Here’s a question that occurs only to madmen and geneticists: How do you get a gene that kills an organism to spread through a whole population of that organism?
You can either make your gene deadly, and thus impossible to pass on, or not, and thus useless as a vector of attack. The solution has long been to try “silent” genes that can spread with no negative effects, either introducing a deadly weakness to a man-made chemical we withhold for a while, or by waiting for deadly activation by such a chemical. But 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 genes that spread with astonishing speed, quickly killing entire populations.
Such an animal is currently sitting in a laboratory at Imperial College London, an apocalypse 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 a subcategory of life on Earth. The name for this power is called gene drive.
Gene drive is simply the use of some strategy to artificially increase a gene’s inheritance rate. Such strategies are found all over nature, but despite decades of theorizing, nobody had a really viable way for mankind to harness this functionality through biotechnology. That’s changed thanks to the incredible advances in direct gene editing we’ve seen over the past half-decade, in particular the CRISPR/Cas9 gene editing suite.
These “molecular scissors” are actually borrowed from viruses, allowing scientists to swap out a gene in a living organism for one of their choice, edit it right into the genome so it will be passed on as the cells reproduce. If you can get your gene spliced into the “germ cells,” the pre-sperm or -egg cells of these organisms, then you can even introduce a chance that it will be passed on to the next generation — classically, without gene drive, you can introduce 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. When we splice in our 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 our spliced-in sequence. The other will carry the same gene it would have, regardless.
So, if our spliced-in gene lowers evolutionary fitness, then all that will happen is the other half of the offspring will thrive, and the infected individuals will be quickly bred out of the population. And even if it’s a seemingly harmless silent gene that does nothing at first, it will still spread too slowly to change the overall population much at all.
Our mosquito doomsday device gets around these problems by applying two innovations.
The mosquito species Anopheles gambiae is a major carrier of dangerous malaria parasites in sub-Saharan Africa, where 90 per cent of annual malaria deaths occur. Malaria infects more than 200 million people each year and causes more than 430,000 deaths.
Now, a team of researchers led by Imperial College London have genetically modified Anopheles gambiae so that they carry a modified gene disrupting egg production in female mosquitoes. They used a technology called ‘gene drive’ to ensure the gene is passed down at an accelerated rate to offspring, spreading the gene through a population over time.
Within a few years, the spread could drastically reduce or eliminate local populations of the malaria-carrying mosquito species. Their findings represent an important step forward in the ability to develop novel methods of vector control.
Normally, each gene variant has a 50 per cent chance of being passed down from parents to their offspring. In the Imperial team’s experiments with Anopheles gambiae, the gene for infertility was transmitted to more than 90 per cent of both male and female mosquitoes’ offspring.
The technique uses recessive genes, so that many mosquitoes will inherit only one copy of the gene. Two copies are needed to cause infertility, meaning that mosquitoes with only one copy are carriers, and can spread the gene through a population.
This is the first time the technique has been demonstrated inAnopheles gambiae. The team targeted three different fertility genes and tested each for their suitability for affecting a mosquito population through gene drive, demonstrating the strength and flexibility of the technique to be applied to a range of genes. The results are published today in the journal Nature Biotechnology.
“The field has been trying to tackle malaria for more than 100 years. If successful, this technology has the potential to substantially reduce the transmission of malaria,” said co-author Professor Andrea Crisanti from the Department of Life Sciences at Imperial.
“As with any new technology, there are many more steps we will go through to test and ensure the safety of the approach we are pursuing. It will be at least 10 more years before gene drive malaria mosquitos could be a working intervention,” added Professor Austin Burt from Imperial’s Department of Life Sciences.