A powerful new technology could be used to manipulate nature by “editing” the genes of organisms in the wild, enabling researchers to block mosquitoes’ ability to spread malaria, for example, or to make weeds more vulnerable to pesticides, Harvard scientists said Thursday.
In an unusual step, however, the Boston team called for a public debate on the wisdom of its audacious idea, which the scientists say could lead to inadvertent species extinctions, new genes spreading through the environment in unexpected ways, and unforeseen ecological ripple effects.
The Harvard group, in a paper published in the journal eLife, described a technology called a “gene drive.” It would allow scientists to make changes to the DNA of organisms that would spread rapidly in the wild.
For years, researchers have tinkered with genomes to try to produce a fuel, drug, or crop with a specific quality, but the new technology is not nearly so limited in scope. It is conceived of as a way to alter the world outside the lab or beyond the boundaries of a farm field.
“This is a much more open-ended kind of use, because the context is the environment itself,” said Gregory E. Kaebnick, a research scholar at the Hastings Center, a nonpartisan bioethics research institution in New York, who was not involved in the research. “I would be opposed to playing around with this technology unless there are very significant benefits.”
Science often works quite differently, with new technology developed and deployed before the public has had a chance to fully weigh in, as with genetically modified food.
“We thought it was really kind of important to let the public know that we’re pretty sure this is possible, given everything we know about molecular biology, before we present it as a fait accompli,” said Kevin Esvelt, a technology development fellow at Harvard University’s Wyss Institute for Biologically Inspired Engineering, a leader of the work.
Esvelt and his coauthors see enormous potential for gene drives, ranging from helping to stop malaria, a disease that kills more than half a million people each year, to curbing the spread of invasive species.
“I’ve had ecologists . . . say getting rid of the carp from the Great Lakes is one example . . . I might be willing to accept,” said George Church, a professor of genetics at Harvard Medical School and leader of the work. “It just shows that one ecological problem outweighs another one.”
But without careful forethought and oversight, it is possible that the powerful technology could go awry. People with malicious intent could use a gene drive to try to cause a species to crash or a crop to fail.
Dana Perls, who advocates on food and technology issues for the nonprofit organization Friends of the Earth US, said the unintended effects are a key concern. Perhaps a dramatic reduction in a mosquito population would eliminate a major source of food for a species of bird, disrupting a food chain.
Because gene drives offer the prospect of manipulating many generations of a wild species, she said, the risks have to be very carefully weighed.
That’s why, in addition to the technical scientific paper, a larger group — including ecologists, policy experts, and biologists— simultaneously published a paper in the journal Science outlining the regulatory gaps that need to be filled. They made 10 recommendations to manage the risks. For example, the authors suggest that “reversal drives” that can undo the genetic manipulation be tested before any genetically modified organisms are released.
“This is where I think the debate should start: You will have an opportunity to say, ‘Do we really want to do this?’ and if the answer is yes, what kind of systems do we have in place, what kind of safeguards,” said Todd Kuiken, a senior program associate in science and technology innovation at the nonpartisan Woodrow Wilson International Center for Scholars, who was involved in the work. “I think scientists particularly need to understand there may be technologies that, once you debate them, the public may decide we don’t want to move forward on this.”
The gene drive idea was first proposed a decade ago by Austin Burt, a professor of evolutionary genetics at Imperial College London who saw that a natural mechanism that allows some “selfish genes” to bend evolution’s rules might be a way to change large populations. Those selfish genes use a molecular trick to ensure they are passed on to most members of the next generation, even if they do not have any beneficial effects.
Normally, organisms that reproduce sexually carry two copies of each gene, and each parent hands one copy down to offspring. That means a typical gene has a 50-50 chance of being passed down. An engineered gene drive improves those odds. It contains a modified gene, coupled with an enzyme that will shred the normal, unaltered copy of the gene. When a cell tries to repair this damage, it will often use the unshredded copy, including the gene drive, as a template. That means more than half the offspring — in some organisms nearly all — will carry the new gene.
A team of Harvard researchers realized that a two-year-old genome-editing technology called CRISPR would probably make it possible to engineer gene drives that target a wider range of genes in a wider range of species. They presented the idea in January at a workshop partly funded by the National Science Foundation, which convened diverse thinkers to debate the repercussions.
From that discussion at MIT. scientists decided it was important to present the idea and start a thoughtful public debate, even though the work is in its earliest stages, far from the time when anyone is ready to release organisms into the wild.
Burt, using a different technology, recently showed that in a laboratory, it is possible to create a gene drive that could tip the gender ratio toward males in a mosquito species responsible for malaria transmission in Africa. Such imbalance would help reduce mosquito population and spread of the disease.
“I’m glad people are finally paying attention,” Burt said. “. . . You wouldn’t want unthinking application of it, and you wouldn’t want accidental escapes from a population inside the lab getting outside the lab.”
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