The code breaker, p.23
The Code Breaker, page 23
Zayner now runs from his garage an online biohacking supply store, The ODIN, which creates and sells “kits and tools that allow anyone to make unique and usable organisms at home or in a lab.” Among its products, in addition to the frog-muscle kit, are a “DIY bacterial gene engineering CRISPR kit” ($169) and a “genetic engineering home lab kit” ($1,999).
Soon after Zayner started his business in 2016, he got an email from Harvard’s George Church. “I like the stuff you’re doing,” Church wrote. They chatted, eventually met, and Church became the “business and scientific advisor” to The ODIN. “I think George is a collector of interesting people,” Zayner says, correctly.3
Most of the biologists who work in academic labs are contemptuous of what they see as Zayner’s shoddy methods. “Josiah’s stunts demonstrate a reckless pursuit of publicity and a lack of scientific understanding,” says Kevin Doxzen, who works in Doudna’s lab. “Encouraging curiosity and inquiry within the public is a valuable pursuit, but selling kits that suggest you can engineer frogs in your kitchen, human cells in your living room, or bacteria in your garage attempts to simplify a technology that isn’t simple. It saddens me to imagine high school teachers spending their shrinking budgets on kits that simply don’t work.” Zayner dismisses such criticism as coming from academic scientists trying to protect their priesthood. “We put the DNA sequences and all of our data and methods for our kits online for everyone to judge.”4
* * *
The impromptu CRISPR procedure Zayner performed on himself at the San Francisco conference did not have a noticeable effect on the muscles of his somewhat scrawny body. That would have taken a prolonged series of treatments. But it did have an effect on the world of CRISPR regulation. By being the first person to try to edit his own DNA, he showed that the gene genie would someday be out of the bottle, which he insisted was a good thing.
Zayner wants to make the genetic engineering revolution as open and crowdsourced as the early digital revolution was, when coders like Linus Torvalds created the open-source operating system Linux and hackers like Steve Wozniak gathered at the Homebrew Computer Club and talked about liberating computers from the exclusive control of corporations and government institutions. Genetic engineering, he insists, is no harder than computer engineering. “I almost failed out of high school,” he says, “but I was able to learn how to do this stuff.” His dream is that millions of people around the world will take up amateur bioengineering. “We now all have this ability to program life,” he says. “If millions of people took it up, that would immediately change medicine and agriculture, contributing so much to the world. By demonstrating how easy CRISPR is, I want to inspire people to do that.”
Isn’t it dangerous, I ask, for everyone to have access to this technology? “No, it’s fucking exciting,” he counters. “No great technology has flourished until people had complete access to it.” He has a point. What truly caused the digital age to blossom was when computers became personal. It happened in the mid-1970s with the advent of the Altair and the Apple II, devices that democratized control of computing power. First hackers and then the rest of us got to play with our own computers and produce digital content. The digital revolution was kicked into an even higher orbit in the early 2000s with the birth of the smartphone. As Zayner says, “Once we have people doing biotechnology at home, like we did with computer programming, so many amazing things will be contributed.”5
Zayner will probably have his way. CRISPR technology is on the verge of becoming easy enough that it will not be confined to well-regulated labs. It will also be advanced by rebels and rogues on the far edge of the frontier. In this way it may follow the path of the digital revolution, much of which, from Linux to Wikipedia, was driven by crowdsourcing. In the digital realm, there isn’t a clear line separating amateur from professional coders. The same might soon be true of bioengineers.
Despite the dangers, there could be benefits if biotech followed this route. During a pandemic, it would be useful if societies could tap the biological wisdom and innovation of crowds. At the very least, it would be good to have citizens who could test themselves and their neighbors at home. Contact tracing and data collection could be crowdsourced. Today, there is a sharp line dividing officially sanctioned biologists from do-it-yourself hackers, but Josiah Zayner is dedicated to changing that. CRISPR and COVID could help him blur those lines.
