The 1918 Spanish Flu—Why We Were So Vulnerable

Part One of Three in a series of articles tracking the rise and fall of the 1918 Flu

By Bruce Fleury, Ph.D. for The Great Courses

Epidemic diseases have often changed the course of human history—the death of a world leader, an epidemic before a great battle—but few diseases have accomplished it through sheer brute force. The deadliest epidemic of all times wasn’t smallpox, wasn’t the Black Death—it was the 1918 Flu. In one year, an estimated 50 to 100 million people died out of a global population of 1.8 billion. In America alone, 675,000 people died of the flu.

Army Hospital No. 4. Fort Porter, N.Y. during the 1918-19 ‘Spanish’ Influenza pandemic. (Image: Everett Historical/ Shutterstock)

Note from the editor:

This is the first article in a series of three that covers the flu of 1918.
In his 24-lecture series, “Mysteries of the Microscopic World,” Dr. Bruce Fleury covers the world of bacteria, viruses, fungi, and other organisms, collectively known as microbes.

In Lecture 11 of the series (the first of three lectures on the deadliest epidemic of all time), he speaks about the virus that caused the 1918 flu, investigating its structure, method of infection, and strategy for evading the human immune system.

Even though when this course was produced we were still years away from the first reported cases of COVID-19, it gives context to our current climate to look back on this stage of our world history and witness how it affected the entire world.

Below, you can read his lecture in its entirety, and watch the full video.

More Americans died of the flu in a single year than in World War I, World War II, Korea, and Vietnam combined.

It was one of the great watershed events in the history of the world, but it has remained shrouded in a cloud of silence ever since. The usual explanation is that World War I took center stage. But it is also true that flu survivors were so horrified, they didn’t want to remember. During one of the most productive periods in American literature, there are only a few mentions of the flu.

Thomas Wolfe describes the death of his brother in Look Homeward Angel, and Katherine Anne Porter tells of her own brush with mortality, and laments the death of her fiancé, in Pale Horse, Pale Rider. Some of the scenes that I am going to describe will disturb you. And yet, history compels us not to look away, lest we fail to learn the lessons paid for by the suffering of our parents and our grandparents. The 1918 Flu also shows us, for better or worse, how society responds to a public health crisis. By learning how and why we were so vulnerable, we may be better equipped to save ourselves when that next global pandemic strikes.

If you are upset by the chilling story that I am about to tell, ask yourself this: If it was so bad that we can barely stand to hear about it nearly a century later, how much more horrible must it have been for those who actually lived through it? And in answering that question, you might also realize the answer to another question: If it was so terrible, why have most of us never even heard of it?

Prelude to a Pandemic

Let’s go back in time to a simpler era—before television, computers, iPods, and the internet. In the summer of 1918, the United States was enjoying warm weather and general prosperity. For most people, their biggest worry was the war in Europe, World War I—the war to end all wars. The flu had passed through the previous spring bringing mild fever and aches, but nothing unusual. Most of its victims were among the very young or the very old—the typical “U-shaped” curve of flu mortality: a high incidence of juvenile mortality; not too many people dying in the middle-age groups; and then when we get into the 50s and 60s, it starts to rise rather steeply again.

Flu was nothing new. The first global flu pandemic goes back to 1580. It started in Asia and swept across Europe; 9,000 people died in Rome and many Spanish cities were virtually depopulated. From 1700 to 1900 there had been at least 16 major epidemics of influenza, some of them deadly. An outbreak in 1729–1730 claimed 1,000 lives a week in Europe. The last major pandemic was in 1889–1890, the first of what were later called the Asian flus. Why do so many flu epidemics start in Asia? As we’ll learn later on, it’s probably due to the large numbers of people living in close proximity to large numbers of chickens and ducks.

Nobody knows exactly where the 1918 Flu began, but evidence points to Haskell County, Kansas. Local physician Dr. Loring Miner was seeing dozens of his patients stricken by an unusually virulent form of the flu between January and mid-March of 1918. As we learned in Lecture 7, virulence is a measure of the relative severity of a disease, usually determined by its mortality rate. By the middle of March, the flu had faded away as quickly and as mysteriously as it had appeared. Dr. Miner was so concerned with its intensity that he reported it to the U.S. Public Health Service, who published his cautionary note, but otherwise ignored it.

