Genetics and Genetic Engineering

Genetics and Genetic Engineering. The second half of the twentieth century brought a cornucopia of genetic marvels. Cloned human genes like insulin became the basis of genetically engineered medicines. Genetically‐based diagnostic tests predicted the probability of hereditary diseases like colon cancer (in adults) and Tay‐Sachs (in developing fetuses). Futuristic medical interventions, like gene therapy, were in the testing stage. American scientists were at the forefront of many of these discoveries, and American society was consequently often the first to confront the ethical and social implications of the biological revolution.

Though these developments seemed of relatively recent stamp, genetic engineering of the old‐fashioned, methodical sort had in fact been a feature of agriculture for centuries, whether breeding beefier cattle or juicier peaches. At the turn of the twentieth century, upon the rediscovery of Gregor Mendel's laws of inheritance, American genetics research rose to prominence, especially at Columbia University, where Thomas Hunt Morgan identified a Mendelian pattern of inheritance in fruit fly mutations and, in 1910, linked a particular mutant trait to maleness—arguably the first mapping of a gene to a particular chromosome. In 1913, A.H. Sturtevant, an undergraduate in Morgan's lab, discovered that genes are arranged in linear fashion along chromosomes, establishing the basic principle of all subsequent genetic mapping.

As counterpoint to this basic research, a number of biologists became tantalized by the possibility of improving human society through genetic manipulation. This movement, known as eugenics, first arose in England but was embraced with great fervor by some American researchers, in part as a reaction against the great wave of immigration from southern and eastern Europe. The eugenicists ascribed a genetic component to such human traits as loyalty; humor; a propensity for crime and violence; and even “thallasophilia,” a genetically predetermined love of the sea said to be inherited by ship captains. The American eugenics movement, led by the biologist Charles B. Davenport of the Carnegie Institution of Washington, D.C., was attacked both for poor research techniques and its taint of racism. Nonetheless, the Eugenics Record Office at Davenport's Cold Spring Harbor Laboratory on Long Island remained in operation until 1942.

Two years later, in 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarthy at Rockefeller University first established the molecular nature of heredity by implicating deoxyribonucleic acid (DNA) in the inheritance of bacterial traits. But the modern era of genetics began in 1953 with the discovery of the double‐helix structure of DNA by James D. Watson, an American doing research in England, and Francis H.C. Crick. From that seminal discovery flowed decades of fabulously productive basic research into the biology of heredity.

DNA, an unusually long and supple molecule garrisoned in the nucleus of cells, contains in its pattern of chemical components (or bases) a code of instructions telling a cell how to make all the proteins essential to life. Discrete segments of DNA, known as genes, contain the instructions for particular proteins; the estimated 50,000 to 100,000 human genes are transmitted to offspring during the process of reproduction. By 1966 the basic genetic code was understood, and by 1969, the Harvard University biologists Mark Ptashne and Walter Gilbert, working independently on two separate organisms, had demonstrated that genes are not constantly active but rather are “regulated”—that is, turned on and off in response to environmental cues and stimuli.

By the early 1970s, molecular biologists had learned enough about DNA and its properties to begin manipulating it—a skill loosely called “genetic engineering.” In 1973, Stanley Cohen of Stanford University and Herbert Boyer of the University of California at San Francisco first achieved what is commonly known as “cloning,” or recombinant DNA. They spliced a piece of frog DNA into the DNA of a common bacterium known as E. coli. When these modified bacteria divided and replicated (which they do on average every twenty minutes), the frog DNA was copied as well. Because of concerns that virulent pathogens might be created by such a technology, biologists voluntarily observed a two‐year moratorium between 1975 and 1977 before resuming cloning experiments.

As a research tool, cloning allowed biologists to replicate DNA of interest—a human gene, for example—many times. Such replication was necessary to provide the raw material for the next step in the revolution: reading the genetic text. Independently, two teams of scientists—led, respectively, by Frederick Sanger in Cambridge, England, and Alan Maxam and Walter Gilbert at Harvard—in the mid‐1970s developed the technology to read, or “sequence,” the chemical instructions in any piece of DNA.

The biotechnology industry, which grew out of these academic experiments, was essentially an American invention. It emerged in the mid‐1970s with the seemingly premature ambition of developing drugs using the techniques of molecular biology. In 1977, collaborators at the City of Hope Medical Center in Duarte, California, and Genentech, Inc., a company based in south San Francisco, for the first time synthesized a piece of human protein‐encoding DNA—the gene for a brain hormone known as somatostatin—and inserted it into bacteria, which read the instructions and produced a form of the protein. A year later, the same researchers cloned the gene for human insulin, inserted it into bacteria, and coaxed single‐celled organisms to manufacture this essential hormone. This process, with many refinements, provided the basis of the world's first genetically engineered product, human insulin, which won approval from the federal Food and Drug Administration in 1983 for the treatment of diabetes. Inspired by the success of Genentech, an estimated thirteen hundred biotech companies sprang up in the United States alone by the close of the twentieth century.

The notion of mapping and sequencing every human gene first gained serious attention in May 1985, at an informal meeting of biologists at the University of California at Santa Cruz. The initiative grew into the three‐billion‐dollar, fifteen‐year federal effort known as the Human Genome Project, launched in 1990.

This vast sequencing project generated considerable ethical controversy. As more and more disease‐related genes—such as those associated with such devastating illnesses as Huntington's disease (a progressive, incurable neurological disorder) and colon cancer—were discovered through the genome project, geneticists and physicians faced the dilemma of whether to inform persons at risk even though no treatment was available. Medical consumers sometimes indicated their ambivalence about such tests. When the Utah‐based biotech diagnostics company Myriad Genetics marketed a genetic test for an inherited form of breast cancer in 1997, for example, most eligible women chose not to use it.

The ultimate stunt of genetic engineering—cloning a human being—was solely the province of science fiction until April 1997, when Ian Wilmut and his colleagues at the Roslin Institute in Scotland reported that they had cloned a sheep named Dolly. American bioethicists generally warned against human cloning, but subsequent press reports suggested that several U.S. laboratories were actively pursuing the cloning of human beings. As the explosion in genetic research continued, the temptation of eugenics grew ever more alluring. As James Watson remarked in 1997, “Common sense tells us that if scientists find ways to greatly improve human capabilities, there will be no stopping the public from happily seizing them.”
See also Bioethics; Biological Sciences; Medicine: Since 1945; Science: Since 1945.

Bibliography

James D. Watson , The Double‐Helix: A Personal Account of the Discovery of the Structure of DNA, 1968.
Horace Freeland Judson , The Eighth Day of Creation: The Makers of the Revolution in Biology, 1979.
Daniel J. Kevles , In the Name of Eugenics: Genetics and the Uses of Human Heredity, 1985.
Stephen S. Hall , Invisible Frontiers: The Race to Synthesize a Human Gene, 1987.
Daniel J. Kevles and Leroy Hood, eds., The Code of Codes: Scientific and Social Issues in the Human Genome Project, 1992.
Robert Cook‐Deegan , The Gene Wars: Science, Politics, and the Human Genome, 1994.
Susan Wright , Molecular Politics: Developing American and British Regulatory Policy for Genetic Engineering, 1972–1982, 1994.

Stephen S. Hall