Gene Therapy for Some Diseases Called Close at Hand

The understanding of genes and their role in causing a wide variety of genetic diseases has developed so rapidly that scientists now believe they are only a couple of years from a payoff--gene therapy to correct those diseases.

Stanford University, one of the pioneers in genetic engineering research, gave a glimpse of how much science is betting on this new therapy when it announced this week the establishment of a privately funded, $50-million Center for Molecular and Genetic Medicine, which it says will bridge the gap between molecular biology and clinical medicine.

Dr. Paul Berg, a Nobel Prize winner and the director of the new center, calls it one of the most ambitious projects ever undertaken at the university. He said about 400 researchers, including students, will work there. It is scheduled for completion in 1988.

Berg, who won his Nobel in 1980 for recombinant DNA research, told a symposium that advances in identifying genes responsible for some diseases and in cloning normal genes to replace defective ones occurred at a pace that was “almost unimaginably explosive.”

As many as 3,000 genetic diseases are known, but only a small number of these--those that are caused by a single gene--are in the category that will initially be considered as targets for gene therapy.

Berg said that between 300 and 400 single-gene diseases have now been identified and replacement genes for approximately 100 of them have been cloned. Although many of the diseases are rare, they collectively account for a sizable number of childhood admissions to hospitals, he said.

Examples of single-gene diseases are sickle-cell anemia, cystic fibrosis, several kinds of congenital immunodeficiency ailments and Tay-Sachs.

All of these conditions result when a gene responsible for controlling an essential protein is either lacking altogether, or overproduces or underproduces its product.

For a number of these diseases, genetic engineering already has been responsible for the development of tests that can be conducted on pregnant women to see whether the fetus is affected. But for most of them, Berg said, therapy so far is either lacking or ineffective.

One of the techniques that researchers plan to use to introduce a new gene into the patient was described at the symposium by Dr. David Martin, a University of California, San Francisco, researcher and vice president for research of Genentech Inc., a leading genetic engineering firm.

Martin has been concentrating on two genes that control the manufacture of enzymes essential for the normal function of T cells in the immune system. A child born with either gene defective soon dies of infection.

Within the next one to three years, Martin proposes to use a special kind of virus--called a retrovirus--to introduce a healthy gene into the cells of a patient with one of these immunodeficiency diseases. The retrovirus has been selected because of its special capability of integrating itself into the human’s own genetic material.

The scientist proposes to seed the new gene by placing it in bone marrow, which then will be transplanted into the patient.

Human trials on several other kinds of single-gene diseases are also expected to be under way soon at five other centers in the United States. They are Baylor College of Medicine in Houston; the University of California, San Diego, in association with the Salk Institute; UC San Francisco in association with Genentech; Harvard University, in association with the Massachusetts Institute of Technology, and the National Institutes of Health in Bethesda, Md.

The advances in molecular biology have triggered concerns among some groups that the technologies may be growing more rapidly than the ability to control them. This concern has arisen partly out of fear that the new technology will be used to produce basic changes in genetic material that could be inherited by the next generation.

However, according to a report on gene therapy published in December by the federal Office of Technology Assessment, the type of therapy to be used in the next few years is not designed to cause inherited changes.

Such changes, if and when they ever are authorized, would involve genetic alterations aimed at either sperm or egg.

“Inherited alterations . . . are unlikely to be undertaken in humans in the near future because they are technically too difficult, are perceived as ethically problematic and may not prove superior to existing technologies,” the report said.

The type of therapy that is on the horizon is aimed at so-called somatic, or body, cells that do not possess the capacity of passing the newly acquired genes on to the next generation.

If therapy for single-gene defects works, then the researchers plan to tackle more complex genetic illnesses that also require changes in only the somatic cells. These could include Huntington’s disease and a number of autoimmune illnesses that result in the body’s immune system attacking its own tissues. Scientists believe that rheumatoid arthritis and multiple sclerosis are examples.