Fluctuating funding and flagging interest hurt coronavirus research, leaving crucial knowledge gaps

Journalists covering the emergence and spread of the new coronavirus in China are awash with emails from public relations firms urging them to interview this expert or speak to that specialist. Some are infection control practitioners, others emergency planning specialists, still others people who advise the travel industry or study the weather.

Conspicuously absent from these proffered experts are scientists who actually research coronaviruses.

That’s because the field is small and modestly funded, and until very recently, was not viewed as a fertile patch on which to build a career. There’s been a boom-and-bust phenomenon in coronavirus research over the past two decades, as a series of animal viruses — SARS, MERS, now 2019-nCoV — have triggered outbreaks in people, causing a flurry of interest that subsides until the next flare up.

The waxing and waning interest in coronaviruses has perpetuated gaps in the scientific understanding of the pathogens. Scientists don’t know how long people remain immune to a coronavirus after being infected. There are still looming questions about transmission. There aren’t any drugs approved specifically to treat coronaviruses. Work begun to test existing drugs to see if they were effective against SARS was abandoned when that threat faded; having that information now would have given doctors in China help they badly need.

“When this [new] epidemic began, I think there were three or four of us who answered the majority of the calls. Because there are very few of us who are really doing this,” said Dr. Stanley Perlman, a professor of microbiology and immunology at the University of Iowa.

“I’ve trained a lot of people. Most of them don’t go into coronavirology,” he added.

“What’s surprising and what’s striking,” said Vineet Menachery, who studies coronaviruses at the University of Texas Medical Branch in Galveston, “is that the field is not hugely different than it was 20 years ago when SARS emerged. … There’s not a deep bench in the coronavirus field.”

There was little interest — and little money — in coronavirus research in the late 1990s. At that point, the only known human coronaviruses were ones that cause colds — not the highest scientific imperative. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in the lead-up to the SARS outbreak in 2002-2003, his agency devoted between $3 million and $5 million a year to research into the coronavirus family.

After the explosive SARS outbreak, which infected more than 8,000 people and killed nearly 800 worldwide (none in the U.S.), NIAID coronavirus funding increased tenfold, rising to a high of $51 million a year or two later. But within a few years annual funding settled back down to an average of about $20 million a year, toward the end of the decade, Fauci said.

Menachery, 37, began studying coronaviruses while working as a postdoctoral fellow under coronavirus expert Ralph Baric at the University of North Carolina in 2010. That was seven years after the SARS outbreak was extinguished, but a couple before another coronavirus, Middle East respiratory syndrome, or MERS, started infecting people who had close contact with camels on the Arabian Peninsula.

Menachery was interested in studying how pathogens interact with human immune systems. Baric’s lab had just started exploring how coronaviruses manipulate and interact with the host. Scientifically, it was a good fit. But career prospects-wise, it was a risky choice.

“When I was working in Ralph’s lab, the viability of coronavirus research was definitely a question,” said Menachery. “Could you build a career on coronaviruses was really a question in 2010.”

Lisa Gralinski, who is a research associate in Baric’s lab now, agreed.

“In the 10 years between the emergence of SARS and the emergence of MERS, you definitely had to be thinking about a broader context for your research for it to seem significant to the general public and to the NIH, when writing grants,” she said.

The uncertainty drove some scientists to choose other lines of research.

It created an age gap among coronavirus researchers — some older, established scientists like Perlman and Baric, very few intermediate career people, and more recently, some younger scientists who have joined the field.

“So these guys are all probably under 35 and the rest of us are over 60,” said Perlman, acknowledging the situation is not ideal. “We were worried before they entered.”

Funding stabilized after the emergence of MERS, said Gralinski, though it never reached the post-SARS high-water mark. Fauci said in the years since MERS began jumping from camels to people — sometimes igniting large hospital-based outbreaks when an undetected case infects other patients — NIAID funding for coronavirus research has leveled off at about $27 million a year.

The emergence of the new virus is going to change that figure, likely considerably, Fauci said. “I don’t know how much it’s going to be. But I think it’s going to generate more sustained interest in coronaviruses because it’s very clear that coronaviruses can do really interesting things.”

Menachery expects there will be more interest in entering the field, though he noted that because the dangerous coronaviruses can only be worked on in high containment laboratories — biosafety level 3 — they aren’t the easiest pathogens to research.

“I think there will be more depth in the field because I can reasonably say with three [new viruses] in 17 years, I don’t know if we’ve seen our last one,” he said. “We’ve gone through these cycles over and over again. [But] it may be that this coronavirus establishes coronaviruses a little bit more.”

That would be a boon for the scientific understanding of the viruses, given that the publication of coronavirus research papers, too, has followed those cycles.

The number of scientific papers that included the word “coronavirus” in the title or abstract jumped dramatically after the SARS outbreak began in 2002, according to an analysis of scientific content in the Web of Science Core Collection conducted for STAT. The database culls papers from more than 21,000 peer-reviewed, scholarly journals around the globe.

But when concerns faded as the outbreak was contained, and multiyear grants dried up, the pace of publication slowed. There were just 594 papers published on coronaviruses in 2011, compared to a peak of 1,007 papers in 2004.

“It was a success story, but no longer seemed as relevant,” said Gralinski, who studies the role of genetic variation in the severity of viral infections.

That changed after the emergence of MERS. Publication of coronavirus-related research picked up again in 2013 and continued to rise for several years. It appeared to be on the decline again in 2017, which researchers said could reflect the boom-and-bust phenomenon. About one-third of all papers on coronaviruses published between 2002 and 2020 were from scientists in the U.S., and another quarter were written by researchers in China.

    Coronavirus-related papers by country, 2002 to 2020

Scientists who have applied for funding to study coronaviruses say that they feel more pressure to explain why their research is relevant after an outbreak has ended. Those in the field knew that there was much more to be gleaned about the coronaviruses that already circulate in humans — and that a new coronavirus could start making people sick at any time.

But they still had to convince funding agencies of the need for continued research, which Menachery tried to do when writing a grant proposal as a post-doctoral researcher in Baric’s lab in 2010.

“I spent half of the first page — maybe three-quarters of the first page — justifying why we still worked on SARS,” he said.

Menachery got the grant on his second try — but even then, timing was probably a factor. He resubmitted his application in August 2012; a month later news broke that a new coronavirus — MERS — was sickening people on the Arabian Peninsula. The committee that reviewed grant applications met that November.

“I may have gotten it either way, but I don’t think it hurt,” Menachery said, adding that he isn’t sure he would be a coronavirus researcher today if he hadn’t received that first grant.

Some in the research community are hopeful that perception is shifting as the world grapples with another coronavirus outbreak and the need to continue closely studying the viruses becomes increasingly clear.

“In public health, we’re very good at reacting to emergency situations,” Gralinski said. “But preventive monitoring and research can be harder to justify and to sustain.”