Elevating optimal human nutrition to a central goal of plant breeding and production of plant-based foods

1. Introduction

An obvious but rarely stated goal of food production is to provide the human species with the proper nutritional factors to allow each person to reach their full intellectual and physical potential. However, in practice the two most important drivers of food production are optimal yield and minimal cost. The goals predicted for agriculture in the future forecast more of the same; i.e. that plant production will target supplying adequate calories for an ever increasing population, while also addressing the growing concern about the impact of agricultural practices on the environment [1], but not the need for superior nutritive value to enhance human health.

There has been increasing interest over the past several decades in improving the nutritional quality of crops. The wide-scale release of lines of quality protein maize (QPM) now being cultivated in Africa, Asia and Latin America [2] is one of the fruits of concerted efforts of breeders to improve nutritional quality of crops. The upcoming releases of biofortified crop varieties planned by programs such as HarvestPlus (www.harvestplus.org) and AgroSalud (www.agrosalud.org/) also illustrate the increasing interest in enhancing nutritional quality of crops. Nevertheless, enhancement of nutritional value of crops is high on the list of goals or accomplishments of rather few plant breeders, even though improved nutritional value is of critical importance for human well-being. In a hungry world, where the rate of increase of food availability trails behind the rate of increase of the demand for food, it is unlikely that enhanced nutritional value of crops can be a goal in itself. This will be particularly true when goals for enhanced nutritional value are for single nutrient traits rather than overall nutritional quality of crops. In this paper, we propose fundamental changes in current strategies of plant breeding, crop production, and food and feed processing to better facilitate the goal of production of more highly nutritious plants and plant-derived foods.

To develop commercial varieties of crops with enhanced nutrition, it may be essential to link nutrition to a commercial driver such as yield. In the case of crop lines biofortified for mineral nutrients, yield increases can go hand in hand with nutritional quality [3]. Unfortunately and inadvertently, high yield, pest resistance and low cost can also select against the best human nutrition, which we have called “The Breeder's Dilemma” [4]. In this paper we will point out more examples of this conflict and describe their origins. The exciting challenge for the future is to adjust research priorities in the way plant selection and plant breeding are accomplished to overcome this conflict. The ultimate goal is to create a sustainable food-production system that meets the needs of the global population in terms of calories and concomitantly addresses important needs for balanced amino acids, balanced essential fatty acids, optimal trace and macro- minerals, and vitamins, with foods low in toxins or anti-nutrients. The food production methods will need to account for the potential conflicts between optimal nutritional quality for humans and agricultural animals and the physiological needs of plants for growth and defense against pests and disease.

2. Evolutionary context of plants as food

Cereal grains are archetypical of the role of staple crops in the diet of modern humans and the effort invested in their breeding. Three cereal grains: wheat, maize (corn), and rice, constitute 75% of the world's total caloric intake. Over 50% of all the protein consumed by humans worldwide is low nutritional quality protein provided by wheat, maize, rice, barley, sorghum, oats, rye and millet [5]. From an evolutionary perspective, our modern reliance on grains is a dramatic shift away from the diet to which humans have evolved. Earlier than 15,000 to 100,000 years ago, Homo sapiens survived via hunting, fishing, and foraging. After about 10,000 - 15,000 years ago, during what might be considered as possibly the first ‘agricultural revolution’, a confluent series of factors contributed to domestication of plants including cereal grains as sources of food. The advantage of such grains was that they could be stored over several years, thereby being a reliable source of food during unfavorable conditions.

