Biotechnology and Potential Nutritional Implications for Children

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PEDIATRIC NUTRITION

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BIOTECHNOLOGY AND POTENTIAL NUTRITIONAL IMPLICATIONS FOR CHILDREN Alvin L. Young, PhD, and Charles G. Lewis, PhD

Biotechnology does not describe a single procedure or process but encompasses a diversity of means for using living matter to develop useful products. Biotechnology in the form of breeding of plants and domestic animals for superior food quality has been used by humans for millennia. The special power of modern biotechnology comes from genetic engineering (recombinant DNA), that is, the ability to transfer genes by nonsexual procedures. This technique allows scientists to take one or several genes from one organism, such as a pig or a tomato plant, and insert these genes into a completely different organism, such as a bacterium, to produce a bacterium with those new genes. Other tools of biotechnology include polymerase chain reaction (PCR), immobilized enzyme techniques, fluorescent in situ hybridization (FISH), enzymelinked immunosorbent assay (ELISA), fermentation technology, biosensors, monoclonal antibodies, and antisense RNA and DNA technology. This article explores the potential implications of these molecular biologic techniques for pediatric nutrition. The children of the United States and of other developed countries have access to a varied, abundant, and nutritious food supply; however, this ready availability of high quality food must not be taken for granted. Recent climatic and world events remind us how vulnerable our food supply is to drought, flooding, frost, disease, insect infestation, and contamination. From the Of£i.ce of Agricultural Biotechnology, Office of the Assistant Secretary for Science and Education, U.S. Department of Agriculture, Washington, D.C. (ALY); and the Metabolism and Nutrient Interactions Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, Beltsville, Maryland (CGL)

PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 42 • NUMBER 4 • AUGUST 1995

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Biotechnology already is being used to monitor and to protect food and food products so they will be safe for human consumption. Biosensors have been and are being developed to detect food spoilage, exposure to nonrefrigeration temperatures, degradation of nutrients, presence of pathogens, microbial and fungal toxins, presence of moisture, and chemical and biologic contamination during food processing and storage. The world's population is approaching the steep portion of an exponential growth curve. Even today, half of the world's children are not adequately nourished. These observations imply that the potential of biotechnology to enhance the quality and safety of our food supply, and therefore the quality of human lives, is not trivial. The pace at which advances in biotechnology can provide changes in food-producing plants and animals and in food science exceeds our ability to predict the nutritional significance and impact these changes might have on the pediatric population, but this article provides an overview of areas where the tools of biotechnology might affect nutrition in children. Recombinant DNA methods can benefit pediatric nutrition in two distinct ways: (1) somatic gene therapy could have a nutritional impact on inborn errors of metabolism; and (2) genetic engineering could be used to alter the nutrient profile of a food to instill a desired health benefit. Compelling evidence suggests that, after the age of 2 years, the amount of dietary saturated fat should be monitored to help prevent coronary artery disease in old age. Thus, genetically reducing the amount of saturated fat in animal foods and food products would be beneficial in reducing serum cholesterol. There has been considerable excitement over the potential benefits of dietary antioxidants such as beta-carotene, vitamin C, and vitamin E in preventing cancer; however, scientific evidence for the benefits of dietary antioxidants has not been unanimous. The antioxidant-cancer story has become complicated by reports that antioxidant vitamins did not protect smokers from getting lung cancer,2 nor did they prevent the development of polyps in the large intestine or rectum. 1S Still other studies suggest that beta-carotene supplements may lower blood and tissue levels of vitamin EP Thus, there may be complex dietary interactions among antioxidants. These studies do not provide definitive evidence against a putative role for antioxidants as anticancer agents, but they do provide reasonable doubt. Many epidemiologic studies strongly support the contention that diets rich in fruits and vegetables lower the risk of cancer; however, the emphasis on the antioxidants in fruits and vegetables may be misplaced because of other potential cancer-preventing compounds in these foods. Thus, to achieve the potential rewards of biotechnology, rigorous examination of the potential health roles and interactions of dietary nutrients is necessary before genetic alterations are made in foods.