And there it might have ended, except for one unalterable fact: We were at war. Flu victims can spread the disease for up to a week. In an isolated place like Haskell County, the flu might have quickly died out after being passed back and forth among the local population. But in wartime, people are moving between populations more often, and in greater numbers. The timing of the epidemic could not have been worse.

Some 300 miles down the road from Haskell County was Camp Funston, part of the huge Fort Riley military complex. Camp Funston had a higher population than usual due to wartime training. Because of the cold weather that year, soldiers were crowded together indoors with insufficient clothes and blankets, jammed closely around the few working stoves. In early March, soldiers began to report to the infirmary with flu-like symptoms. Within days, several thousand were stricken, but only 38 of them died—not enough to quarantine a camp in wartime.

Troop movements soon spread the flu to many other army camps; 24 of the 36 largest camps reported an outbreak of flu in the spring of 1918, along with 30 of the country’s 50 largest cities. But it was relatively mild, if highly contagious. The first wave of flu was so mild, in fact, that several doctors refused to believe it was even influenza. British doctors writing in The Lancet, for example, didn’t think it was the flu because the symptoms were too mild, and “of very short duration and so far absent of relapses or complications.”

This is a transcript from the video series Mysteries of the Microscopic WorldWatch it now, Wondrium.

Unwanted Passenger on the Leviathan

Soldiers from Fort Riley were loaded onto troop ships by the thousands. In the last six months of World War I, over 1.5 million soldiers crossed the ocean to go to war in Europe. It was the largest such movement of people in the history of the world. The troop ships were loaded to capacity with young men, most of whom were fated to die in the sausage-grinder of the western front. But many of them were dead before they even reached the shore. Those overcrowded troop ships became terrifying charnel houses, disgorging sick and dying soldiers by the thousands.

Members of the Fifty-Seventh Pioneer Infantry were already ill with the flu. As they marched from Camp Merritt, New Jersey, to board the troop ship Leviathan, they soon began to drop out of ranks. Trucks and ambulances scooped up those too ill to continue, but the rest soldiered on. By the time they reached the ship, most of them had gone 24 hours without sleep and several hours without food. Those sick and broken soldiers were hurried on board; 120 more were taken off the ship before it departed—they turned out to be the lucky ones.

Conditions aboard the troop ship Leviathan became so bad that a detail of soldiers actually mutinied rather than go below decks. Nighttime was the worst, as one official report describes, with: “scenes which cannot be visualized by anyone who has not actually seen them. … The decks became wet and slippery [with blood], groans and cries of the terrified added to the confusion of applicants clamoring for treatment, and altogether a true inferno reigned supreme.”

Recently, while touring the Smithsonian in Washington, D.C., I came across a scale model of the Leviathan and I was floored. I sat in front of it for half an hour thinking of what had gone on inside that ship. But the Leviathan that you will see in the Smithsonian is the cruise ship before it became the troop ship, with people gaily waving from the deck, and confetti in the air. As everyone walked by, I wanted to tell them what had happened aboard that ship; what a terrible thing to have undergone.

Learn more about how trade, travel, and technological innovations provide new opportunities for the evolution or dispersal of pathogens.

Of the estimated 2,000 victims on board, at least 70 died en route, 31 more the day it docked, and 14 more the following day. Many of the sick soldiers fled the death ship that the Leviathan had become as soon as their orders allowed, spreading the disease to fresh troops. Hundreds more died on shore in the days that followed. The Fifty-Seventh Pioneer Infantry, one of the units aboard the Leviathan, recorded 195 flu deaths in the few days after disembarking. That scene was repeated over, and over, and over again all throughout England and Europe. The troop carrier, the Olympic, had 1947 troops infected, over 140 died.

Disease Begins to Spread

No one was prepared to deal with the thousands of sick and dying men, confined in the living hell that those troop ships became. The flu soon spread to French and British troops, and allied soldiers took it home to civilians when they went on leave. The virus spread rapidly through soldiers, POWs, and civilians, spreading to Germany, Russia, China, India, Southeast Asia, and down into Spain, becoming a true global pandemic. It was dubbed the “Spanish Flu,” but only because the press started to take notice as it happened to be hitting Spain.

