“Do you want to see Zika?” Robert Tesh asked the question not ten minutes after I stepped into his office. He whisked me next door to his lab and pulled a box of glass ampoules out of the fridge, each half-full of what looked like dirty snow. Here was Zika, frozen and dried: the virus causing panic in the Americas because of its increasingly likely link to brain defects in babies.
For Tesh, Zika has long been one of his “orphan viruses,” of only fleeting interest even to the people who make the study of mosquito-borne illnesses their specialty. As director of the World Reference Center for Emerging Viruses and Arboviruses at the University of Texas Medical Branch in Galveston, Tesh and his predecessors have amassed 7,000 virus strains, freeze-dried for long-term storage. About ten of those are versions of Zika, and they have spent years in the reference center, to little attention.
Then came the epidemic in Brazil, the photos of babies born with heads too small to seem real, the World Health Organization’s declaration of a public health emergency. On a recent Friday alone, 11 labs contacted the Galveston center to request Zika strains and reagents for detecting the virus. Sharing this stuff is exactly what the reference center exists to do, though the timing is a bit inconvenient: The center’s dedicated shipping person had recently left.
Inside the university’s medical branch, Zika research is accelerating. With a critical mass of mosquito-born disease experts, as well as facilities like the reference center and a high-containment lab for breeding mosquitoes like the ones spreading Zika, the Galveston medical center was one of the the first places outside of the CDC to jump on Zika. A team spent Christmas setting up experiments in Brazil. Back in Texas, they’re already running studies to figure out how to better diagnose Zika, confirm the link to microcephaly, replicate the disease in mice and primates, and potentially create a vaccine. “We’re hitting this virus from all possible angles,” says Scott Weaver, a medical entomologist leading the charge at the medical center, where a couple dozen researchers are hammering away.
If anyone saw a sliver of Zika’s coming shadow, it was Weaver. In 2009, he and William Reisen of UC Davis published a paper on emerging threats in their field. “We put Zika in the paper, which is kind of amazing because you usually get these kinds of things wrong,” Weaver says. He still seems a bit dazed by his premonition. Weaver feels the thrill of being right, of suddenly having the whole world cast its attention toward his obscure corner of science. But he also has the sinking feeling that he was right about something going very, very wrong.
Some mosquito-borne virus experts come to the field by way of mosquitoes; some by way of viruses. Weaver's in the first group. His office, on the top floor of the Galveston National Lab---the shiniest building on campus---has a shelf of mosquito memorabilia: a hand puppet, a sculpture mounted on a spring, and (his favorite) a bug-shaped spark plug. It’s the most anatomically correct, he says, pointing out the head, thorax, and abdomen in the same even tone he uses whether telling jokes or discussing molecular biology.
As college student in Maryland, Weaver got a summer job hunting down mosquitoes for the public health department. The job took him all over the county, through remote marshlands and DC suburbs. He loved the field work. When he began graduate school at Cornell, he focused on mosquito transmission of an obscure virus that causes Venezuelan equine encephalitis. From there, Weaver went on to study other tropical diseases---yellow fever, dengue, chikungunya, and Zika, which have all become notorious as they’ve spread out of the tropical zones. “I have a long history of working on obscure viruses,” he says, “but all of a sudden some of them are behaving very badly, so they’re no longer obscure.”
When Weaver first started working on it, Zika had just registered the tiniest of blips on the public health radar. The virus commonly circulated in low levels in Africa and America. But in 2007, it jumped to a Pacific Island called Yap, where it infected nearly three-quarters of the population. A few years later, Weaver got a grant to study how yellow fever and chikungunya circulated among mosquitoes in Senegal. Those same mosquitoes spread Zika, so he threw it in the mix. “Frankly it would have been impossible for me or anyone else to get grant to work on Zika,” he says. The National Institutes of Health had never funded a grant dedicated to it before this month.
In 2015, Weaver started hearing from his collaborator Albert Ko at Yale, an epidemiologist who has spent years studying yet another obscure disease called leptospirosis in Brazil. The patients Ko was tracking in the northeastern city of Salvador suddenly started getting Zika. Then the microcephaly cases started appearing. At a December meeting in Brazil---planned before the Zika outbreak, coincidentally---Weaver and Ko decided it was time to send a team.
“It was ‘We’re completely inundated, can you come today?’,” says Nikos Vasilakis, one of two researchers from Texas who went down to Brazil. They called in favors, the consul general of Houston got involved, and Shannan Rossi, a fellow researcher at the medical branch who is married to Vasilakis, got her visa for Brazil in 24 hours---a bureaucratic miracle.
Vasilakis and Rossi still have the slightly unruly air of graduate students, with his skull ring and her printouts of XKCD comics lining the lab bench. The two met 15 years ago working at the pharmaceutical company Wyeth, went through graduate school at UT Medical Branch together and, aside from a year in Pittsburgh, have worked there ever since.
The low-key Christmas vacation they imagined at home in Texas blew up into a last minute trip to Brazil. The reason that Zika had flown under the radar for so long is that it’s hard to diagnose: The symptoms are often indistinguishable from those of better known viruses such as yellow fever, dengue, and chikungunya, and typical field tests can’t distinguish between these viruses either. On top of that, 80 percent of people infected have no symptoms at all. The Texas team wanted to make sure their Brazilian collaborators could reliably detect Zika in fetal tissue---which could help suss out the link to microcephaly.
