The 1918 Flu 3 The Search for the Virus



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The 1918 Flu 3 - The Search for the Virus 


  • In our last lecture, we looked at how the City of Philadelphia coped with the deadly second wave of the 1918 Flu

  • In our final lecture on the flu, we’ll see how the lingering effects of the flu helped set the stage for World War II

  • And we’ll follow modern medical detectives, as they race to recover the virus, and learn its secrets…

  • As the end of World War 1 approached, rumors of armistice began to fly

  • But President Woodrow Wilson was determined to fight to the death and to concede nothing to the aggressors

  • Wilson proclaimed that:

  • “To fight, you must be brutal and ruthless… Force, force to the utmost, Force without stint or limit, the righteous and triumphant Force which shall make Right the law of the world, and cast every selfish dominion down in the dust.”

  • President Wilson met with Lloyd George and Clemenceau in Paris in early 1919 to work out the terms of surrender

  • The third wave of the flu just was hitting Paris at that time, with flu-related deaths back up to 2,676 in February

  • One of those victims was Wilson’s daughter

  • One of Wilson’s aides writes:

  • “There seems to be millions of throat germs going around, and a number of diplomats have lost their voices altogether. The Old World is badly germ-ridden. It is soaked with disease.”

  • On Thursday April 3d, Wilson was struck by a coughing spell so severe he had difficulty breathing

  • The attack was so sudden that Dr. Cary Grayson, Wilson’s White House physician, at first thought that Wilson had been poisoned

  • Wilson was very ill, with severe diarrhea and a fever over 103 degrees

  • He lay in bed for several days, and couldn’t even sit up until the fourth day

  • George and Clemenceau came to Wilson’s rooms to continue the talks, but the talks went poorly

  • Wilson was gaunt and haggard, with a pale face and sunken eyes, but he continued to drive himself relentlessly

  • Herbert Hoover grew concerned that Wilson had changed after his illness, becoming stubborn and unwilling to listen to advice

  • Secret Service agent Col. Starling noted that Wilson “lacked his old quickness of grasp, and tired easily”

  • Wilson became paranoid, insisting that his home was filled with French spies!

  • He grew obsessed with trivial details, such as who was using official vehicles

  • Lloyd George refers to Wilson’s “nervous and spiritual breakdown in the middle of the Conference”, attributing it to overwork and harsh criticism by the press

  • Gilbert Close, Wilson’s secretary, wrote:

  • I never knew the President to be in as difficult a frame of mind as he is now. Even while lying in bed he manifested peculiarities.”

  • And then Wilson suddenly announced a complete change of face, conceding to Clemenceau virtually every point he had previously fought so hard to make

  • Later authorities speculated that Wilson had suffered a mild stroke, ignoring his bout of flu, an idea that persists to this day

  • And for good reason…

  • Flu is not normally associated with neurological or psychological problems

  • The 1918 Flu, however, was the exception to that general rule, and left many victims with permanent mental damage

  • Dr. Charles W. Burr, a specialist in mental complications from influenza, wrote in 1918 that the typical flu survivor might face long-term mental problems

  • “To make a decision about some trifling matter tires him, and an important matter requiring any deep thought, for even a short time, must be put to one side.”

  • Did Wilson’s concessions result from his struggle with influenza?

  • A careful examination of his state of mind before and after the flu strongly suggests that his illness changed his attitude and behavior profoundly

  • Whatever the cause, by caving in to Clemenceau’s harsh treatment of Germany, Wilson helped to create the conditions that ultimately led to the next World War

  • Adolf Berle jr., later to be appointed Assistant Secretary of State says in his letter of resignation to Wilson:

  • “I am sorry that you did not fight our fight to the finish and that you had so little faith in the millions of men, like myself, in every nation, who had faith in you. Our government has consented now to deliver the suffering peoples of the world to new oppressions, subjections and dismemberments – a new century of war.”

  • Between adding to the miseries of the first World War, and contributing to the rise of the Second World War, the 1918 flu had a big impact on human history

  • What if it were to return today – would we be prepared to fight it?

