Technological Trends and Applications in Biotechnology
Webster's defines biotechnology as “applied biological science.¹ The U.S. government, however, employs a more comprehensive definition: both the old and new biotechnologies comprise “any technique that uses living organisms (or parts of organisms) to make or modify products, to improve plants or animals, or to develop microorganisms for specific uses.”² The “new” biotechnology has been defined by the U.S. government as “the industrial use of rDNA, cell fusion, and novel bioprocessing techniques.”³ This being said, the definition that in the long run may be the most descriptive relative to the world economy was produced by Vivian Moses and corporate biotechnology pioneer Ronald Cape: “making money with biology.” 4
Biotechnology already has been employed successfully to manufacture new medicines, improve agricultural production, and produce drugs from metabolises of marine organisms, and it shows great promise in such other areas as remediating environmental pollution. But its most rudimentary applications are in fermentation-that is, the use of microorganisms such as molds and bacteria to produce food products. This application is as old as the history of human civilization. Fermentation technology originated in ancient China, where foods were fermented by molds, and in Egypt, where beer brewing and bread-making were combined enterprises. 5 Bread, cheese, yogurt, vinegar, soy sauce, bean curd, beer, and wine are a few examples of the modern products of fermentation.
The unique characteristics of microorganisms have only begun to be exploited to improve life on this planet, taking into account, of course, the role of microorganisms in the cycling of nutrients and in global climatic processes. But the new methods and technologies are only emerging from old ones. For example, by the end of the eighteenth century, farmers had learned to rotate crops in order to plant crops that restored nutrients to nutrient-poor soil. And even before the science of genetics was understood, new varieties of crops and animals were being bred by selection for desired qualities.
Some milestones in the history of science indicate the source of this new technology. In the field of medicine, Edward Jenner, who in the last decade of the eighteenth century observed that milkmaids did not succumb to smallpox, began inoculation with cowpox, or Vaccinia virus, to prevent smallpox infection. About the same time, Louis Pasteur, best known for his work that led to the process of pasteurization and the identification of microorganisms as causative agents of disease, studied fermentation in wine and wrote an important book on winemaking. And around the turn of the century, German bacteriologist and physician Robert Koch identified microorganisms as the causes of anthrax and tuberculosis.
The first industrial use of a pure culture of a bacterium was accomplished by Chaim Weizmann in 1917 when he developed the fermentation of cornstarch by the bacterium Clostridium acetobutylicum, thereby producing acetone for explosives manufacture. Gregor Mendel, an Austrian monk whose studies on the pea plant elucidated inheritance of traits via hereditary factors, conducted seminal work in genetics in 1865. Although Mendel's work was ignored until 1900, his findings, once rediscovered, fit well with what was by then known about chromosomal activity during cell division, or mitosis. The first half of the twentieth century was an exciting time, with major gains in knowledge of genetic inheritance. Thomas Hunt Morgan of Columbia University, working with the fruit fly, Drosophila melanogaster, showed that genes, or the units of heredity, were the constructs of chromosomes. His student A. H. Sturtevant, who later joined him when he moved to the California Institute of Technology, made a number of breakthrough discoveries showing genes were linked, comprising chromosomes. 6 He thus began the science of genetic mapping, a technique essential to the new genetics.
In the 1930s and 1940s, genetics research was moving inexorably in the direction of the upcoming explosion of knowledge at the molecular level. Researchers such as Barbara McClintock 7 and Marcus Rhoades 8 studied linkage and mutable characteristics in maize (corn), providing a view of genes as more mutable and variable than the simple Mendelian genetics allowed. Meanwhile, research on what comprised genetic material moved forward rapidly. In 1928, Frederick Griffith had found that a “transforming principle” was able to alter traits in the bacterium Streptococcus pneumoniae. 9 By 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty of the Rockefeller Institute had identified the “transforming factor” as deoxyribonucleic acid, or DNA.10 From that moment, scientists in many laboratories labored to determine the chemical structure of the DNA molecule. Finally, in 1953, James Watson and Francis Crick's short paper described the breakthrough for which everyone was waiting. 11
GENETIC ENGINEERING: A NEW WORLD
Twenty years after Watson and Crick's paper, the first stones were laid in the path to commercial genetic engineering. Stanley Cohen of Stanford University, Herbert Boyer of the University of California (San Francisco) Medical School, and their teams succeeded in cloning a gene into a bacterial plasmid-the first recombinant DNA (rDNA) - and in 1980 they received a patent for this technique. 12 Also in 1980, the U.S. Supreme Court ruled in Diamond v. Chakrabarty that microorganisms could be patented, opening a new commercial avenue for genetic engineering. 13
The first U.S. biotechnology company, Genentech, was founded in 1976. By 1994, it had been joined by more than 1,300 other companies in the United States alone (Figure 1). 14 The years 1981-1987 were watershed ones for U.S. biotechnology: an average of 90 companies were formed annually, for a total of 631 companies established during this period. 15 In 1981, the first U.S.-approved biotechnology product reached consumers: a monoclonal antibody-based diagnostic test kit. The following year, the first recombinant DNA pharmaceutical, Genentech's Humulin (recombinant human insulin), was approved for sale in the United States and Great Britain. Humulin's 1993 sales were $560 million. 16 The same year, the first recombinant animal vaccine for colibacillosis was approved in Europe.
Although most biotechnology companies are still not consistently profitable, more and more products are entering the market. 17 In 1993, Amgen's Neupogen, human granulocyte colony-stimulating factor, was the best-selling U.S. biotechnology drug, netting $719 million (Table 1). 18 In 1994, at least four new drugs were approved in the United States, along with a recombinant “housekeeping” enzyme and diagnostics. One new product in another area was Calgene's Flavr Savr tomato, engineered for better taste and shipping tolerance through the addition of a “backwards” gene that induces the tomato to produce only small amounts of the ripening enzyme, polygalacturonase. Thus the tomato can be picked before ripening and left to ripen slowly without adding artificial ripeners. 19 Although it did not need approval at the time of its development, the recombinant tomato underwent review and was approved in 1995 by the U.S. Food and Drug Administration (FDA).
TABLE 1 Top Ten Biotechnology Drugs, 1993
SOURCE: Ernst and Young ILP.
In 1994, U.S. biotechnology companies had a market value of $41 billion, R&D expenditures of $7 billion, and 103,000 employees-this in an industry that did not exist 20 years ago. By comparison, the U.S. pharmaceutical industry, which has invested heavily in biotechnology, had R&D expenditures of $13.8 billion in 1994. Poor economic markets and policy questions in the United States held down the number of companies formed in 1994, but instead of being in a downturn, the U.S. biotechnology industry may be maturing, to eventually take on a new role in the global economy. And instead of being aggressively entrepreneurial, with the intention of becoming the next Merck, the newly emerging companies may well serve in the future as a reservoir of corporate research for large pharmaceutical firms, which, in turn, will develop and market the output.
