1Unite de Pathologie Vegetate, INRA-Avignon, Montfavet France
2Dept. Plant Sciences and Plant Pathology, Montana State University, Bozeman, MT, USA
Plant breeders, challenged to create more nutritious crops, face seemingly radical choices that constitute a "breeder's dilemma". In the search for higher yields and lower farming costs, have breeders inadvertently selected for crops with reduced nutritional quality? To create foods that keep pace with our growing u nderstanding of what constitutes healthy diets, plant breeders may need to make a-significant shift away from traditional selection criteria. Subsidizing crop nutritional value rather than yield could be an important and economical driver for this shift in perspective.
The wide variety and availability of DNA and proteomic tests for human health and disease treatment are among the principal technological consequences of the Human Genome Project. This is leading to a growing understanding about the molecular basis of human health and of genetic predisposition to diseases such as obesity, type 2 diabetes mellitus, cardiovascular disease, and colorectal and other cancers. The pivotal role that diet plays in both the cause and the remediation of these and other health problems is also becoming increasingly clear. Our challenge is to narrow the growing gap between what we should eat to maintain optimal health and the nutritional quality of the staple foods in modem diets.
Plants are a fundamental constituent of the human diet, either as direct sources of nutrients or indirectly as feed for animals. Modem plant breeding has been historically oriented towards high agronomic yield, easy and consistent processing, and disease and pest resistance. This strategy may have unwittingly led to the proliferation of foods that are at the root of certain dietary problems. The biochemical quality of certain staple plant foods - and not simply the quantities consumed - might be a predisposing factor for obesity and cardiovascular disease as will be illustrated below. Furthermore, some plants, while efficient as feeds for animal production, may adversely impact the nutritional qualities of animal-based foods. For example, they might not provide sources of certain types of polyunsaturated fatty acids. Creating staple foods that are more nutritious might require selecting crop cultivars that are lower yielding, more sensitive to pests, possess unusual flavors or other uncommon properties, or otherwise do not meet traditional criteria of plant breeders. Creation of oil crops and animal feeds that enhance the hea1th-promoting quality of animal-derived foods might involve some concerted genetic modification of our current crops or replacement of traditional canola-, soy-, wheat- and com-based products with new crops.
Wheat breeding, for example, has been historically oriented toward increasing yield and the amounts of amylopectin, gluten and protein. Amylopectin and gluten contents insure baking and processing qualities. However, after cooking, amylopectin (branched starch) is more readily digestible than amylose (straight starch). Results of feeding trials suggest that quickly digested starch such as amylopectin promotes the development of insulin resistance in rats. The relatively slow time course of this condition resembles the normal development of insulin resistance in humans 1. Insulin resistance is the leading risk factor for type 2 diabetes mellitus and is aggravated by obesity 2. In contrast, consumption of high-amylose foods normalizes the insulin response of hyperinsulinernic human subjects. This has potential benefit for diabetics 3. Gluten, the major storage protein in wheat (and similar proteins in barley and rye) causes an autoimmune response that damages the small intestine of certain genetically predisposed individuals. The damaged mucosal lining of the small intestine leads to chronic malnutrition whose symptoms are impaired physical health and emotional state. This genetic disorder is known as celiac disease. According to the Nlli Consensus Development Conference Statement on Celiac Disease (June 2004), this disease has been under-9iagnosed by the medical community and may affect as many as 0.5-1% of people in the US and Europe.