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RECOMBINANT DNA TECHNOLOGY AND GENE THERAPY

Recombinant DNA technology enables the cloning or construction of any DNA nucleotide sequence and transferring that sequence across natural species barriers. The recombinant DNA either contains the genetic information for a protein, or it alters the expression level of an endogenous gene. Recombinant DNA technology is being used to produce transgenic animals whose hereditary DNA has been augmented by the addition of DNA from a source other than the parental germplasm. Very simply, gene transfer is used in the laboratory to alter the genetic material of cells so that they can produce more or different chemicals or perform new functions. 41 The plasmid, a circular piece of DNA, is removed from a bacterium and cut open using restriction enzymes. A gene of interest, (e.g., somatotropin gene or interferon gene) is cut out of the chromosomes of another organism and inserted into the plasmid using ligase enzymes. The plasmid recombinant DNA is cloned and transferred to target cells via an appropriate vector. The bacterium duplicates the plasmid and transfers it into the host cells. The transformed host cells are screened for the presence of the recombinant DNA molecule by their ability to produce the gene product of interest. An excellent example of a potential application of recombinant DNA technology is correction of inborn errors of metabolism in which failure of a metabolic pathway occurs as a consequence of the absence or inactivation of an enzyme. At present, these inborn errors are treated by nutritional therapy. For example, dietary phenylalanine or galactose intake is restricted in children with phenylketonuria or galactosemia, respectively, and vitamin B6 is supplemented in children with homocystinuria. With nutritional therapy, however, the diet must be carefully monitored because the dietary manipulations may lead to secondary nutrient deficiencies, and growth may not be maintained at an optimal level. Genetic screening and gene therapy as alternatives to nutritional therapies for inborn errors of metabolism are still in the future. Potentially, however, when an enzyme responsible for an inborn error is known and the gene responsible for the synthesis of that enzyme is found, then the defective gene could be replaced with a working one by somatic cell therapy. Screening for the defective gene would not be restricted to newborns and children but could also be performed on the embryo by preimplantation genetic diagnosis and on the fetus by amniocentesis or chorionic villus sampling. Correcting the defective gene would serve as both treatment and cure, because the child would then be free of both the inborn error of metabolism and of a life-long diet therapy regimen. Today, perinatal screening covers only a few inborn errors of metabolism, and thus the future of gene therapy is closely tied with the progress of the Human Genome Project. The objective of this massive international research initiative is "to create an encyclopedia of the

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human genome-a complete map and sequence. Indeed, the sequence will be the ultimate map, a tool useful for all time and a source book for biology and medicine."25 Through the Human Genome Project, our knowledge of the structure of human DNA is increasing rapidly, and new genes are being characterized almost weekly. As more genes related to inborn errors are discovered and cloned, larger segments of the population can be screened, and the defective genes replaced. Genetic testing and therapy potentially will be used to diagnose and treat genetic diseases which have a nutritional impact on children. For example, cystic fibrosis (CF), a lethal inherited disorder, is the result of a mutation in the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR)9, 12, 24 and affects more children in the United States than any other genetic disease. The CFTR gene was isolated and cloned in 1989, and a three-base deletion resulting in the loss of phenylalanine was identified as the major mutation associated with CF.19, 28, 29 With the development of biotechnology, genetic testing for CF could eventually be performed for the general population. The CFTR gene could be cloned for large-scale production of CFTR that could be used for replacement therapy to treat children with CF. Somatic gene therapy using a retroviral vector could be used to provide cDNA for functional CFTR to affected epithelium. Ultimately, biotechnology could provide a cure for CF through gene replacement therapy in which the defective gene would be removed and replaced with a functional gene. Many technical problems remain to be solved in transferring genes for therapeutic purposes in humans. Solutions to these problems will depend on research in gene transfer techniques in the development of transgenic animals. Transgenic animals have many potential uses as research tools for investigating genetic and metabolic functions. They also serve as model systems for studying pediatric nutritional diseases and metabolic disorders, such as diabetes, obesity, hypertension, and hyperlipidemia. Because the pathogenesis of pediatric nutritional diseases cannot be studied easily in children, transgenic animals developed to serve as models of specific human diseases will provide alternative means of examining nutritionally related genetic diseases.

MODIFIED INFANT FORMULA

Mammals synthesize milk as the sole food for their newborn. The milk of each species of mammal provides the specific nutrients and non-nutrient substances to meet that species' requirements for growth, development, and health; however, the mammalian mother is not always able to provide adequate milk for its newborn. Humans have circumvented this problem by substituting the milk of other mammals for their own and by developing modified formulas, but these preparations do not supply all the nutritional and non-nutritional requirements for optimal development. IS Through advances in biotechnology, potentially the