Today, however, because most of the U.S. biotechnology industry is centered on health care products and many of the companies were started on the basis of licensing agreements or research from the university community, the decrease in corporate start-ups, as well as financing, is causing a basic change in the structure of the industry. Smaller companies are merging; large companies, such as the major pharmaceutical companies, are acquiring smaller biotechnology ventures; and, because there is little money available in the investment market for corporate growth, companies are looking to strategic alliances, both in the United States and abroad, to shore up finances and financial opportunities. This development may prove beneficial for Asian pharmaceutical or biotechnology companies looking for products in return for allowing access to the Asian market. But many of the developing countries, lacking homegrown pharmaceutical giants, will have to look elsewhere for role models for their own fledgling biotechnology industries.
The United States is not the sole benefactor of biotechnology growth. In 1993, 386 biotechnology companies were located in Europe, most in Great Britain, Germany, Belgium, and the Netherlands (Figure 2). 20 From 1986 to 1992, about $657 million was pumped by venture capitalists into the European biotechnology industry. The major biotechnology players in Western Europe are Belgium, Denmark, France (whose 1991 market for biotechnology products was $115 million, $29 million of which were imports), Germany, Italy (with a 1995 biotechnology market estimated at $1.5 billion), the Netherlands (whose 1991 biotechnology product and process sales equaled $220 million), Sweden, and the United Kingdom. In 1993, Canada had 310 biotechnology companies, with revenues of $1.67 billion and 61 percent of total sales from exports. 21 Ten percent of Canada's biotechnology exports go to Japan, while an additional 10 percent go to China, India, South America, and the Caribbean. A handful of companies are scattered in South and Central America (mainly in Brazil and Mexico) and Asia (excluding Japan). Approximately 200 biotechnology companies are located in Australia and an additional 40 in New Zealand. Japan's biotechnology industry differs from the entrepreneurial industry in the United States, Canada, Europe, and Australia in that much of Japan's biotechnology R&D is carried out by universities and research institutes or in cooperation with its large pharmaceutical firms, food corporations, brewing companies, or electronics giants. The R&D outlays of Japan's top ten pharmaceutical companies are only one-fifth of similar outlays by U.S. companies. 22
In most developing nations, there is little in the way of commercial biotechnology, but governments and researchers acknowledge the importance of the field, and government and nongovernmental organization support have led to establishment of biotechnology-related centers. For example, the International Center for Genetic Engineering and Biotechnology (ICGEB), initiated by the United Nations Industrial Development Organization (UNIDO) but now supported by Italy and India, has two laboratories: one in Trieste, Italy, and the other in New Delhi. Research groups from 32 member countries are affiliated with ICGEB. 23
The M. S. Swaminathan Research Foundation in Madras is a leader in the promotion of biotechnology at the village level in India. Other prominent biotechnology research institutes in India are New Delhi's Energy Research Institute and a national institute of cellular and molecular biology in Hyderabad. Hindustan Lever, a subsidiary of Lever Brothers, has a large corporate biotechnology division in India (Kamaljit Bawa, University of Massachusetts, personal communication, October 28, 1994).
In the Far East, the Hong Kong Institute of Biotechnology, under the auspices of the Chinese University of Hong Kong, was established with the help of overseas Chinese scientists. 24 Hong Kong also has a Biotechnology Research Institute. Of the many biotechnology-related research departments and institutes in the People's Republic of China, one of the oldest and best known is the Shanghai Institute of Biochemistry. 25 The International Vaccine Institute being established in South Korea is receiving financial assistance from the United Nations Development Fund and the Japanese government. 26 Thailand's National Centre for Genetic Engineering and Biotechnology, which has a marine biotechnology laboratory, was begun with support from the U.S. Agency for International Development (USAID). Aquaculture is a major theme of other biotechnology research centers and university departments in Thailand.
Worldwide, many national and international organizations maintain laboratories that carry out research in biotechnology, mostly related to agriculture. One example is the International Rice Research Institute in the Philippines. Another is the Biotechnology Centre for Animal and Plant Health, established by the European Union, in partnership with the Queen's University of Northern Ireland in Belfast, which focuses primarily on disease control. 27
In Africa, the French molecular genetics researcher Daniel Cohen and his organization, Association Ifriqya, are planning to establish the Institute for Genome Research for Developing Countries (IGRDC) in Hammamet, Tunisia, in 1996. 28 The Agricultural Genetic Engineering Research Institute (AGERI) in Cairo, Egypt, is cooperating with Michigan State University's Agricultural Biotechnology for Sustainable Productivity (ABSP) project, supported by USAID. 29 The African network of Microbiological Resources Centres (MIRCENs), although not a research group per se, is organized to support research projects in soil microbiology, biotechnology, natural resources management, vegetable production and protection, and food and nutritional technology at research organizations and universities throughout Africa south of the Sahara. 30 The International Laboratory for Research on Animal Diseases (ILRAD) is located in Nairobi, Kenya.
MARKET SEGMENTS AND RESEARCH AREAS
In the United States, and to a lesser degree in Canada and Europe, the bulk of the biotechnology industry is in the biomedical field: therapeutics and diagnostics make up 68 percent of the U.S. industry, 43.7 percent of the Canadian industry, and approximately 43 percent of the European industry. From 1993 to 1994, therapeutic product sales in the United States increased 24 percent, for a total of nearly $20 billion.
Agricultural biotechnology also represents a growing segment of the industry: 8 percent in the United States, 20 percent in Europe, and 28 percent in Canada. The U.S. agricultural biotechnology market increased its sales by 158 percent in 1993, with aquaculture the most rapidly growing sector. 31
The chemical, environmental, and services segment, which makes up only 9 percent of the U.S. biotechnology industry, increased its sales by 81 percent in 1993, totaling $70 billion. 32 This segment comprises 10 percent of the Canadian industry.
