By Kevin Esvelt

from GeneWatch 30-1 | Jan-March 2017

As one of the scientists who first described how CRISPR could create gene drive systems capable of altering wild populations, I am morally responsible for the consequences. I'm writing to you in the hope that the people most critical of the very idea can help. Bluntly, gene drive is an example of how the current scientific enterprise causes our technological power to grow faster than our ability to ensure it is developed wisely. But because it affects the shared environment, gene drive may also be the key to improving the system - namely, by causing it to favor collective oversight. And to do that, we need your help.

To be clear: I am not asking you to change your views on gene drive or any other technology. I certainly don't expect you to support any real-world deployments, nor even continued research. Unlike what you might have heard, CRISPR-based drive systems cannot cause any species to go extinct unless everyone in the world deliberately chooses that outcome. But there's no question that they give entirely too many people the ability to unilaterally alter wild populations. Just because natural forms of gene drive are present in every species doesn't mean it's right for us to harness the phenomenon.

After all, many people hold the natural world sacred. They may believe that any attempt to change it - even to preserve the remainder - is immoral. Others believe that ecosystems are so complex and potentially fragile that the risk of accidentally causing a catastrophic and irreversible change is too great. I've met extremely gifted people who maintain that all technologies increase the ability of the powerful to oppress the powerless, and consequently work to halt them whenever possible.

I respect the intent behind each of these positions, although my own values and assumptions differ. I may be the leading scientific skeptic of our ability to develop gene drives with wisdom and humility, but I continue my research on local drive systems because I'd rather try to solve ecological problems with biology, not bulldozers. The smallest possible change capable of solving a serious problem may be genetic. If so, we should start small, have independent groups study the consequences, and scale up if appropriate.

I say all of this not to change your mind, but to make it clear that a total ban on gene drive research would be tremendously damaging to my own laboratory. Even so, if you decide to call for such a ban, I will understand. I won't agree, but I will publicly stand up for your right to share your views and criticize my research. More, I hope you will carefully scrutinize everything that my colleagues and I are doing.[1] After all, the more people who try to imagine what might go wrong, the better our chances of avoiding mistakes. You might think of something that we've missed. And since I am morally responsible for the consequences, I will listen to your concerns.

The problem is that many key decisions aren't similarly advised by others. They're made by small groups of elites behind closed doors. Even though these people cannot reliably anticipate the consequences of their actions, no one can check their logic or suggest alternatives because no one else knows a decision is being made.

This isn't a new state of affairs, of course; the same sad description sums up most of human history. The difference is that technology is now powerful enough that some of those decision-making elites are scientists.

That's a particular shame because doing research behind closed doors violates the central tenet of science.

The "scientific method," such as there is one, simply involves constructing societal systems to reward people who carefully scrutinize and challenge existing models of the world. Get enough people to look for flaws in the predictions of a theory, and eventually they'll find some - and by doing so, help improve our understanding.

But why restrict that encouragement to professional scientists? We don't have a monopoly on insight. The more people who participate, the greater our understanding.

Sadly, the scientific enterprise began before we could share our research proposals and results with everyone in the world. And it evolved to punish scientists who do. Anyone who shares a good idea is ipso facto allowing other laboratories to throw more money and hands at it, publish first, and claim all of the credit. So no one does.

Everyone would be better off if we all knew what everyone else was doing, because then we wouldn't be searching blind. We could rationally decide to collaborate or compete depending on the interests and capabilities of others. Doing science would also be much more fun, because we wouldn't have to live with the nagging worry that we might be wasting years of our lives pursuing a project that someone else would do anyway.

The current state of affairs is a tragedy for science. But why should you care?

Because a world in which ever more powerful technologies are developed in secret by people who cannot reliably anticipate the consequences is a disaster waiting to happen.

Worse, it's a world in which ever more people lack a voice in decisions that could affect them. Gene drives are a perfect example. Even though most CRISPR-based drive systems pose few - if any - ecological risks, that's small consolation when some researchers can single-handedly loose constructs that could eventually alter entire wild populations. They might even do so accidentally while trying to do something else, entirely ignorant of the consequences for the social fabric.

That's not a world I particularly want to live in, but none of us has much of a choice. We decided to publicly detail CRISPR-based drives precisely to raise awareness of this risk. We let people know before running experiments in order to encourage outside scrutiny, and my group is now working on ways of precisely restoring populations to their original state. But even if we succeed, it won't be enough.

Because gene drive is just one powerful technology. There will be more. The problem is systemic: we are encouraging scientists to open boxes without allowing anyone else to take a look or offer an opinion. That's not a system anyone would rationally design. Sadly, it's now easier to engineer biology than culture. And it's particularly difficult to change a system from the inside.

You are not on the inside. In fact, you're already engaged with the one issue that could help change the system: gene drive technology itself. As the U.S. National Academies' report stated,

"The best course of action is to ensure that the people who could be affected by a proposed project or policy have an opportunity to have a voice in decisions about it. Experts acting alone will not be able to identify or weigh the true costs and benefits of gene drives."

In short, the status quo cannot hold. Simply building a drive system capable of spreading in the wild risks affecting others in the event of an accident. Hence, gene drives cannot be ethically developed behind closed doors. That means they're a lever capable of changing the system... but only if enough people on the outside grab on.

So oppose gene drive research if you feel that you must. But please help use its very existence to change the system. The path is clear: pressure scientific journals, funders, and policymakers to require all research proposals involving any kind of gene drive to be made public. Give everyone a chance to voice concerns and make suggestions before experiments begin, when we can still change the design to improve safety.

If that sounds like a good idea for other fields, I couldn't agree more. But as with all things ecological, we should begin by making the smallest possible change - in this case, to the one field that demands it - and see if it works. Success will create a precedent that could then spread to other technologies with shared impacts, and perhaps far beyond. A few extra voices could make all the difference.

So help science be true to itself. Use gene drive to open its doors, and let the daylight in.


Kevin M. Esvelt is an assistant professor at the MIT Media Lab, where he leads the Sculpting Evolution Group.





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