  • One of the most fascinating aspects of the 1918 Flu is a detective story, the search in modern times for an intact virus

  • This search is no idle exercise

  • In the wrong hands, the virus could make a formidable weapon


  • But if we can find one, maybe we can figure out why it was so incredibly deadly

  • And if we can decode its genes, we might find a way to fight it, or any similar virus

  • We are more vulnerable today than our parents were, in so many ways

  • We’ve made great advancements in public health and medical technology, but our recent changes in lifestyle and diet have left us much closer to the brink, should the deadly flu be unleashed in our lifetime

  • Think about how quickly the 1918 Flu was spread by rail and ocean liner

  • Our modern network of interstate highways and global airlines would disperse such a killer much faster, and more effectively

  • Our increasingly interconnected global trade system is also more easily disrupted – we are less self reliant, economically speaking

  • A global pandemic might trigger a cascade of economic collapse, and shortages of critical items

  • Our growing reliance on refrigerated and frozen food means that our homes contain a significantly greater amount of perishable food

  • Remember how Philadelphia’s stores closed down as the flu spread?

  • With a minimum of canned goods and dry foods in our pantries, most of us would soon run out

  • In 1957, a typical American family ate only about 90% of their meals at home

  • Their kitchens contained about 20% perishable foods, mostly fresh fruits and vegetables

  • The modern American household eats at home only 62% of the time, and 48% of the food at home consists of perishable items

  • Let’s face it - if McDonalds and Burger King were to close, a significant portion of my immediate family would probably starve to death within a month!

  • Being more vulnerable means we have to be better prepared, and that preparation starts with a better understanding of what made this flu virus so dangerous

  • But where to begin?

  • Few samples were preserved at the time – people didn’t really know what viruses were, much less how to preserve them

  • So how to find a sample of the deadly virus?

  • The answer is simple - look in the lungs of the dead…

  • The U.S. Army had preserved many samples of lung tissues from dead soldiers

  • They had soaked samples in formaldehyde, then encased them in paraffin (wax)

  • The original orders to preserve tissues from diseased military personnel came from none other than Abraham Lincoln

  • Jeffery Taubenberger, of the Armed Forces Institute of Pathology, along with his colleague Ann Reid, began trying to isolate the virus from a scrap of lung tissue from a young soldier

  • Meanwhile, Dr. Kirsty Duncan, anthropologist, geographer, and amateur virologist, had become obsessed with solving the mystery

  • She reasoned that only burial in permafrost would have preserved the 1918 virus that long

  • A four-year search led her in 1997 to a frozen cemetery in Spitsbergen, a tiny wind-swept isle 600 miles north of northern Norway

  • Several coal mines on the island were active in the early 1900’s, operated by the Arctic Coal Company

  • Duncan knew the flu had hit Norway, and wondered if any miners had carried it to Spitsbergen

  • She finally narrowed her search to the mining town of Longyearbyen, a seasonal mining town - fish in spring, mine in winter

  • Most local records had been destroyed in WWI, but she tracked down old coal company diaries, held by a local schoolteacher

  • She found a cemetery with six young miners from Norway, who died of the flu just after leaving ship, and were buried in the frozen soil

  • As she was assembling an expedition to exhume the bodies, Taubenberger was closing in on the prize

  • He contacted Duncan, and the two of them collaborated for a while, but they soon parted company…

  • Duncan found Taubenberger and Reid too cautious and methodical – and Taubenberger found Duncan too flamboyant

  • Duncan’s expedition prepared to don moon suits to prevent the release of live virus…

  • But the elaborate exhumation proved a bust

  • The bodies were buried too close to the surface, and were badly decayed

  • Keep an eye out for reruns of Virus, a 1995 NBC TV movie, based on a Robin Cook novel

  • It features a fictional “Kirsty Duncan” type, racing to unearth the 1918 bug in order to fight a modern epidemic…

  • Meanwhile, Taubenberger had been contacted by a retired pathologist, Dr. Johan Hultin

  • Hultin had beaten Duncan and Taubenberger to the punch by almost 50 years…

  • As a young graduate student in 1949, he had also been intrigued by the elusive 1918 virus, and became determined to find it

  • He decided to make the virus the subject of his dissertation

  • He tracked down a mass grave of 72 flu victims in Brevig Mission, Alaska in 1951