Medical biotechnology mainly includes recombinant drugs and enzyme-mediated diagnostic kits, but the rational design of drugs, where a drug is modeled to fit a particular molecule, yielding a limited response that can result in control of the disease process, has become a significant part of this field. By learning more about the basic biochemistry of normal and abnormal cellular function, scientists eventually will produce drugs that will prevent the abnormal growth of cancer cells, or will permit detection of the abnormalities in the DNA that signal the onset of cancerous changes, thereby preventing cancer from occurring. Another intent is to circumvent the immune response to one's own tissue that occurs in such autoimmune diseases as multiple sclerosis and lupus erythematosus. The hope also is to use small molecules to combat degenerative neurological diseases or to induce neurological cell regrowth in such conditions as Alzheimer's disease, amyotrophic lateral sclerosis, head and spinal injury, and cerebrovascular accident or stroke. 33 Some of the already successful recombinant drugs include recombinant human insulin, growth hormone, interferons, tissue plasminogen activator, erythropoietin, and other blood cell-stimulating factors. Thus biotechnology and pharmaceutical companies legitimately have high hopes for the economic and medical potential of the next generation of drugs.
Among the most successful of the antibody-based diagnostics are pregnancy test kits, which now are so simple that in the United States they can be purchased over the counter and used at home. Human immunodeficiency virus (HIV) test kits are being sold worldwide and are manufactured in many parts of the world. The U.S. market for monoclonal antibodies, the majority of which are used in such test kits, was estimated at $1.2 billion this year and to be nearly $4 billion by the turn of the century. As test kits become both more accurate and easier to use, test kit manufacturers foresee wide applicability, even in rural settings, by technicians with minimal training. Some companies, for example, have sent personnel to China and South America to train technicians in the proper use of their test kits.
Monoclonal antibodies were expected to become major tools for the treatment of a variety of diseases, but recent problems with monoclonal antibody-based septic shock treatments caused several companies such as Xoma, Centocor, Chiron, and Synergen to abandon drugs in clinical trials. 34
Recombinant vaccines are expected to make a major contribution to the health of the world's population. Recombinant hepatitis B vaccine already is used worldwide. Although an HIV vaccine would have enormous use, especially in those countries where HIV is widespread, little success has been achieved and not much is on the horizon, at least at present. Research on HIV vaccines that would be beneficial to those people outside the developed nations, who suffer from a different strain of HIV than that found in the United States and western Europe, is not being pursued aggressively. 35 In contrast, vaccines against malaria, respiratory syncytial virus (RSV), rotavirus (which causes severe, life-threatening diarrhea in children), Streptococcus pneumoniae (which causes bacterial pneumonia), and cholera, are being pursued actively and will have an immediate impact on global health. 36 Although new vaccines and vaccine combinations could improve the health of many children worldwide, 37 a recent study showed that the world vaccine market stands at a mere $3 billion, 38 a relatively insignificant value when compared to the $1.2 billion world sales of just one new biotechnology drug, recombinant human erythropoietin (Amgen's Epogen). 39
Drug delivery systems are an important segment of the biomedical component of the biotechnology industry. 40 New methods of administering vaccines - by injection, intra-nasally by spray, time-release methods, and others still under development-and even drugs, could revolutionize health care in developing nations and in poor or rural communities in developed countries. 41
Other, much smaller and more specialized medical biotechnology markets include treatment regimens, such as gene therapy. In gene therapy, which currently is employed for research purposes only, a normal gene is put into abnormal cells using a carrier such as a virus. In “cellular therapy” a patient's cells are treated. An example of this is autologous bone marrow transplants, where a patient's bone marrow is removed, cleansed of cancer cells if they are present, grown in tissue culture, then reinjected into the patient-who usually has an advanced cancer-after the patient undergoes therapy to destroy the remaining bone marrow. Because such techniques are prohibitively expensive, they are used sparingly. Gene therapy requires high-technology medical centers and a high level of training for all staff members involved in patient care. Clearly, even in developed nations these treatments are available only to the very wealthy, the very well insured, or enrollees in sponsored clinical trials.
Agricultural biotechnology is expected to become the predominant application of biotechnology in developing countries. In Africa, 42 Asia, Central and South America,43 and the Middle East,44 development of transgenic plants, biological pest control, tissue culture techniques for agriculture, microbial products for nutrient cycling, pathogen diagnostics for crops, and genetic mapping of tropical crops are major concerns. In developed nations, the term value added is used to denote the economic value of agricultural biotechnology products. Thus agricultural biotechnology in the United States, Canada, Europe, Japan, and Australia aims to produce products, such as fruit, vegetables and grains, whose genetic manipulation will provide new products that will cost more or bring greater profit to commercial entities than the standard hybrid product. Today in the United States the best-known commercial agricultural biotechnology products include Calgene's Flavr Savr tomato; Monsanto's recombinant bovine somato-trophin (BST) or growth hormone, which yields increased milk production by cows; frost-resistant strawberries; and biological pest control, which may include the introduction of genes from Bacillus thuringiensis and other bacteria, fungi, or viruses into plants, rendering the plants pest-resistant, 45 and the production of biopesticides via gene isolation and fermentation. Less well known is the production of recombinant rennin, an enzyme used in cheese manufacture, approved by FDA in 1990 . 46
Transgenic plants are those in which foreign genes have been introduced to improve a specific quality or characteristic of the plant. In the case of the Flavr Savr tomato, transportability is improved, an important factor in areas where fruits and vegetables must be transported long distances to market. Since the developed nations-such as the United States-are dependent on Central and South American countries for fruits, especially during winter and early spring, before the harvests in Florida and California, these technologies could increase the marketability of imported crops. Moreover, the introduction of foreign DNA could improve the protein quality of some foods, an important consideration for developing countries not only for human foods but also for animal feeds. Researchers also are working on improving the nutritional qualities of food starches and oils.
Biological pest control, a technique used in Asia for several millennia, has made great strides since the United States began to import B. thuringiensis into the United States from China in the late 1970s. 47 B. thuringiensis is engineered for inclusion in many plants, including grains, and it also is manufactured by recombinant techniques for use as a spray. Other means of biological pest control include virus resistance incorporated into the plant genome. 48 A virus-resistant squash is being reviewed by the USDA for approval in the United States; China is marketing a virus-resistant tomato; and potatoes resistant to virus are undergoing testing in Mexico. Scientists in Costa Rica are working to introduce virus-resistant genes into the criollo melon. 49 Recently, investigators identified a number of genes within crops themselves that confer disease resistance. 50 Thus it is only a matter of time until such genes are introduced into nonresistant species.
An important field in agricultural biotechnology will be the use of marker or “reporter” genes within transgenic species. 51 These genes are attached to functional genes introduced into plant cells, where their presence will indicate if the functional genes are working. Recently, researchers at the U.S. Department of Agriculture and University of Wisconsin inserted a gene for green fluorescent protein, derived from the jellyfish, Aequorea victoria, into orange tree cells. 52 This is a unique melding of agricultural and marine biotechnology and is an early example of more unique genetic introductions to come.
