{"id":151456,"date":"2020-01-13T12:00:55","date_gmt":"2020-01-13T12:00:55","guid":{"rendered":"https:\/\/www.transcend.org\/tms\/?p=151456"},"modified":"2020-01-11T09:53:57","modified_gmt":"2020-01-11T09:53:57","slug":"the-gene-drive-dilemma-we-can-alter-entire-species-but-should-we","status":"publish","type":"post","link":"https:\/\/www.transcend.org\/tms\/2020\/01\/the-gene-drive-dilemma-we-can-alter-entire-species-but-should-we\/","title":{"rendered":"The Gene Drive Dilemma: We Can Alter Entire Species, but Should We?"},"content":{"rendered":"

A new genetic engineering technology could help eliminate malaria and stave off extinctions \u2014 if humanity decides to unleash it.<\/em><\/p><\/blockquote>\n

\"\"<\/a>

A Drosophila melanogaster fruit fly engineered with a gene drive that caused it to have red fluorescent eyes.
Craig Cutler for The New York Times<\/p><\/div>\n

8 Jan 2020 – <\/em>One early summer evening in 2018, the biologist Anthony James drove from his office at the University of California, Irvine, to the headquarters of the Creative Artists Agency, a sleek glass-and-steel high-rise in Los Angeles. There, roughly 200 writers, directors and producers \u2014 many of them involved in the making of science-and-technology thrillers \u2014 were gathered for an event called Science Speed Dating, where James and other scientists would explain their work. The sessions were organized, James told me, \u201cin hopes of getting the facts at least somewhat straight.\u201d<\/p>\n

Attendees were assigned to different groups, so each scientist had just seven minutes to describe his or her work to one group before running to the next room and starting over. \u201cThere were a lot of stairs, so I would get really out of breath,\u201d James recalled. \u201cI would arrive panting.\u201d He also felt a bit overwhelmed. There were executives in expensive suits, young men and women looking unaccountably dressy in ripped jeans and, according to James, a disconcerting number of people wearing hats. Few, if any, had a deep knowledge of genetics; one participant in particular kept referring to \u201cthe dark genome,\u201d as though that were a thing. \u201cI had to tell him, \u2018Real geneticists don\u2019t usually talk that way,\u2019\u2009\u201d James said.<\/p>\n

James began his presentation with a brief overview of mosquito-borne diseases like malaria and Zika. Then he turned cautiously to talking about his own area of scientific expertise: an obscure but powerful invention known as a gene drive. James began by noting that two brown-eyed human parents can sometimes produce a blue-eyed child, though only if both parents carry a copy of the recessive gene. A gene drive, he explained, was a tool that in some species could turn such events into a near certainty. For one thing, it guaranteed that a particular gene would be inherited, even if only one parent had it. And it would automatically insert the chosen gene into both copies of the offspring\u2019s DNA, effectively turning a recessive trait into a dominant one. That alone, James explained, \u201clets you change the odds, so you get blue eyes 99 percent of the time.\u201d<\/p>\n

What made the gene drive truly strange and remarkable, though, was that it didn\u2019t stop with one set of offspring. Generation after generation, it would relentlessly copy and paste the gene it carried, until it was present in every descendant. \u201cFor most of the people in the room, you could tell it was the first they\u2019d heard of this,\u201d James recalled. \u201cYou could see their eyes getting big.\u201d<\/p>\n

This mattered, James explained, because it allowed you to change not just a single creature but \u2014 potentially \u2014 an entire population, and quickly. A few months after the technique was discovered in 2014, James engineered two mosquitoes to carry a gene drive that was tied to a gene for red fluorescent color that would target the mosquitoes\u2019 eyes. He then put each into a box with 30 ordinary purple-eyed mosquitoes. As the mosquitoes bred, they produced offspring: roughly 3,900 after two generations. (Mosquitoes lay a lot of eggs.) Under the normal rules of inheritance, there should have been an equal number of red-eyed and purple-eyed mosquitoes. Instead, when James opened the boxes to check on the offspring, all but 25 of the 3,900 mosquitoes had red eyes.<\/p>\n

Leigh Dana Jackson, a producer who was adapting a fantasy novel called \u201cThe Fifth Season\u201d for television, was one of the people who saw James\u2019s talk. \u201cI was fascinated by the fact that this was already real,\u201d he told me. It wasn\u2019t hard to imagine the Hollywood version of the gene-drive story: the rogue scientist determined to destroy global agriculture by breeding an unstoppable army of insects (working title: \u201cThe Plague\u201d); the corrupt corporate titan who, warned that gene drives can mutate wildly, silences the researcher, determined to see a return on his investment.<\/p>\n

So far, at least, the reality is less lurid. Gene drives have yet to be tested outside the lab, and even the most developed project to date \u2014 the anti-malarial gene drive in Anopheles mosquitoes \u2014 won\u2019t be widely available for at least another five years. But many scientists and public-health experts believe that the benefits could be significant. Besides combating malaria, gene drives could be used to alter, or even eliminate, other disease-causing insects, from the sand flies that transmit leishmaniasis to ticks that carry Lyme disease in the United States. (Because the spread of a trait happens over generations, a gene drive works best in species that reproduce quickly, like insects and rodents, rather than in, say, elephants and people.) They could also be used to protect endangered species. In the Gal\u00e1pagos, environmental groups like Island Conservation and the International Union for Conservation of Nature have explored using an \u201call-male\u201d gene drive \u2014 one that results in only male offspring \u2014 to eliminate the rats that are decimating the native bird and turtle populations, which are currently managed with poisoned bait. And among agricultural researchers, gene drives have been floated as a strategy for combating invasive crop pests<\/a>, like the spotted-wing fruit fly, without pesticides.<\/p>\n

