News Focus
Chemistry confronts global food crisis CHEMRAWN II brings scientists and representatives of the world agricultural system to Manila to discuss how chemistry can be harnessed to increase future food supplies James H. Krieger C&EN, Washington
In the world today, 450 million people are on the edge of starvation or suffer from malnutrition to the extent that it affects their mental and physical processes. Some 10 million children die each year because of malnutrition, hunger, and associated diseases. At least 600 million to 650 million people are likely to be seriously undernourished by the end of this century. These statistics from the Food & Agriculture Organization of the United Nations are staggering. So are the implications. If food production is to meet the demands of burgeoning world population, it must be increased over the next several decades by four times current food production to accommodate both a doubling of the population and an increased demand brought about by a higher standard of living. And this must be done without adding significantly to the amount of land that currently is in agricultural production. It is against this backdrop that CHEMRAWN II took place in Manila early this month. CHEMRAWN is the acronym for the Chemical Research Applied to World Needs program of the International Union of Pure & Applied Chemistry. Jointly sponsored by the International Rice Research Institute at Los Banos, the Philippines, the international conference was organized to deal with the theme, Chemistry and World Food Supplies: The New Frontiers. "If we are to increase food production fourfold, and not increase available land significantly, this means more intensive farming," says Bryant W. Rossiter, chairman of CHEMRAWN II, and director of the chemistry division at Eastman Kodak's research laboratories in Rochester, N.Y. "And generally speaking, more intensive farming means more chemical input," he adds. Food production incorporates a great variety of disciplines. And chemistry is a strong component of
CHEMRAWN: Chemistry solving world problems The CHEMRAWN concept—chemical research applied to world needs—was born in 1975 in Madrid. At a meeting there of the International Union of Pure & Applied Chemistry, the union took note that what was once of interest just to chemists now is of interest to the entire world. It also was decided that bringing chemistry to bear on world problems required more than just a meeting of scientists. To be effective, the enterprise had to deal with the whole human system. The first CHEMRAWN conference on future sources of organic raw materials took place in Toronto in July 1978. CHEMRAWN III is scheduled for June 1984 at The Hague, the Netherlands. It will deal with resource material conversion to meet future needs: (bio-) chemical process bridges. Beyond that, other CHEMRAWN conferences are being planned on chemistry of the resources of the oceans, the molecular basis of human disease, and the chemistry, acquisition, and preservation of water resources. For CHEMRAWN II, a proceedings volume will be edited by L. W. Shemilt of McMaster University, Ontario. The book will be available from Pergamon Press early in 1983.
nearly all of them, as well as being a discipline itself. But CHEMRAWN II had to do with more than just food science; it had to do with the entire agricultural system. Thus, the conference drew representatives of government agencies and funding institutions, as well as scientific experts from universities, research institutes, and industry— chemists, biochemists, agronomists, entomologists, soil scientists, nutritionists, and many more—all told, the movers and shakers of the world food system. Some 700 delegates came from 40 or so countries, developed
and developing, to grapple with the problem. The problem is short term: How to augment and expand what W. David Hopper, World Bank vice president for South Asia, calls the "betters." These include maintaining the research momentum to provide better irrigation, better crop varieties, better use of fertilizer, better methods of controlling pests and pathogens, and many more—in short, the technologies that have provided such great increases in food production in recent years through the so-called green revolution. The problem also is long term, 30 years and beyond: How to achieve the quantum leap to new technologies (such as genetic engineering) that will make it possible to cope with immense future demands. In approaching the problem the way it did, CHEMRAWN II was striving for three goals. One goal was to use experts to sort out those areas that would have the greatest chance of success, those that would be most cost-effective, and to make recommendations to the parties who fund research as to what their possible priorities might be. A second goal was to bring together scientists and decision makers from developed and developing countries to determine which research areas in developing countries do not require hefty expenditures, large factories, or heavy capitalization. "There is no way possible, even with modern technology, that the major grain-producing and -exporting areas in the world— the U.S., Canada, and Australia— could become the food basket of the world," Rossiter says. Moreover, he adds, developing nations desire to be self-sufficient in food. The third CHEMRAWN goal was to find mechanisms for improving technology transfer under conditions acceptable to all parties involved. Hence, Rossiter says, industry was included as a major partner in the search for ways of increasing cooperation among governments, industries, and funding agencies. For technology Dec. 20, 1982 C&EN 9
News Focus Chemistry and food: Complexity at many levels If a single word can be used to characterize food production, that word is "complexity." This attribute can be seen, for example, at the macro level—involving politics, economics, and sociology. It operates at the micro level—involving agronomy, entomology, botany, and many more. And it is expressed elegantly at the molecular level—through chemistry, plant physiology, molecular biology, and their counterparts. In few agricultural areas is that complexity—the interplay within and between levels—more clearly expressed than in pest and disease control. One striking example is the interaction among pests, diseases, and weeds. Such interactions are not rare events, says John R. Finney, biological group manager of Imperial Chemical Industries' plant protection division in the U.K. Indeed, they are frequent, he points out, particularly if the indirect effects of one damaging organism on another are taken into account. It is possible, he says further, to find examples of nearly all the 18 possible interaction combinations, positive and negative, among the three components. Furthermore, the interactions between pest organisms are extremely diverse and no formal classification system has been developed. The interactions may be direct or indirect, single-step or multiple-step, and natural or induced—the latter particularly, but not exclusively, as a result of the use of agrochemicals. For example, there is direct competition. When powdery mildew was controlled on barley leaf surface by the specific, systemic fungicide ethirimol, it resulted in an increase in a fungal pathogen caused by decreased competition on the leaf surface. There is indirect interaction. Activities of one organism provide microenvironments in which other organisms thrive. For example, aphids excrete honeydew, which serves as the growth medium for molds that reduce the quality of many crops. And stem borers create microenvironments favorable for development of many diseases, including bark cancer of cocoa, and wood rot of tea. Weeds are sources of virus inoculum for crop plants—for example, three very common weeds in the U.S. are carriers of tobacco rattle virus and two of them also are carriers of potato virus X. Induced interaction is another of the possibilities. Control of a nematode, which infected rice and a weed species, stimulated weed growth more than rice
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growth and the increased weed competition resulted in reduced rice yields. The herbicides EPTC and dinoseb, used to control weeds in leguminous crops, alter the susceptibility of navy beans to a pathogenic fungus by increasing exudation of electrolytes, amino acids, and sugars from root and nearby tissues. Not to be ignored, says Finney, is the effect of external factors on pest, disease, and weed interactions. Degree of cultivation, irrigation, fertilizer use, crop variety, rotational practice, and agrochemical use have huge effects on crop plants and their complexes of damaging and beneficial organisms. "Their importance," he says, "cannot be overstressed." In the end, says Finney, crop production is an industry, and farmers employ the most cost-effective solutions available to their problems, provided the solutions are judged to be acceptably safe in the environment. Farmers tend to prefer broad-spectrum agrochemicals because they usually are cheaper than several more specific products, even though the latter often have less effect on nontarget organisms. The future, Finney says, undoubtedly will see continuous progression toward integrated pest management. But progress, which will be based on longterm, multidisciplinary programs, is likely to be slow. J. C. Davies of the Centre for Overseas Pest Research of the Overseas Development Administration, London, agrees. It would, he says, be erroneous to suggest that integrated pest control is a panacea. The method is logical, but calls for concerted effort for it to be widely applicable on food crops. And implementation demands considerable flexibility. Integrated pest control, by definition, uses a multicomponent approach and presupposes a knowledge of the ecosystem, crop, and pest, Davies explains. Integrated pest control implies a conception of a managed resource as a component of a functioning ecosystem, where action is taken to restore, preserve, or augment checks and balances in the system, and not necessarily to eliminate species. It requires an understanding that the mere presence of a potential pest organism capacity does not constitute a pest problem, unless verified by an economic or other yardstick. Also required is automatic consideration of all possible pest control options before action is taken, and application of all possible techniques in as compatible a manner as possible.
