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GENETIC ENGINEERING

A Powerful and Awesome Skill

In 1982 scientists took the gene that produces human insulin and inserted it into E. coli, a microorganism that lives in intestines. Genetic engineering, "the most powerful and awesome skill acquired by man since the splitting of the atom," had harnessed the hereditary mechanisms of bacteria. Genetic engineers manipulated bacterial genes in an effort to produce new medicines and cures for human diseases. These bacterial microorganisms became capable of manufacturing human insulin for diabetics, human growth hormone for dwarfism, and the antiviral-anticancer drug interferon. Also known as "gene splicing" and "recombinant DNA," genetic engineering showed promise for producing important new vaccines and even safer older vaccines. There were hopes that the quality of life could be improved by manipulating human genes once the complete set of genetic instructions on human DNA (called the human genome) was mapped.

Recombinant DN A and Medicine

DNA (deoxyribonucleic acid) is the blueprint for life in all organisms. Its sequences of paired chemical bases are the hereditary information needed to produce proteins, the building blocks for all life. These proteins are large molecules, so they could not be artificially synthesized in the way the sulfa drugs or vitamins were. Genetic engineering began in the 1970s with the discovery of restriction nuclease enzymes. These "biological scissors" were able to recognize and chemically cut apart specific chemical sites along a DNA molecule. Another enzyme, ligase, permitted a gene snipped from one DNA molecule to be attached to a similar site in the DNA of an unrelated organism, even in another species. It was this hybrid that was called "recombinant DNA." The process of gene therapy got the desired gene into a cell by piggybacking it onto inactivated viruses known for their ability to penetrate cells. The first genetically engineered drug was human insulin, produced when the human gene responsible for insulin production was spliced into a bacterium, which then produced human insulin. In 1985 a more efficient copying procedure was developed. Called polymerase chain reaction (PCR), it could create many copies of a DNA sequence from a few originals. Until the advent of recombinant DNA, vaccination against some diseases involved using killed or weakened microorganisms. Some risks were still involved in using the vaccines, because errors in making them could introduce infectious live pathogens into the vaccinated individual. Recombinant DNA made it possible to transfer the genes that caused the disease to a harmless microorganism and use it as the vaccine instead.

Gene Therapy

Genetic disorders can be caused by chromosomes as in the case with trisomy 21, or Down's syndrome. More than three thousand human diseases can result from a defect in a single gene. Most are very rare, but others, such as cystic fibrosis, are much more common. Some of the most common genetic disorders such as diabetes mellitus and coronary artery disease result from many genes, making them much more complicated to analyze and treat genetically. Certain viruses can cause cancerous tumors by integrating their genetic information into the chromosomes of the human cells they infect. These defective genes cannot be treated by surgery, nor can many of the illnesses they cause be cured. But if their DNA sequences could be altered in some way, the new set of genetic instructions could save or improve a life. Such treatment is known as gene therapy.

The First Step. The first approved experimental transfer of new genes into human beings took place on 22 May 1989. Steven A. Rosenberg and R. Michael Blaese of the National Cancer Institute, and W. French Anderson of the National Heart, Lung, and Blood Institute, used a retrovirus, a special form of virus easily used in the laboratory, to transfer genes safely into the white blood cells of five consenting patients, all with advanced melanoma, a form of skin cancer, who had life expectancies of less than ninety days. The transformed white blood cells, which regularly detect and destroy cancerous cells before they can become established as a deadly tumor, continued to be detectable for several months after being transferred to a human subject. The first major step toward gene therapy was taken.

Controversy

Genetic engineering could be used for humans in two different ways. The technology could be exploited to make products such as insulin, or to learn more about human biology. The most controversial possibility for genetic engineering was gene therapy that had the potential to change the human organism itself. In 1975 famed scientist Paul Berg convened a landmark meeting in California of one hundred scientists from around the world to study the safety and propriety of certain scientific research relating to genetic engineering. It was the first time a group of scientists got together to police themselves and to think of the implications of their research. They declared a moratorium on certain experiments until they knew more about genetic engineering. In 1983 Robert Sinsheimer, a molecular biologist and the chancellor of the University of California, Santa Cruz, urged the world to consider the dark side of genetic engineering. He asked three crucial questions: "Is it safe? Is it wise? Is it moral?" Many people were against interfering with nature. They feared that strange new anti-biotic-resistant viruses would be created in genetics laboratories and accidentally released into the world.

Federal Regulation

Since the recombinant DNA technique was first introduced in 1973, genetic material has been transfered thousands of times without accidents. In 1980 the U.S. National Institutes of Health (NIH) relaxed or eliminated most restrictions on work with all but disease-causing bacteria. For genetic therapy, in the fall of 1985 the NIH approved national guidelines for improving transplanted genes into a patient's body cells to correct an otherwise incurable disease. But it excluded any experimental treatment that could be passed on to the patient's children through his or her genes. By 1986 the biotechnology field had grown so rapidly that President Reagan had to update its coordination among many federal agencies. Responsibility for overseeing the multiple aspects of genetic engineering was to be shared by six agencies: the Department of Agriculture, the Environmental Protection Agency, the Food and Drug Administration, the National Science Foundation, the Occupational Safety and Health Administration, and the National Institutes of Health. Some critics of biotechnology feared it could be used unwisely in business and industry, Genetic testing might be used to help employers and health insurance companies predict tendencies of employees to develop certain health problems. This could lead to denying people employment or dismissing them from their jobs. By the end of the decade there were still few laws regulating the use of genetic information. One of the most controversial issues of the new power over biology was human reproductive engineering. In 1987 the Vatican issued a statement against reproductive technology, which it condemned as unnatural. The Roman Catholic Church felt that birth, death, and the lottery of genetic heredity belonged forever in the hands of a superior power and was not for humans to try to change. By 1989 the question of "whether to make perfect humans" was not yet solved by scientists, ethicists, or ordinary Americans.