Though it has decimated poultry flocks and has become common in cattle, bird flu remains rare in humans, with just 70 confirmed cases nationwide. For the moment, the virus has not evolved the ability to transmit from person to person, though a recent study from Scripps Research Institute scientists found that it needs little additional mutation to make that jump.
Gathering at Scripps Research’s third annual Pandemic Preparedness Symposium last week, researchers working in virology and chemistry did not bother to debate whether or not H5N1 avian influenza will clear this rapidly shrinking hurdle. But some were worried that the current turmoil in Washington, D.C., could slow the nation’s ability to nimbly respond when this microscopic threat inevitably gains the ability to cause a global pandemic, potentially causing more deaths than COVID-19.
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This, argued virologist Angela Rasmussen, is not the moment for any sort of friction in the flow of information between government agencies and the private sector, which will need to collaborate quickly to deploy medical stockpiles, isolate the new strain and begin working on an updated vaccine.
“How are we going to find out if H5N1 has acquired the ability to be efficiently transmitted? How are we going to find that primary cluster of human cases and be able to contain it before it spreads outward to the point that it’s not containable?” Rasmussen said.
A principal research scientist at the University of Saskatchewan, Rasmussen is known for her often-attacked work tracing the origins of the COVID-19 pandemic to a “wet” market in Wuhan, China. She was by far the most outspoken at the symposium in La Jolla, where her presentation included a slide that decried “the destruction of American readiness.”
Projected on the event’s massive auditorium screen, the billboard-sized message referenced recent government actions targeting public health, medicine and science, including an order on Jan. 21 for federal agencies, including the U.S. Centers for Disease Control and Prevention, to pause all outside communications.
She also referenced news that the government recently fired and then tried to re-hire workers in a U.S. Department of Agriculture lab that, as The Associated Press put it, “were part of an office that helps oversee the national network of labs USDA relies on to confirm cases of bird flu and other animal diseases.” The presidential order to withdraw the United States from the World Health Organization also got a mention as did a recent freeze of federal grant funding.
Such actions, she said, increase the likelihood that H5N1 spreading from person to person will first be spotted in hospitals.
“I have nightmares about the fact that we won’t know that an H5N1 pandemic has started until we see that a hospital system has filled up with patients,” Rasmussen said. “It’s going to be worse, I think, in terms of the number of deaths and severe illness; it’s also going to be hugely economically impactful because of the effect on species that are critical to our food supply.”
That statement got some collegial pushback from immunologist Alessandro Sette, co-director of the Center for Vaccine Innovation at La Jolla Institute for Immunology. He noted that there are significant similarities between H5N1 and other flu virus types, such as H1N1, that have long circulated among humans.
Prior encounters with similar viruses, he argued, are likely to convey some level of protection for some people. T cells, specialized white blood cells critical to defeating invading viruses, can persist in the body long after infection, helping fight similar infections in the future. This phenomenon seemed to occur in 2009 when older people often fared better at fighting off H1N1, the novel flu strain that jumped to humans from pigs.
“Older people did better … because they had been exposed to the 1957 circulating H1N1,” Sette said. “So, pre-existing immunity in flu, it’s a real thing in terms of disease.”
Making it clear that he does agree with Rasmussen’s overall concerns, and that H5N1 is a significant threat, he said his comments were intended to broaden the discussion by noting that there “may be a sizable cross-reactive immunity that could come in handy.”
Rob Kirchdoerfer, a virologist at the Institute for Molecular Virology at the University of Wisconsin whose work was instrumental in understanding the structure of the SARS-COV-2 spike protein, agreed that this is a particularly fraught moment.
He concurred with several who worry about “reassortment,” a phenomenon where two different viruses infecting the same cell may swap genetic material, allowing changes that can help them make sudden leaps in adaptation to a new type of host.
“You have this virus, which I would probably say is still pre-emergent,” Kirchdoerfer said. “It is jumping between species. It jumps into humans. It’ll jump back into animal species, (and) I don’t think we know what the H5N1 that’s going to cause the pandemic is actually going to look like, and that’s actually more scary to me, because you have all of this opportunity for evolution and drift and reassortment, and so I (find) that absolutely terrifying.”
Rasmussen agreed that there remains some uncertainty as to the characteristics of the virus that will end up gaining the ability to move from person to person. Some subtypes appear in early reports to be mild while others, such as one type presented at last week’s pandemic conference, are known to be particularly lethal.
This recognition that there are several subtypes currently in play, all active simultaneously, is a level of nuance that Rasmussen, who holds a doctorate in microbiology from Columbia University, said is being used to downplay the true severity of the H5N1 threat.
“My big fear is that these … normal disagreements and uncertainties that are inherent to the scientific process are going to be weaponized against the scientific community to prevent us from actually doing the work we need to do to answer some of them,” Rasmussen said. “That is going to have tremendous consequences in terms of our ability to respond and in terms of our ability to actually mitigate potential loss of life.”
But that’s not to say that nobody has done anything to prepare for the advent of an H5N1 pandemic. At the urging of scientists, especially those gathering at symposiums like the one in La Jolla, the federal government has spent millions stockpiling both the chemicals and other components needed to rapidly manufacture new vaccines and also on doses designed to match earlier strains of H5N1.
A recent writeup from the Congressional Research Service says that there had already been 5 million doses of H5N1 vaccine produced, “with the expectation of 10 million doses by early 2025.” Some antiviral drugs such as Tamiflu, which can reduce the severity of illness after infection, are also estimated to have at least some effect against the virus. The stockpile report indicates that the government has “68 million antiviral courses on hand.”
Deploying those resources with as much dexterity as possible will, experts say, be the difference in the lethality of a coming H5N1 pandemic.
Rasmussen said that “back of the envelope” calculations she performed with a colleague indicate that pandemic bird flu could mean “7 to 10 million dead people” in the worst-case scenario, though skillful use of stockpiled resources could bring that number down. If accurate, the toll would be much worse than was the case for COVID-19, which killed or was the contributing cause of death for 1.2 million Americans, according to CDC estimates.