Gene drives: are we ready?

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Image credit Kim from Flickr

 

Imagine you had the power to hit a switch and watch the mosquitoes that carry malaria go extinct. To release a weapon that would wipe out cane toads while you watched it on the news from the comfort of your living room. To make the global rice produced have better nutrition, to make endangered species more resistant to predators.

Would you flick the switch?

Such is the promise of gene drives, a system that in the last two years we’ve been able to start building. A gene drive is basically a tool that rams a biological variation – say, eye colour or disease resistance – through an entire population. This enables more powerful control over other species than we’ve ever had before. But with this power comes risk. We’ll get to that.

To start thinking about how gene drives work, let’s begin by considering how traits are normally spread through a species. Imagine we had a fly in the lab with a mutation that gave it white eyes. If we carried its container outside and let it fly away, how long would it take for its new mutation to spread around Melbourne university, giving all the flies white eyes. Assuming it didn’t get eaten by something or die and was able to reproduce, and that the other flies didn’t think it was a freak, that is. In this situation, classic Mendelian inheritance would apply. The fly could have a maximum of two copies of the white eye gene, and as they’d be on different chromosomes, it could only pass one on. So each of its offspring would have one white copy, and one normal copy. Their descendants from mating with other wild flies would each have a 50/50 chance of getting a copy of the white gene passed down to them, and so on. How long would it take to spread? Well, it could take forever. Because it’s actually not spreading. It’s like putting a drop of red food colouring into a bathtub. The white eye variation basically gets diluted across the entire fly populations, with an occasional white fly here, another there. Not a great way of changing a species.

Now imagine we took the same fly and put a CRISPR gene drive system inside it. This system is set up with your gene of interest in the middle of a packet. It has special sequences on each side, containing copies of the genes for the CRISPR molecular scissors(Cas9) as well as the gene you want changed and ID for where the scissors need to cut. In this powered up form, the gene is ready for spread. Let’s release the fly again. This time, once more the second generation of flies have one copy of the white eye gene and one copy of the wild type. But then the gene drive kicks into gear. The CRISPR packet produces a copy of the Cas9 molecular scissors and the ID patches telling them where to target. But we’ve programmed these patches to match to the normal copy of the fly eye colour gene on the other chromosome. So the scissors cut out the normal copy, leaving us with just one copy of the gene, the white eye version, in the cell. Now, at this point, the fly contains one chromosome that’s just been broken in two, a messy and potentially dangerous situation. The fly’s DNA repair systems kick in. It needs to fix the hole, and it does so by copying the missing sequence from the other chromosome. But it inadvertently ends up copying over our white eye gene, as well as the entire CRISPR system that caused the break in the first place. End result: two copies of the white eye gene, just like the parents. If this happens for every generation, white eyes would spread across Melbourne, completely taking over.

This type of gene drive could enable the genetic engineering of entire populations, provided a few simple conditions are met. The population must reproduce sexually, indiscriminately, and often. One such species is the mosquito. They swarm around, feast on blood, mate, and lay eggs. They also spread some of the world’s worst diseases. Unsurprisingly, gene drives have come to the attention of researchers seeking to eliminate malaria. They’ve already come up with a genetic alteration that prevents the most common malarial mosquito from passing malaria on to humans. But what they lacked was a way to make this spread to mosquitoes in the wild. Now with a gene drive being built for the mosquitoes, the goal of preventing malarial spread is much closer to being realised. Others have considered using gene drives ecologically to control invasive species such as the cane toad. If you drove a gene through the population that decreased their fitness or made them partially sterile, you could cause a massive population collapse, possibly bringing relief to many endangered species that are struggling to cope with the toads.
That’s the good news. But the sheer power of the technology has many people calling for caution, including some key researchers involved. If just a few flies released into the wild could spread their gene drive through an entire population, would it be any different if they escaped? If gene drives in Cane toads in Australia spread to the species’ native habitat in South America, that could also be devastating. Many scientists involved in the field put their names to an article in Science calling for researchers to adopt extra safeguards to prevent that from happening. A few months ago, the National Academy of Science also released the findings of their study on the risks associated with gene drives.

One prominent gene drive researcher is Kevin Esvalt, director of the Sculpting Evolution group at MIT,  He’s particularly interested, not so much in the environmental cost, but in the social cost for science if we get this wrong. He says, “popular trust in science and scientists depends on our ability to act responsibly.”  Kevin and other researchers have not just been thinking through how to run experiments safely to reduce the chances of a gene drive escaping. They’re working hard to develop gene drives in ways that take these risks into account. Such ideas include the reversal drive, a fail-safe gene drive which can undo the changes made by a gene drive let go in the wild. Another interesting idea is the daisy chain gene drive, built to flare up but then die out in a short amount of time, a bit like a fire running out of fuel before it can get going.

Gene drives are promising, but risky, and it’s really important we get the balance right. What do you think? Are we ready for them? What kind of tests or safeguards would be good to include? Let me know what you think in the comments!