Wednesday, 19 September 2018
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Gene drives: Feral science or feral solution?

Gene drives: Feral science or feral solution?
23 Jun
10:11

A new genetic technology bankrolled by the United States military has the potential to wipe out feral mice and malaria — but scientists are treading carefully, warning it could have unintended consequences.

Pioneering MIT biologist Kevin Esvelt knew he was onto something big — when the idea first came to him.

He had his epiphany walking over a bridge in Boston.

“I happened to see a turtle in the water, which was pretty rare,” he said.

“I was looking at it thinking ‘is anyone going to edit any of these organisms with CRISPR?'”

CRISPR is a new genetic engineering technique that allows scientists to modify, delete or insert genes into organisms more easily and accurately than was previously possible.

“I thought, ‘we’re probably not going to engineer the environment in that way’,” Professor Esvelt said.

But the idea he came up with next is so powerful it prompted him to call for a radical new transparency in science.

“The concept does not appear anywhere in science fiction — now it looks like we can do it.”

What is a gene drive?

Professor Esvelt’s big idea was that of the self-propagating gene drive.

A gene drive is a genetic mechanism that skews the odds in favour of a specific gene being passed onto subsequent generations, in a way that allows it to spread preferentially across a species.

Gene drives occur naturally, but Professor Esvelt, who heads up the Sculpting Evolution Group at MIT’s Media Lab, has come up with a recipe for building synthetic gene drives.

The technology could allow scientists to select certain genes to propagate in wild populations of animals to render them infertile or unviable.

“That’s a very useful tool for controlling and eradicating invasive pest species”, said Professor Paul Thomas, a geneticist from the University of Adelaide.

For example, researchers are developing gene drives that could carry a gene resistant to malaria into mosquito populations prone to the deadly parasite.

“To date, gene drives have only been demonstrated to work in insects — mosquitos and fruit flies — and also in yeast,” Professor Thomas said.

But that looks set to change.

A feral problem

Professor Thomas is part of an international consortium called GBIRd (Genetic Biocontrol of Invasive Rodents) developing gene drives to target feral rodents on islands.

Islands only make up 5 per cent of the world’s land mass, he said, but are the site of 80 per cent of extinctions and contain 40 per cent of endangered species.

“Mice and rats cause devastation on islands,” Professor Thomas said.

“[They] get into the nesting sites of migratory birds. They eat the chicks and birds.”

For birds that travel thousands of kilometres to a very specific breeding site this spells death and disaster for their species.

Traditionally, rodenticide baits have been used to poison pesky rats.

But when 90 per cent of the world’s islands reportedly contain feral rodents that’s a huge undertaking — and there’s the risk of poisoning native animals too.

“They are a very non-specific, blunt tool,” Professor Thomas said.

“They do work, but it’s labour intensive and not particularly humane.”

Professor Thomas’s team are on the cusp of confirming whether they have a gene drive that will render female mice sterile.

“We’ve got our fingers crossed we’ll get results within the next few weeks to tell us whether our gene drive experiments have worked or not,” he said.

They’ve also carefully modelled the potential for a gene drive to spread in mice.

“We estimate that if we seeded 100 mice in an island population of around 50,000 mice that might eradicate that population, under certain conditions, within four or five years,” Professor Thomas said.

But computer models can’t predict all unintended consequences.

Unmasking science

Uncharacteristically for a scientist, Professor Thomas is keen to talk about the research before his experiments have concluded and been published.

“There’s a lot of interest from members of society about whether this is an appropriate technology to use,” he said.

“When we are talking about gene drives, we are talking about a gene that could spread through the population.

Professor Thomas said he and his colleagues want people to know about what they’re doing.

“We want to engage in a conversation with stakeholders so we can inform the debate about whether gene drives are going to be a viable proposition for pest suppression,” he said.

Synthetic gene drives are yet to be trialled in the wild, but if one is found to work for feral mice, the next step will be field trials on remote islands.

Dr Owain Edwards at CSIRO, also part of the GBIRd international consortium, said strict criteria are guiding their search for suitable sites, including islands off the coast of Western Australia.

Feral animals often have an ingenious ability to escape containment — and Dr Edwards said this is an important consideration.

“We are very interested in making sure that the releases are biosecure, contained and unlikely to get to other islands or the mainland,” he said.

“We also need to know about the fauna on the islands and to get a clear understanding of the genetic diversity of populations.”

Dr Edwards said the risk of gene drives wiping out other species like native rodents was low.

“A gene drive is one of the technologies we have that has the lowest chance of affecting other species,” he said.

“It is spread only by sexual reproduction, and in general species will only sexually reproduce with members of the same species.”

As another control the researchers have picked genome sequences that are only present in the species being targeted.

“Much of the effort is focused on controls and fail-safe mechanisms that can be engineered into the gene drive,” Dr Edwards said.

This includes developing a self-limiting gene drive.

“An in-built generation counter would put a break on their activities,” Professor Thomas said.

Professor Esvelt said designing gene drives that can be contained or reversed is a vital priority.

“The very first thing we tested was that our proposed containment strategies worked,” he said.

“If a gene drive is released to alter a given ecosystem it will affect everyone who lives there — you cannot opt out.”

Military money funding gene drives

The US Military’s Defense Advance Research Projects Agency (DARPA) is funding Professor Thomas’ work, a collaboration with North Carolina State University, to the tune of “in the millions”, he said.

According to documents obtained through a freedom of information request by the Third World Network, DARPA has allegedly provided up to $US100 million for various gene drive projects.

A DARPA representative did not respond to Science Friction’s request for comment.

Their website states the Safe Genes program aims “to protect warfighters and the homeland against intentional or accidental misuse of genome editing technologies; prevent and/or reverse unwanted genetic changes in a given biological system; and facilitate the development of safe, precise, and effective medical treatments that use gene editors”.

Gene drive technology may offer a novel solution to malaria, but some are concerned it poses a grave threat to public health if it was used for nefarious purposes like bioterrorism.

For example, could gene drives be unleashed that promote mosquito borne-diseases rather than prevent them?

Are backyard biohackers at risk of coming up with a gene drive beyond the gaze of regulatory authorities?

That’s a long way from what’s motivating Professor Thomas, who seems unphased about taking money from the US military to fund his research.

“It doesn’t alter in any way the experiments we wanted to do.”

Whether gene drives become a new frontier for bioterrorism remains to be seen.

In the meantime, a genomic war on feral mice looks set to be waged sometime in the near future.

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