“The important and almost incomprehensible fact about the Spanish influenza is that it killed millions upon millions of people in a year or less. Nothing else - no infection, no war, no famine - has ever killed so many in as short a period. And yet it has never inspired awe, not in 1918 and not since…”
So says Alfred Crosby in “America’s Forgotten Pandemic…
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, or the Black Death…
It was the 1918 Flu
An estimated 50 to 100 million people died, out of a global population of 1.8 billion
In America alone, 675,000 people died
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
And Katherine Anne Porter tells of her own brush with mortality, and laments the death of her fiancée in Pale Horse, Pale Rider
Some of the scenes I am going to describe during our next three lectures 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
And by learning how and why we were so vulnerable, we may be better equipped to save ourselves when the next global pandemic strikes
If you’re 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 may also realize the answer to another question I will pose today – If it was so terrible, why have most of us never even heard of it?
So let’s go back in time, to a simpler era, before television, and computers, before Ipods, before the Internet…
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
This is the typical “U-shaped” curve of flu mortality
Flu was nothing new…
The first global flu pandemic may have been in 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 sixteen 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 Asiatic 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
No one knows exactly where the 1918 Flu began, but evidence points to Haskell County, in Kansas
Local physician Dr. Loring Miner saw dozens of his patients stricken by an unusually virulent form of flu in January to mid-March of 1918
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, however, 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 move between populations more often, and in greater numbers
So the timing of the epidemic could not have been worse!
Some 300 miles 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 winter 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 the 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 the 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.”
Soldiers from Ft. 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 who were fated to die in the sausage-grinder of the Western Front
But many of them were dead before they even reached the shore
Overcrowded troop ships became terrifying charnel houses, disgorging sick and dying soldiers by the thousands
Members of the 57th Pioneer Infantry were already ill with the flu
As they marched from Camp Merritt, New Jersey, to board the troop ship Leviathan, they began to drop out of ranks
Trucks and ambulances scooped up those too ill to continue, but the rest marched on
By the time they reached the ship, most of them had gone 24 hours without sleep and several hours without food
Conditions aboard the troop ship Leviathan, were so bad that a detail of soldiers actually mutinied, rather than go below decks!
Night time 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”
Of the estimated 2,000 flu 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 as soon as their orders allowed, spreading the disease to fresh troops
Hundreds more died on shore in the days that followed
The 57th Pioneer Infantry, one of the units aboard the Leviathan, recorded 195 flu deaths in the few days after disembarking
This scene was repeated over and over again throughout England and Europe
Aboard the troop carrier Olympic, for example, 1,947 troops were infected, and over 140 died
No one was prepared to deal with the thousands of sick and dying men, confined in the living hell that the troop ships became
The flu soon spread to French and British troops
Allied soldiers took it home to civilians when they went on leave
The virus spread rapidly through soldiers, POW’s, 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 88th Combat Division in France are typical…
Total combat casualties (killed, wounded, missing, or captured) = 90 men
Total deaths from the flu ? = 444!
Something happened aboard those troopships, or perhaps in the foul and crowded trenches, that turned the flu into a savage killer…
The second wave of infection was now poised to fall like a hammer blow on an unsuspecting population
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 altered the original strain
Or maybe two different viruses had fused together to create a new strain
We’ll briefly consider each of these three explanations
The spikes lock onto a type of sialic acid sugar 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 pirate grappling hooks…
And I’m told, that if you listen very carefully with a stethoscope at this stage, you can even hear the little pirate “arrhh’s”
Well, that’s why flu is an upper respiratory disease
It’s designed to cling to a molecule that protrudes from cells in the throat and lungs
Now the virus is stuck onto the outside of the cell
The virus is absorbed into the cell, through a process of phagocytosis, in which small particles can be surrounded by the cell membrane and drawn inside, leaving the particle wrapped in a tiny 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
This strategy, however, leaves them exposed 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
Remember that what we refer to as a gene is simply a series of coded instructions along a length of DNA or RNA that codes for the assembly of 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 recipes for proteins – each separate gene is a separate recipe
It’s like taking a file card box of recipes and taping them end to end – that’s how strands of DNA & RNA are built
And, while we’re on the subject - 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 packag
Viruses contain relatively few genes – 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
They replace some of the host cell’s genes, and reprogram the cell to make 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, wrap each new core in a fresh membrane, and exit the cell to spread the infection
Within ten hours of infection, the cell releases 100,000 to a million or more new flu viruses!
But, 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, like a tiny box with four miniature propeller blades
These “blades” slice through the receptor sites as the virus emerges from the cell, preventing it from being stuck
Now we can better answer the question we posed earlier - why did this mild strain of flu suddenly become so 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 a new strain?
