Proposed genetic therapy on infants prompts loud scientific, religious debate Calif. researcher seeks to treat genetic defects

September 06, 1998|By NEWSDAY

A pioneer in genetic therapy is proposing experiments that might be the first to change an individual human's germ line, the cells reserved to make sperm and eggs.

The idea, experts say, is expected to prompt hot debate on a number of fronts: scientific -- involving possible unexpected downstream effects on other genes; humanitarian -- if the research fails, a mistake might persist through later generations; and even religious -- some argue the germ line is God's blueprint for humanity, don't mess with it.

"I want to force that debate," said Dr. W. French Anderson, a researcher at the University of Southern California School of Medicine in Los Angeles, whose team is submitting the proposals.

The experiments, recently submitted for consideration by a federal review committee, call for inserting genes into fetuses as a way to fix severe genetic defects before the babies are born.

By working with fetuses, Anderson hopes the curative gene will have greater cell coverage with tiny patients' compared with attempts at therapy later in life. He hopes to cure two genetic diseases -- ADA deficiency, a rare immune deficiency syndrome, and alpha thalassemia, a severe inherited form of anemia common in Asia.

Although Anderson and his colleagues aren't ready to experiment yet with human fetuses (their first work will be in lab dishes, then in animals), they've submitted preliminary documents to the National Institutes of Health committee that oversees such work, anticipating a national debate on the issue.

In an interview, Anderson said his goal is to spur exploration of the ethical and societal pitfalls early, while tissue culture and animal experiments are being done. He said he hopes to begin human experiments in about two years.

Already Anderson and his colleagues have engineered the special viruses needed to carry the genes into fetuses. "We have built the vectors [viruses] and are starting the tissue culture phase [of experiments]," he said. The next experiments will be in animals such as mice, sheep and monkeys.

The big difference in human experiments, Anderson said, is that for the first time "the likelihood is high that at least some of the germ line cells will be affected."

"We don't know what will happen," he added. "But if the gene goes in and causes a problem, now there is a problem not only in this fetus. If it survives there, the gene persists in the germ line of all the descendants."

Dr. Robertson Parkman, a longtime member of the NIH Recombinant DNA Advisory Committee, said Anderson's desire to get the debate going "is perfectly valid. It's necessary that we begin to discuss how we're going to evaluate the introduction of genetic material into the human germ line."

When human gene therapy trials started at the beginning of this decade, the experiments were aimed at so-called "somatic cells," targeting cells such as bone marrow that would not pass genes on to the next generation.

When the possibility arose for doing experiments with germ-line cells, it "was just shelved," said bio-ethicist Thomas Murray. "We were going to just put that aside and focus on somatic cell therapy. But some people felt it should not just be shelved, but banned forever."

Murray, director of the Center for Biomedical Ethics at Case Western Reserve University in Cleveland, said other ethicists and observers "wanted to retain an open mind, not embracing it, but saying let's revisit once we know more about somatic cell therapy. I'm one of those people."

Another was ethicist LeRoy Walters, director of the Kennedy Center for Ethics at Georgetown University in Washington.

About five years ago, Walters began arguing that debate on germ-line therapy should start soon. He could not be reached for comment.

Murray noted, however, that "we're now at the point where we ought to be assessing these arguments."

There are also other issues to be considered beyond potential damage to the germ line, the researchers said. For instance, if something goes wrong while putting new genes into a fetus, both the fetus and the mother may be in peril. Additionally, if the result of gene therapy is only a partial cure in an infant who would normally die, the treatment may produce an individual who suffers through life needing expensive and difficult care.

Anderson is no stranger to such controversy. He and Drs. R. Michael Blaese and Kenneth Culver, all three then at the National Institutes of Health, ran the first approved human gene therapy experiments.

They tried to cure two young Ohio girls of ADA, the severe combined immune deficiency syndrome. Children born with this disorder have no natural immunity, and unless cured must live inside germ-free chambers, huge plastic bubbles.

The first two experiments were partially successful; the girls did establish immune function, but it must be maintained with periodic shots of an expensive drug called Peg-ADA. Still, both girls can live relatively normal lives.

Anderson said the problem in those first two attempts was that not enough of the girls' white blood cells picked up the normal gene -- which makes an enzyme called adenosine deaminase. The reason for trying experiments in-utero, he explained, is because cell division is occurring rapidly in a developing fetus, and there's a far better chance the engineered virus will infect many more cells.

Pub Date: 9/06/98

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