For evidence of how deep Boston’s brainpower bench is, consider the response by local researchers when the panic over the Zika virus erupted in South America last winter. Virologist Dan Barouch — who had been working for years in his lab at Beth Israel Deaconess Medical Center to develop a vaccine for HIV — pounced, trying to identify a Zika vaccine, and in a hurry. Meanwhile, Jim Collins, an MIT professor and synthetic biologist at Harvard’s Wyss Institute, led the development of a cutting-edge system that could diagnose Zika quickly, cheaply, and accurately, helping to reduce the impact of the outbreak until a vaccine is ready to be rolled out.
Barouch and Collins were both moved by the explosive spread of Zika and the devastating birth defects it was leaving in its wake. Each enlisted collaborators from around the globe, and each led his team to groundbreaking results in record time. Yet Barouch and Collins did their work independent of each other, even though their Boston labs sit in the same building off Longwood Avenue, just five floors apart.
Barouch and his team began their vaccine hunt in late January, taking three different approaches to introduce Zika to cells in the hope of spurring the body’s immune response. One used the traditional vaccine approach of a full, purified, inactivated Zika virus, while two others used only a piece of Zika genomic material, delivered to the body as “naked DNA” or via a strain of the common cold known as the adenovirus.
Two and a half months later, they had their first results. They began daily checks of the levels of viremia — the presence of virus in the blood — of the mice they had vaccinated before infecting them with the Zika virus. “On day one, we didn’t see any virus, so we got a little excited,” recalls Peter Abbink, one of Barouch’s chief lieutenants. “By day three, we were trying to stop ourselves from shaking. On day seven, when we still did not see any viremia in the vaccinated mice, we were jumping. We had to replace a couple of the ceiling tiles.”
By June, they found the vaccine had been just as effective in the monkeys they had infected a few weeks after the mice. All three versions of the vaccine worked, but the most potent immune response came from the one using the inactivated virus. “The implications were so profound,” Barouch says, “because it meant that it would at least be very likely that we will be able to control this epidemic with a vaccine.”
The 43-year-old director of Beth Israel’s Center for Virology and Vaccine Research acknowledges that plenty of crucial steps stand between publishing journal articles on a proof-of-concept vaccine in non-human primates and developing an effective vaccine approved for humans. Still, he says, “it’s rare for results like this to come out so fast and so clean.” His lab, one of several now working to develop a Zika vaccine, has begun a phase 1 clinical trial in humans to assess safety and side effects.
Until a vaccine is widely available, it will be critical for medical workers in the field to be able to diagnose Zika rapidly and reliably. Current diagnostics can take days or even weeks, cost hundreds of dollars per test, and often confuse Zika with dengue fever.
That’s what makes the work by Collins and his colleagues so promising. Their method freeze-dries microscopic sensors onto paper disks and uses sophisticated CRISPR gene-editing approaches to detect tiny differences in genetic profiles. When blood or urine samples are collected from a patient, they interact with the sensors and display a change in color if Zika is present, like a home pregnancy test. This approach is compact, easily portable, and produces highly accurate results in 2½ hours or less at a cost of just pennies per test.
“This was one of the most meaningful experiences I’ve had in my academic life,” says the 51-year-old Collins. “We didn’t know we were going to get the attention of the world.”
As with the vaccine work, the innovation here is still in proof-of-concept stage. But as a weapon in the global fight against Zika, it should make it to the field even faster than a vaccine. Moreover, Collins, who began his work in diagnostics at the peak of the Ebola crisis in 2014, has designed a workflow for how this new platform could be adapted to meet future crises.
“We need to create a national response to the next pathogen,” Collins says, “because it’s coming.”
Whatever it is, there’s a good chance that when it arrives, researchers in Boston will be fighting it from the front lines.