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modification of the composition of infant formulas to more closely resemble human milk will be possible. Human milk proteins are qualitatively and quantitatively different from cow's milk proteins. Human milk has comparatively less total protein, of which whey proteins are the majority, whereas proteins in cow's milk are mainly caseinsY By altering the relative expression of bovine protein genes, theoretically, increasing or decreasing specific protein components in cow's milk would be possible. For example, lactoferrin is an iron-binding protein that has beneficial bacteriostatic properties in the infant gut. The human cDNA for this protein has been cloned. If adequately expressed when inserted into the bovine genome, it could significantly improve cow's milk nutritional value for the infant. Lipids are the primary source of calories for the infant. Recombinant DNA technology potentially could improve the lipid composition of cow's milk for human infants. Comparison of the fatty acid composition of human milk with cow's milk shows significant differences. 18,20 Human milk contains very few short-chain fatty acids, fewer saturated and more polyunsaturated fatty acids, and less cholesterol than cow's milk. Acetyl coenzyme A carboxylase regulates the rate of fatty acid synthesis in mammary gland. The genetic coding sequence of this large and complex enzyme has been defined,23 and once the regulation of this enzyme is understood, transferring regulatory genes into the bovine genome should be possible, thus altering the composition of lipids in cow's milk. Milk is a complex mixture of nutritive and non-nutritive compounds important to the development of the neonate. Its non-nutritive elements include hormones, enzymes, growth and immune factors, such as pituitary hormones, prostaglandins, lipases, glutathione peroxidase, epidermal growth factor, and specific antibodies to pathogens. 14, 43 Because the composition of these substances are all, to a large degree, determined by the genetic make-up of the female, biotechnology potentially could be used to modify cow's milk to duplicate the non-nutritive elements of human milk. Human milk contains anti-infective factors, including lactoferrin, immunoglobulin A, and oligosaccharides, that provide breast-fed infants with more protection against the development of acute and chronic diseases than do formula-fed infants.14 Free oligo saccharides bind to pathogens and prevent their binding to the membranes of the infant cells so that pathogens are excreted harmlessly. Biotechnology could potentially allow for synthesis of these critical free oligosaccarides for commercial use as supplements in infant formula to provide anti-infective benefits that are, to date, unavailable to formula-fed infants (5. Roth, Neose Pharmaceuticals, personal communication). Genetic modification of cow's milk is a realistic goal. How quickly cow's milk may be modified to mimic human milk may depend on the use of transgenic animals for experimental purposes, Because of the biochemical and biophysical complexity of milk, preliminary evaluation of proposed genetic changes may be done in model systems, such as transgenic animals or transgenic mammary glands. Transgenic animals

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have already been produced successfully for the expression of milk protein genes 7, 21, 33, 39 and for analyzing intestinal epithelium differentiation. 3D,36 Commercial use of the products of transgenic animals is still several years away, however. FOOD ALLERGY

Infants who are fed cow's milk or formula during the early stages postpartum have an increased susceptibility to immediate food-allergic reactions and possibly to subsequent food-allergic reactions later in life. Cow's milk and soybeans most frequently initiate allergic responses in children because of the food allergens in caseins, whey proteins, and soybean trypsin inhibitors. In a food-allergic reaction, food-specific IgE antibodies, bound to sensitized mast cells and basophils, bind with the food allergen to initiate the release of mediators such as cytokines and platelet-activating factor. 32,34 Following the initial response, these mediators may induce an IgE-mediated late-phase response. 32,34 Because identifying and removing the responsible food allergen generally leads to elimination of symptoms, elimination of the food allergen from the diet has been the standard therapy once the diagnosis has been made. Biotechnology currently is being used to synthesize compounds that potentially could regulate the allergic reactions at one or both of the biphasic responses to food allergens, however. Other approaches to treating food allergy might be to eliminate the plant or animal gene responsible for the synthesis of the allergen, or to genetically alter the allergenic part of the molecule. A novel approach would be to synthesize oligosaccharides that could be used as a drug to block the binding of the food-allergen-specific IgE antibodies to mast cells and thus block the initial events in the food-allergic reaction (5. Roth, Neose Pharmaceuticals, personal communication). Oligosaccharide-based therapies would also be appropriate for non-IgE-mediated food hypersensitivity as seen in colitis, malabsorption syndrome, and celiac disease. Ultimately, therapy for infants who are genetically predisposed to food allergies would correct the gene responsible for excessive production of IgE antibodies or other abnormal immune responses. PREGNANCY AND ATHLETIC STRESSES

