Germline Gene Therapy Concerns

Scientist doing stem cell research
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The science of gene therapy finally seems to be coming of age as this powerful technology reaches a point where it can help those with some of the most difficult to treat genetic diseases. Its approval for general medical use for a number of diseases appears imminent. In fact, the European Medicines Society has already approved its first gene therapy drug.

However, all the examples and trials to date involve somatic cell therapy.

That is, they only change the genetics of cells in the patient other than the germline sperm or egg cells.

Germline Gene Therapy Concerns

Gene therapy on germline cells generates a lot of controversies because any changes become heritable (since progeny receive the manipulated DNA). This makes it possible, for instance, to not only correct a genetic defect that causes bubble boy syndrome in the patient, but to also eliminate the defect permanently in subsequent generations of that family. This example is a relatively rare genetic disease but there are many others, for example, Huntington's disease or Duchenne muscular dystrophy, that are more common and could, theoretically, be eliminated in families suffering from these disorders.

While eliminating a disease entirely in a family is a spectacular benefit, the concern is that, if something unforeseen occurs (such as the leukemia the was introduced to some of the first group of children treated for an immune deficiency syndrome using a gene therapy approach), the genetic problem is passed onto the unborn children of future generations.

The concern regarding propagating gene therapy germline errors or side effects to future generations is certainly itself serious enough to halt any consideration of germline genetic therapy but mistakes are not the only issue.

Genetic Enhancements Is Not a Concern Now

Another concern is that this sort of manipulation could open up the possibility of inserting genes to provide perceived beneficial characteristics, such as increased intelligence, a tendency to tallness, or even specific eye colors.

However, moral concern over using this technology for genetic enhancements is not really an immediate practical question as science does not have a firm enough grasp of the genetics involved with most of these sort of complex characteristic to make gene therapy approaches to alter any of them even feasible at this point.

Controversies Over Germline Therapies and the Scientific Method

In the late 1990's there was a significant amount of discussion concerning the potential of germline gene therapy and the ethical concerns that accompany it. There were a number of articles dealing with this subject in Nature and the Journal of the National Cancer Institute. The American Association for the Advancement of Science even organized the Forum on Human Germline Interventions in 1997, where scientific and religious representatives seemed to focus on what should or should not be done, rather than the actual state of the science at that point.

Interestingly, however, there is little current discussion of germline therapy. Perhaps the tragedy of Jesse Gelsinger, who died as a result of a severe allergic response during a gene therapy trial at the University of Pennsylvania in 1999, and the unforeseen development of leukemia with the infants treated for an immune disorder in the early 2000's have engendered a certain level of humility, and produced a better appreciation of the of careful controls and cautious experimental procedure.

The current emphasis seems to be more on producing solid results and robust procedures to build upon as opposed to pushing the envelope forward to achieve new spectacular cures. Certainly, astounding results will occur but, to produce practical and safe treatments, many rigorous, methodical, and often plodding scientific studies are necessary.

Future Potential for Germline Therapies

As progress in the field advances, however, and the human genetic manipulation becomes more robust, predictable, and routine, certainly the question of germline therapies will re-emerge. Many already draw clear divisions and guidelines on what is permissible or not. For example, the Catholic church has issued specific guidelines as to the type gene therapy it deems appropriate.

Few would be foolhardy enough to consider germline therapeutic trials today given our current limited understanding of this very complex procedure.

Although researchers in Oregon are actively pursuing a very specialized form of germline gene therapy that just alters DNA compartmentalized in the mitochondria. Even this work, though, has drawn criticism. Even with a much better understanding of genomics and genetic manipulation since the first gene therapy test in 1990, there are still large gaps in understanding.

It is likely that, eventually, there will be compelling reasons to undertake germline therapies. Creating guidelines about how future applications of gene therapy should be regulated, however, would only be based on speculations. We can only really guess at our future capabilities and knowledge. The real situation, when it arrives, will be different and likely shift both the ethical and scientific perspectives.