The Promise of Nutrigenomics

INTRODUCTION

The tools of modern molecular biology have transformed many areas of science, from searching for a cure for cancer to understanding the evolutionary relationships among species. Few areas, however, stand to see more of a transformation than the science of nutrition. In the coming years a confluence of factors is promising to make nutrition and, in particular, nutrigenomics, an area in which some of the most exciting and cutting-edge research in biology will take place, as well as offer a wealth of benefits to human health.

In light of this, the Institute of Medicine held a 2-day workshop, Nutrigenomics and Beyond: Informing the Future. Its purpose was to explore the state of the science, examine its potential, and discuss how that potential might best be realized. The following is a summary and synthesis of the presentations and the discussions from the workshop.

KEYNOTE ADDRESS

Presented by Bernadine Healy, Health Editor for U.S. News & World Report

Why Nutrition and Genomics Are Important

Bernadine Healy, former director of the National Institutes of Health (NIH) and now health editor at U.S. News & World Report, opened the workshop. She remarked that nutrition research has always had the



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Nutrigenomics and Beyond: Informing the Future - Workshop Summary The Promise of Nutrigenomics INTRODUCTION The tools of modern molecular biology have transformed many areas of science, from searching for a cure for cancer to understanding the evolutionary relationships among species. Few areas, however, stand to see more of a transformation than the science of nutrition. In the coming years a confluence of factors is promising to make nutrition and, in particular, nutrigenomics, an area in which some of the most exciting and cutting-edge research in biology will take place, as well as offer a wealth of benefits to human health. In light of this, the Institute of Medicine held a 2-day workshop, Nutrigenomics and Beyond: Informing the Future. Its purpose was to explore the state of the science, examine its potential, and discuss how that potential might best be realized. The following is a summary and synthesis of the presentations and the discussions from the workshop. KEYNOTE ADDRESS Presented by Bernadine Healy, Health Editor for U.S. News & World Report Why Nutrition and Genomics Are Important Bernadine Healy, former director of the National Institutes of Health (NIH) and now health editor at U.S. News & World Report, opened the workshop. She remarked that nutrition research has always had the

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Nutrigenomics and Beyond: Informing the Future - Workshop Summary potential to benefit human health in important ways. In the 1920s, for example, one of the early successes of the fledgling NIH was the discovery by Joseph Goldberger that he could cure pellagra, a deficiency disease characterized by dermatitis, diarrhea, dementia, and eventual death, by the simple expedient of adding baker’s yeast to the diet. (It would take another decade to identify niacin as the ingredient in baker’s yeast that was the factor that prevented pellagra.) Unfortunately, Healy said, the field of nutrition has been woefully neglected by the biomedical community over the years. Medical schools, for example, spend little time teaching nutrition to medical students; and academic researchers find it difficult to get funding for nutrition research. Part of the reason for that neglect, historically, was the perception in the first half of the 20th century that nutrition was “women’s work” that was best left to home economics departments; and, indeed, many of the early leaders in the science of nutrition were women, including Ellen Swallow Richards, the first woman admitted to the Massachusetts Institute of Technology and its first female instructor, and Lenna F. Cooper and Lulu C. Graves, who founded the American Dietetic Association. Healy experienced that neglect firsthand in the early 1990s when, as NIH director, she pushed for a bionutrition initiative to bring different fields together to do integrated systemswide research on food and nutrition. According to the document outlining the proposed initiative, “Bionutrition research employs molecular and genetic techniques to study the metabolic and behavioral consequences of food and nutrients and explores the fundamental role nutrition plays in health maintenance and disease treatment. It encompasses studies on nutrients at the cellular level, the metabolic functioning of nutrients in living organisms including humans, blessedly, and studies on gene-nutrition-environment interactions.” The initiative failed to gain support, in part because of the difficulty of convincing scientists from different areas to come together in a cross-disciplinary project, but also because it failed to capture the interest of either the politicians who would be funding it or the broader public. It was, in Healy’s words, “dull, totally and utterly dull.” That is not a problem with nutrigenomics today, as the field has already captured the public’s imagination. A number of commercial nutrigenomics websites, for example, offer to analyze a person’s DNA and provide advice on what foods to eat and what foods to avoid. If anything, the problem with nutrigenomics could be raising expectations too high. “This is a young field,” Healy said, “and you could kill it off very quickly by overpromising.” Nevertheless, the promise is real. For the first time, researchers have the tools to understand how genes and nutrients interact on the molecular level—to drive hard science into nutrition, as Healy put it. The human