Much of the improvement in crops depends on improved plant tissue culture techniques and techniques for plant micropropagation. In tissue culture, individual cells are separated, genetically modified for desirable traits, and grown on nutrient media. Hormonal growth enhancers, nutrients (some of which are produced by tissue culture), and other additives determine the viability of the cells maintained in culture. In micropropagation, tiny plantlets are grown from cells started in tissue culture, all genetically the same, for distribution to farmers.
Agricultural production can be increased not only by direct manipulation of plants, but also by the addition of naturally occurring or genetically manipulated microorganisms. 53 Some of these organisms can be grown in batch fermenters; others require nurturing on host plants.
Agricultural products do not necessarily result in food products for the consumer market. Better plastics and biodegradable disposable items may be produced from plant extracts or refuse. Plant refuse, such as corn husks and stalks, also can be used to produce alcohols and other fuels such as ethanol. Finally, plants and animals can be genetically engineered to produce drugs and other biologically active molecules. In fact, the entire tobacco program of the USDA is now funded only for research on production of bioactive compounds from transgenic tobacco plants.
Not to be forgotten, plants, like humans, become diseased. Thus it is essential that simple diagnostic tests be developed for early detection of disease.
Marine biotechnology, which represents a small segment of the biotechnology industry-in the United States, approximately 85 companies or about 7 percent of all biotechnology companies-has applications in medicine, agriculture, materials science, natural products chemistry, and bioremediation. Because of the proximity of most of the world's tropical nations to the oceans, as well as their climates, these nations are particularly well suited to pursue marine biotechnology.
Aquaculture, a branch of marine biotechnology, is closely related to agriculture and is often included under that classification. Worldwide, marine aquaculture produced 14 million metric tons of fish in 1991, 54 with a market value of approximately $28 billion. 55 Demand for seafood worldwide is expected to increase by 70 percent over the next 35 years, 56 but this increase comes at a time when the world's fisheries are overexploited or “commercially extinct.” 57 Thus world aquaculture will need to increase production sevenfold by the year 2025 in order to meet the demand. USDA has predicted that biotechnology will aid in the improvement of captive management and reproduction of species, leading to more efficient species that make better use of food supplies and the production of healthier organisms with improved food and nutritional qualities. Furthermore, aquaculture can produce organisms for use as biomedical models in research, reservoirs for bioactive molecule production, and agents useful in bioremediation. Aquaculture is no longer a means of producing luxury foods, such as lobsters; it is a critical solution to the world's fisheries problems.
Algal aquaculture, an ancient art in Asia, produces not only seaweeds, but also food supplements, such as the omega-3 fatty acids and beta carotene, through microalgal cultivation. 58 The polysaccharides of algae are a valuable commodity and a much sought-after natural product.
One of the first approved biotechnology products offered on the market was an rDNA vaccine against colibacillosis. Thus animal husbandry was among the first sectors into which a commercial biotechnology product was introduced. Transgenic animals, such as pigs and cows, can be engineered for traits allowing better survival in marginal habitats, the production of more meat of higher quality, or even the production of recombinant pharmaceutical molecules for the human health care market.
Techniques for in vitro fertilization (IVF) were perfected in cattle, allowing breeders to produce multiple embryos from the cows and steers with the best qualities. Cows other than the genetic mothers can then carry the offspring. Biotechnology also can improve the health of these animals with new vaccines and diagnostic methods, 59 leading to increased trade in meat, animal products, and live animals (trade now is often restricted because of fears of spread of disease). For example, USDA, the Yale University School of Medicine, and Virogenetics, Inc. (a Troy, N.Y., biotechnology company specializing in vaccines) have produced a genetically engineered vaccine against Japanese encephalitis in swine, using Vaccinia virus and canarypox virus, 60 that is now undergoing field tests. Because the United States is concerned about importation of this disease from Asia, the market for the vaccine may be significant.
The production of single-cell protein (SCP)-a mass of microorganisms along with their nutrient contents-for both animal feed and human food has at least a 30-year history. 61 Initially, hydrocarbons were used as source material for the nutrients, but higher prices for petroleum rendered SCP non-cost-effective, thereby slowing research on SCP over the past two decades. Bacteria and yeasts have been used to ferment petroleum products, methanol, methane gas, lignocellulose, spent sulfite liquor byproducts of paper mills, molasses, whey, and other industrial fermentation byproducts. Increased efficiency, however, will be necessary before such processes are viable economically.
Bioremediation represents a large market force in biotechnology, but its potential has only recently been recognized. For example, U.S. federal laws requiring cleanup of toxic waste sites, surface-mining areas, 62 watersheds, and other polluted sites have caused the U.S. environ;nental remediation market to expand exponentially. 63 Indeed, in 1993 product sales increased in the chemical, environmental, and services category by 81 percent, to a total of $69.9 billion. 64
According to a recent National Research Council report, the U.S. bioremediation market will continue to grow rapidly and should reach $500 million a year by the year 2000. 65 A less conservative estimate is that $1.7 trillion will be spent on remediation of hazardous waste sites in the United States within the next 30 years! 66 This market does not even include known contamination sites in former Soviet bloc nations. Western nations have offered-but not paid-close to $1 billion for cleanup of these areas, 67 and clearly a sizable percentage of these sites will undergo some bioremediation. In 1993, 10 percent of Canada's biotechnology companies were working in environment-related areas-waste management, biomass, remediation and recycling, and materials reuse. 68 Europe, unfortunately, has as yet too few firms in environmental biotechnology for a statistically valid evaluation. 69
Both naturally occurring organisms and genetically modified organisms (GMOs), especially microorganisms, are used in environmental bioremediation. Current practice includes altering the environment of the naturally occurring microorganisms to make them work more efficiently; “bioaugmentation,” which, in general, involves the addition of nutrients, most commonly nitrogen and phosphorus; and controlling the oxygen and water contact. 70 Hydrocarbon contamination-oil spills-is currently remediated using this technology. Other contaminants, however, are more recalcitrant. Some of the aromatic compounds, polychlorinated biphenyls (PCBs), and other substances can be removed using genetically engineered microorganisms (GEMs), modified to degrade the target substance or to function in a particular type of environment. 71 The naturally occurring white rot fungus, Phanerochaete chrysosporium, can degrade PCBs, DDT, cyanide, TNT, and other toxic soil pollutants. 72 Cellular components, such as enzymes and biological surfactants, also can be used for environmental cleanup.
The Exxon Valdez oil spill cleanup provided a valuable case study in bioremediation. The application of oleophilic fertilizer resulted in enhancement of biodegradation through enrichment of those microorganisms that degrade oil,73 although some questions remain about the efficacy of this technique. 74 Other fertilizers also were used, along with specific nutrient enhancement and the addition of microorganisms. 75 The conclusion: bioaugmentation clearly was effective, but the addition of microorganisms has yet to be proven of value.
