I

t’s a technology that scientists say could fundamentally alter entire populations.

The Pentagon has expressed alarm about what terrorists might do with “gene drives.” Meanwhile, scientists are researching how they could be used to stop the spread of intractable diseases like malaria.

So how did a group of college students come close to creating a gene drive as part of a science competition?

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It started innocently enough. The team of students at the University of Minnesota were looking for a project to enter into the the international synthetic biology competition iGEM. Some were taken by a paper by George Church, the famed Harvard geneticist, that described how a gene drive worked and how to build one.

A gene drive is a sequence of DNA inserted into a cell that “drives” certain genes through the entire population by forcing them into every offspring.

“We thought it was super cool, but we immediately started thinking of some of the negative implications,” said Sarah Lucas, at the time a junior and the leader of the team.

Because the gene drive forces specific genes to spread quickly through a population, an accidental — or intentional — release of an organism with a gene drive could have massive ecological effects. So, the team decided to build a “reversal drive,” which could undo the effects of a gene drive.

The students fell short of creating an actual gene drive. But they came close enough to demonstrate that you may not have to be a scientist or academic researcher to change the genetics of an entire population.

MIT professor Kevin Esvelt, a gene drive expert, told STAT that this project was not dangerous — but that any undergraduates who want to attempt such work in the future should talk to someone like him first, a recommendation iGEM is adopting as policy.

“The dangers are that [a] team is working on a project that either accidentally or deliberately results in something getting outside the lab,” said Piers Millett, director of safety and security for the competition. No countries have laws governing how gene drives can or cannot be used in the lab, Millett said.

In the weeks since the competition, iGEM’s safety board has established a policy about how students can work with gene drives, and what they should do to prevent accidental release. The guidelines could become a global model.

“I know some government regulators will be watching very closely about how this is dealt with inside of iGEM,” Millett said, noting that some members of iGEM’s safety committee work for regulatory agencies, for instance in Canada and the Netherlands.

MN Gene drive students
Students from the University of Minnesota present their project at the iGEM competition in Boston. From left to right, Kathryn Almquist, Carolyn Domroese, Ajinkya Limkar, Sarah Lucas, Chase Bowen, and Sophie Vrba. Justin Knight/iGEM Foundation

‘The yeast of our worries’

The group of students first started mulling the creation of a gene drive in the spring with the aim of mitigating its risk, not amplifying it, by building a “reversal drive,” which could undo the effects of the gene drive. Such a reversal drive had been built in yeast last year, but the students were unaware of that at the time.

iGEM has a library of off-the-shelf parts that the teams can order, but the gene drive was not one of them, so the team had to figure out how to build it themselves. They downloaded the genetic sequence for a gene drive from the supplement to a Church paper, chopped it in half, and sent it away to a DNA synthesis company that provides free DNA to iGEM teams. They also designed a reversal drive and sent away the sequence, divided into thirds. (The drives themselves were too big for the synthesis company to print as whole elements.)

And the students did take precautions.

They planned to use a so-called “split drive” configuration, where most of the gene drive would be put into the yeast’s genome, while a key component was isolated in a separate bit of DNA. Even if the yeast escaped, both components of the drive would not spread to all of the offspring. They also used a special strain of yeast that can only survive if it’s constantly fed four lab-provided amino acids, minimizing the chance of an escaped yeast cell surviving in the wild.

The students spent the next few months trying to stitch the pieces of the drives together, stymied by contaminated lab equipment and a fridge that wasn’t cold enough. By the time they had to submit their work for the October competition, they had only managed to assemble two of the three parts of the reversal drive, and none of the gene drive.

Meanwhile, iGEM safety officials were keeping a close watch from a distance. They knew about the project before the competition — teams have to upload information about their work to a wiki — and they understood that the team had taken safety precautions, so there was no immediate danger, said Kenneth Oye, an MIT political science professor and cochair of iGEM’s safety committee. But the title of their project — “Shifting Gene Drives Into Reverse: Now Mosquitoes Are The Yeast Of Our Worries” — indicated that other organisms might be on the table.

