The fall and rise of gene therapy

May 8, 2000
Web posted at: 4:31 p.m. EDT (2031 GMT)

A stunning and long-awaited announcement arrived from France recently: Two children were successfully treated -- and hopefully, cured -- by gene therapy. They were born with Severe Combined Immune Deficiency (SCID), or "boy-in-the-bubble disease.'' This genetic defect prevents their bone marrow from producing a working immune system, leaving them with no ability to fight off even the most basic illness or infection. Gene therapy has been long promised as a way to treat the kind of defect that causes SCID. But that promise has been elusive over the 10 years since research began, and the technique has suffered a series of recent setbacks. So while the French announcement comes just in time to bolster gene therapy's potential and burnish its public image, it adds urgency to questions about how much risk we should allow in gene therapy research, and how far to go in applying what we learn.

What's your opinion?

Research not therapy

The French success represents part of a long-time research program, built on the work of numerous scientists. The children who seem to be cured are fortunate to have been included at the end -- rather than the beginning -- of such experimentation. But even they were subjects in highly prospective research with uncertain outcomes.

Even the term "gene therapy" is somewhat misleading, giving the impression that it yields the same kinds of benefits as other medical treatments. The hope is that someday gene therapy will be as reliable and commonplace a remedy as antibiotics. But until it becomes a proven treatment, gene therapy offers subjects the risks of research with fewer of its benefits. Those benefits will be realized mostly by future patients.

The death of 18-year-old Jesse Gelsinger in a gene therapy trial at the University of Pennsylvania drove home that point. The incident led to Congressional hearings and increased federal scrutiny and oversight of gene therapy programs.

How far do we go?

The apparent success in treating SCID bodes well for gene therapy's future application against other diseases. The challenge will be deciding how far to go. Should gene therapy be restricted to only serious diseases? Should it be used to enhance traits or characteristics like memory or intelligence? Maybe the most important question is whether gene therapy should be used on eggs and sperm, so-called germ cells.

Gene therapy works for SCID because the disease results from a sort of typographic error in just one of the approximately 100,000 genes that constitute our genetic makeup. And since the mistaken gene affects the bone marrow, the cells that need to be "fixed" are relatively easily removed from the body, genetically engineered, and then returned to the body where they will perform normally.

But most other cells will be much harder to target for gene therapy, making the technique much less efficient and potentially creating undesirable genetic changes. Gene therapy on an egg or sperm cell may overcome this problem, since any correction there will affect the individual that develops from it. But such efficiency carries heavy responsibility, because altering genes in eggs or sperm will affect all future generations descending from them.

There is great promise in a technology that cannot only treat disease but can permanently cure it at the level of our genes. And therein lies the rub. It is difficult to undo genetic changes, especially when they may persist many generations into the future. So we must think about how we will assure that our genetic legacy is not only what we hope, but what our descendants can accept.