Sometime in the 1990s, an Indonesian crime lord  named Ponten Ginting made a deal with a demon.

He asked for wealth and power,  and his wish was granted. But instead of paying up, he stiffed the demon.

In 2006, though Ponten was already deceased,   members of his family began to fall  ill with a mysterious affliction. Local magical practitioners consulted the spirits,   and their message was clear:  it was time to pay the piper. Seven members of the family, they said,  would be claimed by the vengeful demon.

Though some of them received  state of the art hospital care, others distrusted medical authorities and  sought out local ritual experts instead. After all, who was better at dealing with demons? But the medical authorities feared  a different cause: H5N1 influenza.

Bird flu. As some of the Gintings fled for the remote  hills of Sumatra, responders raced to keep up, isolating their contacts and testing  for the presence of the virus. Only one of the Gintings had been  closely exposed to infected birds.

That meant this could be the big one:   a strain of avian influenza that  could spread from person to person. At the time, bird flu was known to  kill up to 60% of those it infected. If the responders failed to contain the outbreak,   a pandemic could claim the  lives of one billion people.

Fortunately, the outbreak fizzled. Exactly seven of the Gintings  died, just as predicted. The antiviral drug Tamiflu was distributed to   the Gintings’ close contacts, but  many of them declined to take it.

To them, the demon explanation was sufficient. After all, no birds were obviously sick, and no  one outside the Ginting family had fallen ill. Ponten had tampered with supernatural  forces he should have left alone.

It just made sense. The Gintings’ story tells us two things. One, that people tend to act  rationally according to their   own beliefs – not according to  what experts want them to do.

And two, that the next flu pandemic  is just one stroke of bad luck away. Seasonal flu alone kills half  a million people every year. The next pandemic, if it’s H5N1,  could kill many times that number.

Bird flu is out there. In fact, it’s increasingly out there. While it’s impossible to know when  and where a pandemic will begin, bird flu is getting more and  more chances to make it happen.

Eventually, it’s going to figure it out. My name is Pardis Sabeti, and I’m a professor  of infectious disease at Harvard University. Among other things, I study how to combat  emerging infectious diseases, like bird flu.

However we respond to H5N1, those  tools will be the ones we have to   use against the next pandemic  flu, and the one after that. Will we vanquish bird flu, and  everything that comes next? Or will we be complacent and  allow many millions to be lost?

Here’s why bird flu is almost  inevitable, and what we can do about it. [♪ INTRO] The Ginting family believed that a  demon was responsible for their illness. But if you’ll allow us a metaphor, maybe it’s not  all that strange to think of the flu as a demon. One that’s out to get all of us.

One that’s dogged us for much of recorded history,  shifting its shape to strike in different forms. This demon is clever, so to outwit it,  we need to understand how it operates. In the case of H5N1 avian flu,   we know exactly what needs to happen for  it to become able to easily infect humans.

Dr.

Webby: This is a virus that's  still very, very much a bird virus. So, you know, it's not a virus that  certainly infects humans very well,   doesn't transmit between humans. And so this virus has got to change. It's got to change in a way that switches  it from preferring to replicating in birds   to preferring to replicate in  humans for a pandemic to occur.

Dr.

Sabeti: That’s Dr. Richard  Webby, a virologist and expert   in host-microbe interactions at  St. Jude Children’s Hospital. And because H5N1 is infecting more  and more birds and animals every year, we also know that it’s getting  more and more chances to achieve   the changes it needs to easily infect humans.

Dr. Gronvall: Viruses have  lots of mutational options to them,   and they produce a gazillion of themselves. And so they explore the full range  of their genetic possibilities,   often in every infection that they have.

And so, you know, we're basically giving them lots   of shots on goal as we're giving them  opportunities to, to infect people. Dr.

Sabeti: That’s Dr. Gigi Gronvall,   a professor at Johns Hopkins University  and an expert in pandemic preparedness. We’ll be hearing more from  both of these experts later. Basically, H5N1 is a problem  because it’s… everywhere.

It’s infecting wild birds  on nearly every continent,   giving it lots of opportunities  to cross over to humans. And when it does, it can be incredibly bad. So how did the demon get to this point?

First, let’s look at its history. In the year 412 BCE, the father  of medicine himself, Hippocrates,   treated patients with symptoms of influenza. And it’s only picked up steam since then.

