My perspective on extending genetic research to germ line DNA editing is in line with the recent guidance from the International Society for Stem Cell Research (ISSCR).
Rather than positioning early, and perhaps prematurely, the ongoing conversation is best taken forward with open engagement and presentation of additional scientific data, as it becomes available. Without additional ethical germline research, supported by industry & regulators, the topic of whether there is reason for undue concern cannot be fully addressed scientifically, apart from debating the broader question of should we (which is conditional imo). To reach any natural conclusion will take time and further industry wide clinical application of non-germline editing technologies, acceptance of less invasive genetic modification technologies, such as mitochondrial transfer, and the implementation of other embryo technologies for human benefit.
An observation that underlies the issue is perhaps the historical fear factor effect of the "dual-use dilemma." That is to say the mere fact that there exists a possibility of misuse of scientific discoveries has in the past created significant barriers to progress and inhibited otherwise important developments in the timely advancement of research efforts to eradicate human disease & suffering. Human cloning wasn't on the agenda when Dolly was born, however the realization that SCNT technology had a possible "dual-use" potential has hobbled otherwise beneficial therapeutic sources for ES cells. The entire field of "embryo" science has itself been caught up in an unproductive polarization issue of creation, life & intervention for cell science application. Even today only a very small percentage of the public actually know science is able to establish ES cell lines across all "embryo" technologies in a non-destructive ethical manner for personal & universal cellular treatments. This generally needs to be factored in when discussing the topic as it's unethical in itself not to address the fundamental reasons for many objections to "embryo" science and how it has clouded the perspective of delivering solutions to those in need. Solutions need to be sought, compromise established & educational outreach in the mass media targeted to this very point to end the divisiveness. This germline debate presents an ideal opportunity for such rapprochement.
How is early genetic modification of DNA at the germ/embryo stage going to be any different than the hES cell source miscues of the past unless the rhetoric of the applied technological benefit conversations reflect the lessons learned?
Getting ahead of the issue is important, as it is with all emerging technological innovations that involve health. However, ensuring the safe sector development of recombinant DNA isn't the same as the ethical impact of human cloning, creating tens of millions+ supernumerary IVF embryos, engineering synthetic eggs/sperm & embryos, conducting germ line editing for disease or introducing DNA species' enhancements et al. These topics aren't challenges for science to overcome alone, they are fundamentally moral & ethical questions of benefit and use. They require careful scientific study, presentation in an open forum (not pay walled), thoughtful inclusive dialogue, education and public outreach.
Perhaps Leadership should suggest specific beneficial goals and propose a working version of a current dual use limitation charter when addressing the issue in the public framework. This will enable the field and public to express themselves within a clearly defined yet productive manner - i.e. what is potentially acceptable to Leadership and what isn't at this stage. Otherwise I can see the conversation repeating itself along the same lines as the media spin of scientific hyper reporting for readership numbers & incorrect assumptions of SCNT=human cloning, which was & still is an acknowledged no-go area in embryonics. Remember this concern set the tone for almost 20 years now of fallout in the field, not as a result of any specific efforts to progress human cloning but for the open door it presented. This was irrespective of the inherent scientific value in autologous ES cells & the sound pursuit of careful research driven embryo based technologies.
History has presented a number of important dual use dilemmas over the course of human history, nuclear power may have been/is the most impactful to human life: energy versus war; restraint versus force; detente versus annihilation; rule of law versus rogue use... One can do the trade offs in perhaps more applicable sciences, for example: synthetic life forms; biological constructs; chemical engineering et al. We live in a never ending cauldron of possibilities where all outcomes increasingly exist as a result of human ingenuity. The rule of law and our moral codes are the only binding principles that the community can foster to fundamentally shape human will. If there is a need for new laws then do so with factual education, public debate and openness centered around a health priority of "for the people" being paramount. However, competitive currents in science run deep today and as such active participation with guidelines would seem the only logical course.
If there were publicly exposed real life cases where germ line modification would alleviate suffering & disease in newborn children then I would recommend that be shared as widely as possible. Certain neurological diseases have been mentioned - if germline science is the only way forward in some of these cases it's important to publicly state that & make it clear why. These and other indications may very well be the first cases where there is a real need to use germline/embryo editing, however somatic cell gene therapy is without doubt the immediate and overwhelming priority.
I sketch below a fictitious scenario whereby a family has no choice, unless assisted by science - would it be ethical and morally correct to deny them their human rights to bear healthy children, should a technology be available to solve their case?