The most important nutritional use of biotechnology may be for target populations with unique needs. After the initial rapid and critical periods of growth during fetal development and the first and second years postnatally, growth and development are more moderate until the adolescent growth spurt. The availability of nutrients significantly influences growth and development of the adolescent. Yet teenagers often exhibit poor dietary habits; they may skip meals, rely greatly on fast foods, develop eating disorders, and experiment with lifestyles that

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may put them at nutritional risk. If we add to the demands of the adolescent growth spurt additional stresses, such as pregnancy, then the adolescent is at even greater nutritional risk. The nutritional vulnerabilities and risks of teenage pregnancy to the pregnant woman and to the fetus are known. 4,17 The growth and developmental needs of both the teenager and fetus make achieving optimal nutrition difficult for the pregnant adolescent. Food-processing biotechnology could be used selectively to alter the metabolism of microorganisms to produce foods with the desired nutrient profile and modified food products that have the nutrients to help target populations (e.g., pregnant teenagers) satisfy dietary requirements. The nutritional needs of the pregnant teenager are of a dynamic nature and are different for each individual, depending on her prepregnancy nutritional status, her biologic maturity, and the interaction between her stage in the adolescent growth spurt and the progression of the pregnancy. Perhaps moreso than in adult pregnancy, the outcome of a teenage pregnancy is equally as important to the mother as it is to the newborn. If the pregnant teenager's nutritional status is to provide for optimal development for her and the fetus, then biologically functional measures are required to monitor the progress of the pregnancy. It is conceivable that biosensor biotechnology and nanotechnology (i.e., the ability to manufacture objects to precise atomic specifications) could be combined to develop minute sensors capable of functional measures that would continuously provide information on nutritional status and maternal and fetal health. Adolescent athletes are another group potentially at high risk for nutritional imbalances that may be alleviated by biotechnology. Intensive exercise adds dramatically to the nutritional requirements of the athlete during the adolescent growth spurt. Adolescent athletes routinely complain that they do not eat many nutritious foods before practice or competition because the foods leave them with a heavy, stuffed feeling. After practice or sporting events, the athlete complains that he or she does not feel like eating. Adolescent athletes are usually aware that nutrition is important, but their knowledge about nutrition, nutritional intake, and weight-loss practices is poor. 22 For example, adolescent athletes may risk their health and nutritional status if they believe that body weight manipulation is important to their physical performance. Inadequate nutrient intakes are commonly cited among adolescent athletes for iron, calcium, zinc, water, and calories. 22, 31 Ironically, this practice can lead to poor athletic performance, reduced linear growth, and puts the athlete at increased risk for physical injury. Many adolescent athlete diets do not supply the standard recommended energy intake .for the athlete's age, height, and weight. These athletes are significantly energy-deficient when the additional energy for their activity level is included. 22 The adolescent athlete can meet his or her nutritional needs by selecting nutritious foods that provide adequate calories. If proper food choices are not made during the adolescent stage of the life cycle for whatever reason, the consequence is a disruption in growth

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and development that could be permanent. Biotechnology could be used to develop nutrient-dense foods and food products that are elevated in specific nutrients and nutrient bioavailability for iron and calcium, which tend to be inadequate in the adolescent athlete's diet, and lower in nonnutritive substances that may cause gastrointestinal disturbances in an active individual. CHILDREN AS CONSUMERS

During the past 20 years, changes in family structure and in the work environment have affected the lives of children. Many children live in single-parent families or in families in which both parents work. 10, 35 Of these children, two thirds prepare their own evening meals or snacks without supervision. Fewer families sit down to traditional meals together or eat the same foods. Many teenagers prepare and eat more meals at home than their parents do. Children rely heavily on frozen foods, fast foods, snacks, and the microwave oven. They generally do not read nutrition labels, and they do not eat a variety of foods. They select foods like frozen pizza, frozen TV dinners, canned soups, canned spaghetti, and macaroni, and they do not select many fresh fruits or vegetables. 10, 16, 35 Food manufacturers are aware of the buying power of teenagers, and they are interested in what teenagers look for when they shop. A recent survey suggests that teenagers are concerned with price, taste, convenience, and brand name when they select foods. 16 Nutrition is not one of their main concerns. Therefore, potential means of providing good nutrition to children and adolescents may be through the development of novel foods that have specific health benefits, of foodprocessing and preparation methods that eliminate the inclusion of unhealthful substances in foods, and of quantitative and qualitative changes in the nutrient profile of foods. DESIGNER FOODS, NUTRACEUTICALS, AND MEDICAL FOODS

