BOARD CERTIFICATIONS and LICENSES: 1973 Certified in Internal Medicine Certified in Medical Oncology Licensed to practice Medicine in California and Maryland HONORS: Phi Beta Kappa Alpha Omega Alpha Fellow of the Life Insurance Medical Research Fund Upjohn Achievement Award Arthur S. Flemming Award Public Health Service/Meritorious Service Medal Third Mullin Lectureship/University of Scranton Fourth Biennial Chemistry as a Life Science Lectureship/Rutgers University Alpha Omega Alpha Distinguished Professor/Dartmouth Medical School Robert T. Wong, M.D. Endowment Award/University of Hawaii Foundation Samuel Rudin Award/Columbia Presbyterian Hospital First Annual Award for Outstanding Achievement in International Health Harvey W. Wiley Medal/FDA Commissioner's Special Citation Health Leader of the Year Award/Commissioned Officers Association, 1990 Dr. Frederick Stohlman Lecture Award/Volga Wilsede Meeting Lifetime Science Award/Institute for Advanced Studies in Immunology & Aging GENE THERAPY Senator HARKIN. Thank you very much, Dr. Broder. The first thing that caught my attention was the gene therapy experiment that was done last fall on a little girl with a previously incurable disease that shuts down the immune system. I was going to ask you about that, but you tell me that at this point it looks as though it has been successful. Dr. BRODER. This is an important collaboration between the Cancer Institute and my distinguished colleague's Institute, Dr. Lenfant, the Heart, Lung, and Blood Institute. It represents the work of Dr. French Anderson, Dr. Michael Blaese, Dr. Steve Rosenberg, with active participation of a very important scientist from your State, sir, Dr. Culver. We feel that while this is preliminary and should not be taken to mean that we now have a standard, conventional treatment for this unusual immunodeficiency, our scientists are convinced that there has been, in fact, a real improvement in this child's immune function, and at least from an experimental point of view, we consider this aspect of the experiment to have made successful progress. We are not ready to say we now have conventional curative therapy for this unusual form of a disease, and we should use some caution as to how to extrapolate these findings. Senator HARKIN. Has her immune system returned to normal? Dr. BRODER. It has not returned to normal, but we do have evidence of an improvement in what are called lymphocyte functions and her ability to recognize foreign substances, so-called antigens, that might be thought of as invaders of her body. She is making a response to certain types of antigens that she would not normally have made. Senator HARKIN. How much longer will she be undergoing this therapy? Dr. BRODER. Well, this is viewed as a case-by-case thing. We do not have any background. There is no textbook we can look at. This is the first patient on Earth who has received this particular approach. And to be candid with you, I would have to say that from our point of view we are learning as we go along, I do not think it would be appropriate for me to tell you that we know the precise schedule. But if she continues to be successfully treated, we will certainly continue the procedures as long as we think she is benefiting from them. But this is a first case, and it is very difficult to make an extrapolation. A second child has been treated and it is too early for us to say at this point whether there is progress or not. Senator HARKIN. The same immunodeficiency? Dr. BRODER. The same immunodeficiency. And two patients with cancer, as I mentioned, have been treated using related technology, but for a different purpose. Again, in that setting, it is too soon for us to say whether this approach is adding to the overall benefit of the patient. But it is no longer possible to say we will at some future time enter into the world of gene therapy for this purpose. We have already entered that world. UNCONVENTIONAL TREATMENTS Senator HARKIN. I do not know if you want to add anything to what Dr. Raub had said earlier in my question about the nonconventional things. You met also with Congressman Bedell. Dr. BRODER. Sir, I would like to say that I think it is very important for a variety of reasons for the National Cancer Institute to remain open to new ideas and to create a specific bond of trust with the public that it is open to new ideas and that all ideas compete on a level playing field. In that context, perhaps I could say that we have responded to an Office of Technology Assessment report that you touched on. We have made certain suggestions for increasing lines of communication, and we have an internal program in our organization-a cancer therapy evaluation program that is receptive to hearing new ideas and that will pursue new ideas. I would say that on three occasions in my recent memory we have followed up on what are called unconventional ideas. For example, laetrile was an unconventional idea, and we actually did an NCI funded clinical trial with laetrile. There was a great deal of controversy over a drug called hydrazine, and we, in fact, are doing a study with hydrazine to answer some questions. And we will ask our scientists to participate. NCI funding instruments will help do those studies. And finally, there was a randomized study, an appropriate control study, using vitamin C which was quite controversial at the time. I would say the latter, the vitamin C study, has considerable scientific implications, and, in fact, we are integrating vitamin C and related vitamins, small micronutrients, in a chemoprevention program both in the United States and abroad. We have a very large scale program in the United States and in China, and we feel that it is quite likely that some aspects of vitamin C or ascorbic acid and other related vitamins are likely to have biologically important activities in the world of chemoprevention, that is, preventing cancer before it occurs. We do not have all the data on that point. But the reason for me to give you this background is to signal you our understanding of your concerns. We know where you are coming from. We understand your concerns, and we try to remain open to new ideas. I would say that every major advance in cancer that we accept as conventional treatment today at one time was somebody's outlying idea, was some crazy person's idea, until it was accepted in the mainstream. And so, that would be true for