Gene drives tested safely
A “gene drive” is a gene editing technique that biases the inheritance of a genetic element or trait so that it rapidly increases in frequency in a population. In a fast-breeding species, this means that, within just a small number of generations, almost the entire population will carry the gene drive. This could be used to protect an endangered species by conferring resistance to a pest, or even to eradicate or neutralise a problem or invasive organism, and scientists are testing these concepts in insects - and even in mammals - at the moment. But with this power comes enormous risk: what might happen, for instance, if an experimental gene drive escaped the confines of the laboratory and ran amok in the wild? For this reason, gene drive technologies have been engineered with in-built Achilles Heels. But are these constructs really “field relevant”? Speaking with Chris Smith, Jackson Champer has built and tested some to find out…
Jackson - In this study we developed ways to study gene drive in the lab without risk of them spreading in the wild if they were accidentally released.
Chris - We need to back up a little bit. First up, what is a gene drive?
Jackson - A gene drive is basically a piece of DNA that's part of an organism's genome that contains a nuclease, which is something that can cleave a very specific portion of DNA. It cleaves a bit of DNA on a chromosome that does not have the gene drive, and then copies itself onto that chromosome. So instead of the organism passing down a gene drive to only half of its offspring, it passes it down to all of its offspring thus allowing the gene drive to spread through an entire population. You can almost describe it as a cut and then a copy paste to fix the cut.
Chris - And what sorts of genetic elements are people talking about pasting in and driving through a population like this?
Jackson - Well there's two basic types of gene drive: a "population modification" gene drive, where we basically try to spread a genetic payload through the entire population. This could be something like a special gene that prevents mosquitoes from transmitting malaria. The other type of gene drive is a "population suppression" gene drive. This type of gene drive is designed to completely eliminate a particular species, either from a small region or globally. And this of course has been best studied in malaria mosquitoes. So there could be two ways to use gene drive to get rid of malaria: either make the mosquitoes unable to transmit the malaria, or get rid of the mosquitoes in the first place.
Chris - The worry is, of course, that, if one does this, once you set these hares running you might not be able to rein them back in?
Jackson - Right. There are some strategies that could potentially let you rein-in a gene drive, though it's still an open question on how effective these might be. What we were most concerned with in our manuscript is if someone were to develop a gene drive and then, by accident, it was released into the wild, it could then either spread it to all the organisms, or suppress them, which would be an undesired result if this happened by accident. So we came up with a way for scientists to study these gene drives in insects without worrying about any negative consequences, if some of these insects were accidentally released from the laboratory
Chris - How does that work?
Jackson - Well we used two different strategies for this. One was using a special target site. These gene drives need to cleave DNA at a very precise spot in order for the gene drive to work. And we simply made it so that that spot was an artificially-inserted piece of DNA. That means that our gene drive can only work in these lab insects that have this synthetic target site. If it met a wild-type insect, it simply wouldn't be able to cleave and thus would not be able to spread in the population. The other method we used was simply to not use a complete gene drive. Instead, we used a split-drive strategy in which one of the important components of the gene drive was provided separately. This separate component would not copy itself, thus preventing the gene drive from having an exponential spread in wild type organisms. This split drive could only spread if we provided it with this supporting element in the lab.
Chris - Of course one criticism of this is that this is still, nevertheless, a laboratory and these sorts of artificial constructs do not exist in nature. So while that's great because it enables you to study this - and the behavior of gene drive technologies - without the risk of an environmental escape, one must ask how relevant is this?
Jackson - In this study we took many performance measurements of both of these different types of gene drives and we found that they worked the same basic way that a full standard homing type gene drive would work according to some of our previous studies. Because of this, we believe that the things we learn about gene drive in the lab using these safe drives - the synthetics, target sites and split drives - will be fully applicable to full gene drives that might later be released in the wild.
Chris - This obviously applies to insects. What about when we try and take this further afield, if we want to, say, go to a remote island that's now being plagued by rats and other rodents and eradicate those; is what we're seeing in drosophila relevant to other species?
Jackson - Yes it is. It seems as though the same basic mechanisms of gene drives and the ways to improve them will likely be the same across species. That said, just because you have a gene drive in the fruit fly doesn't mean you're going to have a gene drive in a mouse right away. There's still a lot of important experiments you would need to do to make a gene drive in a new species. But, at the same time, you can still apply a lot of the lessons that we can learn from the fruit fly traditionally in biomedical literature.