Evidence suggests that the relationship between nutrition and the health of an individual should be considered as a continuum from fetal through old age. 6 ,13 The well-being of adults and elders may be determined, in part, by their consumption of nutrients during infancy. Thus, the pediatrician must consider two components of the infant's and child's diet: (1) its immediate, short-term effect, ensuring that the diet provides the necessary nutrients to meet growth and development requirements; and (2) the long-term effects that diet might have on later ability to live a healthy adult life. Biotechnology is being used to develop a class of foods that have been called functional foods, designer foods, medical foods, or nutraceuticals. A nutraceutical theoretically can be a natural or a genetically

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altered food designed for a specific health benefit. Although much of the research on the relationship between diet and nutrients and their protection against disease is still in the preliminary stage, the so-called nutraceuticals potentially could provide a new class of processed foods that will protect children against diseases such as cancer, cardiovascular disease, stroke, and osteoporosis. The theory is that children who consume nutraceuticals will show an average decline in disease rates when they reach adulthood, thus enabling them to live longer and healthier lives. Through genetic engineering, genes for the synthesis of desirable or therapeutic compounds (e.g., the potential cancer-preventing genes for beta-carotene in cauliflower) may be added to foods. Another source of potential nutraceuticals is the use of enzyme bioreactor systems to convert natural foods into nutraceuticals. A novel approach has been to immobilize mycelium on special columns for the production of pectinase-macerase. This pectinolytic enzyme mixture can then be used for liquefaction of fruits and vegetables to produce a drinkable liquid product for children that would contain significant amounts of vitamins, minerals, and fiber, and be low in calories. Such a drink could provide nutrients, help to lower blood cholesterol level, and help to fight obesity. It could potentially replace the large amounts of soft drinks that teenagers consume. Childhood is the recommended time to initiate preventive measures against adult coronary heart disease,5 such as the gradual lowering of dietary fat intake after the age of 2 years by reducing dietary saturated fatty acid and cholesterol intake and increasing mono- and polyunsaturated fatty acid intake and complex carbohydrate intake. Genetically engineered fruit and vegetable drinks will help children meet these goals. Increased availability of lean meat could be a goal of transgenic research on pigs. Pigs treated with recombinant porcine somatotropin show a dramatic reduction in body fat and modest increase in muscle mass. 8 Transgenic cereals and wheat that produce more soluble and insoluble fibers are being developed. In the area of microbial genetics, the process of enzymatic intersterification and starter cultures are being developed for the production of oils with a more desirable fatty acid profile, reduced cholesterol, and fewer calories. Fried foods form a large percentage of foods consumed by preteens and teenagers, contributing a significant amount of fats and calories to children's diets. Starter culture biotechnology has already produced flavor-enhancers, altered texture, and improved digestibility of foods. It also is being used to develop artificial barriers to inhibit absorption of fat by foods that are fried in oils. There is interest in dietary components that may be cancerinhibitors. 26,42 Researchers are aware of some dietary components that may be tumor-promoters. 3 Children who consume these promoters, in theory, may have initiated latent transformed cells with the genetic potential to progress into cancer cells 20 or 30 years later. Much interest has been placed in the phytochemicals, beta-carotene, retinoic acid,

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ascorbic acid, and tocopherols as potential cancer-inhibitors. Recent attention has focused on their ability to scavenge free radicals and act as antioxidants. 4o Many antioxidants are best obtained from fruits and vegetables, but unfortunately, consumption of this food group by most individuals, including the pediatric-age group, does not meet current recommendations. 38 If children will not increase their fruit and vegetable consumption, increasing the density of antioxidants in this food group could be another approach to altering their diet. Using biotechnology, scientists are developing cauliflower that will synthesize beta-carotene, and carrots that synthesize five times their normal level of beta-carotene. These and other alterations of fruits and vegetables will allow children to obtain more antioxidants by eating their usual servings of fruits and vegetables. A convincing relationship between dietary caloric intake, obesity, and cancer incidence has also been shown, l and the use of biotechnology to reduce fat and calories and increase fiber in food would also be beneficial for decreasing the risk of cancer in children as they age. BIOTECHNOLOGY FOOD GUIDE CUBE

