Although the USA is frontrunner in biotechnology, the utilization of modern biotechnology in plant breeding for US field crops is still in its initial stages. Biotechnology directed at traditional plant breeding goals is now utilized on a limited scale. For biotechnology-derived industrial products, however, neither the science and technology nor the production and marketing details have yet been worked out for any crop. A view from Donald Duvick.

In the field crops seed industry, the application of modern biotechnology can be divided into two fields: (a) biotechnology in aid of plant breeding for traditional goals, and (b) biotechnology in aid of the production of industrial products in plants. The tables on pages 16 and 17 offer a short overview of the state of the art of research in both fields (with emphasis on industrial products) and the extent to which biotechnological products have reached the market.

Traditional plant breeding goals
Plant breeders intend to use biotechnology as a tool to increase efficiency of traditional methods, with particular attention to improving disease and insect resistance, or adding novel kinds of herbicide tolerance. The achievements to date of biotechnology in aid of traditional field crop plant breeding goals can be summarized as follows: (1) the identification of novel genes for desired traits, such as insect resistance or herbicide tolerance, and their incorporation into the crop genome by means of genetic transformation; (2) the improvement of speed and efficiency of incorporation of desirable new genes by utilization of closely linked, selectable molecular markers, and; (3) the utilization of molecular markers to identify important quantitative trait loci (QTL). A QTL is defined as a chromosome segment carrying groups of genes with a significant cumulative effect on a quantitative trait.
Only a few of these products have reached the US market. The ultimate value of the new traits and tools, and the size and extent of market demand for the new products remain to be established.

Industrial products in plants
During the past decade advances in biotechnology have shown that plants can be genetically altered to produce new products for industrial use. Commercial seed companies and also chemical and pharmaceutical companies are now interested in producing novel chemicals in plants. The expected benefits are that the new products may cost less to produce and their production may entail less environmental contamination. These assumptions are not yet tested in the field or in the processing plant.
Up to this time, 1995, only one product, lauric acid in rapeseed, has been commercialized. 1995 was its first year of production, and it is too soon to know if it will be successful. All other products are either several years from production, or in the experimental stage, or exist only in concept. All of these projected products (with the exception of lauric acid in rapeseed) have been more difficult to make in plants than had been expected, and sometimes they are more difficult to extract from plants than envisaged. The products can be categorized as follows:
Sterols and alkaloids. Both are difficult to manage with biotechnology, in part because they are secondary metabolites and therefore have complicated biosynthetic pathways. Little effort is spent on them at this time, although one US company, AMOCO, has worked on the production of beta-carotene and lycopene for use in adding yellow colour to egg yolks and chicken fat.
Protein products. No biotechnology-produced products in this category are yet ready for the market. Most plant protein products are intended for use as food or feed, and not for industrial use. It is expected that relatively strong public concerns about genetically engineered products in the food chain will apply to proteins that are genetically altered. For these reasons plant breeders prefer to use classical breeding methods to alter amounts or quality of existing plant proteins that are used for food or feed. Classical plant breeding methods are usually able to make needed changes in plant proteins for food or feed use.
Novel oils. Crop species of choice for production of novel oils in the USA will most likely be rapeseed, sunflower, and soya beans. Oils made from these oil-seed plants can be modified with classical breeding methods. For example, induced mutation can block key steps in fatty acid synthesis and result in desired changes in fatty acid composition within the inborn limits of biosynthetic variability of the crop species. Genetic transformation can increase the diversity of oil production in crop plants even further; genes from distant plant species or from other organisms such as bacteria can be incorporated into a crop plant genome. However, one first must know if the crop plant has the necessary enzymes to assemble and store the foreign product. Insufficient knowledge about biosynthetic pathways for oil production is a limiting factor to further progress.
Carbohydrates. The production of industrial carbohydrates in the USA is centred on starch from maize. Classical breeding techniques may be able to develop new starch variants with use in industry. Biotechnology might be able to make additional useful changes, enabling crop plants to produce unique starch types now found only in other species. One might even find it useful to move starch-producing genes from one crop plant to another, such as from potato to maize. Potato starch is uniquely phosphorylated and therefore useful for making certain kinds of paper. Biotechnology also may some day be able to transform high yield carbohydrate producers such as maize plants into factories that produce polysaccharides for industrial use. One possibility could be to make polysaccharides now obtained from algae, such as carrageenin and alginates.

Effects of patents
The advent of biotechnology to plant breeding has brought in new opportunities for patenting in the USA, and new attitudes toward intellectual property protection (IPP) in general. The present climate is one of vigorous protection of intellectual property relating to plants, on the assumption that since one cannot be sure how much protection is needed it will be best to protect all possible. This attitude hinders some needed research and development efforts. Some patents seem excessively broad to others in the industry. Seed companies are learning how to deal with intellectual property rights but at a high cost, especially in comparison to the cost of protecting products of classical plant breeding. Increased expenses include those for more legal counsel, for extensive record keeping on the part of researchers, and the cost of delays in implementing improvements until legal safeguards are in place. A further new factor in the property rights field is that universities and governmental research organizations now protect products of their research. This means that increasingly, commercial firms working with plants and plant products need to deal with these public institutions as though they also were commercial firms, sometimes collaborators and sometimes competitors.
The problem of excessively broad or possibly unneeded patents eventually will take care of itself. As courts and regulatory agencies review contested patents, generally accepted boundaries gradually will be established. Because patents on plants, plant products and processes are a new phenomenon it is to be expected that several years of experience will be required before all parties reach more or less general agreement on the best ways to use IPP.
 

