Gene drive pioneer warns CRISPR-based pest control may spin out of control

  Last updated January 31, 2018 at 4:59 pm

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One of the pioneers of gene drive technology, which uses CRISPR genome editing to promote inheritance of particular genes in a population, says that his initial suggestion that these systems might be useful for conservation efforts “was a mistake”.


Gene drive systems distort the rule that there is a 50:50 chance of a gene copy being passed on. This promotes the inheritance of a particular copy of a gene from the parent to offspring. When coupled to a genetic trait that affects an individual’s survival or ability to reproduce, it becomes a powerful tool that can be used for population control or even local elimination. (Image: Kevin Esvelt)


In a new paper, Kevin Esvelt of MIT and Neil Gemmell from the University of Otago in New Zealand argue that gene drives which promote infertility and ultimately eliminate pest populations “may be uncontrollable”.


“The bottom line is that making a standard, self-propagating CRISPR-based gene drive is likely equivalent to creating a new, highly invasive species.”


Introducing such a system “without the permission of every other country harbouring the target species would be highly irresponsible,” they say.


New Zealand is considering using gene drive technologies as part of an ambitious program to eliminate the country’s rats, possums and stoats by 2050. These introduced mammals cause havoc with the unique biodiversity of New Zealand, including the national icon Kiwi. In areas where there is no control of these predators more than 90% of kiwi die before they are a year old.


Not to be outdone, here in Australia we of course have our own massive problems with invasive species, and a special report from the Australian Academy of Sciences earlier this year suggested that gene drives here could be used to reduce the population of black rats on Lord Howe Island, cane toads in the tropics, European carp in the Murray Darling Basin and rabbits across the continent.


Gene drives could be used to eliminate feral species by targeting genes needed for fertility. Or they could be designed to lead to a population of all males. An advantage of gene drives for feral species control is that they avoid the use of traps of poisons, reducing animal suffering.


Because the introduction of only a few modified animals into the ecosystem could be enough for a gene drive system to spread through a whole population, there is a risk of spread of the gene drive beyond the original target area. A gene drive targeted to rats on New Zealand, the authors suggest, could wipe out the rodent population. But there would still be gene drive altered rats present for a few years. This poses a risk that either rats could spread unintentionally to new areas, by stowing away on ships, or could even be deliberately moved. There’s historical precedence for this. The calicivirus, developed in Australia to control rabbits, was smuggled into New Zealand by farmers in 1997 after an application through formal channels to introduce it had been knocked back.


To avoid out of control spread of gene drives, the researchers propose two different methods to create built-in limits.  One is a “daisy drive”, where elements are linked in a daisy chain.  Over generations the links in the chain run out and the drive stops. Another is the “Trojan female” technique, which causes a mutation in the females that makes all her male offspring infertile.


“We should not even consider building drive systems likely to spread indefinitely beyond the target area,” argues Kevin Esvelt and Neil Gemmell, “All proposals and research should be open from the earliest stages, with scientists and supporters actively inviting dialogue with those who have reservations.”


Other scientists agree that while bringing this issue to attention for community discussion is hugely important, this paper overstates the current state of the research.


“No-one is currently advocating for the use of the experimental and untested technology of gene drives as they are conceived in their most basic way,” says Professor Peter Dearden from the University of Otago. He points out that an area often overlooked with the application of this technology is the assumption that establishing gene-drive modified rats into a resident feral population is trivial. “It is not,” says Prof Dearden, “Indeed all the evidence is to the contrary, that trying to establish rats within a population of already established rats is very difficult.”


“There is a great temptation to look for ‘silver bullets’,” agrees Professor Barry Scott of Massey University.


“There is an underlying assumption in the article that gene drive systems could be developed for most pests and that they will work. We already know from recent experiments that evolution of resistant alleles that cannot be cut and copied will inevitably evolve in the population, which they reference, but there are still major challenges, some probably still unforeseen, associated with the reproductive biology and population genetics that may well limit the feasibility of the system actually working in the field.”


“Contrary to the hype, gene drive technology for mammals is still highly theoretical, and I must emphasise that no such research is currently being conducted in New Zealand,” says Dr Andrea Byrom, Director of New Zealands Biological Heritage National Science Challenge.


“We have literally years of technological development ahead of us before we could proceed with deployment in the field, and future use of gene editing technologies, including gene drive, will be in the hands of the public of New Zealand to decide.”


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