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Without going along with all details of the alarm of Jacobsen and Esvelt 
here, I surely recommend we all be alarmed.
Chandler
>>>
>>>
>>>   Deleting a Species
>>>
>>>
>>>     We are on the brink of being able to genetically engineer an
>>>     extinction. Should we?
>>>
>>>     Rowan Jacobsen <x-msg://149/author/rowan-jacobsen> Jun 20, 2018
>>> Illustration: Diego Patiño)
>>>
>>> In a windowless London basement, behind three sets of locked steel 
>>> doors and a wall of glass, thousands of /Anopheles gambiae/ 
>>> mosquitoes <https://psmag.com/tag/mosquitoes> cling like Marvel 
>>> <https://psmag.com/tag/marvel> supervillains to the sides of white 
>>> mesh cubes. The room is negatively pressurized, so air is constantly 
>>> sucked inward to ensure that the mosquitoes, which have been 
>>> subjected to a new and astonishingly powerful kind of genetic 
>>> engineering, never escape.
>>>
>>> If the modifications to these whining mosquitoes were perfected, and 
>>> they were somehow able to make their way to sub-Saharan Africa, they 
>>> would have an effect on their kin unlike any animal that has ever 
>>> existed. The /Anopheles/ are equipped with a genetic tool that 
>>> ensures that they are either sterile—they can't produce viable 
>>> eggs—or, if fertile, that they will pass that sterility gene on to 
>>> nearly every offspring. And the same would be true for their 
>>> descendants, which would continue to spread the genetic sabotage 
>>> into future generations.
>>>
>>> If some future version of the mosquitoes were released, these deadly 
>>> modifications could spread through the African tropics, crashing the 
>>> population as they went. And because /Anopheles/ is the primary 
>>> African vector for the parasite that causes malaria, its collapse 
>>> would likely take down malaria with it. Within a few years, the last 
>>> great scourge of humanity 
>>> <https://psmag.com/magazine/engineering-the-end-of-malaria>, which 
>>> kills upwards of half a million people per year, would be vanquished 
>>> on the African continent. It would be one of the greatest health 
>>> achievements of all time. And yet the intentional eradication of a 
>>> species is not something we should pursue without a lot of 
>>> foresight, and the release of highly invasive genetically modified 
>>> organisms <https://psmag.com/tag/genetically-modified-organisms> 
>>> (GMOs) into the wild is itself deeply disturbing.
>>>
>>> Known as a gene drive, the ability to force particular genes into 
>>> future generations of an entire species 
>>> <https://psmag.com/environment/scientists-genetically-modify-organisms-in-wild> 
>>> only became available to humans with the development of CRISPR 
>>> <https://psmag.com/tag/crispr>, the gene-editing tool that has 
>>> enabled us to make precise changes to an organism's DNA. Kevin 
>>> Esvelt <http://www.sculptingevolution.org/kevin-m-esvelt> was a 
>>> fellow at Harvard University's Wyss Institute for Biologically 
>>> Inspired Engineering <https://wyss.harvard.edu/> in 2013 when he 
>>> figured out how to build a gene drive. In a 2014 paper, he proposed 
>>> several applications for his invention, including hobbling weeds 
>>> that had become resistant to herbicides, reducing malaria-carrying 
>>> mosquitoes, and eliminating invasive rodents on islands, where they 
>>> wreak havoc on indigenous birds and plants.
>>>
>>> A version of this story originally appeared in the June/July 2018 
>>> issue of Pacific Standard. Subscribe now and get eight issues/year 
>>> or purchase a single copy of the magazine.
>>> /A version of this story originally appeared in the June/July 2018 
>>> issue of //Pacific Standard//. //Subscribe now/ 
>>> <https://psmag.com/subscribe>/and get eight issues/year or 
>>> //purchase a single copy/ 
>>> <https://psmag.com/back-issue-subscriptions>/of the magazine./
>>> (Photo: The Voorhes)
>>>
>>> Many traditional conservationists were horrified by the prospect, 
>>> yet other groups embraced it. The Gates Foundation made gene drive a 
>>> centerpiece of its anti-malaria efforts, and the eco-warriors at 
>>> Island Conservation <https://www.islandconservation.org/>, who have 
>>> long used poison to combat invasive mice and rats, seized on gene 
>>> drive as a more precise weapon in their war to save native species. 
