The dark history of influenza

“Influenza: The hundred-year hunt to cure the 1918 Spanish Flu pandemic” by Dr. Jeremy Brown

It was a global pandemic at a scale never seen in hundreds of years. It was believed to have been originated in North China, which predated the general outbreaks in Europe and America by few months. And the disease “was found in the spray and mucus from the throat, nose, and mouth. It could be spread through droplet infection by sneezing and coughing, and by hand-to-mouth contact.”

Despite the striking similarities, this, of course, was not Covid-19, but the 1918 influenza pandemic. It was dubbed the worst influenza pandemic in recorded history, infected around 500 million people (about one third of the total population back then) where it is estimated that between 50 and 100 million people died.

So, what happened? According to the author, Dr. Jeremy Brown, the experts have settled on 4 explanations for why so many people died in that pandemic:

1. The virus had a protein on its surface that prevented the production of interferons, which normally functioned to signal our immune system that our body have been attacked. Then healthy lung cells that transfers oxygen into the bloodstream are hijacked by the penetrating virus which destroyed them and replaced them with dull fibrous ones that are incapable of transporting oxygen.
2. With the patients’ bodies weakened and their lungs damaged, they caught bacterial infections such as staphylococcus or streptococcus which were deadly in this era before antibiotics. This is what the experts believed to be the main cause of the majority of deaths in the 1918, not from the flu virus itself but from these secondary infections.
3. The flu virus triggered an overreactive immune response that turned the body against itself. Normally, a wound causes an inflammation (necessary to fight infections) and the inflammation is mediated by other kind of messenger protein called cytokines. And once the infection is healed, our cells stop producing cytokines and our immune system returns to its normal state. But in many of 1918 flu victims, the return to normal didn’t happen and instead their lungs suffer from “cytokines storm”, an overproduction of these messenger proteins, which in turn destroy healthy cells along with invading ones. When the cytokines storm strikes, the immune system spirals out of control.
4. The rapid spread of the virus is due to living arrangements at the time, where people were living in tenements or barracks due to war, working-class families shared beds, soldiers slept side by side.

Attacking the lungs? cytokines storm? We might as well change the label to Covid-19 and the symptoms wouldn’t be out of place.

So what did they do to cure it? The immediate prevention measures tick all the contemporary boxes: wearing mask, social distancing, while businesses, schools and theatres were shut down. The book then shows the gruesome “remedies” for the flu pandemic, the trial and errors that would make us think that we’re sure glad to live in a more modern time. Remedies such as bloodletting, enemas, a shot of mercury, enormous dose of quinine, etc that are not only worthless in curing flu but also dangerous (bloodletting was the same procedure that killed George Washington).

Moreover, we often take for granted all the progresses that have happened in history, since a procedure as trivial as consuming aspirin to cure our flu symptoms can have deadly side effects during the 1918 pandemic, as back then doctors still haven’t figure out the safe dosage of aspirin that we should consume, hence people weren’t only dying from the flu but a lot died due to aspirin overdozed.

But eventually, the pandemic was over after 2 years and 3 waves, and the world proceeded to have the Roaring Twenties. So what cured it? Here’s the harsh truth, the pandemic was over because people who got infected either died or developed immunity. It became endemic. In other words, it was simply due to herd immunity that was developed over 2 years and not from a super cure that emerged to save the day (but at a very high cost of 50-100 million deaths). A rather anti-climactic ending, don’t you think?

This is where the book, written in 2018, then switches into a more technical elaboration that focuses on the 100 years of evolution of medicine since that 1918 pandemic and the journey to once and for all attempt to cure the disease of influenza. Now it is almost impossible to summarise every discovery in this review, but the following are the most important and relevant ones.

So, a virus is a box of chemicals that does not have the structures of a basic cell. They have no mitochondria (so they cannot make energy), they have no ribosomes (so they cannot build proteins), they lack lysosomes (which get rid of waste and toxins), they cannot metabolise, they cannot replicate on their own. So in order to reproduce, they must invade living cells. Viruses infects bacteria and plants, birds, fish, reptiles, and mammals.