Pathak: plant resistance to insects The plea at this time, Davies says, must be for more base data to be gathered on the components of integrated pest control on food crops in developing countries and for more targeted and sustained research. "It is an unfortunate truism," Davies maintains, "that where a crop is a subsistence food, the amount of information on any aspect of it—agronomic, pestwise, or otherwise—in a subsistence grower situation is small." It is vital, Davies says, to encourage the involvement of many disciplines— plant breeding, agronomy, pesticide chemistry, socioeconomics, economics, and more. Such involvement is crucial for formulating strategies that in the long term are socially, environmentally, politically, and economically best for the bulk of the farmers who produce the bulk of the world's food for local consumption—namely, the small farmers of limited means operating in marginal conditions, where inputs are few and risks high. But agriculture is nothing if not complex, and Davies notes that pest control is but one aspect of a package of agricultural technology, with integrated pest control itself a package. Even the components in the agricultural technology package are themselves subject to rapid change. Almost everywhere at present, Davies says, donor agencies and world bodies are stressing change in traditional systems—encouraging increased fertilizer use, commissioning irrigation projects, improving mechanization, or simply introducing new crops and cultivars. In these situations, he says, pest
Finney: crop production is an industry control strategies must be dynamic and perspectives realistic. Davies notes that an important issue in pest control is the rapid growth of knowledge in the field of plant breeding and the development of pest-resistant cultivars. But the complexities of the biochemical basis of pest resistance are only beginning to be unraveled, according to Mano D. Pathak, director of research and training at the International Rice Research Institute in Manila. This lag has been due partly to the complexity of the factors contributing to resistance, Pathak says, but it also has often been due to lack of close collaboration between entomologists and organic chemists. For studies on the chemical basis of
Beevor: semiochemical controls
resistance, a detailed analysis of the various aspects of insect/host plant interaction is a prerequisite. Moreover, the situation is further complicated because pest resistance may often be governed by different chemicals in different plant varieties. Nevertheless, says Pathak, during the past few years, it has been demonstrated that plant resistance to insects can play an immense role in practical pest management. Also, there are indications that the chemicals responsible for resistance to insects in certain rice varieties have the potential of becoming commercial pesticides. Pest resistance is of three general types. One type is nonpreference, called antixenosis, in which a plant has characteristics that make it unattractive to insect pests for oviposition, feeding, or shelter. A second is antibiosis, in which the host plant adversely affects the bionomics of the insects feeding on it. And the third is tolerance, by which the damage to the host plant is only slight despite its support of an insect population large enough to damage susceptible hosts severely. At present, Pathak says, there is no evidence that the tolerance of plants to insect attacks is influenced by any chemical. Chemicals are involved, however, in antixenosis and antibiosis; and their effects have been observed in studies of resistant plants. Stimulants to feeding, for example, are glycosides, organic acids, flavonoid aglycones, carbonyls, phospholipids, or terpenoids. They are generally secondary substances, not known to have a primary function for plants or insects. The resistance of certain rice varieties to the brown planthopper has been attributed to lower contents of aspartic acid, asparagine, valine, alanine, and glutamic acid, all of which are feeding stimulants. Feeding deterrents also play a role. A higher concentration of oxalic acid has been shown to inhibit feeding by the brown planthopper on a resistant rice variety. And the resistance of sorghum to grasshopper feeding has been shown mainly as a result of dhurin, a cyanohydrin glucoside. Ovipositional stimulants and deterrents have an effect. For example, an assay of various fractions of carrot leaf extracts against the carrot fly found that methyl isoeugenol and asarone—two phenyl propanoids—stimulated oviposition. Certain rice varieties resistant to the striped stem borer have been shown to contain an ovipositional deterrent factor, whereas susceptible varieties contain some ovipositional at-
tractant factor; spraying of the extracts from these plants on rice varieties dramatically altered the ovipositional behavior of the borer moths on them. Antibiotic factors include toxic chemicals, among them alkaloids, phenolic compounds, flavonoids, and terpenoids. And insect nutrients may have a possible role. For example, varieties of rice resistant to the brown planthopper were shown to have a lower asparagine content than those of the susceptible varieties, and young planthopper females emerging from nymphs reared on the resistant variety with a lower asparagine content had underdeveloped ovaries containing very few mature eggs, whereas those reared on susceptible varieties had normal ovaries with full complements of eggs. A different approach to insect control that seemingly has much potential is the use of pheromones, the communication chemicals of insect species, and other such behavior-modifying semiochemicals. They can be used in baited traps for population monitoring, or they might be used for mass trapping. Mating disruption is another possibility. However, says Peter S. Beevor of the Overseas Development Administration's Tropical Products Institute, London, despite the many factors apparently favoring pheromone development, their practical application has been far more complex and has taken far longer than originally anticipated. Indeed, Beevor points out, certain of the intrinsic factors that make semiochemicals so suitable as pest control agents in fact operate as strong deterrents of commercial development, although some exceptions can be foreseen. For example, the minute amounts of pheromone required in trapping systems are of no real interest to larger agrochemical companies, Beevor notes, and firms supplying traps typically are small venture companies. Even these rely on obtaining a large markup on complete systems of trap, dispenser, and pheromone. For communication disruption, larger amounts of pheromone are required. But here, Beevor says, the specificity of pheromones is the problem. In general, a different product will be required for each pest, so the market for any one product is limited. Thus, he says, the use of semiochemicals as control agents will tend to be restricted to major crops or crops of exceptionally high value, and to those with one or two dominant pest species or one species in a pest complex that is difficult to control with conventional insecticides.
Dec. 20, 1982 C&EN
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News Focus transfer to take place, he explains, it must take place on a fair and equitable basis. If it slants too strongly in the direction of industry, the developing nations aren't going to be interested. If, on the other hand, conditions are so severe that industries can't sustain their research efforts, which are very costly, then they will lose interest. The first fallout from CHEMRAWNII may not be long in coming. Even as the conference in Manila was ending, a group of delegates was preparing to head to Los Banos for a three-day workshop to be held at the International Rice Research Institute. The workshop—on chemical research priorities for improving food supplies in developing countries— was organized by the U.S. National Academy of Sciences' Board on Science & Technology for International Development (BOSTID) at the invitation of and with funding from the U.S. Agency for International Development. For the workshop, BOSTID brought together 35 participants from developing countries in Asia, Africa, and Latin America, and 16 from developed countries—all of them experts in one or another of the four topical areas to be covered: soil fertility and plant nutrition, plant growth regulators and plant-pest relationships, food science and technology, and aquaculture and integrated farming systems. The aim of the workshop was to build on the discussions and conclusions of CHEMRAWN II to identify specific high-priority chemical research needs that bear on agricultural productivity and food technology in developing countries. David Mog,
