WHY THIS MATTERS IN BRIEF
Scientists now have the knowledge and the tools they need to create, and deliver, Doomsday genes which can selectively target and exterminate entire species.
Here’s a question that occurs only to madmen and geneticists…
How do you get a gene that kills a species to spread through a whole population?
You can either make your gene deadly, and therefore impossible to pass on, or not – and make it useless. The solution in the past has been to try to create what are known as “silent” genes that can spread throughout a population with no negative side effects, for example, either introducing a deadly weakness to a man made chemical into a species genome, or creating dormant but deadly genes that can be activated when the right trigger presents itself.
Recently, with the advent of advanced new in vivo gene editing technology, it’s become possible to make genes that seem to defy evolution – and that means we could soon start releasing animals carrying doomsday, or, extinction genes, that spread with astonishing speed and which eventually kill off an entire species, or even entire ecosystems.
It sounds like the stuff of science fiction and nightmares, and many argue that that is where this type of technology should stay.
However, such an animal exists, and it’s currently sitting in a laboratory at Imperial College London. An apocalyptic mosquito carrying a gene that could one day end its entire species. It represents a controversial proposal to end the scourge of Malaria, which kills hundreds of thousands of people each and every year, by wiping out the mosquitoes that spread the disease. It also represents a fundamentally new ability for humanity – the power to easily and selectively snuff out an entire subcategory of life on Earth. And the new name for this technology? Gene Drive.
Sounds rather benign doesn’t it? Except for the fact, when combined with an extinction gene, which for example, in this case introduces sterility into an entire population, it’s anything but.
Gene Drive is a methodology that artificially increases a gene’s inheritance rate – these are found throughout nature, but despite decades of theorising, nobody, until now, and spurred on by the advent of CRISPR, a revolutionary gene editing technique that’s also goes under the moniker of the “Genesis Engine“, had a viable way to harness it.
CRISPR’s “molecular scissors” are actually borrowed from viruses, allowing scientists to swap out one gene in a living organism for another gene, for example a doomsday gene, of their choice, and if you can get your gene spliced into the germ cells of a species then you can guarantee that the new trait will be passed down through the generations – classically, without Gene Drive, you can introduce only a 50% chance.
The chance is 50% because germ cells, like virtually all other cell types in humans and mosquitoes, have two copies of our genome, so when scientists splice in their attack gene, it will end up sitting across from a second, totally normal copy of the gene it just replaced. This means that when the two copies get pulled apart to form the half-genomes of two new, separate sperm cells, only one of those new sperm cells will have the spliced in sequence. The other will carry the same gene it would have, regardless.
So, if the spliced in gene lowers “evolutionary fitness”, then all that will happen is the other half of the offspring will thrive, and, as a result the infected “genetically crippled” individuals will be quickly bred out of the population.
Imperial College’s doomsday mosquito gets around these problems by applying two innovations.
First, it forces itself into 99% of a mosquito’s sperm cells, and thus into 99% of its offspring. It can do this by exploiting the natural process of the genomes proof reading abilities. Once the synthetic gene has been spliced in to replace a target gene, scientists can design the system to intentionally damage the other, natural copy of that target gene. Do enough damage and the cell’s machinery shows up to repair it back to normal. But what’s normal? Well, the DNA double helix provides a template and the repair enzymes end up using the spliced in gene as the guide for what the “natural version” is supposed to look like.
Once the natural version of our gene has been “repaired” into the engineered version, both alleles, or copies, of the gene have the new man made sequence. Now, when the germ cell divides into two sperm cells, both those sperm cells get the modified version of the gene. So now, no matter which of those sperm cells goes on to fertilize an egg, the resulting mosquito will inherit the inserted attack gene. And the germ cells of those offspring get the Gene Drive effect, carrying it on to the next generation, and the next, and the next and so on and so on.
But there’s still a problem. If infected mosquitoes give birth to 99% weakened mosquitoes, then those mosquitoes will simply get bred out by normal individuals from completely separate parents, and the attack will go nowhere. The key to this mosquito “bomb” is that while 99% of offspring get the engineered gene, that gene doesn’t cause any problems when there’s only one copy.
So, try to follow the counting here.
Scientists splice one copy of their experimental gene directly into a germ cell, where it then destroys and replaces the other copy and makes itself into the cell’s sole version of that gene. Then, the germ cell splits into two sperm cells, each of which has one infected copy in its half-sized genome. This infected half-genome then fertilizes a non-infected egg through normal breeding with another mosquito, combining to make a new mosquito with one copy of our synthetic gene, from our infected male’s sperm cell, and one copy of the natural gene, from the uninfected female’s egg cell.
Now, 99% of our infected male’s offspring are infected with a single copy of the gene we inserted, and become carriers who display no adverse effects. Most regular genes spreading through the mosquito population by natural processes have to spread without the Gene Drive ability to power them into 99% of offspring very quickly, meaning that even very advantageous genes won’t be able to spread as fast as our silent, seemingly useless one. With no downside to bias evolution against it, our gene will spread through the population in just a scant few generations.
Eventually, it will reach such a level of saturation in the population that these fully functioning carrier mosquitoes will begin to mate with one another through sheer chance, each donating infected sperm or egg cells 99% of the time, and thus giving rise to virtually all double-infected offspring. It’s these offspring, with both copies of the gene infected from conception, that express the genetic attack. The females of such mating events are completely sterile, while the males are free to continue breeding and passing on the disease.
What this means is that by the time the Gene Drive starts creating a substantial number of sterile, double-infected mosquitoes, the overall population will already have been infected too heavily to breed it out. With Gene Drive to keep the gene spreading in spite of evolution, the process should continue until there are simply no viable female mosquitoes left to breed with. By the Imperial College team’s calculations, this gene drive approach could completely wipe out a population of mosquitoes in as little as 11 generations, or about a year.
To put this into perspective, in this case, this is a genetic modification that wipes out Malaria by wiping out the Mosquito. In human terms you could compare it to wiping out HIV by wiping out humans, and while there are arguments for both sides of the fence the fact that we now have the technology, and the fact, furthermore, that we’ve already used it to create what’s come to be known as the Doomsday Mosquito humanity will find itself in moral and ethical deadlock.
Do you cure the disease that kills millions of people by genetically engineering a species to go extinct? And if we can genetically engineer one species to go extinct then which species is next? Us?
The last one, as terrifying as it might sound isn’t as far fetched as you might think, and governments around the world have already put this “ultimate bioweapon” on their watch list. As our understanding of this technology and this capability advances, and as costs continue to plummet, it is increasingly easy to see how one day a terrorist group could use it to quietly and subtly kill off an entire race, or population, of people. And if you think that that’s a giant leap then worryingly it isn’t.
Thanks to the Human Genome Project we can already identify and categorise individuals with specific traits – everything from the colour of their hair to the colour of their skin – as well as their evolutionary lineage and thanks to the rise of CRISPR and Synthetic Biology we now have the tools we need to help us create entire artificial genomes from scratch. By 2036, for example, scientists believe that they might even be able to use CRISPR technology to make the worlds first artificial human (ethics allowing, which of course they won’t, or at least ion the short term).
If we have the technology to eliminate an entire species from the face of the Earth – forever, then the only thing preventing us from pulling the genetic trigger is our moral compass and our belief in our ability to control the outcome and the next time there’s a mass extinction event it might not be an asteroid that’s the culrpit.