Genetic Engineering and the Fermentation TechnologiesBiotechnology—an introduction Biotechnology involves the use in industry of living organisms or their components (such as enzymes). It includes the introduction of geneti- cally engineered micro-organisms into a variety of industrial processes. The pharmaceutical, chemical, and food proc- essing industries, in that order, are most likely to take advantage of advances in molecular ge- netics. Others that might also be affected, al- though not as immediately, are the mining, crude oil recovery, and pollution control in- dustries. Because nearly all the products of biotechnol- ogy are manufactured by micro-organisms, fer- mentation is an indispensable element of bio- technology’s support system. The pharmaceuti- cal industry, the earliest beneficiary of the new knowledge, is already producing pharmaceu- ticals derived from genetically engineered micro-organisms. The chemical industry will take longer to make use of biotechnology, but the ultimate impact may be enormous. The food processing industry will probably be affected last. This report examines many of the pharma- ceutical industry’s products in detail, as well as Fermentation There are several ways that DNA can be cut, spliced, or otherwise altered. But engineered DNA by itself is a static molecule. To be any- thing more than the end of a laboratory exer- cise, the molecule must be integrated into a sys- tem of production; to have an impact on society at large, it must become a component of an in- dustrial or otherwise useful process. The process that is central to the economic some of the secondary impacts that the technol- ogies might have. Because the chemical and food industries will feel the major impact of bio- technology later, specific impacts are less cer- tain and particular products are less identifi- able. The mining, oil recovery, and pollution control industries are also candidates for the use of genetic technologies. However, because of technical, scientific, legal, and economic un- certainties, the success of applications in these industries is more speculative. The generalizations made with respect to each of the industries should be viewed as just that—generalizations. Because a wide array of products can be made biologically, and because different factors influence each instance of pro- duction, isolated examples of success may ap- pear throughout the industries at approximate- ly the same time. In almost every case, specific predictions can only be made on a product-by- product basis; for while it may be true that bio- technology’s overall impact will be profound, identifying many of the products most likely to be affected remains speculative. success of biotechnology has been around for centuries. It is fermentation, essentially the process used to make wine and beer. It can also produce organic chemical compounds using micro-organisms or their enzymes. Over the years, the scope and efficiency of the fermentation process has been gradually im- proved and refined. Two processes now exist, both of which will benefit from genetic engi- 49Page 550 . Impacts of Applied Genetics—Micro-Organisms, Plants, and Animals neering. In fermentation technology, living or- ganisms serve as miniature factories, convert- ing raw materials into end products. In enzyme technology, biological catalysts extracted from those living organisms are used to make the products. Fermentation industries The food processing, chemical, and pharma- ceutical industries are the three major users of fermentation today. The food industry was the first to exploit micro-organisms to produce alcoholic beverages and fermented foods. Mid- 16th century records describe highly sophisti- cated methods of fermentation technology. Heat processing techniques, for example, anticipated pasteurization by several centuries. [n the early 20th century, the chemical in- dustry began to use the technology to produce organic solvents like ethanol, and enzymes like amylase, used at the time to treat textiles. The chemical industry’s interest in fermentation arose as the field of biochemistry took shape around the turn of the century. But it was not until World War I that wartime needs for the organic solvent acetone—to produce the cor- dite used in explosives–substantially increased research into the potential of fermentation. Thirty years later after World War 11, the phar- maceutical industry followed the chemical in- dustry’s lead, applying fermentation to the pro- duction of vitamins and new antibiotics. Today, approximately 200 companies in the United States and over 500 worldwide use fermentation technologies to produce a wide variety of products. Most use them as part of production processes, usually in food process- ing. But others manufacture either proteins, which can be considered primary products, or a host of secondary products, which these pro- teins help produce. For genes can make en- zymes, which are proteins; and the enzymes can