For now, though, much of the potential of gene drives is still highly speculative, and there are an appreciable number of unknowns. In a cautiously supportive 2016 report<\/a>, the National Academy of Sciences warned that \u201cconsiderable gaps in knowledge\u201d remain around gene drives\u2019 ecological and evolutionary impacts. Could a gene drive stop one virus only to open the way for another, more virulent one? Could it jump from one species to a related one? What would be the environmental effects, if any, of altering the genes of entire species? How about eliminating a species entirely?<\/p>\n

For the speed daters, at least, those questions seemed to resonate. \u201cYou\u2019re thinking, O.K., if you\u2019re talking about a benevolent scientist using this, great,\u201d Jackson told me later. \u201cBut what about the alternative?\u201d During the Q. and A. session afterward, Jackson recalled, one attendee seemed especially alarmed, pressing James about how gene drives could be used in the hands of an unscrupulous foreign power. \u201cHe was the Jeff Goldblum character!\u201d Jackson joked.<\/p>\n

Hollywood, of course, isn\u2019t a precise litmus test for how a new technology is likely to be received by the public. But it\u2019s also not a bad approximation. Like screenwriters, most of us tend to gravitate toward the more extreme examples of a technology\u2019s potential, its ability to save the world or to destroy it. Gene drives seem almost tailor-made to tap into our worst fears: a powerful, invisible technology that spreads of its own accord, carrying out a fundamental transformation of nature. It\u2019s a situation that practically invites us to imagine evil corporations on the move, or secret military experiments running amok.<\/p>\n

As Alta Charo, a professor of law and bioethics at the University of Wisconsin, Madison, says of our genetic-engineering capability, \u201cAt a very instinctive level, there\u2019s a sense that these are things humans are not supposed to be doing.\u201d She went on: \u201cIn the years when gene drives weren\u2019t very effective, they also weren\u2019t very risky. It\u2019s a funny situation: When the technology is weak, you want to make it better. But when that happens, suddenly all these things you were imagining actually become possible. You can make that new animal, or you can wipe out that whole species. And if doing that turns out to have been a bad idea, it means you\u2019re going to have to deal with the consequences.\u201d<\/p>\n

One paradox of scientific<\/strong> breakthroughs is that they can seem at once flukish and inevitable. Researchers may toil incrementally for decades, unsure whether their work will ever lead to anything, only to find that they have suddenly developed a technology that raises all kinds of real-world questions to which no one has the answers.<\/p>\n

\"\"<\/a>

Three Drosophila melanogaster fruit flies engineered to carry a gene drive. The blue-eyed fly is an early attempt to study the use of a gene drive to create sweeping changes in a fly\u2019s DNA. Craig Cutler for The New York Times<\/p><\/div>\n

Gene drives emerged in just this way: Malaria researchers spent almost two decades trying to create gene drives with the aim of curbing disease, but no one was able to make them work very well. In his 10 years of attempts, James managed to increase the chance that a trait would be inherited by just 1 or 2 percent. Then, almost by chance, a new development transformed gene drives from a backwater science into a vanguard technology.<\/p>\n

In 2014, Valentino Gantz, a 30-year-old graduate student in biological sciences at the University of California, San Diego, was struggling to finish his thesis \u2014 an abstruse project about wing development in flies. Fruit flies typically have five large veins in their wings, but those with a particular genetic mutation will grow only four. Gantz had spent six months trying to see if the gene controlling the missing vein in one species of fly would do something similar in another.<\/p>\n

The project wasn\u2019t going very well. Genetic engineering is finicky work. Gantz started by fabricating a gene that caused the mutation for the missing vein; then he used a hair-thin glass needle to inject that into fly eggs, each the size of a grain of sand. The process worked, according to Gantz, roughly one time in a hundred. Even then, the resulting fly got only a single copy of the defective gene, and it took two to produce the missing vein. Because the gene was recessive, moreover, there was no way to tell just by looking which adult fly received it. Gantz\u2019s only option was to blindly engineer, and crossbreed, scores of flies, in hopes that two carrying the recessive mutation would eventually find each other and mate. But so far, despite hundreds of hours of work, Gantz had failed to generate even a single mutated fly.<\/p>\n

Then he had a radical idea. Gene editing relies on a tool called Crispr, which is itself a gene, originally found in bacteria. With some modifications, Crispr can be used to cut and paste pieces of DNA almost like a word processor. Gantz decided to use Crispr to insert not just a particular altered gene but also a copy of the Crispr editing tool itself: The two would be tied together. This created a kind of serial copy-and-paste function; the altered gene would be inserted into both copies of the DNA, rather than just one, effectively turning a recessive trait, like a missing vein, into a dominant one.<\/p>\n

The ability to generate double-recessives would have been a valuable lab tool in itself. But there was more. Put engineered DNA into most cells \u2014 skin cells, brain cells and so on \u2014 and it will create a one-time change in the individual who receives those cells. The exception is if the altered DNA is put into a germ cell: the cells that turn into sperm and eggs. Gantz and his thesis adviser, Ethan Bier, a professor of cell and developmental biology at U.C. San Diego, decided to try putting the Crispr editing machinery into a germ cell, along with the gene it was originally tied to. This, they hoped, would cause it to copy itself relentlessly into every egg a fly laid, essentially guaranteeing that a trait would be inherited and keep spreading with each generation.<\/p>\n

Scientific research is full of tantalizing ideas that don\u2019t pan out, and Gantz and Bier suspected that this might be one of them. \u201cI would say pretty much everyone assumed it wasn\u2019t going to work,\u201d Gantz told me. \u201cThe feeling was more like, \u2018Hey, why not try it?\u2019\u2009\u201d<\/p>\n