Joseph Bondy-Denomy
CHAPTER 34 DARPA and Anti-CRISPR
Threat assessment
The possibility that CRISPR would be used by hackers or terrorists or foreign adversaries began to worry Doudna. She raised these concerns when she attended a 2014 conference where a researcher described how a virus could be engineered to carry CRISPR components into mice and edit a gene so that the mice would get lung cancer. A chill went through her. A tweak or a mistake in the guide could easily make it work in human lungs. At another conference a year later, she questioned a graduate student who had coauthored an article with Feng Zhang describing a similar CRISPR experiment that caused cancer in mice. These and other experiences led her to join an effort funded by the U.S. Defense Department to find ways to protect against the misuse of CRISPR.1
Ever since Cesare Borgia hired Leonardo da Vinci, military spending has driven innovation. This became true for CRISPR in 2016 when James Clapper, the U.S. Director of National Intelligence, issued the agency’s annual “Worldwide Threat Assessment” and it included for the first time “genome editing” as a potential weapon of mass destruction. As a result, the Defense Advanced Research Projects Agency (DARPA), which is the Pentagon’s well-funded research arm, launched a program called Safe Genes to support ways to defend against genetically engineered weapons. It dispensed $65 million worth of grants, making the military the largest single source of money for CRISPR research.2
The initial DARPA grants went to seven teams. George Church at Harvard received one to study the reversal of mutations that come from exposure to radiation. Kevin Esvelt at MIT was tapped to study gene drives, which can accelerate a genetic change through a population of organisms such as mosquitoes and mice. Amit Choudhary of Harvard Medical School got funding to develop ways to switch on and off genome editing.3
Doudna’s grants, which would eventually total $3.3 million, covered a variety of projects, including looking for ways to block a CRISPR editing system. The goal was to create tools that, as the announcement put it, “might someday be capable of disabling weapons employing CRISPR.” It sounded like the plot of a paperback thriller: terrorists or enemy states unleash a CRISPR system that can edit organisms, such as mosquitoes, to be super-destructive, and Dr. Doudna in a white lab coat has to rush in to save us.4
Doudna assigned the project to two young postdoctoral students who had just joined her lab, Kyle Watters and Gavin Knott. They focused on a method that some viruses use to disable the CRISPR systems of the bacteria they are attacking. In other words, bacteria developed CRISPR systems to ward off viruses, but then the viruses developed a way to shut down those defenses. It was an arms race the Pentagon could understand: missiles being countered by defense systems being countered by anti–defense systems. The newly discovered systems were dubbed “anti-CRISPRs.”
Anti-CRISPR
Anti-CRISPRs were discovered in late 2012, just as Doudna and Zhang were racing to turn CRISPR-Cas9 into a human gene–editing tool, by a doctoral student at the University of Toronto, Joe Bondy-Denomy. He stumbled upon the discovery by trying something that should not have worked: he attempted to infect some bacteria with a virus that should have been defeated by the bacteria’s CRISPR system. In a handful of cases, the attacking viruses survived.
At first he assumed he had botched the experiments. Then a thought occurred to him: perhaps the wily viruses had developed a way to disarm the bacteria’s CRISPR defenses. That turned out to be right. The viruses had been able to infiltrate the bacteria’s DNA with a little sequence that sabotaged their CRISPR system.5
His anti-CRISPRs didn’t seem to work on CRISPR-Cas9, so the discovery got little attention at first. But in 2016, he and April Pawluk, who had worked with him on the original paper, identified anti-CRISPRs that disabled the Cas9 enzyme. That opened the floodgates for other researchers to join the hunt, and soon more than fifty anti-CRISPR proteins had been discovered. By then Bondy-Denomy had become a professor at the University of California, San Francisco, and he collaborated with Doudna’s lab to show that the anti-CRISPRs could be delivered into human cells to modulate or stop CRISPR-Cas9 editing.6
It was a basic science discovery about the wonders of nature, showing how the amazing arms race between bacteria and viruses evolved. And once again, it became an example of basic science leading to useful tools. The anti-CRISPRs could be engineered to regulate gene-editing systems. That would be useful for medical applications that needed to time-limit a CRISPR edit, and they could be used as a defense against systems created by terrorists or malevolent enemies. Anti-CRISPRs could also be used to shut off gene drives, the CRISPR systems that are designed to make a genetic change that spreads rapidly through a fast-breeding population such as mosquitoes.7
* * *
Doudna was successful in delivering on the projects for DARPA, and her Innovative Genomics Institute at Berkeley was able over the next few years to receive grants for new research topics. Like Church’s lab at Harvard, it was asked to study how to use CRISPR to protect against nuclear radiation. The leader of that $9.5 million project was Fyodor Urnov, who was an undergraduate at Moscow State University during the Chernobyl disaster. The mission was to save soldiers and civilians exposed to a nuclear attack or disaster.8
The labs that received Safe Genes grants gathered once a year with Renee Wegrzyn, the program manager of DARPA’s Biological Technologies Office. Doudna went to one meeting in San Diego in 2018 and was impressed by how good Wegrzyn was at promoting collaboration among the labs that received military funding, just as DARPA had done in the 1960s when it was creating what became the internet. She was also struck by the incongruity of the conference. “We were eating outside in the beautiful weather under swaying palm trees,” she says, “and we were talking about radiation sickness and genome editing being used to create weapons of mass destruction.”9
Enlisting our hacker
On February 26, 2020, just as the COVID-19 plague was taking hold in America, a group of U.S. Army generals, Defense Department officials, and biotechnology executives walked past an imposing statue of a seated Albert Einstein and into a ground-floor room of the stately marble headquarters of the National Academy of Sciences in Washington, D.C. They were there to attend the conference, The Bio-Revolution and Its Implications for Army Combat Capabilities, sponsored by the army’s Research and Technology Program. Among the fifty or so participants were some distinguished scientists, most notably George Church, as well as one outlier: Josiah Zayner, the biohacker with multiple ear piercings who had injected himself with a CRISPR-edited gene at a San Francisco synthetic biology conference.
“The building was nice, but the cafeteria was shit,” Zayner says. And the conference? “It was really boring. A bunch of people who didn’t really know what they were talking about.” At one point, he scribbled in his notes, “Speaker sounds like she has taken Xanax.”
