'We should not be in the business of extinction'

A cheap and radical tool that enables geneticists and researchers to edit genomes easily by removing, adding or altering sections of the DNA sequence is causing a stir among scientists.

The CRISPR-Cas9 uses gene-drive technology, which promotes the inheritance of a particular gene to increase its prevalence in a population, and it’s available on the internet for about $300.

It raises the question: Could biohobbyists flood the natural world with organisms concocted in basement labs? Science fiction — via works such as “Frankenstein,” “Jurassic Park” and “Westworld” — tells us that’s not something we’d want.

An Arizona State University researcher has stepped into the conversation, co-authoring a paper published in the journal Science, advising care and providing a roadmap to using gene-drive technology.

“What folks would be worried about, potentially, is you could genetically modify an organism with this gene-drive system with the expectation of reducing an individual species, like say a population of mosquitos — but it drives that species to extinction,” said James Collins, co-author of “Precaution and governance of emerging technologies” and Virginia M. Ullman Professor of Natural History and the Environment in the School of Life Sciences at ASU.

“Or you could set out that as your goal. Then you begin to get on a very slippery slope. … We should not be in the business of extinction.”

Collins also is co-chair of the National Academy of Sciences' Committee on Gene Drive Research in Non-human Organisms: Recommendations for Responsible Conduct, a panel of 16 experts who released a lengthy report in June on the topic.

It was a rare instance of ethics beating technology out the door.

“What you want, ideally, is to be ahead of the release of a new technology and have thought about what the ethical, legal and social implications are that of technology so that you're not in a situation of trying to close the barn door after the horses are out,” Collins said. “So with gene drives we are in that advantageous position of being ahead of technology and having this kind of report in place.”

Emma Frow is an assistant professor with a joint appointment in the School of Biological and Health Systems Engineering, and the Consortium for Science, Policy and Outcomes.

“There’s a reasonable history of science being aware of the implications of the technologies and trying to take steps to put in safeguards for their own research and work,” Frow said. “This type of gene-drive technology is causing particular discussions and interest within the scientific community because it’s radically different than what previous technologies could do.”

Previous genetically designed organisms were designed not to survive out of the lab or on their own, she said.

“Gene drives are explicitly designed to spread,” Frow said. “It’s almost a different approach.”

'This isn't a natural process'

People have tampered for thousands of years with horses, crops and pets, but it was through a natural process. This isn’t a natural process, said Andrew Maynard, a professor in the School for the Future of Innovation in Society at ASU and director of the Risk Innovation Lab — a unique center focused on transforming how we think about and act on risk, in the pursuit of increasing and maintaining “value.”

“Effectively, what we’ve got is a vastly expanded tool kit for playing around with genetic codes,” Maynard said. “Now we can reprogram and modify genetic codes far faster, far easier and far more sophisticatedly than we have ever done before. The thing that is unique about gene drives is the ability to force that genetic change through subsequent regenerations. In a way, we’re borrowing again from nature, so we’re not doing something that has never been seen before in nature, but we’re co-opting it and using it in a way which you don’t see occurring naturally.”

Gene drives can speed nature up and also create aspects never seen in nature before.

“You could create novel traits that would be very long time occurring through a process of natural selection or never get there through the process of natural selection,” Collins said. “So this enables you to move beyond certain kind of boundaries that are tougher to overcome through natural selection. With natural selection, you work with the variants you have at hand. These techniques allows you create variations that you don’t have at hand.”

The technology isn’t so much new as it is different from what has come before, according to Collins. It falls between the cracks of the Environmental Protection Agency, the Food and Drug Adminstration, and the U.S. Department of Agriculture. There’s no consensus on how to handle it.

A report from the Office of Science and Technology Policy at the White House on new forms to genetic modification, including gene drives and how to think about all of this, is due out soon.

Risk panic vs. innovation thrill

The struggle in using the science is between two concepts — risk panic and innovation thrill — both of which were demonstrated by the Manhattan Project building nuclear weapons during World War II.