Some ethnological and archeological studies suggest that almost immediately after transition to grain-based diets, humans experienced reductions in stature, increases in infant mortality, a shrinkage of life spans, increases in infectious diseases and multiple nutritional deficiencies, including iron deficiency anemia and mineral disorders impacting both bones and teeth [5-7]. It has been argued that widely differing assumptions about different preagricultural regimens have little impact on the estimated dietary essential omega-6/omega-3 fatty acid ratios, for example, which have major health impacts as discussed later [8]. We should note that there are other detailed ongoing studies of the Neolithic demographic transitions of instances where human populations rose 200 fold in a short period of time illustrating the disagreement about aspects of the Paleolithic diet [9]. However, it is well accepted that our foods have changed at a considerably greater rate than our inherent physiology and the underlying genes, which have changed rather minimally in the last 10,000 years [10, 11] and essentially not at all in the past 40-100 years [12]. Modern progress in hygiene and developments in medicine have led to reduced infant mortality and longer average life spans, especially where cereal grain based diets could be supplemented with other sources of nutrients. Nonetheless, many of the negative consequences of the transition to grain-based diets remain with us today. The inadequacies of high carbohydrate and grain-based diets have been summarized at length [5, 7, 13]. Furthermore, over the last 200 years, as the population has become more urban, there has been a striking separation of food production from food consumption. Transportation of food away from its source of production has amplified the roles of marketing, intermediary distribution, and processing; and shelf life considerations have influenced the choice of varieties grown, thereby leading to reduced importance of traditional local foods.

The inadequacy of cereal grains as a primary food for humans arises from the fundamentals of plant physiology. Plant seeds are packed with compounds stored as sources of energy for supporting germination. Their carbohydrate, protein and lipid profiles reflect the specific requirements for seed and seedling survival. This nutrient profile, especially after selection during domestication [14], is far from optimal for human or animal nutrition. For example, the seeds of most cultivated plants contain much higher concentrations of omega-6 fatty acids than omega-3 fatty acids than is desirable for human nutrition [15, 16], with few exceptions such as flax, camelina (Camelina sativa) and walnuts. Temperature is an important regulator of the ratios of the unsaturated fatty acids in plants, with growth at colder temperatures in temperate climates favoring the production of the omega-3 fatty acids in seed oils and moderate to warm temperatures favoring expression of the omega-6 and saturated fatty acids [17-19]. Seed germination during cold temperatures requires higher concentrations of polyunsaturated triglycerides that are in liquid form even at sub freezing temperatures. Cold tolerant crops such as camelina and flax contain seed oils that are high in omega-3 oils, possibly enabling germination in cold soils. However, the major oil crops, such as corn, soy, sunflower, safflower, and canola are warm- and hot-season crops that are high in omega-6 oils. High dietary intake of omega-6 oils impedes the desaturation and elongation of the omega-3 oils to produce the long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [16, 20, 21]. Higher intakes of omega-3 fatty acids and lower intakes of omega-6 fatty acid are correlated with decreased all-cause mortality, coronary heart disease, stroke mortality, bipolar depression, postpartum depression [22] and the reduction in the incidence of a number of cancers [23, 24], and these issues will be discussed in more detail later in this paper.

In addition, many seeds contain compounds such as phytic acid which tightly binds zinc and iron to assure sufficient reserves of these minerals. Phytic acid-bound zinc and iron are insoluble and unavailable for assimilation by animals and humans, even though they are present in a diet [25]. And finally, certain cereal grain proteins can be antigenic. Between 0.5% to 1.0% of Western, Arabian, and Indian populations are genetically predisposed to celiac sprue syndrome, an autoimmune type of inflammatory disease of the small intestine triggered by the ingestion of wheat gluten (alpha-gliadin) [26]. Clearly, seeds have not evolved to be ideal foods for animals and humans, and in fact they are anything but ideal foods for us. Likewise, other of our staple crops that are high in rapidly metabolized carbohydrates, such as potatoes or crops used as sources of sugars, are far from ideal sources of nutrition for humans (for a detailed overview of this subject see Taubes [13]). Breeding strictly for yield can exaggerate these nutritional inadequacies. We have described this problem as a breeder's dilemma, in that selection strategies for yield are frequently in conflict with selection for nutritional quality [4].