>>> New Zealand is considering using a gene drive in its push to 
>>> eliminate invasive rodents, weasels, and possums by 2050. Kevin 
>>> Esvelt wants to engineer mice that are immune to the bacterium that 
>>> causes Lyme disease, whose cycle of transmission goes from mice to 
>>> ticks to people. Dengue, Zika, and several other mosquito-borne 
>>> diseases are promising gene-drive targets. A lab in California is 
>>> working to limit the damage caused by an invasive species of fruit 
>>> fly, and labs in Australia and Texas are developing "daughterless 
>>> mice" (capable of conceiving only male offspring). The first 
>>> gene-drive field trials are anticipated within the next decade.
>>>
>>> With earlier-generation GMOs, such as Monsanto's Roundup Ready 
>>> crops, arguments often hinged on the potential for those genes to 
>>> escape into the environment. Conservationists believed escape was 
>>> inevitable, while corporations downplayed the risk, but nobody was 
>>> suggesting that GMOs be let loose in nature—until now.
>>>
>>> When I first heard about gene drive, I thought of "ice-nine," the 
>>> form of water in Kurt Vonnegut's 1963 novel /Cat's Cradle/ that is 
>>> solid at room temperature and acts as a seed crystal for adjacent 
>>> water molecules, turning them solid. At the end of /Cat's Cradle/, 
>>> the frozen body of a man who has committed suicide by drinking 
>>> ice-nine falls into the sea, and all the world's oceans and rivers 
>>> are forever frozen, extinguishing most life on Earth. Gene drives 
>>> have similar dystopian potential. In theory, a single lab could 
>>> alter the entire planet. And the technology has arrived far quicker 
>>> than our ability to grapple with its staggering implications.
>>>
>>> Gene drives work by gaming inheritance 
>>> <https://psmag.com/environment/should-we-fight-invasive-species-with-genetic-engineering>, 
>>> forcing their way into the genetic make-up of future generations. 
>>> Sexually reproducing species usually have two versions of each of 
>>> their genes, one inherited from each parent, and they randomly pass 
>>> one of those to each offspring. Individuals that inherit more useful 
>>> genes thrive, and are therefore more likely to reproduce and pass on 
>>> those good genes, while individuals that inherit disadvantageous 
>>> genes are less likely to get the chance to reproduce. In this way, 
>>> evolution causes detrimental genes to disappear from the gene pool.
>>>
>>> Conventional genetic engineering is limited by the rules of 
>>> reproduction. Most engineered traits have a 50/50 chance of being 
>>> passed down, and unless a trait confers some advantage to the 
>>> organism, it should eventually disappear. Since most genetic 
>>> engineering to date has bred traits that benefit people, not the 
>>> organisms themselves, so far no GMOs have made significant inroads 
>>> into nature. But a gene drive can practically guarantee inheritance. 
>>> And since beneficial genes are favored by natural selection anyway, 
>>> the unique value of engineering a gene drive lies in propagating a 
>>> detrimental trait, possibly even all the way up to extinction.
>>>
>>> To make a gene drive, you start with the gene-editing tool CRISPR, 
>>> which consists of two parts: a gene-slicing enzyme and a string of 
>>> genetic code that tells the enzyme where to cut. CRISPR is 
>>> shockingly easy to use 
>>> <https://psmag.com/news/re-coding-for-conservation>. You don't need 
>>> a world-class lab, and you don't have to be a genius. I've created 
>>> antibiotic-resistant bacteria in a friend's kitchen. You just order 
>>> your CRISPR from a DNA-synthesis company (the going rate is $65 plus 
>>> shipping), specifying the exact 20-letter sequence of DNA you want 
>>> it to target. It arrives as a few drops of liquid in a test tube. 
>>> You add that liquid to another test tube containing cells of the 
>>> organism you want to modify, along with any new DNA you want 
>>> inserted, then heat it up. The CRISPR finds the spot, makes the cut, 
>>> and the new DNA gets stitched in place.
>>>
>>> Kevin Esvelt was part of the team at Harvard that helped develop 
>>> CRISPR, and he was the first to realize that the CRISPR mechanism 
>>> itself could be inserted directly into an organism's genome to 
>>> create a gene drive. Once there, the CRISPR would eliminate the 
>>> natural counterpart of the gene it is attached to, and the cell 
>>> would copy the functioning, genetically engineered version of the 
>>> gene (containing the CRISPR) in its place. The organism would then 
>>> have two working copies of the CRISPR gene, one of which would be 
>>> guaranteed to be passed down to each of its offspring, where the 
>>> process would repeat, until virtually every individual in a 
>>> population carried the engineered trait.