common problems of chemistry and food supplies. But, as CHEMRAWN II speakers emphasized continually, science and technology are only one of several considerations in increasing food production. For example, David Hopper points out that the stool of agricultural progress in developing countries has three legs that have come to light in the past 20 years. One leg of the stool, he says, is technology. It must be technologically feasible to increase yields and to raise output. And, he adds, there must be a transfer mechanism between the farmers' fields and the research stations or scientists' laboratories, where the technologies are discovered, developed, and refined. A second leg of the stool is economics. Incentives must exist, HopRossiter: more intensive farming per points out. Just telling farmers to BOSTID staff member in charge of raise yields and increase their farming the workshop, explains that although activity because there is a national biotechnology is an important area need for food and a lack of foreign for consideration, the current work- exchange to import it is not enough, shop was designed to avoid covering he says. There must be some price the same ground as that of a work- mechanisms, some profit mechashop on priorities in biotechnology nisms, with the kind of assistance by research for international develop- which the farmer will find it profitament, held by BOSTID this past July ble to undertake the risks of innovation. in Washington, D.C. Rather, it is attempting to comThe third leg of the stool, Hopper plement that workshop. The three- says, is organization. Basically, it's the part aim is for workshop participants question of how fertilizer gets delivto identify the research projects ered. Behind increases in fertilizer judged to have highest priority in use, he explains, must lie an industrial their respective countries; to suggest policy for a country; it either produces specific opportunities for research or it buys. There must be a transporcollaboration that would make ef- tation system—a whole set of instifective use of chemical research to tutions—that carry fertilizer from the solve some of their food production factory or port of entry out to the problems; and to evaluate the po- farmers' fields. This system must be tential for an international network accompanied by credit to enable a of cooperating scientists working on farmer to buy the fertilizer. Also, if a farmer is going to buy the fertilizer and pay back the credit, he must have a market to sell his products. The stool must have all three legs. If any leg, or any part of one, is missing, agricultural progress falls in jeopardy, Hopper says. The point is emphasized by M. S. Swaminathan, director general of the International Rice Research Institute. "The magic wand that can eliminate hunger," he says, "is not in the hands of scientists. It is in the hands of political leaders." A related point of view comes from James C. Ingram, executive director of the Food & Agriculture Organization's world food program. Appropriate technologies must be found, he S. Nagakura, president of IUPAC; Arturo R. Tanco Jr., agriculture minister of the says, Phi- to increase agricultural production in developing countries— lippines; Bryant W. Rossiter, chairman of CHEMRAWN II; Ferdinand E. Marcos, prèsparticularly those that reduce proident of the Philippines; and Cesar E. Virata, prime minister of the Philippines, listen duction costs and that will benefit to a speaker
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small farmers more than they have so far benefited from the green revolution. But, he says, uwe need constantly to remind ourselves that we are involved in a no-less-than-gigantic effort to modernize traditional societies whose values and complexity we only partly understand." Thus, Ingram says, it is not altogether self-evident that future growth in agricultural output in developing countries depends upon much greater expenditure on research. For example, a number of studies, he notes, suggest a strong, positive correlation—in countries as far apart as Brazil, Kenya, Nepal, and Malaysia—between primary education and increased farm output, with rates of return sometimes as high as 20%. This, he says, fits with similar studies on the relationship between educational levels—of the mother sometimes even more than the father— and progress in other economic and social sectors. Ingram says he would be the first to argue that the progress made to date would not have taken place without the new technologies developed by research. However, he adds, "it also is arguable that in the future the main effort should be concentrated on the application at the farm level of existing knowledge, including knowledge about appropriate farming practice and systems." Thus, he says, it would be wise for those seeking additional funds for agricultural research not to overemphasize the importance of increased food production per se without showing awareness of the complexity of the relationship between increased food output and reduced hunger and poverty. There is indeed much margin for improvement in food production in just broader and more intensive application of current technology. As Ingram notes, an enormous gap exists between yields obtained in agricultural research stations and those obtained by farmers. There also is a considerable gap between yields obtained by the best farmers and average yields. And, as Swaminathan points out, there has been substantial progress so far. For example, he emphasizes that although according to the latest Food & Agriculture Organization estimates, the number of seriously undernourished people in developing countries rose by about 75 million in the 1970s, during the same period it was possible to nourish fairly adequately more than two thirds of the 230 million people who were added to the population in these countries.
two and a half times the present 4.5 billion, or between 10 billion and 12 billion. After that, the population probably will fall. "That's too many people," Porter says, but it is the limit. Hopper, however, is not so sanguine. "I think it will be another 100 years," he says, "before we reach the level of stabilized populations." It is sobering, Hopper says, to recognize that today in Asia—the arc from Afghanistan to Japan, including the subcontinent and China, but excluding Soviet Union Asia—the population has just reached about 2.5 billion—the total world population in 1950. Asia, he says, added almost 800 million people in the past two decades. Between now and 2000, Asia will add about 380 million people. The Von Planta: government cooperation industrial countries, including Japan, will add 80 million in that period. "With that number coming into the Also, food production succeeded in keeping up with population growth in reproductive age group," Hopper about half of the developing asks, "where are we going to put [their countries—and the more successful offspring]? And what is the implicaones have more than half of the tion of that for the long-term growth rates of population?" world's population. It is true, Hopper says, that birth Still, the specter of overpopulation looms ahead. And not all observers rates now are beginning to drop in view the future in this regard in ex- most Asian countries, although not in most African countries. Births are actly the same way. Sir George Porter, director and dropping from levels of between 40 Fullerian Professor of Chemistry at and 46 per 1000 to between 30 and 40 the Royal Institution, London, points per 1000. China is an exception, with out that the population problem is a rate substantially below 30. But it also is true, Hopper adds, expected to be a temporary one. The birth rate is falling nearly everywhere, that death rates still have a long way he says, and in fact has never risen. to go. The death rate in China is What's happened is that the death about seven per 1000; in the bulk of rate has fallen. It can't, however, go South Asia it is about 15 per 1000. "I on falling. When everyone lives out a do not see the decline in death rates full lifespan, it will stabilize. Thus, stopping that easily," he says. As for the question of food, Hopper demographers expect the population of Earth eventually to reach about notes that population growth is only one blade of the scissors. There is, he says, a much more insidious, much more important growth rate, or component of growth, in food demand. "What happens," Hopper asks, "when people get higher incomes? Because they will have higher incomes. Development is taking place." Growth rates of Asian countries, he points out, have been reaching 6% per year, substantially ahead of population growth. Per capita incomes are rising, and as they rise, it is quite clear what happens: People demand better quality diets. They move from taking just 400 lb of grain per year to demanding more milk, more meat, and more poultry products, with their higher grain equivalents. "There's no question in my mind," Hopper says, "that 20 years from now, Hopper: rising incomes, food demand demand will be up from 400 lb [of Dec. 20, 1982 C&EN
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News Focus Chemistry and food: Direct application most obvious role Chemicals supplied directly to plants represent one of chemistry's more visible roles in food production, whether the chemicals are fertilizers, herbicides, or plant growth regulators. In developed countries, these substances have racked up countless agricultural successes. Nevertheless, many areas for development remain, especially for meeting needs of developing countries. A major thrust in fertilizer development is to make the materials more cost-effective, according to Donald McCune, managing director of the International Fertilizer Development Center in Muscle Shoals, Ala. These efforts are aimed at formulation and manufacturing of the materials, as well as their handling, storage, and distribution. Nitrogen loss, for example, is a significant constraint on cost-effectiveness. Such losses can occur through ammonia volatilization, nitrification-denitrification, leaching, and runoff. In some cases, McCune says, only about a third of the applied nitrogen is actually utilized by the crop. Ammonia volatilization is a prime cause of nitrogen loss, particularly when urea is used to supply nitrogen for flooded rice. It also can be important for surface-applied urea on unflooded upland soils. Urea, McCune explains, is converted to ammonia and carbon dioxide by urease, which is present in soil. The ammonia can escape to the atmosphere through the floodwater. Experiments are being conducted with urease inhibitors, added to urea in amounts ranging from 0.5 to 5 . 0 % . Among the still-too-costly chemicals being tested as inhibitors are phenol phosphorodiamidate, catechol, thiourea, dimethylphenol, and benzoquinone. In preliminary greenhouse tests, McCune says, phenol phosphorodiamidate was "spectacularly successful" in decreasing ammonia losses from flooded soils from 3 0 % without the inhibitor to about 4 % with it. Nitrification inhibitors are another approach being studied as a way to prevent nitrogen loss. In this case, McCune explains, nitrification is a twostep biological process in which ammonium ion first is converted to nitrite by nitrite-forming bacteria; then the nitrite is converted to nitrate by nitrate-forming bacteria. In flooded soils lacking air circulation, the nitrate ion can be converted to gaseous nitrogen and nitrous oxide by microbes that destroy the nitrate ion to obtain oxygen, thus allowing
