This week, the FDA is holding hearings to examine the use of a new IVF technique that could allow women with mitochondrial disease to have children who are genetically their own without the risk of passing along the condition. The proposed treatment involves yanking out the nucleus of a donor egg and popping in a nucleus from the mom-to-be. Studies of monkeys have demonstrated that this method can be used to produce healthy monkeys; studies of humans thus far have demonstrated the potential to create what appear to be viable embryos. Shoukhrat Mitalipov, the Oregon-based researcher who has done both human and animal studies, is interested in moving to clinical trials – or as Dina Fine Maron puts it in Scientific American, “human clinical trials.”
The issue of oocyte modification was debated last year in the UK, where the government has opted to allow nuclear transfer to be used on an experimental basis. The story got major play in the press there, as it has here, with catnip headlines about ‘3-parent babies.’ There are some serious questions to be answered about the risks – the first studies using human eggs showed an increased rate of abnormal fertilization, although zygotes with an appropriate number of pronucleii seemed to develop normally. Minimizing the risk of harm to any child born of this technique is an important focus of the regulatory agencies and if we can’t do it safely, we shouldn’t do it at all – which brings me to the other question under debate: should we do it at all?
Marcy Darnovsky of the Center for Genetics and Society, a non-profit organization that leans precautionary on the use of reproductive technologies, has been waging a one-woman war against nuclear genome transfer, protesting the UK decision in Nature, circulating a petition to the FDA to decry human germline modification and penning an OpEd for the N.Y. Times entitled “Genetically Modified Babies.” Darnovsky brings up safety issues but the heart of her objection is the slippery slope argument. We have informally agreed not to make changes in the germline that will be passed down to subsequent generations – not to tinker with eggs and sperm. This is a step over that line. If we do this, what else will we do? It could, she says, “open the door to further germline manipulations.”
Last winter, I attended a panel on the ethics of germline manipulation where participants debated a resolution to prohibit genetically engineered babies. Lee Silver (Princeton) and Nina Farahany (Duke Law) represented the anti position (i.e., let’s NOT prohibit genetically engineered babies) and won the debate by focusing on – wait for it — nuclear transfer for mitochondrial disease! Forbid genetic engineering, they argued, and you rule out this potentially game-changing therapy for afflicted families hoping to give their kids a life free from the burden of life-long, incurable disease. In other words, another slippery slope argument, only the other way round – accept the concept of regulation in any form, let the bureaucrats in, and you cut yourself off from progress and doom families forever to suffering that could have been prevented.
The thing is, I am not at all convinced this example – like many other models we construct — represents anything other than itself. I don’t mean to say it’s trivial. But mitochondrial replacement therapy isn’t a reasonable stand-in for the complex issues associated with genetic engineering, like trait selection or eugenics. You can make the case that mitochondria are more like the bacteria we harbor in our gut than they are like nuclear DNA , in terms of how they affect our health and well being. Gut bacteria have DNA too. If we gave the 3-parent child a fecal transplant, would we have a 4-parent child? (Is that a bad thing? Cool or creepy?)
The problem with slippery slope arguments is that they don’t relieve the obligation to assess each and every situation on its own merits. They don’t provide some easy moral clarity or regulatory guidelines. Everything exists on some sort of continuum, whereby you can draw a straight line from the ludicrous to the patently unacceptable. When does life begin? It’s a tightrope, with one end tied around infanticide, and the other clasped in the hand of some guy out of a Monty Python sketch singing “every sperm is sacred.” Every decision we make is about drawing a line. And every ethical quandary worthy of the name is unique enough that it deserves its own weighing of the pros and cons.
Are you concerned about doing PGD for later-onset conditions? This is a line some people have suggested, between what is a good and a bad use of preimplantation technology. What if that condition is Huntington’s? Okay, what if it is a BRCA 1 mutation? Or what if it is a subtly increased risk of Parkinson’s disease? Each of these is a very different scenario. Every family is going to experience those risks differently. The fact that you can draw a line from here to there does not automatically absolve you of considering the facts at hand in each case, the good that can be done, what stands to be gained, what may be lost. It’s very hard to take away happiness for one person based on what might (someday, somewhere, possibly, in a related case) happen to somebody else.
The thing is, it would be so much easier if we could find that certainty. Slippery slope arguments are a plea to make things stand still for a moment, so a person can get their bearings. Anyone who works in genetics can relate to that sentiment. But history is itself a slippery slope from a turbulent past to an uncertain future, and we don’t have the luxury of stepping off. So what should we do about nuclear transfer for mitochondrial disease? Well, let’s make a decision based on mitochondrial disease and the very sensitive nature of the human embryo, which may not take kindly to this manipulation. Let’s not make it the last word on anything. Let’s not pretend we are now for all time choosing to abandon sufferers to their fate, or opting for GATTACCA. It’s hard enough and scary enough without conjuring up the ghosts of battles to come.
The DNA Exchange 