Is the cure for COVID-19 in the Rocky Mountains?

HAMILTON, Montana: It's entirely possible that the secret to understanding - perhaps even vanquishing - the coronavirus rests in this quiet town of 5,000 nestled at the edge of the wilderness.

Hamilton is home to Rocky Mountain Laboratories, run by the National Institutes of Health. Outside, the campus looks west toward the meandering tributaries of the Bitterroot River and panoramic views of the snow-capped Bitterroot Mountains. Inside, in a windowless, air-locked room, elite virologists in positive-pressure suits, hooked up to oxygen hoses, handle the world's deadliest pathogens, from avian flu to Ebola to plague.

The lab normally has 450 employees. But right now it is largely empty, with 50 to 75 people working feverishly around the clock on only one illness: COVID-19.

Why Rocky Mountain Laboratories?

There's still so much we don't know about the novel coronavirus. And the race to unravel its many mysteries and develop a vaccine against it is a global effort without precedent. Dozens of governments and private companies have poured vast resources into hundreds of studies and trials. And yet, when it comes to coronavirus research, the center of the universe may just be Rocky Mountain Labs - one of only nine federal facilities in the country with a biosafety Level 4 capacity, the highest.

The lab has five research teams focused on COVID-19, and they have already made critical contributions to our understanding of the virus. As The Times reported last week, crucial vaccine trials in rhesus macaque monkeys using a vaccine from Oxford University were performed by a team led by Vincent Munster. Another team quickly built a reliable animal model to grow the coronavirus in cell cultures and has demonstrated early effective results of therapeutic drugs to treat the virus in animals.

A third group has submitted research on effective disinfection methods for N95 respirator masks using ultraviolet light. Similar work out of the lab has tested how long the virus can live on various surfaces. Those striking electron microscope images of the spiky coronavirus you've seen in almost every online article about the virus? Those came from here, too.

First alerts

Emmie de Wit, the head of the lab's molecular pathogenesis, first heard about the virus in late December. She got an alert from an infectious disease list-serv called ProMED about a pneumonialike illness in Wuhan, China. Dr. de Wit, who began studying coronaviruses in 2003, told me over the phone that the alert immediately caught her eye as something to monitor.

By early January, she'd heard rumors that it was caused by a coronavirus. "That's when it became interesting for us," she said. "We started thinking, 'OK, we have the skills to contribute to research on this. And so we started to make a plan."

Dr. de Wit and her fellow virologists made a checklist. They started with steps they could take as soon as the gene sequencing data of the virus went online. They made plans for how to create an animal model of the virus (reproducing the virus inside live animal cells) once they could get access to it. They waited and watched the news out of China. It wasn't until on the night of Jan. 10, when a postdoctoral fellow at the lab looked at the sequence of the virus, that Dr. de Wit knew what was coming. It appeared the virus was targeting a specific receptor on cells called ACE2, the same receptor targeted by both SARS and the virus that causes the common cold.

"The alarm bells went off then because it suggested that it could be both very prevalent and very contagious," Dr. de Wit said. The lab immediately made plans to be fully prepared as soon as researchers could get the live virus.

Dr. de Wit told me that the weeks since then have been a blur. For the last month her team has worked to test the antiviral drug remdesivir in rhesus macaques. The findings - which showed the drug "significantly reduced" the progression of the disease and lung damage in the animals - made national news as the drug continues to move into human trials.

Tireless work

She and her colleagues work seven days a week, arriving in the lab early and coordinating to make sure they're socially distanced, including inside the air-locked biosafety lab where they're handling the virus.

The researchers have been told to take extra precautions to avoid infection in the lab and in their lives outside. "It's long days at work and then come home and eat and sleep," Dr. de Wit said. She goes to the grocery store early on weekend mornings to avoid crowds. The stakes are high: If they get infected, their potentially lifesaving work would have to stop indefinitely.

"At first it was all so fascinating and new from a scientific standpoint," she told me. "But then I began to see we could get a pandemic. That's when I got worried. It's a weird experience because you're scientifically fascinated, but on a personal level, you start to think more seriously about what this means for the people you love if this keeps spreading."

