Coming: A Historic Experiment

By Dick Thompson

For scientists, and possibly for all humanity, a watershed event is about to take place. Biologists have long been closing in on a goal that is both alluring and frightening: to alter the genetic code of a human being. They have transplanted foreign genes into bacteria, fruit flies, even mice. Now medical researchers at the National Institutes of Health are ready to take the big step: within the next two months they will perform the first authorized gene transplants into humans.

The doctors intend to inject cells containing a gene from the bacterium E. coli into cancer patients at NIH. The gene itself will have no therapeutic power, but it will help the researchers monitor the effectiveness of an antitumor treatment. More important, the transplantation techniques being developed for the experiment could someday be used to cure several genetic ills, possibly including Huntington's disease, sickle-cell anemia and some types of muscular dystrophy. Says NIH director James Wyngaarden: "We have reached an important milestone in medical history."

The work combines the efforts of three top NIH scientists: Steven Rosenberg, an expert in cancer therapy, and W. French Anderson and R. Michael Blaese, two master gene manipulators. For several years Rosenberg has been developing a novel cancer treatment using a type of cancer-fighting cell called TILs (tumor-infiltrating lymphocytes). He removes TILs from cancer patients and clones large quantities of the cells in the laboratory. When this army of cells is reinjected into the patients, their tumors can shrink significantly. In one experiment with metastatic melanoma patients, 60% of them benefited from the therapy. But Rosenberg still needs to know how the TILs move through the body and why they do not always work.

That is where gene transplants come in. Anderson has developed a technique using a "marker" that will let Rosenberg follow the progress of the TILs. The marker is the E. coli gene that makes a cell resistant to the antibiotic neomycin. Anderson has been able to tuck that bacterial gene into a virus and then implant the virus into TILs. Once inside the TILs, the gene becomes fully functional.

In the upcoming experiment, Rosenberg plans to inject ten terminally ill patients with TILs carrying the marker. Periodically, he will remove bits of tumor from the subjects and douse the samples in neomycin. If some cells survive the dosing, he will know the TILs have reached the tumor.

This limited test is only the beginning. The NIH researchers and others elsewhere are planning to transplant genes that could actually help people fight cancer and other diseases. For example, scientists hope to give patients genes that will enable their bodies to mass-produce such anticancer agents as interleukin-2 and tumor necrosis factor. Anderson believes the day is not far off when it will be possible to transplant a gene containing instructions for the manufacture of CD4, a substance that combats the AIDS virus. Ultimately, researchers think they may be able to conquer some hereditary diseases by replacing defective genes with normal ones.

As promising as all that sounds, some critics oppose the NIH experiments on the ground that they set disturbing precedents for tampering with human genetics. Last week activist Jeremy Rifkin, a longtime opponent of genetic engineering, filed a federal suit to block the NIH project, saying such techniques could create "possibilities for tremendous social abuse." Rifkin fears that people with genetic abnormalities may be coerced into having potentially dangerous operations in order to qualify for insurance or Government benefits.

Evan Kemp Jr., a member of the Equal Employment Opportunity Commission, who joined the Rifkin protest, fears that industrial workers might be pressured to undergo gene transplants. Suppose, he says, that a company is exposing its employees to a toxic chemical. Instead of getting rid of the poison, the firm might try to alter the genes of the workers to make them more resistant to the chemical.

Such a scenario is conceivable, admit the supporters of gene therapy, but hardly inevitable. Confident that the courts will reject Rifkin's case, Rosenberg, Anderson and Blaese are going ahead with preparations for their historic experiment. They acknowledge that the power to alter genes could be abused. But they firmly believe that if the technology is used carefully, the potential benefits to humanity far outweigh the risks.