Trinity’s immunologists are playing a key role in answering that question
By Susan Pedwell
In the early Middle Ages, the Plague of Justinian killed 5,000 people a day in Constantinople. By the time it ended one year later, more than 25 million people in Europe and Asia had died. In the mid-1300s, the Black Death wiped out over half the population of China and reduced the world population by over 100 million. Then in 1918, Canada lost 50,000 citizens to the Spanish Flu and the world lost at least 20 million people (some estimates are as many as 100 million). All three plagues were transmitted by animals—the Justinian Plague from rats, the Black Death from other rodents and the Spanish Flu from pigs.
Could a plague of such staggering proportions occur today? Now we have sanitation systems and vaccines that protect us from viruses and diseases. Hospitals stand ready with infection prevention and control protocols. And if there is an outbreak in one part of the world, scientists can instantly communicate with others to contain the epidemic. So why, then, do some predict that the next plague could kill tens of millions of people?
Professor Michael Ratcliffe, former Chair of the Department of Immunology at the University of Toronto and Trinity College’s Dean of Arts, characterizes a plague as “something that has the capacity to wipe out a substantial part of the human race. “We don’t know what the next plague is going to be,” says Ratcliffe, “but we do know it’s inevitable.”
Fortunately, scientists and researchers are forging brave new pathways in our understanding of immunological threats, helping to arm us with advanced tools that our ancestors could never have imagined. Trinity magazine interviewed Ratcliffe to learn how to ride out the next “Big One.”
Trinity: Where do plagues come from?
Ratcliffe: Virtually all plagues have originated in the animal world. Ebola, for example, is carried by fruit bats. When an infected fruit bat is eaten by a great ape (gorillas, bonobos, orangutans and chimpanzees), the ape becomes infected and dies. In many parts of Africa, villages rely in part on what they call “bush meat” for survival, and a great ape carcass has a lot of meat on it. Data shows that Ebola outbreaks appear to move in a predictable direction, in the direction of fruit bat migration.
Trinity: Could the Ebola virus cause a plague?
Ratcliffe: Ebola has some of the criteria of a plague. It’s highly infectious, easily transmissible and highly pathogenic. And certainly in parts of Africa, Ebola has wiped out whole villages.
But the symptoms of Ebola come on very quickly after an infection. Pretty much as soon as you’re infected, you know you’re sick, making it easy to identify and quickly isolate infected individuals. In fact, when Ebola first appeared in human populations in Africa, villages would treat an infected person by isolating them in a hut at the edge of the village with enough food and water for a week. After a week, they either walked out—or didn’t.
Contrast this short latency period of Ebola with that of HIV. Once you’ve got HIV, there are flu-like symptoms, then an extended period of time when you’re infectious without being symptomatic. HIV is a classic example of latency; it provides time for the organism to spread through populations. But if the disease has a very low latency, as Ebola does, then it’s unlikely to be spread so widely.
Trinity: How can we survive the next plague?
Ratcliffe: Find a desert island and hide. This is a light-hearted suggestion, but let’s contrast it with where you don’t want to be. You don’t want to be in a major city with a developed public transit system that packs people together. You don’t want to be in a multi-ethnic environment that has global connections with the rest of the world.
Trinity: Are you describing Toronto?
Ratcliffe: Yes! These international linkages are exactly why Toronto was an epicentre for severe acute respiratory syndrome— SARS—in 2003. By the time SARS was contained, it had killed more than 900 people, including 44 Canadians, most of them in Toronto.
Trinity: Beyond living in isolation, where can we put our faith?
Ratcliffe: In drugs. Many of the anti-viral drugs are very effective. If you have HIV and it’s identified relatively early, your life expectancy is not much different from anybody else’s, because the anti-viral drugs are really good at preventing virus production and the spread of the virus. However, drugs do not typically prevent infection.
When the next plague comes along, I’d be surprised if the drug companies don’t eventually come up with something. Whether that drug will com in time is a separate question.
Trinity: What do you personally do to keep the pathogens away?