Many biological methods have been proposed for treatment of contaminated sites. For example, one method familiar to many backyard gardeners, homeowners, and farmers is composting, where bacteria and fungi decompose organic material; another is treating polluted soils in the presence of oxygen. 76 Composting has been used to clean oiled shoreline waste 77 and soil contaminated with TNT. 78 For some techniques that can be utilized in situ, where the contamination occurs, oxygen and nutrients are injected, using specialized equipment. Monitoring equipment may have to be brought on-site to establish efficacy and to provide a means of controlling degradation events.
In phytoremediation, heavy metals are removed from contaminated soils by plants that take up the metals and concentrate them. The plants then can be burned, both to recycle the metals by producing ores and to produce electricity. 79 Researchers are now studying how to produce transgenic plants with improved metal uptake capabilities.
Ex situ remediation is carried out in a bioreactor or filtration system, sometimes in a processing plant or other facility but not necessarily on-site. One interesting combination of in situ and ex situ bioremediation is the use of Sea Sweep, an absorbent composed of a treated material made from wood chips. After its use in cleaning oil spills, the material is gathered up and degraded by composting. 80
Soybean and rice hulls, rice bran, and sugar beet pulp have been found to bind metals and other industrial waste products and may prove useful in the environmental remediation 81 of solid or semisolid waste, liquid waste, sewage, and industrial and agricultural wastes. Many methods exist, including bioreactors and biofiltration.
The biological treatment of raw sewage is widely employed and is an example of how environmental cleanup can result in improved public health. The next step, which municipalities and cities throughout the world face, is what to do with the sludge that remains, as well as solid wastes (garbage). In some communities, sludge is sold for conversion to fertilizer. 82
Water treatments include not only treatment of wastewater, but also treatment of polluted natural bodies of water. In situ treatments consist of the use of microorganisms and localized bioreactors; ex situ, treatments are carried out in wastewater treatment plants. Microorganisms are being modified for use in wastewater treatment, and new methods-such as immobilization of microorganisms - are being developed to achieve increased microorganism contact with the biomass. Anaerobic wastewater treatment employing methanogenic bacteria that produce methane as a byproduct 83 may be especially useful where an affordable supply of energy, the methane gas, is needed.
The environmental test kit market is growing as kits become smaller and easier to use and portable field testing equipment, such as ion chromatographs, becomes available. Thus environmental monitoring can be carried out, with the use of sensors, on a continuous basis. A town in the Czech Republic, for example, has attached sensors to an illuminated scoreboard that gives continual readings of air pollutants. 84
Another aspect of environmental biotechnology is improvement of air quality and prevention of both the carbon dioxide buildup and ozone depletion that occur when pollutants are discharged to the atmosphere. The environmental biotechnology company Envirogen is studying organisms for bioremediation of air contaminated with halogenated hydrocarbons. 85
Ore extraction has caused massive environmental degradation in many parts of the world. For example, Brazil's waterways are polluted with mercury as a result of gold mining. In northern Russia, within the Arctic Circle and near its border with Finland, as much as 2,000 km² of forest were destroyed by the sulfurous byproducts of nickel mining. 86 engineering of microorganisms or the use of naturally occurring microorganisms to remove ores is likely to reduce or eliminate this kind of pollution at mine sites, as well as play a role in the bioremediation of the environmentally impacted mining regions.
Silviculture and the Role of Forests
The world's forests are being destroyed at a frighteningly rapid pace, the swiftest in history. Mature tropical forests, which are estimated to have covered 1.5-1.6 billion ha of the earth's surface, have been slashed in half, and forested land areas continue to decrease. 87 Canada is one of the leaders in biotechnology-based forestry services, earning $25 billion in 1992. Although most of this income is from the paper and pulp industry, bioremediation of effluent and the addition of bacteria to the paper-making process to decrease toxic effluent and improve paper quality are important research goals. Canadian researchers also are working on trees produced via tissue culture to aid in forest restoration. Investigators in Europe, Canada, and the United States have found that invading forest weeds capable of destroying native forest understory or preventing growth of young trees can be controlled by mycoherbicides. 88
Increased carbon dioxide has a major effect on the world's forests 89 since 90 percent of all carbon contained in terrestrial vegetation is in the forests. Increased atmospheric carbon results in increased growth of temperate and boreal forests. Thus it has been suggested atmospheric carbon be decreased by reducing the use of fossil fuels and increasing the use of biomass-based fuels that release little or no carbon dioxide. Another suggestion is that massive, managed tree plantations be established. 90 Although the latter is not feasible, biomass energy production is a particularly attractive method for developing countries. Studies to determine the effects of increased carbon dioxide are under way, and researchers are studying microorganisms associated with forest trees to devise new methods of altering carbon partitioning. 91 In the United States, the Electric Power Research Institute is analyzing the use of halophytic, or salt-tolerant, plants to sequester carbon dioxide. These plants have added potential as biofuel and to remediate toxic wastewater. 92
Nonagricultural Marine Biotechnology
The oceans represent the last great frontier for the discovery of new materials, medicines, and foods. Marine biotechnology can be applied in many areas outside those related to food production. 93 Marine natural products are applicable in fields as far ranging as molecular biology and bioremediation, to adhesives and pharmaceuticals. Enzymes isolated from thermophilic Archaea, microorganisms originally thought to be bacteria, some of which live in deepsea hydrothermal vents, are essential to molecular geneticists doing DNA sequencing. Agar, an important ingredient in nutrient substrates for growth of microorganisms in culture, and agarose, used to make gels for biochemical genetics and protein studies, are derived from algae.
The marine bacterium Acinetobacter calcoaceticus RAG-1 emulsifies hydrocarbons. Metal-concentrating marine bacteria also have been identified and may prove useful in marine bioremediation. The strength of adhesives produced by such marine organisms as mussels and barnacles has been recognized, and with the advent of modern biomolecular techniques scientists have been able to study and duplicate some of these materials. Some of the most potent natural toxins known to science are produced by marine organisms. These toxins could be used in research applications, such as studies of the neuromuscular junction, where much of their toxic activity is concentrated. They also could yield potent antineoplastic drugs. All these possibilities confirm that monitoring of the marine environment may yield clues about environmental degradation and that studies of marine ecology, including the problem of pollution of shorelines by bacterial pathogens, will provide improved human health.