  • But the expedition was a failure – he found several bodies, but was unable to recover any of the virus

  • 46 years later, in 1997, he read an article in Science by Taubenberger, and decided to try digging at Brevig again

  • While the world was watching Kirsty Duncan, Dr. Hultin flew back to Brevig

  • He checked into a local motel, and began digging for new samples with his pickaxe

  • Most of the bodies he found were badly decayed, but one obese victim, dubbed “Lucy”, was fairly well preserved

  • Heavy layers of fat around her lungs had protected them, and Hultin collected several tissue samples

  • He sent the infected frozen samples to the Army pathology lab via UPS, the US Post Office, and FedEx

  • Those were the days…

  • This time Hultin was successful, and Lucy yielded several viral fragments

  • Taubenberger used these samples, together with the Army samples he had collected, to sequence several viral genes

  • Although we have solved one mystery, finding intact genes from the 1918 virus, several mysteries remain unsolved

  • Why did the flu kill so many young adults?

  • Why were the three waves so closely spaced?

  • Where did it come from?

  • To this day, no one knows why the flu hit young adults so heavily, producing a W shaped curve rather than the usual U shaped curve of flu mortality (explain pattern of mortality…)

  • It may be that the healthy immune systems of young men and women were their undoing

  • And that’s a novel concept - can there be such a thing as being too healthy?

  • Remember that the sheer devastation of the lungs of soldiers was comparable to the damage done by mustard gas

  • Some doctors think that this damage was partly due to a deadly over reaction by the immune system, a cytokine storm

  • Maybe this cytokine storm was particularly intense in those with the healthiest immune systems

  • Or perhaps young adults in 1918 had especially high levels of tuberculosis, leaving their damaged lungs ripe for invasion by influenza

  • The unbridled virulence of the flu probably contributed to its ultimate undoing

  • Flu is driven by “herd immunity”

  • It needs to constantly hop from one population to the next, as each host population either dies out or acquires resistance

  • We would expect to see waves of flu spaced several months apart

  • Major antigenic shifts would be required every two or three years to survive herd immunity

  • But the three waves of the 1918 Flu were very close together

  • Each wave should have been months apart, but in some areas the three waves of the flu were only weeks apart

  • And in a few places, the waves were so close together, that it’s difficult to say where one ended and the next began

  • In the Northern Hemisphere:

  • The first wave lasted from Spring to Summer

  • The second wave lasted from Summer to Fall

  • And the third wave lasted from Fall to Winter

  • This tight spacing remains a mystery

  • It lends some support to the argument that the second wave was a hybrid virus or a mutant strain

  • A hybrid or mutated strain would be sufficiently different to overcome the partial immunity of survivors of the first wave

  • Cycles of the 1918 Flu are so out of step, that many scientists have come to doubt the validity of the whole idea of epidemiologic cycles, at least where the flu virus is concerned

  • Maybe the patterns formed by the hyper-mutable virus are just too unpredictable

  • Or perhaps we are missing a much larger pattern…

  • One hypothesis suggests that H1, H2, and H3 flu strains are “macrocycling”, competing with one another in cycles lasting about 68 years

  • There are three types (or genera) of flu: A, B and C

  • Type A is the most dangerous, infecting humans and other mammals (including pigs) and birds

  • Type B infects humans and seals (!)

  • Type C infects humans and pigs

  • Each type can have many subtypes, and each subtype can have several variants

  • Remember the H spikes and N spikes on the flu virus?

  • There are 16 known subtypes of the H antigen, and 9 subtypes of the N antigen

  • Flu viruses before 1957 are designated subtype H1N1 (the 1918 Flu)

  • The 1957 pandemic was caused by a new subtype H2N2, which left 2 million dead

  • The 1968 Hong Kong Flu was H3N2 – it left 1 million dead in its wake

  • Both the H2N2 and H3N2 subtypes are a mixture of bird and pig flu genes

  • The molecular evidence suggests that the 1918 Flu was H1N1, a novel strain of bird flu, which later spread to swine and humans

  • There are no known records of epidemics among poultry at that time, but ironically, bird flus are usually asymptomatic for birds – they carry it, but don’t suffer from it!