So when, on the afternoon of Sunday, Oct. 30, the Minnesota team stood in front of hundreds of students, faculty advisors, and judges to give their research presentation, there were a lot of questions to answer. And most of those questions involved safety.

Oye was one of the questioners. His motives, he said, were twofold: to make sure the team knew what they were doing and to send a public message to the other students in the room.

“There was a larger purpose: to make clear to everyone in the room that this is something you don’t screw around with,” Oye said. “Let me rephrase that. This is a technology [for which], even if you’re simply investigating and researching, care is required.”

“There was a larger purpose: to make clear to everyone in the room that this is something you don’t screw around with.”

Kenneth Oye, cochair of iGEM’s safety committee

But exactly what that care should consist of is a subject still in flux, even among biosecurity experts. Some of the preeminent scientists in the field of gene drives authored a Science paper last year laying out safeguards, but without any laws or regulations governing the work, a scientist can always buck the advice of her colleagues.

The do-it-yourself biology community, where members of the public can tinker with genes and cells, has its own patchwork of experiences with the cutting-edge technology. Maria Chavez, a board member of BioCurious in Silicon Valley, said that nobody in her community has asked to do projects involving gene drives, and that if someone did, “we would have to have a long conversation with them,” and the lab’s safety committee would have to sign off on the project, as is required for all projects. Shaun Moshasha, founder of Open Bio Labs in Charlottesville, Va., said his facility doesn’t allow gene drive research to take place.

iGEM’s safety committee has also pondered the possibility of gene drives in the past. The team, which includes professors and regulators from around the world, sits down every year with regulators and law enforcement personnel for a private meeting to discuss how to handle emerging biotechnologies. Last year, gene drives came up.

But at that time it had only been eight months since the first published paper describing this type of gene drive in yeast. Oye wasn’t expecting undergraduates to make an attempt until at least 2017.

Oye said that the 2015 meeting was an “exploratory” discussion about what to do about gene drives, but they didn’t make a formal decision.

Esvelt, who attended the 2015 safety meeting as an advisor, remembers it differently. He said they reached an agreement: no gene drives at iGEM.

If that was iGEM policy, it was not communicated to the Minnesota undergraduates. They were unaware that their project might attract such attention until they arrived in Boston in October.

“We were very surprised at the interest in our project,” said Kathryn Almquist, a sophomore on the team. “We didn’t realize how big of a deal this was.”

IGEM Poster
The University of Minnesota students’ research poster describes their attempt to create a reversal drive. University of Minnesota iGEM team

Driving onward

In the weeks since this year’s competition, iGEM organizers have set down a detailed policy on how their students should approach gene drives.

From now on, any team who wants to do a project involving gene drives must participate in a video conference with experienced gene drive researchers to discuss the safety procedures they are using for their project and will also be required to agree to safeguards laid out in the 2015 Science paper, including strict review of protocols by biosafety authorities; using molecular techniques to ensure that, even if organisms escape, their gene drives won’t spread; and a ban on transporting organisms with gene drives from one lab to another. Information on iGEM’s website will make clear that working with gene drives requires special clearance. And iGEM’s biological warehouse, from which teams can order parts, will not stock off-the-shelf gene drives.

Meanwhile, for the Minnesota students in the center of the storm, there are mixed feelings about the work they’ve done so far, and what comes next.

“We hadn’t really anticipated how much of an impact this would have,” Almquist said. She said she was relieved that they didn’t end up assembling the complete gene drive: “We are maybe not experienced enough to be dealing with [this technology].”

Meanwhile, sophomore Ajinkya Limkar said that the controversy inspired by their project has only motivated him further.

“It was, I guess you could say, a great feeling, that what you’re doing can have the potential to change the world, and hopefully for the better,” Limkar said. He thinks the team may continue the project next year.

And whatever the outcome for these students’ project, it’s not the last time gene drives will come up — at iGEM or outside it.

“These are kids,” Oye said. “If they can do stuff, you know it’s coming soon, and it’s likely to be something that would be relatively common.”

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