Biotechnology

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Biotechnology, broadly defined, refers to the manipulation of biology or a biological product for some human end. Before recorded history, humans grew selected plants for food and medicines. They bred animals for food, for work, and as pets. The ancient Egyptians learned how to maintain selected yeast cultures, which allowed them to bake and brew with predictable results. These are all examples of biotechnology. In more recent times, however, the term "biotechnology" has mainly been applied to specifically industrial processes that involve the use of biological systems. Today many biotechnology companies use processes that make use of genetically engineered microorganisms.

Following 1953, when Thomas Watson and Francis Crick published their famous paper on the double helix structure of DNA, a series of independent discoveries were made in chemistry, biochemistry, genetics, and microbiology, which together brought about a revolution in biology and led to the first experiments in genetic engineering in 1973. Because of this revolution, scientists learned to modify living microorganisms in a permanent, predictable way. Bacteria have been made to produce medical products, such as hormones, vaccines, and blood factors, that were formerly not available or available onlyat great expense or in limited amounts. Crop plants have been developed with increased resistance to disease or insect pests, or with greater tolerance to frost or drought. What has made all these things possible is the collection of biochemical and molecular biological techniques for manipulating genes, which are the basic units of biological inheritance. These are the techniques used in genetic engineering or recombinant DNA technology.

The fusion of traditional industrial microbiology and genetic engineering in the late 1970s led to the development of the modern biotechnology industry. Using recombinant DNA technology, this industry has brought a long and steadily growing list of products into the marketplace. Human insulin produced by genetically engineered bacteria was one of the first of these products. It was followed by human growth hormone; an anti-viral protein called interferon; the immune stimulant called interleukin 2; a tissue plasminogen activator for dissolving blood clots; two blood-clotting factors, labeled VIII and IX, which are administered to hemophiliacs; and many other products.

The production of certain chemicals has already become an important biotechnological industry. Vitamin C is a prime example. Humans, as well as other primates, guinea pigs, the Indian fruit bat, several species of fish, and a number of insects, all lack a key enzyme that is required to convert a sugar, glucose, into vitamin C.

No single bacterial genus or species is known that will carry out all of the reactions needed to synthesize vitamin C, but there are two (Erwinia species and Corynebacterium genus) that, between them, can perform all but one of the required steps. In 1985 a gene from one of these genus (Corynebacterium) was introduced into the second organism (Erwinia herbicola), resulting in a new bacterial form. This engineered organism can be used to produce a precursor to vitamin C that is converted via one chemical reaction into this essential vitamin. The engineering of many other microorganisms is being used to replace complex chemical reactions. For example, amino acids, needed for dietary supplements, are produced on a large scale using genetically modified microorganisms, as are antibiotics.

Another important class of compounds produced by biotechnology is enzymes. These protein catalysts are used widely in both medical and industrial research. Proteases, enzymes that break down proteins, are particularly important in detergents, in tanning hides, in food processing, and in the chemical industry. One of the most significant commercial enzymes of this type is subtilisin, which is produced by a bacterium. Because many stains contain proteins, the manufacturers of laundry detergents include subtilisin in their product. Subtilisin is 274 amino acids long, and one of these, the methionine at position 222, lies right beside the active site of the enzyme. This is the site on the enzyme's surface where the substrate is bound, and where the reaction that is catalyzed by the enzyme takes place. In this instance the substrate is a protein in a stain, and the reaction results in the breaking of a peptide bond in the backbone of the protein. Unfortunately, methionine is an amino acid that is very easily oxidized, and laundry detergents are often usedin conjunction with bleach, which is a strong oxidizing agent. When used with bleach, the methionine in subtilisin is oxidized and the enzyme is inactivated, preventing the subtilisin from doing its work of breaking down the proteins present in food stains, blood stains, and the like.

To overcome this problem, genetic engineering techniques were used to isolate the gene for subtilisin, and the small part of the gene that codes for methionine 222 was replaced by chemically synthesized DNA fragments that coded for other amino acids. The experiment was done in such a way that nineteen new subtilisin genes were produced, and every possible amino acid was tried at position 222. Some of the altered genes gave rise to inactive versions of the enzyme, but others resulted in fully functional subtilisin. When these subtilisins were tested for their resistance to oxidation, most were found to be very good (except when cysteine replaced methionine: It too is easily oxidized). So now it is possible to use laundry detergent and bleach at the same time and still remove protein-based stains. This type of gene manipulation, which has been called "protein engineering," has already been used for making beneficial changes in other industrial enzymes, and in proteins used for medical purposes.

Biotechnology companies are continuing to produce new products at an impressive rate. Numerous clinical testing procedures for human disorders such as AIDS and hepatitis and for disease-causing organisms such as those responsible for malaria and Legionnaires' disease (a lung infection caused by the bacterium Legionella pneumophila), are based on diagnostic testing kits that have been developed by biotechnology companies. Many of these assays make use of recombinant antibodies, while others rely on DNA primers that are used in the polymerase chain reaction to detect DNA sequences present in an infecting organism, but not in the human genome.

Trangenic plants are now grown on millions of acres. Many of these plant species have been engineered to produce a protein, normally synthesized by the bacterium Bacillus thuringiensis, which is toxic to a number of agriculturally destructive insect pests but harmless to humans, most other non-insect animals, and many beneficial insects such as bees.

Like all industries, the biotechnology industry is subject to rules and regulations. Legal, social, and ethical concerns have been raised by the ability to genetically alter organisms. These have resulted in the establishment of governmental guidelines for the performance of biotechnology research, and specific requirements have been set to control the introduction of recombinant DNA products into the marketplace. General governmental guidelines for biotech research are published on the Internet at http://www.aphis.usda.gov/biotech/OECD/ usregs.htm. Guidelines for plant genetic engineering and biotechnology are available at http://sbc.ucdavis.edu/Outreach/resourc e/US_gov.htm.

Before Captain James Cook, the famous English sailor and navigator, had his men drink lime juice (which contains vitamin C) during extended sea voyages, many sailors fell ill or died of the vitamin C deficiency known as scurvy.

Agricultural Biotechnology; Biotechnology and Genetic Engineering, History Of; Cloning Genes; Cloning Organisms; Gene Therapy; Genetic Testing; Genetically Modified Foods; Hemophilia; Polymerase Chain Reaction;; Recombinant Dna; Transgenic Animals; Transgenic Microorganisms; Transgenic Plants.

Glick, Bernard R., and Jack J. Pasternak. Molecular Biotechnology: Principles and Applications of Recombinant DNA. Washington, DC: ASM Press, 1998.

Marx, Jean L. A Revolution in Biotechnology. Cambridge, MA: Cambridge University Press, 1989.

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Rudolph, Frederick B., and Larry V. McIntire, eds. Biotechnology: Science, Engineering, and Ethical Challenges for the Twenty-first Century. Washington, DC: Joseph Henry Press, 1996.

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