How bats in the basement could save lives during the next viral outbreak
Researchers join forces with Royal Ontario Museum bat biologists to create a 'vaccine bank'
By Sharon Oosthoek
Three storeys below the Royal Ontario Museum, a couple of freezers full of bat tissues just might hold the key to keeping the next pandemic at bay. They are the reason Western virologist Ryan Troyer has a standing date every Friday morning at precisely 9 a.m. with the ROM’s assistant curator of mammalogy, Burton Lim.
“Yeah, I’m driving into Toronto every Friday to collect frozen bat tissues,” says Troyer. “We really know how to have a good time.”
In the past two decades, there have been three major coronavirus outbreaks in humans – all likely related to viruses found in bats. The first was severe acute respiratory syndrome (SARS) in 2003, then came the Middle East respiratory syndrome (MERS) in 2012, and now SARS-CoV-2, the cause of the global COVID-19 pandemic. Because humans are increasingly encroaching on wildlife habitats, experts predict more opportunities for animal-to-human virus transmission and more outbreaks.
Even though the current pandemic means there’s a lot of red tape with working with bat tissues, Troyer and his team are committed to getting all the special permissions and following all the biological safety protocols. By sequencing and studying bat coronaviruses that jump to humans, the team might just make the difference between a localized outbreak and a pandemic.
Friday mornings, Lim leads Troyer and his students down into the museum’s sub-basement. Screened for COVID-19, physically distanced, masked and gowned, they carry with them spreadsheets detailing the provenance of each precious sample, most of which Lim collected himself during research trips to Southeast Asia and China.
Lim and his colleagues have been collecting and freezing mammal tissues in liquid nitrogen since the late 1980s, in order to study taxonomy and genomics. The ROM’s frozen bat tissue collection is one of the best in the world, containing nearly 15,000 specimens representing 15 of 21 families, 120 of 220 genera, and 400 of 1,400 species from 30 countries.
“When I told Ryan they were frozen in liquid nitrogen, his eyes popped open,” recalls Lim. That’s because unlike traditional preservatives such as ethanol, liquid nitrogen allows the specimens to flash freeze at -196°C, which halts the natural degradation of RNA and DNA. With the genetic material intact, scientists can better isolate and identify it.
In the freezer room, Troyer and his students don insulated gloves to guard against freezer burn and carefully remove each sample to slice off a small piece. Then they place the piece in a tube filled with a special preservative that will keep it from degrading, while rendering any viruses in the tissue inactive.
It takes them most of the day to collect 200 samples, which they drive back to London in carefully packed cardboard boxes. Once they deliver the boxes to Western’s state-of-the-art Imaging Pathogens for Knowledge Translation (ImPaKT) Facility, Troyer and his colleague Stephen Barr – also a virologist at the Schulich School of Medicine & Dentistry – study the samples to see which contain coronaviruses.
Barr and Troyer also look for viruses in bat droppings donated by bat biologists from around the world, including Brock Fenton, a world-renowned bat biologist, professor emeritus in Western’s Faculty of Science, and research associate at the ROM.
The Western team has so far found dozens of types of coronaviruses in the bat tissues and droppings, most of which have already been identified. They are not even halfway through scanning samples and expect to find many more.
Recently, they have developed high-throughput methods for safely determining which spike proteins can enter human cells. These methods only involve the spike proteins, not live infectious coronaviruses, which not only speeds up the screening process, but also eliminates any risk of infection.
“We know SARS likely originated in bats and spread to other animals, where they evolved and became better at getting into mammals, including humans,” says Barr. “We want to identify those viruses that have the ability to get inside human cells because once inside, they start to study our viral defences and evolve ways to hide from it and become a ‘smarter’ virus. The SARS-CoV-2 variants that are currently emerging around the world are a good example of how the virus has adapted to get into our cells better and how it has found a new way to hide from our immune system.”
The team will then isolate the spike RNA from each transmissible coronavirus and use it to generate a seed vaccine. The goal is to create a bank of spike vaccines in much the same way today’s COVID-19 vaccines were produced.
“We are developing a resource we can go to next year, or in 10 or 20 years, when the next outbreak occurs,” says Barr. “We can then pull out the closest-matched seed vaccine for rapid expansion.” Barr estimates Western’s bank of seed vaccines could hasten vaccine development by as much as six months, which could save untold lives.
“We’re never going to prevent all transmissions of disease from animals to humans,” says Troyer. “But we need to prevent them from going from a limited-scale outbreak to a pandemic.”