3. The Green Revolution

The green revolution was very successful in raising overall yields of foods, and in particular cereal grains. The breakthroughs in breeding came first in wheat and rice. Dwarfed lines were selected for high yield and agronomic characteristics, such as insect and disease resistance. These relatively quick technical fixes, along with increased fertilizer and herbicide use, tripled the yields of cereal grains as well as other staple crops such as potatoes. The increased yields helped those nations on the brink of starvation traverse to a period of relative food security. These spectacular results in increased food production were due to the visionary leadership of a small core group of agriculturists who clearly defined the principal limiting factors in cereal grain production and organized a global cadre of scientists, economists and politicians to carry out their mission of increasing crop yield (This unprecedented accomplishment of Dr. Norman Borlaug and his colleagues was recognized with a Nobel Peace Prize in 1970). Generous funding by the Rockefeller and Ford Foundations and later by a wide range of donors (primarily Western governments) facilitated implementation of the Green Revolution project and global adoption of high yielding grain varieties [27].

However, the predominant breeding and production strategies engendered by the Green Revolution gave us more high-carbohydrate, low-quality-protein cereal grain diets. These diets in Asia and South America have reduced the percentages of poor and malnourished (in rising populations), although they have not been as effective in Sub Saharan Africa, where the percentages of malnourished are increasing. We find it hard to ignore the fact that many people (more than 1 billion) are severely malnourished according to estimates reported in an FAO press release from June 19, 2009 (http://www.fao.org/news/newsroom-home/en/). The increased yields of Green Revolution cereals led farmers to switch from legumes to cereals. The high-yielding cereal crops lack balanced essential amino acids, balanced essential fatty acids, vitamins, minerals and additional quality factors. Apparently, the priority to fend off starvation did not give sufficient consideration to nutritional quality, perhaps for technical as well as strategic reasons. In retrospect, inadequate nutrition may have contributed to downward cycles of poverty and health [28].

Malnutrition handicaps its victims with fatigue, lethargy, susceptibility to pathogens, and a range of health complications, thus limiting their ability to care for themselves, to obtain and benefit from education, and to contribute to society. Efforts to document the costs of malnutrition for human health and for society provide powerful testaments to the extent of these losses [29, 30]. Malnutrition has multiple causes including lack of food (production), lack of resources to procure food (poverty and infrastructure), and impairment of ability to absorb nutrients (disease) [31]. When malnutrition is due to problems of food availability or procurement it is also often associated with limited food diversity and nutritional quality. In fact, lack of access to a diversity of foods is an indicator of poverty, and conversely dietary diversity has been proposed as an indicator of food security [32]. Diets that are heavily based on cereal grains or on a limited number of other staple crops may lack sufficient amounts of certain essential nutrients. In contrast, diets based on a diversity of foods tend to contain more complete nutrient complements. Thus, overwhelming reliance on cereal grains intensifies malnutrition and complicates delivery of adequate nutrients to modern humans. The deficiency of many of the staple crops and lack of dietary diversity particularly aggravates malnutrition during weaning of children [33]. On the other hand, many chronic diseases are on the rise in developed countries that depend less on staples for essential nutrients. In this case the nutritional quality of staple crops used as animal feed effects the nutritional quality of the animal products consumed by people. In developed countries there is a profound concern about the increasing medical and social costs of chronic diseases. Improving the nutritional quality of staples and animal products consumed, especially their pro-/anti-inflammatory properties, arguably has great potential for having beneficial effects on the health and well being of the population, as well as reducing the costs of medical care, as will be developed further in this paper.

4. Law of the Minimum

Justus von Liebig's two hundredth birthday passed in 2003 with little fanfare, compared to that of Darwin. Nevertheless, Liebig imparted a rule-based paradigm that is one of the foundational principles of agriculture: Liebig's Law of the Minimum. In biological systems, certain inputs are essential. Optimal growth and/or performance will be limited by the least available of these essential inputs. For example, plants require light, water, nitrogen, potassium, phosphorous, and sulfur. Among these requisite elements, one is usually the limiting factor. If the plant lacks enough sulfur to grow, further addition of any of the other elements will not really help. Extra potassium cannot compensate for the missing sulfur. Addition of sufficient sulfur will allow the plant to grow until one of the other elements becomes limiting. Accordingly, agronomic efficiency and optimum plant growth is best obtained by balanced fertilization relative to water and light availability. For instance, adequate nitrogen fertilizer is required for high protein production in plants that do not fix their own nitrogen from the atmosphere, but the addition of nitrogen need not outpace other limitations.

