This article first appeared in The Checkup,MIT Technology Reviewsweekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first,sign up here. This week marks a strange anniversaryits five years since most of us first heard about a virus causing a mysterious pneumonia. A virus that we later learned could cause a disease called covid-19. A virus that swept the globe and has since been reported to have been responsible for over 7 million deathsand counting. I first covered the virus in an article published on January 7, 2020, which had the headline Doctors scramble to identify mysterious illness emerging in China. For that article, and many others that followed it, I spoke to people who were experts on viruses, infectious disease, and epidemiology. Frequently, their answers to my questions about the virus, how it might spread, and the risks of a pandemic were the same: We dont know. We are facing the same uncertainty now with H5N1, the virus commonly known as bird flu. This virus has been decimating bird populations for years, and now a variant is rapidly spreading among dairy cattle in the US. We know it can cause severe disease in animals, and we know it can pass from animals to people who are in close contact with them. As of this Monday this week, we also know that it can cause severe disease in peoplea 65-year-old man in Louisiana became the first person in the US to die from an H5N1 infection. Scientists are increasingly concerned about a potential bird flu pandemic. The question is, given all the enduring uncertainty around the virus, what should we be doing now to prepare for the possibility? Can stockpiled vaccines save us? And, importantly, have we learned any lessons from a covid pandemic that still hasnt entirely fizzled out? Part of the challenge here is that it is impossible to predict how H5N1 will evolve. A variant of the virus caused disease in people in 1997, when there was a small but deadly outbreak in Hong Kong. Eighteen people had confirmed diagnoses, and six of them died. Since then, there have been sporadic cases around the worldbut no large outbreaks. As far as H5N1 is concerned, weve been relatively lucky, says Ali Khan, dean of the college of public health at the University of Nebraska. Influenza presents the greatest infectious-disease pandemic threat to humans, period, says Khan. The 1918 flu pandemic was caused by a type of influenza virus called H1N1 that appears to have jumped from birds to people. It is thought to have infected a third of the worlds population, and to have been responsible for around 50 million deaths. Another H1N1 virus was responsible for the 2009 swine flu pandemic. That virus hit younger people hardest, as they were less likely to have been exposed to similar variants and thus had much less immunity. It was responsible for somewhere between 151,700 and 575,400 deaths that year. To cause a pandemic, the H5N1 variants currently circulating in birds and dairy cattle in the US would need to undergo genetic changes that allow them to spread more easily from animals to people, spread more easily between people, and become more deadly in people. Unfortunately, we know from experience that viruses need only a few such changes to become more easily transmissible. And with each and every infection, the risk that a virus will acquire these dangerous genetic changes increases. Once a virus infects a host, it can evolve and swap chunks of genetic code with any other viruses that might also be infecting that host, whether its a bird, a pig, a cow, or a person. Its a big gambling game, says Marion Koopmans, a virologist at the Erasmus University Medical Center in Rotterdam, the Netherlands. And the gambling is going on at too large a scale for comfort. There are ways to improve our odds. For the best chance at preventing another pandemic, we need to get a handle on, and limit, the spread of the virus. Here, the US could have done a better job at limiting the spread in dairy cows, says Khan. It should have been found a lot earlier, he says. There should have been more aggressive measures to prevent transmission, to recognize what disease looks like within our communities, and to protect workers. States could also have done better at testing farm workers for infection, says Koopmans. Im surprised that I havent heard of an effort to eradicate it from cattle, she adds. A country like the US should be able to do that. The good news is that there are already systems in place for tracking the general spread of flu in people. The World Health Organizations Global Influenza Surveillance and Response System collects and analyzes samples of viruses collected from countries around the world. It allows the organization to make recommendations about seasonal flu vaccines and also helps scientists track the spread of various flu variants. Thats something we didnt have for the covid-19 virus when it first took off. We are also better placed to make vaccines. Some countries, including the US, are already stockpiling vaccines that should be at least