>>>
>>> With conventional genetic engineering (top), there is usually a 
>>> 50/50 chance of an engineered trait being passed down, but a gene 
>>> drive (bottom) can practically guarantee inheritance, allowing an 
>>> altered gene to spread through a population.
>>> (Illustration: Diego Patiño)
>>>
>>> It was a brilliant insight, with enormous implications. According to 
>>> the unwritten rules of science, Esvelt's next move should have been 
>>> to quietly create a gene drive in his lab and then publish a paper 
>>> announcing the achievement to the world and staking his claim to it. 
>>> Instead, he paused to consider the consequences.
>>>
>>> When I first met Esvelt in 2017 at Editing Nature 
>>> <https://www.editingnature.org/>, a summit convened at Yale 
>>> University's Institute for Biospheric Studies 
>>> <https://yibs.yale.edu/> to weigh the ramifications of engineering 
>>> the wild, I was struck by his demeanor. He seemed haunted and 
>>> tightly wound, as if he'd just come from a dark future he was hoping 
>>> to save us from. His boyish smile and wispy blond hair reminded me 
>>> of Tintin, but his gravelly, leading-man's voice vibrated in an 
>>> unusual timbre. Like the long /dungchen/ horns of Tibetan monks, it 
>>> seemed to resonate with both awe for the world and sorrow for its 
>>> eventual passing.
>>>
>>> As soon as Esvelt realized how easy it would be to build a gene 
>>> drive, he knew he had a potential ice-nine on his hands. "This thing 
>>> self-scales," he told the biologists, conservationists, and 
>>> ethicists gathered at Yale that day. "You can't run a field trial. 
>>> You can't introduce it anywhere in the endemic environment without 
>>> having it spread probably to every population."
>>>
>>> After his 2013 discovery, Esvelt knew others would soon hit upon the 
>>> same insight, and he felt that the runaway nature of gene drive was 
>>> not something that could be trusted to biotech specialists working 
>>> in isolation. "Your decision to go ahead and build it in the lab 
>>> means that you are performing an experiment that could affect other 
>>> people," he said. "And if you don't tell them that you're doing it 
>>> in advance, you're actively denying them a voice in the decision. 
>>> And frankly, that's wrong."
>>>
>>> Esvelt pictured the headline sure to follow an accidental gene-drive 
>>> release: "Scientists Convert Entire Species to GMOs. Is CRISPR to 
>>> Blame?" He feared that a botched trial could turn the public against 
>>> the technology and destroy its vast potential. So shortly after 
>>> their breakthrough, he and his colleagues at the Wyss Institute 
>>> called a meeting of top ecologists, biologists, ethicists, and 
>>> national security experts. They explained the technology to the 
>>> group, and discussed the best plan of action. And their remarkable 
>>> conclusion was that the only way to ethically explore the potential 
>>> of gene drive was to change the culture of science. "We need to at 
>>> least tell other people what we are thinking of doing before we even 
>>> begin experiments," he explained. "This is difficult, because every 
>>> incentive in science points against it. If you share your brilliant 
>>> idea, you're inviting some larger, better-funded lab with spare 
>>> hands to steal it, get it working first, publish, and get the credit."
>>>
>>> Esvelt decided to make an example of himself. He published his paper 
>>> before doing any experiments, with the hope that all gene-drive 
>>> research would follow the precautions and protocols he laid out, the 
>>> most important of which was pre-registration of all experiments so 
>>> they could be vetted by all potential stakeholders. Since then, he 
>>> has spent as much time lobbying against the unwise use of gene 
>>> drives as he has advocating for them, sometimes using language that 
>>> distresses his fellow scientists. "We are walking forwards blind," 
>>> he said in a 2016 interview 
>>> <https://splinternews.com/this-scientist-is-trying-to-stop-a-lab-created-global-d-1793857858> 
>>> that is frequently cited by gene-drive opponents. "We are opening 
>>> boxes without thinking about consequences. We are going to fall off 
>>> the tightrope and lose the trust of [the] public."