Gantz bred a round of fruit flies that had been engineered to carry both the Crispr machinery and a single copy of a recessive gene for yellow coloration. As the first batch was maturing, Gantz peered into the vials, only to see what appeared to be ordinary brown flies. \u201cI told Ethan, \u2018It didn\u2019t work,\u2019\u2009\u201d Gantz recalled. \u201cI was really crushed.\u201d Bier advised him to wait a bit longer, to let the pupae develop. When Gantz looked again the next morning, he saw one fly that was yellow, and then another, and another. \u201cThat\u2019s when I started jumping,\u201d he told me.<\/p>\n

It still wasn\u2019t clear, though, whether the copy-and-paste process would continue in the flies\u2019 offspring, so Gantz prepared a second round of flies, made by breeding the first-generation yellow flies with ordinary brown ones. At the same time, he and Bier began writing a paper on their discovery<\/a>, with a plan to add the inheritance results at the last minute if the experiment ended up working out.<\/p>\n

The second generation of flies was due to mature on Dec. 28, and as the date approached, Bier and Gantz spent hours discussing the possible results. On Christmas Day, Bier invited Gantz to come over to his house for lunch. The two talked for most of the day, hashing out details related to the paper and wrestling with the ethical and safety issues that their breakthrough might raise. \u201cThat afternoon, we went through all the worries,\u201d Gantz recalled. What would happen, for instance, if some of the engineered flies got out and began spreading their mutation in the wild? There was also the question of whether such a tool could be used as a weapon \u2014 say by sabotaging the pollinators that support agriculture, or by altering the genes of innocuous wild insects so they could transmit disease. \u201cAt one point, we were thinking, Should we even publish this?\u201d Gantz remembered.<\/p>\n

As a check, Bier phoned another scientist, Hugo Bellen, who is well known for his work in fruit-fly genetics. As Gantz recalled it, Bellen told Bier, \u201c\u2009\u2018When you have a result, it\u2019s unethical not<\/em> to publish it.\u2019 So we decided to go ahead.\u201d<\/p>\n

Read more about Crispr and the possibilities of gene editing technologies.<\/a> <\/em><\/strong><\/p><\/blockquote>\n

Gene drives are<\/strong> the latest in a string of new genetic tools designed to help us improve our environment or our lives. But while we\u2019ve become adept at making technological breakthroughs, we\u2019ve mostly failed to create real forums for talking about them. \u201cThere are big philosophical questions that have been raised at various points but never answered,\u201d says Ben Hurlbut, a historian of science at Arizona State University. \u201cLike, What does a good future look like, and who gets to decide?\u201d<\/p>\n

With populism growing and fewer people willing to trust the judgment of regulators and scientists, the rhetoric around complex innovations has become increasingly polarized, with both sides stuck fighting a high-stakes battle for public opinion. Many scientists I spoke to cited the introduction of genetically modified foods as a turning point; the backlash effectively crippled the field. \u201cThe level of organized skepticism around genetically engineered foods was a whole new phase,\u201d Charo told me. For one thing, the process \u2014 which involved, for example, grafting a flounder gene into a tomato to make it frost-resistant \u2014 struck most people as vaguely creepy. Perhaps more distressing, though, was that the technology was controlled primarily by the global agricultural giant Monsanto, which not only held the patents to the new seeds but also quickly began an aggressive global marketing campaign to persuade farmers to switch to its trademarked seed lines.<\/p>\n

\"\"<\/a>

An Anopheles stephensi mosquito equipped with a gene drive and engineered so that it cannot transmit malaria.
Craig Cutler for The New York Times<\/p><\/div>\n

\u201cWith genetically engineered foods, in the earliest years, Monsanto really set the context,\u201d Charo says. \u201cAnd it was a mess. Their financial interest in the intellectual property and their regulatory interest in making sure these products were able to come to market got conflated with the science, so nobody was willing to trust the kind of research they were doing. The end result was that all G.M.O. research got tainted.\u201d<\/p>\n

Todd Kuiken, a researcher at the Genetic Engineering and Society Center at North Carolina State University, says that \u201cit was basically a lesson in how not to do things.\u201d But, he pointed out, the \u201cMonsanto Mistake\u201d also alerted researchers to the need for a more transparent and collaborative approach. With gene drives, groups like Target Malaria, a nonprofit research consortium administered by Imperial College, London, and funded in part by the Bill and Melinda Gates Foundation, have stressed that the deployment of modified mosquitoes in Africa should be \u201can African decision.\u201d Local and national governments would work with regulatory organizations like the United Nations and the World Health Organization, which have proposed frameworks for testing and releasing genetically modified mosquitoes. In the United States, recent developments in genetics, including gene drives, have created a boom market for ethicists, as well as for so-called engagement specialists, who have the unenviable problem of figuring out how to get people to be genuinely thoughtful about a confusing and highly technical area of research.<\/p>\n

So far, at least, the process has been rocky. At the United Nations Convention on Biological Diversity in Sharm el Sheikh, Egypt, in November 2018, a coalition of activist groups compared gene drives to the atomic bomb and accused researchers of using malaria as a Trojan horse to cover up the development of agricultural gene drives for corporate profit. Scientists working with the Gates Foundation, in turn, accused activists of trying to hijack the meeting and dismissed calls for a global research moratorium. \u201cThe report I\u2019ve had so far is that there\u2019s been a lot of yelling,\u201d one policy expert told me glumly.<\/p>\n

