THE TIDE HAS COME IN AND THE LINE IN THE SAND IS GONE: DECISION TIME ON HUMAN GERMLINE ENGINEERING

For decades we have speculated about what it might mean to be able to change the genes of an embryo. Not to be able to treat disease, or to prevent disease, or even to generate extra embryos in order to pick the best of the litter, but to get in there, to insert ourselves into the process by adding variation that nature in its evolutionary wisdom, has not made available. Germline engineering, it is called by some. Tampering with humanity, by others. Playing God.

The language betrays an unease that is both non-specific and widespread. The stakes are enormous. If we can alter a child’s DNA to make the child smarter, stronger, less susceptible to cancer or heart disease, why would we not do it? There are a multitude of answers, but perhaps the most compelling one is this: we don’t know what we don’t know. A generation raised on nuclear fears does not trust the intentions of man; a generation facing the fallout of climate change has no faith in humanity’s ability to foresee long-term consequences.

Let’s spill a little ink on some of the other qualms as well. Expensive genetic technology will exacerbate inequality in a world where the haves and the have-nots are increasingly at odds. It will make life harder for those who are not helped, the ultimate children left behind. It will enshrine the prejudices of those who control the technology. “What do you see?” I ask my students. “Taller,” they say. “Smarter.” “Blond hair and blue eyes.”

“Heterosexual,” says one boy, with a sad shrug.

Anxieties about the personal and social costs of tampering with humanity are as old as Icarus, who flew too close to the sun on his homemade wings. Inchoate fears have accompanied every step forward in genetics. We want better children, “ said Leon Kass, in a Washington Post editorial in 2003, “but not by turning procreation into manufacture or by altering their brains to give them an edge over their peers. We want to perform better in the activities of life–but not by becoming mere creatures of our chemists or by turning ourselves into tools designed to win and achieve in inhuman ways.” Evidence from polls suggests that society agrees with him in theory, but does that mean individuals would be willing to forego perceived advantages for their own children? Does it mean that they should?

In response to threats real and perceived, genetics has lived for decades with germline engineering as our line in the sand. Gene therapy for the individual, but no changes to DNA that will be passed along to successive generations. Frankly, this was an easy point to concede, when no credible means of accomplishing the goal safely was in view. But out there, in the absence of regulation, in the unconstrained global marketplace, in the power of what might someday be possible, the question lurked, not answered, just deferred.

Last month, twin editorials in Nature and Science served notice that the time has come to make some hard decisions. Things long envisioned as a part of our future are suddenly edging into the present, thanks to the stunning success of the CRISPR/Cas9 system of DNA editing.   A recent article by Antonio Regalado in the MIT Technology Review posits that we are teetering on the cusp of successful human germline alteration, and that in fact we may already be there (the article says that papers claiming successful embryo modification have been submitted to journals, but no evidence is in print — yet). In response, a veritable who’s-who of the genetics world (including Jennifer Doudna, a co-inventor of CRISPR) have called for a time out – a moratorium on human germline research while the world considers whether or not the technology – and the technologists – are ready for prime time.

Although the array of voices joining in this chorus are impressive, don’t overestimate this show of unanimity. The arguments in favor of a pause are diverse, and don’t represent the same long-term goals. There are three major types of arguments made against proceeding with germline manipulation, often conflated, and it is important to sort them out. The first line of argument concerns safety alone. Some signatories, such as Harvard’s George Church, see the ‘pause’ as simply an acknowledgment that safety and efficacy data are not yet available. Others are anxious to avoid the threat of a public outcry that could complicate the use of CRISPR/Cas9 for less controversial uses.

Essentially everyone agrees that if it isn’t safe enough you can’t ethically proceed, although defining ‘safe enough’ could be contentious.

A second set of arguments reflects concerns that some practices, though perhaps not dangerous themselves, will lead us in the direction of something more fraught. These slippery slope arguments are consistently employed in appeals to a popular audience, in part because they help make complicated issues accessible, and in part because they allow those making the argument free rein to speculate on the most click-worthy of potential scenarios. “The technology could be used to create, say, a unicorn, or a pig with wings..” suggests a Daily Beast article entitled, New DNA Tech: Creating Unicorns and Curing Cancer For Real?

For realz. And you wonder why I don’t care for slippery slope arguments.

