LONDON – Most powerful new technologies are double-edged. Cars are a vast improvement on horses as a means of transportation, but they also kill more than three thousand people a day and they are a major source of pollution.
So here comes another double-edged technology, and its edges are very sharp. Gene drives can spread an engineered mutation through an entire species with amazing speed, which means that you could, for example, make the breeds of mosquitoes that transmit the malaria parasite to human being immune to the parasite themselves. (You could also just wipe those species of mosquito out, but then a lot of birds and bats would starve.)
The idea of a gene drive was first suggested 12 years ago by Austin Burt, an evolutionary geneticist at Imperial College in London. What drew his attention were certain naturally occurring “selfish” genes, known as homing endonuclease genes, that can get themselves passed on to the next generation more than the usual fifty percent of the time.
Burt suggested that you might use those genes to build a “gene drive” that would spread some desirable quality (like immunity to malaria) through an entire population in a relatively short time. But back in 2003 the task of manipulating genes was still difficult, lengthy, and unreliable.
It took Burt and his colleagues another eight years to create a homing endonuclease that could find and cut a gene in mosquitoes. Other scientists were working to make artificial protein systems that would do the same job, but it was slow and painful work. Then came CRISPR.
CRISPR (it stands for “clustered regularly interspaced short palindromic repeats”, but never mind) refers to bits of viral DNA that bacteria carry in their genomes. With the help of an enzyme called Cas9, these CRISPRs protect the bacteria from attacks by hostile viruses. In 2012 researchers managed to modify this CRISPR/Cas9 system into a gene-editing tool.
CRISPR/Cas9 has transformed the business of genetic engineering, making it fast, accurate and cheap. It allows researchers to cut and paste practically any gene into any organism, and it has spread through the world’s biology labs like wildfire.
Almost immediately Kenin Esvelt of Harvard University recognized that CRISPR is basically a homing endonuclease, and in July of last year he and his colleagues publicly proposed turning it into a gene drive and listed some of the possibilities that opened up.
It could, Esvelt said, “potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species.” Sick of the cane toads that infest Australian fields? Modify them so that their skin is no longer poisonous to predators, and watch the problem go away.
“Since the 1970s we’ve been able to genetically engineer individual organisms,” Burt said. “With gene drive, we could change the genetics of vast populations.” And we have gone from zero to 60 in less than a year.
Last January, Esvelt’s lab made a gene drive in yeast. In March, biologists Valentino Gantz and Ethan Bier at the University of California, San Diego, reported online in Science that they had created a gene drive in fruit flies. They had introduced a drive for yellow color into females, bred them with normal males — and between 95 and 100 percent of the offspring were yellow.
They then started collaborating with Anthony James, a molecular biologist at the University of California, Irvine, who has been working for 30 years on genetically modifying mosquitoes so they can’t pass on malaria. Using CRISPR/Cas9, the team are now within a year of a non-malaria-carrying mosquito ready to be released into the wild — but they won’t do it.
James’ team have no intention of doing that until there are clear and agreed rules for this sort of thing. They are well aware of the risk of unforeseen side-effects: “We’re not about to do anything foolish,” says James.
One of the precautions James took was to work with an Indian breed of mosquito, so that if one escaped from his California lab it wouldn’t find anyone to mate with. In the same spirit, as soon as Esvelt created a gene drive for a species of yeast he immediately set to work creating another drive that could over-write the first, canceling the genetic changes it made. If things went wrong, the second one could be released and would spread just as fast.
As Esvelt said, “the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application.” You bet your boots it does.
This is a technology that can change the entire character of a wild species very quickly (or wipe it out) if just one individual that has been genetically altered in the lab accidentally escapes and breeds, because the mutation will be passed on to ALL its descendants, and all of theirs, ad infinitum.
And, of course, we are also talking about the possibility that people with evil intentions might take common, harmless insects and make them lethal to human beings. This technology will have to be handled with very great care.
Gwynne Dyer is an independent journalist and military historian based in London.