Risk panic is irrational fears paralyzing development of new technologies. It’s the superego of the two — being so scared of results that the tech is mothballed. Los Alamos scientists weren’t sure if the bomb they were building would set the atmosphere on fire or not. They agreed the project could not be allowed to continue if this were the case. (When the numbers proved that chance was less than 3 in 1 million, they went ahead.)

The second concept is innovation thrill. It’s the id of the duo. Go ahead and do it, just because you can. Robert Oppenheimer was a proponent of the notion. “He talked about this notion of innovation thrill, and you argue about what to do only after you have your technical success,” Collins said.

Neither is better than the other, Collins and his co-authors said. What’s needed is a predefined roadway, with checks and balances.

Too much precaution can stifle science, Collins said. But if you think about the ability to take an organism and completely change the nature of that organism, you can see a future rife with unintended consequences.

Locusts swarm and obliterate crops. What if you reprogram them so they never swarm? Sounds great, but what happens if that swarming is essential to other ecosystems? What if the swarm is bad for people but good for the broader environment?

“If you take something out of the natural environment which has evolved over hundreds of thousands of years, and more than that, there are likely to be some unintended consequences,” Maynard said. “If you go back and have a look at how we’ve used species to deal with environmental problems — 'if you have a rat problem, you bring in cats' approach — we’ve seen that time and time again, when you bring in an organism to deal with a problem, that organism becomes the next generation’s problem. Then the question is: As we begin to genetically engineer organisms, do we have the same problem? Does it become the next generation’s problem to deal with?”

Obstacles as safeguards

One caveat is this is not easy to do. The likelihood of a bright hobbyist creating some horror of a lifeform that actually survives is tiny.

Frow has judged the International Genetically Engineered Machine for years. It’s an international competition for students interested in synthetic biology. Student teams are given a kit of biological parts to build and test biological systems in living cells, ranging from bacteria to mammalian cells. These are undergrads in well-funded institutions with academic support, and they still struggle, Frow said.

“It’s really hard,” she said. “It’s pretty unusual for teams to come in with proof that what they’re thinking about works.  We’re talking about smart undergrads. It’s not trivial for them to do this. … Right now it’s still really hard.”

Another obstacle to unleashing a science-fiction nightmare is the ecological modeling.

“We need to be a little bit careful here when we talk about the danger of this technology,” Frow said. “It’s not one mosquito or one fruit fly escaping the lab. It’s unlikely to propagate through the entire population. Scientists are trying to figure out what portion of the population you’d have to release.”

There are safeguards in place at the university level, Collins said, codes and guidelines of ethics and principles.

However, there’s nothing equivalent at the national level, no consensus on how to handle the technology.

“The national framework is uncertain at this point, as far as the gene-drive technology is concerned,” Collins said.

The national committee Collins co-chaired was a mix of natural scientists and social scientists interested in the ethical, legal and social implications of the technology. They came to the conclusion that scientists should seek input from stakeholders and then turn their proposals to the public for deliberation.

“You want to get input from the stakeholders and from the public as you’re going along, relative to constructing the initial hypothesis and designing these experiments, and — in the case of these gene drives — whether or not you want to actually release them into the environment,” said Collins, who has served on similar government panels.

Human history is fraught with ideas that seemed really great at the time, Maynard said.

“What we’re seeing now with technology and innovation is that we don’t have enough time to clean up the mess,” he said. “That’s especially true with gene drives, where we can move so fast that the consequences can potentially overtake us before we deal with problems that emerge. … You just say, ‘We’ll create an even better, more powerful gene drive to correct the problems of the previous gene drive.’ Where does that end?”

The paper’s examination of the National Academy’s report recognizes we need to be ahead of gene drives, but it’s also a really important technology. Paralyzing worry about consequences can’t hold us back.

“Those are, I think, really important points,” Maynard said. “It’s encouraging to see the science community beginning to think critically about what you can do early on to make sure that a novel technology is responsible and beneficial. The bigger challenge is how do you go outside the science community?”