The death of an Arizona teenager who underwent human gene therapy sent shock waves through the medical community last September. It is also bringing into focus ethical questions regarding this emerging field of treatment.

The death of 18-year-old Jesse Gelsinger eventually prompted the Food and Drug Administration to halt gene experiments at the University of Pennsylvania's Institute for Human Gene Therapy.

The Tucson teen had been taking part in an experiment involving genetic delivery vectors, modified viruses that enter a person's cells to deliver healthy genes to their chromosomes (the blueprints of each person's body).

These genes would then augment existing defective genes. The delivery vectors in this case were viruses similar to the cold virus, which were added directly into Gelsinger's bloodstream. It is not clear why Gelsinger's body reacted so strongly to the treatment.

Science of Life

In light of Gelsinger's death, the Muscular Dystrophy Association announced that it has stopped funding its own gene therapy clinical trial at the University of Pennsylvania Institute. Also, The Washington Post recently reported that there have been several other deaths associated with previous human gene therapy trials.

Gelsinger's tragic death points up the risks of gene therapy: that of curing heritable diseases that are now considered incurable.

In 1990, two young girls underwent gene therapy for a rare blood disease called ADA deficiency, which causes a suppressed immune system. Both girls had remarkable recoveries and are now leading normal lives. Because they also continued to receive conventional medical treatment, the degree to which the genetic repair of their white blood cells was responsible for their health is not certain. Yet the results of these and similar studies seemed to indicate that the risk of negative reactions to gene therapy were minimal, according to an article by Dr. W. French Anderson, in the April 30, 1998, edition of the scientific journal Nature.

Given the potential therapeutic promise of gene therapy, are those calling for a halt to clinical trials overreacting?

Dr. Arthur Caplan of the University of Pennsylvania thinks so.

“Some of the concern about gene therapy research is warranted,” the secular bioethicist told the Register. “But calls to bring research on gene therapy to a halt most certainly are not. … Pulling money out of gene therapy basic research is at best stupid, given the promise the field holds for those with incurable diseases.”

He added, “Gene therapy is in its infancy. If we want to apply more oversight to it, that would be very easy to do.”

According to Peter J. Cataldo, director of research of the National Catholic Bioethics Center in Boston, the morality of gene therapy depends on its method and purpose.

“We must distinguish between germ-line genetic manipulation [manipulation of eggs or sperm] and somatic cell therapy [nonreproductive human tissue cells],” Cataldo explained. “The ethical analysis differs in these two.

“Catholic teaching on these is based on the dignity of the human person — the body-soul unity of the human person. Somatic cell genetic therapy, in principle, can be morally acceptable if there is informed consent and the risks are not disproportionate to the benefits.”

Gelsinger's treatment fell under the category of somatic cell therapy, and is considered ethical, Cataldo said.

He continued: “Gene therapy can be a morally good thing in that it is direct therapy to alleviate disease, and it is consistent with the Church's support of science and medicine.”

But, Cataldo added, “Germ-line therapy is not really a therapy at all, as it does not really benefit the individual but the offspring. It is manipulating the genome of the reproductive gametes [egg or sperm chromosomes] so inherited disease can be eliminated in future generations.

“The enormous risks are therefore unacceptable. Catholic teachings have not eliminated the use of gene therapy and knowledge of genetics, but only those uses of this knowledge and technology that do not truly serve the human person.” Germ-line therapy would involve in vitro (test tube) manipulation of human eggs and/or sperm, which is problematic.

A further issue, according to Cataldo, is “genetic enhancement directed at the attributes of an individual, such as memory, strength, intelligence, etc. This kind of manipulation is not therapeutic. The major moral problem of genetic enhancement is that it does not respect the body/soul unity of the human person.”

The Holy Father has spoken about genetic therapy and research.

In his 1983 address to the World Medical Association he states, “A strictly therapeutic intervention whose explicit objective is the healing of various maladies such as those stemming from deficiencies of chromosomes will, in principle, be considered desirable, provided it is directed to the true promotion of the personal well-being of man and does not infringe on his integrity or worsen his conditions of life.”

In an address to the members of the Pontifical Academy for Life, Feb. 24, 1998, the Pope also warned against potential abuse: “It is unlawful to carry out any intervention on the human genome unless it is aimed at the good of the person, understood as a unity of body and spirit; nor is it lawful to discriminate between human subjects on the basis of possible genetic defects discovered before or after birth.

“Furthermore, we ask political leaders and scientists to promote the good of the person through scientific research aimed at perfecting appropriate treatments that are feasible and without disproportionate risks.”

Concluded Cataldo: “Gene therapy can be a morally good thing in that it is direct therapy to alleviate disease, and it is consistent with the Church's support of science and medicine.”

David Beresford, a Ph.D. biology student, writes from Lakefield,Ontario.