Lederman shared Evans’ apprehension about the potential for a smallpox epidemic. “There’s an urgent need for a new vaccine,” he says. Smallpox vaccinations ended in 1978, meaning that the roughly 5 billion people worldwide under the age of 40 have not been inoculated.

Lederman, a former associate professor of medicine at Columbia University, was prepared to commit his company to coming up with a solution. He was convinced that the secret to a better vaccine could be found in horsepox, a lesser-known cousin of smallpox. Horsepox isn’t known to be harmful to humans, but its genetic makeup is closely related to smallpox. In theory, the closer one can get to a virus’s origins, the more effective the vaccine that can be derived.

Evans was intrigued. But the Centers for Disease Control maintains a single sample of horsepox, extracted from an infected horse in Mongolia in 1976, and Evans said it was unlikely he would be able to use the sample for commercial purposes. There was another option for getting their hands on some horsepox, Evans told Lederman: They could ­re-create the virus from scratch using synthetic DNA, similar to the way researchers had synthesized polio a decade earlier. The horsepox genome sequence had been published by researchers in 2006, offering up a road map for the virus’s revival.

Evans didn’t know if he could succeed. Despite his Cassandra warnings, no one had ever engineered a virus in the smallpox family. Lederman decided the attempt was worth the gamble. He offered Evans’ lab $200,000 to try to bring horsepox back to life.

When I ask Evans if he had any doubts about ­re-creating a cousin of smallpox, he hesitates. “You do think about that,” he says, “I don’t like controversy.” He had seen what had happened when polio was synthesized and had spoken with those researchers. Evans accepted that many would not agree with his choice. But he also believed, emphatically, that people already knew how to create such a virus–it was just that no one had achieved it yet. This was his chance, then, to prove that a synthetic version of a poxvirus was not only conceivable but a looming reality. “As long as people kept debating whether it was possible,” Evans notes, “nothing was ever going to be done about it.” It was time to put those questions to rest.

In 2016, with approval from the University of Alberta’s biosafety office, Evans purchased 10 DNA fragments from GeneArt, a DNA synthesis company based in Regensburg, Germany. The synthetic DNA, which arrived by FedEx as vaporized powder, was harmless. “If you wanted to, you could eat it,” Evans says, “My guess is that it would have a fizzy tang, like Pop Rocks.”

SYNTHETIC BIOWEAPONS How worried should we be about warring countries or terrorists turning synthetic viruses, bacteria, and microbes into bioweapons? For some doomsday scenarios—the creation of, say, a wholly manufactured monster mashup of bad viruses—the answer is not very. But there is still plenty to freak out about. Last year, the US Department of Defense commissioned a report from bio­security and synthetic biology experts to assess the threats. Here are some of their most urgent warnings, ranked by concern level. —SARASWATI RATHOD REVIVED VIRUSES (HIGHEST) : A bioterrorist, armed with basic lab equipment and online databases filled with genetic blueprints for deadly viruses, could conceivably re-create a fatal disease like smallpox or the Spanish flu. Illnesses with relatively small genomes, like polio, are easier to resurrect than more genetically complex diseases like smallpox or herpes.

MICROBIOME INTERLOPERS (HIGHEST) : Microorganisms inhabit our guts, mouths, and skin and help us in many ways. A rogue microbe slipped into the mix could, in theory, cause our good bugs to produce harmful chemicals. In practice, this would be really hard to do, but the novelty of this technique put it on the list of top concerns.

SOUPED-UP BACTERIA (HIGHEST) : Because their genomes are more stable, bacteria tend to be easier to modify than viruses. While you might not be able to get the building blocks for a deadly pathogen (like the one that causes anthrax) from a mail-order genetics company, you could modify a more benign bacterium to make it resistant to antibiotics or able to produce more toxins.

MUTATED VIRUSES (HIGH) : Introducing mutations into a virus’s genome almost always leads to a gentler form of the bug. That’s how a vaccine for measles was created. But scary stuff could also be made. In 2014, researchers found that just five mutations could transform an avian flu into an airborne virus—making it far more likely to spread (at least among ferrets).

MODIFIED IMMUNE SYSTEMS (MEDIUM): It might be possible to develop and deliver a specially engineered virus or chemical capable of suppressing the body’s defenses or turning them against it. However, the human immune system is highly complex, and we still don’t fully understand it, making manipulation difficult.

The arduous job of assembling the horsepox genome fell to Evans’ research associate, a young microbiologist named Ryan Noyce. Noyce wears his dark hair short and favors socks that read “Get shit done.” Like Evans, he has devoted his career to studying the nuances of viruses.