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the nitrogen to be lost to the atmosphere. Compounds being tested as nitrification inhibitors include a sulfathiazole-formaldehyde reaction product, 2chloro-6-(trichloromethyl)pyridine, dicyandiamide, and nitrapyrin. As with urease inhibitors, the nitrification inhibitors show promise. But two basic problems remain, McCune says. They must be made more cost-effective, and a practical method must be developed to incorporate them into nitrogen fertilizers. The work on such inhibitors is only one effort among many taking place across a broad fertilizer development front. Some other examples: reducing urea hydrolysis or ammonia volatilization loss by combining urea with a metallic ion in a complex that also might provide micronutrients; manipulating phosphate fertilizers to make them more economically and agronomically optimum for the humid tropics and acid soils than those developed for temperate agriculture; preventing dusting, caking, or moisture absorption of weak granules of urea or ammonium nitrate, which may become a big problem for humid tropical countries, by incorporation or application of conditioners; and developing catalysts for ammonia synthesis that would involve highly reactive metal powders effective at low temperature and pressure, making the process less energy intensive. Herbicides present a different picture in relation to developing countries. In 1980, 9 3 % of all herbicides (by value) were used by Europe, North America, and Japan. Relatively little is used in developing countries. And, says J. R. Corbett, director of R&D at FBC Ltd.'s Chesterford Park Research Station, U.K., because of the cost of discovering and developing new herbicides, it is likely that they will become available for the lesser-developed parts of the world only if they are developed first for use by the advanced countries. Still, Corbett notes that in many places in the world, the size of a person's holding is governed not by the amount of land bought, but by how much can be planted before the weeding must begin. This, he says, suggests that herbicides should find a ready use. Although herbicides aren't the sole answer to weed problems, Corbett says, they are a major input in most control systems, and it is essential that new compounds continue to be developed. He points to five recent major advances that are significant: commercial production of a chiral compound—some-
thing normally very difficult to produce economically—for control of wild oats; post-emergence herbicides for grass weeds; the translocated broad-spectrum herbicide A/-phosphonomethylglycine (glyphosate), with the advantage, among others, that its site of action is the enzyme 5-(carboxyethenyl)-3-phosphoshikimate synthase, an enzyme not found in animals (thus contributing to the compound's safety); development of safeners, or antidotes, a way of chemically conferring selectivity that increases the safety of a herbicide to a crop but doesn't alter significantly its ability to kill weeds; and development of chlorsulfuron, a sulfonylurea herbicide with a very high level of activity. The latter development points in one direction to the future. There are two reasons, Corbett says, why further highly active herbicides are likely to be sought. On environmental grounds, it must be preferable to apply the minimum amount of any chemical. Also, if only a small amount of chemical is required, it follows that more complex, and therefore more costly, molecules can be synthesized as potential herbicides. The future presents a number of challenges for herbicides. But, unlike with pesticides, resistance by target species isn't likely to be a significant one. There is a relatively slow rate of development of resistance to herbicides, compared to other pesticides, Corbett notes. This situation, he says, is probably due to a combination of low selection pressure by the herbicide, lower fitness of resistant weed strains in the absence of herbicide, ability of susceptible survivors of herbicide treatment to produce relatively more seeds in the thinned population, and the large soil reservoir of susceptible weed seeds that will dilute out the seeds from resistant biotypes. Unsolved weed problems do, however, present a challenge. Among these are perennial weeds, water weeds (from a herbicide safety standpoint), parasitic weeds, and so-called volunteer weeds—the previous crop. It probably is a basically correct generalization, Corbett says, that, as herbicides are used more and more, the significant weeds come to resemble the crop—for example, wild rice and wild beet. Herbicides, Corbett says, are unlikely to have to cope with totally new crops, although they will be required to control weeds infesting improved strains of crops that will be developed. In contrast, he says, "there is no doubt whatsoever that new weeds will emerge in the future." They may arise by sudden genetic
change, accidental or deliberate distribution, chemical selection of particular species (now the most important factor altering weed problems), or cultural selection due to a broad change in an agronomic system. It should be possible, Corbett says, to discover herbicides that could act at an application rate of milligrams per hectare. Even if this theoretical possibility isn't achieved, he says, grams per hectare should become the application rate of the future, rather than the current kilograms per hectare. Herbicides represent the extreme in plant growth regulation. As a class, plant growth regulators hold a very broad potential for future development activity for directly applied chemicals. Plant growth regulators interfere with NickelI: new plant growth regulators the endogenous hormonal pattern in a plant. They can be natural or synthetic, and the effects can be morphogenetic or metabolic. The idea of interfering with a plant's hormones isn't new. The use of indolebutyric acid to induce rooting in a wide variety of plants dates back to the 1920s. But industry has been looking harder at such compounds of late, says Louis G. Nickell, vice president for R&D at Velsicol Chemical Corp., Chicago. With the successful introduction of plant growth regulators for some important crops and because of their commercial uses—for ripening in sugarcane, for example, and for increasing the length of time of latex flow between tappings in rubber trees—industry increasingly has turned its interest to the search for new plant growth regulators within the past few years, Nickell says. McCune: preventing soil nitrogen loss He points out, however, that the task is more demanding than that of searching for a new herbicide. Complexity and costs, he says, are estimated to be 10 to 100 times greater. Nevertheless, the field is extremely attractive and has large potential payoffs. The potential is extremely diverse. Flowering can be hastened, slowed down, or prevented; plants can be made to grow taller or shorter; flowers and fruits can be made to fall off prematurely or to stay on; maleness or femaleness can be increased; sprouting can be prevented or induced; rooting can be initiated or prevented; senescence can be initiated early or delayed; metabolic products such as sugar can be increased or decreased. Johan Bruinsma, a professor in the department of plant physiology of the Agricultural University, Wegeningen, the Bruinsma: synthetic plant hormones Netherlands, explains that at least five
different groups of phytohormones (plant-produced hormones) interplay in the hormonal pattern. Three are derived from the mevalonate pathway: Cytokines are adenine derivatives with an isoprene unit as a side chain; abscisins are trimers of these units; and giberellins are tetramers. Two other groups are derived from amino acids: auxins and ethylene, which, Bruinsma maintains, must be regarded as a true hormone. Hormones produced at a particular site can be translocated through vessels, from cell to cell, and in the case of ethylene, in the gas phase of the plant. At other sites, they can interfere in the local hormonal patterns or be inactivated by breakdown or conjugation. As inactive conjugates, they can be stored and later possibly set free again and redistributed as active materials. "It is particularly our lack of understanding of these problems of hormone transport and metabolism," Bruinsma says, "that is at present one of the main obstacles for progress in the regulation of matter distribution and organ vitality in plants." For application in field crops, however, phytohormones are less suitable than synthetic substances, partly because they are liable to metabolic inactivation by the plant. Synthetic substances, Bruinsma says, often are much more stable in the plant and consequently their effects are more persistent. Synthetic substances can operate by simulating hormonal action or by affecting biosynthesis, translocation, or metabolism of a hormone, thereby changing the amount of a hormonally induced product. One problem with application of plant growth regulators is that because phytohormones exert a variety of effects, the regulators are likely to do so, too, leading to undesired side effects that might reduce or even remove the beneficial effect. Another problem is that when plant growth regulators are sprayed on foliage or applied to the soil, the molecules that penetrate the plant may be translocated to unexpected sites and exert undesired effects. Even if the desired effects are achieved, Bruinsma points out, application in practice can be hampered or even prevented by such other factors as different responses among varieties, toxicological danger for producer and consumer, and costs of production and evaluation. In practice, he says, plant growth regulators are being developed only for large crops of considerable economic value.
