Spanish Flu: a warning from history

Perhaps until recently, the Spanish flu has been what some people call a "forgotten pandemic." But it was a huge global calamity. In terms of the number of deaths, we say between 50 and 100 million, much more than the victims of the First World War, approximately around May, May 1918, when the carnage of the First is known. The World War is graphic and horrendous, but at the same time this unknown enemy is beginning to sweep the United States, Europe, the trenches and is recorded by the Spanish press and is known as the 'Spanish flu' because they are neutral. Well, at that time, in the 1920s, they estimated that maybe 20 million had died.

By the end of the 20th century, that number increased to 25 million. In the 21st century, scientists and historians are now coming together to work much more closely. This virus has killed more people in the first 25 weeks than HIV/AIDS has killed in 25 years. Those mortality statistics are staggering! We don't know exactly why the flu. Strains are much more serious than others and why some of them would be more likely to kill people or cause very serious illness. What is unique about avian and pandemic viruses is that they replicate deep in our lungs. When our cells detect this, they very strongly trigger an immune response that leads to an influx of white blood cells and fluid into our lungs and restricts the amount of airspace we have to breathe.

The symptoms are very graphic and very striking, so it is said that some people drowned in their own phlegm, so if it hit or affected the lungs, people would squirt blood from their ears and nose. Descriptions of people turning blue or purple so you know it was really bad and people just fell in the streets. Those who succumbed to the flu were in the age group of 20 to 40 years, which is very unusual for an influenza epidemic or pandemic and scientists. and historians are still investigating why. There are actually two ways people died in 1918: either they died from the initial flu infection or they died from an enormously strong immune response to that virus when their lungs simply filled with fluid as they tried to attack the virus that entered their lungs. lungs.

So traditionally everyone said, "Well, it's the trenches. You know the conditions of the war and that's why it was so fatal, but when you think about it, you know how it spread so quickly around the world to places that are not part of the theater". of war. I think the traditional explanation is that it starts in Kansas in a military camp and then the troops take it to the trenches, to Europe, but there are still a lot of unknowns. Thus, mathematical modelers have long been interested in the 1918 pandemic and one of the questions is trying to unravel how it spread around the world and what exactly its routes have been.

Given perfect data, you could work backwards and try to infer where it came from. Where does it arrive in a country, does it arrive several times or thinking about several countries, where is the first place? If you understand the origin of a pandemic, then you will understand where it comes from and maybe you can stop it in the future. It was almost certainly originally bird flu, but we also know that that flu or something very similar affected pigs at the same time. Maybe it's someone who works very closely with poultry or who works very closely with pigs or has some other exposure like that.

One of the really big open questions in flu research and flu public health is: How does the virus adapt from one species to another? How, for example, does a virus from pigs or birds reach humans and then begin to be transmitted? So the key question is: how does the virus adapt within that person to stop being a swine virus or a bird virus and become a human virus? in other words, being able to transmit from human to human and it's probably some very rapid evolutionary process that's happening within that human and in many cases it won't be successful, but in some cases we will be successful and that's when the virus can start to spread between humans and become a flu pandemic and then remain in humans as normal seasonal flu.

Just as people were celebrating Armistice Day and there was hope that it was fading, but then it resurfaced and a much more deadly and virulent strain emerged. So this second wave really spread like a forest fire that affected a third or a quarter of the world's population and was short-lived, so it died out not long after, maybe in 1920/1921, but in the sense that it was short-lived. What happened is that the virus continued to be transmitted between humans, in fact it continued until 1957 to be transmitted between humans and probably what happened there is that the virus adapted to humans.

It wasn't this avian or swine virus that came in and accidentally became more pathogenic in humans. In a lab here in Cambridge we study both seasonal flu and pandemic flu from the point of view of: how does the virus evolve? And how can we predict that evolution and make vaccines to try to artificially evolve the virus both in the lab and on the computer to understand what it will do next and make vaccines against the strains that will evolve in the future? So this is the basic science of the study of evolution trying to predict that evolution.

Something that no one has ever been able to do with a complex organism. And then work to use that knowledge to make better vaccines. On the pandemic flu side, we do something similar: we look at how that virus is changing, how that virus changes in birds, and how it changes in birds and other species, and we try to see what possible variants there might be. but vaccines that can protect against all the variants we see may need to be manufactured again. The flu is very difficult to eradicate because it is constantly mutating and changing its genetic information.

We work on the flu virus and in particular on the enzyme that copies the genetic information of the virus when it enters our cells. Specifically we are interested in how this enzyme is able to perform this activity and how it inserts mutations into a viral genome that leads to the formation of new strains for which we need to develop new vaccines. And we're also interested in knowing when this enzyme breaks down, how it triggers innate immune resistance and helps cause disease. We really don't know why we haven't seen a pandemic as deadly as the one in 1918.

Scientists and public health officials are extremely concerned about the national risk register, which is how our government plans for all risks to civil society. in the United Kingdom. There are only two events that measure up in terms of the most catastrophic and they are a terrorist event or an influenza pandemic. There is a real threat that pandemics such as the H5 and H7 influenza viruses could occur, which have already infected nearly 2,000 people and killed about half of them. With the H7 viruses there has been some not very efficient person-to-person transmission and it hasn't really taken off.

If any of those viruses were adapted to transmit really well between humans, there is a real concern that it could be as bad as the 1918 virus and that is why so much research is being done for the public good to try to understand what is happening and so a lot of work done by the public health people and preparing in the hospitals in case something like this happens. Well, experts like to say it's not if... but when? As a mathematician, this has happened many times in the past and will probably happen again. The 1918 pandemic is difficult due to lack of data, but the most recent influenza pandemic we had was in 2009 and there is very good data on that pandemic.

If we understand how the 2009 pandemic spread, maybe that tells us something we can use to help control future pandemics. We cannot stop them, the alternative is at least to better allocate our resources to try to reduce the number of cases in each place. Looking back a hundred years, to the last pandemic, also invites the question: a hundred years from now, what will we be like in terms of how well we will be protected against the flu? Or what things could we do to protect ourselves in some situations? We will surely be in a situation where we know more about what viruses are in the world and where they are, surveillance will be much better.

We will surely be in a better situation where we will have better medicines and better vaccines because we know more about the virus, we know more about its weaknesses, we know more about our immune system and we know how to enable it to fight those pathogens. better. At some point we will have a universal vaccine that will protect us against the flu for the rest of our lives. When this is another question. There are a large number of approaches and very good ideas for doing this. There are already attempts to do so that are at a fairly advanced stage.

It could be ten years from now, it could be twenty, thirty or forty years from now, we really don't know.