Gene therapy -- a largely positive process

by Ed Berger | 5/10/00 5:00am

Inscribed on the portal over the Oracle at Delphi is the Socratic injunction, "nosce te ipsum"; know thyself. In the year 2002, biologists will have fulfilled one aspect of that injunction by completing the Human Genome Project. Now and for the first time, we have available the essential blueprint for humans in the form of a DNA sequence. In spite of the fact that there are very few biologists who really believe that Genes 'R Us, that sequence does contain the full complement of information required to construct a person and, as a consequence, it represents a rich resource for future biomedical research. While it will certainly take several decades to fully comprehend the meaning of those instructions, the human genome project has already produced some practical outcomes. We now have available many new genetic tests that detect the presence of malady producing forms of specific genes, such as cystic fibrosis. Additionally, the field of biotechnology has converted human DNA sequences into gold, by mass producing large amounts of rare and therefore valuable human proteins, such as human growth hormone, used for the treatment of hereditary dwarfism. What I want to focus on here is how the human genome project has enabled the development of gene therapy, and how the development of gene therapy raises several profound ethical concerns.

Soon after biologists isolated the normal form of several human genes, it became clear that they could use those normal genes to treat or even cure people who had been born with two defective copies of that same gene. The therapeutic use of human genes comes in two varieties. Somatic cell gene therapy utilizes a technology for introducing the normal form of a gene into somatic, that is body, cells of a person suffering a genetic malady using a viral "vector." For example, the news recently reported the successful use of somatic cell gene therapy by a French group of physicians to cure two children born with a hereditary form of severe combined immune deficiency, the so-called "bubble" children. In these cases a normal gene is introduced into the patients own blood cells. Another recent report of somatic cell gene therapy claimed some success in treating patients with hemophilia. This technology is still in its early stages of development and the majority of clinical trials, thus far, have not been completely successful. The recent and tragic death of a Pennsylvania teenager being treated by gene therapy for ornithine transcarbamylase deficiency raised a number of ethical issues, primarily concerned with the principle of informed consent. But from an ethical point of view, somatic cell gene therapy raises no new concerns. The technique is really no different than treating a diabetic with insulin, only now the insulin gets produced by the patient own genetically modified cells.

The second form of therapy is called germ line gene therapy. In this case the normal form of a human gene is physically inserted into the chromosome of an egg, sperm or fertilized egg, in one way or another. The inserted normal gene not only rescues the infant from some genetic disorder that it would otherwise express, but that normal gene goes on to be inherited by the future children of that rescued infant. The technology required for human germ line gene is already available. Indeed, there are many commercial companies that apply this technology to produce "transgenic" animals or plants, and the current controversy over "Frankenfoods" is really a controversy over the safety and integrity of transgenics. Because germ line gene therapy affects future generations it is a form of eugenics, so the application of this procedure to humans has raised novel ethical issues. Space limitations prevent me from developing my argument fully, but my position, in a nutshell, is as follows.

In an ideal world, where all scientists can be depended on to observe the strictest standards before engaging in germ line gene therapy, all of the arguments against developing and using it have serious flaws. It does seem that one can draw a non-arbitrary line between negative and positive eugenics, and there is not even any good theoretical argument against positive eugenics. Germ line gene therapy will not deplete the gene pool or adversely affect evolutionary development. However, in the real world, some scientists will exaggerate the benefits and minimize the risks. Germ line gene therapy produces few benefits that cannot be attained by a less risky way. In the real world, these benefits do not warrant taking even small risks that could have long-term disastrous consequences.