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 
Well said, Laura!
I loved reading this blog post and wish your candid and thought provoking comments would make it to a larger audience. The next 10 years are going to be both exciting and ethically challenging in genetics, unlike anything we’ve seen before. One of my biggest concerns is making technologies available before we’ve adequately studied the outcomes. I see this already occuring in the field of NIPT, in that marketing seems to be “running the show” instead of the science and data. It is it OK to have sensitivity and specificity of a test based on an N=1?? Or, take the argument of a terminal cancer patient having access to medications before they are FDA approved. It’s one thing to skip the “checks and balances” with a terminal patient who can give consent, but quite another to produce a child that had no say in the matter. Is this ethical to let parents decide? Will there be wrongful birth lawsuits if the child has some abnormality from the technology? I was in a recent ethics meeting and a physician was talking about advances in surgery and how many patients died before certain techniques were perfected, and this was an acceptable part of the surgical “learning curve”. Do we feel the same way with IVF/nuclear transfer? Is it ok to sacrifice a few infants/children before we perfect this in the real world application? I don’t have the answers and can argue both sides. I would love to see more ethical debates like this within the genetics community. Laura- have you thought about bringing your blog/discussions in the format of NSGC/ACMG sessions?
Hi Libby. Thanks for the kind words and the very interesting dilemmas you set out. I’ve done some interesting sessions at NSGC but never anything similar to what you describe. Would be fun though! We have monthly discussions at sarah lawrence that cover some of this territory. It would be great to hear more from the counselors who have experience in the field. If anyone was iterated I would definitely be up for it!
I generally agree with your comments/conclusions, however the comparison of mitochondria to gut bacteria is seriously lacking. It is generally accepted that mitochondria as cellular organelles are the result of billions of years of evolutionary symbiosis between eukaryotes and bacteria, but if you removed mitochondria from our cells, we’d die. Disturb gut bacteria and you may get dysentery. Mitochondria play a critical role in energy creation, proper cell death and most likely many other cellular processes we don’t yet understand. Your argument is not well served by hand waving away the importance of mtDNA and mitochondria. Otherwise, wholly agree with how society should proceed with scientifically-proven SAFE technology.
No disrespect to the mitochondria! Although possibly I have more respect than you for the importance of gut bacteria. In fact, there are suggestions they may be implicated in some behavioral disorders, among others. My basic point – and I’ll stand by this — is that although you are in big trouble when mitochondria fail, they don’t play a role in the sort individualized traits and features we are discussing when we talk about eugenics and trait selection.
Ha- good point about the gut bacteria! And, for the record, I absolutely stand behind you standing behind the main point that mitochondrial DNA does not impact individualized traits. This is not about eugenics, despite a vocal faction painting it that way. Keep up the good writing.
I once had a British genetic counselor say to me, “You Americans…you’re so obsessed with the slippery slope argument.” Ever since, I’ve wondered if this true. Is the slippery slope argument an “American” creation? or did we Americans simply co-opt this argument, fall in love with it, and forget that any others exist? Do other countries and cultures fall back on the slippery slope as a scare tactic any time something makes them feel uncomfortable or threatened?
I think the community affected the most by the possibility of oocyte modification–the men and women who hope to conceive a child unaffected by a mitochondrial disease–would be the best spokespersons to respond to the accusations that IVF with oocyte modification is “creating designer babies”. Arthur Caplan perhaps simplified the discussion best by focusing on why this technique is being considered in the first place: “The goal of the experiment in genetic engineering is not a perfect baby but a healthy baby.”
When people discuss stem cell therapies as a way to promote health and extend life expectancy in mature adults, we never say researchers and clinicians are trying to create “designer adults”, nor would we make the assertion that people being treated with stem cells are being tweaked and prodded with the goal of perfection. In all likelihood, everyone would agree that stem cell therapies are being created with the focus on health, not perfection. Yet parents who want a baby born with cells that will live instead of die are accused of wanting perfection.
Thanks for this thought provoking post, Laura. I will admit that I am one who feels the slippery slope conversations are important. Not because I want to deny technological progress – but we need to think carefully about the possible implications of new scientific technologies as we move forward. It is hard and scary to consider each ethical dilemma that these new technologies present, and while I agree that each of these individual questions deserves a unique look – to me it seems incredibly important that we keep talking about the big picture meaning of all of this. Here is a link to another blog post on this topic by Nathaniel Comfort – http://genotopia.scienceblog.com/402/three-parent-babies-and-eugenics/ The article concludes- “It is the false and dangerous belief that science alone can be a guide to civil society. The further science takes us, the more we need the humanities to deepen our understanding of where the science is taking us.” As genetic counselors our priority is advocating for the individual needs of our patients. Hopefully we can continue to engage with thoughtful people outside of our profession, as we consider the meaning and implications of this technology for society.