The historical record is patchy for a long time  after that, but the first recorded flu pandemic, where the disease spreads over a wide area,  likely occurred sometime in the 16th century. And since the start of the 20th century, we’ve  had flu pandemics in 1918, 1957, 1968, and 2009. In other words, we’re under  regular assault by this demon.

And the H5N1 flu virus is one  of its most frightening faces. Every flu virus has eight genes – a crack team  of eight minions, each with their own specialty. Whenever you hear flu referred  to as H-number-N-number, that’s in reference to two of its key  minions: hemagglutinin and neuraminidase.

Hemagglutinin is the most important  one for our purposes today. It’s the team’s safecracker. It recognizes a type of sugar molecule on  the surface of cells, called sialic acid, and uses that to break the virus in.

In the normal seasonal flu you might  get, the safecracker is either H1 or H3. Both are experts in breaking  and entering in human cells. H5 specializes in infiltrating bird cells.

If it stays that way, that’s good  for us, albeit not great for birds. Dr.

Webby: One of the biggest host  range barriers between avian hosts   and human hosts is the sugars  that this virus likes to bind to. So it's a virus that's got to  get inside a cell to replicate. Flu viruses bind to a sialic acid  sugar on the surface of the cell. They bind to that and then that  gets the virus inside the cell.

In avian hosts, that particular sialic acid is in   a slightly different form than  what is most common in humans. Dr.

Sabeti: Basically, a  slight chemical difference   between bird cell sugars and human  cell sugars is what keeps H5N1 out. If H5 ever learns the trick to  consistently breaking in using   human sugars instead, we’re in for a bad time. Our immune systems have seen H1 and  H3 before, and they know what to do. But almost no one’s immune system has  ever met an H5 – as far as we know.

But every once in a while, H5 can –  just barely – get its foot in the door. Let me show you what happens when it does. But as a warning, we’ll be talking  about the death of a young child.

Sometime around 1996 in southern China,   the influenza virus learned to  take on a new form in birds. In 1997, a three-year-old boy named Lam Hoi-Ka   played with some baby birds  at a school in Hong Kong. Did your kindergarten teacher ever bring in an  incubator and let you watch baby chicks hatch?

It might have been something like that. Five days later, the child was dead. His lungs were ravaged – but so were his  kidneys, his liver, and even his blood.

As far as we know, he was the first  human victim of H5N1 avian flu. Authorities raced to find the cause, but when  they did, they couldn’t believe their eyes. Bird flu wasn’t supposed to infect humans.

It wasn’t supposed to be possible. Yet more cases began to spring up. In total, eighteen infections  would be detected, with six dead.

Eventually, the authorities  ordered a drastic step. Dr.

Webby: That particular virus was probably  born within the live poultry markets in Hong Kong. It was born within those systems,   within the chickens and ducks and  other species in those markets. So, when the authorities in Hong  Kong decided to depopulate all of   those birds, they got rid of that  particular form of the H5 virus. Unfortunately, the precursors  and close cousins of that virus   were still circulating in southern China.

Dr.

Sabeti: That is to say – killing  virtually all of Hong Kong’s poultry   stopped the 1997 outbreak, but it didn’t  destroy the demon virus at its source. It would strike again. So, why was this first outbreak so scary? It’s not just that our immune systems  don’t know what to do with H5.

It’s that so far, by flu standards,   H5 is especially deadly and  causes especially severe disease. Beginning with the 1997 outbreak, H5N1 has had  a case fatality rate as high as 60% – that is,   60% of cases detected resulted in death. Keep that figure in mind, though,  because we’re going to need it later.

If you extrapolate that number to a global  pandemic, and if you assume that the virus   doesn't get milder as it gets better  at jumping between humans, you end   up with the unimaginable global  crisis of 1 billion people dead. Now, that is a hair-on-fire,  worst-case scenario for a few reasons. One, the case fatality rate can’t account  for infections that aren’t detected,   and there are definitely  infections that go undetected.

Those undetected cases are likely  to be the ones that are less severe,   so the real case fatality rates  usually get lower with more detection. Two, viruses can get milder as they begin to  transmit more efficiently among the population. So a bird flu pandemic probably  wouldn’t kill a billion people,   but that doesn’t mean it wouldn’t be really bad.

Dr.

