Extinction on demand
Gene drive technology could rid the world of rats forever. But is that really what we want, asks Charlie Mitchell.
It’s one thing to play God within one’s own environment. But what happens if your experiment spreads across borders, into places that can’t object? What if New Zealand, with good intentions, causes an international ecological incident?
It’s a question authorities need to seriously consider in their pursuit to cleanse this country of predators, a new study argues. And it needs to be sorted out quickly.
A study released today by the Sustainability Council, with funding from the Law Foundation, examines the potential impact of gene drives and New Zealand’s role in globally governing the technology as the push towards Predator-Free 2050 accelerates.
A gene drive is an emerging technology with intimidating implications. By altering the genome of a handful of individuals and releasing them into the wild, you could circulate a particular gene among the entire population.
In rats, for example, you could edit a gene that ensures it only produces male offspring and spread it through the population with a gene drive. After around a decade of breeding daughterless rats, you would eventually have none left; a bloodless end to a species.
The major issue is that, once a gene drive was let loose, it could be difficult to control. It would spread through the population like genetic wildfire, with no respect for geographic or political boundaries. While it could theoretically be reversed by releasing another gene drive cancelling out the original, it could spiral out of control once it has spread widely.
If that was to happen, there could be serious political implications. What if, a couple of decades from now, we release rats, which have been genetically edited to produce only male offspring, in a certain part of the country.
A farmer in the United States – where rats cause many billions of dollars of damage to crops each year – decides to smuggle a gene-edited rat from New Zealand to kill the rats damaging her crops.
Modelling has shown just one gene-edited rat has a small chance of spreading the gene widely in a new population. A dozen gene-edited rats would make it virtually guaranteed.
If that happened, the gene drive could spread wider and wider, until much of the United States had lost its rats. Then it spreads into Canada and Mexico, then further into South America. At that point, you would assume it would get everywhere.
While we may hate rats, in some countries they are a dietary staple, and in others they pollinate plants and spread seeds. Like all species, they are native to somewhere – in this case, much of Eurasia.
So what would happen if New Zealand triggered this cascade? No-one knows.
‘‘If New Zealand is serious about exploring the use of gene drive to help protect native species, it should be leading development of the international rules required, as that will not be easy,’’ say the study’s coauthors, Sustainability Council executive director Simon Terry and projects director Stephanie Howard.
There is ‘‘real urgency’’ for a global agreement to govern gene drives, they say. While it remains theoretical, research is gathering pace, and the technology is likely to become viable within a few years.
‘‘A country that is otherwise vigilant to biosecurity risks should be alive to the ways in which gene drive releases in other countries could provide a significant biosecurity threat,’’ they say.
‘‘This is why New Zealand should back strong international rules.’’
THE SCIENCE
Even science-fiction authors didn’t imagine a world in which we could genetically engineer entire species, taming the law of evolution that has ruled the Earth since life began.
The most likely way a gene drive would work is through a technique called CRISPR, which was developed in 2012.
CRISPR, put simply, allows scientists to find and replace any section of DNA.
They do this by programming a piece of code matching the section they want to replace and attaching it to a protein, which finds the matching section in the DNA sequence. The protein cuts that DNA sequence and the programmed section replaces it.
When the technology becomes more advanced, CRISPR could be used for socalled ‘‘designer babies’’, altering the genes that produce traits around intelligence or physical features. Some think it could be used to recreate extinct species.
But for now, it’s more likely to be used to create crops that are more nutritious, or resistant to climate change, or to cure diseases that result from defective genes.
Shortly after the CRISPR technique was discovered, another potential use was found, one with enormous consequences. Gene drives had been mooted in the 1990s, but were not technically feasible, until CRISPR.
When two individuals breed, each one contributes 50 per cent of the offspring’s genes. If you were to edit a rat’s genome with CRISPR so it could produce only male offspring, there would be a 50/50 chance its offspring would have that gene. Over the generations, a smaller and smaller number of rats would have it, until it was diluted out.
But a gene drive can overcome this natural law of inheritance and turn a 50 per cent chance into a guarantee.
A gene placed into a genome with CRISPR can be programmed to selfpropagate. It would effectively copy and paste itself over the partner’s gene, meaning the offspring would be able to inherit only the edited gene.
Every rat born from the gene-edited original would be male, as would every rat born in subsequent generations.
The process is slow because it moves only vertically, down generations. But for species that reproduce quickly, like rats, you could likely eradicate them within a decade, without killing a single one.
If New Zealand is serious about exploring the use of gene drive to help protect native species, it should be leading development of the international rules required, as that will not be easy.
Simon Terry, Sustainability Council executive director and Stephanie Howard, projects director
‘EXTINCTION ON DEMAND’
The polite term for this is ‘‘sculpting evolution’’, but it has also been described, more ominously, as ‘‘extinction on demand’’.
If this particular gene drive was used in New Zealand and went wrong, it could change the world and put New Zealand at the centre of an international conflict. If another country used it, it could affect New Zealand’s own ecosystems.
The American scientist credited with developing a gene drive method using CRISPR, Dr Kevin Esvelt, has urged extreme caution. He thought gene drives could be used for New Zealand’s PredatorFree 2050 project, and said so when he visited in October.
Esvelt’s concern now is that it could go terribly wrong. He says he should not have published the idea that CRISPR could be used to control invasive species, without considering the massive implications first.
‘‘I bitterly regret making that [statement],’’ he said in a public meeting at the University of Otago. ‘‘I was very foolish back then and thinking about the technical limitations, as opposed to the broader social and international implications.