Natalie Kofler, who attended the conference and runs a global initiative for the responsible development of genetic technologies, described the atmosphere as \u201cpretty raw.\u201d Kofler told me that nongovernmental organizations like Target Malaria tend to be dismissive of activists\u2019 claims, which in turn feeds into the activists\u2019 sense of not being heard. \u201cThere\u2019s a general idea that these groups aren\u2019t scientific, so their arguments are less valid,\u201d she says. On the other hand, she went on, some activist groups have started behaving in ways that are deliberately inflammatory. A handful of small NGOs, collectively known as SynBioWatch, have taken to describing gene-drive researchers as a cabal and using tactics more typical of political misinformation campaigns (filing FOIA requests for thousands of emails, then publishing the result \u2014 a banal mix of research chitchat and conference planning \u2014 framed as a \u201ctrove\u201d of hidden evidence). Several scientists I spoke with described feeling embattled; one had recently been subject to a public-information request for her university emails, filed by an activist who also made derogatory remarks about her and her child. Another described seeing online forums hijacked by groups seeking to conflate gene drives and G.M.O.s. Over the summer, a Canadian organization known as ETC Group released a deck of cards showing the potentially alarming uses to which gene drives could be put. One card featured a cartoon image of a gene-drive honeybee that could supposedly be controlled with a beam of light; another showed an aggressive-looking anti-malarial mosquito with the vague but ominous warning, \u201cCovers up the real story of gene drives.\u201d<\/p>\n

Jim Thomas, a co-executive director for ETC Group, acknowledges that the honeybee example was highly speculative, though he noted that someone filed a patent for such an idea. But he defends it as a necessary counter to what he regards as a misleading focus on \u201chigh-profile savior applications\u201d like anti-malarial and conservation efforts. \u201cThe discussion from the beginning has been framed around those best-case scenarios,\u201d Thomas says. \u201cAnd there\u2019s a sort of unwillingness to discuss where this technology will go from there. Our sense, at least, is that this is an agricultural technology: that it will have its biggest application in agriculture and the food system. And it\u2019s also a technology that\u2019s of interest to the military. But there\u2019s no discussion about that.\u201d<\/p>\n

Playing to fears around worst-case scenarios can be a powerful tactic. Dietram Scheufele, who studies scientific and political communication at the University of Wisconsin, Madison, says that scientists are generally much worse than activist groups at shaping public opinion, in part because they tend to rely on logical reasoning and facts, while activist groups are more likely to tap into unconscious values and emotions \u2014 like using the term \u201cFrankenfoods\u201d to describe G.M.O.s. \u201cIt\u2019s really a brilliant bit of framing,\u201d Scheufele says. \u201cThe message is: \u2018Science is putting together two things that don\u2019t belong together. And that stuff gets out of control and out of the lab, and it\u2019s all because of scientific hubris.\u2019 And then you have the scientific response, which is someone saying: \u2018Actually, that\u2019s not quite right. Let me explain this complicated thing to you. … \u2019\u2009\u201d<\/p>\n

For the layperson, sorting through such disparate viewpoints can be confounding. \u201cIf you talk to most of the members and delegates at the conference, they haven\u2019t even heard of gene drives before now,\u201d Kuiken says. \u201cAnd then they hear people saying that we\u2019re either going to end malaria with this or else it\u2019s going to destroy the planet and hand control to Big Ag. I mean, what do you do with that?\u201d<\/p>\n

The first place a gene<\/strong> drive will most likely be used is the landlocked West African country Burkina Faso. Abdoulaye Diabat\u00e9 is a vector biologist and the head of the medical entomology laboratory at the Institut de Recherche en Sciences de la Sant\u00e9, in the country\u2019s second-largest city, Bobo-Dioulasso. He told me that in Burkina Faso, malaria-carrying mosquitoes were already resistant to the pyrethyroid insecticide used on bed nets and that disease rates were beginning to climb. \u201cIf you look at the insecticide-resistance profile of Africa, you\u2019ll see that the heart of it is in West Africa,\u201d Diabat\u00e9 said when I spoke to him by phone last spring. \u201cSo when we were approached by Imperial College in 2012 about anti-malarial gene-drive mosquitoes, we thought, This is really something fantastic, really relevant for us, and we need to get involved in it.\u201d<\/p>\n

In collaboration with Target Malaria, Diabat\u00e9\u2019s team conducted research<\/a> and also began a gradual process of outreach and education. \u201cWe have tried to reach out to a lot<\/em> of people,\u201d Diabat\u00e9 said. \u201cFrom the grass-roots level, at the villages, to the top levels of the government \u2014 as well as journalists, other scientists, the religious community, the regional authorities.\u201d<\/p>\n

The person in charge of outreach in the villages, Dr. L\u00e9a Par\u00e9 To\u00e9, said the group began simply by taking stock. \u201cWe did a kind of baseline investigation,\u201d she told me. \u201cWhat\u2019s the level of understanding of malaria? And we found that most people knew that malaria is transmitted by mosquitoes. But they also thought that rain can transmit malaria, or that it was caused by sweet food. So there was some confusion.\u201d<\/p>\n

Par\u00e9 To\u00e9 and Diabat\u00e9 began by explaining the biology of mosquitoes and walking residents through the lab\u2019s routine activities: collecting mosquitoes to study breeding patterns or measuring the species\u2019 range. \u201cWe also talked about the concept of research,\u201d Par\u00e9 To\u00e9 said, \u201cbecause we needed to explain this idea to the community. It was new.\u201d<\/p>\n

The primary local language, Dioula, had no word for \u201cgene\u201d or \u201cgenetically modified,\u201d so Par\u00e9 To\u00e9\u2019s team also worked with linguists to develop a lexicon of terms. As Par\u00e9 To\u00e9 described it to me, the group began by canvassing residents. \u201cWe would say, \u2018Do you have a word in the local language that can explain these ideas?\u2019 Then they come back with some words.\u201d<\/p>\n