The records of the Eighty-Eighth Combat Division in France are typical—total combat casualties (that’s killed, wounded, missing, or captured): 90 men; total deaths from the flu: 444. Something happened aboard those troopships, or maybe in the foul and crowded trenches, that turned that flu into a savage killer. The second wave of infection was now poised to fall like a hammer blow on an unsuspecting populace.

Why had this mild strain of flu suddenly become so virulent? Several hypotheses have been proposed: A new and entirely different strain had emerged, or perhaps a genetic mutation had altered the original strain, or maybe two different viruses had fused together to create a new strain. We’ll briefly consider each of those three explanations. But before we can do that, we need to take a few minutes to consider how the flu virus actually works.

Cell Structure under the Microscope

Viruses are mysterious little creatures. They generally consist of a core of RNA or DNA surrounded by a membrane or capsule. RNA is a single strand of genes; DNA is two complementary strands joined together in that classic double helix. Unlike cells, viruses cannot replicate by themselves. They need to take over the protein synthesis factory in a living cell and reprogram it to make copies of the virus.

Influenza is an RNA virus with eight separate genes enclosed in a membrane covered with spikes. The virus is very, very, very small, about 1/10,000 of a millimeter. Move over angels—viruses are so small that an area the size of the head of a pin could hold a billion of them.

There are two kinds of spikes on the outside of the virus, called H spikes and N spikes. It’s these spikes, incidentally, that give the name for the different types of flu, like H5N1. The H spikes, hemagglutinin, cause red blood cells to clump together, or agglutinate. The N spikes are a type of enzyme. An enzyme is a catalyst—a protein that can affect or alter the course of a chemical reaction. The short version is that it’s like putting a puzzle together on a tabletop. The table (the enzyme) isn’t changed by the act of assembling the puzzle, and it can be used over, and over, and over again to help assemble more puzzles.

Learn how the geometry of a sphere explains how bacteria survive.

The immune system, in its efforts to locate invaders, looks for unique groups of amino acids (little bits, little fragments of proteins) called epitopes. Molecules or cells that have epitopes in their structure or on their surface are called antigens.

Every organism has a different pattern of epitopes sticking out on the surface of its cells. That’s actually kind of hard for us to visualize because we think of cells as these smooth little circles—maybe because that’s the way the teacher made us draw them in high school biology lab. But, in fact, the outer surface of a cell is a very complex surface, with lots of little bits and pieces of molecules and compounds sticking out in all directions. The immune system can recognize these epitopes—these little projections—as cellular ID tags, and uses them to separate self from non-self.

Both H and N spikes act as antigens, as do two proteins that are inside the core of the virus, and they can be readily identified by the immune system. The two core antigens, incidentally, are the same in all type A flu viruses, and are diagnostic for type A flu. Small changes in antigen structure are called antigenic drift; they create very similar strains called variants. Larger changes, called antigenic shifts, create different strains called subtypes. It is these major antigenic shifts in H and N antigens, these new subtypes, that are responsible for major new outbreaks of flu.

When the virus attacks, it sticks to the outside of a cell by its H spikes. The spikes lock onto a type of sialic acid sugar that’s found on the outside of cells in the lungs and throat. They repeatedly bind to the sialic acid receptors, like a VELCRO® strip, or like tiny little pirate grappling hooks. (And I’m told that if you listen very carefully with a stethoscope at this stage, you can even hear all of those little pirate “arrhh’s.”) Well, that’s why flu is an upper respiratory disease: It is specifically designed by evolution to cling to a molecule that protrudes from cells in the throat and in the lungs.

Ghost in the Cell

The virus is absorbed into the cell through a process of phagocytosis, in which small particles can literally be surrounded by the cell membrane and drawn inside, leaving the particle wrapped in a tiny little bubble of cell membrane called a vesicle. Many other kinds of viruses fuse themselves to the surface of the cell in order to inject their contents, but this strategy leaves them open to discovery by the immune system. By slipping inside the cell membrane intact, and by wearing the cell membrane like a wolf in sheep’s clothing, the flu virus makes itself invisible to the many wandering immune system cells that are scouting the body for trouble. Once primed inside the cell, the virus sheds its envelope and releases its RNA genes.