And then there are those who are concerned about the potential negative consequences of the technology itself. Those voices too are a part of the quorum calling for a moratorium.   One Science co-author, stem cell researcher George Q. Daley, told the New York Times that the ability to modify our germline “raises enormous peril for humanity.” The Times quotes lead author and Nobel Laureate David Baltimore as saying “I personally think we are just not smart enough — and won’t be for a very long time — to feel comfortable about the consequences of changing heredity, even in a single individual.”

So presuming the world agrees to a pause – and presuming what Baltimore calls our “moral authority” is a thing in science, because it sure as hell isn’t in other spheres of would-be influence – what are we to do with the downtime? Editorials across the board call for a public discussion, so let’s start right here. I’ll go first. Four points:

  1. The tide has come in and the line in the sand is gone.

I don’t say that flippantly, because I understand the allure of a line. A line means you don’t have to think everything through every time. It suggests someone has an answer. It says some things are right, and some things are wrong, and somebody has gone to the trouble of figuring out which are which. But sad to say, it isn’t so. We don’t know. There’s too much at stake to arbitrarily rule out whole fields of research based on the need to avoid existential distress.

All the slopes on which we practice are slippery. Subtleties matter. Details matter. We are going to have to figure these things out case by case. Accept this and move on.

  1. Change has its price, and the good comes along with the bad.

Articulating a risk, or describing a negative consequence, is not adequate evidence in and of itself that something is bad and we should not do it. Vaccinations and IVF do have negative consequences for some individuals. There are risks. Those risks are well outweighed by the benefits. This is inarguable (do you hear me, Internet? Inarguable). Conversely, the fact that a subset of humanity can be helped by some practice is not in itself an argument that it must be allowed to move forward. There are times when individual’s best interests have to take a back seat to the needs of society. In China, where sex selection is rampant, the number of women ‘missing’ in the past 25 years is equal to the entire female population of the United States. Ask them how that’s working out.

Our debates are filled with people talking at one another, one side telling us why we should be afraid, and the other pointing out that it is a terrible thing to stand in the way of progress when people are in pain. The thing is, they are both right. Don’t imagine that there is some secret formula that will allow us to have the benefits of new technology and not experience any negative consequences.

  1. Realistically, we don’t have the option to stop moving forward.

When the cave people discovered fire, do you think perhaps one of them pointed out the danger? I mean, this stuff burns. Our great-great grandchildren will live in a different century. We may have something to say about what that world looks like, but we will not have the option of handing them a world that looks like ours, and neither did our ancestors.

  1. Consensus, not government regulation, will govern practice.

 Sticking out your hand and saying no is not a useful response. Suggesting regulation without acknowledging who will be doing the regulating is not a useful response. In the end, in a world where all the players can vote with their feet, consensus and not regulation will dictate behavior once the whistle blows and the timeout is over.

What do you think? Please join the conversation.

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3 Comments

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3 responses to “THE TIDE HAS COME IN AND THE LINE IN THE SAND IS GONE: DECISION TIME ON HUMAN GERMLINE ENGINEERING

  1. Pingback: Cells Weekly - April 12, 2015 - Stem Cell Assays

  2. Carolyn Riley Chapman

    Great essay on this topic and I think your four points at the end are realistic. Although we can’t stop forward movement, we must all feel challenged to think of how we want to shape consensus. And there is the not-small issue that any individual’s choice to proceed with germline modifications is not solely autonomous. In other words, once it’s allowed, the playing field is permanently altered.

  3. Maureen

    Very well-articulated! Indeed, there is no clear right or wrong answer when it comes to the issue of germline engineering. Humankind owes it to itself, however, to have a constructive conversation, rather than an argument, about the issue. One thought is that people opposed to germline engineering might feel differently if they focused on the technology’s ability to rid suffering rather than to cause harm. What if we could prevent needless suffering by changing the fate of children who are genetically predestined for an illness such as a neurodegenerative disorder? Many would see that as a beautiful thing. The issue arises when people consider how this technology could be abused to create a hierarchy based on people’s genetic “fitness” by eliminating naturally occuring diversity. The sad thing, though, is that pretty much anything that does good can also cause harm. Take for example computers. These machines allow society to automate innumberable processes and access vast amounts of information to expedite progress. However, with computers comes hacking, which leads to security breaches, fraud, manipulation and more. Were all of these consequences considered before the invention and the initial implementation of computers? To be honest, I have no idea. Regardless, computers were created and are now widely used, and many would say that the benefits of these machines outweigh the disadvantages. What I’m trying to get at is this: Should we throw away something potentially life-improving and life-saving only for fear of the “what-ifs”?

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