Dec. 20, 1982 C&EN
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News Focus growth rate, this will not be so for long, he says. Thus, a major concern must be the technological and associated policy problems that underlie the issue of food supply in these African nations. They are encumbered with soils that are very difficult to handle, range-management problems, and substantial livestock problems. Crop adaptations are necessary, and there is little possibility of major irrigation as in Asia. The fundamental problem in Africa, Hopper concludes, is to match a set of technologies with potential for the future with appropriate policies. If Hopper's overall assessment isn't exceedingly gloomy, however, it is based on certain assumptions. One assumption is that present research efforts will continue and be fruitful. This means that since current expenditures are running into diminishing returns on research, new aveNyle C. Brady, plenary session chairman for the CHEMRA WN meeting and senior nues as- and additional resources and larger expenditures will be necessary sistant administrator for science and technology for the U.S. Agency for International to maintain the research momentum. Development (right) is awarded the Presidential Award of the Golden Heart by Philippine president Ferdinand E. Marcos (center) during the plenary session. Brady This is effort applied to the "betters," former director general of the International Rice Research Institute in the Philippines he says, will add marginally to the at Los Bahos capacity to produce food. But, the total of the marginal gains should be grain] per capita to about 700 lb per nology, that the investment should be enough (provided a special effort is capita.'' It will be 700 lb, he says, if moving toward $2500 to $3000 per made for Africa) to stay ahead of population growth rates, on average, grain can be produced at the present hectare. price range. If not, food prices will "But," Hopper says, "if you start and feed most of the world's people. begin to rise worldwide in response to multiplying that by 200 to 300 million That's the technological side of the that pressure. hectares, you come up with some supply question, Hopper says. There The nearer term is perhaps not so very, very sizable amounts of money. also is a social and political side. great a problem, albeit with excep- And that's precisely the kind of agriMuch has been learned in the past tions and qualifications. New vari- cultural development expenditure 20 years on the role of various actions eties have raised grain yields sub- that governments are being asked to that governments can take to prostantially. And governments have make, that aid institutions are being mote agricultural growth and agriimproved land through the extension asked to assist in underwriting." cultural development. Hopper recalls, of irrigation. With irrigation, it is Although such efforts will continue for example, that 20 years ago, there possible to increase the intensity of to grow in Asia, he says, in Latin were a series of important governland use by improving yield per hec- America there still is a potential for ments, such as that of India, "that tare per day through a combination of land expansion—quite a substantial were quite happy farming the fields of intercropping, sequential cropping, one—especially if crops and varieties Kansas and Saskatchewan, living adjustment of maturity times, and so can be adapted to utilization of the ship-to-mouth on food assistance and forth. acid soils, and if technologies can be getting paid for doing it." They took Hopper expects that this approach found that will improve the livestock the food, he explains, sold it in their for Asia will be a satisfactory gener- potential and increase the livestock marketplace, and in effect re-lent the ator of increased output for the next carrying capacity of the soils. Hopper money they received for food. It was 20 to 30 years. He thinks that output doesn't foresee a major food problem an important item in balancing the can stay ahead of population growth. in Latin America in the next 30 government budget. But, he says, it will require a contin- years. Today, Hopper says, it's known uation of very substantial investAfrican countries south of the Sa- that technology and farm incentives ments in irrigation, investments that hara Desert, on the other hand, rep- are basic to what can be done in agriare substantially larger than those resent the great tender spot of the culture. The African nations generally needed for traditional irrigation sys- world, Hopper says. At present, the have to learn that fact. The policies of tems. He estimates that traditional expectation is that if this area got into most governments in Africa, he irrigation systems could be built in substantial difficulties, international maintains, have been policies against areas such as India or Bangladesh for food assistance from the reserves of agricultural growth and agricultural about $300 to $400 per hectare. The the surplus-food-producing nations, output; it is necessary to turn those amount now going into irrigation primarily in North America, could be policies around before much can be systems is about $1000 per hectare. made available to meet the food re- done to ensure even a return to forAnd, Hopper adds, there are some quirements of what is still a fairly mer output levels in Africa. who would argue that $1000 per hec- small population. There also is a social element in tare still is too little for today's techBut at the African population farmers' actions—a farmer's indi16 C&ENDec. 20, 1982
vidual role vs. his social role. In most of the developing world, farms are small and fragmented. It doesn't do very much good for one farmer to apply pesticides to his fields, leaving his neighbor's fields infested. Collective social action of some kind must be taken, Hopper points out, to handle the system. "We're not very good at finding out how that social action can be undertaken, how it is organized, and how it is handled," Hopper says, "but we will be before 30 years are over." He expects that there will be substantial movement in most of the developing countries toward the optimal mix between individual incentives to farmers and the social action that farmers must participate in if they are to gain the real advantages of new technology. An important element, not only of technology but of policy, is the nature of chemical industry contributions to future development. And, indeed, government policies are much in the minds of the industry's officials. "One thing is clear," says Louis von Planta, chairman of the board of Switzerland's Ciba-Geigy, Ltd. "Chemistry cannot simply be expected to solve the problem of the world's food by itself. It needs the active cooperation of governments." On the other hand, he says, "it is a fact that even governments will not succeed in finding practical solutions without involving the chemical industry." Von Planta outlines the roles he sees as necessary for governments and industry to play if there is to be a fruitful future collaboration. He is convinced that many of today's world food problems could be solved if the knowledge possessed by industrial enterprises could be exploited better and more comprehensively. But, he says, this desirable end often is prevented by technical aid being far too frequently regarded as a one-way street. Nobody today still holds the opinion that the state and industry are two independent institutions, von Planta says. Industry, he says, acknowledges that it is part of the state and is prepared, within the framework of its responsibility, to contribute to the objectives set by the state. For internationally operating companies, he adds, this means subordinating their business operations to the sovereignty of the governments of the host countries. This is especially true for the chemical industry. Moreover, von Planta says, since agricultural problems are complicat-
dialog, where profitability often is alleged to be synonymous with greed and exploitation of the weak by the strong. The chemical industry, von Planta maintains, stands ready to make investments not only in research and development but also in product information, toxicological data, safety instructions, and application techniques. However, it must have some reasonable opportunity to recover its investments through the sale of its products and services. "An enterprise is able to offer technical aid," von Planta says, "only if a country is prepared to guarantee the rights of industrial intellectual property and is further willing to give a fair return for the technical knowledge utilized." Drawing on French experiences, Swaminathan: a political magic wand Pierre Roessler, a member of the ed by the traditions and sociological board of Union des Industries structures existing in different Chimiques, provides examples of how countries, these traditions and the chemical industry and others, structures must be respected and, as given the proper environment, can far as possible, preserved. It isn't cooperate in technology transfer. He, enough, he says, for the chemical in- too, emphasizes that the combining of dustry to offer agricultural products, chemistry with the production of food such as fertilizers and pesticides, that cannot be reduced to mere technical are good in themselves. It must look solutions or simple trade problems, for solutions that meet the specific interacting as it does with socioecocircumstances and requirements of nomic systems. An example is that of pesticides the individual countries. Increase in agricultural yield and productivity and the numerous difficulties in the must not be given its head at the cost way of their general use. One difficulty is the fragmentation of the of existing social structures. On the other hand, von Planta says, market. In Nigeria, for example, 18 governments must recognize that million farmers each produce an avunder a market economy system, a erage of 500 kg of cereal per year. commercial organization must oper- There also is a lack of purchasing ate profitably if it is to continue to power. For the same overland disexist at all, and therefore to perform tance, the cost of transporting a pessatisfactorily. This is the point, he ticide in West Africa is eight times says, at which major misunder- higher than that in a European standings exist in the international country. And frequently, storage equipment is unsuitable. On the whole, the cost of a pesticide in relation to the value of production is five times higher for an African farmer than for a European farmer. Yet pesticides, Roessler says, could reduce post-harvest losses (currently estimated at 20% in developing countries) to 5%. And, he points out, it is precisely the developing countries that have the most vital need for this type of technical assistance. Roessler describes one specific cooperative example resulting in the adaptation of pesticides for use in ultralight volume. A problem faced by countries such as Senegal with a scarcity of water is that of using pesticides in the normally diluted form. It takes, for example, up to 1000 kg of water to dilute pesticides for treatOffermanns: outwitting microorganismsment of 1 hectare. Dec. 20, 1982 C&EN
