Monday, March 30, 2020

The Deadliest Virus: The Science and Politics of the Flu Pandemic of 1918

HASKELL COUNTY

In Haskell County, Kansas, in late January of 1918, Dr. Loring Miner began to see a new form of influenza in his patients that frightened him because it was so deadly; and as someone who read the Greek classics, he might have worried about whether this could come to resemble the plague in Athens described by Thucydides.  Although it cannot be proven, historian John Barry--in his book The Great Influenza--presents the circumstantial evidence for inferring that this was the origin of the flu pandemic of 1918-1920 that would spread over the whole Earth and kill over 50 million people, making it the deadliest pandemic in history.  Although the coronavirus that has caused the COVID-19 pandemic differs from the H1N1 flu virus that caused the 1918 pandemic, studying that earlier viral pandemic helps us understand what we're facing now.

Dr. Minor was so disturbed by the disease he saw spreading around Haskell County that he notified the U.S. Public Health Service, which published this one-sentence notice in its Public Health Reports journal (April 5, 1918): "On March 30, 1918, the occurrence of 18 cases of influenza of severe type, from which 3 deaths resulted, was reported at Haskell, Kans."  Actually, March 30th was not the correct date.  Minor first saw these "cases of influenza of severe type" in January and February.

Dr. Minor took pride in being a man of science.  He set up a laboratory for use in his medical practice.  He followed the recent developments in modern medical science such as the germ theory of disease.  And so he was prepared to recognize that he was seeing a new infectious disease in which a microbe--a bacterium or virus--was being transmitted by human contact.

Today scientists believe the H1N1 virus originates in marine waterfowl and jumps over to pigs before infecting human beings.  Haskell County was a farming area with lots of pigs from which the human infection might have started.  Since Haskell County was a sparsely populated and isolated area of southwest Kansas, the virus that first appeared there might have died out and failed to spread around the world were it not for the circumstances of wartime.

In February, young men from Haskell County were being drafted into military service for The Great War and sent to Camp Funston, three hundred miles away on the Fort Riley military reservation.  On March 4, a private at Funston reported ill with influenza.  Within three weeks, more than eleven hundred soldiers were admitted to the hospital with flu.  Pneumonia developed in 237 of these men, and 38 died.  When influenza kills, it kills through pneumonia.  This death rate was unusually high but not high enough to draw attention.  Soldiers from Funston were being shipped out to other military camps around the U.S., where they infected others; and these infected soldiers were then shipped to Europe, from where the epidemic spread around the world.

In the wartime camps, the men were crowded together in ways that permitted the quick transmission of the virus.  This is similar to the situation in Athens in 430 BC: in the circumstances of the war with Sparta, the people of Attica were crowded inside the walls of the city of Athens, so that once the infectious agent arrived (probably a virulent bacterium coming into the port of Piraeus), it spread quickly from person to person.

The first lesson here is that if these severely virulent infectious agents had been identified early enough--in Athens and in Haskell County, or in Camp Funston--and if the first people infected had been completely isolated from other people, then there would have been no epidemics.


DEATH RATES

In the spring of 1918, the flu epidemic spread around the world; but while some of those infected died, the disease was generally mild.  Still, the debilitating effects of the disease were severe enough that German commander Erich von Ludendorff blamed influenza for weakening so many of his soldiers that his last great offensive against the Allied powers stalled, which was the last chance for Germany to win the war before the fresh American troops arrived in Europe.

In the fall of 1918, a more deadly form of the virus caused a second wave of the pandemic with a horrifying death rate around the world.  By the end of the pandemic in 1920, 0.65% of the population of the United States had been killed--about 675,000 people.  In the developed world, Italy had the highest death rate--1% of its population.  In the less developed world, Mexico had a death rate of between 2.3% and 4%.

If the COVID-19 pandemic proves to be as lethal as the 1918 flu pandemic in the U.S., that would mean deaths at 0.65% of the present U.S. population of 330 million, which would be about 2,145,000 deaths.  This should be considered in the context of the normal yearly death rate: about 2,800,000 deaths from all causes, which include deaths from heart disease (650,000), cancer (600,000), accidents (170,000), influenza and pneumonia (56,000), and suicide (47,000).

The other day, Anthony Fauci predicted that the number of deaths from the coronavirus in the U.S. could eventually be as low as 100,000 or as high as 200,000.  If this turns out to be correct, then the COVID-19 pandemic will be much less deadly than the 1918 pandemic--killing 0.03% to 0.06% of the total population as opposed to 0.65%.