>>>
>>> Not since Robert Oppenheimer has a scientist worked so hard against 
>>> the proliferation of his own creation. "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 in 1954. "That is the way it was with the atomic bomb."
>>>
>>> And that is how it has been with gene drive. Esvelt now runs 
>>> something called the Sculpting Evolution group at the Massachusetts 
>>> Institute of Technology 
>>> <https://www.media.mit.edu/groups/sculpting-evolution/overview/>. 
>>> When I sat down in his office and asked him if he had convinced many 
>>> scientists to forego the technical sweets, he shrugged. "It will 
>>> never happen unless we change the incentives," he said. "Most 
>>> scientists, however supportive in theory, say they just can't take 
>>> the risk." The allure of scientific immortality—or at least tenured 
>>> professorship—is simply too strong, and while those working with 
>>> gene drives claim to follow rigorous safety protocols, few are 
>>> willing to openly share what they are inventing behind the closed 
>>> doors of their labs.
>>>
>>> We are on the cusp of a gene-drive explosion. Many agricultural 
>>> pests are potential targets, as are weeds that have evolved 
>>> resistance to Roundup. California's cherry growers are funding 
>>> gene-drive research to eliminate the spotted-wing fruit fly, which 
>>> lays its eggs in soft fruits. Tata Trusts of India recently gave the 
>>> University of California–San Diego $70 million to train a new 
>>> generation of Indian scientists to use gene drives for agriculture 
>>> and disease control. And in the fall of 2017, the biotech firm 
>>> Oxitec <https://www.oxitec.com/> released genetically engineered 
>>> diamondback moths (which infest broccoli, cabbage, and other 
>>> brassicas) in a field trial in upstate New York. The moths carry a 
>>> gene that kills females in the larval stage, and though there is no 
>>> gene drive involved at present, it would be a logical next move.
>>>
>>> The most vocal critics of gene drives have been two conservation 
>>> organizations, Friends of the Earth <https://foe.org/> and the ETC 
>>> Group. Jim Thomas, co-executive director of ETC, told me that, for 
>>> all the emphasis on curing disease and saving endangered species, he 
>>> sees "Big Ag" lurking in the background. "Ultimately, I think that's 
>>> where this technology lands," he said. "It becomes a kind of 
>>> insecticide. If there's money to be made here, that's what’s going 
>>> to drive it." Thomas sees potential for abuse in the developing 
>>> world. "How does a powerful technology shift power relations? And 
>>> what does that mean for those that are marginalized and vulnerable?"
>>>
>>> In September of 2016, 30 environmental luminaries, including Jane 
>>> Goodall, David Suzuki, and Vandana Shiva, joined with ETC to publish 
>>> an open letter calling for a moratorium. "We believe that a powerful 
>>> and potentially dangerous technology such as gene drives, which has 
>>> not been tested for unintended consequences nor fully evaluated for 
>>> its ethical and social impacts, should not be promoted as a 
>>> conservation tool," they wrote. "Given the obvious dangers of 
>>> irretrievably releasing genocidal genes into the natural world, and 
>>> the moral implications of taking such action, we call for a halt to 
>>> all proposals for the use of gene drive technologies."
>>>
>>> Friends of the Earth joined ETC in bringing the call for a 
>>> moratorium to the December 2016 meeting of the United Nations' 
>>> Convention on Biological Diversity <https://www.cbd.int/>, which 
>>> covers the equitable use and regulation of biological resources, 
>>> including genetically modified organisms. The Convention has 
>>> previously halted controversial technologies such as ocean 
>>> fertilization and sterile-seed crops by establishing moratoria, but 
>>> with gene drive it merely called for better risk-assessment. Friends 
>>> of the Earth and ETC vowed to continue to rally support for a 
>>> moratorium, which will be debated in Montreal this July and then 
>>> voted on at the next meeting in Egypt this December.
>>>
>>> (Illustration: Diego Patiño)
>>>
>>> Most gene-drive scientists accuse these groups of exaggerating the 
>>> risks of genetic engineering and playing to the public's fears, but 
>>> Natalie Kofler, who founded Yale's Editing Nature initiative to 
>>> facilitate public deliberation around gene editing, thinks it's 
>>> vital to take their point of view seriously. "The followers of those 
>>> groups share a worldview with many people that I discuss this with 
>>> on a daily basis," she told me. "They feel deeply that it is wrong 
>>> to tamper with the DNA of wild things. There's a sacredness to it 
>>> that we shouldn't mess with. And that is a worldview that is very 
>>> quickly dismissed by scientists and technologists. And because it's 
>>> not being acknowledged as something valid for discussion, I think 
>>> it's creating a huge polarization."