somewhat effective against H5N1 (although it is difficult to predict exactly how effective they will be against some future variant). The US Administration for Strategic Preparedness and Response plans to have up to 10 million doses of prefilled syringes and multidose vials prepared by the end of March, according to an email from a representative. The US Department of Health and Human Services has also said it will provide the pharmaceutical company Moderna with $176 million to create mRNA vaccines for pandemic influenzausing the same quick-turnaround vaccine production technology used in the companys covid-19 vaccines. Some question whether these vaccines should have already been offered to dairy farm workers in affected parts of the US. Many of these individuals have been exposed to the virus, a good chunk of them appear to have been infected with it, and some of them have become ill. If the decision had been up to Khan, he says, they would have been offered the H5N1 vaccine by now. And we should ensure they are offered seasonal flu vaccines in order to limit the risk that the two flu viruses will mingle inside one person, he adds. Others worry that 10 million vaccine doses arent enough for a country with a population of around 341 million. But health agencies walk a razor-thin line between having too much vaccine for something and not having enough, says Khan. If an outbreak never transpires, 340 million doses of vaccine will feel like an enormous waste of resources. We cant predict how well these viruses will work, either. Flu viruses mutate all the time, and even seasonal flu vaccines are notoriously unpredictable in their efficacy. I think weve become a little bit spoiled with the covid vaccines, says Koopmans. We were really, really lucky [to develop] vaccines with high efficacy. One vaccine lesson we should have learned from the covid-19 pandemic is the importance of equitable access to vaccines around the world. Unfortunately, its unlikely that we have. It is doubtful that low-income countries will have early access to [a pandemic influenza] vaccine unless the world takes action, Nicole Lurie of the Coalition for Epidemic Preparedness Innovations (CEPI) said in a recent interview for Gavi, a public-private alliance for vaccine equity. And another is the impact of vaccine hesitancy. Making vaccines might not be a problembut convincing people to take them might be, says Khan. We have an incoming administration that has lots of vaccine hesitancy, he points out. So while we may end up having vaccines available, its not very clear to me if we have the political and social will to actually implement good public health measures. This is another outcome that is impossible to predict, and I wont attempt to do so. But I am hoping that the relevant administrations will step up our defenses. And that this will be enough to prevent another devastating pandemic. Now read the rest of The Checkup Read more from MIT Technology Review's archive Bird flu has been circulating in US dairy cows for months. Virologists are worried it could stick around on US farms forever. As the virus continues to spread, the risk of a pandemic continues to rise. We still dont really know how the virus is spreading, but we do know that it is turning up in raw milk. (Please dont drink raw milk.) mRNA vaccines helped us through the covid-19 pandemic. Now scientists are working on mRNA flu vaccinesincluding universal vaccines that could protect against multiple flu viruses. The next generation of mRNA vaccines is on the way. These vaccines are self-amplifying and essentially tell the body how to make more mRNA. Maybe theres an alternative to dairy farms of the type that are seeing H5N1 in their cattle. Scientists are engineering yeasts and plants with bovine genes so they can produce proteins normally found in milk, which can be used to make spreadable cheeses and ice cream. The cofounder of one company says a factory of bubbling yeast vats could replace 50,000 to 100,000 cows. From around the web Bird flu has been circulating in US dairy cows for months. Virologists are worried it could stick around on US farms forever. As the virus continues to spread, the risk of a pandemic continues to rise. We still dont really know how the virus is spreading, but we do know that it is turning up in raw milk. (Please dont drink raw milk.) mRNA vaccines helped us through the covid-19 pandemic. Now scientists are working on mRNA flu vaccinesincluding universal vaccines that could protect against multiple flu viruses. The next generation of mRNA vaccines is on the way. These vaccines are self-amplifying and essentially tell the body how to make more mRNA. Maybe theres an alternative to dairy farms of the type that are seeing H5N1 in their cattle. Scientists are engineering yeasts and plants with bovine genes so they can produce proteins normally found in milk, which can be used to make spreadable cheeses and ice cream. The cofounder of one company says a factory of bubbling yeast vats could replace 50,000 to 100,000 cows.