A controversial procedure that can spread particular genes through an entire wild species has been demonstrated in mammals for the first time.
Researchers in the US showed that a “gene drive” could rewrite the genetic makeup of mice so that the rodents carried DNA that had been designed by the scientists.
Gene drives work by breaking the normal rules of inheritance to ensure certain genes, often modified versions, are passed on from one generation to another at a higher rate than normal.
The procedure has drawn huge interest from researchers because of its potential to combat diseases such as malaria by rewriting the genetic makeup of mosquitoes that carry the malaria parasite.
Experimental gene drives have already been used to make disease-carrying mosquitoes infertile. If these insects were released into the wild, it is likely mosquito populations would crash.
Other gene drives have boosted the insects’ resistance to infection by the parasites.
Many scientists suspect that the same approach might prove a more effective alternative to the laborious and costly eradication projects used to clear remote islands of invasive species.
Last year, the world’s largest eradication effort finally declared South Georgia free of the mice and rats that had devastated its wildlife for more than 250 years.
But, for all their potential, many researchers are cautious about gene drives because those that go awry could cause substantial damage to ecosystems.
In 2016, the US National Academies of Science ruled that far more work was needed to understand and control gene drives before they can safely be used in the wild.
Kimberly Cooper, a biologist at the University of California in San Diego, wanted to create a gene drive in mice – not to eradicate rodents on far-flung islands, but to make animals with the kinds of mutations that underlie human diseases. This could help scientists better understand some of the most common afflictions.
Writing in the journal Nature, the researchers describe how, after a number of failed attempts, they found a way to genetically engineer mouse embryos so the females spread a modified gene through future generations faster than the normal rules of inheritance allow. The procedure did not work in males, but instead created mutations in the animals.
“Our findings suggest that doing this in mice is more complicated than it was in insects and that does raise questions about whether this will ever be as efficient as you’d need for wild release,” Cooper said.
One concern is that the mutations left in the males made them resistant to the gene drive, which could scupper its use to eradicate invasive rodents.
Cooper still sees a use for the gene drive in the lab. It could be used to create animals which carry multiple genetic faults linked to human diseases such as cancer, diabetes and arthritis, she said. “The hope is you could make all of these changes individually and understand each of them and then breed them all together.”
Christophe Boëte at the University of Montpellier said that while the work was a proof-of-principle for a gene drive in mammals, it suggested that using the approach to control invasive species was a distant prospect.
“Their results highlight that such a tool for population eradication in the wild is far from being available. The low efficacy means that it would take many generations and favours selection for resistance against the drive,” he said.
“This of course is only the tiny technological part of the issues. They are many other ethical, regulatory and ecological aspects to considered with the utmost importance before embarking further on such an approach in conservation biology.”
Cooper said it was crucial for researchers who work on gene drives to be responsible and to discuss their work with broader society.
“There will always be people who are not happy because there are people who think the work should just not be done. I don’t know that that’s really practical,” she said.
“But it is tricky, because who gets a voice? If everyone has a voice then nothing gets done. The people I know who are working in this area are very cautious scientists and it’s important to say that this is an incredibly powerful technology for good.”