Genetic Engineering and Biotechnology: An Overview
HUMAN BEINGS RELY ON THE EARTH'S bountiful Supply of life for a. wide variety of essential substances. We survive by consuming the edible portions of plants and animals, and our clothes and kooes are composed at least in part of biologically derived materials.'. Microorganisms are used to make bread, to convert milk into cheese:, and to brew alcoholic beverages. Common substances like vinegar? vitamins, and monosodium glutamate are manufactured using mic rofciial "factories." Antibiotics are extracted from various strains of moulds and bacteria.
Overr these course of time, human ingenuity has gradually worked on these organisms. People have selected plants, animals, and microoirganisms with the most useful characteristics from among those in the environment. They have bred individuals from same or closely related species to produce offspring with new, more desirable combinations of traits. Among the results of this genetic husbandry have been improved varieties of crops and livestock, industrial microbes that are hardier and more efficient, and novel Antibiotics.
During the past 15 years, researchers have begun to acquire a new and unprecedented degree of control over the genetic constitution of living things. The techniques of genetic engineering, and in particular recombinant DNA, have made it possible to manipulate genetic material on these smallest possible scale individual genes. The effect on molecular biology, immunology, and other scientific disciplines has been little short of revolutionary. Says Douglas Costle, former administrator of the Environmental Protection Agency, "While it is probably true that physics was the science of the first half of the century, it is almost certain to be molecular biology in what remains of this century and well into the next." The development of genetic engineering has been a direct result of generous governmental funding for basic biomedical research since World War II, and it is this research that has benefited most immediately from the new techniques. "The impact of this technology has been enormous at the scientific level," says Philip Leder of Harvard Medical School. "Prior to 1973-74, when these experiments began, all that geneticists knew about the existence of genes they inferred from their properties-Recombinant DNA technology changed that in a stroke. In so doing, it altered genetics from a purely inferential science to, at least in part, an analytical, observational science."
Overr these course of time, human ingenuity has gradually worked on these organisms. People have selected plants, animals, and microoirganisms with the most useful characteristics from among those in the environment. They have bred individuals from same or closely related species to produce offspring with new, more desirable combinations of traits. Among the results of this genetic husbandry have been improved varieties of crops and livestock, industrial microbes that are hardier and more efficient, and novel Antibiotics.
During the past 15 years, researchers have begun to acquire a new and unprecedented degree of control over the genetic constitution of living things. The techniques of genetic engineering, and in particular recombinant DNA, have made it possible to manipulate genetic material on these smallest possible scale individual genes. The effect on molecular biology, immunology, and other scientific disciplines has been little short of revolutionary. Says Douglas Costle, former administrator of the Environmental Protection Agency, "While it is probably true that physics was the science of the first half of the century, it is almost certain to be molecular biology in what remains of this century and well into the next." The development of genetic engineering has been a direct result of generous governmental funding for basic biomedical research since World War II, and it is this research that has benefited most immediately from the new techniques. "The impact of this technology has been enormous at the scientific level," says Philip Leder of Harvard Medical School. "Prior to 1973-74, when these experiments began, all that geneticists knew about the existence of genes they inferred from their properties-Recombinant DNA technology changed that in a stroke. In so doing, it altered genetics from a purely inferential science to, at least in part, an analytical, observational science."
In just a decade of work with recombinant DNA, researchers have industrialized nations. But because it directly affects such basic human concerns as food production, health care, and energy availability, it is likely to eventually have worldwide implications. As Leder says, "It is impossible for us to say with confidence that something reasonable cannot be done using this technology."
Any technology that deals so directly with the basic processes of life inevitably raises compelling questions. The early debates about the safety of recombinant DNA research have quieted, but new issues have taken their place. Will the release of genetically engineered organisms into the environment pose threats to human health or to natural ecosystems? How should the ability to alter the genetic makeup of human beings be managed? Is new legislation necessary to regulate
the products that are likely to be manufactured with genetic engineering. Should the U.S. government be encouraging the development of the American biotechnology industry in light of the considerable competition expected from biotechnology companies abroad.
Any technology that deals so directly with the basic processes of life inevitably raises compelling questions. The early debates about the safety of recombinant DNA research have quieted, but new issues have taken their place. Will the release of genetically engineered organisms into the environment pose threats to human health or to natural ecosystems? How should the ability to alter the genetic makeup of human beings be managed? Is new legislation necessary to regulate
the products that are likely to be manufactured with genetic engineering. Should the U.S. government be encouraging the development of the American biotechnology industry in light of the considerable competition expected from biotechnology companies abroad.
