Scientists want to stop the next pandemic before it starts. Here are the tests they're building to do it

Md Ashif Ikbal sees connections between the pandemic and the climate crisis. And he has been working on solutions to both.

Ikbal, who is pursuing his Ph.D. at Arizona State University, works as a graduate research associate in assistant professor Chao Wang’s lab in the school of Electrical, Computer and Energy Engineering. Wang and his team recently released a study detailing their design for a new type of pathogen-detecting technology that they say is more efficient and accurate than existing techniques.

It’s a new way to test for viruses, at a time when viral testing has been put front and center for communities and individuals alike.

Wang and his team also say their test could be tailored more readily than existing tests to detect any novel virus that emerges around the world. And the threat of new viruses is becoming more urgent as human activities encroach on wild spaces and drive deforestation and biodiversity loss.

Ikbal, Wang and the rest of their team aren’t the only ones in Arizona working to prevent the next pandemic from spiraling out of control. On a local level, scientists are sequencing genomes, surveilling animal populations and researching ecology and environmental policy to better understand and limit the threat of novel infectious diseases.

For Ikbal, who is from the southern tip of Bangladesh, the research hits close to home. He says the future humans are creating feels immediate to him.

“If the sea rises another couple of inches, most of my neighbors will be underwater,” he said. “So those kinds of things always play on your mind. What's going to happen in 10 years’ time, 20 years’ time?”

If current warming trends continue, rising sea levels will displace as many as 20 million people in Bangladesh alone by 2050, according to a report from the National Resources Defense Council. Meanwhile, a team of scientists estimated last summer that the probability of observing pandemics similar to COVID-19 may double or even triple in the coming decades, a direct result of environmental change.

That’s partly because many novel diseases originate in animals, and though there is no conclusive consensus on the origins of this pandemic, many scientists think SARS-CoV-2 spilled from animals into humans, too. In addition, environmental change exacerbates conditions that make pandemics worse, especially for vulnerable populations, including famine, drought, air pollution and more.

Ikbal himself just recovered from a 10-day bout with COVID-19, and credits the vaccine with his ability to overcome the virus. But well before that, he had an interest in biotechnology and health in addition to sustainability. He says that the untimely deaths of two close relatives spurred his interest in helping to save other human lives.

“You have family members, you want them to have a natural, fit and long life. But when (a family tragedy) happens, you tend to be more like … ‘is there any way that we could have probably prevented this thing to happen?’”

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The future of testing

When Wang first started working on a new type of testing technology over three years ago, he was focused on a different disease: Ebola. Though Ebola never had the same catastrophic impact in the United States as it did in West Africa, an outbreak in the Democratic Republic of the Congo in 2019 killed more than 2,000 of the over 3,300 people it infected, according to a report from the Kaiser Family Foundation.

So Wang and his collaborators set to work, combining techniques from electrical engineering and bioscience. The idea was to attach special molecules, called nanobodies, to tiny particles of gold. The nanobody-spiked gold flecks, which are only one-thousandth the width of a strand of hair, act like magnets for a virus.

Researchers can collect a biological sample (say, a blood test) in a test tube and pour in a solution containing the gold nanoparticles. If the disease of interest is also in the test tube, the nanobodies will pull it in, forming microscopic clumps. Because the nanobodies are tailored to attract only a certain kind of pathogen, the gold will only get weighed down if the pathogen is present.

Those clumps, which become large enough for gravity to send them sinking through the solution in the test tube, fall to the bottom. The more pathogen is present, the more gold will end up at the bottom, and the less will remain suspended in the fluid in the tube.

That’s where the electricity part comes in: When an LED light shines through the tube, the intensity of the color reveals how many particles are still bouncing around. That color corresponds to how much, if any, of the virus was in the sample.

Wang says that was exciting because they could accomplish the whole process in one test tube, and the amount of gold needed is so minuscule that the cost stays low. The results took three to four hours to develop, but they were accurate and were less subject to human error than other lab tests.

In 2019, at the time they first invented the technique, Wang had hoped that developing cheaper, simpler and more effective diagnostics would make a difference in the field, where disease responses to threats like Ebola can sometimes be slowed by a lack of funding or socioeconomic factors. “It's not the (tests) that are more complex, but the ones that are simpler” that make an impact, Wang said.