  • In the wild, ducks are believed to be the natural reservoir for avian flu

  • Samples of avian flu isolated from preserved wild birds in museum collections are very similar to those collected today

  • The 1918 Flu, however, is a different type of avian flu

  • Remember our earlier discussion of competitive exclusion?

  • Flu is rather unusual in that new subtypes tend to drive old subtypes into extinction

  • Only one subtype at a time usually exists in humans (and usually only one variant)

  • The reason may be that each new subtype provokes a general immune response to flu

  • This conveys partial immunity against a variety of other variants, including older strains of flu

  • So when the older strains cycle back into fresh populations, the door may be already closed

  • The 1976 swine flu, an H1N1 variant, caused an international panic!

  • Nobody likes to get a flu shot

  • But in 1976, a record forty million of us lined up to do just that – I was one of them, along with President Gerald Ford

  • Private David Lewis, a fresh recruit at Fort Dix, NJ, was the first to die of the flu, collapsing in the middle of a five-mile hike

  • Flu had been spreading through the barracks for weeks, but no one had died from it

  • Only four of the many flu victims at Fort Dix had the unknown swine flu virus

  • And only Private Lewis died

  • But because the fatal flu turned out to be H1N1, it revived fears of the 1918 pandemic, and that was enough to push the panic button

  • Once the military released the story about the Fort Dix outbreak, the press ran wild, exhuming horror stories of the 1918 pandemic

  • The publicity prompted the US Health Service to call for a mass vaccination with a little tested vaccine

  • Many people died, or experienced severe medical problems after getting their flu shots – was it merely a coincidence, or was the vaccine actually dangerous?

  • By May 1980, over 3,917 lawsuits had been filed, seeking over $3.5 billion in damages

  • 300 people died of the flu vaccine, according to the lawsuits, but only Private Lewis is known to have died of the flu

  • If nothing else, the 1976 swine flu scare prepared us for another epidemiological nightmare

  • A modern outbreak or a terrorist attack with weaponized flu would require a similar scheme of mass inoculation

  • In 1997, an explosive outbreak of avian flu broke out in Hong Kong, a new strain of bird flu called H5N1

  • The savagery of this new virus led to renewed urgency to understand the Doomsday Flu

  • 1.5 million chickens were slaughtered to stop the disease in its tracks

  • 6 out of 18 infected people died - it could have been the beginning of a new pandemic

  • But rapid quarantine, and the destruction of every chicken in Hong Kong, stopped it in its tracks

  • H5N1 is currently the most dangerous type of flu in circulation

  • Many experts think that if this bird flu ever manages to fully cross over into humans, it would kill untold millions of people

  • The H5N1 mortality rate stands at 59%!

  • In March 2005 H5N1 broke out in Vietnam, Indonesia, and North Korea, adding still more victims

  • 295 people have died from H5N1 since 1997

  • Its full designation is HPAI A(H5N1), the HP stands for highly pathogenic

  • This form of flu is epizootic, meaning that it occurs in non-human species

  • It is also panzootic, which means that it infects many different species of animal

  • Although it still hasn’t evolved to efficiently cross over to humans, all the danger signs are there – it’s lethal, it’s spreading very rapidly through avian populations, and it has already caused sporadic human infections

  • Flu expert Robert Webster says:

  • “This virus right from scratch is probably the worst influenza virus, in terms of being highly pathogenic, that I've ever seen or worked with. Not only is it frighteningly lethal to chickens, which can die within hours of exposure, swollen and hemorrhaging, but it kills mammals from lab mice to tigers with similar efficiency.”

  • A multi-billion dollar international effort is currently underway to study H5N1 and prepare for a possible future outbreak

  • Why do so many strains of flu continue to originate in Asia?

  • The most likely explanation is the large number of people living in close proximity to domesticated pigs and birds, a recipe for a new pandemic

  • Between 1968 and 2004, China went from 5.2 million pigs to 508 million pigs, and from 12.3 million poultry to 13 billion poultry

  • Was the 1918 Flu an Asiatic flu?

