Altered Fates

The Promise Of Gene Therapy

When Does Gene Doctoring Go Too Far?

March 07, 1986|By Peter Gorner and Jeff Lyon.

The true fathers of gene therapy most likely will never win Nobel prizes. Their reputations have been badly damaged by what many view as premature, and thus unethical, attempts to cure fatal disease by giving patients new genes.

But the brouhaha stirred up by past attempts cannot compare with the maelstrom of controversy yet to come. Egos and expertise will clash like cymbals as the technology of gene splicing keeps racing along so fast that it laps ethical debates about what it all means.

The first pioneer to tangle with taboos over tinkering with genes was American virologist Stanfield Rogers, who in 1969 was studying a benign virus that produces warts in rabbits.

Rogers was fascinated by a phenomenon he discovered by accident: the virus, the Shope papilloma virus, somehow lowered the level of the amino acid arginine in the blood of laboratory workers who had been inadvertently infected.

Other than that, the workers suffered no ill effects. Hence, Rogers reasoned that anybody who happened to have too much arginine in his blood could theoretically be cured by the virus. However, he knew of no such people. ``We had uncovered a therapeutic agent in search of a disease,`` Rogers was to say later.

One day, though, Rogers was reading an account in a British medical journal that told of two young German sisters, aged 18 months and 5 years, who were desperately ill with seizures, palsy, and severe retardation--all because of too much arginine in their blood.

What would happen, Rogers wondered, if the papilloma virus were injected into the sisters` bodies?

In 1971, after having received permission from the girls` family and their physician, Rogers flew to Germany with a vial of virus. He had no idea how much the girls should be given and he and colleagues proceeded with caution. Too much caution, perhaps: ``The dose of virus first used was about one-twentieth of that which we had previously found harmless to mice,`` Rogers later said.

``As might be expected from this tiny dose, no effect whatever was found in the condition of the children.``

Subsequent attempts using slightly more virus were inconclusive. But before he could proceed any further, Rogers was capsized by a wave of professional criticism from colleagues who labeled his work rash and irresponsible. His funding dwindled, and chastened, he turned to studying viruses in plants.

No further experiments were tried for nine years. Then in 1980, Martin Cline, chairman of hematology at the University of California at Los Angeles, ignored the lesson that Rogers had so painfully learned.

Cline wanted to put healthy hemoglobin genes into patients suffering from beta thalassemia, a progressively fatal blood disorder. Without waiting for approval from his home university`s human testing review committee, he flew to Israel and Italy, where he had already obtained permission to treat two young women.

Cline`s results were similarly inconclusive, but while he was abroad, UCLA rejected his application, saying more animal work was needed before any human experiments were tried.

More trouble followed after the National Institutes of Health (NIH) found Cline in violation of federal guidelines as well, stripped him of $190,000 in grants (half his federal funding), and let him know he was on bad paper.

The furor was so great that Cline resigned as chairman of his department at UCLA.

The stories of Rogers and Cline underscore the ethical quandaries posed by the prospect of human gene therapy. Scientists no less than churchmen and politicians are troubled by our newfound ability to manipulate the genes of human beings and other organisms.

The controversies are many. A litany of agonizing issues must be resolved by society in coming years.

Among them are these:

-- Safety. No one knows for sure what will happen when a new gene is put into a person. Premature experimentation runs the risk of unleashing something dangerous and irreversible into the human gene pool.

-- Abortion. Medicine`s enhanced ability to detect genetic diseases before birth will almost certainly lead to more abortions and political wrangling. In Illinois, for example, a controversial new law might forbid the most sophisticated prenatal testing unless it can be shown to be beneficial to the fetus.

-- Body cell versus sex cell therapy. Body cell (or somatic) therapy affects only the patient whose disease is being treated. Sex-cell (or germline) therapy involves changes in the patient`s sperm or egg cells that would be passed on to future generations and could cause cataclysmic changes in the species. The distinction has been called the Maginot Line of genetics. -- Eugenics. The ability to manipulate genes for medical purposes might prompt broader applications such as the intentional ``improvement`` of the human species. A variety of traits, ranging from intelligence and physical prowess to character and even ethnic type could conceivably be altered some day.