I stumbled upon the lab after seeing it mentioned in passing in news reports. I was shocked to find it was less than an hour's drive from my home in Montana. It felt improbable that the eyes of the global medical community were fixed on a small town near the Idaho border. But this is far from the first time that Rocky Mountain Labs has changed the way the world understands diseases.

Around 1900, a new, deadly plague roared through the Bitterroot Valley. It produced a fever and a dark rash that caused the region's inhabitants to name it "black measles." When no treatments worked, Montana brought in medical investigators to try to determine the cause.

A University of Chicago researcher named Howard Ricketts, working out of a makeshift tent, isolated the bacterium that caused the disease and replicated it in guinea pigs. Eventually, he showed it was transmitted via tick bite. The disease became known as Rocky Mountain spotted fever. Before long the doctors working in the valley managed to create a vaccine by collecting ticks, grinding them with a mortar and pestle and treating the mixture with formaldehyde.

By 1930, the Rocky Mountain Labs campus began in earnest and merged with the National Institutes of Health. Since, the lab has been at the forefront of infectious disease discoveries in the United States. During World War II, the lab produced the yellow fever vaccine for American soldiers and was a national vaccine factory. In 1981, a Swiss-born entomologist at the lab, Willy Burgdorfer, identified the tick-borne bacterium that caused the then-mysterious Lyme disease.

The lab's work on prion diseases and neurodegenerative infections shed light on Lyme, a deer-borne illness, chronic wasting disease, as well as mad cow. Its researchers have also contributed to Ebola vaccine breakthroughs and have sent teams to West Africa to conduct research in hot zones.

Stellar legacy

Dr. Marshall Bloom, the associate director for scientific management at Rocky Mountain Laboratories, notes that three important infectious diseases of the 20th century were not only identified here but also that the pathogens that cause them are named for lab investigators: Rocky Mountain spotted fever (the bacterium is Rickettsia rickettsii, named for Howard Ricketts), Q fever (Coxiella burnetii, named for Herald Cox), and Lyme disease (Borrelia burgdorferi, named for Willy Burgdorfer).

During a two-hour Zoom call, Dr. Bloom, who has been with the lab since 1972, proudly rattled off high points of its 120-year history from memory. For him, the past successes are proof of a larger concept of preparedness: investing in infectious disease research during times where the country isn't in the middle of a deadly pandemic allows us to respond quicker when disaster strikes. The lab's work on older diseases - like the 1918 influenza or coronaviruses like SARS and MERS - advance scientific discoveries but also give researchers a jump when emerging threats appear.

"The possibility that we might face a pandemic was not a surprise to us," Dr. Bloom said. This cut down on preparation time and could shorten the timeline on precious discoveries that could pave the way for a vaccine or effective coronavirus therapy.

In an email, Dr. Bloom's boss, the National Institute of Allergy and Infectious Diseases director Dr. Anthony S. Fauci, cited the lab's "significant and unique contributions in the field of emerging infectious diseases" as "strong evidence for the critical need for long-term funding of basic research."

In recent years Dr. Fauci has paid multiple visits to the lab and given lectures at Hamilton's performing arts center. Dr. Bloom remembers Dr. Fauci's last lecture, in October: Dr. Fauci discussed his work with previous presidents, going back to Ronald Reagan and the AIDS epidemic. Then he mentioned President Trump. "I don't know what the future holds or how he'll respond, but I'd bet at some point during his administration this president will have to confront a disease threat," Dr. Bloom remembers him saying. "It was prescient."

Despite being one of the select people in the world to experiment with the virus up close, Dr. de Wit has the same questions and uncertainties we do. "On one hand, I can be optimistic because I've seen the speed and progress for myself. On the negative side, it'll be a while before we truly have this under control," she said. "Like anyone, we all have worries about relaxing too much."

With the eyes of the world watching, Dr. de Wit and her colleagues are immersed in the minutiae of the virus. "We have to get this right the first time because there is no room for error," she told me.

But on occasion she's reminded that the work she does isn't just globally relevant, but also hits close to home. One day, leaving the lab, she noticed a bright scrawl of letters outside the gates. While she was inside carefully working with the deadly virus, Hamilton residents had written messages in chalk along the sidewalk and on rocks. "Thank you!" they read.