What if, with the stroke of a molecular cleaver, you could fix what you think is wrong in your family tree? Thanks to the work of Berkeley professor Jennifer Doudna and the MIT’s Feng Zhang, we now have the ability to edit, crisply and precisely, gene sequences in our cells that for whatever reason we think need editing. We can do it using an editing system, CRISPR-Cas9, that we borrowed from bacteria and so easy that amateurs working in their garages can apply it. Chinese scientists have already reported trying out this tool in human embryos. They did not have overwhelming success, but the latest tweaks to the system may have addressed some of the problems.
The possibilities with precision editing of our genome are almost limitless and range from the critical to the cosmetic. For fatal inherited conditions like Huntington’s disease, it could mean editing the causative gene variant in sperm or eggs to ensure that later generations don’t have it. For families who have these devastating diseases, that potential sits achingly close on the horizon.
But the spectrum of possibilities sweeps from preventing fatal diseases to more subtle modifications, such as editing out or in neutral traits according to parental aesthetic or, as has already begun, targeting gene variants linked to neurobiological conditions like autism.
This latter end of the spectrum gives rise to the fear that our individuality could be tailored or homogenized away thanks to these editing capabilities, one of the concerns that have been the focus of some of the brightest experts in the field, including Doudna herself. While she supports continued research into the applications of gene editing in humans, she has called for a thoughtful discussion about the ethics and appropriate use of the CRISPR editing tool, saying:
I certainly don’t think the time is right for real clinical application of human embryo editing right now.… how we get to a point with the research in this field where you can see a prudent path forward to a clinical application. Do we have enough regulation in place already for doing this kind of work, or do we need to have additional regulatory measures put in place?
Given that CRISPR is still a technological toddler with remarkable superpowers, of course we don’t have enough regulation in place. While clinical use of CRISPR to prevent devastating fatal disease is a pretty clear-cut case of appropriate use, the rest of the spectrum fades into an ethical muddle, and the line between OK use and inappropriate use may well be a blurry one.
Some, including NIH director Francis Collins, have called for a ban on CRISPR-related research involving the human germline (which originates sperm and eggs) whereas others, like George Church of Harvard Medical School, have emphatically argued against such a ban (Church is founder of a biotech company that applies CRISPR in pig embryos to produce pigs appropriate for human organ transplantation).
In a Nature editorial, Doudna calls a complete ban “impractical,” but she has outlined five steps to ensure that editing of the human germline, including standardized evaluation methods to assess effectiveness, international cooperation to devise guidelines, and a "cautionary halt," temporarily, to this kind of editing until the ethics are sorted out.
Although Church argues in a Nature editorial of his own that existing regulations might provide the boundaries that Doudna suggests, that seems unlikely. As a Nature explainer notes, laws related to germ cell editing vary considerably worldwide, although representatives from 20 countries have just wrapped up a US/UK/China-hosted meeting to address these questions. Church also argues that abuse of this tool is inevitable and that banning it would send it straight to the black market. That’s probably true, but that doesn’t mean that we can’t do as Doudna suggests and hit the pause button to develop an ethical and guidelines framework for those who don’t plan to engage in shady practices.
And while some, including Church, bring up a sort of Boys from Brazil fear narrative—even Doudna has confided that the specter of Hitler has haunted her dreams—another just as weighty concern is homogenization of our behavioral individuality.
Church argues in his Nature editorial that “replacing deleterious mutations with common variants is unlikely to lead to unforeseen effects and is probably reversible.” But what about effects we can somewhat foresee but aren’t necessarily universally viewed as desirable? If we do move full speed ahead on germline editing, what has begun as one targeted swipe at an autism-related variant could expand into a total blitz against any neurobiological condition that falls outside of some norm.
Yet shades of these conditions or even their unambiguous manifestations are linked to some of the richest and most importance expressions of human innovation and creativity we’ve known. The link between mental disorders and creativity, for example, might trace to gene variants that drive both. If we pinpoint target variants to edit away schizophrenia or bipolar disorder or depression, for example, will we be editing out a John Nash or a Temple Grandin or an Abraham Lincoln?
In addition, while Church’s argument about no unforeseen effects might be quite applicable to correcting, say, a Huntington variant or a cystic fibrosis variant, we aren’t even close to having a handle on how behaviorally related variants interact downstream with other genes to create the variable weave of individual human behavior. With the thousands and thousands of molecular interactions that result in who we are, how do we trace the reverberating effects of a deliberate gene edit? Because just as changing a word in this sentence affects more than just that word, altering the sequence of a gene could lead to a cascade of effects that are unforeseeable and unpredictable in the shape of emergent properties.
In the short term, the lines seem clear. Church’s call to focus on benefits over risks is indisputably rational in one distinct situation: Fatal conditions deserve attention and the energies of the best scientific minds in applying this precision tool to addressing and preventing them. But as for the rest, it would best for us not to rush into the breaches that CRISPR editing creates but rather to consider the people—the individuals—who ultimately will arise from these edited genomes. How much will we compromise in our attempts to control and homogenize, and what unforeseen consequences will we unleash?