Ratcliffe: I don’t take vitamins; there’s no real need to if you eat a balanced diet. Humans have evolved over hundreds of thousands of years to be able to obtain the vitamins they need from a diet that includes meat, grains, fruits and vegetables.
And to my knowledge, none of the advertised probiotic-containing foods, such as yogurt, have any proven clinical benefit whatsoever under normal circumstances, certainly in part because the levels of bacteria in a typical carton of yogurt are miniscule compared with the number of bacteria normally residing in our gut. If a course of antibiotics might have disturbed normal gut flora, probiotics might help but strong evidence is pretty much lacking.
To prevent catching a cold and many other contact-mediated diseases, I wash my hands regularly, especially after travelling on the subway. I avoid shaking hands if I have a cold, and I’m not offended when others do the same. But is handwashing enough to prevent succumbing to the next plague? Clearly not.
Trinity: What are your thoughts on vaccination?
Ratcliffe: There is no doubt that vaccination has saved more lives than any other innovation during the course of human evolution, with the exception of the provision of clean drinking water.
I find it frustrating when people still quote the study that vaccination can cause autism since that study was admitted to be fraudulent. Parents who refuse to get their children vaccinated put their kids’ lives in danger.
Since the onset of childhood vaccination, greater than 90 per cent of child deaths from measles have been in unvaccinated children. It is not enough to say that since there is no significant incidence of measles in North America, children don’t need to be vaccinated. The recent outbreak in measles that tracked back to an amusement park in California likely originated from a visitor from the Philippines, where measles is still quite common.
Trinity: How many diseases have vaccines eliminated?
Ratcliffe: Only one: Smallpox. And it took 200 years to eradicate it.
But vaccines have been enormously effective in reducing the incidence of TB and diphtheria. They have made massive reductions in what used to be the “normal” childhood diseases.
There are dozens of diseases that we can prevent from infecting vaccinated individuals, but some of these diseases may exist in animal pools. So we constantly need to keep vaccinating. No animal pool carries smallpox, and this is one of the key characteristics of smallpox that made it feasible to eradicate it completely. It’s simply spread from human to human by contact.
We’re close to eradicating polio, but the problem now is more political than medical. There are a few parts of the world— Afghanistan, Northern Pakistan—where there is still polio because there’s a reluctance to let in Western medicine to vaccinate populations.
Trinity: Can vaccinations save us from the plague?
Ratcliffe: When a plague starts, the first thing the scientific and health-care community have to do is identify what it is and develop a precise molecular characterization of the virus or bacteria. Then we can start to develop a vaccine. But just because a vaccine exists, it doesn’t mean the problem is solved. There are all kinds of other considerations that come into play, such as ethics, distribution and cost issues.
Trinity: Is Canada ready for the next plague?
Ratcliffe: Canada certainly has stockpiles of vaccines against what we already know about. Is the next plague going to be about something we know about? Probably not. But now we have a system in place that will allow us to do the discovery research to develop the vaccine rapidly. We’re a lot readier now than we were pre-SARS. That was a huge wake-up call.
Canada did a brilliant job in identifying SARS. There were collaborations between Toronto where the patient base was, the isolation facility in Winnipeg that was able to culture and purify the virus, and the sequencing facilities in Vancouver that were able to absolutely characterize the virus. It was a textbook example of productive collaboration. What they developed was a precise molecular characterization of the virus. Once you know that, then you can start to develop vaccines. There is a vaccine for SARS now, but SARS actually ended as a disease before the vaccine was generated.
Trinity: Any predictions on what the next plague might be?
Ratcliffe: One of the most likely candidates is a new variant of a flu virus. So far we’ve been lucky that the most pathogenic flu viruses were not very infectious so didn’t spread rapidly. Maybe that’s because viruses are not trying to kill you; they’re basically trying to spread. But it’s certainly possible that a very pathogenic flu virus becomes adapted to humans so spreads more easily.
Trinity: Is there a danger that a virus will wipe out our species?
