Infectious disease: Making — and breaking — the animal connection

Most of the emerging diseases that threaten us humans — including SARS-CoV-2, the virus causing the Covid-19 pandemic — are zoonotic, meaning the microorganisms that cause them come from another animal. In an era of increasing urbanization, it may seem that many of us are keeping wild animals at safe distances. But the intricate network of global connections in the modern world, and the number of people living on the margins of humanity’s ever-expanding habitat, mean that we may never have been as accessible to ambitious new pathogens as we are today.

Epidemiologist Jonna Mazet of the University of California, Davis, believes that to prevent zoonotic diseases, we must realize that the health of wild and domesticated animals is inextricably linked with our own — and we should study and protect them and ourselves together. The executive director of UC Davis’s One Health Institute, Mazet has been at the helm of a variety of projects inspired by this view. She is a member of the brand new Standing Committee on Emerging Infectious Diseases and 21st Century Health Threats, a group put together in March by the US National Academies of Sciences, Engineering, and Medicine to provide scientific guidance to the ongoing response to SARS-CoV-2 and other emerging pathogens.

Today’s advanced diagnostic tools make it easier than ever to identify dangerous viruses and other microbes that make their homes in other animals, Mazet and her virologist colleague Brian Bird wrote in the 2018 Annual Review of Animal Biosciences. For more than a decade, they have worked to find as many potential human pathogens as possible, while at the same time helping to build the capacity to respond to them in dozens of countries. Knowable Magazine asked Mazet about her work and how humanity can do a better job of keeping other dangerous pathogens from making the jump to our species.

This interview has been edited for length and clarity.

In the past decade, you’ve been the director and lead scientist at the PREDICT project, with the goal of moving “to a proactive approach in which pathogens of pandemic potential are discovered at their source before large-scale epidemics occur in people.” How many have you found so far?

As part of this project, we have taken about 170,000 samples from individual wild animals and people in 30 countries. This led to the discovery of approximately 1,200 viruses belonging to families that are known to have the potential to infect people and cause epidemics, including more than 160 potentially zoonotic coronaviruses.

We have also identified about 40 risk factors for those viruses to spill over and spread between humans. An important one is if a virus is encountered by people who are using the landscape in different ways.

Another one is the ability of a virus to infect multiple species. For this reason, our team also took samples from outbreaks in animals, such as avian influenza in wild birds or poultry. The usual host of a microbe often does not show clinical signs of disease, so emerging diseases tend to be most severe in species that are naive to them.

Virological factors, such as the nature of their genetic material, are also important. For example, RNA viruses are more worrisome than DNA viruses because of their ability to spread and mutate more rapidly.

I can tell you that in our final ranking of the most risky ones, the coronaviruses were absolutely at the top of the list.

Did the project also reveal which animals pose the greatest risk? Are bats really the worst threat?

Initially, I was concerned that we were just finding more things in bats because we had started studying them more. But after all the sampling we’ve done, I can say that in bats, we do find quite a bit more diversity of the viral families that are known to have caused epidemics and pandemics in the past.

Many bat species live in large groups, of sometimes up to a million, so they provide plenty of opportunity for viral mixing. There are also a huge number of bat species, and all those species have different viruses.

But we have to be careful about our message here: We need bats. They are pollinators, they disperse seeds, they eat the insects that threaten our crops and our health. We should leave them alone, not get rid of them.

We are almost sure that eradicating bats would not help. They will have more babies in response to the drop in population numbers, and bats may also be attracted from other areas and bring in new diseases. The other thing we have found is that if you stress animals, they tend to shed more disease-causing organisms. The same is often true for humans.

You are now involved in an even more ambitious project, the Global Virome Project, to “identify the bulk of the viral threat” in the world. It is estimated that there are some 1.67 million yet-to-be-discovered viruses from key zoonotic families, and that up to half of them could spread to humans. This would be fascinating scientifically, but even if it is possible to identify them all, will it help us stay healthy?