What we refer to as a gene is simply a series of coded instructions along a length of DNA or RNA that codes for putting together a particular protein; proteins are the building blocks of life. Each strand of RNA or DNA consists of a long series of genes, which are basically recipes for proteins; each separate gene is a separate recipe. It’s kind of like taking a file card box of recipes and taping them end to end—that’s how strands of DNA and RNA are basically built. What we call a chromosome is really just a series of genes on a single very long strand of DNA, all coiled up into a tiny little package.

Viruses contain relatively few genes, and these are usually on a single strand of RNA or DNA. But the flu virus has multiple strands of RNA, each with only one or two genes. The RNA genes of influenza—once primed and liberated in the cell—hijack the cellular factory replacing some of the host cell’s genes and reprogramming the cell to make thousands, and thousands, and thousands of copies of the flu virus. The flu genes replicate and group together in sets of eight to form a new core, and each set of eight is wrapped up in a fresh membrane, and then they exit the cell to spread the infection. Within 10 hours of infection, that cell can release 100,000 to a million or more new flu viruses.

Theoretically, new viruses should become trapped as soon as they exit the cell by the very same sialic acid receptors they stuck to on the way in. That’s where the N spikes, the neuraminidase spikes, come into play. They have a blunt tip, kind of like a little box with four miniature propeller blades. These little blades slice through the receptor sites as the virus emerges from the cell and prevent it from being stuck.

The Bigger Picture

Now we can better answer the question we posed earlier: Why did this mild strain of flu suddenly become so amazingly virulent? Was it a new and entirely different strain? Had a genetic mutation altered the original strain? Or did two different viruses fuse together to create an entirely new strain? The fact that survivors of the first wave of the flu had some immunity to later waves tells us that the second wave wasn’t an entirely new strain, but an altered form of the virus that caused the first wave. That re-energized strain might have experienced a mutation in its new host.

A mutation is just a change in genetic information, a change in the recipe that determines how proteins are put together (like your chocolate chips are suddenly butterscotch chips). And even a small change in the exterior antigens of a microbe can cause the immune system to fail to recognize it anymore. The influenza virus has an extremely high rate of mutation. It makes it a real genetic chameleon from the standpoint of the immune system. Many mutations are stopped in their tracks because DNA has a built-in proofreading mechanism, so every time DNA is replicated for cell division, it is very carefully checked to make sure everything is as it should be. But, RNA lacks that proofreading mechanism, so mutations of RNA aren’t repaired or eliminated, and that means that an RNA virus, like the flu, has a much higher mutation rate than a DNA virus—thousands and thousands of times higher. We call it hypermutability.

Learn about how the vast majority of microbes are harmless or even beneficial to humans.

While mutations provide the new variation essential for natural selection to work, they come with a cost. It’s kind of like taking a hammer and throwing it into a jet engine—you might get incredibly lucky and change it for the better, but more often than not you’re going to break it. That means that as many as 99 percent of the newly created flu viruses are basically damaged; they can’t infect another cell. But that also means between 1,000 and 10,000 viruses from each infected cell can not only still infect other cells, but may now be even more lethal than it was before, and better able to hide from the immune system.

Mutations are thought to be the explanation for antigenic drift—small changes that create new variant forms. But they can’t adequately explain the more dangerous antigenic shifts, where the virus becomes more radically different. Antigenic shifts—like the change that caused the second wave of the 1918 Flu to be so virulent—could result from the fusion of two different types of flu viruses from hybridization. That seems rather a tall order—how can you jam two viruses together? But the way the flu virus reproduces actually makes it relatively easy.

Remember that the eight genes of the virus are on several separate strands of RNA. If two subtypes—two variants—infect the same cell at the same time, each is making thousands of copies of its own eight genes, which are all now scrambled up together inside the same cell. When the genes are reassembled in groups of eight to form a new core, and sealed into a fresh viral envelope, the two types can very easily mix together. So the new virus will still have all eight genes that it needs to survive, but those eight genes are now going to be a random mixture of the genes of both types of the flu virus. It’s only by reconstructing the virus that we can determine its origin and test this hybridization hypothesis about its virulence.

