Gene Therapy for Fetuses?

Published on
November 6, 2011

Gene therapy is experiencing a renaissance, with many of the recent successes in children. For some conditions, the younger the child, the better the genetic correction, because affected tissues degenerate with time. This is the case for adrenoleukodystrophy (ALD), the "Lorenzo's Oil" disease that strips the insulation from brain neurons. One goal of the not-for-profit Stop ALD is to team gene therapy with newborn screening, to help boys before they begin to lose abilities.

Should we attempt gene therapy even earlier? Before birth?

Fetal gene therapy is already being done in non-human animals, presumably in preparation for phase 1 clinical trials. Gene therapy is technically more challenging than inserting a shunt to drain a hydrocephalic brain or repairing an open spine, because it entails delivering gene-carrying viruses to affected cells and not anywhere else. It is fetal medicine on a different scale.

Carson Strong, a professor of human values and ethics at the University of Tennessee Health Science Center, argues in Human Gene Therapy that a phase 1 clinical trial on human fetuses is probably too risky, because this part of the FDA drug approval process tests safety, not efficacy. The fetus likely has nothing to gain. However, Strong describes two ways to address the problem by adjusting not the benefit part of the ethical equation, but the risk: use doomed fetuses.

Why not experiment on fetuses so sick that they wouldn't survive long after birth, if they even make it that far, or on fetuses scheduled for termination? The latter were indeed used to develop amniocentesis, chorionic villus sampling, and cord blood collection, technologies that have benefitted many. Using these fetuses without a future, Strong suggests, offers the possibility of examining their tissues to track the gene therapy. I envision the sliced eyeballs of some of the dogs in my gene therapy book, a necessity before people with Leber congenital amaurosis received the gift of sight.

Correcting a genetic defect before birth sounds like a great idea, but I'm uncomfortable with how we get there. At the risk of sounding pro-life, I do not think that fetuses in utero – unable to live ex utero, yet metabolizing, transcribing genes, their neurons firing and muscles contracting – should be subject to such experimentation, even if doing so could ultimately save lives.

It isn't the idea of "therapeutic misconception" – expecting phase 1 trials to debut miracle cures – that bothers me. Instead, I sense a more fundamental disconnect: the healing intent of gene therapy coupled with the difficult decision to end a pregnancy.

The situation isn't the same as studying development gone awry in extra embryos genetically destined for disease, the "leftovers" of couples selecting embryos that escaped a family disease. That's not an intervention, it's observation. And it happens during the first two weeks of the prenatal period, before the notochord has appeared and certainly before it has blossomed into a nervous system. Early embryos and fetuses are part of a continuum, yes, but in terms of what they can and cannot possibly feel, they are not the same.

To paraphrase the mathematician Ian Malcolm in Jurassic Park: just because we can doesn't mean we should. Let's focus gene therapy research on children who need it now.