The fact that survivors of the first wave of the 1918 Flu had some immunity to later waves, tells us that the second wave was not an entirely new strain, but an altered form of the virus that caused the first wave
The re-energized strain might have experienced a mutation in its new host
Mutations are alterations in genetic information, changes in the recipes that determine how proteins are put together
And even a small change in the exterior antigens of a microbe, can cause the immune system to fail to recognize it
The influenza virus also has an extremely high rate of mutation, making it a real genetic chameleon from the standpoint of the immune system
DNA has a proofreading mechanism built in, which stops many mutations in their tracks when the DNA is replicated for cell division
RNA, however, lacks the 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 – what we call hypermutability
While mutations provide the new variation that is essential for natural selection to work on, they come with a cost
It’s like throwing a hammer into a jet engine – you might get 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% of the newly created flu viruses are damaged, and can’t infect another cell
But it also means between 1,000 to 10,000 viruses from each infected cell can not only still infect other cells, but may now be even more lethal than 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 (hybridization)
That seems rather a tall order – 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 or variants infect the same cell at the same time, each makes thousands of copies of its own eight genes, which are now all mixed up together in 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 easily mix together
So the new virus will still have all eight genes, but it will now be a random mixture of the genes of both types of the flu virus
Only by reconstructing the virus can we determine its origin and test this hybridization hypothesis about its virulence
We’ll talk more about the hybridization hypothesis in our final lecture on the flu
The virus could also have strengthened through passage from host to host
It is easy to demonstrate in the lab that as a new virus infects new victims, it seems initially to strengthen with each passage
In the end, we just don’t know where the killer flu of 1918 came from
Perhaps the 1918 flu was born from the war itself, taking advantage of the new ecosystem presented by trench warfare
John Oxford claims that it first emerged in a massive field hospital complex in Étaples, in north-west France, in the winter of 1915-1916
The symptoms were like those of the later pandemic, and the area had goose, duck and pig farms that could have harbored the virus, plus 24 varieties of possibly mutagenic chemical warfare gas
There was little doubt, however, that fall’s killer flu was a close relative of the bug that had swept through the previous spring
Survivors of the first wave of flu were moderately immune to the second wave
The flu now struck with savage intensity
Fevers ran so high that doctors often misdiagnosed the flu as malaria
The usual bone and joint pains were so severe, some doctors thought they were dealing with dengue fever, also known as breakbone fever
Lung damage was so severe that doctors compared it to the damage done by mustard gas
Pockets of gas bubbled up under the skin from ruptured lungs
The immune system reactions were so strong that they often created a disastrous feedback loop called a cytokine storm, the immune system version of a nuclear attack
We’ll talk more about the role of cytokines in our two lectures on immunity
Cytokine storms can destroy the ability of the lungs to exchange gases
This 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
The extreme cyanosis fueled rumors among the soldiers that the flu was really the Black Death
Autopsies revealed extensive damage to the lungs, heart, and brain
Although flu is not normally associated with neurological problems, victims were often left with permanent nerve damage and even psychosis
The 1918 Flu virus also attached to the cells lining the lungs, not just to cells in the upper respiratory cells, as it usually does (we’ll learn why in our last lecture on the flu)
This left people open to secondary lung infections, and pneumonia in the weakened flu victims was often the bigger killer
Pneumonia can be caused by bacteria, but it’s really a general term for lung damage that can be viral, bacterial, or even chemical
Casualty figures for Fall of 1918 show the brutal power of the renewed virus in decimating the American, British, and French allied forces…
In September, October, and November of 1918, American Expeditionary Forces recorded nearly 112,000 military hospital admissions for flu or pneumonia, with over 9,000 deaths
French forces admitted about 132,000, with over 10,000 deaths - and British force recorded nearly 63,000 admissions with 3,600 deaths
A total of over 307,000 flu casualties in only three months, with nearly 23,000 dead!
And we’ll never know how many 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 world wide 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 5- 10 % of the world’s young adults died
The 1918 Flu was a W curve instead of U (explain…)
Why did so many young adults die?
We’ll learn the answer to that question in our final lecture on the flu…
Now that we know how the flu virus is structured, and how it infects cells and hides from the immune system, we’ll be better prepared to appreciate the detective story we’ll weave in our lecture about the search for a living virus
But first, we’ll witness the return of the now transformed and deadly flu from Europe to America
And we’ll look at the city of Philadelphia as a case study of the American experience with the pandemic, and an illustration of how society responds to a medical crisis