The same Law of the Minimum paradigm can be applied to human nutrition. Calories, proteins (i.e. essential amino acids), essential fatty acids, minerals, or vitamins can limit growth and cognitive development. Beriberi (vitamin B1 deficiency), scurvy (vitamin C deficiency), and pellagra (niacin deficiency) are classic examples of how a single nutrient deficiency can have severe consequences on human health. In complex human diets, the limiting factor or imbalance of nutrients can be elusive and may well vary from individual to individual. Furthermore, diets can be deficient in multiple nutrients simultaneously [34, 35]. These deficiencies can be partially masked by our ability to store excess caloric intake as fat, which is often misinterpreted as an indication of adequate nutrition. Obesity can result from consumption of an overabundance of calories or consumption of an unbalanced diet, so that much of the excess consumed carbohydrates and fats are stored. The human body strives to regulate blood sugar levels, and carbohydrates in excess of what can be burned for energy or stored as glycogen must be converted to fat [13].

Zinc is an example of an element that can commonly be limiting for both plant production and human development. Zinc can be deficient in soils due to geological and pedological history of a region or its deficiency can be caused or compounded by continuous grazing and cultivation of land that eventually depletes essential elements from the soil. The calcareous soils in much of the Middle East, Africa and Australia exhibit a low availability of zinc. This deficiency carries through to the animal and human populations because not only is yield reduced, but forage and grain from the stunted plants are also deficient in zinc. Symptoms of zinc deficiency in humans range from stunted growth in children, to geophagia in pregnant women, and abnormal behavior ranging from lethargy to violence in young adults [36-38]. It is no surprise that zinc is important in biological systems since zinc has many catalytic, structural and regulatory functions in cells. For example, about 100 enzymes are dependent on zinc as a catalyst. The multitude of references on the structural, regulatory and catalytic roles of zinc are brought together on a university website (http://lpi.oregonstate.edu/infocenter/minerals/zinc/) Thus, a deficiency in zinc will affect numerous enzyme functions, greatly reducing cellular efficiency. A coordinated research effort in Turkey supported by NATO successfully addressed this zinc deficiency in soils and mandated zinc sulfate amendment of 300,000 tons of NPK fertilizer [39]. This effort has resulted in considerably higher crop yields in the Central Anatolian Plateau, and we might presume that zinc soil amendments resulted in more zinc availability in cereals, vegetables and animal products from the region, thus providing adequate zinc in foods to the consumers there.

5. Single Component Targets of Enhanced Nutritional Value

A review of the research on nutritional enhancement of crop plants reveals the focus on enhancement of single nutritional traits, such as provitamin A in Golden Rice [40] or increased lysine in wheat [41] or barley [42]. A number of other approaches to enhancing plant nutrition have been recently summarized [43]. While these efforts are certainly commendable, they are piecemeal approaches, frequently using plant species for experimentation that do not meet widespread agricultural needs, and have been focused on rather conventional physiological limits, with certain exceptions (viz. Golden Rice).

The complex biochemistry involved when a human body assimilates, metabolizes, and utilizes nutrients is now a much more tractable science than even a decade ago. The genes, protein isoforms, signaling networks, and the microbiome that influence these processes are becoming much better understood at the cellular level, as illustrated in part by the Human Metabolomics Database (http://www.hmdb.ca/), for example. Furthermore, so-called “diseases of civilization” in modern humans are being better characterized [44] and changes in gene expression hence in basic physiology due to the transition from a physically-active to a more sedentary way of life are being elucidated [45]. It is widely recognized that “systems biology” has the potential to increase the understanding of how nutrition influences metabolic pathways and homeostasis, how this regulation is disturbed in diet-related diseases, and to what extent individual genotypes and epigenetics contribute to such diseases [46]. These insights are being complemented by a re-evaluation of optimal human nutrition from the perspective of evolutionary adaptation and by comparison of the apparent needs of humans with those of other primates [47, 48]. It is evident that numerous human diseases are linked to or aggravated by nutritional choices and those habits that we attribute to life-style. These go beyond some of the better understood afflictions that are clearly caused by diet and, in particular, by the nature of plant foods, such as favism [49], neurolathyrism [50], goiter and cretinism [51], and pellagra [52]. As genetic components of disease are uncovered, the often dominant role played by diet and lifestyle in health, and the interaction of diet and genes is becoming increasingly evident (examples include Type 2 diabetes [53], coronary heart disease [16], psychiatric disorders [54], Alzheimer's disease [55], celiac sprue disease [56, 57], death from all causes and depression [22], and etc.). Furthermore, the link of human behavior – violence and aggression in particular – to nutrition is becoming more evident [58]. Given this current trend of discovery, and the relatively modest role that genetics appears to play in complex diseases (www.cdc.gov/genomics/public/index.htm), it seems likely that in the coming decades the connections between health and nutrition will grow very substantially and will be much more fully recognized. The nutrients that we selected for discussion below come from this contemporary perspective.