Webby: So it’s certainly not going to be 60%. I can almost guarantee that, but I  do think it would probably be the,   you know, probably the worst—the worst flu  pandemic that, you know, we have recorded. Dr.

Sabeti: Dr. Webby told us that  that’s because the virus still has   plenty of capacity to cause severe disease. It’s really difficult to try and guess what  the actual case fatality rate might be,   with some experts putting  it at more like 15 to 30%. Keep in mind that even a 1% case fatality rate  would be a completely awful thing to have happen.

COVID-19 hovered around a 1% fatality  rate in the United States prior to 2023,   and everyone still remembers  how horrible that was. The 1918 flu was proportionally deadlier  – its case fatality rate was 2.5%. Basically: Even if H5 isn’t as  deadly as we think it could be,   it’s still the deadliest version of  influenza we’ve ever encountered.

After the 1997 outbreak, health authorities all   over Southeast Asia were on  high alert for this threat. And in 2003, the alarm bells  sounded in Hong Kong once again. In late 2002, a mysterious respiratory disease  was causing deaths in Guangdong Province, China.

Though the Chinese government initially tried to   downplay this outbreak, it  reached Hong Kong in 2003. H5N1 was known to be circulating in wild birds at  the time, and several human cases had cropped up. The natural question experts asked themselves was:   Was this the beginning of the  long-feared bird flu pandemic?

As it turned out, no. This wasn’t bird flu, or a flu at all. This was a demon of a different kind:   a type of virus thought to be mostly  harmless, called a coronavirus.

And yet the disease caused by this coronavirus,  called SARS, killed in similar ways to flu,   by causing a storm in the lungs known  as acute respiratory distress syndrome. SARS required similar healthcare  responses to severe influenza,   like ventilators and hospital beds. And SARS spread in similar ways  to flu, though a bit less readily.

That means that although it wasn’t flu,   SARS was a stress test for how we would  handle an outbreak of disease similar to flu. So, Dr. Gronvall, how did we do?

Dr. Gronvall: We did not learn enough from SARS. We saw that there was this zoonotic  spillover from animals to people.

That's the way more than three quarters of new  diseases—new infectious diseases come about. We never did develop a vaccine. We never did really develop tests for it.

What we did learn is that these  things can happen and that public   health can contain it if, if we're lucky. Dr.

Sabeti: And we did contain it. The SARS pandemic ended with only about  8500 cases, of which about 11% were fatal. The outbreak was stopped before it could  get any worse thanks to old-fashioned,   boots-on-the-ground epidemiology. What I mean by that is finding cases, finding who  they’ve been in contact with, and isolating them   before it’s too late – that’s “contact tracing,”  the thing we kept hearing about during COVID.

SARS proved that it really can work. And yet, hospitals and healthcare workers were  overwhelmed in places with the worst outbreaks. So we didn’t exactly pass our  stress test with flying colors.

While we were earning that C, maybe a B-,  the threat of bird flu was growing stronger. As I mentioned, the safecracker that is H5  needs to undergo some very specific changes   to be able to infect humans more easily,  as well as to spread from person to person. But the more opportunities it gets,  the more likely that is to happen.

And several times in the 2000s,  it came terrifyingly close. Once again, we’re going to  tell a very sad story here. It’s the tragic case of an 11-year-old  Thai girl named Sakuntala Premphasri.

Around August of 2004, the chickens in  her rural village all sickened and died. Within a few days, Sakuntala herself fell ill. Though she was taken to a hospital for  treatment, nobody guessed bird flu.

Eventually, she was admitted for pneumonia. Pranee Thongchan, her mother, was a garment  worker whose job was 200 miles away. When she heard the news, she did what any mother  would do and rushed to the girl’s bedside.

We can only imagine what she went through as   she cradled the girl in her arms  for the last hours of her life. Yet things were about to take another turn. As Pranee attempted to return  to work, she too fell ill.

Not only had she already gone  through the very worst thing a   mother can – the disease would take her life, too. Pranee’s considered one of the first certain  cases of human-to-human transmission of H5N1. Her occupation didn’t put her into contact  with birds that could make her sick,   but she was in very close contact with Sakuntala.

Imagine if, in the depths of her grief, as she  tried to move on with her life and her job,   one of her coworkers had caught the disease  from her, and it had spread from there. It’s worth noting that Pranee’s sister, Pranom,   also got sick, but she was given the  antiviral drug Tamiflu and recovered. That brings us back to 2006, to Ponten Ginting,  his supernatural dealings, and his children.