help make alcohol, methane, antibiotics, and many other substances. Proteins, the primary products, function as: enzymes such as asparaginase which are used in the treatment of leukemia; q q q q structural components, such as collagen, used in skin transplants following burn trauma; certain hormones, such as insulin and human growth hormone; substances in the immune system, such as antibodies and interferon; and specialized functional components, such as hemoglobin. Fermentation technologies are so useful for pro- ducing proteins partly because these are the direct products of genes. But proteins (as en- zymes) can also be used in thousands of addi- tional conversions to produce practically any organic chemical and many inorganic ones as well: (See figure 16. ) Figure 16.-Diagram of Products Available From Cells isolated B Raw material Product In (A) DNA directs the formation of a protein, such as in- sulin, which is itself the desired product. In (B), DNA directs the formation of an enzyme which, in turn, converts some raw material, such as sugar, to a product, such as ethanol. SOURCE: Office of Technology Assessment.Page 6
Ch. 3—Genetic Engineering and the Fermentation Technologies . 51 carbohydrates, such as fructose sweeten- ers; lipids, such as vitamins A, E, and K; alcohols, such as ethanol; other organic compounds, such as acetone; and inorganic chemicals, such as ammonia, for use in fertilizers. Fermentation is not the only way to manufac- ture or isolate these products. Some are tradi- tionally produced by other methods. If a change from one process to another is to occur, both economic and societal pressures will help deter- mine whether an innovative approach will be used to produce a particular product. Alan Bull has identified four stimuli for change and in- novation: 1 1. abundance of a potentially useful raw material; 2. scarcity of an established product; 3. discovery of a new product; and 4. environmental concerns. And conditions existing today have added a fifth stimulus: 5. scarcity of a currently used raw material. Each of these factors has tended to accelerate the application of fermentation. 1. Abundance of a potentially useful raw ma- terial.—The use of a raw material can be the driving force in developing a process. When straight chain hydrocarbons (n-al- kanes) were produced on a large scale as petroleum refinery byproducts, fermenta- tion processes were developed to convert them to single-cell proteins for use in ani- mal feed. 2. Scarcity of an established product.—The new-found potential for producing human hormones through fermentation technol- ogy is a major impetus to the industry to- day. Similarly, many organic compounds once obtained by other processes—like citric acid, which was extracted directly ‘/. ‘I”. lhJll, 11. [:. FllWrCM)Ci, and (:. Rat ledge, kficrobia/ Techndo,gv: (~urrent Sfafe, Future Prospects, Z$lth Symposium ot’ the Society for (kllf>l’iil hlicrut)iub~y al 1 llll)f~rsitv uf (:iilllt)l’itl~f~, April 1979 ((:illllt)l’idg(’, l’;ll~lillld: (kmt)ridge [~l;ilwrsit}~ Press, 1 979), pp. 4-8. 3. 4. 5. from citrus fruits—are now made by fer- mentation. As a result of more efficient technology, products from vitamin B12 to steroids have come into wider use. Discovery of a new product.—The discovery that antibiotics were produced by micro- organisms sparked searches for an entirely new group of products. Several thousand antibiotics have been discovered to date, of which over a hundred have proved to be clinically useful. Environmental concerns. —The problems of sewage treatment and the need for new sources of energy have triggered a search for methods to convert sewage and munici- pal wastes to methane, the principal com- ponent of natural gas. Because micro-orga- nisms play a major role in the natural cy- cling of organic compounds, fermentation has been one method used for the conver- sion. Scarcity of a currently used raw materi- a/.—Because the Earth’s supplies of fossil fuels are rapidly dwindling, there is intense interest in finding methods for converting other raw materials to fuel. Fermentation offers a major approach to such conver- sions. Fermentation technologies can be effective in each of these situations because of their out- standing versatility and relative simplicity. The processes of fermentation are basically identi- cal, no matter what organism is selected, what medium used, or what product formed. The same apparatus, with minor modifications, can be used to produce a drug, an agricultural prod- uct, a chemical, or an animal feed supplement. Fermentation using whole living cells Originally, fermentation used some of the most primitive forms of plant life as cell fac- tories. Bacteria were used to make yogurt and antibiotics, yeasts to ferment wine, and the filamentous fungi or molds to produce organic acids. More recently, fermentation technology has begun to use cells derived from higher plants and animals
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