6. Methods for Enhancing Nutritional Traits in Plants

Do breeding and selecting for nutritional quality require approaches that are not already part of those currently employed to enhance crop quality? Here we argue that there is a critical need for innovation to surmount such paradoxes [4] that tend to decouple improved nutrition from yield. Overcoming this dilemma is critically important for nutritious cultivars to be competitive with other high yielding cultivars.

Firstly, it should be noted that progress has been made with traditional approaches to improving crop nutritional quality. The original selections of high protein mutants of maize that led to QPM were identified in a mutagenized population using traditional breeding techniques [119, 120]. The resulting breeding lines had higher lysine and tryptophan relative to the wild type, had altered endosperm and proved to be devoid of two storage proteins (19 and 22 kD alpha zeins). In wild type maize, the major seed storage proteins are deficient in lysine and tryptophan, which contribute to the poor nutritional quality of the seed. The extensive screening that has also led to the identification of low phytate lines of maize, barley, wheat and rice is feasible for other crops such as sorghum and millets, as reviewed previously [121].

More recently, molecular and transgenic methods have been used to develop plant lines with increased nutritional value [43]. Concerning protein quality, the content of essential amino acids can be raised by engineering with feed-back insensitive biosynthetic enzymes and by inhibiting their normal catabolism [122], by displacement of low quality endosperm proteins (i.e. zein, hordein) with higher quality endosperm proteins, or by decreased degradation of amino acids [123]. For example, the lysine content in soybean or rapeseed transformed with bacterial genes encoding feedback insensitive lysine synthesis genes is nearly double the lysine content of the parental lines [124]. In a further attempt to enhance lysine concentration in grains, a feedback insensitive dihydrodipicolinate synthase from maize has been expressed in rice [125]. Higher lysine plants can also be engineered by gene suppression techniques. Maize was generated with reduced levels of expression of zein protein in the endosperm [122, 126]. The plants compensate by increased production of non-zein proteins, which resulted in an improved amino acid balance, but also in higher levels of the free amino acids, asparagine, aspartate, and glutamine (see section 5.1 for the down-side of high levels of free amino acids in human nutrition, but which might well be beneficial for animal feeding). High lysine maize plants were also generated by decreasing expression of the gene encoding lysine ketoglutarate reductase, an enzyme that catabolizes free lysine in maize kernels [127]. Efforts have also been made to identify plant proteins that are inherently rich in lysine and to increase their lysine content where possible. For example, mutagenized forms of genes for the barley chymotrypsin inhibitor 2, that code for proteins with increased frequencies of lysine residues compared to the wild type protein, have been incorporated in vectors for transformation of sorghum [121]. Direct transfer of a lysine-rich pollen-specific protein from potato, without subsequent mutations, led to an increase of protein content and up to a 50% increase in lysine content of maize [128]. Likewise, phytases or proteins that confer the capacity to accumulate micronutrients have been transferred to grains from micro-organisms or from other plant species in efforts to exploit transgenics for crop improvement [121]. Enhancing the nutritional quality of plants will often require modifying complex synthetic or metabolic pathways rather than single gene systems. In light of this, a method of combinatorial nuclear transformation has been developed to generate a diversity of combinations of transgenes for a complex metabolic pathway in a plant. This novel technique has been exploited to generate a library of metabolic phenotypes for the carotenoid pathway in maize [129].