The eldest daughter Puji  was the first to fall ill,   possibly through exposure to poultry next  to the market stall where she worked. It appears six other family members  caught the disease from Puji. Only after that does it appear that one of the  sons, Dowes, caught the virus from one of them.

He developed the symptoms so much later than everyone   else that it’s unlikely for him to  have gotten it from Puji directly. In other words, this outbreak represented  transmission from person to person,   and then to another person – something  that had not been seen before. Fortunately, it stopped there.

A local ritual expert claimed to have  protected the remaining family members   from black magic by creating a  protective boundary around them. The only remaining son, Jones,  became gravely ill, but recovered. And residents of the community, knowing full well  of the patriarch Ponten’s dealing with demons,   blamed black magic for the  illnesses – not influenza.

They refused to take Tamiflu  when it was given to them. I want to emphasize that this isn’t  foolish behavior – not according to   the way these people understand the world. In public health, it’s important to  try to reach people where they are,   not convince them they’re wrong.

Otherwise, they may distrust  efforts to help even more. We’ll come back to that idea. In both of these outbreaks, we  can see two main tools being used.

One is contact tracing. The other is oseltamivir, an antiviral  drug sold under the brand name Tamiflu. Oseltamivir works by blocking  the activity of neuraminidase,   one of those other minion genes we talked about.

It’s given to manage symptoms in patients  who are already having bad cases of flu. It can also be used to try to  prevent flu symptoms from developing. Now, that all sounds great, and  at the time of these outbreaks,   it was believed to be one of the best  weapons for fighting the influenza virus.

However, since then, support for the use  of oseltamivir has declined slightly. One mega-review in 2013 suggested that  neuraminidase inhibitors like oseltamivir   don’t do much in terms of preventing  symptoms in otherwise healthy people. At least, not enough to be worth the side   effects or the virus potentially  evolving resistance to the drugs.

Yet, these drugs do seem to be great for  avoiding death in severe cases and   shortening the duration of symptoms,  at least when it comes to seasonal flu. And the CDC recommends using oseltamivir for   post-exposure prophylaxis in folks  who have been exposed to bird flu. So we haven’t thrown it out the window, but at  the same time, we probably need to concentrate   on multiple strategies to make sure we’re  ready for the next time the demon strikes.

Which it did, in 2009. Dr. Gronvall: The 2009 H1N1  pandemic was pretty unexpected.

Everybody had, for years, been preparing for  H5N1, and it was going to be coming from Asia,   Southeast Asia perhaps, but definitely  somewhere not around the United States. Dr.

Sabeti: The 2009 so-called “swine  flu” originated in North America. It was an H1N1 virus, which happens to employ the   same two primary minion genes as  the devastating 1918 flu pandemic. And while this H1N1 wasn’t the same virus,  it had some things in common with it. Three viral lineages, including one descended  from the 1918 strain, all infected pigs.

They held a sort of genetic white elephant  gift exchange, and emerged as a novel virus   just unfamiliar enough to our immune  systems to trigger a new pandemic. You might remember the swine flu as having   been “mild.” But the demon is  cruel, and mild is relative. Even as the disease spared older  people – which is uncommon for   flu – it was devastating in pregnant people.

Dr. Gronvall: And at the time I was pregnant and   just anxiously awaiting the vaccine  and eventually was able to get it. But I had the fun experience of having my OB  tell me, 'cause he knew me as a professional   as well as being my doctor, say, "Oh, we  lost another healthy woman last week to H1N1." Dr.

Sabeti: The 1918 flu was also especially  dangerous in those who were pregnant,   so perhaps the 2009 version inherited  that tendency from the older virus. We might also be able to explain why the 2009 flu   spared seniors – which has  implications for bird flu. There’s a concept in immunology  called original antigenic sin. This somewhat poetic name basically just  means you never forget your first flu.

And depending on how old you are, your first  flu might be different than someone else’s. See, after the flu successfully causes a pandemic,  it doesn’t just kick its heels up and retire. Rather, it embeds itself in the human population,  spreading in seasonal waves around the world.

Pandemic flu becomes seasonal flu. That means, if you were born between  1918 and 1957, your first flu was H1N1. Between 1957 and 1968, it was  H2N2, after 1968 it was H3N2,   and of course, H1N1 is now circulating  as well – so it can be either one.