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News Focus Chemistry and food: Words of caution on environment nutrition As with most technological endeavors, increasing the supply of food is not without its darker side. Although in this case benefits would seem to far outweigh risks, nevertheless there are environmental and nutritional considerations to be taken into account. One environmental consideration is that of pest management. "Clearly," says David Pimentel, professor of insect ecology at Cornell University's College of Agriculture^ Life Sciences, Ithaca, N.Y., "the continued use of various pest controls, including both nonchemical and chemical pesticides, is essential to food and fiber production in the world." But, he points out, in past decades, despite the use of both, pests have continued to destroy, during growth and in storage, almost half of all food produced in the world. The benefits to society from pest control practices are immense, Pimentel says, probably amounting to several billion dollars each year. However, he adds, as with all intervention that manipulates and controls natural species populations, some environmental and social costs result. More emphasis is being placed on nonchemical controls these days. But Pimentel points out that although chemical pesticides are known to cause more environmental and social problems than do nonchemical alternative controls, the use of nonchemical biological and cultural controls is not without risk. "The problems with nonchemical controls," Pimentel says, "have not received adequate attention." One obvious concern with chemical
pesticides is human poisonings when people come in contact with pesticides by various means. Pimentel notes that there are estimates that about 500,000 pesticide poisonings are reported annually in the world. What proportion of these are fatalities isn't known, he says, but it could be about 5000 annually. Beyond that, there are effects on agroecosystems. For example, when insecticides and other pesticides are used, not only is a pest destroyed, but there can be a severe impact on natural enemies of the target pest. And when these natural enemies are destroyed, outbreaks of pests not previously a problem in the target crop can result. Additionally, pesticides have been found to have reproductive effects, increasing reproduction in invertebrates. And they can reduce species diversity and thus alter ecosystem functions. They may be taken up and concentrated in the tissues of organisms. Pesticides that reach soil and affect the soil microfauna directly or indirectly may alter the decomposition and nutrient cycling in agroecosystems or natural ecosystems. Use of pesticides sometimes results in pest populations' developing resistance. Pesticides have in some areas reduced populations of honey bees and wild bees, essential for pollination. And they sometimes cause crop damage. Pimentel estimates that for each dollar invested in the U.S. for pesticide control, about $4.00 is returned in increased crop yields. He calculates that several of the nonchemical alternatives, such as host plant resistance and biological controls, return about $30 per
dollar invested, since once the technique is developed little or no costs are associated with use. "Few appreciate," says Pimentel, "that on nearly all U.S. agricultural land some nonchemical control alternatives are employed." The most widespread is host plant resistance. But, Pimentel says, some of the biological and cultural controls can result in some adverse impacts upon the environment. He notes, for instance, that one of the potential risks of introducing insects and other invertebrates to control arthropods or weeds is that a biocontrol species may itself become a pest. The technology of controlling insects, weeds, and pathogens by employing such microorganisms as viruses, bacteria, fungi, and protozoans has been growing rapidly, Pimentel says, with notable successes. Some are specific but some are not. For example, a nuclear polyhedrosis virus that attacks a particular caterpillar can parasitize other caterpillars in at least seven genera of five families. Vertebrate biological control agents have caused more serious environmental problems than have invertebrate agents, Pimentel says. For example, the Indian mongoose, originally introduced to Jamaica and other Caribbean islands in 1877 to control rats in sugarcane fields, effectively controlled the Norway rat, but enabled competing tree rats to increase. Gaining host plant resistance by genetically changing the chemical or physical nature of crop plants to resist pests has some risks, Pimentel notes. Plants use many different chemical compounds as defenses against animal and microbial attack, and some of these chemicals are toxic to both humans and domestic animals. Beneficial invertebrates may be affected adversely by crops bred for resistance. For example, nectar can be contaminated by the alkaloids, saponins, and cyanogens that occur in plants. And differences of morphology among crop varieties also have influenced the ability of natural enemies to locate and control pests. Other types of practices likewise can have adverse effects. Diversifying crops to regulate pest damage creates problems in employing commercial harvesting equipment; in addition, certain mixed-crop cultures can support greater Use of chemical pesticides for crop protection will help increase food output numbers of endogenous pests than can However, greater emphasis is being placed nowadays on nonchemical con- a monoculture. Escaping one pest by changing planting time can make a crop trols
18 C&ENDec. 20, 1982
Bender: new foods, new problems more susceptible to other pests. The mulches used in organic agriculture can increase populations of various pests such as slugs, snails, and mice, and at the same time reduce soil temperatures, resulting in seed rotting, poor germination, and slow crop growth. Pheromones and other behavioral chemicals presently used have few risks, Pimentel notes. But, he says, some potential exists for problems. For example, although the behavioral chemicals are relatively specific, they still may have side effects on the behavior of nontarget species. And a potential risk is that resistance can develop in an insect population, rendering the technique ineffective. In the nutritional area, Arnold B. Bender, a professor in the department of food science and nutrition at Queens College, University of London, points to the problem presented by the difference between chemical analysis and biological availability. The objective of measuring the nutrient content of a food, he explains, is usually to ascertain how much is available to the consumer. "This," says Bender, "is probably the most difficult problem facing the nutritionist and virtually impossible to achieve." Two indexes are used—chemical/ physical measurement and animal bioassay—but in either case, Bender points out, these have to be extrapolated to humans. Some analytical methods, he says, have been so thoroughly examined over the years that they are accepted as providing a reasonable index of available nutrients and are certainly adequate for comparisons before and after process-
ing and to determine the stability of nutrients on storage. But Bender expects new varieties and novel foods to be a principal means of increasing food available for growing populations. These new foods, he says, present a new problem. The new foods, Bender points out, may contain substances that interfere with the standard assay, and, similarly, novel methods of processing may introduce errors. Moreover, such new foods may introduce materials into the diet that interfere with the bioavailability of nutrients present in traditional foods, or they may replace traditional foods of known nutritional value. Comparisons of nutrient contents of new foods or those processed by novel means can be made by standard physical/chemical/microbiological techniques. "But this can only be regarded as a preliminary step," Bender says. "They must be verified by trials on animals with metabolic needs and pathways similar to those in man. Furthermore, if the food is to become a major part of the diet, then human trials will be necessary." Determining nutrient availability is a knotty problem, at best, even with traditional foods. Chemical and physical measurements of nutrients, Bender explains, are precise, usually rapid and reproducible, but suffer two drawbacks: The color developed with a particular chemical reagent or determined by physical measurements such as light absorption depends on the presence of a specific chemical grouping in the molecule and so is not specifically measuring the biologically active material. Also, such measurements may be enhanced or repressed by the presence of other substances present in the food. There are three further considerations with food. First, the active substance may be present in one or more of a variety of chemical forms—there are, for example, three forms of vitamin B6, more than 10 forms of vitamin A, and eight major forms of vitamin E. Second, a micronutrient will be present in a food or tissue in extremely small amounts—on the order of parts per million or less. And third, substances may be present that enhance or inhibit the physical/chemical reaction. Animal bioassays are long and laborious and very expensive. They also are very imprecise, since in all biological work there is considerable variation among animals, and extremely large variations among laboratories.
Pimentel: pest controls are essential Only a very limited number of experiments have been carried out on human subjects. Yet, Bender points out, even though these human experiments reveal very large variations among subjects, as do laboratory animal assays, these are the true estimations. The human trials, Bender says, provide the information required—namely, the proportion of a nutrient actually available. The animal assays measure the potency of the substance relative to a pure substance, although such measurements then have to be extrapolated to humans. So, Bender says, these results show very large variability of "true" values, whereas chemical/physical methods provide precise and reproducible results that may not be the true values. "Hence," he says, "the dilemma." Further compounding the nutrient situation is the practical problem of measuring the amount of a nutrient that is available from the diet as a whole. It is a problem, Bender says, almost impossible to ascertain, and beyond the ken of the laboratory analyst. He notes some investigations in progress, however, that are providing some information in this area. For example, one study has shown the vast range of absorption of iron from foods depending on changes brought about through processing and on the presence of phytate (a component of corn and other seeds), egg yolk, and tea taken at the same time as the iron-containing food. Meal components can have a sixfold effect on the proportion of iron absorbed. Dec. 20, 1982 C&EN
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News Focus To tackle this problem, an association was formed in 1978 in cooperation with the Senegal Agronomy Research Institute for first an experimental program and then a general one. The association included a pesticides manufacturer, RhônePoulenc Agrochemie; an agricultural equipment research center, Centre d'Etudes et d'Expérimentation du Machinisme Agricole et Tropical; and agricultural equipment manufacturers, Berthouc, Technova, and others. Through this association, a technique for using pesticides in a more concentrated form, or ultralight volume, was developed. Part of the development was to design new vaporizer equipment. Since then, the new technique has been adapted by the Senegal institute and applied to peanuts and cotton. The same technique, Roessler says, has been applied in the Sudan and in Chad. A further example of cooperation provided by Roessler deals with the correction of protein deficiency of cassava, a basic food in many countries. To overcome this problem, a protein enrichment process was developed jointly by a technical university, Université Technique de Compiègne; a design company, Adour-Enterprise; and an engineering company, Speichim. The effort has led to the isolation of a variety of amylolytic yeasts for increasing the amino acid content of cassava. Fermentation equipment has been designed and is available in different modules—from 1 ton per day to 1 ton per hour.