These and other difficult questions are being asked with a special urgency. Biotechnology is growing so quickly, and its ultimate influence is so wide-ranging, that it is straining the capacity of public and private institutions to deal with it. "We are running out of time," explains Senator Albert Gore, Jr., "in the sense that the technology is developing so rapidly that we are going to have to make some tentative decisions without the base of understanding that a democracy requires for subtle and difficult decisions. Requests for field tests of genetically engineered organisms are already beginning to be made, as companies proceed with their research programs. The first authorized human gene therapy experiments are expected to be conducted later this year. Both of these facts underscore how important it is to develop a coherent set of scientific and ethical guidelines to help us evaluate the implications of this technology."
The Molecular and Microbial Products of Biotechnology
Most of the products being developed in biotechnology fall into one of two very broad categories: chemical substances that can be made using genetically engineered organisms, and genetically engineered organisms themselves. Included in the first category are the wide variety of compounds that have drawn the attention of pharmaceutical manufacturers. Genetically engineered microorganisms can be used to produce hormones like insulin and growth hormone, other biological response modifiers such as interferons and neuropeptides, blood products like clotting and antishock factors, vaccines against previously unpreventable diseases, new antibiotics, and many other kinds of biologically active molecules.
In addition, the availability of large quantities of these previously scarce molecules enables researchers to learn more about their function in the body, which will result in new therapeutic agents. The ability of genetically engineered microorganisms to produce valuable chemical compounds will also lead to applications in many other industries, including the food processing, chemicals, and energy industries. Among the numerous substances whose production could be
affected by biotechnology are alcohol, enzymes, amino acids, vitamins, high-grade oils, adhesives, and dyes. Biotechnology will also make possible the synthesis of novel chemical compounds in these commercial sectors.
The use of biological processes in industry places special demands on manufacturing. Generally, biological conversions entail a fermentation process. Nutrients and raw materials are supplied to living cells in a reactor vessel; the cells convert the raw materials into products; and the products are withdrawn, separated, and purified. These bioconversions must be carefully monitored and controlled. Indeed, the development of economical fermentation equipment and methods is one of the greatest challenges facing biotechnology today. But not all genetically engineered microorganisms will be used in fermentation processes. Some are being designed for use in the environment. Many of these will have agricultural applications, but others might be used to degrade wastes or toxic substances, to leach or concentrate minerals from ores, or to increase the extraction of oil from wells.
An important subset of the molecular products of biotechnology are the proteins known as monoclonal antibodies. These are produced not through recombinant DNA techniques but through the fusion of a tumor cell with an antibody-producing white blood cell. The result is a
virtually immortal clone of cells producing antibodies that are chemically identical. Monoclonal antibodies have already found a wide range of uses in research, because of their remarkable ability to attach to specific molecular configurations. They are also being used in a number of in vitro diagnostic tests to detect the presence of disease or other conditions. At the same time, investigators are examining their possible uses within the body to expose diseased areas to scanning instruments, to confer passive immunity against disease, or to carry biologically active agents to diseased tissues.
Biotechnology in Agriculture
Many of the products being developed for use in human health care have agricultural analogs. New or cheaper drugs, vaccines, and diagnostics will all cut the toll of disease and lost productivity that continues to be a major concern in agriculture. Furthermore, genetically engineered microorganisms will be used to produce feed additives, growth enhancers, and other compounds that will boost agricultural yields.
But biotechnology has a fundamentally different capability in agriculture. It can potentially be used to change the genetic constitution of microorganisms, plants, and animals to make them more productive, more resistant to disease or environmental stress, or more nutritious. In doing so, biotechnology, like the green revolution before it, could have a dramatic effect on the problems of food production and hunger around the world. Probably the first application of this type will involve the genetic engineering of microorganisms. Researchers are working to produce
microorganisms that will supply plants or animals with essential nutrients, protect them from insects or disease, or provide them with compounds that influence their growth. A central concern of this work is the competitiveness of the genetically engineered microorganisms in
agricultural environments, since the microorganisms will generally have to survive and multiply to perform their functions.
The genetic engineering of plants and animals is a far more daunting technical task than the genetic engineering of microorganisms, but this is where the greatest potential benefits lie. Researchers have already succeeded in inserting functional genes into plant cells, in regenerating whole plants that express the gene, and in having the gene passed on to offspring. In this way, they hope to eventually be able to transfer into plants such traits as resistance to pesticides, tolerance to environmental conditions such as salinity or toxic metals, greater nutritive value or productivity, or perhaps even the ability to fix nitrogen from the atmosphere. However, major technical barriers still prohibit the genetic engineering of most of the agriculturally important food crops. For instance, the majority of desirable agricultural traits are likely to arise from the interaction of many different genes, making it difficult to transfer these traits between plants. A major current limitation on research in this area is the paucity of basic biochemical knowledge about plants. To take one example, the genetic origins of almost all agriculturally useful traits are not yet known.
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