>>>
>>> Still, Kofler finds the idea of a ban on research "totally 
>>> ridiculous." This is a brand-new technology, she said. "Right now we 
>>> don't know nearly enough about how it works, how the public 
>>> perceives it, or how it will impact the environment to take stances 
>>> of opposition or support. Right now, we need to be comfortable to 
>>> stay in the gray zone—to comprehensively explore this issue with the 
>>> degree of openness and transparency that it deserves. So, if 
>>> anything, more research—scientific and sociological alike—needs to 
>>> take place."
>>>
>>> Jim Thomas points out that there's a difference between a moratorium 
>>> and a perpetual ban: "There's a feeling that taking a judicious 
>>> pause and taking the time to think carefully means nothing is ever 
>>> going to move forward. But that's not what a moratorium is."
>>>
>>> When the stakes are as high as they are with gene drive, who could 
>>> argue with a judicious pause? People in Africa, Esvelt says. Every 
>>> year you delay work on gene drives, another half-million people die. 
>>> "Who am I to tell somebody who's lost children to malaria, and has 
>>> more children at risk, that they can't do it because somebody else 
>>> doesn't agree? Why should some people get veto power over a 
>>> technology that could save the lives of other people's children?"
>>>
>>> And yet, despite that sentiment, Esvelt keeps making things more 
>>> difficult for his colleagues. Last November, I along with several 
>>> other journalists received an unusual email from him. "I'm writing 
>>> because we have a couple of papers coming out next week that are 
>>> personally embarrassing for me, but are likely consequential enough 
>>> for gene drive, conservation, and science policy that you might find 
>>> them interesting," he wrote. What followed was a surprising 
>>> statement: "My decision to list invasive species control as a 
>>> potential application of gene drive in our original 2014 /eLife/ 
>>> paper was an embarrassing mistake.... It was profoundly wrong of me 
>>> to even suggest it." Additional modeling, he explained, showed that 
>>> gene drives were even riskier than he'd thought. For that reason, 
>>> one of his new papers concluded, with the possible exception of 
>>> malaria, "we should not even consider building drive systems likely 
>>> to spread indefinitely beyond the target area."
>>>
>>> The new papers triggered a wave of fresh panic in the media. "'Gene 
>>> Drives' Are Too Risky for Field Trials, Scientists Say 
>>> <https://www.nytimes.com/2017/11/16/science/gene-drives-crispr.html>" 
>>> reported the /New York Times/. Most of the coverage focused on 
>>> Esvelt's mea culpa, and when we met in his MIT office shortly after, 
>>> I asked him if that was the reaction he'd expected.
>>>
>>> "Of course!" he responded. "I'm not totally naive. 'Inventor tries 
>>> to stuff genie back in bottle'—that's a story. It doesn't happen 
>>> very often that a scientist says, 'I was wrong.' Maybe it should 
>>> happen more often."
>>>
>>> Esvelt believed that other researchers were underestimating the risk 
>>> of engineered organisms escaping a field test, even on an isolated 
>>> site, in part because of a wild card beyond the scope of any 
>>> mathematical model—human nature. "You build it, you try it anywhere, 
>>> and someone who has an interest is going to move it illegally to 
>>> take advantage. It would be totally cost-effective for someone to 
>>> hire mercenaries to fly in, capture mice, and fly out again. But 
>>> that's not the sort of thing most scientists think about."
>>>
>>> I was reminded of Jeff Goldblum's chaos mathematician in /Jurassic 
>>> Park/. "If there's one thing the history of evolution has taught 
>>> us," he warns the park's designers, "it's that life will not be 
>>> contained. Life breaks free. It expands to new territories and 
>>> crashes through barriers painfully, maybe even dangerously.... Life 
>>> finds a way."