Fauci is assuming that the COVID-19 pandemic is inherently just as deadly as the 1918 flu epidemic, so that if nothing at all were done to suppress this epidemic, it would kill over 2 million people in the U.S.  He is also assuming that reducing the deaths to 100,000 to 200,000 requires all of the stringent measures for suppressing the epidemic that he has recommended--including self-quarantining, social distancing, and the partial shutdown of the U.S. economy for three months or more.  These policies for controlling this pandemic were developed some years ago by public health professionals who had studied the history of the 1918 pandemic to see what worked and what failed to contain the disease (Jester, Uyeki, and Jernigan 2018; Jester et al. 2018).


PHILADELPHIA

One of the most instructive cases from the fall of 1918 is Philadelphia.  On September 7, 300 sailors arrived from Boston at the Philadelphia Navy Yard.  On September 11, 19 sailors reported ill with symptoms of influenza.  Public health officials were aware of the deadly epidemic that had broken out in Boston's military bases, and so they feared that the same could happen in Philadelphia.  On September 18, some officials met with Dr. Wilmer Krusen, Director of the Philadelphia Department of Public Health, and they advised him that stringent measures would be needed to avoid the spread of the flu throughout the city--banning public meetings, closing businesses and schools, and quarantining the Navy Yard and civilians who had been infected.  The largest parade in Philadelphia's history was scheduled for September 28, a Liberty Loan parade designed to sell war bonds.  Krusen was warned that he should cancel this parade because the flu would spread quickly through the hundreds of thousands of people crowding the parade route.

Krusen rejected their advice, and he decided to do almost nothing to prepare for a possible epidemic emergency.  He did not want to cancel the parade or publicly acknowledge the epidemic because he thought that would weaken the morale of the public for supporting the war effort.  Indeed, wartime censorship prohibited newspapers from reporting about the epidemic.  The flu was called the "Spanish flu" because Spain was neutral in the war, and there was no censorship in Spain, so the Spanish newspapers reported the spread of the flu in Spain.  People then incorrectly assumed that the flu had originated in Spain.

On October 1, three days after the parade, every bed in all of Philadelphia's 31 hospitals was filled.  Hospitals refused to accept patients, who tried to bribe the nurses to care for them.  On that one day, 117 people died.

On October 3, five days after the parade, Krusen banned all public meetings in the city and closed all schools, churches, theaters, restaurants, and saloons.

On October 5, 254 people died.  The next day, 289 people died.  In some of the hospitals, over one-fourth of all the patients died each day, and their beds would immediately be filled by new patients.

The bodies began piling up.  Undertakers ran out of caskets, and they had no place to put the corpses.  People wrapped up corpses in sheets and pushed them into corners of their homes.  Some people were too sick to even move the corpses off their beds.

The symptoms of the disease were horrifying--with blood pouring from eyes, noses, ears, and mouths.  The lungs filled up until breathing was impossible, and with no oxygen in the arteries, people's bodies turned a dark blue color.

Normally, the death rate for flu is higher for the very young and the very old.  But this flu also killed young adults in the prime of their lives--from age 20 to 40.  This seemed odd because normally young adults have the strongest immune systems that allow them to fight off the flu.  In this case, however, the flu virus provoked the immune system into a massive attack on the body, and the lungs filled with debris and fluid.

Despite the high death rate, most of those infected survived.  (President Trump showed his ignorance when he said that in the 1918 epidemic most of those who contracted the disease died.)  There was no cure for the disease, but those who had caregivers so that they could rest while being fed and hydrated were most likely to recuperate, and then they would have immunity to the disease.  Nursing saved many lives.

As was the case with the plague in Athens, this flu epidemic brought out the best and the worst in human nature.  Many doctors, nurses, and others cared for the sick even though they were risking their lives.  But many others refused to care for others--even friends and family members--because they were afraid of having any contact with the sick.

In one week in the middle of October, 4,597 people died in Philadelphia.  After that, the number of deaths began declining.  The epidemic had reached its peak.

In Philadelphia, as in the rest of the country, the public policies for handling the epidemic came almost entirely from city and state governments.  There was no national policy coming from the federal government.  President Woodrow Wilson did not even speak publicly about the epidemic.

In some towns, public officials issued orders for partially closing down public life and quarantining people in their homes, but often these orders were not extreme enough to be effective.  In a few cases, however, a few small towns and communities were able to isolate themselves totally, and they escaped with no or very few deaths.


GUNNISON COUNTY

One example is Gunnison County, Colorado, which was the subject of a 2006 study by the Center for the History of Medicine at the University of Michigan Medical School.