Our staple crops may also have inherent deficiencies that may contribute to emerging dietary problems. Com is a case in point. About 60% of com seed proteins consist of prolamins (or zeins) which are almost completely devoid of the essential amino acids lysine and tryptophan. Attempts to select com lines with enhanced lysine and tryptophan have invariably led to reductions in zein content. The resulting com lines bad soft chalky endosperm and consequently also suffered increased mechanical damage during harvest. They also were more susceptible to diseases and were lower yielding and thus have never led to significant commercial interest 4. Com-based diets (animal or human) require lysine and tryptophan supplementation for adequate protein synthesis. Tryptophan is also the precursor for the synthesis of some neurotransmitters and for niacin . Historically, pellagra developed where com is an important dietary staple and where protein intake is low. This disease is caused by niacin deficiency due to the absence of its precursor, tryptophan, in the diet. Symptoms are severe dermatitis, diarrhea, dementia and eventually death 6. Pellagra is rather uncommon today outside of all but the poorest regions of the world. But in those parts of the world where com is still an important component of the diet, there may be other consequences of low tryptophan consumption that we are ignoring. The neurotransmitter serotonin, synthesized in the brain from tryptophan, is responsible for feelings of well-being, calmness, personal security, relaxation, confidence and concentration; it is a key player in overall mood and in aggressiveness 7 and in the development of depression. Could consumption of tryptophan-rich foods play a role in reducing the prevalence of depression and aggression in society?
Lipids also play an important role in human health from both the standpoint of caloric intake and as a source of essential fatty acids. The ratio of omega-3 to omega-6 polyunsaturated fatty acids in our modem diet has escalated from an optimal ratio of 1:1 or 1:2 to a current ratio of 1 :25 to 1:30. Tbjs non optimal ratio results from high consumption of red meats rather than cold-water fish, a lack of plant sources of long chain omega-3 fatty acids in our diets and the use of animal feeds rich in omega-6 versus omega-3 fatty acids. Development of cookirtg oils has led to widespread availability of mono- and poly-unsaturated oils such as canota and soy that have greatly replaced saturated fats. Unfortunately, these oils are relatively low in long chain omega-3 fatty acids and high in omega-6 fatty acids. This skewed ratio is a key factor in the prevalence of cardiovascular diseases, inflammations and auto-immune diseases 8 9. Fish oils, high in long chain omega-3 fatty acids, cannot replace plant-derived oils for widespread use in cooking and feeds. There is need for crops that can provide abundant quantities of these fatty acids.
It is axiomatic that one of the aims of plant production is the reduction of crop loss from predation and disease. But we wonder if in our efforts to boost yields to feed growing populations we haven't overlooked what pests could be telling us about the nutritional value of crops. Plants and bacteria are the only organisms that can synthesize the full complement of protein amino acids. Animals must consume certain pre-formed amino acids. The ten essential amino acids are the same for all animals. (There are a few exceptions to this rule about the nutritional needs of heterotrophs, such as aphids and termites that harbor bacterial symbionts that can make essential amino acids and furnish them to their hosts (10,11). Nevertheless, plant-derived food that is nutritionally good for insects, rodents, deer and nematodes, for example, is fundamentally good food for humans. Likewise, many of the compounds that plants produce to inhibit herbivory - such as alkaloids, cyanogenic glycosides, glucosinolates and terpenoids - have wide spectrum activities across the animal kingdom. Furthermore, most animals are equipped with taste receptors and internal feedback mechanisms that allow them to sort through stimuli to obtain necessary nutrients and avoid toxins. Hence, if crops are bred for undesirability to insects could this mean something with regard to the quality of these crops as food for humans? Corn and wheat are both deficient in lysine and methionine and there is some effort to increase the content of these amino acids in these crops. Could this lead to increased desirability to pests? We are not proposing that plant breeding ignore or enhance the susceptibility of crops to pests. Rather, we are pointing out that this is part of the breeder's dilemma in selecting more nutritious crops.