As soon as the 2009 pandemic broke  out, researchers speculated that   anyone born prior to 1957 might have  some immune protection against H1N1. And while it’s not 100% certain, the idea  does seem to be supported by the evidence. One group of researchers has  applied this concept to bird flu.

They were studying two types,  H5N1 and another avian flu, H7N9. And they noticed a strange age distribution  in which patients got infected with which flu. Specifically, H7N9 is more dangerous  in patients who were born before 1968,   and H5N1 is more dangerous in those born after.

The researchers suggest that for some reason,   the H1s circulating prior to 1968 seem  to provide some protection from H5. That would explain why older  folks were less vulnerable to H5. Meanwhile, H3 may promote  some protection against H7,   hence why younger people were more  vulnerable to H5, but less so to H7.

This does provide a glimmer of hope. Especially with H1 circulating again, we might not  be quite as defenseless against H5 as we thought. Which is good.

Because here in the 2020s,  the demon is closing in. You might recall a very different respiratory  disease pandemic that occurred beginning in 2019. In fact, you might be wondering  why we’re so worried about flu   when the big one hit, and it wasn’t flu at all.

Well, it’s because just like with SARS,   how we responded to COVID-19 sheds light on  how we might respond to the next flu pandemic. Dr. Gronvall: I think we would be more  stretched thin during a flu pandemic   now than we were during covid because there has  been less interest in going into public health.

At first there was a big surge,  and then that has leveled off. I think that there is even more dissonance in the   public sphere of how people  think about public health. And so I think that it's going to be  hard to get expert messages across.

So I think it really all depends, I think people,   good leadership can really  try to turn this around. Consistent public health communication can help,   but there are negative forces that really  make it a lot harder than it needs to be. Dr.

Sabeti: We did learn a few  important things from COVID-19. We developed testing, and we even turned  around vaccines in record time. COVID-19 also showed that we  can share data and scientific   insights way faster than we could in the past. Rather than waiting to publish formally in a  journal, a scientist can upload a paper to a   preprint server, and another scientist halfway  around the world can read it the same day.

But… we learned a lot of other stuff, too,   about how easily hospitals can  run out of beds and ventilators. To put it mildly, we also learned that  misinformation can spread quickly,   and that it can affect people’s behavior. We learned that people won’t always act  purely in the interests of protecting others,   nor will they defer to experts  just because they’re experts.

So you might say COVID has helped us  a lot in preparing for a flu pandemic. But there’s another side to that coin. Many of us are just tired of  thinking about pandemics – and   that fatigue causes things to break down,  just when they need to be at their strongest.

Dr. Gronvall: I think we have some of the elements in place,   but I worry that our diagnostic testing  is not quite up to where it needs to be. We had recommended a lot more interaction  between the private sector and government,   public health, to be able to roll  out diagnostic tests more quickly.

And I'm not sure that we're there yet. So I think the lesson is that  you can't let systems wither   and deteriorate so that you can't ramp them up. Dr.

Sabeti: We’re tired, and we’re distracted. Unfortunately, us not wanting a pandemic to break   out doesn’t mean the demon will  politely wait until we’re ready. While we were all distracted  by COVID-19, it made its move. During the 2010s, it kind of  seemed like H5N1 had gone quiet.

Nobody talked much about bird flu then. But it was an illusion. Dr.

Webby: It didn't cause a  lot of outbreaks in poultry   and there wasn't a lot of human infections either. But we also got to, when we talk  about activity with this virus,   we've also got to remember that surveillance,  meaning actively going out and looking for   this virus, hasn't been constant  throughout all this time as well. So some of that dip in activity in the 2010s,  some of it's probably reduced to a little bit   of lack of funding over that time period  to go out and actively look for the virus. So a little bit of virus changes  over that time, probably a little   bit of circulation without us even knowing.

Dr.

Sabeti: H5N1 was slowly spreading  through its native hosts, wild birds. As early as 2005, researchers realized  this was going to be a problem. You see, birds are well known  for their ability to fly. Even though the early outbreaks we’ve  talked about were all in Southern or   Southeast Asia, H5N1 didn’t stay there for long.

It spread to the rest of Asia and North Africa,  where it’s been especially troublesome in Egypt. From there it traveled to Europe, and settled in  across all of Asia, Africa, and the Middle East. Then, in 2021, something changed.