  • Some think it began as an avian virus in China

  • Many agree that the killer flu, or a very close relative, caused mild local epidemics in 1916-17

  • We mentioned the likelihood of Kansas as its point of origin in humans, but a recent paper by John Oxford claims that it first emerged in a massive field hospital complex in Étaples, in north-west France, in the winter of 1915-16

  • The symptoms were very similar to those of the subsequent pandemic

  • Was the 1918 Flu a swine flu or an avian flu?

  • Taubenberger was originally certain that the 1918 Flu virus came from American pigs, but his later research demonstrated that it was an avian flu

  • Flu expert Robert Webster claims that it was definitely swine flu, and was probably circulating in mammals for some time before 1918

  • Taubenberger, however, remains unconvinced, pointing out that swine flu was not described by veterinarians prior to 1918

  • Gavin Smith, in a 2009 paper in Nature, hypothesizes that the virus is a blend of avian flu and swine flu

  • Pigs can catch both human and avian flu, making them a veritable viral blender

  • The 1918 Flu may therefore have been part pig, part bird, and part human

  • H1N1 has become one of the most common causes of respiratory disease in pig farms in North America

  • Hence the “swine flu” designation for H1N1, despite the fact that it’s ultimately comes from birds

  • The 2009 Swine Flu epidemic was an H1N1 subtype, like the 1918 flu, one reason that doctors over reacted to the 2009 outbreak

  • Initial analysis of the 2009 swine flu pandemic, incidentally, indicates a higher mortality rate for young adults, just like the 1918 flu, and once again caused by extreme cytokine storms

  • In 2004, a team from the University of Wisconsin at Madison took two genes from the 1918 Flu virus, the ones that code for the H and N spikes, and stitched them into the genes of mice

  • They created special strains with both genes, or with just the 1918 H or N genes

  • The spliced N gene all by itself proved to be relatively benign

  • The mutated H binding protein, however, proved to be one of the primary factors that made the 1918 flu so incredibly virulent

  • The same team, in 2008, found a key set of 3 genes from the 1918 virus that allowed it to target cells in the lungs, rather than just the usual upper respiratory cells that flu viruses attack

  • In 2005, Taubenberger’s team announced that they had finally decoded the entire genome of the 1918 Flu

  • They used the Army’s specimens and fragments recovered from Hultin’s “Lucy”, and concluded it was an avian virus that had found a new host in humans

  • Whether pig, bird, or human, or a combination of all three, if the 1918 Flu does return, we may be prepared for it this time

  • Terrence Tumpey’s team, in 2006, spliced genes from the 1918 bug into a modern virus

  • He then tested an experimental DNA vaccine developed by the NIH, and found it to be effective against the live reconstructed 1918 virus

  • Mice infected with the lab bug all died

  • All of the 10 vaccinated mice survived

  • And so we’ve seen mankind on both the winning side, and the losing side, in our age-old struggle with microbes

  • We conquered the germ of laziness, but were decimated by the 1918 Flu


  • And as we’ll learn in our next four lectures, there’s a very good reason why we’ve managed to survive the evolutionary arms so far

  • Our highly evolved immune system gives us a deadly weapon to use against our microscopic rivals


Directory: ~bfleury -> darwinmed -> darwinmedlectures
darwinmedlectures -> Although our evolutionary heritage has saddled us with some significant health problems, in the long run it has served us well…
darwinmedlectures -> The 1918 Flu 1 – a conspiracy of Silence
darwinmedlectures -> Germ Theory
darwinmedlectures -> Although our evolutionary heritage has saddled us with some significant health problems, in the long run it has served us well…
darwinmedlectures -> In our last lecture, we looked at the ways that trade, travel, technology and agriculture can provide new habitats and new dispersal routes for microbes
darwinmedlectures -> The Evolutionary Arms Race Remember the Red Queen in Alice in Wonderland?
darwinmedlectures -> The 1918 Flu 2 The Philadelphia Story
darwinmedlectures -> The 1918 Flu 1 – a conspiracy of Silence
darwinmedlectures -> So say the Laws of Manu, an ancient Brahmin text on moral conduct Man is a moral animal…
darwinmedlectures -> Pandora's Box Remember the legend of Pandora's Box?


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