Cancer, Diet, and Funding: Food or Pharmaceuticals?

The chemoprevention field could be characterized as being in a double-blind double bind. One side of the field emphasizes taking a "whole food" approach to using food to prevent cancer. That approach entails having scientists closely monitor everything a necessarily small group of subjects eats over a necessarily short period of time. Such studies pick apart the complexities of diet and its possible roles in keeping cancer at bay. But the small numbers and short time frame put any conclusions on statistically shaky ground. The other side analyzes the effect of one thing at a time--usually a supplement or combination of supplements. Such approaches ignore the complexity of dietary interactions and consequently yield unexpected and perhaps incomplete results. One large trial that tested beta carotene as a potential chemopreventive found that it actually increased cancer rates in smokers; a then-unknown dietary mechanism actually changed the supplement's touted antioxidant activity into a prooxidative machine.1 Backers of each supplement and supporters of whole foods have long disagreed on the other's experimental approaches and clinical roles.2 However, at a September chemoprevention conference in Washington, D.C., sponsored by the American Institute for Cancer Research, practitioners of both experimental methodologies and proponents of each clinical approach reached a sort of agreement: Not enough money--and perhaps not enough scientific respect--is being lavished on either preventive approach. Bernadette Marriott, University of Arizona researcher, trotted out a list of "nutraceuticals" currently in vogue, including shiitake mushrooms, mistletoe, and saw palmetto. She warned that most data on those plant-based products is actually market data from groups involved in promoting them. "Many studies are short-term and use small groups," she added. "That's why we need to get many people involved in this research." Steve Clinton, Ohio State University oncologist, noted that the rise of molecular biology has perhaps harmfully eclipsed the success of public health. Public health efforts started decreasing rates of diseases such as tuberculosis and rickets even before causes and biological mechanisms were fully understood. The same approach could--and should--be applied to cancer. However, molecular biology could also play a better role in prevention. "We really don't have the kind of biomarkers of antioxidant activity that we need," he noted. He added that, even with last year's 9 percent increase to the National Cancer Institute (NCI) budget, the chemoprevention field still remains underfunded. "We're not going to make the kind of progress that the public demands with that kind of budget." Beyond budget remains bias against whole-food research, maintained Phyllis Bowen, a University of Illinois at Chicago nutrition researcher. "It's very difficult for nutritionists like me to get through study sessions. We need to test our dietary advice in clinical trials also." Peter Greenwald, director of the NCI's division of cancer prevention, agreed that problems facing both the whole food and supplemental approaches may be as much cultural as scientific. The scientific community and the National Institutes of Health seem to be unconvinced that a strong need exists to invest in nutritional sciences, he said. "And that's a national problem," he added--especially since the best evidence indicates that at least a third of all cancers have dietary components. Each approach could benefit from large-scale, randomized, double-blind trials, he noted, echoing other speakers. But the political will and scientific skill to do so must first be marshaled. Following his talk, Greenwald discussed both the politics and science behind chemoprevention with news editor Paul Smaglik. An account edited for space and clarity follows: Q: You seem to have a good idea about the kinds of research needed to advance this field. What are the obstacles to doing so? A: It's a combination of factors. We need major biomedical research institutions to develop a culture where research on lifestyles, diet, and prevention is mainstream. The economic forces aren't on that side to the extent they are on the diagnostics and therapy side. I think an important thing is to build up the base of young scientists ... that we strengthen the basic foundations of nutritional science and tie that into studies of diet modification and intervention. It really takes a lot of [work] to build depth in the field. Q: What's the explanation for the seeming rift between whole-food boosters and supplement supporters? A: There are people who uncritically support the use of supplements and alternative medicine on the one hand. On the other, there are physicians who reject it out of hand. There is somewhere in the middle where we can take sound scientific approaches to understanding supplements and alternative medicines and food constituents so we can go forward on a sound scientific basis. Q: Methodologically, it seems easier to test one supplement in a randomized trial, rather than look at whole foods. Is it possible to soundly investigate whole diet in clinical trials? A: You can only do [a large, randomized, double-blind trial] as an intervention trial with a pill and a placebo. It would be very hard to do with any confidence in diet modification. I think you can do smaller intervention trials. There was a polyp prevention trial that had 2,000 people. It takes a lot of effort and attention, and there is a little bit of crudeness compared to these studies with 20,000 people. But I think they can get valid results if they are done with care. Peter Greenwald Q: This is seemingly a fairly specialized field. How does nutrition and chemoprevention apply to the study of life sciences as a whole? A: Just about every biomedical research field could contribute to knowledge and have an impact on studies of diet, nutrition, and cancer--from the most basic understanding of mechanisms such as genetic susceptibility. One example of that is there are single nucleotide polymorphisms (SNPs) that may have an impact on colon cancer risk in relation to whether you eat meat. There are reports of these [susceptibilities] that have to be validated. The basic knowledge is going to contribute, because these are common pathways whether they are affected by what you eat or what drugs you take or other aspects of your life. There's a big area related to the animal research that has impacts on nutrition. You can use transgenics and knockouts ... to study nutritional science. The next thing after genes is proteins--that's certainly part of nutrition. Q: Are molecular biologists ignoring nutrition? A: I think they are not focusing on it enough as an issue per se, to really understand how it affects the determinants of cancer, how it affects risk, and how you can modulate it. I think part of it is that the field does not have the level of respect ... of modern scientists. Q: What are some studies you'd like to see done that aren't being done right now? A: The first things I'd like to see right now are more multidisciplinary research groups that are focused on diet and nutrition in cancer. It's not one study; I think what we need is infrastructure in terms of depth of scientific talent that is dedicated to this area. I see that as more important than any one trial. Q: How does industry relate to apparent lack of activity in nutritional chemoprevention research? Obviously, pharmaceutical companies are more focused on looking for small molecules. Don't scientists go where the grants are? A: I think there are a lot of opportunities for partnerships with industry. It's happening now to some extent. Issues such as intellectual property, which can be big obstacles in some areas, can be less so here with the food industry. We've actually had a lot of cooperation and partnership in the supply of chemopreventive agents, whether it be constituents in packaging, or development of placebo controls. That's going very well now. However, there aren't as many industries dedicated to prevention as there are to diagnostics and therapy. The food industry's main thrust is food, not disease. Q: What did this conference accomplish as a whole? A: The American Institute for Cancer Research has made a major contribution in bringing a focus to this area. The fact that they had over 400 participants is a big step in what we're used to seeing for [conferences in] diet and nutrition. Paul Smaglik can be contacted at psmaglik@the-scientist.com. G.S. Omenn et al., "Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease," New England Journal of Medicine, 334:1150-5, 1996. P. Smaglik, "Food as medicine: nutritionists, clinicians disagree on role of chemopreventive supplements," The Scientist, 13[11]:14, May 24, 1999.

Cancer, Diet, and Funding: Food or Pharmaceuticals?

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