Zayner likes being irreverent, and despite what he says, I got the feeling that he actually enjoyed the conference. He was not initially scheduled to give a talk, but he made such an impression that he was called on to speak impromptu. The military officials had been complaining that they had trouble recruiting quality scientists. “You need to open up your labs and maybe start a biohacker space to interact with the people more,” Zayner told them. He pointed out that the military had done that with computer hackers. Government labs staffed by the do-it-yourself biology community, he said, could come up with solutions the military could use.
Some of the other speakers bought into the idea that the military should enlist help from, as they put it, “non-traditional communities.” As one official said, “citizen science” can be tapped to improve the military’s ability to identify threats. One of the industry scientists took note of the novel coronavirus spreading out of China, which was still a few days away from causing national alarm. They should imagine a world, he said, where such viral pandemics were common; in such situations, it could be useful to enlist citizen-scientists to figure out ways to deploy real-time detection methods and crowdsource the collection and analysis of data. It was an important point, one that Zayner and the biohacker community had been trying to make.
By the end of the meeting, Zayner was pleasantly surprised by the desire of officials to enlist the hacker community in the effort to deploy CRISPR to fight pandemics and to protect soldiers. “Everyone staring at me and surprised I came,” he jotted in his notebook. Then, a little bit later: “People coming up to me thanking me for coming.”10
PART FIVE Public Scientist
This was a new room, rich with hope, terrible with strange danger.
A dim folk memory had preserved the story of a greater advance:
“the winged hound of Zeus” tearing from Prometheus’ liver the
price of fire. Was the world ready for the new step forward?
Certainly, it will change the world. You have to make laws to fit it.
And if plain people did not understand and control it, who would?
—Excerpted from James Agee’s cover story, “Atomic Age,” on the dropping of the atom bomb, Time, August 20, 1945
James Watson and Sydney Brenner at Asilomar
Herbert Boyer and Paul Berg at Asilomar
CHAPTER 35 Rules of the Road
Utopians vs. bioconservatives
For decades the idea of creating engineered humans belonged to the realm of science fiction. Three classic works warned of what might happen if we snatched this fire from the gods. Mary Shelley’s 1818 novel, Frankenstein; or, The Modern Prometheus, was a cautionary tale about a scientist who engineers a humanlike creation. In H. G. Wells’s The Time Machine, published in 1895, a traveler to the future discovers that humans have evolved into two species, a leisure class of Eloi and a working class of Morlocks. Aldous Huxley’s Brave New World, published in 1932, describes a similarly dystopian future in which genetic modification produces an elite class of leaders with enhanced intellectual and physical traits. In the first chapter, a worker gives a tour of a baby hatchery:
“We decant our babies as socialized human beings, as Alphas or Epsilons, as future sewage workers or future…” He was going to say “future World controllers,” but correcting himself, said “future Directors of Hatcheries.”
The idea of engineering humans moved from the realm of science fiction to the realm of science in the 1960s. Researchers began to crack the genetic code by figuring out the role played by some of the sequences of our DNA. And the discovery of how to cut and paste DNA from different organisms launched the field of genetic engineering.
The first reaction to these breakthroughs, especially among scientists, was an optimism that bordered on hubris. “We have become the latter-day Prometheus,” biologist Robert Sinsheimer declared, with no sign that he understood the Greek myth. “Soon we shall have the power consciously to alter our inheritance, our very nature.” He dismissed those who found this prospect troubling. Because the decisions about our genetic future would be guided by individual choice, he argued, this new eugenics would be morally different from the discredited eugenics of the first half of the twentieth century. “We should have the potential to create new genes and new qualities yet undreamed,” he exulted. “This is a cosmic event.”1
The geneticist Bentley Glass, in his address on becoming president of the American Association for the Advancement of Science in 1970, argued that the ethical problem was not that people would embrace these new genetic technologies but that they might reject them. “The right that must become paramount is the right of every child to be born with a sound physical and mental constitution,” he said. “No parents will have a right to burden society with a malformed or a mentally incompetent child.”2
Joseph Fletcher, a professor of medical ethics at the University of Virginia and lapsed Episcopal minister, agreed that genetic engineering could be considered a duty rather than ethically problematic. “Producing our children by ‘sexual roulette’ without pre-conceptive and uterine control, simply taking pot luck, is irresponsible, now that we can be genetically selective,” he wrote in a 1974 book, The Ethics of Genetic Control. “As we learn to direct mutations medically, we should do so. Not to control when we can is immoral.”3
Opposing this biotech utopianism was a group of theologians, technoskeptics, and bioconservatives who became influential in the 1970s. Princeton professor of Christian ethics Paul Ramsey, a prominent Protestant theologian, published Fabricated Man: The Ethics of Genetic Control. It is a turgid book with one vivid sentence: “Men ought not to play God before they learn to be men.”4 The social theorist Jeremy Rifkin, dubbed by Time America’s “foremost opponent of genetic engineering,” coauthored a book titled Who Should Play God? “Once, all of this could be dismissed as science fiction, the mad ravings of a Dr. Frankenstein,” he wrote. “No more. We are not in the Brave New World yet, but we are well along the road.”5
