Gene therapy refers to the repairing or replacing of malfunctioning genes that cause a deleterious illness or condition. There are two forms of gene therapy: somatic and germline.

Somatic and germline therapies

Somatic therapies are used to replace or repair malfunctioning genes that are expressed in such conditions as cystic fibrosis or sickle cell disease. Since these therapies attempt to remedy the causes rather than alleviate the effects of disease, they presumably will provide more effective and beneficial medical treatments. Although initial attempts to develop somatic gene therapies proved largely unsuccessful, experimental treatments since the mid 1990s of severe combined immunodeficiency disease (SCID) and sickle cell disease have renewed public optimism regarding its potential efficacy.

Like somatic therapies, germline therapies attempt to repair or replace malfunctioning genes. The principal difference is that the corrected gene, rather than the deleterious one, is passed-on to subsequent generations. Consequently, the potential benefits or effects of germline therapies could be much more widespread than those of somatic therapies. As of 2002, no experimental procedures employing human germline techniques had been undertaken.

Ethical and moral objections

In principle, somatic gene therapy has raised few ethical objections. Because these therapies treat the underlying causes of disease at the molecular level rather than concentrating on affected organs or compromised biological processes, somatic therapies have been largely perceived as more sophisticated and potentially more effective extensions of established medical procedures. So long as these therapies are safe, there is nothing inherently wrong in deploying them. The issue of safety, however, came to the forefront with the death in 1999 of a patient undergoing an experimental genetic treatment for ornithine transcarbamylase (OTC) deficiency, an incident that prompted calls for greater public oversight or regulation.

The prospect of germline therapy has proven much more controversial. The primary objection is that humans should not attempt to construct the genetic inheritance of future generations. This objection usually takes one of two forms. First, since so little is known about the complex relationship between genes and larger environmental factors, it would be imprudent to introduce genetic alterations that would be inherited by future generations. Although the goal would be to eliminate a severely debilitating disease or condition, there might be unintended or unforeseen consequences that would adversely affect subsequent generations. Individuals carrying a recessive deleterious gene, for example, might in the future incur certain survival advantages in response to changing environmental factors. Since the effects of germline therapy are so much more widespread than those of somatic therapies, large populations could be potentially devastated. The seemingly harmless or even beneficial intervention into the human germline could wreak havoc down the road.

The second form of this objection invokes a more sweeping moral imperative. Humans do not have a right to shape the genetic endowment of their descendants, and correspondingly, individuals have the right to be born with unaltered genomes. People must simply resist the temptation to play God in shaping the destiny of humans, both as individuals and as a species.

The principal defense against this objection, in both its forms, is that it does not sufficiently take into account the nature of evolutionary change, thereby imposing unwarranted responsibilities regarding the possible fate of future generations. Other than identical twins, there are no unique genomes that parents do not have a right to alter or that offspring have a right to inherit in an unaltered form. Human reproduction entails the creation of a unique genome, derived from the genes of parents but also including mutations. It is difficult to imagine what an unaltered genome might be in the future in evolutionary terms. If individuals have a right to inherit an unaltered genome, then presumably cloning should become the preferred method of human reproduction. In addition, many argue that the prudential claim that current ignorance should prohibit germline interventions is unwarranted. Every action entails unforeseen consequences, and it is not known whether failing to intervene will prove better or worse than intervening. It cannot be known in advance whether the consequences of germline therapies will be any more or less devastating than those of natural selection upon future generations.

Some religious and moral concerns have also been raised, not so much with the prospect of genetic therapy per se, but with the fear that their introduction might exacerbate some already troubling trends. For instance, it is argued that the growing knowledge of human genetics is not being used, at least initially, to develop more effective therapies, but to prevent the birth of offspring with debilitating or undesirable genetic traits. Some fear that parents will turn increasingly to embryonic testing and screening techniques, such as preimplantation genetic diagnosis, to prevent the implantation of embryos carrying certain genetic abnormalities, leading in turn to the destruction of embryos deemed to be undesirable.

The issue is further compounded because the same techniques being developed as therapies may also be applied to select, and perhaps someday enhance, certain genetic characteristics of offspring. The bar of parental expectation would then be raised dramatically regarding what constitutes a desirable or even healthy child. The prospect of so-called designer babies will exert social pressure on parents not only to prevent the birth of offspring with severely debilitating conditions, but to select or enhance their genetic endowment in the hope of giving their children the best possible start in life. Although the development of genetic therapy is motivated by a humane impulse, its advent could fuel parental anxieties and prejudicial attitudes toward individuals with physical and mental disabilities, thereby unwittingly supporting a new, implicit, and insidious form of eugenics.

Proponents of genetic therapy counter that these worries are both unfounded and inflammatory. Legal protections against discrimination can be enacted as needed. Moreover, the best way prevent the destruction of so-called undesirable embryos is to develop effective genetic therapies as quickly as possible. More importantly, the distinction between genetic therapy and genetic selection and enhancement is spurious. Any therapy is also an enhancement, because the restoration of health is presumably an improvement over illness. In addition, many non-genetic medical procedures are enhancing, rather than therapeutic, in character, and genetic therapies will make them more effective. Genetically enhancing an individual's immune system, for example, is merely a more effective form of inoculation. Despite the moral and religious objections, the development of effective gene therapies may alleviate the suffering of many people.

See also BIOTECHNOLOGY; DNA; ETHNICITY; EUGENICS; EVOLUTION; GENE THERAPY; GENETIC ENGINEERING; GENETIC TESTING; GENETICALLY MODIFIED ORGANISMS; GENETICS; HUMAN GENOME PROJECT; MUTATION; NATURE VERSUS NURTURE; PLAYING GOD; REPRODUCTIVE TECHNOLOGY

BRENT WATERS