Screening of varieties with altered nutritional quality can also be accomplished via classical chemical analyses. Most chemistry laboratories in universities have gas chromatographs and high performance liquid chromatographic equipment necessary to quantify levels of fatty acids, amino acids, and other nutrients and anti-nutrients. The problem of cost per sample sometimes necessitates preliminary screening, however high throughput methods can foster screening of populations of thousands of M-2 mutant plants, as has been done in searching for plants with an unusually high level of omega-3 fatty acids [130]. Bioassays of seeds, using nutrient-dependent microbes, can be developed for almost any nutrient, and these can be used as an inexpensive first screen for nutrient content (as described below). In cassava breeding for elevated provitamin A carotenoids, initial screening has been based on visual assessment of root color [131].

Innovative approaches to selecting for highly nutritious crops might be simple and counterintuitive. Deploying predators might be one example. Insects [132] and certain rodents [133] have an uncanny ability to find plants that have increased content of essential amino acids such as lysine, methionine and threonine. Plant breeding lines unusually attractive to herbivores might also have unusually high levels of desirable amino acids. Baby chicks develop a high preference for a diet containing lysine only three days after hatching [134]. We are aware of a maize breeder who uses rodents in his barn as a preliminary screen to detect which lines are higher in lysine (Dave Christensen, private communication). Leaf bioassays with the lysine auxotroph Leuconostoc mesenteroides (Pediococcus cerevisiae (ATCC 8043)), in conjunction with the appropriate amino acid assay medium, can be used to verify the content of amino acids [135]. The Leuconostoc agar plate assay of half seeds can also be used to select for seeds with higher lysine content, as in the case of wheat and safflower seeds.

Predation might also be used to select varieties with decreased antinutritive content Cassava is cultivated throughout the tropics for its starchy roots that provide food for over 500 million people, as well as for livestock feed and industrial products [136]. There are over 5000 known phenotypically distinctive cassava varieties. All contain varying concentrations of the cyanogenic glucosides linamarin and lotaustralin, which are hydrolyzed to hydrogen cyanide (HCN) by endogenous linamarinase, when the tissue is damaged. The Tukanoans of northwestern Amazonia cultivate high-cyanogenic potential cassava (Kii) in preference to low-cyanogenic cassava (Makasera) [137]. Processing of the more toxic Kii is labor intensive relative to the Makasera. However, Kii produces significantly higher yields in comparison to Makasera. Insect predation is more intense on the less toxic Makasera, perhaps explaining the lower yields. Morant and colleagues [138] have demonstrated that the level of glucoside in plants can be increased by genetic engineering. Such plants have increased resistance to predation. Alternatively, gene silencing can be used to reduce the levels of glucosides resulting in plants with reduced content of anitnutritive compounds.

Insect preference might also be used to select for other nutritional attributes or possibly to introduce desirable traits into a population. For example, honey bees show a preference for oilseed pollen with high caloric value [139]. In an unrelated study, bee foraging preference was correlated with essential amino acid content [140]. These preferences might facilitate transfer of linked traits into outcrossed populations.

Another counterintuitive approach would be to use plant pathogens to select for plant lines that enhance the growth of debilitated (for example, auxotrophic) strains of the pathogens. Plant pathogenic bacteria and fungi are often capable of growth on minimal media without amino acids. However, mutants of Ustilago or Pseudomonas auxotrophic for a particular amino acid can be used as bioindicators of amino acid levels in a breeder's population. Genetic libraries of plant pathogens (e.g. Ustilago maydis, Pseudomonas syringae, and Ralstonia solanacearum) provide a wide range of auxotrophic strains to choose from. The usefulness of this method has not yet been demonstrated.