\"\"<\/a>

Valentino Gantz, who invented the gene-drive technique with Ethan Bier, in his lab at the University of California, San Diego.
Craig Cutler for The New York Times<\/p><\/div>\n

Afterward, the group hired a linguist, Dr. Daouda Traor\u00e9, to develop a glossary, which they checked against their own list and then field-tested. \u201cFor us, the most important thing was not to find a Dioulan term that was the equivalent of a particular phrase, like \u2018genetic modification,\u2019 but to find a way to explain what the concept actually means,\u201d Traor\u00e9 added. \u201cThe whole process took quite some time.\u201d<\/p>\n

At the same time, Target Malaria began working with the country\u2019s regulatory agencies, including the National Biosafety Agency and the Ministry of the Environment, to create a staged approvals process. The first step, in 2016, was importing 5,000 mosquito eggs modified so that the males were sterile but did not carry a gene drive. (A release of sterile mosquitoes took place in July.) Assuming the current process continues, the first gene-drive mosquitoes would eventually be brought in from Italy \u2014 Burkina Faso does not have the lab facilities that would allow scientists to securely develop gene-drive mosquitoes \u2014 then further bred and tested in the lab to see, among other things, how effectively they can compete and mate with the endemic strains. (The main malaria-carrying mosquito in West Africa is Anopheles gambiae, but lab versions of the species are genetically different from wild Anopheles.)<\/p>\n

Even so, Delphine Thizy, who acts as a liaison between Target Malaria and communities in Burkina Faso, estimates that it will be at least five years before the process to bring gene-drive mosquitoes to Africa can begin, and most likely a decade before anti-malarial gene-drive mosquitoes become available for any country to use (following approval by the World Health Organization). But she also cautions that the process could be much slower and that \u201cif people reject it, it might just stop.\u201d<\/p>\n

While most African countries remain opposed to G.M.O. crops \u2014 in part because of their connection to multinational corporations \u2014 support for gene-drive technology to counter disease has so far remained high. (At the African Union summit meeting in 2016, the assembly established a panel to explore the use of emerging technologies, including the use of gene drives to eliminate malaria.) According to Hudu Mogtari, who works on regulatory support for emerging technologies for the pan-national African Union Development Agency, one important shift has been the collaboration between African and European scientists in the development of the technology, which has helped dispel accusations that Target Malaria is practicing \u201ccolonial medicine\u201d and brainwashing villagers and African leaders \u2014 arguments that he says are primarily being pushed by Western anti-G.M.O. groups. \u201cThis is not something homegrown \u2014 that\u2019s very obvious,\u201d he told me. \u201cThese are professional activists.\u201d<\/p>\n

In August 2018, AUDA also started a program designed to facilitate discussion around an anti-malarial gene drive, with the goal of helping experts and ministers from different West African countries create shared guidelines for the technology. \u201cWe are dealing with a living modified organism that can cross borders,\u201d Mogtari said dryly. \u201cSo we don\u2019t have answers to some of the concerns that are being raised. But at least this platform would allow those concerns to be discussed.\u201d<\/p>\n

In the meantime, he added, the agency has started hosting information sessions for scientists from other fields, whom he describes as influential but often uninformed. \u201cWe have radio stations, TV stations, that will call up a scientist and say: \u2018We have heard about this gene-drive technology. What do you say?\u2019 But this may be a professor in a completely different field who has nothing to do with genetics or genome editing! And instead of being honest and saying, \u2018I don\u2019t know,\u2019 they will talk. And whatever this person says, that will determine what people think. Because the lay public\u2019s view is, once you say the person is a scientist, they must know everything.\u201d<\/p>\n

At the information sessions, Mogtari recalled, questions have ranged from comparatively informed (Would eliminating Anopheles affect the food chain?) to more absurd (Would modified mosquitoes suddenly become able to transmit H.I.V.?). When I mentioned this to Dr. Diabat\u00e9, he laughed. \u201cPeople don\u2019t have a really good understanding of the biology of mosquitoes, and the malaria parasite, and how the interaction between these two allows a mosquito to transmit a certain disease,\u201d he said. \u201cBut these are concerns that people have very often, so you have to address it.\u201d<\/p>\n

Mogtari agreed. \u201cUsually when people attend the meetings for the first time, you can tell from their comments,\u201d he told me. \u201cIt\u2019s things they have picked up from the media. About how mosquitoes will grow to the size of helicopters. Or how you can have something that\u2019s half human, half mosquito. And it\u2019s good, because as we hold our meetings, you really see the change. People who are vehemently against this, when the facts are given to them, they change their minds completely. And, you know, it\u2019s gratifying, when you go through that process. But there also are a lot more people out there. Not everyone can come to these meetings.\u201d<\/p>\n

How will technology transform humanity?<\/a><\/em><\/strong><\/p><\/blockquote>\n

In his book<\/strong> \u201cThe Wizard and the Prophet,\u201d the journalist Charles C. Mann writes that there are two kinds of people: wizards, who see science and technology as our best hope for human survival, and prophets, who believe that the human race will survive only if we can limit our growth and live simply, reversing the changes wrought by modern agriculture, development and consumption.<\/p>\n

In practice, most of us are a bit of both. We want cars and airplanes, laptops and electric lights, cheap food and medications that work. Our lives, we understand, are far better than they would have been 200 years ago, let alone 400. Despite all this, it\u2019s hard not to worry about the cost. Deforestation, climate change, entire species gone from the earth \u2014 it reads like a catalog of our sins, the price of our progress. More than that, we suspect that it will be our undoing.<\/p>\n

