Human Gene Therapy Test Receives Key U.S. Approval

A key federal advisory panel Tuesday approved two ground-breaking research experiments involving the first use of human gene therapy in this country to treat life-threatening disease, including an often-fatal type of cancer.

“This is truly an historic occasion,” said Gerard J. McGarrity, chairman of the Recombinant DNA Advisory Committee of the National Institutes of Health, which evaluated and approved the proposals.

The experiments must also be endorsed by the NIH director and the Food and Drug Administration, but their approval is considered a virtual certainty.

“This is the first step toward developing treatments that do not now exist for incurable diseases,” said Dr. W. French Anderson of the National Heart, Lung and Blood Institute, a lead researcher on the projects. “There is a whole range of diseases that can be affected, the most immediately obvious being genetic diseases and cancer. Right behind them are AIDS and cardiovascular diseases.”

The proposed tests represent a milestone in genetic research. In the experiments, normal genes developed in a laboratory will be inserted into the cells of patients whose own genes lack the coding needed to stimulate production of disease-fighting hormones or enzymes.

The experiments will be performed on individuals suffering from melanoma, a potentially lethal skin cancer, and in children with adenosine deaminase deficiency, an inherited and incurable immune system deficiency.

The melanoma treatment will be performed on patients who are in an advanced stage of the disease, for which there are no effective therapies, and who would otherwise be expected to live only about four months.

The melanoma experiment will involve inserting a gene that causes cells to produce tumor necrosis factor, a powerful hormone that kills tumors by cutting off their blood supply.

The gene will be put into white blood cells called tumor-infiltrating lymphocytes, which typically attack cancer. Scientists at the National Cancer Institute have learned how to remove the critical white cells from the patient, grow billions of them in the laboratory and return them to the patient’s body with the new genes.

“This, to me, represents the logical progression of everything I’ve done for the last 10 years,” said Dr. Steven A. Rosenberg, a leading cancer institute researcher who is conducting the study. “It will be very significant if this works. Hopefully, if it works, it will be applicable to cancers other than melanoma.”

Melanoma strikes about 28,000 persons annually and kills about 6,300. The incidence of the disease is increasing at a rate of about 4% a year, according to the American Cancer Society. It is curable by surgery only if detected very early.

Rosenberg said that he would begin the experimental treatments “within days of when we have FDA approval.”

The proposed treatment for the immune deficiency involves replacing a gene that stimulates production of adenosine deaminase, an enzyme that is crucial to the proper functioning of the immune system.

As with the cancer treatment, researchers plan to grow the patient’s own white cells in a laboratory, add the critical gene, then return the cells to the patient’s body with the hope that the new cells will stimulate production of the enzyme, thus restoring the immune system.

Anderson said that the experiments probably will begin in the fall with two to four patients. The disease is rare, afflicting only about 30 children worldwide at any time.

Several treatments for the immune disorder already exist. These include bone marrow transplantation, which is not often successful, and a new drug approved by the FDA last March, PEG-ADA, that replaces the enzyme and has been effective in many cases.

Jeremy Rifkin, president of the Foundation on Economic Trends, a public interest group that examines the social and ethical implications of biotechnology, said that he has “serious reservations” about the immune disorder gene experiment because other treatments are available for the disease. “I can’t understand why any parents would want their kids to try this,” he said.

Rifkin, who for many years has warned of the potential for abuse in human genetic engineering, said that he does not oppose the melanoma experiment. “If this is all these patients have, they should try it,” he said.

The tests will be the first in the United States involving insertion of genes in human patients for therapeutic purposes.

In May, 1989, genetically engineered cells were injected into human patients for the first time, but not as therapy. The genes were used as “markers” to track the movement of cancer-fighting white blood cells in the body.