Gunnison was a small mountain town in southwest Colorado, far away from any major population center but on a major rail line.  The city of Gunnison had a population of 1,329.  The County had a population of 5,590.

On October 8, 1918, the day after the Governor of Colorado and the State Board of Health had issued a warning about the flu epidemic reaching Colorado, the schools in Gunnison County were closed, and county officials introduced mandatory social distancing measures.  Gunnison police officers blocked all roads into the county, and anyone stepping off a train at the station would be arrested and quarantined for five days.  In effect, they isolated themselves from the entire world.  In early November, however, Mrs. Ellen Gavette, a 25-year-old, met her infected sister at the train station, who was returning from a trip.  They both self-quarantined themselves, but a few days later, Mrs. Gavette died from the flu.

On January 20, 1919, the schools were reopened, but attendance was not mandatory.  On February 5, the order of protective sequestration was lifted after almost four months of shutdown.

In mid-March of 1919, however, Gunnison was hit by the third wave of the flu epidemic, with over 100 cases of flu.  This time, there was no attempt to shut down the county.  At least 5 young people died from pneumonia.  But this death toll was remarkably low compared with the 8,000 deaths across Colorado.

This shows what a small community can do to almost completely isolate itself to escape contamination.  But this hardly seems practicable for larger communities over long periods.


MODERN SCIENCE AND THE MEDICAL MASTERY OF NATURE

The flu pandemic of 1918 was the first time that a fully modern science of medicine and public health confronted an aggressive global attack on humanity from nature.  For at least 2,500 years, until the end of the 19th century, medical practice was largely ineffective in preventing or curing sickness, because it lacked the scientific knowledge of the natural causes of disease and the scientific power to protect human beings from disease.  Doctors in the Hippocratic tradition of medicine, beginning in ancient Greece, could carefully observe the symptoms of disease to infer causes, but they did not probe deeply into nature with experimental methods or instruments to uncover the deepest causes.  So like the Hippocratic physicians, Thucydides could provide meticulous observations of the symptoms of the plague in Athens, which might help in the search for its natural causes; but he could not see its microbial causes, nor did he employ controlled experiments to see what preventative or curative treatments might work.

A few years ago, researchers collected DNA from teeth in an ancient burial pit in Athens dated to around 430 BC.  Testing the pulp for bacteria, they found a match to Salmonella enterica serovar Typhi, which is the bacteria responsible for typhoid fever, and this disease has many of the symptoms of the plague as reported by Thucydides.  Since the Athenians were crowded into Athens with unsanitary living conditions, it is easy to imagine how typhoid fever could have spread (Papagrigorakis et al. 2006).

By the end of the 19th century, scientists had identified typhoid fever as an infectious disease caused by a specific type of bacterium that is spread by food or water contaminated with feces.  Later, they developed an effective typhoid vaccine that was used successfully by the British army in the Boer War and in World War I.  Advances in public sanitation and hygiene--such as disinfecting drinking water--have also brought steep reductions in outbreaks of typhoid fever.  Later, in the 1940s, doctors began using antibiotics to reduce mortality from typhoid fever.  This is one of many diseases brought under control by modern medical science by the beginning of the 20th century--including smallpox, diphtheria, tuberculosis, cholera, malaria, yellow fever, and bubonic plague.

The germ theory of disease was the key idea for science confronting these infectious diseases--the idea that tiny living organisms invisible to the naked eye invade the body, multiply, and cause disease, with specific diseases caused by specific germs.

And yet, despite this success in the modern scientific battle with infectious diseases, scientists failed in their efforts to fully understand and control the flu epidemic of 1918.  They knew that isolating people worked in slowing or stopping the spread of the disease.  But beyond that, they were ignorant.  They could not even agree that the disease was influenza, because the symptoms looked so unlike normal influenza, that some scientists thought this was some new kind of disease.  They failed to find either a preventative vaccine or a curative serum for this disease.  Their only consolation was knowing that most people infected would recover if they were confined to bed rest and nursing care, and that those who recovered would have immunity.

The critically important part of their ignorance was that they could not identify the pathogen--the microbe that was the infectious agent of the disease.  Some thought it was a specific kind of bacteria--the "influenza bacillus."  Others thought it was some kind of virus.  Bacteria had been intensively studied, and they were visible through a microscope.  Viruses had been identified as microbes that were different from bacteria, but viruses could not be seen in their microscopes, and there was debate over exactly how they differed from bacteria.

