectively. And, the other thing that I’m doing is developing international teams like the one we have here to collaborate, and we have, for example, two teams in Korea, and one in Taiwan, one in China, and teams forming in Australia and Singapore, and other places.
Lemberg: Lee, thank you. Well, not to be blue sky, but it sounds as if big breakthroughs would be very possible once the technologies have, well, become more sensitive and specific.
Hartwell: Yeah, I think if the technology improves, progress will be very, very rapid, but I think, even with existing technology, applying it in sufficient scale will also provide breakthroughs in this field.
Lemberg: Oh, you mean over a large population.
Hartwell: I mean, well, no, more, I’m talking about . . . by scale, I mean a sufficient number of laboratories . . .
Lemberg: Oh, OK.
Hartwell: And, a large enough discovery effort, all working on the same tissue samples, sort of dividing and conquering the problem, much as we did for sequencing the genome. And, I think the same kind of attitude is needed here, the same kind of quality control standards and size of activity. At first, it would require only a small number of tissue samples and things for the initial discovery effort, and then, larger populations, when it’s trying to validate those markers. But, at the present time, the whole diagnostics area is held up at the discovery phase. That’s the limiting point.
Lemberg: And, might this, overall, effort involve ten years, or twenty?
Hartwell: Well, my feeling is that, you know, if we get a sufficient scale of activity, which seems to be developing now, and funding for this, and by the way, there’s been a new foundation that’s just stepped into this arena, the Canary Foundation, founded by Don Listwin. If we get a sufficient scale of activity going right away, I’d say in five years, that we will be very effectively discovering hundreds of biomarkers for each disease site. And then, it would require another five years or so to validate those in much larger populations.
Lemberg: And then, the same techniques could be applied to other chronic diseases, arthritis, for example.
Hartwell: I think any disease is subject to the very same discovery methods. That’s why it’s so exciting to work on this technology and methodology because it’s so broadly applicable to medicine. And, at the present time, I think the real limitation in medicine is, you know, accurately diagnosing what’s going on in the body at an early enough stage, before it becomes completely acute. And, I think it is possible for all diseases. There are probably thousands of proteins that could inform us of our health on a weekly or monthly basis, you know, in another ten years.
Lemberg: So, real-time monitoring.
Hartwell: Yeah, that should be fairly easily attained, you know, once we actually know what molecules to be looking for.
Lemberg: OK, great, Lee, please tell me if I’m thinking correctly here. Is this overall area, would you categorize these as phenotypic tests?
Hartwell: Yeah, yes, definitely phenotypic tests, and, you know, sort of complement the genotypic tests, which come from DNA sequencing. And, you know, what’s going to be very useful, ultimately, are a series of tests where you can go out into a completely healthy population, and by looking for these kinds of diagnostic molecules, determine people who are just at risk, but don’t even have any disease yet, and then, other markers for early stage disease.
And then, these very same molecules can, then, be used to make imaging agents that can image, for example, cancer, where it is, how big it is, its sort of physiological state. And, one can even think about, you know, attaching therapeutic cargo to those molecules to deliver to the diseased site.
So, I think these kinds of markers that are specific for the disease will have many uses.
Lemberg: And, Lee, this makes me think of nanotechnology delivery systems, for example.
Hartwell: Um hmm, yeah, nanotechnology is very much the same thing, I mean, you know, if we have a protein biomarker that you can find in blood that is shed by the tumor and is, for example, indicative of early stage disease, you would make an antibody to that, and maybe attach some cargo to that that would light up or provide a therapeutic response. Well, antibodies are nanotechnology, so it’s definitely in the nanotechnology realm.
Lemberg: That’s great. Lee, thanks. OK, so I’m getting that the best overall approach to the phenomenon of cancer, is early detection.
Hartwell: Yeah, I’m very passionate about that, because if you look at the statistics for, you know, cancer over the last thirty years, there’s been very little improvement in cancer outcomes.
Lemberg: Yes.
Hartwell: Maybe it’s gone from, you know, 50% survival to 60% survival, but, you know, for thirty years of work, and huge numbers of billions of dollars spent by the pharmaceutical companies trying to make therapeutics, it’s hard to make the case that therapeutics have really been very successful.
And, this is a much less expensive and proven way to fight this disease because we know at all cancer sites, if you find it early, that you cure it, and we have good examples, both in colon cancer, and cervical cancer, that if you start screening people for early disease, you reduce mortality dramatically.
Lemberg: Earlier in our conversation today, you were talking about the half a dozen or so cellular pathways involved in cancer pathogenesis, and suggested the protein markers and possibly, the DNA sources, that these might be targets for the pharmacologic industry. You know, for me, this doesn’t make much sense. The target approach, as you suggested, doesn’t seem to have had any real effect over the years.
Hartwell: Well, we have one good example, and that’s Gleevec, for chronic myelogenous leukemia. It’s not effective for late stage disease, but it is a miracle drug for early stage disease.
Lemberg: Right.
Hartwell: And, of course, leukemia is not something you can just surgically remove, even if you detect it early. So, you know, there will be a role for therapeutics, and I don’t want to completely say that one should abandon the targeted therapeutic approach, but I think one should balance it with an equally aggressive activity toward early detection.
Lemberg: Got it, Lee, thank you. Well, we’ve got less than two minutes left, Lee, and I’d certainly like to hear about ongoing programs at the Hutch.
Hartwell: Well, we’re very committed to this, as one approach. We, also, are very committed to prevention of cancer, and that involves discovering the causes of cancer. And, when that’s been possible, for example, certain viruses that cause cervical cancer, and bacteria, when it causes gastric cancer, then you can take vaccine approaches and things. And, when it’s smoking, you can just eliminate that from your lifestyle. So, prevention is sort of the first place, and then, for therapeutic approaches, we’re very committed to immunotherapy, using the immune system to fight cancer, and that has proven effective in bone marrow transplantation for leukemias and lymphomas.
Lemberg: Great. Lee, thank you so much for taking the time to speak with us today.
Hartwell: Yeah, it’s a pleasure, thank you.
Lemberg: You’re welcome. Our guest is Hartwell, President and Director of the Fred Hutchinson Cancer Research Center, located in Seattle, Washington.
Posted by David Lemberg at 02:24 PM | Comments (0)