Saturday December 09, 2017

Gene drive research could wipe out disease, or a species. Here's why the U.S. military funds it

The combination of gene drive and gene editing technology could override the checks and balances of natural selection.

The combination of gene drive and gene editing technology could override the checks and balances of natural selection. (vchal/Shutterstock)

Listen 13:45

Newly released emails show that a branch of the U.S. military is spending millions of dollars on research into a gene editing technique that has the power wipe out entire species.

Gene drives are a controversial new tool that could be used to fundamentally alter the DNA of a species. Use of the technology sets off alarm bells for critics who are concerned about the U.S. military funding the research, despite its positive potential to eliminate deadly malaria mosquitoes.

This week, The Guardian publicized documents released under the Freedom of Information Act between scientists at the University of North Carolina who are investigating "gene drive" technology and the U.S. Defense Advanced Research Projects Agency or DARPA, which is funding the work.

One concern is that a gene drive could override the checks and balances of natural selection.

Critics such as members of the ETC Group, a technology watchdog that originally published the documents, worry about the risks to the environment and, given that DARPA is a branch of the U.S. military, the potential weaponization of gene drive technology. For instance, could it be applied to destroy an enemy's crops?

All this comes as experts from the United Nationals Convention on Biological Diversity met in Montreal this week to debate a moratorium on gene drive research. They'll discuss the ban further next year in Egypt.

Dr. Kevin Esvelt is one of the pioneers behind the technology. Esvelt is an assistant professor and leader of the Skulpting Evolution group at the MIT Media Lab in Cambridge, Mass.

His group aims to solve problems such as the invasive rodents and ticks that spread Lyme disease, by adapting tools from nature, including gene drive.

His current research is funded by DARPA.

This transcript has been edited for length and clarity.

Bob McDonald: First of all, what is a gene drive?

Dr. Kevin Esvelt: Normal genes spread through populations only if they can help their organism reproduce. But hundreds of millions of years ago, nature invented a new kind of strategy, that is, genes that can spread even if they don't help their organism reproduce. You might say, "Well, how can they do that?" And the answer is by changing the odds that they can be inherited.

BM: So that's how nature does it, and that's part of natural selection. What are we doing with that system?

KE: If you have a problem with something like malaria, what we can't do is use biology. We can't use nature's toolbox. The reason is when we alter an organism, we pretty much always reduce its ability to reproduce ... So why would we want to? Well, imagine a world in which mosquitoes are as harmless as houseflies because they simply don't care to bite humans, a world where endangered species and delicate ecosystems are saved from invasive rodents without having to use pesticides and rat poisons. Now that's a world that would solve these natural problems by harnessing nature's best innovations. It's a lovely image. But in order to do that we need some way of altering a wild population in a way that natural selection will permit us to do. So one way is to take this concept of a gene drive from nature and attach the change that we want to spread, say the inability for a mosquito to spread disease.

DARPA's Safe Genes Program

Elements of the U.S. Defense Advanced Research Projects Agency's Safe Genes Program. (DARPA)

BM: So you want to change the genetic makeup of the mosquitoes.

KE: That's been the most popular application. What's really brought this to a head is our ability to now contemplate trying it. I played a very minor role in developing CRISPR, which is this molecular scalpel that we can use to precisely cut and therefore edit just about any DNA sequence in any genome throughout the kingdoms of life. But one day I wondered, "Well, what would happen if you encoded CRISPR in the genome along with the change you're trying to make?" That is, you program the organism to do genome editing on its own. Then if that organism mates with a wild one, the offspring will inherit your new change and the CRISPR system for making that change. In the reproductive cells of the offspring, it will cut the original version and replace it with the new version. All of its offspring are guaranteed to inherit [this] and editing will happen again and again. This is a form of gene drive. It's exactly how a number of natural genes spread in the wild. They cut chromosomes that don't carry them and get copied over in their place.

BM: So here you're putting your artificial gene or the gene that you want into the organisms and then it just spreads naturally as they reproduce.

KE: That's right. By ensuring that instead of having only a 50 per cent chance of being inherited they can have up to a 100 per cent chance.

 Anopheles gambiae mosquitoes

Anopheles gambiae mosquitoes are the major malaria vector in Africa. The disease kills nearly half a million people every year. (Johns Hopkins Malaria Research Institute)

BM: In what ways could this be weaponized? 

KE: Any technology can be used for ill. It's the technology that is a neutral tool, but some technologies are more dangerous than others. If you can engineer a mosquito to not carry disease, you can engineer a mosquito to better carry disease. But it doesn't really matter what you can do as long as it is slow, obvious and easily blocked. It's not much of a threat. So the interest here is ensuring that it is in fact slow, obvious and easily blocked.

BM: Is this also the case for other areas of gene drive technology? 

KE: All gene drive systems spread vertically — parents to offspring. They're all obvious to sequencing, as best I can tell, and they can all be countered the same way. Where it is a risk is socially and diplomatically. This is what utterly terrifies me. What would the public response be if someone accidentally released a gene drive system into the wild? What if someone were trying to test it in a local area but it escaped and began to spread even if it didn't do any harm. And again, I'm not worried about harm. Doesn't matter if it can be countered or not. That would conclusively show that we cannot be trusted with a technology of this kind, and that would be tragic because malaria kills nearly half a million people every year. The decision about whether to do something about [malaria] really needs to be up to Africans who are affected by it. And so we decided this is the sort of thing that people should not be tinkering around with in the laboratory, without telling people what they are doing, because the difference between ecological technologies — Eco Tech for short — and what you normally work on in the laboratory is that you can't opt out of the shared environment. That is, it may be possible to live without a smartphone but you can't live without breathing the air, drinking the water and eating the food of the earth. 

BM: Now why would the U.S. military be interested in this?

KE: First, let me say why I am not concerned that the military is taking an interest, and that is I don't think that this is a technology that is particularly vulnerable to misuse. It's slow because it only spreads vertically over generations — parents to offspring. It's obvious that if you sequenced the genome, or really sequence DNA from the environment, you will see it. You can't miss it and once you see it you know how to build the counter. It's very possible to build a version that overwrites the first one and undoes whatever change it made.

Kevin Esvelt

Kevin Esvelt doesn't believe gene drive technology is particularly vulnerable to misuse. (Massachusetts Institute of Technology)

But, that requires that you know what to look for and that you can make the counter quickly. So we need to ensure that we can do that. And that's one of the goals of the Safe Genes program, to ensure that we can remove engineered genes from populations. That's one reason why they're supporting our work.


Editor's note

Quirks & Quarks asked DARPA about why it funds research into gene drives. This is part of the agency's answer.

"The science of gene editing overall, including gene drive technology, has been advancing at a rapid pace in the laboratory. These leaps forward in potential capability, however, have not been matched by advances in the biosafety and biosecurity tools needed to protect against potential harm if such technologies were accidentally or intentionally misused, nor does data exist on how such technologies would actually function in the far more complex real world."

DARPA says its mission is "to prevent strategic technological surprise" and that it created the Safe Genes program to develop a toolkit, for instance, to address potential health and security concerns related to the misuse of gene editors and to understand how gene editing technologies work.

"DARPA is not funding any open release of modified organisms," the agency said.

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One of the five research projects that DARPA is funding on gene drives is Esvelt's study into a control on self-propogating gene drives called daisy drive.

Last month, Esvelt and Neil Gemmell of the University of Otago in New Zealand published a commentary in the journal PLOS Biology calling for safe guards to prevent gene drives from pushing a gene trait to spread in the wild without limits. He and his colleagues are calling for more accountability and transparency around applications of gene drive technologies.