Molecular biology as aid for traditional plant breeding goals  Type of research  State of the art in R&D  Current constraints in R&D and/or marketability  Current/future marketability  New herbicide tolerant varieties  * Successful releases of herbicide resistance in maize, soya beans, sunflower and rapeseed.  * Acceptance by farmers depends on superior yield performance and other agronomically desirable traits;  * Size and extent of market demand remains to be established.  * Farmer experience with herbicide tolerant varieties is increasing.  Varieties with novel insect resistance  * Series of genes from Bacillus thuringiensis (Bt) are readily available.  * Acceptance depends on ability to develop insect resistant varieties in a way that will prevent rapid development of new insect genotypes overcoming the novel resistance genes.  * One type of resistance is readily available at this time (i.e., a series of genes from Bacillus thuringiensis (Bt) that produce endotoxins specific for certain kinds of insects).  Molecular markers to identify important quantitative trait loci (QTL)  * Some QTL have been tentatively identified but most of them seem to be associated with only one or a few parental strains.  * Currently available technology is expensive.  * The cost of using molecular markers is coming down;  * More powerful experiments to detect universally useful QTL will be devised in the next decade.

 

Molecular biology as aid for the production of industrial products in crops variations of products made by the plant species of choice:  Type of research  State of the art in R&D  Current constraints in R&D and/or marketability  Current/future marketability  Proteins  * Plants can be genetically altered to synthesize novel proteins such as antibodies;  * Plants can be engineered to produce antigens which act as vaccines.  * Extracting special proteins might be difficult because of the large number of secondary metabolites in plant tissues;  * Purifying the extracted proteins to meet medical standards might be difficult. * Produced on a large scale, antibodies might be useful for immunotherapy;  * No products are ready for the market yet.  Oils  * Research is concentrated on rapeseed, sunflower and soya beans;  * Several laboratories are identifying and cloning key genes for production of oils or waxes with industrial use, with the intention of using them in crop plants, via genetic transformation. Proposed products are: erucic acid, lauric acid, petroselinic acid, gamma-linolenic acid, jojoba wax, and epoxy fatty acids.  * Insufficient knowledge about biosynthetic pathways for oil production is a limiting factor in further research progress.  * In 1995, Calgene Inc. produced transgenic rapeseed producing high volumes of lauric acid, using a gene that functions in the developing oilseed of the the California bay tree (Umbellularia californica);  *Du Pont is testing genetically modified soya beans with increased oleic acid and reduced saturated fats contents. Transwitch was used to turn off critical genes.  Carbohydrates  * US research and production is centered on starch from maize;  * Naturally occurring genes such as waxy, amylose-extender, dull, and shrunken-1 can be used to modify native maize starch;  * Genetic transformation may allow production of starch with novel desired properties.  * Maize starch is treated as a generic component widely used for the production of high fructose corn syrup (HFCS), fuel alcohol, glucose and dextrose, but modified native maize starch is used very little on an industrial scale;  * No genetically engineered starch products are available to date.  * Market for HFCS is considerable (ca. 35 per cent of caloric sweetener market in the USA).  * Markets for modified native maize starch are very small.

Changes in marketing
Plant-produced industrial products will need to compete with non-plant products already on the market, for example in cost of production and product quality. In theory, producing industrial products in plants should cost less, because the plants can use free sunlight and air, and relatively low priced land and water as raw materials. But the small size and dispersed and variable nature of many potential markets for plant-produced industrial products will affect the profitability of producing these products in plants. The fractured nature of the market for plant-produced industrial products contrasts sharply with the traditional markets for farm seeds. The potential US market for hybrid seed corn, for example, can be as high as US$ 2 billion, whereas markets for the industrial products that might be produced in crop plants often are counted in tens of millions of dollars.
Potential customers for plant-produced industrial products are of broadly divergent types including paper manufacturers, paint companies, and pharmaceutical companies. This diversity contrasts strikingly with the relatively homogeneous group, farmers, that traditionally has comprised most or all of the seed company customer base. In most cases the potential industrial customers have no acquaintance with the seed companies and no knowledge of what industrial products they might be able to make. Conversely, the seed companies have no acquaintance with many of their potential customers in industry.
Compared to seed companies, chemical companies producing industrial products from crops know many of the customers for the industrial products, in fact, they themselves are often the customers. They often have well-developed biotechnology groups, founded to serve other aspects of their business. They can support plant breeding with biotechnology to a greater degree than is possible for most seed companies.
However, chemical companies are usually inexperienced in plant breeding and seed sales, and they have no built-in base of farmer customers who know them and are willing to try their new varieties. To remedy this problem the industrial companies are buying seed firms or are making collaborative arrangements with independent seed firms. Such collaborative arrangements can be especially advantageous to small seed companies. They usually cannot afford to support biotechnology research to the degree that is needed to develop new varieties able to make industrial products.
Seed firms, on the other hand, are also now making collaborative arrangements, downstream to food companies and chemical companies, and upstream to farmers who produce the new specialty crops. A special kind of vertical integration is developed by the seed companies, to help in production and distribution of the new class of small-volume plant-produced industrial products with highly specific end uses. This new kind of integration is intended to assure breeders that years of effort in developing the novel crop varieties would be recompensed by profitable seed sales or by some other kind of compensation. It also would assure farmers that growing a perhaps lower yielding crop, and handling it separately, would be recompensed by a higher price for the crop. It would assure the business firms who bought the crop that they would have a steady flow of feedstocks of known quality.
Donald N. Duvick

Pioneer Hi-Bred International Inc. (retired), Johnston, Iowa 50131, USA. Phone/Fax (+1) 515 278 0861; E-mail duvick@aol.com