7. Beyond Crop Improvement: Enhancing Plant-Product Nutritional Quality

Horticultural practices and harvesting crops at the optimal state of maturity are obvious considerations for optimizing nutritional quality of plants [141]. In addition, post harvest processing of plant tissues has been used for millennia to enhance nutritional quality via either the release of nutrients that may otherwise be bound by plant tissues or by elimination or destruction of toxins and anti-nutrients. These include cooking (thermal processing), fermentation, germination, milling, and soaking of plant parts - and of seeds in particular. For example, thermal processing is well-known to enhance the nutritional quality of grain legume proteins by inactivating trypsin and haemagglutinins [142]. Heating can also destroy anti-nutrients such as goitrogens, thiaminases and phytates [143]. Germination of seeds (sprouting) exploits the natural breakdown of food reserves for plant growth and is accompanied by an increased activity of many enzymes such as amylase, protease, phytase and lipase that can enhance nutritional value of seeds as food for humans [142]. However, post harvest processing is not always advantageous for nutritional quality. A Pan American Health Organization publication summarizes the lability of fats, proteins, amino acids and vitamins with regard to conditions of food processing [144]. Salt, heat, alkaline or acidic conditions, light, and copper cooking utensils can decrease concentrations of vitamins A, C, B₁ and B₂ and of folate and carotenoides, for example. The digestibility of some proteins, such as kafirins (prolamin storage protein) in sorghum, can be reduced via heating [145]. Nevertheless, post harvest processing is an important strategy for balancing the physiological constraints of plants for their health and vigorous growth with the nutritional needs of humans. We focus below on the particularly interesting possibilities offered by fermentation.

8. Toward Humanistic Nutrition

Many of us who have become agricultural scientists were motivated by the challenge to ‘solve the world food problem’ or to ‘feed the planet’. This goal is evolving beyond the objective of providing caloric diets for bare existence. Today the crucial challenge is to more optimally nourish humans, to provide optimal fuels and building blocks so that sub-optimal nutrition does not impair the functioning of human minds and bodies and prevent the attainment of full human potential.

We have described some of the initial efforts to improve the nutritional value of crops as food for humans, however, we believe that there is tremendous potential for significantly more nutritional enhancement of crops. But this enhancement will not occur as long as maximum and stable yield is the over-riding driver of the economic competitiveness of plant varieties. Some more powerful driving force is needed to trigger a change from scattered, piecemeal improvement of individual nutrients in a multitude of foods to creating more complete foods that provide the highest overall balance of necessary nutrients. This is especially important for peoples with access to a limited diversity of foods, be it for reasons of availability, culture or choice. One driver for enhanced nutritional value of crops may be the self interest of subsistence farmers who largely grow crops for their own consumption, which places them outside the influence of quality standards set by marketing boards. It should also be kept in mind that the nutritional value of staple crops fed to animals influences the nutritional value of the animal products utilized for human food, which is an extremely important factor for the nutritional state in developing and developed countries.

To meet the challenge of optimally nourishing human potential, the ties among the scientific and socio-economic disciplines related to food and diet - including agriculture, food processing, food transport, sociology, nutrition, and medicine – need to be much more integrated into approaches to food production that address key attributes of the human condition. One of these key attributes is that human potential is in large part defined by optimum biological functioning of the human body. A second of these key attributes is the human desire for self-determinism. ‘Humanistic nutrition’ is the name we propose for a food production system that addresses and integrates these attributes of the human condition. The tools available to implement such a humanistic nutrition project are partly the products of basic research in genetics, plant physiology, biochemistry, and the emerging new integrative field of systems biology [46, 155]. The traditional fields of research have diverged into disparate and often poorly-communicating scientific disciplines such as food science, plant genetics and breeding, plant pathology, soil science, nutrition, toxicology, food microbiology, epidemiology, human/animal/plant biochemistry, and various fields of medicine. The goals of each discipline have largely become compartmentalized and most research, publication and funding mechanisms tend to reflect this stratification. The US National Science Foundation has recently increased funding for multidisciplinary approaches, to encourage investigators to overcome the tendency of scientists to stick with ever narrower subjects, with which they are comfortable. To advance ‘humanistic nutrition’ these all disciplines must somehow also be brought to interact more effectively with the health and medical sciences, as well as with the socio-economic sciences and government bureaucracies. Much greater understanding of optimum human nutrition in health, disease prevention and disease must be emphasized in all medical training and the medical establishment must move from a system of treatment to a system of prevention and health optimization. Farm subsidies or food aid programs, directed principally or even exclusively toward crops with more optimal nutrition, might be drivers for the increased interaction of these disciplines. It should also be kept in mind that the nutritional content of staples that are fed to domestic animals has a very large bearing on the nutritional value of the animal products for human consumption.