This seems especially true at a time when a single rogue scientist has the power to upend years of careful constraint. While the Convention on Biological Diversity was underway, He Jiankui, a researcher at the Southern University of Science and Technology in China, announced that nine months earlier, he had used the gene-editing technique Crispr to alter embryos<\/a>, which he then implanted in the womb of a woman. That woman gave birth to twin girls, creating the world\u2019s first genetically edited babies. The news caused an uproar, in part because He created the embryos despite an agreement among researchers that germ-line editing in human embryos was still too risky to be used outside the lab. The director of the National Institutes of Health, Dr. Francis S. Collins, issued a scathing statement citing the \u201cdeeply disturbing willingness by Dr. He and his team to flout international ethical norms.\u201d Even though He was later sentenced to three years in prison, the genie was out of the bottle.<\/p>\n

In practice, a working gene drive is harder to make, and to deploy, than a single edited embryo. But the risk is clear: There are limits to the effectiveness of scientific self-policing. As Jim Thomas of ETC Group says: \u201cSo far, all the proposals around gene drives are things like voluntary ethics codes and agreements between funders. They\u2019re not binding in any way, so to what extent they can be enforced and who would be liable in the event of problem \u2014 there\u2019s none of that.\u201d<\/p>\n

\"\"<\/a>

An Anopheles stephensi larva with fluorescence from a gene drive, in the lab of the biologist Anthony James at the University of California Irvine. Craig Cutler for The New York Times<\/p><\/div>\n

Since the United Nations convention, Kofler and others working on gene-drive regulation have emphasized the need for community involvement and \u201cinformed consent\u201d \u2014 both as a moral good (people deserve to have a say in decisions that will affect them) and for practical reasons (people are more likely to reject a technology if it feels imposed from the outside). Both sides also support the creation of a neutral global regulatory system: something trusted, transparent and enforceable, with punitive liabilities. But it would most likely be hard to agree on what a \u201cneutral\u201d system should look like. As Thomas sees it, the global institutions that are already engaged in the discussion around gene drives \u2014 the United Nations, the World Health Organization \u2014 are unfairly influenced by scientists and gene-drive proponents. \u201cWe need to move away from an expert-o-cratic process,\u201d he told me.<\/p>\n

But it\u2019s hard not to feel nervous about a regulatory system in which lay and expert opinion is given equal weight. Do we really want the process of scientific research and technology to become democratic \u2014 one in which fundamental decisions about public health, like vaccines and vector-control measures, are put up for a vote? It is difficult for most of us to sift through a welter of complex facts and claims, however much we may push for \u201cinformed consent.\u201d \u201cWhat does \u2018public engagement\u2019 really mean in this context?\u201d says Elizabeth Heitman, an ethicist at the University of Texas Southwestern who has studied the public reaction to emerging technologies. \u201cIt means talking about a developing science with a lot of uncertainties and a really steep learning curve.\u201d<\/p>\n

Like most of the researchers I spoke with, James regards the uncertainties around gene drives more as questions to be answered than as perilous or unknowable unknowns. \u201cWhen I\u2019ve talked with people about these things, they usually say, \u2018But you don\u2019t know what\u2019s going to happen!\u2019\u2009\u201d James told me. \u201cBut that\u2019s why you do experiments. That\u2019s why you do them for years.\u201d<\/p>\n

If this attitude sounds slightly wishful \u2014 no lab experiment can capture every possible interaction or effect of a gene drive in the wild \u2014 it also seems to reflect something more fundamental: the gap between how scientists and laypeople think about efficacy and risk. James told me that he grew up as one of 10 children in a family that was often financially strapped but also intellectually rigorous. His mother, who grew up in Minnesota, studied library science. His father was a mathematician and aerospace engineer for North American Rockwell, where, among other things, he helped design rocket engines for the Apollo spacecraft. As an interracial family in the 1950s \u2014 James\u2019s father was black, his mother white \u2014 \u201cthere wasn\u2019t a lot of bowing to institutional doctrines,\u201d he told me. Instead, the children absorbed a mix of pragmatic calculation and logical reasoning. \u201cWith that many kids, you had to be pretty empirical in your decision-making.\u201d<\/p>\n

In college, James decided to major in biology and began working in a lab that was trying to find the genetic roots of development by studying abnormalities in fruit flies \u2014 an early version of Gantz\u2019s research. At the time, James recalled, he had a roommate whose huge, shaggy dog became infested with fleas. When James complained, the roommate suggested making a collar of eucalyptus buds, which he argued would function as a natural repellent. James had a better idea. \u201cI thought, I can fix this in half an hour,\u201d he recalled. The lab\u2019s stores included a bottle of the pesticide malathion, and that evening he brought a small amount of the powder back to the room \u201cand sort of sprinkled it around.\u201d By the next morning, the fleas were gone.<\/p>\n

When James told me this story, I wondered if he understood how disturbingly incautious it made him seem. But as he went on, I realized this might not be a fair reading. As part of the same conversation, James mentioned that his great-grandmother, who was Creole, fled New Orleans in the late 1800s in order to escape a yellow-fever epidemic \u2014 one that would later kill more than one-tenth of the entire population of Memphis.<\/p>\n

At the time, yellow fever was thought to be an infection that was carried on dirty clothes and spread through physical contact. A few years later, a military physician, Maj. Walter Reed, and a Cuban physician and scientist, Carlos Finlay, proved that Aedes aegypti mosquitoes were causing the outbreaks. The result was a sweeping eradication campaign. Lakes and swamps were drained. Those that remained were coated with oil or pesticides that killed mosquito larvae. The project saved thousands of lives and transformed the United States. Would doing the same to the forests and savannas of Africa be more or less invasive than using a gene drive to eliminate Anopheles mosquitoes?<\/p>\n