chemotherapy, radiation therapy, and so on. These were all outside the mainstream. They were unconventional in their era. VITAMINS AND CHEMOPREVENTION Senator HARKIN. I appreciate that very much, Dr. Broder. I just jotted down that when you mentioned prevention, you said that vitamin derivatives have some indication of being a preventative measure. You just said that again. Dr. BRODER. That is correct. Senator HARKIN. You have some ongoing studies. Dr. BRODER. Yes, sir. We have a very strong commitment to what is called chemoprevention, and that means using micronutrients, sometimes vitamins, sometimes natural substances, sometimes certain hormones that are related to hormones in the body not necessarily for the purpose of treating cancer, but to prevent cancer. It is my personal view that prevention should be our highest priority. Prevention of a disease is always better and more cost-effective than attempting to treat a disease once it has occurred. An ounce of prevention in today's dollars is probably worth a kilogram of cure. And I feel that we have made progress in this area. We have certain vitamin A derivatives, which are included in the broad family of retinoids and substances such as beta carotene. These are related to the vitamins that one might have in the body. They definitely have been shown to be active-this is not speculative, they have been shown to prevent certain types of cancers. For example, we have some progress in preventing the development of second head and neck cancers in individuals who are at risk because they already have a first cancer of the head and neck. And we have been able to show that in some cases you can prevent a second disease. The whole area of chemoprevention is very exciting because there is an economy of scale involved. Almost anything that we could traditionally talk about that benefits cancer prevention-almost anything-would seriously augment our ability to prevent heart disease and other things, and so there is an economy of purpose here. I haven't discussed this specifically with Dr. Lenfant, but my instinct is that he would support that. WOMEN'S HEALTH: DIETARY FAT AND CANCER Senator HARKIN. Last, speaking about prevention and throwing in a little controversy here, obviously you know I am very strong in looking at prevention because I agree with you totally on looking at prevention as being more cost-effective and a better way to approach it. Let me ask you about the diet fit study. I understand that the question of whether or not we should proceed with this has become controversial. I have to tell you I don't understand completely the controversy, but I know I am getting mail on it and I am getting Dr. BRODER. That comes as a complete surprise to me. [Laughter.] Senator HARKIN. I want to know what you think about this. Should we proceed? What are the key points in this debate? Why has it become so controversial? Dr. BRODER. The key points in this debate are because a number of scientists and lay people of high intellect and goodwill are looking at the same set of facts and coming to opposing conclusions. This is clearly one area where a number of people of extremely learned experience are looking at the same set of facts and are coming to opposing conclusions. If I could summarize in brief some of them, and I would be happy to follow up for the record with more details. [The information follows:] LARGE SCALE STUDIES OF LOW-FAT DIETARY CHANGE ON CANCER An initiative to test whether a change in diet could reduce breast cancer incidence was proposed by the National Cancer Institute's Division of Cancer Prevention and Control (DCPC) in 1984. This proposal was based in part on evidence accumulated during the 1970's suggesting that diet was strongly implicated in certain cancers. In 1981, a widely referenced study evaluating the causes of cancer mortality hypothesized that from 10 to 70 percent of cancer deaths could be attributed to diet, with a "best estimate" of 35 percent. Not all scientists accept this estimate, but if accurate, it is roughly the same as the percentage of deaths due to tobacco. Shortly after publication of the study, the National Research Council produced an NCI-sponsored report summarizing the growing evidence of a relationship between diet and cancer. During this period, NCI had increased its emphasis in cancer prevention with a particular focus on understanding the role of diet in cancer and identifying ways to reduce cancer incidence. It is worth stressing, however, that while many scientists believe that diet plays a role in cancer, there are uncertainties about the precise role of total calories, fiber, and other dietary factors. In addition, there also are divergent views among respected scientists about the best research approaches to address these uncertainties. The accumulation of evidence regarding fat and cancer, and other evidence regarding the potentially protective effects of increased dietary fiber, led NCI to establish interim dietary guidelines suggesting that Americans consume no more than 30 percent of their calories from fat and that they increase their dietary fiber from approximately 10 grams per day to between 20 to 30 grams per day. These guidelines were prudent actions based on laboratory, animal, and epidemiologic studies. Recently the Department of Agriculture and the Department of Health and Human Services (DHHS) published dietary guidelines carrying the same recommendations, and for the first time, the DHHS is now suggesting the 30 percent figure (for daily fat intake) in its publications. - Evaluating the impact of dietary change on cancer requires a large number of subjects (an estimated 20,000 to 30,000 subjects) and high cost some estimates have ranged up to $150 million over a ten-year period. The proof that dietary change effects lower cancer rates as well as lower cardiovascular disease rates is extremely important to the Nation's health. NCI's initiatives have included a feasibility study of a large-scale dietary intervention to test the impact of low-fat diet on breast cancer, an investigator-initiated grant proposal (termed DIET-FIT by the investigators) submitted in 1988, but not funded, and the newly approved (1990) contract-based Women's Health Trial Feasibility Study. A number of issues have been raised by both the scientific community and the public about the feasibility of such studies and their costs. A chronology of these efforts follows. |