Although a relatively minor consideration for developed nations at this time, energy production from biological waste products will prove important in the future, at first for developing nations, and later for those countries that no longer can afford to depend on petroleum products. 94 Production of methane from biogas digestors can be carried out on a local or industrial scale. A variety of hexose sugars can be used for the fermentation production of ethanol, but major sources are sugarcane, maize, wood, cassava, sorghum, Jerusalem artichoke, and grains. Waste whey also may be used. Bioconversion processes yield such byproducts as single-cell protein and enzymes for biocatalysis. 95
On the cutting edge of biotechnology research-currently too small to be even a blip in the marketplace-are biosensors, bioelectronics, biomaterials, and biocomputing (the use of biomolecules in electronic equipment), as well as the development of molecular machines or submicroscopic molecules, some of which are biological in origin, to carry out specific mechanical or energetic functions within the body. 96
Biosensors have applications in medicine, especially in diagnosis and therapeutics; 97 in process control, where biosensors could be used to determine changes in pH, conductivity, molecular concentration, or other measurable phenomena; 98 in bioremediation, where bioluminescent organisms could function as reporters; 99 and as environmental sensors. 100 For military use, biosensors could be linked to biocouplers to transmit a sensed event, via a biochip, to a computer system. 101 These could be used for environmental monitoring, terrain monitoring, or monitoring of personnel. They also could be used to detect chemical, toxic, and biological warfare (CTBW) agents.
The military could use biomaterials as protective clothing against CTBW agents, or as medical materials such as artificial bone and other tissue, or even as agents of warfare, causing engine malfunctions in enemy vehicles. 102 Nano-machines produced from biological molecules may be used as biosensors, in nano-scale manufacturing processes, 103 or even as methods of drug delivery. 104
Biocomputing will use biological material and reactions in computer chips.
Bioinformatics-the development of information systems on biology-is a worldwide effort in which all nations, no matter what their developmental stage, can participate.
Safety and Public Acceptance of Genetically Engineered Products
Monsanto's recombinant bovine somatotrophin, a drug expected to increase the milk production of a herd of cows by approximately 10-20 percent, received FDA approval in 1994, but a campaign against its use began long before BST was approved. Concerns were expressed that people who drank milk produced by BST-treated cows would be affected by the hormone and that these cows would be more likely to develop an infectious mastitis, requiring antibiotic treatment and thereby adding antibiotics to the milk supply. Although it has been concluded by the FDA and others 105 that BST is safe, an economic consequence of treating more than 800,000 of the 9.5 million cows in the United States with the hormone has been an increase in milk production and a decrease in milk prices. 106
For plants, it is feared that genetically engineered crops will become weeds or will transfer the introduced genes to native crops, which, in turn, would become weeds. 107 Another concern is that the genetically engineered crop itself may become a pest. 108 Other fears are that plants genetically engineered for virus resistance will cause the emergence of new viral pathogens that could affect other crops, that plants genetically engineered to produce toxins may inadvertently cause illness or death in animals feeding on them, and that engineered plants may out-compete wild plant species, altering habitats and affecting other species within those habitats. 109
To allay fears and guarantee that genetically modified organisms are employed responsibly, field testing should be done safely so that GMOs pose little or no risk; 110 indiscriminate field testing of GMOs should be discouraged. Investigators involved in field testing of GMOs should adhere to UNIDO's Voluntary Code of Conduct for the Release of Organisms into the Environment, as well as local and national regulations. 111
Public acceptance of the products of genetic engineering is a major obstacle to be overcome. For example, some chefs in the United States have banded together to boycott the Flavr Savr tomato, and there have been requests that milk from BST-treated cows be labeled as such, or, conversely, that milk from cows not treated with BST be so labeled, although FDA discourages such labeling. 112 Consumers Union opposes the use of BST and the European Union has banned its use. 113 Ironically, most Americans are unaware that some cheeses are manufactured using recombinant rennin.
It is hoped that public education will allay some of these fears. 114 Farmers need factual information as well to assist them in deciding to use GMOs and other products of biotechnology. 115
BIOTECHNOLOGY'S POTENTIAL IMPACT ON DEVELOPING COUNTRIES
Although it appears that developing nations can choose widely from the bountiful areas of biotechnology, each nation will, in fact, determine what will fit best within its social, cultural, and economic framework. Because many of these countries depend on their own agriculture to feed their populace, their major biotechnological thrust is likely to be in agricultural improvements.
Food crops that are better sources of nutrients, have greater yields, are more tolerant of extreme conditions, and resist disease are likely to have major effects on the food-growing regions of the world, especially in the developing countries. Simple methods to improve plant growth, such as the application of biofertilizers to crops, may require little in the way of technology and would be easy to implement. In India, for example, the introduction of earthworms and their castings (excrement) to degraded lands, along with other biofertilizers, has recovered land for agriculture. 116 Biological pest control, employing deterrent sprays produced by GMOs into which genes that code for production of natural pesticides have been cloned from plants, bacteria, or fungi, uses a technique-spraying-with which farmers are well acquainted. Disease-resistant animals, animals that can survive harsher conditions, and animals that are more efficient utilizers of feed also could have an important effect on world agriculture.
Training in tissue culture and micropropagation techniques may aid in the establishment or expansion of a locally based industry. For example, the Cycad Specialist Group of the International Union for Conservation of Nature and Natural Resources (IUCN) has suggested that local people be encouraged to raise cycads for sale from seeds or vegetative propagation in order to protect endangered plants from exploitation by commercial collectors, who pay little. 117 Such a cycad nursery program is under development in Mexico. Training programs in tissue culture and micropropagation techniques are being carried out in Costa Rica and also would be beneficial to the Colombian cut-flower industry. 118
The products of medical biotechnology are most likely to be of immediate benefit to developing nations, especially vaccines against the major scourges of the less-developed world such as malaria, hepatitis, dengue fever, HIV, and tuberculosis 119; the diagnostics and drugs needed to treat endemic diseases and highly infectious diseases; and the drugs and technologies that will have the widest range of applicability to increase the health of the populace. Although specialized drugs may not be major commodities in the developing nations at this time, some biotechnology firms are nevertheless optimistic. For example' Amgen's Neupogen, which is used to treat neutropenia associated with cancer chemotherapy or bone marrow transplantation (prohibitively expensive therapies) is now distributed in China. Neupogen has been approved for use in some countries for severe anemias. Epogen, human recombinant erythropoietin, is used to stimulate red blood cell production, especially in kidney dialysis patients. In 1993, Johnson and Johnson, which markets the drug in Europe and for the U.S. non-dialysis market, chalked up Epogen sales of $650 million.120
Many developing countries, as well as the former Eastern European bloc, have serious environmental problems that are highly amenable to bioremediation. 121 For example, much of Eastern Europe suffers from a legacy of heavy manufacturing, mining, and weapons testing without environmental controls. Poland's Vistula River is so polluted that its waters cannot be used at all. Approximately 80 percent of water samples tested from 200 river systems in the former Soviet Union showed bacterial and viral contamination levels so high that they were a threat to public health. 122 Asian rivers-even those in developed countries such as Taiwan-are among the worst in the world, containing raw sewage and industrial wastes that compromise public health and threaten entire ecosystems. Nevertheless, in many developing nations environmental cleanup has a lower priority than feeding and protecting the health of the population at large. Countries have pledged aid to the Eastern European countries, but it has not been forthcoming. 123 The World Bank just approved a $110 million loan to Russia, which will be supplemented by $90 million from the European Union, the United States, and other countries for environmental remediation. 124 Thus there is now an excellent opportunity to encourage and implement the efficient and cost-effective use of this technology.