Then a new virus appeared, and the challenges were magnified. A three- to four-hour response time wasn’t good enough.

“The (coronavirus) pandemic happened, and I grabbed two of my students in my office and told them … ‘You know, I think this is time to make an impact. It’s a once in a lifetime opportunity,'” Wang said.

So they accelerated the project. They needed some way to make those little gold magnets act faster. They tried several techniques, but finally they settled on centrifugation — basically, using existing mechanical devices to spin the tubes really fast, speeding up the separation of the nanoparticles from the rest of the solution.

It worked. Now the test only takes 15-20 minutes — about the same amount of time as your average rapid antigen test, but with the potential for the precision of a PCR. In addition, the nanobodies that make the test work can be generated for any novel pathogen in just one to two weeks, according to Liangcai Gu, an assistant professor of biochemistry at the University of Washington who collaborated on the project.

Wang and his team say more development will be needed in order for the tests to be distributed commercially, but for now, Ikbal says their lab’s main contribution was to help demonstrate that their test could be applied to diseases beyond Ebola.

“If it takes three to four months to develop the detection system, then (a new) infection might as well be out of hand,” he said. “The process that we have developed is applicable for COVID and not only for COVID, but for any other new infectious disease that might arrive. … That’s the main advantage of this method.”

It’s an advantage that other scientists say is needed to help stop the next pandemic before it spirals out of control. “We're always battling that ability to have those rapid and accurate point of care screening tools,” said Hayley Yaglom, a genomic epidemiologist at TGen’s pathogen and microbiome division who has formerly worked in disease surveillance with the Arizona Department of Health Services.

It’s just one part of a wider landscape of pandemic prevention and response that Yaglom says “utilizes all these other technologies” – for example, genomic sequencing to understand the full genetic code and origins of infectious diseases, or identifying targets for new vaccines.

But the process Yaglom has spent her life on involves animals, and it’s a project she continues in Arizona today.

Animal surveillance

Skunks with rabies, prairie dogs that carry the plague and housepets with COVID-19 are all in a day’s work for Yaglom. She hopes that by seeking out and keeping track of diseases in fauna, scientists can prevent the worst effects from hitting humans.

“Human, animal and environmental health (are) all interconnected,” she said. “How do we use that to drive forward our methods of thinking and understanding about what exists and what's coming down the line?”

Most recently, she’s been trying to answer that question by investigating the four-legged companions that most often come into contact with humans — domestic dogs and cats. Yaglom says that of the 110 pets they’ve tested so far in Arizona, about 35 % have tested positive for COVID-19.

As far as they can tell, none of those animals gave the virus to their owners. But they’re interested in the data because if human-to-animal or animal-to-animal transmission continues, it could create opportunities for the virus to mutate and potentially spill back to humans. Keeping tabs on a variety of species could also help scientists understand how the virus passes from one animal to another.

It’s a pressing mystery for epidemiologists and zoologists. In other parts of the country, large populations of deer are testing positive for the coronavirus (according to a study from Penn State, that number totals as many as 60% of deer sampled in December 2020 in Iowa). And in Hong Kong, pet hamsters likely transmitted the coronavirus to at least two humans, resulting in further human-to-human spread, according to a recent preprint in the Lancet.

Yaglom says SARS-CoV-2 is so new that scientists are still trying to understand just how far it can spread in animal populations, and what the implications might be for humans. That, she says, is why it’s important to seek out more information from the animal world.

“In infectious diseases … If we don't look for it, we're not going to find it. And when we look for it, we will find it,” she said.

She added that in 2022, she and her colleagues beyond TGen, including researchers at local zoos, the U.S. Department of Agriculture and the Arizona Game and Fish Department, plan to continue expanding maintenance and monitoring programs to examine the effects of the pandemic on animals in captivity, as well as wild animals. She says they will collect samples to test for the presence of the coronavirus or antibodies against it, as well as other viruses or microscopic life of interest.