What are the technological routes to developing highly nutritious foods, and particularly staple crops? Clearly, genetic and metabolic engineering are likely to be very effective (and in some cases the only possible) routes to modify our current staple crops via insertions of specific genes, gene silencing and immunomodulation. Gene insertion has been used to create rice high in provitamin A 12 and gene silencing has led to slight increases in lysine and tryptophan contents of wheat 4 . Recently, heavy chained antibodies from llamas have been used to immunomodulate starch branching enzyme A in potatoes leading to higher amylose content of tubers 13. We also need to seriously consider alternative plant species as candidates for major staple crops. To create gluten free grain crops or enhance omega-3 production in plants, should breeders focus on genetic modifications of wheat, canola or soy, or could alternative plant species more efficiently and effectively lead to solutions for the associated dietary problems? To avoid damage of more nutritious crops by pests, breeders might need to design multi-line or composite crops. Each component of these crops might lack a specific nutrient, but the composite would have all of the essential amino acids, for example, in optimal quantities. This might avoid enhancing their desirability to pests. The route to more nutritious crops might also involve consideration of the full gamut of enlightenment arising from genomics, proteomics and metabolomics as applied to humans, nematodes, insects, plants, etc. and what they are telling us about the biochemical differences between health and disease. Furthermore, to create widespread acceptance of nutritious crops, breeders may need to bravely address the biology of food addiction and satiation, two very real drivers of food preferences.
Breeders have always confronted dilemmas; it is their stock in trade. The breeder's dilemma we describe arises from the confrontation between the emerging data-driven insights into the physiology of human health and traditional agricultural practices and economics of food production. Wholesale creation of highly nutritious crops may threaten current commodity crops. Solving the breeder's dilemma requires a radical shift in perspective. Improving our diet is an investment in human capital. It will have important positive spillovers for education, behavior, and could ultimately improve quality of life. Can we eventually consider that gains in work time and higher learning performance, for example, are part of the economic results of plant breeding programs? Can an economic system that subsidizes yield be converted to one that, by subsidizing crops with high nutritional quality, concomitantly reduces other costs to society related to human health?
1. Byrnes, S.E., Miller, J.C. & Denyer, G.S. Amylopectin starch promotes the development of insulin resistance in rats. J. Nutr.125, 1430-1437 (1995).
2. Hirosumi, J. et al. A central role for INK in obesity and insulin resistance. Nature
420, 333-336 (2002).
3. Behall, K.M. & Howe, J.C. Effect of long-term consumption of amylose vs amylopectin starch on metabolic variables in human subjects. Amer. J. Clin. Nutr.
61, 334-340 (1995).
4. Huang, S. et al. Improving nutritional quali ty of maize proteins by expressing sense and antisense zein genes. J. Agric. Food Chern. (2004).
5. Heine, W., Radke, M. & Wutzke, K.-D. The significance of tryptophan in human
nutrition. Amino Acids 9, 91-205 (1995).
6. Breoton, B.P. Pellagra and paleonutrition: assessing the diet and health of maize
horticulturists through skeletal biology. Nutr. Anthropo/. 22, 2-9 (1994).
7. Young, S.N. & Leyton, M. The role of serotonin in human mood and social interaction: Insight from altered tryptophan levels. Pharm., Biochem. Behavior 71 (2002) 857-865 71, 857-865 (2002).
8. Kris-Etherton, P.M., Harris, W.S. & Appel, L.J. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106, 2747-2757 (2002).
9. Simopoulos, A.P. Omega-3 fatty acids in inflammation and autoimmune diseases.
J. Amer. Call. Nutr. 21, 495-505 (2002).
10. Douglas, A.E. Nutritional interactions in insect-microbial symbioses: aphids and their symbiotic bacteria Buchnera. Annu. Rev. Entomol. 43, 17-37 (1998).
11. Douglas, A.E., Minto, L.B. & Wilkinson, T.L. Quantifying nutrient production by the microbial symbionts in an aphid. J. Exp. Bioi. 204, 349-358 (2001).
12. Potrykus, I. Golden rice and beyond. Plant Physiol. 125, 1157-1161 (200 l).
13. Jobling, S.A. et al. Immunomodulation of enzyme function in plants by single
domain antibody fragments. Nat. Biotechnol.21, 77-80 (2003).