Solving the world food problem has been focused virtually entirely on the noble goal of alleviating hunger. The second half of the problem, optimally nourishing humans, and hence their potential, amounts to elevating the overall quality of existence in human health and productivity. If the elevation of nutrition is even partially achieved, this will likely have beneficial impacts on attainments in education, will enhance economic development, and will foster the pursuit of happiness and furthermore, do all of this in a sustainable manner. The elevation of human health will reduce the need for medical interventions, enhance the functioning of healthier immune systems, and promises to lower the cost of medical care. Thus, the stakes are very high.

The impediments to enhancing overall nutritional quality of plants are also numerous. These include lack of will and insufficient collaboration among many relevant scientists, patent thickets that hinder collaborations, the reduction of private foundation support during times of economic recession, sudden increases in the cost of phosphate and nitrogen fertilizers with fluctuations in the price of oil, higher disease and pest susceptibility of the most nutritious crops, the lack of enthusiasm for genetically engineered crops in some quarters, and a thicket of government regulation. However, the challenges of creating plant varieties and plant-food production systems in support of humanistic nutrition, and awareness of the critical importance of nutrition for enhancing the quality of life of people across the planet, might well attract a new breed of committed scientists, more focused on tackling novel interdisciplinary paradigms for linking crop and human development. It follows that new policies and approaches to achieve comprehensive training of talented scientists are clearly needed. Better training of health professionals about the importance of nutritional impacts on minimizing inflammation and chronic disease could also provide a means to help turn the economic drivers toward better health through better food.

Part of the challenge in creating a plant-based humanistic nutrition will come through the effort required for validation of the impacts of enhanced nutritional quality of foods on human potential. Such validation will require increasing the linkage and interactions between guiding the production of improved plants with the needs of the biomedical medical sciences. Via this link, humanistic nutrition might play an important role in elevating the attractiveness of the plant and agricultural sciences for young researchers and to more clearly illustrate the importance of these disciplines to addressing world class problems. Validating the benefits of enhanced nutrition on animal health is relatively straightforward, in that diet can be controlled and computer driven formulations are commonly used. Validating the benefits of enhanced nutrition on human potential will involve epidemiological approaches and some intervention to confirm the improved nutritional status of populations, who benefit from improved foods. This type of validation is planned in the context of the HarvestPlus program (www.harvestplus.org) and has also been realized for populations benefiting from QPM (for example, [156]). With criteria for positive validation of health effects, foundation and government grants could require a human nutrition component to plant breeding research. Benchmark physiological assays for effects of nutritional factors on human health could include serum levels of essential amino acids and fatty acids, assaying for a “master regulator” that starts a cascade of events when any one amino acid becomes deficient [157] as well as assays for zinc and other mineral deficiencies (measured in hair). Indicators of basic physiological response could be eventually coupled to socio-economic and public health indicators such as cognitive capacities, frequency of acts of violence, rates of infectious disease and responsiveness of the immune system, for example [30, 158]. These are just a few of the possible impacts of enhanced nutrition on society. Malnutrition is clearly not the only limiting factor in attainment of full human potential and nominally well fed people could also benefit from optimized human nutrition. Thus, a concerted multidisciplinary effort to promote humanistic nutrition in an unprecedented fashion sets an attractive stage to investigate the complex interactions of human nutrition, genetics, health and behavior under diverse environmental and cultural contexts. Mechanistic understanding of biology has been growing at an exponential rate in the “post-genomic era”. As scientists, working in concert, we have before us an opportunity on an unprecedented, never before known in human history, to actively promote the development of health, well being and human potential for the benefit of all.