With its ability to create powerful changes invisibly, genetic engineering can feel eerie to even the most rational of us. Brain-imaging studies of people who strongly oppose genetically modified foods show that simply imagining, say, eating a G.M.O. tomato will cause some people to have a powerful disgust response, as if they were being asked to eat worms. When I mentioned this to James, he seemed unsurprised. \u201cPeople are sort of weird about genes,\u201d he said with a shrug. \u201cThere\u2019s a visceral fear. And it\u2019s hard to talk people out of those sorts of fears.\u201d<\/p>\n

At my request, James led me down to the insectary where his lab at U.C. Irvine breeds genetically engineered mosquitoes to study, for example, whether they can be made malaria-resistant. Because James didn\u2019t work with the malaria parasite itself \u2014 he outsourced that part of the research to a containment facility in San Diego \u2014 the insectary itself was comparatively low-security, but it still had multiple doors, rooms designed to have negative pressure and an industrial-strength plastic curtain of the kind you see on loading docks.<\/p>\n

For all that, the facility felt unexpectedly homely: just four small rooms with wire shelves and containers for the different mosquito crosses \u2014 in this case, movie-theater popcorn tubs sealed at the top, then retrofitted using a piece of mosquito net stapled over a hole in the bucket\u2019s side. (James\u2019s lab goes through a lot of containers, and these were the cheapest his lab tech could find.) The effect was incongruously cheery, like a grade-school science project in some wacky high-tech future. On each tub, the netting was flanked by the word \u201cPopcorn!\u201d on a bright yellow background.<\/p>\n

I asked James if I could see a mosquito carrying a gene drive, and he pointed to one of the buckets. But when I peered in, I couldn\u2019t help feeling disappointed. Although I knew that a gene drive wouldn\u2019t be visible \u2014 it was just a short stretch of DNA, after all \u2014 the TV-watching part of me had still expected something. Instead, I saw what appeared to be an ordinary mosquito \u2014 which, after a moment, felt almost more alarming.<\/p>\n

Among malaria researchers, the main worry isn\u2019t that gene drives will be too powerful but that they won\u2019t be powerful enough. For one thing, it\u2019s unclear whether a gene drive \u2014 which can rapidly change the offspring of hundreds of mosquitoes held captive in a cage \u2014 will do the same in the real world. \u201cIn the wild, mosquitoes are very dispersed,\u201d James told me. \u201cAnd it\u2019s not clear how much they\u2019re interacting with each other \u2014 there are mountains, rivers. It\u2019s so stochastic. If the one male in that area dies, that\u2019s it for that area.\u201d<\/p>\n

\u2018How do you regulate a technology that\u2019s undetectable, self-propagating and can fly?\u2019<\/em><\/strong><\/p><\/blockquote>\n

In the wild, even a small genetic change almost always incurs what scientists call a fitness cost: Either an engineered insect won\u2019t be as hardy as its wild peers or it won\u2019t be an attractive mate. (Simply changing the fur color of a fruit fly from brown to yellow, as Gantz did, for instance, reduces its chance of mating by 99 percent.) More radical changes, like creating a mosquito that produces only male offspring, are likely to face even more resistance. Nature is good at circumventing anything that thwarts procreation.<\/p>\n

Delphine Thizy of Target Malaria told me that because of these factors, the foundation didn\u2019t expect gene drives to actually eliminate malaria. \u201cThe goal is really just to deplete the mosquitoes from an area enough that the parasite-insect-human cycle collapses,\u201d she added. \u201cIf you look at all the obstacles \u2014 the physical obstacles, like geography, as well as the evolutionary pressures \u2014 it\u2019s more likely that even a really well-engineered gene drive won\u2019t spread as well as we\u2019d think.\u201d<\/p>\n

Current research suggests that the spread of gene drives is likely to vary from species to species, with some propagating slowly, if at all, and others more rapidly or widely. Research also suggests that gene drives stay confined to a single species rather than spreading into a related one through interbreeding. But it\u2019s not clear whether that will be true in all species or under all conditions. (Researchers are also working on a variety of containment strategies, including drives that stop working after a few generations.) And it\u2019s very hard to assess what the environmental impact of removing a species, or even altering one, might be. While ecosystems tend to be resilient \u2014 plenty of species have gone extinct already, and it hasn\u2019t led to a systemic collapse \u2014 they\u2019re also complicated and difficult to model. The only way to conclusively determine what happens when a species changes or vanishes may be to try it and see.<\/p>\n

Ethan Bier, who has become deeply involved with the technology since his and Valentino Gantz\u2019s breakthrough, emphasized that the many potential applications are likely to have extremely different benefits and risks. Malaria, he noted, is one of the strongest cases. Studies show that reducing or even eliminating the Anopheles mosquito is unlikely to have a significant environmental effect (few birds or animals rely on it as a food source), and as it is one of 3,500 mosquito species on the planet, its disappearance wouldn\u2019t appreciably dent the insect\u2019s overall diversity. And given that malaria kills hundreds of thousands of people a year, the argument for not using a gene drive would have to be unusually strong. Bier recalled one early conversation in which Gantz asked: \u201cImagine you could genetically engineer a mosquito that would prevent you from getting cancer. Would people still object to it?\u201d<\/p>\n