The virus could also have strengthened simply through passage from host to host. It’s easy to demonstrate in the lab that as a new virus infects new victims, it somehow seems initially to strengthen with each passage—something we don’t really understand. It may be that each new passage provides a fresh opportunity for mutation or hybridization; we really don’t know.

1918 Flu Origins

In the end, we don’t know where the killer flu of 1918 came from. Maybe it was born from the war itself, taking advantage of that new ecosystem presented by trench warfare.

John Oxford claims that it first emerged in a massive field hospital complex in Étaples, in northwest France, in the winter of 1915–1916. The symptoms were much like those of the later pandemic and the area had a lot of goose, duck, and pig farms that could very easily have harbored the virus. Plus it had 24 varieties of mutagenic chemical warfare gas. There was little doubt, however, that killer flu of the fall was a close relative of the bug that had swept through the previous spring, because survivors of the first wave of flu were moderately immune to the second wave.

Now, the flu struck with an amazing intensity. Fevers ran so high that doctors often misdiagnosed the flu as malaria. The usual bone pains and joint pains were so severe, some doctors thought they were dealing with dengue fever, also known as break-bone fever. Symptoms included severe earaches and headaches. Victims often bled heavily from the nose, mouth, eyes, and ears. Lung damage was so severe that doctors compared it to the damage done by mustard gas. Pockets of gas actually bubbled up under the skin from the ruptured lungs of the victims.

The immune system reaction was so strong that it often created a disastrous feedback loop, something we call a cytokine storm; it’s the immune system version of a nuclear attack. Cytokine storms can destroy the ability of the lungs to exchange gas. That severe lung damage led to cyanosis, a blue coloration of the skin caused by the lack of oxygen in the blood. Victims were stained so darkly in some cases it was hard to tell black men from white. That extreme cyanosis fueled rumors amongst the soldiers that the flu, in fact, was really the Black Death.

Autopsies on victims revealed extensive damage to the lungs, the heart, and the brain. That’s rather strange because flu isn’t normally associated with neurological problems, but victims of the 1918 Flu were often left with permanent nerve damage and even psychosis. The 1918 Flu virus also attached to cells lining the lungs, and not just to cells in the upper respiratory tract, as it usually does. This left people open to secondary lung infections; in fact, pneumonia in the weakened flu victims was often the bigger killer. Pneumonia is a general sort of word; it can be caused by bacteria, but it’s really a term for lung damage of any type that’s due to viral, bacterial, or even chemical sources.

Tolls the Flu Took

Casualty figures for the fall of 1918 show the brutal power of that renewed virus in decimating the American, the British, and the French allied forces. In September, October, and November of 1918, the American Expeditionary Forces recorded nearly 112,000 military hospital admissions for flu or related pneumonia, with over 9,000 deaths; French forces admitted about 132,000, with over 10,000 deaths; and British forces recorded 63,000 victims with 3,600 deaths. That’s a total of over 307,000 flu casualties in three months, with nearly 23,000 dead. And we’ll never know how many thousands or tens of thousands more died where they lay in the endless foxholes and trenches of the front. The 8.5 million lost in the “war to end all wars” pales beside the more than 50 million lost worldwide in our battle with the flu.

Unlike earlier epidemics, which took their toll on the very young and the very old, this one took full aim at people in the prime of life. John M. Barry estimates that five to 10 percent of the world’s young adults died in that epidemic. The 1918 Flu wasn’t the usual U-shaped curve; it was a W-shaped curve. We had our usual mortality among the very young, but in those middle-aged groups where it’s usually pretty flat, it spikes up very, very sharply in the 15–34 age category, and then down again until it hits old age.

Now we know how the flu virus is structured, we know how it infects cells, and we know how it hides from the immune system. Next, we’ll witness the return of the now transformed and deadly flu from Europe to America; we’ll take a look at the city of Philadelphia as a case study of the American experience with the pandemic and as an illustration of how society responds to a medical crisis.

This is the first article in a series of three about the 1918 flu pandemic.
Read part two here.

Read part three here.