Building a virus from scratch is like assembling Lego blocks. A decade ago, Evans had improved on a process that uses a “helper virus”—another form of a pox­virus—to kick-start the replication of DNA. In this case, once the helper virus started growing inside a cell, Noyce would use pipettes to introduce a solution containing the horsepox DNA. “You’re laying down a piece here, a piece here,” Evans says, “mortaring them together.” The fragments affix to each other using an enzyme called DNA ligase, which acts as a kind of glue. If the DNA fragments are introduced into a cell in the right way, under just the right conditions, they’ll join together through a natural biological process and hopefully grow into a virus.

Noyce had to get every step of the process exactly right, from the sequence of the fragments to the timing of their insertion into the cell. If any part of the chain fails, the entire process falls apart. “It takes a tremendous amount of planning and timing and design work,” Evans explains.

Every weekday morning at 7:30, Noyce crossed the University of Alberta campus to reach Evans’ dimly lit lab. He’d don his long white lab coat, then spend 10 hours moving between his computer and a microscope, stitching DNA fragments together based on horsepox’s previously published genome sequence.

One day, after 18 months of meticulous work in the lab, Noyce looked through his microscope and saw it: a clearing of cells infected with the horsepox virus. He’d successfully re-­created a poxvirus. But the rush of excitement was quickly tempered by the realization of what of was to come. Noyce believed that if they could help develop better vaccines, that “would outweigh the potential negatives” of reviving a pox. But given the history of the virus, Evans says, “We knew that there was going to be controversy.”

The trio published their findings in the scientific journal PLOS One in January 2018—and the blowback was swift and brutal. Critics accused Evans and Noyce of opening a Pandora’s box that could send humanity back to the dark ages of disease. The Washington Post’s editorial board wrote that “the study could give terrorists or rogue states a recipe to reconstitute the smallpox virus.” Tom Inglesby, director of the Center for Health Security at the Johns Hopkins Bloomberg School of Public Health, denounced the research on National Public Radio: “Anything that lowers the bar for creating smallpox in the world is a dangerous path.” Gregory Koblentz, director of the biodefense program at George Mason University, warned in the journal Health Security that the synthesis of horsepox “takes the world one step closer to the reemergence of smallpox as a threat to global health security.”

The PLOS One paper also triggered calls for tighter regulation. Elizabeth Cameron, vice president of global biological policy and programs for the Nuclear Threat Initiative, a nonprofit that works to prevent attacks by weapons of mass destruction, issued an ominous warning that “the capability to create and modify biological agents is outpacing governmental oversight and public debate.”

Evans still bristles over the criticism, which he feels missed the point. “One of the very irritating things on the reporting on our work was the idea that somehow it was so easy,” he says. “No it’s not. Ryan busted butt to make this.” For now, synthesizing a virus, as Evans and Noyce have, requires a high level of expertise. But while such a feat may be difficult to achieve, even Evans admits that “you make it more accessible to people simply by letting them know it can be done.”

The research paper seemed to spur the federal government to shore up its defenses against the threat that someone could create and unleash a synthetic virus. In June, the US National Academies of Sciences, Engineering, and Medicine released a 231-page study warning that even existing viruses like the common flu could be tweaked in a lab to evade immune responses and resist therapeutics (see sidebar). Several efforts are now underway to better assess potential threats before it’s too late.

Darpa has launched an initiative called Safe Genes to protect service members from the accidental or intentional misuse of genome-editing technologies. The agency is trying to develop military tools to both counter and reverse the effects of synthetically created bioweapons. The Office of the Director of National Intelligence has announced its own initiative to find better methods for detecting and evaluating synthetic bioweapons. The system is designed to prevent rogue actors from getting their hands on the building blocks needed to make a dangerous virus.

To make better screening tools, the government enlisted Ginkgo Bioworks, a biotech startup founded by a group of MIT PhDs. Based in an old Army warehouse along Boston Harbor, Ginkgo’s main business is making custom microbes for use in everything from sustainable agriculture to perfumes. But with its government contracts, the biotech company helped build an algorithm that can recognize any genetic sequence on the “threat list” of potentially harmful viruses and bacteria. The software—a literal antivirus program—would be voluntarily installed on the servers of every company that synthesizes DNA. It’s like a wanted list for genetic riffraff. “If somebody tries to synthesize horsepox, alarm bells go off,” says Patrick Boyle, Ginkgo’s 34-year-old head of codebase. At that point, the DNA company can ask questions of the buyer and, if warranted, deny the sale.