Ratcliffe: It’s unlikely that a single virus will wipe out all human life on Earth because there will always be some individuals who are genetically resistant to the virus.
Trinity: Do you lie awake at night worrying about the next plague?
Ratcliffe: No. I have faith in immunology.
Professor Ratcliffe is Editor-in-Chief of the recently published Encyclopedia of Immunobiology, 1st Edition, a five-volume, 3,000-page international reference text (see Book It for more information).
GUTSY RESEARCHERS
Awareness of the importance of a healthy microbiome in our digestive system is growing, and the food industry has been quick to respond with yogurt, kefir, kimchi and other products that the manufacturers claim will boost the bacteria within the coils of our intestines. Then in May, the Canadian Institutes of Health Research awarded two Trinity immunology professors $2 million each to investigate how the two kilograms of bacteria residing in our guts contributes to disease.
Associate Professor Alberto Martin is sorting through the more than 1,000 species of gut bacteria to identify which microbes induce colon cancer in mice and in individuals who are genetically susceptible. “This is a new frontier,” says Martin, the director of Trinity’s immunology program. “We don’t know everything that these bacteria are doing within our guts.”
By altering the diet and manipulating the gut bacteria, Martin hopes to develop strategies to help prevent the onset of colon cancer, the second leading cause of cancer-related deaths in Canada.
Professor Jennifer Gommerman, meanwhile, is investigating autoimmune disease in Canadians of South Asian descent. “Does global migration affect health and lead to more disease?” asks Gommerman, a Trinity Fellow. “We’re just starting to answer this question.
“Depending on their country of origin, immigrants may be exposed to a different burden of microbial pathogens,” she says. “For example, the prevalent use of antibacterials in our Canadian environment could change the types of microbial exposures experienced by immigrants when they come to Canada, and particularly the types of exposures experienced by their children who are born in Canada.”
The seed funding for Gommerman’s research came from the Connaught Global Challenge Award, a U of T-based competitive grant designed to “heighten U of T’s contribution to important issues facing society through the advancement of knowledge, and the transfer and application of solutions.” The work supported by the award enabled Gommerman to then compete for—and win—the larger Canadian Institutes of Health Research Grant.
While the role of the microbiome in disease has recently captured our attention, acknowledging the importance of what’s going on in our bellies is perhaps long overdue. As Hippocrates observed in 400 BC, “All disease begins in the gut.”
1986
The year U of T’s Department of Immunology was inaugurated, with Trinity College as its academic home, through the help of immunology researchers and Trinity Fellows Dr. Brian Barber and Dr. Robert Painter (who was also Trinity’s incoming Provost at the time). “It seemed like the right moment to add a science role to Trinity College, complementing its long-standing interest in the Humanities and International Relations,” says Painter.
The right moment, indeed. Since then, landmark discoveries in how the immune system develops, how it recognizes pathogens and how the activities of the immune system can be harnessed to fight infectious diseases and cancer have changed the face of health care. —Jennifer Matthews
2015
Following the discovery of a “plague pit,” a mass grave uncovered during construction in East London in 2015, researchers have confirmed the cause of The Great Plague of London. The bacteria Yersinia pestis, which claimed an estimated 50 million lives during the Black Death in the 14th century, is also responsible for The Great Plague, which killed an estimated 100,000 people from 1665 to 1666—a quarter of London’s population at the time.
Trinity Fellow Professor Nicholas Everett was interviewed in September by CTV New about the implications of the discovery, which was confirmed through DNA tests performed on teeth from the ancient skeletons. “This case gives us another example to work with to try to enlarge our understanding of plagues and how they operate,” says Everett. “There are still many unanswered questions about where the plague comes from, how it was transmitted and why it affected some areas more than others.
“We need to learn more about the effects of other factors, like malnutrition, a bad farming cycle or unhygienic living conditions. The answers to these and other questions could ultimately help modern medical researchers to understand, treat and ultimately prevent future plagues.” —Jennifer Matthews
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