PROBLEMS IN ADOPTING THE NEW BIOTECHNOLOGIES
Lack of Capital
For the developing countries, the new technologies will serve as a means of creating wealth 125 through products that not only can be used within the country, but also can be sold on regional or world markets. Barker, 126 however, cautions that any protective tariffs levied by these countries may induce other countries to seek substitutes for products exported by developing countries. For example, high-fructose corn sweetener, a product of the fermentation of maize, accounts for 50 percent of the U.S. sweetener market, a market that previously relied heavily on importation of cane sugar from developing countries. Furthermore, substitutes for other tropical products may become available in a trade atmosphere that discriminates against imports from developing nations. For example, according to the Rural Advancement Foundation International (RAFI), the United States is the world's largest importer of pyrethrum, a natural insecticide from the dried heads of the chrysanthemum, Chrysanthemum cinerariaefolium. Kenya is the world's largest pyrethrum producer; other sources are Tanzania, Ecuador, Rwanda, and Tasmania, located off the coast of Australia. If a U.S. company began to produce a genetically engineered pyrethrum product, Kenya's $75 million annual trade in the material-much of which is derived from plant micropropagation - might be destroyed. 127
Technologies that need little capital investment but would be money-saving or produce better-quality products also need to be considered. For example, a National Research Council advisory panel suggested modernization of the production of traditionally fermented foods at the village level, using affordable technology 128
Developing countries do not have the capital to engage in sophisticated biotechnological research and development. Although they may have the work force-some of whom may be well trained-expensive equipment, reagents, and process control are beyond their economic means. Thus it may be preferable that organisms to be used in developing nations be researched in the more affluent countries, but manufactured (grown or maintained) in the developing countries so that they can reap the benefit of these organisms. China and India and some funded research laboratories in Africa and other parts of Asia have the trained personnel and, in some cases, the necessary equipment. In such instances, the research groups, with additional support in the form of equipment and supplies, could carry out the molecular biology research needed to produce GMOs or related products.
Except for technologies requiring only traditional skills, such as those needed to plant seeds, use of most of the new technologies will require upgrading skills of local people and extensive public education to inform the populace about the technologies. Thus the introduction of value-added, high-technology products must include educational programs.
Property Rights and Biological Prospecting
There are fears, often well founded, within the chemical and biotechnology industries that their patented materials will not be protected in developing nations. 129 Some believe that international agreements, such as the General Agreement on Tariffs and Trade (GATT), will help to assuage these fears. 130 Others see GATT as imposing systems that benefit nations in the North at the expense of the people of nations in the South. 131
This being said, it is a fact that the world's tropical nations possess rich biotas that include especially valuable sources of medically active metabolises and natural products. Some compounds, although not yet characterized fully, are familiar in the local lore of indigenous people. But how do the more affluent nations, which tend to be in temperate climates, gain access to these riches? This question is being debated worldwide, and recent agreements, such as the one between Merck and INBio for extraction from plant material in Costa Rica, have come under criticism. 132
Other questions include: How are indigenous people who supply knowledge, their lands (resources), and their plant matter properly compensated? How are government entities compensated, if such compensation is deemed appropriate? Some indigenous peoples who share their knowledge of native medicine with researchers and corporations that later develop these materials into drugs believe they should be rewarded for their information, in some cases with a patent. A recent review of patent law, however, concluded that this information cannot be protected by patents. 133 Likewise, it has been suggested that unique, indigenous plants be patented, but, again, naturally occurring organisms that are not products of breeding programs or any scientific genetic manipulation are not now patentable. 134 At the very least, however, these plants may be eligible for protection by the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) under newly proposed IUCN categories. 135 Although this convention imparts no economic rights, it gives originating countries some degree of control over who takes the plants, where the plants are sent, and what uses will be made of them. One recently published book suggested that a radical change is needed in the concept of intellectual property, putting value on culturally transmitted knowledge as well as discoveries, 136 but this is unlikely to occur in the near future. Some of these issues were addressed at the Convention on Biological Diversity (also known as the Rio Convention), but they were not spelled out clearly and none of the current agreements fully address them. 137
In dealing with biological prospecting, also called accessing, all sides have to consider both what is fair and what is workable. Recently, a group of international Pew Charitable Trust scholars met to write ethical guidelines for bioaccessing that cover the behavior of and interactions with scientists, gene banks, and intergovernmental organizations. The guidelines propose that scientists treat indigenous peoples with respect, have local people serve as co-researchers, and ensure that the local communities receive equitable compensation for any products derived from locally collected and documented plant, microorganism, or animal-derived resources. Such guidelines will be effective only if there is a way to enforce agreements.
Although the Pew scholars may ask professional organizations to enforce member compliance, they also will append guidelines to an enforceable international treaty such as the Rio Convention. Janzen et al. have explained what a biodiversity research agreement between a researcher and “in-country biodiversity custodians” should include, but currently such arrangements vary. 138 The agreement between INBio and Merck gives the Costa Ricans cash in advance, trained personnel in the form of “parataxonomists” who can identify plants, and a percentage of sales of any products derived. 139 In contrast, the director of a herbarium in a southeast Asian country that has many unique plant species was approached by a large university from outside the region requesting that the herbarium provide it with local plant materials in exchange for vehicles and funding to pay for collecting the plants. The herbarium director, believing quite rightly that the university was taking advantage of his institution's impoverished condition, asked for a cooperative agreement between his institution, local universities, and the organization that requested the plant material, as well as some control over the material. The university was never heard from again and the herbarium director was roundly criticized by his colleagues for letting a “golden opportunity” pass. Although guidelines cannot cover all situations-one scholar involved in drafting the Pew guidelines admitted they do not cover his research situation-they may aid in reaching fair and equitable agreements. The Brazilian government is now considering an industrial property bill that could be used as a model for determining compensatory agreements between the accessors and the sources of biodiversity. 140
An added problem in dealing with biodiversity accessing is enforcement of the Rio Convention. For example, the United States is one of the major forces for worldwide conservation, but it is not yet an official signatory of the convention. President Bill Clinton, without congressional approval, signed the treaty but with interpretative statements on Articles 16 (technology transfer) and 19 (biosafety protocols). 141 A Republican-dominated Congress is not likely to approve the initiative.