At a lab in Salvador, Vasilakis and Rossi worked side by side with scientists from FioCruz---the Brazilian equivalent of the NIH---to work out a test that can pick up the genetic signature of the Zika virus in amniotic fluid and cord blood as well as tissues from stillborn babies collected by obstetricians. The team worked through Christmas Eve and then Christmas, running and rerunning the test to make sure it was picking up Zika and only Zika.
This is easy enough at the lab bench, but hard to ramp up at the beginning of an outbreak, especially without a ready supply of the reagents or a protocol that reliably prevents false positives and negatives. For example, to guard against false negatives, you need to make sure the test is detecting genetic material from Zika, which means you need a sample that you know contains Zika. But the world’s supply of Zika is limited, even with the reference center in Texas cranking away at growing new virus. The Brazilian lab will eventually need to grow its own Zika, or at least snippets of its genetic material. That’s just one example of the layers of complexity necessary for rigorous lab tests.
After ten whirlwind days in Brazil, Vasilakis and Rossi returned to Texas. Now, they wait for the data to roll in from their Brazilian collaborators. But they have plenty of other work to do. They’ve been working ten, twelve, fourteen hour days. “We’re running on caffeine and adrenaline,” says Rossi, who’s also developing an animal disease model for Zika.
Now that they’re back, their experiments have taken on new significance. Lab work is usually so abstract, so removed from the real world. But in Brazil, Vasilakis and Rossi stepped into the hospital, where mothers cradling babies with microcephaly waited to meet with doctors and social workers. “It’s heartbreaking. I don’t think it was something either one of us was prepared for. You see the pictures and you hear about the news stories, but then you see the mothers and their children," says Rossi. "It flavors everything you do from here on out.”
What she really sensed was frustration---the frustration that doctors had no answers. Back home, the university is constantly getting emails asking for advice, usually from pregnant women, and, well, what can you say but spell out the uncertainty?
Science is supposed to revel in the unknown, but so much is unknown about Zika that even the “experts” don’t consider themselves that. “If anybody tells me I’m expert, I’d say, ‘You’re nuts,’” says Vasilakis. But from the outside, he and his colleagues are the most reliable source of information. As Zika awareness exploded outside of virology circles, the attention turned surreal. After appearing on TV, Vasilakis got a call from the owner of a Greek diner on Long Island, where he’d worked decades ago, congratulating him on making something of himself.
The World Reference Center for Emerging Viruses and Arboviruses started in New York in 1952, at Rockefeller Foundation Laboratories. Then it moved to Yale, and then to the UT Medical Branch. In fact, it’s hard to find a virus the Rockefeller Foundation hasn't gotten its gloves on---the organization poured money into virus hunting and surveillance in the mid-twentieth century. The researchers who first discovered Zika in the Uganda forest in 1947 were working at a Rockefeller-funded lab. As one historian put it, “In the field of virus research, the Rockefeller Foundation was a fairy godmother waving her wand over scientists around the world.”
Virus hunting in the 21st century has no such fairy godmother. “In the last 30 years of biology and research on viruses, the emphasis has been on molecular biology,” says Weaver. “It’s hard to even find people who want to do surveillance.” Funding agencies like studies that test a specific hypothesis or tease out the specific inner workings of, say, a virus. That’s reasonable, but it also means that surveillance---casting a wide net and hoping for something interesting to pop up---is not a priority.
At the same time, the danger of emerging viruses is growing. Modern international travel makes it easy for viruses to hop borders, and climate change is expanding the range of disease-carrying mosquitoes. New diseases can hide behind more common infections with similar symptoms: A typical clinic in South American might classify anything that looks like dengue as dengue, but perhaps only a third of these diagnoses are accurate. The rest are lesser-known viruses like Venezuelan equine encephalitis or Oropouche or Mayaro or another hard-to-pronounce name you probably haven’t heard of it. Some of it is probably Zika, too, though most clinics didn’t have the diagnostic capabilities to know for sure. “They hide under the dengue umbrella,” says Weaver. Without resources for surveillance, a new virus can easily fly under the radar.
Chikungunya was the first virus whose spread from Africa and Asia through the Americas over the past decade set off alarm bells. Zika is unlikely to be the last. With Zika hogging all the attention, the White House is now asking for $1.8 billion for research on the virus. But to prepare for the next Zika, you need research infrastructure---for surveillance, for collections of rare viruses, for work that may not seem important until suddenly one day it is. The CDC, where several alums of the UT Medical Branch now work, does a lot of this research, but the academic community around surveillance is small.
Tesh recently celebrated his 80th birthday, and he is still collecting viruses for the reference center. While he and I were talking, he got a call from his long-time collaborators in Brazil, who had just stepped off the plane in Texas. He’s been coaxing them to send over a Brazilian strain of Zika, which foreign researchers can’t access because of Brazil’s tight export laws.
Meanwhile though, the UT Medical Branch has freezers full of viruses. Presumably something else in there could do what Zika has done---break into a larger population, show a surprising or terrifying symptom, expand its range. It's 7,000 potential disasters, or 7,000 potential research bonanzas if the scientists can untangle their secrets. They just have to figure out which one to pay attention to.