>>>
>>> Some of Esvelt's colleagues saw the move as a publicity stunt: 
>>> Instead of drives "likely to spread indefinitely," Esvelt was 
>>> recommending a new, self-limiting type called Daisy Drive that he 
>>> had recently designed. In Daisy Drive, multiple drives are linked in 
>>> an organism's genome in a kind of daisy chain. Drive A drives Drive 
>>> B, and B drives C, and C drives D, and so on. But because nothing 
>>> drives A, it follows normal inheritance patterns and gets quickly 
>>> diluted in the gene pool. Those individuals who don't inherit A have 
>>> nothing to drive B, which then gets diluted in subsequent 
>>> generations. Like the stages of a rocket, the drives continue to 
>>> fall away until the whole system stops working after a set number of 
>>> generations. In theory, Daisy Drive allows you to affect a local 
>>> population for a set amount of time.
>>>
>>> Esvelt now hopes to use a self-limiting drive such as Daisy to 
>>> combat Lyme disease <https://psmag.com/tag/lyme-disease> in the 
>>> northeastern United States, where it has become so prevalent that 
>>> many people no longer risk walking in the woods and fields. Almost 
>>> 40 percent of Nantucket residents have reportedly contracted Lyme 
>>> disease, and that is where Esvelt has proposed to begin his "Mice 
>>> Against Ticks" experiment, as well as on neighboring Martha's 
>>> Vineyard. To make sure the local stakeholders understand the 
>>> implications, Esvelt has been holding community forums on the 
>>> islands since 2016, and most residents seem open to the idea. After 
>>> an initial field test on an isolated and uninhabited island, he 
>>> would release thousands of Lyme-resistant mice on Nantucket and 
>>> Martha's Vineyard. If all went well, the eventual goal would be to 
>>> release Daisy Drive mice on the mainland. The Lyme infection cycle 
>>> would then be broken, and eventually the Daisy Drive would disappear 
>>> as well. After a few generations, the mice would revert to normal.
>>>
>>> A number of self-limiting drives have now been proposed by Esvelt 
>>> and other researchers, but so far they exist only on paper, which 
>>> makes Jim Thomas skeptical. "Precision in biology and ecosystems is 
>>> a bit of a pipe dream," he told me. Ecosystems are remarkably 
>>> complex, and viruses and parasites have tremendous capacities to evolve.
>>>
>>> When I mentioned this critique to Esvelt, he gave me a knowing nod. 
>>> "The thing everyone is overlooking is, how do you know your gene 
>>> drive is going to behave over time the way you intend? We've never 
>>> before engineered something that we anticipate to evolve out of our 
>>> control. Perfect prediction is impossible." But unlike the skeptics, 
>>> he believes you can get close enough to proceed with confidence. 
>>> "You need to model very large populations over multiple generations. 
>>> We can't do that in mice or mosquitoes, but we can in worms."
>>>
>>> And they are. This winter, on the sixth floor of a nondescript MIT 
>>> office building, behind a locked door with a black-and-orange 
>>> Biosafety Level 2 warning sign, I held up dozens of petri dishes 
>>> filled with what looked like twitching, emaciated commas. These were 
>>> roundworms, /C. elegans/, also known as nematodes, and there were 
>>> 5,000 to 10,000 of them per dish, reproducing every three days. "We 
>>> can do 100 generations in a year with a population of 100 million," 
>>> Esvelt told me. "If we really wanted to push it, we could probably 
>>> do a population of a billion. I can't think of another organism that 
>>> would let us do that."
>>>
>>> (Illustration: Diego Patiño)
>>>
>>> One of Esvelt's postdocs placed a dish of worms under a microscope 
>>> and turned on a black light. Through the lens, I could see the 
>>> silvery squiggles snaking through the agar, eating bacteria. Each 
>>> had a glowing red esophagus thanks to a fluorescent gene (originally 
>>> from a jellyfish) that made it easier to track which ones had 
>>> received the genetic modifications.
>>>
>>> These worms will be the first organisms on Earth to harbor a Daisy 
>>> Drive. Their lives will be confined to thousands of test tubes 
>>> managed by a liquid-handling robot that can be programmed to move 
>>> precise amounts of liquid between tubes. Each test tube will harbor 
>>> an isolated population of worms, so the Sculpting Evolution team can 
>>> test what happens when Daisy Drive worms invade a new, unmodified 
>>> population. They can also test whether an engineered drive evolves 
>>> into something unexpected, given enough time and population growth, 
>>> and whether an "immunizing reversal drive" can be built that will 
>>> target such a runaway drive and reset it.