Safety and Ethical Issues
Although problems are associated with the public's perception of the safety of GMOs, 142 numerous field trials have been carried out worldwide, 143 and since 1987 field tests of more than 860 transgenic crops have been approved in the United States; at least another 250 tests have been approved in Europe since 1991. 144 Regulation and safety protocols may be accomplished with the assistance of international oversight organizations and by agreements, or through national or local laws. UNIDO's “Voluntary Code of Conduct for the Release of Organisms into the Environment” was conceived as a basic document from which a more specific code could be built. 145 Governments lacking internal expertise can call on advice from the Stockholm Institute for Environment, funded jointly by the Swedish government and the Rockefeller Foundation. Perhaps a new international nongovernmental commission on GMOs could aid countries that need assistance in formulating regulations and evaluate projects being considered for implementation within their borders.
There is concern that biotechnology-based products may lead to pressure on consumers to purchase value-added products they may not need. The Rural Advancement Foundation International worries that the addition of genetically engineered human proteins, produced by transgenic cows, into infant formula may lead the infant formula industry to undertake aggressive marketing techniques, especially in developing countries. 146 Other questions about safety and efficacy revolve around new medical technologies. Clinical trial requirements are more complex in some countries than in others, and review may be shorter in some countries, allowing a drug to enter the marketplace in Europe, for example, earlier than in the United States. 147 This in itself is not a problem, but it will become one if a drug or vaccine is unavailable in the location with the greatest need. For example, in the recent bubonic and pneumonic plague epidemics in India, a major problem was obtaining vaccine. An effective vaccine against pneumonic and bubonic plague had been manufactured in the United States by Cutter Laboratories, but in 1992 Cutter sold the rights to the vaccine to another company. Because FDA regulations required that the vaccine be treated as a new product and undergo testing, it was not available when urgently needed. 148 International cooperation, and some foresight on the part of governments, should have been able to resolve this problem long before it became an urgent one. Companies may opt for testing a product in a country with fewer controls. For example, because the U.S. National Institutes of Health are delaying tests of a HIV vaccine that many fear will not be effective, the manufacturers are considering carrying out trials in Thailand. 149
Other obstacles to the universal adoption of biotechnology projects and products are cultural, educational, economic, governmental, and infrastructural in nature. If, for example, difficulties are encountered in delivering agricultural products to market, no change in the qualities of those products will overcome the infrastructural problems. In other words, there is no reason to introduce genetically engineered apples that ship better in a region where the apples rot on the trees because they cannot be shipped to market. Introducing a complicated test kit for clinical use by marginally trained employees will not yield the expected public health benefits, especially if requirements such as a”cold chain” are involved. A recent attempt to introduce clinical test kit panels into China failed because the enzyme-linked immunoassay (ELISA) tests, although relatively simple to use by U.S. standards, were deemed too complex and time-consuming by the Chinese distributor.
When introducing new crops, one must be able to distribute the starter material and explain to the farmers how best to plant and grow the crops. 150 In order to vaccinate people against disease, an infrastructure must be in place to ensure that the vaccine reaches the people who need it. The introduction of sophisticated technology into an area where the supply of electricity is erratic will not lead to progress unless changes are made in the way electricity is supplied. Moreover, complicated regulations or corrupt governments can inhibit the flow of new technologies. For example, recently an act of the Romanian parliament was required to import a biotechnology product needed by a local area. 151 And the INBio-Merck agreement is successful in part because the Costa Rican government is not corrupt, but many governments foster corruption or look the other way. 152
Finally, as noted earlier, unless the public understands both the value of and need for advances in biotechnology, problems of acceptance of biotechnology products will persist. 153 Thus biotechnology products and processes, even those discovered and proposed for use in developing nations, should include not only the introduction of the technology but also public education.
What Technologies Will Work in Developing Countries?
What will work? In 1990, a National Research Council committee produced a list of 98 plant biotechnology projects for USAID support in developing countries. The list ranged from the development of restriction fragment length polymorphism (RFLP) maps of such plants as sorghum, cowpea, and potato, to tree tissue culture and studies of the role of biotechnology in plant agriculture. 154 Fruits, vegetables, and grains with improved nutrient content and disease resistance will add significant value to agriculture. Integrated pest management, a form of the “old” biotechnology well known in some of the developing nations, could be expanded.
Marine biotechnology, including aquaculture of fish, algae, and microalgae, is a genuinely viable area for wide application in developing nations, especially in light of the severe overfishing that is occurring today. Many countries, especially those in the Pacific Rim, already have some expertise in this area, and in others expertise could be developed with the appropriate training. Marine biotechnology programs and aquaculture not only will provide food for the table, but also can develop products from natural resources.
Vaccines and pharmaceuticals that improve public health and decrease infant mortality, as well as test kits that permit screening of large proportions of at-risk populations for transmissible, even hereditary, disease will be welcomed into the markets of developing nations. In fact, nations should be encouraged to form the infrastructure necessary to develop their own vaccines, especially “orphan vaccines” for tropical diseases specific to their country. Thailand, for example, is developing its own vaccine production capability.
Programs for alternative energy sources, especially for countries that are dependent on imported fossil fuels, should be encouraged. Methane gas production, as well as the production of bioethanol and other fuels, may be an economically advantageous means of augmenting the use of fossil fuels, hydroelectricity, and nuclear power.
Environmental bioremediation can be used to introduce or upgrade public sanitation, clean polluted soil and water, and clean up toxic environments.
Finally, the development of databases, especially related to depositories of biological material, also may be important projects for international cooperation. The establishment and use of germplasm banks not only will help to preserve biodiversity but also will save food resources for future use.
Because science is international, international advisory panels, oversight groups, biodiversity consortia, research and granting organizations, and scientific societies are agents for problem solving on a global level and pooling resources across national boundaries. International organizations such as the World Bank and the United Nations, together with international treaties such as the biodiversity treaty, can sponsor the establishment of databases and networks that will allow greater international communication and cooperation. The technologies are ready for exploitation; it is the financing and the will to put these technologies into place that are needed.
The excellent and critical assistance of Dr. Myrna Watanabe in preparation of this manuscript is gratefully acknowledged.
1. Webster's Ninth New Collegiate Dictionary (Springfield, Mass.: Merriam-Webster, 1984).
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