Editing The Culture of Science With CRISPR

BROOKE GLADSTONE:  This is On the Media. I'm Brooke Gladstone. So maybe the FOIA Improvement Act could usher in a new era of government transparency. There are still plenty of dark corners where big decisions are made that affect us, one of which is science. Scientists, who rely on attracting funders, keep their discoveries secret until publication so they're not scooped. Biologist Kevin Esvelt, leader of MIT Media Lab's Sculpting Evolution Group, says this culture of secrecy is not only inefficient, it's dangerous. Writing in Nature this month, Esvelt urged the scientific community to open all experiments to public scrutiny, beginning with the revolutionary and potentially world-changing gene editing research he helped advance. Kevin, welcome to On the Media.

KEVIN ESVELT:  Thank you for the invitation.

BROOKE GLADSTONE:  So let’s start with CRISPR. It's a stunningly easy way to edit gene lines. I mean, grad students can do it at home, right? How does it work?

KEVIN ESVELT:  Well, CRISPR is best thought of as a molecular scalpel that can be programmed to very precisely cut and, therefore, to edit any DNA sequence. And it works because when you cut a DNA sequence, the cell needs to fix it because the next time it replicates it needs to have made another copy.

BROOKE GLADSTONE:  So how can you use it? Why is it good for mankind?

KEVIN ESVELT:  Well, what it means is that we can cut a gene that we want to edit and introduce an edited version of that same gene. The cell will use our version to repair the damage. In other words, it makes CRISPR a bit like a pencil. It lets us erase the original sequence and write in a new one.

BROOKE GLADSTONE:  And, thereby, cure certain diseases?

KEVIN ESVELT:  So lots of blood-borne or immune diseases, where the immune system isn’t functioning right or it’s under assault by something like HIV, could potentially be fixed by editing a fraction of the cells to make them immune to the disease. And then those cells could replicate and make up for the ones that are not in yet.

BROOKE GLADSTONE:  We usually think of an organism's genome as being half Mom and half Dad, and this principle limits CRISPR because if you were to, say, alter the genes of one mosquito in order to prevent the spread of malaria and then you took that mosquito and released into the wild, those changes wouldn't show up in all of its offspring; maybe half of them would inherit them. And maybe that genetic change would be naturally selected out of the population over time, right?

KEVIN ESVELT:  That’s exactly right. Whenever we edit an organism, you have to keep in mind that we’re tinkering with something that has evolved to optimize reproduction in its ancestral environment, that is, the environment that that species evolved in. Anything we do to it is probably going to break something important for that because, remember, we’re  altering it for our benefit, say to block malaria, not the mosquito’s benefit. So what that means is that whenever we alter an organism, we tend to assume that natural selection will eliminate our changes over time.

BROOKE GLADSTONE:  Mm-hmm. So now let's move onto your big innovation, CRISPR-based gene drive systems. You realized that with CRISPR you could change the genetic destiny of an entire species.

KEVIN ESVELT:  That's right. We could cause a CRISPR edit to spread through a wild population, if we simply encoded the CRISPR pencil next to the edit. So, in other words, you’re teaching the organism how to edit genomes on its own.

BROOKE GLADSTONE:  So theoretically, we could use a gene drive system to, say, eradicate malaria by introducing just one genetically-altered mosquito into the population?

KEVIN ESVELT:  Yes. It takes a single organism to potentially spread that change to the entire population.

BROOKE GLADSTONE:  Now, the reason why we're talking about this at On the Media is because we care about transparency. And it really bothered you when the US National Academy of Sciences released a long-awaited set of guidelines for conducting gene drive research this month and left out the one that you’ve strenuously advocated for, which is transparency. Why is it so crucial in this case?