>>>
>>> Eventually, the worms could have enough genetic diversity to serve 
>>> as a decent stand-in for any wild population, and all experiments on 
>>> them will be pre-registered for feedback from the scientific 
>>> community. To keep life from finding a way, Esvelt told me the 
>>> project has five layers of safety containment: physical (the 
>>> roundworms are kept in a locked lab, and they aren't nearly as 
>>> mobile as mice, mosquitoes, or fruit flies), ecological (there are 
>>> no wild /C. elegans/ to breed with on the mean streets of 
>>> Cambridge), reproductive (most wild /C. elegans/ are hermaphrodites 
>>> and aren't interested in sex anyway), molecular (the self-limiting 
>>> Daisy system), and more molecular (the gene drive targets a unique 
>>> DNA sequence that has been engineered into the Sculpting Evolution 
>>> worms but isn't found in wild worms).
>>>
>>> If all gene-drive research hewed to these standards, I'd sleep 
>>> better at night. But despite the recommendations from Esvelt, as 
>>> well as the National Academy of Sciences 
>>> <http://www.nasonline.org/>, there are currently no binding rules in 
>>> place. And even if everyone currently working on gene drives behaves 
>>> responsibly—and they seem to be—it's easy to see how, eventually, as 
>>> the technology spreads, someone, somewhere along the way, will get 
>>> sloppy.
>>>
>>> Public alarm grew louder in December of 2017, with the release of a 
>>> cache of 1,200 emails between scientists and other gene-drive 
>>> proponents that had been obtained through the Freedom of Information 
>>> Act. "Gene Drive Files Expose Leading Role of U.S. Military in Gene 
>>> Drive Development 
>>> <http://genedrivefiles.synbiowatch.org/2017/12/01/us-military-gene-drive-development/>," 
>>> announced a press release, which noted that most gene-drive 
>>> projects—including the London mosquitoes, Texas mice, and MIT 
>>> roundworms—were being funded by the Department of Defense's Advanced 
>>> Research Projects Agency (DARPA) as part of its Safe Genes program. 
>>> Although DARPA had publicly announced it was funding the projects 
>>> months earlier, this was not well known to the general public, and a 
>>> number of news outlets ran with the story. The /Guardian/'s headline 
>>> read, "U.S. Military Agency Invests $100m in Genetic Extinction 
>>> Technologies 
>>> <https://www.theguardian.com/science/2017/dec/04/us-military-agency-invests-100m-in-genetic-extinction-technologies>."
>>>
>>> In its response, DARPA pointed out that its goals were defensive: 
>>> "Our feeling is that the science of gene editing, including gene 
>>> drive technology, has been advancing at a rapid pace in the 
>>> laboratory," wrote the agency's chief of communications. "These 
>>> leaps forward in potential capability, however, have not been 
>>> matched by advances in the biosafety and biosecurity tools needed to 
>>> protect against potential harm if such technologies were 
>>> accidentally or intentionally misused."
>>>
>>> The Safe Genes projects focus on learning to limit the reach of gene 
>>> drives and on ways to detect and disable them, but none of that 
>>> comforts Jim Thomas. "This has been the history of bioweapons 
>>> research," he told me. "It's always presented as supposedly 
>>> defensive: 'We have to develop these tools so we can respond in case 
>>> someone else develops them.'" Thomas fears the agency's agenda may 
>>> be much broader. "They're putting a finger in every single major 
>>> gene-drive project so they can be close to them. So they can 
>>> understand how these things work." Thomas worries that Daisy Drive 
>>> is the equivalent of small-scale, tactical nukes. "Once you have 
>>> this illusion that you can locally control a gene drive, then that 
>>> opens the door for using it in agriculture or as a weapon." But few 
>>> experts believe gene drives could make an effective weapon against 
>>> other people—they are just too slow and obvious. There are easier 
>>> ways to wage war.
>>>
>>> During my most recent visit with Esvelt, I asked if he could imagine 
>>> some situations where the technologies were too risky to pursue, 
>>> even in a confined environment. Easily, he said. "There are areas 
>>> where I would say, no research. And have!" It was after hours on a 
>>> cold winter night in Cambridge, and Esvelt was looking even more 
>>> pale and ragged than usual. Still, I pressed him for details. What 
>>> kind of technology would be too dangerous for research? He shook his 
>>> head and said, "There are some things I’ve thought of that I'm never 
>>> going to tell another living soul."