In conservation and agriculture, gene drives could also have a profound effect, with the potential both to save endangered species and to reduce the amount of pesticides currently in use. But these, too, carry risks. New Zealand has discussed using a gene drive<\/a> to eradicate the Australian brushtail possum, which preys on the nests of native birds and is currently controlled with poison traps. But should a few dozen Australian possums with an all-male gene drive be carried from New Zealand back to Australia, they could devastate the native possum population. Agricultural uses are even more fraught. If a corporation wants to use a gene drive to \u201ccancel out\u201d the herbicide resistance that some weeds have now developed, would that really benefit the planet \u2014 or just the corporation that can now sell more of the herbicide that caused the problem in the first place?<\/p>\n

In theory, figuring out how to answer these questions should be the province of the world\u2019s regulatory agencies, and most scientists agree that gene drives will need to be evaluated on a case-by-case basis, akin to how the Food and Drug Administration evaluates the safety of a new treatment or pharmaceutical. But regulating a technology that doesn\u2019t stop at the border of a country or a state is a new problem. Unlike a chemical pesticide, gene drives are inherently mobile \u2014 able to cross borders or potentially even oceans. And while some species, like the malaria-carrying Anopheles gambiae mosquito, exist only in sub-Saharan Africa, others, like the Norway rat, are virtually everywhere. As Kuiken put it: \u201cHow do you regulate a technology that\u2019s undetectable, self-propagating and can fly? If one community doesn\u2019t want it, does that mean that the other four or five communities around it aren\u2019t allowed to move forward? How do you set up an international governance regime that enables you to make those kinds of decisions? So far, I haven\u2019t seen any proposals that get us there.\u201d<\/p>\n

The United Nations and the International Union for Conservation of Nature have created working groups to study the problem and begin to hash out best practices around gene-drive use, though these may be difficult to enforce. A handful of countries have been more rigorous. In June 2018, the National Institute for Public Health and the Environment in the Netherlands passed legislation that included a detailed evaluation process<\/a> for any gene drive to be used outside the lab.<\/p>\n

So far, the United States has yet to take similar steps. Zach Adelman, an entomologist who works on gene drives at Texas A&M, told me that until recently federal agencies \u201cput their head in the sand\u201d around the question of gene drives. \u201cWe\u2019ve been trying to get the attention of regulators to say: \u2018Hey, we\u2019re developing this technology. Can we start to talk about how it might be regulated, and what we need to do, what we need to change?\u2019\u2009\u201d Adelman told me. \u201cAnd that got no traction for a long time.\u201d<\/p>\n

In the past year, the agencies finally began to act. Adelman says that the Department of Agriculture is now working to develop a risk-assessment process for agricultural gene drives, and the Environmental Protection Agency and the F.D.A. are also reportedly taking an interest. \u201cWe\u2019ve lost a few years, but now it\u2019s definitely on their radar,\u201d Adelman says. Still, the agencies\u2019 guidelines remain vague. \u201cFor now, people doing the work have been policing themselves,\u201d Adelman told me. \u201cWhich will work \u2014 right up until it doesn\u2019t.\u201d<\/p>\n

Is it O.K. to engineer the environment to fight climate change?<\/a><\/em><\/strong><\/p><\/blockquote>\n

As I drove back<\/strong> from James\u2019s lab, the sky was hazy. It was summer, and fires were burning in the mountains behind Los Angeles, filling the skies with smoke. In that moment, it seemed as if the prophets were right, and our relentless progression had irrevocably tipped the balance from innovation and growth to disaster and decline.<\/p>\n

Between the artificial-intelligence apocalypse and the designer-babies apocalypse and the actual apocalypse (melting glaciers, plastic in the oceans), it is often hard to escape the feeling that we are, increasingly, using technology to fix problems that technology itself has created. As bees die off because of pesticides, there\u2019s talk of using tiny drones to pollinate crops. Global warming is already generating plans for geoengineering: seeding the stratosphere with reflective particles to limit the sun or filling the ocean with crushed limestone to reduce its acidity. Such practices can feel like a high-tech version of introducing rabbits to keep down the weeds, and then foxes to keep down the rabbits. It\u2019s tempting to say we should just stop meddling. Nature, after all, is supposed to be natural. Should it become possible to alter wild species en masse, at a genetic level, how will that affect our idea \u2014 or, perhaps more accurate, our fantasy \u2014 of an unspoiled world? And what will it mean for our relationship to the other creatures on the planet?<\/p>\n

\u201cThis notion of permanently altering the genetics of an entire species \u2014 it goes against everything I was trained to think,\u201d says Kuiken, who served on the United Nations\u2019 technical experts committee for gene drives. \u201cWhat\u2019s hard to accept is that, at this point, it might end up being our best option. There\u2019s this kind of fantasy that we can go back, that we can restore some lost Eden. But the reality is that we aren\u2019t making those choices.\u201d<\/p>\n

And even if we could, would it make sense to do so? After all, the rise in antibiotic resistance doesn\u2019t mean that we shouldn\u2019t have invented antibiotics at all. Yet innovations inevitably change how we behave, and those changes have consequences. As Kuiken put it: \u201cYou kind of have to accept that we\u2019ve failed, societally. That we\u2019re going to continue to drive, to fly, to throw away plastic, to tear down the rainforest. And if we aren\u2019t going to solve the problems we\u2019ve created by regulating ourselves, it means that we\u2019re probably going to have to use technology \u2014 whether that\u2019s to save species, or human lives, or to make sure that certain plants or coral reefs survive climate change.\u201d<\/p>\n

Kuiken paused: \u201cThat\u2019s part of why all this is so hard. It\u2019s not just a question of whether or not we should use gene drives. It\u2019s about coming to grips with our failures.\u201d<\/p>\n

______________________________________________<\/p>\n

Related Coverage:<\/em><\/p>\n