The expert safecracker, H5,   evolved a new set of tools that made it  even better at getting into bird cells. And that allowed bird flu to spread  explosively all around the globe. 2.3.4.4b doesn’t sound like a  compelling name for a villain. If you were a film producer, you would  send that one back to the writers’ room.

Yet H5s belonging to the subgroup called  clade 2.3.4.4b have taken over the world. It has spread aggressively among wild birds,  quickly outcompeting and replacing older H5s. And it’s spread farther than any  other H5 avian flu that’s come before.

It’s now endemic in Europe, meaning  it’s embedded in the local population   rather than coming through as  migrating birds bring it with them. And while it’s not yet endemic  in North and South America,   at the time we’re making this at the end of 2024,  it’s very much here and causing serious problems. Since 2022, this demon virus –  with its robotic new name – has   been showing up in a troubling number of mammals.

Among other things, it’s been ravaging  populations of seals in South America. It does not seem like it’s worked  out how to spread between mammals   easily – other than the seals –  which is good news for us humans. Rather, these infections seem to be happening   because there’s just so much  virus around in wild birds.

Dr.

Webby: When we look at the virus, this current  batch of H5s and their ability to infect mammals,   it doesn't seem to be that much different than  other H5s that have come over the past 25 years. So again, my gut feeling is that we're  seeing more mammals infected with this   virus simply because there are many more  infected birds, sick, dying birds that   fall out of the sky, and along comes a fox  or a skunk or name your scavenging mammal. They take a big old bite of that infected bird   and get to have a huge dose of  virus and get sick themselves. And because the virus was out there  in the wild birds, there was plenty of   opportunity for domesticated birds to come into  contact with them and become sick themselves.

In 2022, migrating wild birds  in the spring and fall caused   outbreaks in domesticated  fowl in the United States. These outbreaks required the killing  of tens of millions of birds. And this is a real thing we have to think about  when we’re fighting back against the demon.

Bird flu is so deadly in birds that entire flocks  have to be culled if infection is detected. That also has real economic costs to people. If you live in the United States, and you’re not  a vegan, the virus has probably already affected   your life by driving up the price of eggs – an  important source of cheap, vegetarian protein.

That year also saw the United States’  very first human case of H5N1,   in a farm worker involved in  carrying out those poultry culls. Fortunately, the individual experienced  mild symptoms and recovered. That brings us to the present day,   and I’m sorry to say, the demon  appears to be at our doorstep.

More outbreaks among poultry have resulted in  more cullings – and more infections in humans. But there’s a weird twist. Cows are getting bird flu.

They’re not getting it from chickens, by and  large, though they are giving it to chickens. It seems like a single spillover from wild birds   is now spreading among dairy  cattle in the United States. And because there’s not really a system in place  for testing and isolating cattle, and because   cattle are transported all over the country, it’s  spread to multiple herds and multiple states.

I won’t quote an exact number because it will  definitely change by the time you see this. When we were finalizing the research  for this video at the end of 2024,   there had been at least 58 confirmed or  reported cases of bird flu in humans in the US. But again, that number is likely to be  higher by the time you’re watching this.

You can go to the CDC’s  website for up-to-date info. A common infection route seems to be dairy  workers getting milk splashed in their eyes. The good news is that – again, knock on wood,   and we have a really long production schedule  – zero of those people have died so far.

And yet I told you that H5N1 kills somewhere  between 15 and 60 percent of its victims. This gap needs explaining, and  no one has an answer for why. The route of infection seems  to be one potential reason.

The individuals who have been infected by getting   splashed in the eyes tend to show  symptoms in, well, their eyes. Many have had no symptoms  other than conjunctivitis. We do know the H5 safecracker can sometimes break   into the cells of the eye,  so that’s no big surprise.

But the fact that it’s not causing much  mischief in the lungs is definitely a relief. It’s also possible that just getting  splashed with some milk doesn’t give   you a large enough amount of the  virus to make you really sick. Dr.

Webby: Maybe it's infection route. If you're a fox or a bear or a mountain lion  and you chomp into a heavily infected bird,   you're getting lots of virus in the  nose, lots of virus in the mouth. Whereas perhaps on those, a milking parlor  and a dairy cow herd or a flock of chickens,   maybe it's more aerosolized and landing on the conjunctiva in the eye,   landing in the very extremities of  the nasal passages, maybe it's a dose. Again, if you give a higher dose,  maybe you get more severe disease.