>>>
>>> When any new technology arrives, the debate veers toward the best- 
>>> and worst-case scenarios, the big dreams and the big fears. Gene 
>>> drives are going to cure malaria. Gene drives are going to become 
>>> bioweapons. That's our nature. But it's easy to forget how rarely 
>>> the extremes come to be.
>>>
>>> The real test will be after we have a few minor successes 
>>> controlling diseases or agricultural pests with gene drive. Suddenly 
>>> we will have one of the greatest hammers ever invented, and we will 
>>> go looking for nails. Every fast-reproducing plant or animal whose 
>>> behavior we don't like will be a candidate for redesign. Cockroaches 
>>> that hate the scent of garbage. Poison ivy that doesn't cause a 
>>> rash. Fire ants with no fire. There are loose nails everywhere that 
>>> just need a few whacks to make our lives more comfortable.
>>>
>>> "Why not?" goes the counterargument. We've been hammering nature for 
>>> years. Pollution, habitat destruction, pesticides, insecticides, 
>>> greenhouse gases. Yale doesn't convene an ethics panel every time 
>>> somebody clear-cuts a forest or dynamites a reef to harvest the 
>>> fish. Why is it different once genes are involved?
>>>
>>> And yet it is.
>>>
>>> Anyone who's ever taken the time to hike to the pristine valley or 
>>> paddle to the uninhabited island knows the sublimity of finding 
>>> oneself in a place where the agenda is non-human. It's a reminder 
>>> that there are ways of being in the world that have little or 
>>> nothing to do with human ways, patterns of existence that get us out 
>>> of our own heads and expand the conversation of what it means to be 
>>> a quivering coil of DNA on the third planet from the sun. It's a 
>>> form of diversity, and every species is a kind of culture, a 
>>> cohesive and elegant web of quirks, predilections, and traditions.
>>>
>>> We've dammed Glen Canyon 
>>> <https://psmag.com/magazine/when-a-desert-pushes-back-against-human-engineering>. 
>>> We've littered Everest with ropes and oxygen tanks. Our pawmarks are 
>>> all over even the wildest places. But we have yet to conquer the DNA 
>>> of wild things. For the time being, that frontier has been visited 
>>> by only a handful of early explorers.
>>>
>>> In deciding if we have the right to drive a gene through a species, 
>>> we might think of each genome as a national park, an untrammeled 
>>> space in a non-geographical dimension. A refuge from an increasingly 
>>> humanized world. I can hate the whine of a mosquito in my tent and 
>>> still revere the pristine landscape of its genome 
>>> <https://psmag.com/tag/genome>. Engineering that genome would be 
>>> like putting a road system through the Gates of the Arctic. There 
>>> would be some obvious benefits—and something less obvious would be 
>>> lost forever.
>>>
>>> With every new technology, we tend to shoot first and ask questions 
>>> later. It's a dynamic built into the DNA of our culture, which 
>>> rewards the intrepid individuals who plant their flag on the virgin 
>>> coast. Those ice-nine mosquitoes in their negative-pressure vault 
>>> may end up being hugely important. They may, in fact, be a gift. A 
>>> living metaphor of interconnectedness and of consequences, they may 
>>> force us to consider if the time has come to throw out the Age of 
>>> Exploration model and create a new system of science that rewards 
>>> wisdom over cleverness.
>>>
>>> That's a big ask, and it may seem absurd right now, as we survey the 
>>> vast genetic frontier stretching away before us. How could we not 
>>> poke around just a little? But we have a lot of experience with lost 
>>> frontiers at this point, so perhaps there's still time to ask what 
>>> we ought to do with this one. What if, after gazing from the decks 
>>> of their caravels at the towering forests and teeming estuaries of 
>>> the New World, the early explorers went back to their funders in 
>>> Europe and said: Sure, we could make the place safe and productive. 
>>> We could fill it with cities and farms and factories. But here's the 
>>> thing: It isn't bad the way it is. It's full of mysteries and other 
>>> ways of being. So ... this is going to sound crazy, but what if we 
>>> just left it alone?
>>>
>>> /A version of this story originally appeared in the June/July 2018 
>>> issue of /Pacific Standard/. //Subscribe now/ 
>>> <https://psmag.com/subscribe>/and get eight issues/year or 
>>> //purchase a single copy/ 
>>> <https://psmag.com/back-issue-subscriptions>/of the magazine./
>>>
>