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Nutrigenomics and Beyond: Informing the Future - Workshop Summary genome has been sequenced, and DNA microarrays allow researchers to scan quickly thousands of genes to see which ones are being expressed and at what levels, or to pinpoint genetic variations that differ from one person to the next. The different “-omics” disciplines (e.g., genomics, proteomics, and metabolomics) offer a variety of powerful ways to understand what is going on inside the cell in response to nutrients and to see how those responses differ from person to person. Advances in nanotechnology also promise to offer entirely new ways of observing and manipulating cellular functions. Nutrigenomics offers a tremendous opportunity for biomedical scientists. For more than a century, scientists have worked to understand nutrition, but it has never been approached in a rigorous scientific way. Now the tools exist to do the kind of cutting-edge research that can push the field in an entirely new direction, one full of novel scientific insights and valuable applications. It is more than just a matter of having the right tools, however. A number of different factors are coming together that offer the chance to make nutrigenomics a major new area of research. The Women’s Health Initiative has shown, for example, that it is possible to do large-scale clinical trials on specific topics in the field of nutrition, which will be important in nutrigenomics research. Over the past decade, a great deal of work has been done in understanding the precise chemical profiles of foods, so that investigators now have a good idea, for example, of which antioxidants are found in which foods and at what levels. Furthermore, public opinion is now favorable to the approach to medicine embodied by nutrigenomics. People are very interested in functional foods1 and in the idea that foods can have health-promoting or disease-preventing properties beyond the basic nutritional value that they provide. The field of medicine is also showing growing interest in the idea of personalized, targeted treatments and is moving away from the idea that “one size fits all.” In addition, the obesity epidemic has caused many people to be more interested in the general subject of food and how it interacts with their bodies. This convergence of factors offers a rare 1 Functional foods contain nonnutrient compounds (bioactive food components) that confer a beneficial physiologic effect that delays or prevents the onset of chronic disease. These bioactive components do not work in isolation. Furthermore, it is apparent that not all individuals respond to bioactive components in the same way; interactions at the genetic level result in a great deal of variability in response. There are at least 8 million single-nucleotide polymorphisms that may contribute to individual variation in genetic responses to nutrients and bioactive components. Conversely, nutrients can also modify epigenetic events. DNA methylation, for example, is an epigenetic event that occurs in response to nutrient stimuli.

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Nutrigenomics and Beyond: Informing the Future - Workshop Summary opportunity, Healy said. “This is the time for the science of nutrition. This is the moment, and we have to seize it.” INTRODUCTORY COMMENTS TO THE SCIENTIFIC SESSIONS Presented by John Milner, Chief, Nutritional Science Research Group, Division of Cancer Prevention, National Cancer Institute There is, today, an unprecedented opportunity to use foods and food components to aid in achieving the genetic potential of humans, improve the overall performance of humans, and reduce the risk for chronic disease. The field of nutrigenomics holds promise for understanding genetic variability and identifying individuals who will or will not respond to a specific dietary change. A key part of understanding how individual variability affects the response to dietary change lies in data coming from research on bioactive food components. Nutrigenomics is the field of research that serves as the bridge to understanding individual variability in the responses to bioactive foods that are consumed and the expression of nutrient-responsive genes. The current expenditure on nutrition research from federal sources in the United States is approximately $1.2 billion per year. Because this amount of money is relatively small in comparison with the research dollars spent in other areas, it is important that they be spent wisely and in a way that will advance nutritional science. This means finding ways to integrate nutritional science with other basic sciences and with preclinical and clinical models. The Women’s Health Initiative was an important step in setting the stage for nutrigenomics research. The science presented in this workshop is furthering that initiative and moving nutrition science forward toward understanding the role of nutrients and bioactive food components in gene expression.