Dr.

Sabeti: The reason we’re seeing  mild disease isn’t totally clear. It might seem like the demon has lost its fangs. But scientists can clearly  see that’s not the case. Dr.

Webby: It's something that I wouldn't  say exactly keeps me up at night,   but it's something I scratch my head about a lot. Why are there all these signals saying this  is a really, really, really, really, really,   really nasty virus, but at the same time, not  causing much disease in the people in the US. Dr.

Sabeti: Because outside of  the US, cases caused by the same,   2.3.4.4b-derived virus have been severe. One infection was reported in Ecuador  and one in Chile, both in 2023. While neither were fatal, both  caused very serious symptoms. And in case you’re tempted  to chalk the difference up   to the US’s superior healthcare system,  that’s not the difference maker here.

The farm workers becoming infected in the US  sometimes belong to highly vulnerable groups. They may be undocumented, they may  not speak English as a first language,   and they may not have great access to healthcare. So it’s definitely not that.

But this is where we are right now. The demon is all around us. It’s threatening our food supply, and it’s  starting to cause infections more and more often.

None of those infections have spread from  person to person yet – that we know about. But given enough opportunities, it will. And to be clear, the US is not the only  place where a pandemic could begin.

I know, we really like to  make things all about us. A pandemic could start in South America  or Southeast Asia or virtually anywhere. But this cow situation is bizarre, so  it makes sense for all eyes to be on us.

The question now becomes: How do we fight back? We have tools to fight a bird flu pandemic. Some are low-tech, like getting boots  on the ground to do contact tracing,   or to monitor herds of cattle for that matter.

Some are more sophisticated, like Tamiflu. And believe it or not, we have vaccines for H5N1. We know enough about how to make a flu  vaccine to make one for H5 that we can be   pretty confident will work – and scientists  keep an eye on it in case that changes.

A universal flu vaccine is another option. The hunt for something like  that is intense and ongoing. It’s so intense that it’s too much to  go into, even in a video this long.

So in summary: They’re working on it. Other high-tech tools could also come into play. mRNA vaccines, like the ones developed during the  COVID-19 pandemic, could certainly have a place. But to limit speculation, I’d like to  focus on what we could do right now.

Supplies of H5N1 vaccine are limited. But it’s hard to see why we shouldn’t use them to   protect the people we already know are  vulnerable: poultry and dairy workers. Dr.

Gronvall: When it comes to how we handle the   current H5N1 dairy cow crisis, we  have to do things the right way,   you have to try to do things to avoid  stigma for the people who are at most risk. You need to have supportive medical care for those   people and explain what the potential risks are. You also can't just put everything on them.

And I think they should be offered flu vaccines and H5N1 vaccines when we get them. But we need to be doing much more surveillance of the dairy cows as well. Dr.

Sabeti: By the way, the US CDC is  offering free seasonal flu vaccines   to farm workers in the states most affected. Getting vaccinated against seasonal flu probably  won’t prevent them from getting bird flu. But it can reduce the burden of seasonal  flu in case bird flu cases start to pile up. Unfortunately, getting enough bird flu  vaccine in hand could be a challenge.

Sometimes, the economic incentives around  preparing for a pandemic can be… stubborn. Dr.

Webby: We could spend millions to  billions of dollars making H5 vaccine   now and never, ever, ever have an H5 pandemic. So it's tough, but at the same time, the potential  consequences of an H5 pandemic are terrible. So there are going to be resources well  spent either way, in my mind anyway. Dr.

Sabeti: Whether with  vaccines or something else,   we have a responsibility to  protect these farm workers. And what’s more, it needs to be now, not when it  seems like a pandemic is already breaking out. Dr. Gronvall: I think now is the time where  we should be concentrating on providing   those resources, any medical resources to the  people who are most at risk for being infected.

We shouldn't be thinking about waiting  until there's an actual epidemic forming. We should be concentrating on making sure that the  people who are at most risk are most protected. And that includes the people and the animals that  are closest to the dairy cows that are infected.

Dr.

