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In the early 1900s, deep in the woodlands of Central Africa, a virus that had been quietly circulating amid apes for millennia made an unlikely jump to humans.

Precisely how remains a mystery: Scientists suspect a person or persons ate an infected chimpanzee or cut a finger while butchering one, exposing themselves to blood tainted with simian immunodeficiency virus (SIV). It took hold slowly over decades, evolving in ways that made its spread from human to human more efficient.

By 1959, a mysterious illness was spreading in Haiti. By 1981, young men were dying at alarming rates in Los Angeles. By 2022, 36 million worldwide had succumbed to HIV/AIDS, what we now know as human immunodeficiency virus, which is closely related to SIV.

It was not the first nor would it be the last virus to wreak global havoc after jumping from animals to humans: H1N1, which originated in waterfowl, killed more than 50 million during the influenza epidemic of 1918. SARS-CoV-2, believed to have originated in bats, continues to drive the COVID-19 pandemic. In all, about 300 viruses are known to sicken people. It is lost to history just how many of these resulted from animal viruses that jumped to humans. But in recent decades, many more have.

What will be the next one?

That’s the question that keeps CU �鶹ӰԺ virologist Sara Sawyer up at night.

“There are estimated to be as many as 1 million viruses circulating in animals out there,” said Sawyer, a professor of molecular, cellular and developmental biology. “Which ones should we be preparing for next? That’s what I want to know.”

To that end, Sawyer has spent the last 14 years gathering hundreds of samples from primate, rodent, bat and other mammalian species to better understand what evolution has taught them about how to live with viruses. Her hunt has taken her from endangered lemur preserves to homes for retired celebrity chimps (including Michael Jackson’s famed Bubbles).

“I once received part of a coyote heart via FedEx,” recalled Sawyer, a skilled storyteller whose eyes grew wide, hands gesturing excitedly, as she described her life’s work.

In her lab at CU �鶹ӰԺ’s BioFrontiers Institute, she also studies viruses (SIV, dengue, influenza and more), employing cutting-edge genetic sequencing and lab techniques to better understand the answers to important questions: What enables some viruses to jump species and spread unbridled, while others fizzle out? And why can some hosts get exposed without getting sick, while others die?

“There are lots of examples in nature of evolutionary winners — organisms that have figured out how to be resistant,” said Sawyer. “If we can better understand what their immune systems are doing, we may be able to come up with solutions we never thought of before.”

Coming of Age in a Pandemic 

Sawyer was sitting in her seventh-grade health class in Olathe, Kansas, in the mid-1980s when her teacher made a chilling proclamation.

“She said, ‘There is this new disease, and if you have sex, you could die,’” recalled Sawyer.

During these formative years, the nightly news was filled with stories of children orphaned by AIDS in Africa and U.S. celebrities contracting the disease. Just as the generation before her had grown up in the shadow of the influenza epidemic, she was shaped by AIDS.

“That virus influenced my life in profound ways, much like COVID is shaping young people’s lives in ways they don’t know yet,” she said.

Sawyer earned a degree in chemical engineering from the University of Kansas and worked on offshore drilling platforms to bank money for graduate school.

Just as she began a PhD program in genetics at Cornell University, she spotted the 1996 : It was AIDS researcher David Ho, who pioneered the earliest effective drugs for the disease. Clad in aviator glasses, he looked to Sawyer like a rock star.

“I said to myself, ‘I want to be that guy,’” Sawyer said.

Hitting the Jackpot

Today, along with running a lab and teaching classes, Sawyer has gained a global reputation as a leader in her field, with the U.S. government tapping her for consultation on how to prevent and better respond to pandemics, including the COVID-19 pandemic. 

“She has been at the front line of viral disease research asking the big questions that have helped us understand how zoonoses emerge and cross into humans,” said Cody Warren, a postdoctoral researcher who came to CU’s BioFrontiers Institute for the chance to work with her.

As Sawyer explained, hundreds of thousands of viruses circulate unnoticed in the animal world, often without making the animals sick. (SIV, in most cases, does not harm non-human primates.)

“We are all breathing and ingesting animal viruses every day, via the pets we keep, the undercooked food we eat, but they just pass right through us,” she said. 

Sometimes, however, a virus sticks, and when a virus infects a species whose immune system is naive to it, it can run wild.

“The jackpot moment for an animal virus is when it doesn’t just pass through, it gets into our cells and turns our body into a factory for reproducing itself,” she said. “What constitutes a virus jackpot like that? Why that time and not another time?”

Genetics, her lab’s research has found, plays a role.

In one recent study, published in the journal PNAS, Sawyer and Warren show that genetic variations between chimpanzees make a critical difference in how they react to SIV. For instance, some resistant chimpanzees possess a variant of a gene called CD4 that leads to a sugar-like coating forming a protective barrier over the receptor to which the virus attaches.

Such variations between individuals can not only influence how viruses spread within the same species, but also how they jump from species to species, including to people.

“Zoonosis doesn’t just occur when a human encounters a chimp in the wild,” said Warren. “You have to have this magical interaction between the right human encountering the precise chimpanzee that is genetically predisposed to harboring that viral infection.”

Notably, a very small set of humans — about 1 in 300 — also appear to be resistant to HIV. 

“If we could understand what evolution has figured out and make drugs to mimic that, we could protect ourselves,” Sawyer said.

Predicting the Next Pandemic

During a lecture in Sawyer’s undergraduate class on emerging viral diseases in 2019, Warren rattled off a list of recent coronaviruses that jumped from animals to humans via an intermediary host, igniting epidemics: Severe acute respiratory syndrome (SARS-CoV-1), likely jumped from civet cats to people in 2003. MERS jumped to humans via camels in 2012.

“I told them, six different coronaviruses have emerged in humans, two in just the last 20 years, and it is very likely that another one will emerge in the not-too-distant future,” Warren said.

As soon as the first cases of COVID-19 began appearing in headlines, Sawyer’s inbox filled with messages from students, acknowledging she and Warren had called it.

SARS-CoV-2, she notes, was particularly troublesome because it is a respiratory virus that spreads easily, and because most people experience mild or no symptoms — enabling it to continue to spread by the unknowingly infected.

“Deadly is not the best evolutionary state for a virus,” said Sawyer. “If it kills people too fast, it doesn’t spread.”

She feels optimistic that COVID-19 will grow less and less dangerous, morphing into an endemic, cold-like nuisance. But her lab always has a close eye on what’s to come.

“We have a highly fatal bird virus sweeping the U.S. right now, H5N1. Humans can get that virus from birds, and it is 50% fatal, but fortunately it has not yet learned how to spread from human to human,” she said. “That is the only thing separating us from another epidemic at this moment.”

Meanwhile, she stays true to the mission that got her into this work to begin with — the quest to develop a vaccine for HIV.

Yes, COVID-19 has been tragic and deadly, killing 6 million worldwide as of May 2022. But Sawyer asks people to put it in perspective.

“Forty years into the HIV pandemic, caused by a virus from which nobody recovers, and which causes a psychologically torturous disease, we are still losing 2,000 people per day and we have no vaccine,” she said. “We can do better.”

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Illustrations by Eleanor Shakespeare; photos courtesy of Sara Sawyer