capable of altering practically all feed components. About 30% of feed protein passes through the rumen system without alteration. But the other 70% is initially utilized to nourish the microorganisms. A ruminant, therefore, lives predominantly from microorganism proteins formed after the feed proteins have been broken down. For the sulfur-containing amino acids methionine and cystine, the amino acid distribution of the microbial proteins has been found to compare unfavorably with the amino acid distribution of milk and wool. The microbial protein synthesis thus leads to a methionine deficiency. Experiments have shown that by infusing the appropriate amino acid into the second stomachs of ruminants, performance of the animals can be increased. This means, Offermanns says, that there would not only be more wool from sheep, but more protein from feedlot cattle and more milk from dairy cattle. Unfortunately, he points out, infusion isn't a practical method for providing ruminants with supplementary amino acids on a large scale. One way around this problem would be to protect the amino acid supplements. Offermanns outlines the strategy: "We must somehow outwit the microorganisms in the rumen and bring either the feed proteins or—even better—the limiting amino acids through the rumen without their being recognized by the hostile microorganisms. A method of doing this would be to use physical protection through coating or imbedding of the amino acid. Some products using this approach recently have come on the market. A second method would be chemical, involving the amino acid molecules rather than crystals or crystal agglomerates as in the physical approach. Offermanns notes that amino and carboxyl groups are quite capable of participating in a number of reactions that are reversible under certain conditions. Suitable protecting groups for the amino and carboxyl functions also are known. "The trick is in finding the particular products that suit three criteria: protection in the rumen, deprotection in the second stomach/small intestine, and economic feasibility," Offermanns says. Various products have been tested. For example, in iV-hydroxymethylmethionine-calcium, developed by Degussa, the amino group of the meTeams of oxen help villagers in India farm the land. The agricultural yields obtained thionine is protected by the hyby using such primitive methods are low compared to those of developed countries 20
C&ENDec. 20, 1982
These are just two examples of the part chemistry can play in food production. Indeed, in the technology leg of the agricultural progress stool, chemistry turns up in a seemingly endless variety of applications. The applications of chemistry are direct and indirect, they range from basic science to chemical engineering, and they apply to animals as well as crops. One further example of how chemistry might be utilized to benefit food production—one perhaps not very obvious—is in the possible increase in performance of animals through rumen-protected amino acids. Heribert Offermanns of West Germany's Degussa AG, points out that for monogastric animals—fowl and swine—addition of synthetic amino acids to feed is used on a large scale. Some 200 million tons per year of feed mix is supplemented in this way worldwide. The feed industry uses 100,000 tons of synthetic methionine per year and 40,000 tons of synthetic lysine. Supplementation in this way has improved protein utilization by about 20%, corresponding to a savings of more than 5 million tons of protein. Supplying methionine, which is the primary limiting amino acid in poultry feed, by adding methionine-rich fishmeal, as was common in the past, would require 30 million tons of fish per year processed into fishmeal. With ruminant animals, however, such supplementation hasn't been possible because of their multiplestomach system. The first and largest stomach, the rumen, is a fermentation vessel populated by microorganisms
terlinked in several ways, involving both feed-forward and feedback reactions, and that the processes of photosynthesis, translocation, partitioning, growth, and storage must be considered as an integrated whole. For example, greater demand during the grain-growth phase may either enhance or reduce leaf photosynthesis. If there is a high nitrogen or mineral content, as in legume seeds, greater demand will lead to a faster remobilization of nitrogen out of the leaves and thus to earlier senescence and a faster fall in photosynthetic rate. On the other hand, where grain growth is mainly based on carbohydrate storage, as in cereals, and where nitrogen fertilizers eliminate the need to mobilize nitrogen out of the upper leaves, leaf photosynthetic rate can be higher the greater the storage demand. Increasing food production, such as from this Asian rice paddy, would mean more inCurrently, Evans says, photosyntensive farming, which, in turn, would require more chemical input thesis is understood the most, and droxymethyl group, which is pH- forms, both as recombinant DNA storage, the least. A more balanced sensitive. The carboxyl group is fur- technology and in tissue and cell cul- understanding, with relatively more emphasis on what happens in the ther stabilized by formation of the ture. calcium salt. The protecting group Lloyd T. Evans, chief of the divi- growing and storing organs, is provides enough stability against at- sion of plant industry of the Com- needed. tack by the microorganisms in the monwealth Scientific & Industrial One approach to improving yield rumen, but it is cleaved instantly to Research Organization, in Australia, focuses on the enzyme rubisco. Phothe free amino acid under the acidic points out that the processes of pho- tosynthesis involves the coordinated conditions of the second stomach. tosynthesis and of the subsequent action of a large number of enzymes This methionine derivative, Offer- partitioning of its products are among and processes. But the primary target manns says, is marketed under the the most crucial in relation to the for improvement of carbon dioxide name of Mepron and has shown good potential yield of crops. However, he exchange rate has been rubisco— results in feeding studies under suit- says, although humankind has pro- ribulose 1,5-bisphosphate carboxylable conditions. ase/oxygenase. This compound, foundly changed the partitioning of But for the future, Offermanns assimilates in crop plants in the Evans says, probably is the most says, it isn't enough merely to develop course of their domestication and abundant enzyme in the world, comeffective products. A way must be improvement, no improvement on monly representing, as it does, 30 to found to feed the products to the ru- nature has been made with respect to 50% of leaf protein. minants. For example, he asks, what photosynthesis. Rubisco acts not only as a carboxpossibilities exist to supply rumenOne approach for the future, Evans ylase but also as an oxygenase, deprotected amino acids to cattle that says, would be to increase still further pending on the relative concentraare nourished solely from grazing? the partitioning of assimilates into tions of carbon dioxide and oxygen at There still are many questions to be the harvested plant organs—the path the active site. The result is that caranswered, he notes. that has contributed most of the rise bon dioxide exchange rate is reduced If chemistry today is being applied in crop-yield potential so far. Even for substantially by the process of phoin a very broad array of food tech- highly productive crops, he points torespiration. The outcome of large nologies, it seems destined for an even out, further shifts in partitioning and screening programs has shown that greater involvement in the future, further increase in harvest index ap- there is a close positive relationship both as a science and as a component pear feasible. There still is scope for beween carbon dioxide exchange rate of agricultural technologies. For ex- further reduction in nonharvested and photorespiration, but no evidence ample, a common plea from scientists organs, provided there is strong ag- of genotypes with high carbon dioxide in all disciplines, from plant breeders ronomic support for the crops. Other exchange rate caused by slow phototo nutritionists, is for a deeper un- changes along these lines should be respiration. derstanding of the biochemistry un- possible as well. The results of various studies, derpinning the phenomena they are However, Evans says, such changes Evans says, suggest little chance of dealing with. increasing photosynthetic rate in crop could well be approaching exhaustion Such knowledge is indeed a pre- as a source of greater yield potential plants by eliminating photorespirarequisite for some of the technologies by the end of the century. Thus, he tion. Nevertheless, he says, if forms of that seem to hold a great deal of urges that all possible ways of in- rubisco with substantially higher specific activity can be found— promise for the long term. Among creasing the rate of efficiency of these, for example, are possibilities photosynthesis be actively ex- through genetic engineering, for example—a high carbon dioxide exfor increasing the photosynthetic plored. change rate could be maintained with Evans explains that the rates of activity of plants, and the employa reduced investment in rubisco. ment of genetic engineering in several photosynthesis and storage are inDec. 20, 1982 C&EN
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News Focus Thus, the resources freed from photosynthesis could have a major impact on yield even in the absence of any rise in carbon dioxide exchange rate. Although work on rubisco could be very promising, Evans points out several areas that probably are in more need of research stimulation, given that rubisco already is the target of much physiological and genetic engineering research. The other areas include control of leaf senescence and the factors determining the duration of storage processes in harvested organs; control of partitioning of current assimilates, reserves, and remobilized compounds among competing organs of the major crop plants; and control of the rates of transport to, unloading at, and metabolism and storage in the harvested organs of crops. As for genetic engineering, the techniques involved have enormous promise for application in areas of food production. But the scientific consensus is that benefits on any large scale are definitely in the long term. Still, as noted by Harvard University biology professor Lawrence Bogorad in a presentation prepared for the conference, genetic engineering of bacteria that promote or impede plant growth can be carried out now. And available genetic engineering tools also permit the introduction of single genes or many genes into plants. However, Bogorad points out, little is known about portions of genes that are required to control their expression in specific tissues or at specific stages of development. As in so many other areas, progress in genetic engineering requires a great deal of basic research on the molecular genetics and related biochemistry underlying agriculture. For example, Bogorad points out that there is a need to understand mechanisms of ion uptake to devise plants that need lower levels of nutrients, to understand how plant hormones work to modify growth and development of crops, to understand the structure of plant genomes and genes, to understand about gene expression regulatory mechanisms, and many other phenomena. A start already has been made in applying genetic engineering on a basic level to food production. The cloning of the gene for a protein of the foot and mouth disease virus in Escherichia coli for production of the protein by the bacteria has been accomplished, promising a cheap, safe vaccine. And a DNA copy of the potato spindle viroid in E. coli has been 22