That work ties into existing programs that monitor populations of skunks, bats, prairie dogs, gray foxes, birds and other animals for all kinds of disease-causing pathogens including rabies, West Nile virus, hantavirus and even the plague. In the fall and winter of 2021, Yaglom says Flagstaff wildlife partners discovered that a variant of rabies typically found in brown bats was driving a significant rabies outbreak in skunks, suggesting that a spillover event had occurred from the former species to the latter. Tracking that outbreak gave scientists the opportunity to make an animal vaccination plan, protecting local pets and other species, including us.

Rabies still rarely affects humans, and most of the diseases currently being monitored in Arizona don’t pose a significant risk of instigating the next pandemic. But Yaglom says that doing surveillance work before someone ends up in the hospital, regardless of how rare a disease may be, is essential.

“Even from a local level, (we use) these same kinds of technologies and approaches to understand … what is circulating in those communities and then what prevention can be done,” she said.

And around the world, scientists believe those are the tactics that will be necessary on a broader scale to keep future pandemics from happening. In a new review in the journal Science Advances, an international team of researchers calculated that more widely instituting what they call primary pandemic prevention measures, including tactics like expanding viral surveillance, monitoring hunting of wildlife and limiting deforestation, costs less than 1/20th of the value of lives lost to emerging viral diseases.

“Policymakers and the public may neglect threats from low-probability, future catastrophic pandemics,” the team wrote. “This oversight leads us to underestimate expected annual lives lost (and the associated costs) by almost an order of magnitude.”

Global issues, local connections

Many of the root causes of pandemics are also the root causes of the climate crisis, said Aaron Bernstein, one of the coauthors of the review and the interim director of the Center for Climate, Health, and the Global Environment at Harvard. He added that stopping those intertwining problems at the source would not only reduce harm to humans from future pandemics, but also have other benefits to human health.

“One of the points of our paper is to drive home that we cannot make our decision on how to respond, how to address pandemic risk, in absence of understanding what's going on with life on Earth and the climate,” Bernstein said.

He described documented examples of that overlap: For example, exposure to air pollution leads to worse outcomes for people infected with respiratory infections. In addition, drought or lack of adequate water supplies can make pandemic-related hygiene measures more difficult or impossible — an issue that directly affected many in the Navajo Nation as COVID-19 spread across the state.

The pandemic has highlighted a variance in the degree to which different nations, states, governance structures and institutions “can or cannot absorb this kind of shock,” said James P. Collins, the Virginia M. Ullman Professor of Natural History and the Environment at Arizona State University.

Collins, who has spent decades studying emerging diseases in amphibians, said that when he puts together a group of investigators, he aims for a diversity of expertise ranging from the cellular and molecular level all the way to systems of global change. As he has used research to study pathogens in other species, he says that the international, interdisciplinary teams like his and Bernstein’s reflect the urgency and challenges of stopping future pandemics before they start.

Bernstein says primary efforts to prevent pandemics are more equitable. Stopping a disease before it starts means everyone, rich or poor, remains protected. “Tests and drugs will benefit rich people first and sometimes only, and that's morally objectionable,” he said.

But primary prevention, like reactive measures, requires technology — say, satellite imagery to monitor destruction of forests — that’s expensive. Bernstein and his team say they’ve shown that the investment pays off in the long run. Still, Bernstein also acknowledges it’s impossible to stop every spillover event.

That’s a main motivation for efforts like the one Ikbal has joined.

“If you look at the greater picture (of) sustainability and the pandemic as a whole, it is taking a toll on not only the poorer nations, but the poorer people of this country as well,” Ikbal said.

He added that while Arizona may seem removed from emerging disease hotspots or the effects of a changing climate, the issues are salient for local researchers and residents alike.

“We are not shielded from natural disaster, especially the way Arizona is set up, the way Phoenix is set up,” Ikbal said. “I see a lot of similarities between Arizona and Bangladesh. Because in Bangladesh, we have an excess of water … here, we don't have enough. So it's just the opposite side of the coin. But the effects are (the) same.”

Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.

Melina Walling is a bioscience reporter who covers COVID-19, health, technology, agriculture and the environment. You can contact her via email at mwalling@gannett.com, or on Twitter @MelinaWalling.

This article originally appeared on Arizona Republic: Nanobodies, climate study: ASU scientists aim to stop next pandemic