What happens when a known gene mutation is detected in an IVF embryo to a family with a genetic mutation history? Choice & hope drove them to look to protect against the very real & terrible consequence of giving birth to a child that will only suffer and die. If they didn't choose IVF fertility they would have no ability to protect the health of their child. God to them doesn't mean accepting a cruel and unjust outcome that imposes suffering on an innocent if there is an alternative. Don't implant that embryo and select/create more embryos until there is one which doesn't have the mutation? Is that acceptable to those that oppose IVF supernumerary embryo creation? What happens when all the created IVF embryos have the mutations? Don't implant any and send the couple home without solving their problem at considerable cost and emotional stress? Is that ethical?
What happens when the Docs find a potentially suitable IVF embryo but advise that there is a risk that the couple faces that the disease could manifest itself anyway without complete replacement of the relevant DNA strands? Implant without a DNA edit and hope for the best? Try to detect any malformation issues during fetal development? Then what? Fetal intervention? If that's not possible? Try to solve any postnatal genetic issues with best efforts? What if it's too late for any real chance to help and the child is effectively DOA or critical beyond hope and cannot be expected to regain near normal function even with the most advanced modern treatment at the cellular level? Don't risk it?
This on the other hand is not fiction. My brother has a seemingly healthy young 7 yr old son but the child's siblings weren't so lucky. Both were taken to full term, delivered and died. My sister-in-law had excellent medical care and after the loss of the first child, within days of birth, was monitored constantly throughout the 2nd & 3rd pregnancies. Her second child was again naturally conceived and made it through the gauntlet. The 3rd child died weeks after being born "healthy" & welcomed home into the family. They have suffered immensely and you can sense their deep sadness but they have joy & love in their hearts with the one that survived. We pray that little chap makes it all the way but if there were a way to screen the germline of his parents they may not have needed to play Russian roulette. In hindsight and with use of today's technology who would in their right mind try to conceive naturally knowing there was a significant risk, especially after having a previous issue? If a fatal brain disorder could go undetected in today's system and manifest itself in 2 out of 3 full term pregnancies then there is a real need to improve the process. Genetics presents the best hope to protect against such outcomes and it must be taken forward for all families. Parents to be should seek basic genetic testing and those at most risk must be offered IVF & advanced screening as standard. Informed decisions can be made once the available options are presented by the medical experts. If at some point in the future the process includes safe interventional genetics to assist life in being born healthily then I favor presenting such a choice to would be parents, if science has made it possible.
The parents of tomorrow are ultimately responsible for the next generations and therefore should be considered with weight, as with those that have direct experience in the diseases for which this germline technology would apply, if any. I don't believe shock is an emotion the youth of today exhibit when presented with the technology of tomorrow. Rather it would be a shock to all if the very real images of affected children were associated with political inaction to cure, if there was a chance to avoid such pain & suffering.
Having said that the entire field of somatic genetics and cellular therapeutics is just emerging and needs to be the focus to establish itself prior to more advanced possibilities taking over the headlines. The media feed off controversy so it's best to find a way to agree than to publicly disagree, for the sector.
Once the intervention technologies are sound the medical community has an obligation, if not a legal duty, to present the options. In time once the public are familiar with the detection technology their acceptance of the more complex interventional options will become less futuristic and ethically questioned, in those cases where the only guarantee is germ line modification.
Genetics holds enormous promise, as do potent cellular therapeutics. The union of the two, and their by-products, will be a powerful force for good. Early detection, intervention and eventually genetic modifications will be the key to freeing humans from their own frailties, which if managed as a universal community goal will serve rather than enslave generations to come. This future must be controlled and accessible to all.
For the moment though I can't see any reason whatsoever to accept personalized genetic enhancements nor use germline technology, if proven safe, beyond the absolute required need. Intervention to eliminate any possibility of irreversible disease, when a couple has no opinion, is where science can help bear a healthy child free of fatal developmental mutations.
Perhaps in time there will be safe cost effective universal "vaccine" like concepts that edit our DNA in order to eradicate disease, strengthen our physical constructs, enhance our immune systems and extend our cellular longevity. A legacy any generation would envy... That would be a world worth imagining into existence - along with some other wish list items!
Advocacy for cures.
MIT Gene Editing Article
PaulK Blog Interview with Dr. George Church
ARM Moratorium Request
ISSCR Guidance Statement
Genetic Scientists Policy Recommendations (pay walled)
Universal Declaration on the Human Genome & Human Rights - UNESCO
NIH Bioethics Resource