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ease. This, in turn, would open the way to genetic engineering with genes that have complex interactions with one another. "Surely," Bogorad says, "the insights to be gained from these lines of research will have a profound effect on how we think about plant disease and resistance to disease in the last decade of the century." Other possibilities abound. Production costs could be reduced by use of genetic engineering techniques to transfer single genes or groups of genes that are expressed constitutively, producing, for example, a plant variety resistant to a specific herbicide. If it were economically worthwhile, a gene could be introduced to a forage crop for a protein whose presence would alter the nutritional quality of all the cells of a plant, including above-ground parts eaten by foraging domesticated animals. More attractive, says Bogorad, is the prospect of changing the nutritional A BASF agricultural advisor explains the quality of grains by altering the profunction and application of agrochemicalstein composition or the amino acid to South Indian farmers. The Indian gov-makeup of their storage proteins. ernment considers rural development to However, this latter operation rebe the most important aspect of its in- quires more than can be done now, he concedes. It requires not only the industrial policy troduction of a new gene or a modicloned, providing a molecular probe fied form of one already present, but to test plants to see if they carry the also knowledge of the control elements on the gene so that it is exviroid. Further applications seem limited pressed in the seed and not in all parts only by the imagination. For example, of the plant. Bogorad notes that the simplest kinds Whatever the prospects of new of genetic engineering involve the technologies like genetic engineering, introduction, into relatively simple traditional synthetic chemistry will organisms like bacteria, of genes that continue to be applied to generating are always active. An agriculturally bioactive substances. Yet even here useful step at this level, he says, would the winds of change are being felt. be the introduction of a gene for hyThe winds are labeled biorational drogenase into otherwise desirable design. The term describes an apnodulating strains of rhizobium that proach to synthesis of bioactive lack this enzyme. Nodules formed on chemicals, explains Hans Geissbuhroots of legumes by rhizobia that lack ler, director of agricultural research hydrogenase liberate hydrogen gas at CIBA Geigy. Indispensable to the into the atmosphere, using the energy concept, he says, is the application to from photosynthetic products of the synthetic chemistry of appropriate plant to produce the hydrogen rather screening procedures. than to fix nitrogen. The waste is very Ideally, these procedures would be great. On the other hand, bacteria used at four levels during synthesis. with the enzyme hydrogenase recap- The first is morphological, the macture the hydrogen and use it to reduce roscopic observation of effects of a ferredoxin, which can contribute chemical on whole organisms, such as electrons toward reducing nitrogen. insects, weeds, and the like. The secThe analysis of plant disease ond level is physiological, through the caused by bacteria and fungi seems on use of separate or isolated organs, the verge of a revolution, Bogorad organelles, tissue cultures, and others. says, because knowledge of molecular The third is biochemical, making use genetics, gained relatively recently, of testing systems that reflect the promises to lead to the genes involved mode of action of specific enzymes, in pathogenicity. Eventually, it may hormones, neurotransmitters, elecbe possible to identify physically all tron carriers, and so forth. The final the products of genes at several loci level is molecular, using models rethat affect resistance to a given dis- flecting—in both chemical and
physical terms—defined receptor sites of enzymes, membranes, and others. The purpose of using biorational techniques also is fourfold, Geissbuhler explains: to improve the selectivity of bioactive chemicals in relation to nontarget organisms, reducing the incidence of unwanted or undesirable side effects; to assist in improving the diminishing success rate observed with conventional approaches; to facilitate the synthetic chemist's task of selecting, by more rational means, promising lead structures or molecules; and to help the biologist by constantly improving the relevance of his battery of testing systems and procedures. Geissbuhler and his colleagues have analyzed the range of available structural classes of pesticides and growth regulators to determine the extent to which biorational approaches had been used. What they found was that such approaches were exploited in no more than 14 of the more than 60 different classes of chemical structures that eventually reached practical application. The frequency of biorational approaches, he says, was found to be somewhat higher for insect control agents and plant growth regulators than for herbicides and fungicides. Looking at the frequency in terms of the 40-year time scale suggests a slight increase in use of the approach in the seventies, compared to the previous decades, says Geissbuhler. Among the impediments to wider use of the approach, Geissbuhler lists the multitude and variety of target organisms and the multitude of control factors that affect the behavior and fate of bioactive molecules under conditions of practical use. For example, the total of economically important insect pests, crop diseases, and weeds is estimated to comprise roughly 200 different species belonging to almost as many systematic orders, families, and genera. Agricultural scientists are faced with an immense variety of morphological features, physiological mechanisms, biochemical systems and the like— not only of the organisms to be controlled but of the crops to be protected or regulated. Another impediment is that, until recently, efficient and accurate physiological and biochemical testing systems were technically rather complex, labor-intensive, and often of questionable reliability and reproducibility. However, Geissbuhler says, this situation is being overcome rapidly by continuous advances in
Photosynthesis and the distant future The title of the symposium was the Forward Edge. And in presenting his futuristic vision of a world in which photosynthesis—natural or artificial— supplies all energy and food, Sir George Porter, Nobel Laureate and director of the Royal Institution, London, readily admits he perhaps was over the edge. Nevertheless, he says, it is a possible scenario. Food and energy problems are inseparable, Porter notes. It might reasonably be argued, he says, that the principal factor limiting food supply is the shortage of energy. And unlike food, which is a renewable resource, energy from fossil fuels is a diminishing resource. Porter's "futuristic but possible" scenario: A world where photosynthesis continues to supply mankind with energy needs, not only of food but also of fuel, where energy farming takes its place alongside food farming to provide, on a renewable basis, the essential requirements of modern life. The photosynthesis would include purely chemical, nonliving systems. Porter reasons that a realistic energy efficiency of photosynthesis in converting solar energy into chemical potential of 10% should be possible. This figure takes into account the unavoidable losses imposed by the second law of thermodynamics, finite power loss, and inefficiencies caused by broad-band irradiation, as well as further small losses due to reflection, storage, and lower efficiencies at lower levels of insolation. Whatever process is used for producing energy with artificial photosynthesis, the only resource needed (apart from the manufactured materials) is sunshine. And any land surface not too hostile would be suitable. At 10% efficiency, Porter says, 3% of the world's desert areas would suffice
Porter: all food from photosynthesis? to produce present energy requirements, and one third would be required for the rather extreme projection of 10 billion people living at European standards. "This," Porter says, "is the challenge that faces photochemists." Research in the field of artificial photosynthesis is in its early stages, Porter notes, and progress over the past few years has been quite encouraging. It is, he says, a relatively inexpensive subject to investigate and probably will remain so, even at the development stage, because there are few scaling problems. Like agriculture, small-scale trials can be extended rapidly to large areas. There are good reasons for pursuing research in this area now, Porter says. "It may take longer than we think, in which case we need the time to achieve success before existing sources run out. We may be successful earlier than we dared hope, in which case it might soon make a useful contribution to the existing problems in the Third World."
Improvements can only be analytical instrumentation and data achieved by closer cooperation behandling. Beyond these considerations, ef- tween chemists and biologists, forts to develop and exploit biora- -Geissbuhler says. His plea echoes tional design are hampered seriously those of so many of the researchers by a significant and continuing lack of seeking the scientific foundations for basic scientific knowledge concerning the technology leg of the agricultural the physiology and biochemistry of progress stool. "The first priority," he insects, diseases, weeds, and crop says, "is to intensify the acquisition of plants, according to Geissbuhler. In basic scientific knowledge on the addition, basic information at the growth, development, and reproducbiochemical and molecular levels on tion of crop plants, insect pests, disthe mode of action of pesticides is, in eases, and weeds, and to define in general, not good enough to be ex- more detail their respective interacploited systematically for biorational tions and natural defense mechaimprovements and modifications. nisms." • Dec. 20, 1982 C&EN 23