Sabeti: As Dr. Gronvall  told us more than once,   we can’t make it the responsibility of  the vulnerable to prevent a pandemic. We learned from the Gintings, as well as  from countless people during COVID-19,   that people will act in a way they  believe to be their own interests. Good science communication and good  public health leadership will be crucial.

Because as I mentioned, many of the people in  the most danger in the US are undocumented,   or not in a great position to  trust the healthcare system. Building trust in public health is hard. Sometimes, it’s about convincing someone  who sincerely believes a malevolent spirit   caused their illness that Tamiflu is  the best way to protect their community.

Sometimes, it’s about explaining the  need to wear eye protection when milking,   even though people aren’t getting all that sick. It isn’t easy, and people will be mistrustful  and defensive sometimes, because they’re people. Dr.

Gronvall: And so you have  to put structures in place,   you have to have leaders who talk about this. You have to make things available, and  you have to communicate effectively. And this has been done with variable  degrees of success over the last decades.

Dr.

Sabeti: So vaccines, plus  monitoring, plus good leadership. Sounds like a recipe for success. Does that mean we’re ready  for a bird flu pandemic? Dr.

Gronvall: We are not  ready for a bird flu pandemic. Can we get ready? Absolutely.

We're making things a little hard for ourselves. We... I don't know if this is containable  anymore, given the number of herds   that are infected.

If it turns out that this is nothing, great! But this is a great opportunity for us to get  better at figuring out how we can stop something   like this and we should take advantage of that  at minimum, to be able to stop the chains of   infection to figure out what's causing it and  to protect the people who are most at risk. Dr.

Sabeti: We have to act now because,  unfortunately, we can’t see the future. Dr.

Webby: I think if we look at that  from the current situation we're in,   let's think about this virus  running through our dairy industry. Are we prepared for that? Have we been prepared for that? No, not at all.

One, from an ability to respond. Two, from having plans in place as to  what happens if this virus gets into dairy cows. There is no plans for that because one,  this virus doesn't get into dairy cows.

So why would you even have a plan for that? And of course it did, so we needed it. Dr.

Sabeti: Apparently, we  still have some work to do. Fortunately, so does the demon. Despite how close it is, it still  needs to figure out human transmission. It’s had so many opportunities, but so far, it’s failed every single time.

We know, at a molecular level, exactly  what would have to change… and it hasn’t. Dr.

Webby: We are look at its ability to grow  in different cells and in different hosts. It's still very much an avian virus. So from that perspective, it does have to change quite a bit before it could  become human to human transmissible. And the fact that it hasn't done so over the  past 25 years, despite having lots and   lots of opportunities to do so, at least to me  suggests the barrier for this virus to switch   from being a bird virus to being a mammal virus,  a human virus at least, is probably quite high.

Dr.

Sabeti: A bird flu  pandemic could happen tomorrow. Or it could never happen. So why did we say a pandemic is almost inevitable? Well, no one can know that, of course.

But it’s a matter of opportunity. Nothing guarantees that H5N1 will  evolve human-to-human transmission. But its increased presence  in wild birds, poultry, cows,   and humans is giving it the chance  to take as many shots as it likes.

Dr.

Webby: The hardest question to answer  is what is the actual risk of this virus. I can talk in terms of relative risk. So I think in terms of relative risk,   we're probably as high as we've ever been  with H5 virus, just simply because way,   way more exposure of humans to infected animals. Dr.

Sabeti: Relative risk is still relative, and  in absolute terms the risk is probably still low. But the problem is that we currently have  the perfect conditions for it to happen. Dr. Gronvall: Is H5N1 and these  sporadic infections and this ongoing   problem with dairy cows, is this  going to be the next pandemic?

No one can say. What we can say is that there is   no other logical path that we know  of for how you get to a pandemic   than having these infections occur  in animals and spill over to people. Dr.

Sabeti: We are going to have a lot  of choices ahead when it comes to   meeting the challenge this influenza virus poses. Some of it is about science  and technology – making   sophisticated new tools to protect ourselves. Some of it is about leadership  and public health – meeting people   where they are with the information  they need to make good decisions. And some of it is about basic empathy  – making sure the people in the most   danger are protected, no matter who they are.

How we meet the demon in battle  will say a lot about ourselves. And just like with SARS,  COVID-19, or past influenzas,   what we learn will apply to every  flu we have to fight in the future. But with science on our side, I’m  hopeful it’s a fight we’ll win. [♪ OUTRO]