I think PREDICT really provided the proof of concept that it is possible — even in the least-resourced regions in the world — to discover these viruses ahead of time, and begin to understand how to rank them for their importance for surveillance and even early vaccine development. Without that knowledge, I don’t think we will know how to get ready for the ones that are going to be problematic, like SARS-CoV-2.

Rather like the Human Genome Project, I think projects like these drive the technology to become better and cheaper. If you don’t start, you’re never going to make progress. So I think the argument that we’ve had for a decade about what we do and whether it’s important should really be gone, now.

We only need to see a reduction of 0.3 percent of the economic impact of past outbreaks like SARS-CoV-1 to pay for finding all the viruses out there. That’s the break-even point. With the new one, it’s even less.

As communities become aware of the pathogens in their area, they can alter their behavior accordingly. For example, if guano farmers — people collecting bat excrement to use or sell as fertilizer — understand the risks of doing so, they can increase their personal protection.

Meanwhile, countries can improve their capacity for surveillance and diagnosis, allowing them to detect and control new diseases at the source, so they are less likely to get out of control.

Do you think these projects have prevented any epidemics so far?

I can’t tell you what all we prevented, but we do have some ways to measure the impact of where and how we were working. We were able to train about 6,800 people in the countries we were working in, in virology as well as other things that are critical today, such as how to safely work with samples.

Almost all of the people in our teams were from the countries we were working in, which I think is critical for sustainability. People from our project in the Democratic Republic of Congo have participated in the response to the Ebola outbreak in West Africa, and have helped to stop two outbreaks in the DRC.

Even though our country teams are no longer employed by the project, they are often called upon as experts. They are basically back to work, either as volunteers or funded by their governments. So there is evidence that if you really invest in community participation and laboratory capacity, you can stop some of these things at their source.

During the current outbreak of SARS-CoV-2, we’re seeing that many of the people who worked on PREDICT are being named to national task forces. Shi Zhengli, our PREDICT country coordinator in China, was instrumental in the first detection of SARS-CoV-2 and raising awareness about it.

In a way, it seems that SARS-CoV-2 ticked all of the boxes of an outbreak that could have been prevented: A very similar virus was known to have infected people before, and a scientist you’re working with identified the virus very quickly, in a country with a competent government. Still, it took weeks after the virus was identified before a lockdown was enforced, allowing the virus to spread far and wide. How, in general, have governments responded so far to the kind of information you and your colleagues are gathering?

Some policymakers were already engaged, but many have said, “Please keep doing your research, but I’m too busy to think about these kinds of things, I have higher priorities.” I think that needs to change. The main takeaway for me is that we should now use the science to actually impact policies. That includes continuing to refine our knowledge, but definitely integrate the policy with the science as well.

Do you think it is really conceivable then, within our lifetimes, that we’ll have a vaccine ready to be tested as soon as there is an outbreak of any of the viruses you’ve identified as dangerous? The fact that we didn’t even develop one against SARS-CoV-1 does not inspire much confidence.

I do. It’s completely feasible. We’ve been talking to the Coalition for Epidemic Preparedness Innovations, a global partnership, which is supporting the development of vaccines for SARS-CoV-2 and other diseases identified as a priority by the World Health Organization. The US Department of Defense has also used one of the viruses found by the PREDICT project to optimize their vaccine development pathway.

Before this outbreak, the steering committee for the development of the Global Virome Project had abandoned the whole line of thinking around vaccine development and therapeutics, for the reason you’ve mentioned: Nobody did anything for SARS-CoV-1, so why would it be different in the future? I think now we have reason to assume that might change.

There is still a financial problem. There are market-based and even regulatory problems making it difficult to develop vaccines in advance. These will now finally get worked out, if there’s any silver lining to this horrible tragedy. Shame on all of us if they don’t, because we’ve been advocating this for a long time.