Towards the end of the flu epidemic, scientists studying it began to agree that the primary cause was a virus, although the viral infection damaged the lungs in ways that made people vulnerable to secondary bacterial pneumonia infections.  Later, in 1926, Thomas Rivers defined the difference between viruses and bacteria--defining viruses as "obligate parasites," because they cannot reproduce themselves on their own, and so they must invade a host's cells and force those cells to reproduce more viruses.  The invention of the electron microscope in 1931 allowed viruses to be seen for the first time.


THE DISCOVERY AND RECONSTRUCTION OF THE H1N1 FLU VIRUS OF 1918

Over the past hundred years, since the end of the 1918 flu epidemic, scientists have wanted to understand why that flu virus of 1918 was so deadly and how it originated, with the thought that understanding this might help us to protect against any future epidemics that might be equally deadly.

Remarkably, over the past 25 years, scientists have succeeded in sequencing the entire genome of the 1918 virus, reconstructing the virus itself, and tracing its evolutionary history (Jordan 2019).  Scientists extracted the RNA of the 1918 virus from the lung tissue of victims of the epidemic, which had been preserved in a burial site in Alaska and in a U.S. Army collection of specimens.  Through genetic engineering, scientists eventually reconstructed the RNA of the complete 1918 virus.  This fully reconstructed 1918 virus could then be studied by being introduced into mice to see why this virus was so virulent.  This H1N1 virus has eight genes, and it was found that it was the unique combination of all eight genes working together that made it such an exceptionally virulent virus.

Beyond the inherent virulence of the virus itself, researchers identified at least five other factors that made the 1918 epidemic so dangerous.  First, the mobilization of troops in the war put so many people into overcrowded spaces that this infectious disease could spread quickly and widely.  Second, there were no diagnostic tests to identify flu infection; and the health experts did not even know that flu viruses existed.  Third, there were no flu vaccines, and no flu antiviral drugs.  Fourth, there were no facilities for intensive medical care or mechanical ventilation, so there was little that doctors could do to care for their patients.  Finally, there was no coordinated national planning to implement policies for mitigating the epidemic.

In the current crisis over the COVID-19 pandemic, we can see the efforts to overcome all five of these factors to escape a catastrophe like the 1918 flu pandemic.  It's a test of whether medical professionals, public health experts, and politicians have learned the lessons from that experience of 100 years ago.

Some of the horrific predictions about the likely death rate from the COVID-19 pandemic assume that the newly identified "severe acute respiratory syndrome-related coronavirus" (SARS-CoV-2) is just as inherently virulent as the H1N1 virus of 1918.  I am not sure there is convincing evidence for that.

Moreover, even as we battle this new virus, we should be encouraged that the H1N1 flu virus that has been circulating in the human population since 1918 has become must less dangerous than it was in 1918 (Carter and Sanford 2012).  There has been a continuous accumulation of mutations in this virus that have led to its degeneration, so that it is no longer as virulent as it once was.  A high mutation rate can sometimes bring rapid adaptation and evolution, but more likely just the opposite happens.  Deleterious mutations make viruses less adaptive and lead to their eventual extinction.  That seems to have happened to the flu virus of 1918.

The 1918 epidemic showed an extreme level of virulence unlike any other flu outbreak in history.  We can expect that with rapid mutation there will be a "reversion to the mean" as more extreme events are followed by less extreme events.  Once a virus has reached such an extreme of virulence, mutations are likely to make it less lethal rather than more lethal.

We can hope that this will be true for the SARS-CoV-2 virus.


REFERENCES

Barry, John M. 2018. The Great Influenza: The Story of the Deadliest Pandemic in History. New York: Penguin Books.

Carter, Robert W., and John C. Sanford. 2012. "A New Look at an Old Virus: Patterns of Mutation Accumulation in the Human H1N1 Influenza Virus Since 1918." Theoretical Biology and Medical Modelling 9:42.

Jester, Barbara, Timothy Uyeki, and Daniel Jernigan. 2018. "Epidemiology in History: Readiness for Responding to a Severe Pandemic 100 Years After 1918." American Journal of Epidemiology 187 (12): 2596-2602.

Jester, Barbara, et al. 2018. "100 Years of Medical Countermeasures and Pandemic Influenza Preparedness." American Journal of Public Health 108 (11): 1469-1472.

Jordan, Douglas. 2019. "The Deadliest Flu: The Complete Story of the Discovery and Reconstruction of the 1918 Pandemic Virus." Atlanta, GA: Centers for Disease Control and Prevention.

Pagagrigorakis, Manolis, et al. 2006. "DNA Examination of Ancient Dental Pulp Incriminates Typhoid Fever as a Probable Cause of the Plague of Athens." International Journal of Infectious Diseases 10: 206-214.

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