While viruses do not target cells specifically to kill them, the mechanism where they hijack a cell and use it as a reproducing machine might injure, weaken, or destroy the cells as a collateral damage. In fact, if a virus is too lethal, it can destroy the host cells before they can even be used to create viral copies. This mechanism is the same for every virus, no matter how differ they are in the level of deadliness, from common flu to HIV to ebola.

According to Dr. Brown, in the discovery of the anatomy of viruses, “[w]e are especially interested in one particular family of viruses that has the clumsiest name: the orthomyxoviruses. Ortho means “straight,” in Greek, and myxa means “mucus.” The straight-mucus family of viruses includes influenza. Actually, there are three influenza viruses—they go by A, B, and C. Only the A and B strains cause significant disease in humans, and it is the A strain that is responsible for pandemic flu.”

Furthermore, if a mammalian strain and a bird strain of influenza hijack the same cell at the same time, their genes can mix to create an entirely new kind of virus that can turn deadly. This is exactly what happened in 1918 and in Hong Kong 1997, where birds contributed to parts of the influenza virus. While at first, the virus could only infect those who directly handled birds and could not be transmitted from one person to another, it would take only a small mutation for the virus to gain that ability, setting the stage for a new influenza pandemic.

And that is the key word, mutation.

But do not fret just yet, because our immune systems have evolved to prevent and contain the attacks from viruses, bacteria, and other foreign pathogens. The 1st line of defense consists of cells called phagocytes, which operates as a kind of traffic police that are always on patrol. Once they detect pathogens in our system they will envelop them and pull them inside the cell (where the pathogen will be obliterated). Dr. Brown explains, “Phagocytes do not target specific bacteria or viruses. Rather, they have been programmed in our genetic code to recognize pathogens in general. We are born with this innate immunity, and the phagocytes require no prior contact with a pathogen to search for, recognize, and destroy it.”

The 2nd line of our defense are the antigen-presenting cells, which target specific viruses or bacteria. While the 1st line is like a traffic police, this 2nd one is like detectives, they profile a suspect, they digest the pathogen and present some of its building blocks (such as a receptor or protein) to another type of immune cell called a helper T cell. These T cells then proliferate in huge numbers and use the pathogen profile to target the corresponding invader. Dr. Brown elaborates that “[e]ven years after a first encounter with a pathogen, T cells remember their old foe and spring into action. That’s why most of us get chicken pox only once. Our first encounter with the virus produces T cells that are forever on guard in the future.”

Indeed, the immune system does not care how the pathogen entered the body, as it will generate the same immune response regardless whether it came through the normal course of events or through a needle as a weakened form of vaccine. And after that the body is able to fight a similar invader more quickly and effectively the next time around, while if the antigen is new we may still produce antibodies against it but the process is slower and we become sicker for longer as our body adapts.

And that lies the core problem for influenza. The influenza virus throws a wrench into our immune system because it is a shape-shifter. It frequently changes the proteins on its surface, making it difficult for our existing antibodies to identify them. This is why we can catch the flu more than once, why the virus is almost impossible to eradicate, and this so-called “antigenic drift” is also why the flu vaccine needs to be updated every year (remember the key word, mutation).

In addition, there is a larger change that the virus can undergo, dubbed the “antigenic shift”, and this is how we get a flu pandemic. During antigenic shift viral proteins assume an entirely new structure and then the virus will become “novel.” (As in the case of novel coronavirus 2019). These novel viruses are most often arise when human and animal viruses share and swap their genes, and they emerge like entirely new criminals and not old one in disguise, which makes them more undetectable, more sneakier, more prolific, and potentially more deadly.

Antigenic shift generated the 1918 influenza virus and the swine flu outbreak of 2009, where the inflammation caused by the influenza virus can spillover to other problems, or the virus could attack the already existing disease(s) in our body, such as pneumonia, and make them worse by leading to a lung failure, kidney failure, and eventually multiple organ failures that culminated at the death of the patient.

And as Dr. Brown repeatedly mentioned in the book, it is not over yet. The battle against influenza has not been won, and another pandemic like 1918 was just around the corner because the virus itself never really go away and constantly mutating. Well, we now know what happen next in late 2019 and early 2020, with today in 2021 the “double mutation” delta variant is creating a new wave once again.