The U.S. Department of Agriculture has constructed a food guide pyramid to serve as a guide to daily food choices. 37 The purpose of the pyramid is to visually depict food groups that should be selected generously because they contain the least fats and sugars. They are at the base of the pyramid. Food groups that should be selected sparingly because they contain the most fats and sugars are at the tip of the pyramid, and food groups that are intermediate in content of fats and sugars are in the middle of the pyramid for moderate selection. Food surveys suggest that Americans' eating habits only roughly approximate the national dietary guidelines depicted in the food guide pyramid, and the diets of children and teenagers fall furthest from recommended goals.lO, 35, 37 Quantitative and qualitative changes in the lipid, carbohydrate, and protein profile of foods and food products are some of the potential applications of biotechnology. As these changes are accomplished, a healthy diet will become more realistic for children because they could continue to select and eat the foods that they are accustomed to and still meet the suggested national dietary guidelines for a long and healthy life. As novel fats, oils, and dairy products with more mono- and polyunsaturated fats and less cholesterol are developed, as novel sweets with fewer calories are synthesized, and as animal muscle with less saturated fat and cholesterol are genetically produced, then children can select from the top portion of the pyramid more frequently. As more knowledge accumulates about the nutritional needs of children, biotechnology could be used to convert the nutritional knowledge base into practical applications through the development of novel foods and food products. The food guide pyramid could then evolve into a geometric

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cube (Fig. 1), allowing more freedom in food choices and providing better alternatives so that the proposed dietary guidelines and recommendations can be met more easily by children. SUMMARY

The tools of biotechnology have enormous potential to develop new, safe, and nutritious foods and food products that could benefit the immediate and long-term nutritional and health needs of the pediatric population. This is especially true as more emphasis is placed on the prevention, rather than the treatment, of chronic degenerative and metabolic diseases. But the promise of biotechnology for nutritional and health benefits of children's diets must be accepted with cautious opti-

Novel Dairy Products from Milk, Yogurt, & Cheese

Transgenic Animals, Plants for Healthier Meat, Poultry, Fish, Dry Beans, Eggs, Nuts

Derived Beverages, New Foods from Vegetables

Derived Beverages, New Foods from Fruits

Transgenic Grain for Improved Bread, Cereal, Rice, Pasta

DAILY FOOD CHOICES Figure 1. Biotechnology Food Guide Cube. For the future pediatric population, the tools of biotechnology can change the Food Guide Pyramid into a cube that includes potential effects of biotechnology on daily food choices. Note: Phytochemicals are every chemical substance naturally occurring in plants. The National Cancer Institute has identified these 14 classes of dietary phytochemicals that are believed to be biologically active in preventing cancer: carotenoids, coumarins, flavonoids, glucarates, indoles, isothiocyanates, lignans, monoterpenes, phenolic acids, phthalides, phytates, polyacetylenes, sulfides, and triterpenes.

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mism. Many advances in food technology and nutritional composition of food animals and plants have already been made through biotechnology, but they represent only the beginning of the necessary research. These advances have been based on relatively little knowledge of basic human nutritional needs, particularly during the dynamic pediatric period of growth and development. More importantly, these advances have been predicated with no understanding of dietary nutrient interactions. Changing nutrient composition of foods through biotechnology may alter nutrient interactions, nutrient-gene interactions, nutrient bioavailability, nutrient potency, and nutrient metabolism. Biotechnology has the potential to produce changes in our foods and in our diet at a pace far greater than our ability to predict the significance of those changes on pediatric nutrition. The Human Genome Project, which relies on biotechnology, will revolutionize science and medicine. Pediatrics will be one of the first medical specialties to benefit from the outcome of this project as recombinant DNA manipulations will replace diet therapies for treating metabolic diseases. Somatic gene therapy eventually may be the ideal means for diagnosis, treatment, and cure of inherited diseases and metabolic disorders; however, many problems exist, especially in situations in which nutrients are involved in the complex regulation of gene expression. DNA and genes themselves do not determine the fate of an individual. The genetic material provides the potential for the individual, but this potential can be modified by environmental factors. The interaction of nutrients with genes is a major determinant in the final outcome of the individual. Biotechnology promises children a more productive and better quality of life, but achieving the full potential of this promise demands a continued diligent search for knowledge of nutrition and nutrient-gene interactions. ACKNOWLEDGMENTS The authors are indebted to Drs. Myron Winick and Demetrius Albanes for their critical evaluation of this article and for their many helpful suggestions, to Jennifer Madigan for cheerfully providing excellent assistance in typing the manuscript, and to Mark D. Lure for his assistance with the computer graphics of the cube.

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Address reprint requests to Alvin L. Young, PhD Science Advisor and Scientific Director Office of Agricultural Biotechnology Office of the Assistant Secretary for Science and Education U.S. Department of Agriculture Room 3868-5 14th and Independence Avenue SW Washington, DC 20250