KEVIN ESVELT:  We, as a society, now have the ability to alter ecosystems. We can do it together, slowly, carefully, humbly, with collective scrutiny to keep us from making mistakes, or we can do it behind closed doors and scientists can ask people to trust them, despite the fact that they're choosing to do their work behind closed doors. We will not only be safest but we will be able to do the most good if we do everything in the open. What’s more, I don't think that there is a moral alternative. I want people who ideologically object to the very notion of altering nature in any way; I would love for those people to take a close look at exactly what my group is working on and proposing to do and try to find anything they can think of that might go wrong. And if they succeed, if they find something that we can't invent a way around, we can't make it safe, then the  project has to halt, and that’s as it should be.

Right now, scientists do not tell anyone what they are currently doing and planning to do in the laboratory. I think the system would be better if all research was done in the open. Gene drive is the place where we must start. Everyone should have an opportunity to share their concerns and criticism when it comes to technologies that will impact all of us. And we would be foolish to dismiss concerns simply because someone doesn't have a degree.

BROOKE GLADSTONE:  You recently met with a couple dozen Nantucket, Massachusetts residents to seek permission for a CRISPR-based experiment you wanted to conduct there, which would aim to diminish the transmission of Lyme disease. You're not worried that by sharing the design of your study with the public you’ve also invited scientists in the field to scoop you?

KEVIN ESVELT:  By being so open about it and receiving media coverage about it, it will now look bad if anyone else does.

 [BROOKE LAUGHS]

So, to some extent, we are free to take the first step and be rewarded for it. What's hard is for the next person coming behind us.

BROOKE GLADSTONE:  Yeah, it seems to me that this is a little pie-in-the-sky. How you change the tide of money flow?

KEVIN ESVELT:  Well, if funders require that proposals requesting money to perform experiments be made public, that would get us most of the way there. Most science is funded by the government, taxpayers. And, given that, why is it done behind closed doors, which does not benefit taxpayers?

BROOKE GLADSTONE:  So because this kind of research changes everyone's environment, you want the whole public in on it. And  you know what happens when you do that. I mean, genetically-modified anything causes an instinctive clutch reaction in a lot of people, and how do you get past that?

KEVIN ESVELT:  Much of that reaction is precisely because research in genetically-modified organisms did not offer clear and obvious benefits to most people. It was not done in the open. Safeguards were not clearly discussed in advance. And, of course, it was done largely by for-profit companies that people had other reasons to be skeptical of.

In our discussions with the citizens of Nantucket and the Board of Health there, we did see a very different response to a project that would be nonprofit, done in the open, with the communities making all of the key decisions - where the research would be tested, what kind of resistance to Lyme and other tick-borne diseases would be engineered in the mice. We observed a very, very different response from what you typically see when you bring up genetically-modified foods.

BROOKE GLADSTONE:  There seems to be a delicate balance here between the need to educate the public, include it into the discussions about gene drive systems, earn its trust and the fear that the more people know about the technology and tinker with it, the greater the risk. So how do you mitigate the risk on both sides?

KEVIN ESVELT:  It’s a great question. So what am I afraid of? Well, I'm not particularly worried about ecological risks. That is, in fact, I was, I was surprised at how most of my ecologist colleagues are not particularly fazed, even though this technology can be used to suppress populations or possibly even eradicate them entirely.

BROOKE GLADSTONE:  Like getting rid of mosquitoes completely.

KEVIN ESVELT:  Well, there are 3500 species of mosquitoes in the world and six of them are responsible for the vast majority of human disease. Two are invasive in most of the world and the other four are responsible for a child dying roughly every four minutes.

BROOKE GLADSTONE:  From malaria.

KEVIN ESVELT:  Yes. But there's only a few diseases in the world where you have that kind of moral urgency. The only thing I will say is that I don't get a vote because I'm not affected one way or another. It's the people who do live there that are going to have to decide because, make no mistake, our civilization is not sustainable. We must continually invent solutions to make the world a better place. We need popular support for that. Why should people trust scientists who insist on doing their work behind closed doors?

BROOKE GLADSTONE:  Kevin, thank you very much.

KEVIN ESVELT:   Thank you.

 [MUSIC UP & UNDER]

BROOKE GLADSTONE:  Kevin Esvelt leads the MIT Media Lab’s Sculpting Evolution Group.