WASHINGTON — The first experiment in which laboratory-produced genes were introduced into humans has proved the procedure safe, opening the way for an entirely new approach to battling cancer and other life-threatening, even incurable, disorders, researchers reported Wednesday.
The findings, published in today's edition of the New England Journal of Medicine, constitute the first step toward the use of foreign genes for actual medical therapy in humans.
The landmark study "represents the first time that foreign genes have been introduced into people, and it shows that the technique is feasible and safe," said Dr. Steven A. Rosenberg, chief of surgery at the National Cancer Institute and the lead researcher on the project.
"We know how to do it, and we're ready to go," Rosenberg said of the prospect of using genes to treat disease. "We can start within days."
Wednesday's report said the initial experiments showed that the genes that were inserted into the body could survive two months--long enough to be useful in treating diseases. Before the latest experiments, researchers were not certain this could be done.
Researchers said Wednesday that the experiments showed that gene-modified cells could be used to deliver cancer-fighting substances to the tumors of cancer patients, to modify a patient's genes or to correct inherited defects.
The patients involved in the testing suffered no adverse side effects as a result of the gene transfer, the researchers said.
In an editorial accompanying the journal report, doctors Denis Cournoyer of Montreal General Hospital and C. Thomas Caskey of Baylor College of Medicine in Houston said the experiment "constitutes important progress toward the development of human gene therapy."
Further, they wrote, "a wide range of inherited human disorders could in theory be corrected by the introduction of new genetic information into the proper type of . . . cell."
Every cell in the human body contains information that directs its function. This information is stored in the genes, which are made up of DNA, the genetic blueprint of life. When genes are destroyed or damaged, the cell's function is disrupted and disease occurs.
For a long time, scientists have hoped to develop techniques to correct genetic disorders at their source--the genes--rather than treat the resulting deficiencies, as is now the case. A recent explosion of advances in genetic technology has brought that possibility closer.
In May, 1989, Rosenberg, Dr. R. Michael Blaese and Dr. W. French Anderson of the National Heart, Lung and Blood Institute introduced cells spliced with a foreign gene into eight patients. The genes were used as "markers" for the cells but not as therapy.
The study, which reports on five of those patients, said cells containing the new gene could be detected in the bloodstream for up to two months after the procedure, and after nearly 200 days in one patient who had been given a second infusion of cells.
The patients, all suffering from advanced melanoma, a skin cancer that is often fatal, had been given infusions of special cancer-fighting white blood cells called tumor infiltrating lymphocytes, or TILs, into which the foreign gene had been introduced.
Scientists believe that TILs, which can be found in virtually all malignant tumors, may have the potential to destroy cancerous tumors.
The TILs were removed from the patients' tumors and bathed in interleukin-2, a substance that stimulates cell growth.
The researchers then used an altered, harmless mouse virus to insert the new gene--which was made resistant to the antibiotic neomycin--into the TILs.
An antibiotic-resistant gene was used to enable scientists to monitor the TILs, because only the gene-modified cells would survive when blood and tumor samples were later exposed to the antibiotic.
Finally, the TILs, modified with the marker genes, were returned to the patients.
The scientists said they were able to detect gene-modified TILs in the bloodstream of the five patients for 19 to 22 days after TIL infusion, and even later in two of the patients. One patient had gene-modified TILs in the bloodstream on day 51, and another on day 60.
The patient whose gene-modified TILs could be found on day 51 was re-treated with gene-modified TILs on day 94 after experiencing a tumor regrowth. Gene-modified TILs could be detected in this patient's blood on days 121 and 189, probably TILs from the repeat infusion, they said.
Researchers were also able to identify gene-modified TILs from tumor biopsies, they said.
Tumors in three of the five patients were reduced as a result of the TIL-therapy, confirming the benefits of TIL treatment that had been reported in earlier studies. One of the three experienced a remission that has lasted 13 months. The other two died.