‘‘We need to set a precedent that, when a new technology could affect everybody, it must be developed in the open and it should actively invite concerns and criticism from everyone. As someone who develops technology, I would far rather be publicly humiliated than help lead an effort that turns out to go horrifically awry after release.’’
A similar level of caution is coming from New Zealand scientists involved in gene drive technology.
Professor Neil Gemmell, a University of Otago geneticist who co-authored a paper with Esvelt last year about the potential risks of gene drives, says there are many ways in which the technology could go wrong.
‘‘We need to be mindful that our aspirations could have global implications.
‘‘We introduced stoats, weasels, ferrets to control our rabbit population, which we introduced deliberately for meat and fur but became a pest, and then introduced other species to control them, which have become pests in a different way.
‘‘If any country on Earth should be able to look at the lessons of what happens through unintended – but based on the evidence of the day, quite sensible – strategies to control things, it’s New Zealand.’’
The technology has developed so rapidly that it still isn’t clear what all the implications are, he says. There are still issues that needed to be worked through – in particular, a drive would need to be developed that would perpetuate widely but could also be switched off, which is a difficult balance to strike.
New Zealand could be at the forefront of considering these issues, but it must be done cautiously and led by the public, Gemmell says.
‘‘When you’re trying to introduce something quickly, sometimes you make mistakes. In an ecological situation you need time to understand what the ramifications of what you’re doing are going to be.
‘‘With gene drives, it’s OK for people to say no. If, ultimately, the public perception is that it’s too risky, that we shouldn’t do it, then that should be the way it is.’’
With any use of gene drives still years away, now is an ideal time to consider the wider issue of any potential use, says Professor Peter Dearden, director of Genomics Aotearoa.
‘‘We’re seeing people thinking about it, which I think is exactly the right thing to do.
‘‘All of the things being brought up – international governance, or the problems with resistance – the more we think about those problems, the more likely we are to find solutions.’’
He does not think it would be possible to contain a rat gene drive within New Zealand, and gene drives that can be safely contained are still some way off. If the discussion is about releasing a gene drive now, he’d side with the people who have concerns – but concerns now shouldn’t limit investigation.
‘‘What we mustn’t do is use those concerns as an excuse not to do the work. If we do the work and find we can release gene drives that are safe and are beneficial and don’t spread overseas, if we hadn’t done the work, we wouldn’t have known that and lost the opportunity.
‘‘There’s no problem with discussion, no problem with disagreement and argument and thought about these issues, as long as it doesn’t lead to a chill in the research.’’
There are already promising alternatives. Instead of a gene drive that self-propagates perpetually, Esvelt favours an adapted version of the technology that he calls a daisy drive, which would propagate at first and then run out of fuel after a certain number of generations.
Even this could have drawbacks, and has not been tested in a laboratory. But it could be safer than a drive that spreads endlessly.
Esvelt urges the need to be open, and act differently to the likes of Robert Oppenheimer, who also helped develop a world-changing technology.
‘‘When you see something that is technically sweet, you go ahead and do it and you argue about what to do about it only after you have had your technical success,’’ Oppenheimer said.
‘‘That is the way it was with the atomic bomb.’’
‘A CONSTITUTIONAL MOMENT’
At the moment, there is no research under way to use a gene drive for predator control in New Zealand – it’s very much in the theoretical realm.
The Sustainability Council report says New Zealand authorities have not sufficiently considered the consequences of such technology, and New Zealand’s likely role in any use.
‘‘The complacency that has previously typified official thinking needs to be set aside,’’ it says.
‘‘There is real urgency to meeting this governance challenge, given the investment in the technology, the political sponsorship it has attracted and the risks that attend even contained development.’’
In New Zealand, gene drives would be covered by the Hazardous Substances and New Organisms Act (HSNO), meaning it would require approval by the Environmental Protection Agency (EPA), which reports to the environment minister.
Its use, however, would be for conservation. Conservation Minister Eugenie Sage says she has asked officials to take a precautionary approach and not invest in gene drive technology until the Government’s position is clearly defined.
‘‘For animal pest control, there continues to be opportunities to expand the suite of tools available, including new traps and lures, as well as improvements in existing methods,’’ she says. ‘‘Any future use of gene drive or similar technologies would need to go through the full regulatory process before it is able to proceed, including full public engagement at key decision-making stages.’’
While any use of gene drives in New Zealand is on ice, the technology pushes ahead overseas.
The report argues a need for ‘‘collective consent’’ – meaning all potentially affected nations must agree before a nation releases a gene drive. In the case of rats, which are virtually everywhere, this would require nearly global consensus.
There are already international agreements around genetically modified organisms (GMOs), but it has too many gaps to work for gene drives, the report says. Many countries have not ratified them, and the risks are much higher with gene drives than GMOs – there would need to be a liability regime for any unintended damage.
Until then, New Zealand should push for an immediate moratorium on all gene drive releases, until a governance regime is set up, the report says.
‘‘That pledge will be a first signal that the international community has recognised the enormous challenge that this technology presents.’’ As for the technology itself, there is still time for it to develop, and to consider if it is too dangerous to use safely. It may be too dangerous to trust ourselves to use it responsibly, or the ethical implications too large.
‘‘In both its ambition and its potential for severe unintended or unanticipated outcomes, the technology precipitates what has been called a ‘constitutional moment’,’’ the report says.
‘‘The fundamental ethical question it presents is under what circumstances, if ever, is it acceptable to wipe a species off the face of the Earth?’’