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Biotechnology and health

It’s fiction, but America just got wiped out by a man-made terror germ

At “germ games” held in Washington, DC, pandemic planners get a look at the threat posed by synthetic biology.
Larry Canner/Johns Hopkins Center for Health Security

In June 2001, a group of government officials and journalists play-acted their way through a “germ game,” a fictional scenario in which the (then obscure) terrorist group called Al Qaeda sets off an outbreak of smallpox in US shopping malls.

The exercise, called Dark Winter, proved influential in shaping US “pandemic preparedness” policy, promoting the notion that this country, and others, should stockpile vaccines, provide extra hospital beds, and make emergency plans in the event of a global disease outbreak that might never materialize. Dark Winter, since reenacted in schools and statehouses, was effective in part because it proved prescient. Within three months of the exercise the U.S. was hit by the 9/11 attacks and anthrax-laden letters were circulating in the US postal system (though these were allegedly sent by an American military scientist, not foreign terrorists).

Politicians got the message. Today, the US stockpiles enough smallpox vaccine for every man, woman, and child, and large supplies of anthrax drugs, too.

Much has changed since 2001, though, so on Tuesday, May 15, some of the original participants in Dark Winter returned for a new pandemic exercise, CladeX, held at a fancy hotel in Washington, DC. At 9 a.m., foreboding music filled a ballroom, and the lights dimmed around a U-shaped table where a fictional cabinet had taken seats. The players included former Senate leader Tom Daschle (reprising that role), onetime Centers for Disease Control and Prevention chief Julie Gerberding, and Tara O’Toole, the creator of the Dark Winter scenario.

The group’s task: respond to a fictional outbreak. A virus is killing dozens in Frankfurt, Germany, and spreading in Venezuela, though that country’s president denies the problem. It’s moving fast and has a high mortality rate. The leaders immediately must decide whether to shut airports (they don’t) and give assistance to Venezuela (they do), and how to calm the public as fake news spreads paranoia on social media.

First, though, they have to understand the enemy. In the real world, says Jonathan Quick, a doctor who attended the exercise and is the author of a book on preparedness, The End of Epidemics, three out of five novel diseases come from “the bush or the barn.” That is, like Ebola and SARS, they make the jump to humans from animals. In last week’s scenario, the players also initially suspect a zoonotic source but quickly learn that this disease doesn’t fit any known family of viruses, called clades. Could it be man-made?

Eric Toner, a physician specializing in pandemics, designed a “germ game” in which terrorists release a man-made virus.
Larry Canner/Johns Hopkins Center for Health Security

Indeed it is. Someone has genetically modified a mostly harmless parainfluenza virus to kill. The fictional culprit is A Brighter Dawn, a shadowy group promoting the philosophy that fewer people—a lot fewer—would be a good thing for planet Earth. In fact, they want the population to return to preindustrial levels.

The scenario was created by Eric Toner, an emergency physician and pandemic specialist with Johns Hopkins University's Center for Health Security, which sponsored the exercise. Toner carried out meticulous research to come up with a plausible threat using real virology and epidemiological models. The result was so realistic that the organizers chose not to present too many details. “For obvious reasons,” he says. “It does not require a nation-state to do it.”

That may be the biggest change since 2001. Since then, genetic engineering has become easier, and powerful tools like CRISPR are easily obtained. “The most fascinating thing is that technology used to be up here,” says Scott Lillibridge, the onetime head of the CDC’s bioterrorism program and now a professor at Texas A&M. “I can tell you in the 1990s we were thinking about state actors. It was a virus in the freezer. Fast-forward 20 years and the appearance of synthetic biology means that things which used to require a major investment are cheap and easy to acquire.”

In the past, it was enough to stockpile vaccines against familiar germs—smallpox, polio, anthrax. But now an evildoer could create new threats not on anyone’s list of bogeymen. As Bill Gates put it this year, “The next epidemic could originate on the computer screen of a terrorist.”

Yet as real cases such as the Zika outbreak show, science can also move faster in response than ever before. In Toner’s scenario, it’s only a matter of days before the fictional CladeX virus is sequenced, laying naked its genetic code and setting off a coordinated and competitive assault by scientists and vaccine makers. “We’re getting better,” says Lillibridge. “The discussion is more complex, but the ability to focus on the key issues is greater.”

The organizers of the germ-game exercise, who had prepared their recommendations in advance, repeated familiar calls for inter-agency coordination and more public health infrastructure in the developing world. But they also included in their six recommendations a call for international oversight of the most risky types of experiments (say, synthesizing viruses from scratch), perhaps via the United Nations. That’s necessary, they say, because “few countries in the world have explicitly acknowledged the possibility that new pandemic risks could emerge from scientific research or the application of new biotechnological tools.”

What the US should do, according to Hopkins, is invest more heavily in ultra-fast paper diagnostics and new vaccine manufacturing systems that could provide antidotes in months rather than years. All that is within reach, says O’Toole. “We have the capacity, technologically and socially, to defend ourselves,” she says. “But we have to get it into our heads that it’s a real threat, and get the politicians to understand that there is stuff we could do. It’s going to cost money, but not impossible amounts of money.”

That’s not to say CladeX ends well. As in most germ games, a bad outcome is guaranteed. How else to create a teachable moment? By the end of the exercise, a first vaccine has failed, tens of millions have died, stock markets are down by 90 percent, the president is sick, and the US is forced to nationalize the health-care system.

I asked O’Toole if she thought CladeX turn would turn out to be as prescient as Dark Winter.

“I hope not,” she said.

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