Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It

by Gina Kolata

The Black Death finally went away, perhaps because the bacteria had already infected all who were susceptible. But other deadly epidemics continued to sweep the world, and even old diseases, like cholera, sometimes took on a fierce vigor and caused plagues as terrible as any that had afflicted humanity.

In the winter of 1818–19, cholera killed 3,000 of a British army of 10,000 in India that was led by the Marquis of Hastings.

The disease stayed clear of England, however, until 1831, when William Sproat fell ill. The epidemic that followed was the first of a wave of six deadly cholera epidemics that spread across the world, frightening and killing multitudes. British historian R. J. Morris writes that in Britain “the approach and arrival of these epidemics, especially that of 1832, created a crisis atmosphere in the country quite unlike that produced by any other threat apart from a foreign invasion.”

a “normally calm” journal, the Quarterly Review, described cholera as “one of the most terrible pestilences which ever have devastated the earth.”

As the cholera epidemics raged in Great Britain, the newspapers kept a running toll of the cases and deaths, which had “the depressing effect of the tolling of a funeral bell,” Morris writes.

Religious leaders in Britain tended to see the epidemic as a manifestation of the wrath of God and a call for the people to turn to their faith for salvation. Some said God sent the epidemic to counter the “pride” and the “impotent boastings of modern science.”

When the 1832 cholera epidemic in Britain waned, the weary population just wanted to forget it. People had grown tired of reading and discussing an epidemic that had finally dissipated.

The leading medical periodical, the Edinburgh Medical and Surgical Journal, announced it would stop reviewing books on cholera, explaining that its editors reached that decision because of “the multitude of books which have recently issued from the press on the subject of cholera, and our determination no longer to try the patience of our readers.” Cholera disappeared as a subject in newspapers and magazines.

From Sproat to amnesia. It seems unreal. How could something so terrible as an infectious disease that kills half its victims, and gruesomely, be so quickly relegated to the dustbins of history? Morris ventures a guess, actually several guesses. First, he says, people had expected that the terrifying epidemic would cause a massive social disruption. That did not, in the end, occur. And second, “there were no clear ‘lessons.’” The main effect of the epidemic on British society, he claims, was to spur the efforts of a group of public hea...

With the growing and profound knowledge that many diseases are caused by microscopic organisms and that the spread of disease can be prevented, the Western world was transformed.

By the dawn of the twentieth century, for the first time since cities had come into existence 5,000 years before, infectious diseases were staunched to such an extent that cities were able to remain stable, and even grow, without depending on a constant stream of migrants from the countryside. It was a remarkable change.

As the second decade of the twentieth century wound to a close, the memory of a world stalked by infectious disease had dimmed. People had become complacent, almost smug, about disease and death.

The Ladies’ Home Journal proudly declared that the parlor, where the dead had been laid out for viewing, was now to be called the “living room,” a room for the living, not the dead.

Vaughan came to realize that Fort Devens was just the beginning. He had watched as the influenza epidemic spread to the farthest corners of the world, killing millions, crippling armies, until, as mysteriously as it came, it disappeared.

On October 3, 1918, General John Pershing sent out a desperate wire asking for troops and supplies. “Influenza exists in epidemic form among our troops in many localities in France accompanied by many serious cases of pneumonia,” he wrote.

On October 12, he wired again, his tone more urgent, asking for “one base hospital and 31 evacuation hospitals,” saying it was “absolutely imperative” and that along with the hospitals he vitally needed “their nurses and equipment.”

Toward the end of the war, German General Erich von Ludendorff, despairing that his country might have to surrender, began fantasizing that a miracle would save Germany. The flu epidemic, he decided, would demolish the French Army. But when his own surgeon general told him that was not going to happen, he refused to believe it, even having his conviction conveyed to Kaiser Wilhelm, whose spirits it lifted. The German surge...

When soldiers died of the flu, the cause of their deaths was sometimes hidden in euphemisms, Crosby notes. “At a memorial service for the pandemic dead at Fort Meade, Maryland, the presiding officer read the names of the dead one by one to a massed battalion, and as each name rang out, the sergeant of the man’s company saluted and responded, ‘Died on the field of honor, sir.’”

They recall that citizens wore white gauze masks in public in a vain attempt to protect themselves. Funerals were limited to fifteen minutes. Coffins were in short supply. Morticians and gravediggers could not keep up with the demand for their services. In Philadelphia, so many bodies had piled up in the morgue that the embalmers said the conditions were “so offensive” that they would not enter it. Public gatherings were prohibited in many cities and some places made it a crime to cough, sneeze, or spit in public. In Washington, D.C., even the Supreme Court adjourned so that, as Justice Oliver Wendell Holmes put it, they could spare lawyers from having to enter “this crowded and infected place.”

In asking why, Crosby proposes a combination of factors that, he said, acting together accounted for the world’s collective amnesia. For one, he argues, the epidemic simply was so dreadful and so rolled up in people’s minds with the horrors of the war that most people did not want to think about it or write about it once the terrible year of 1918 was over. The flu blended into the general nightmare of World War I, an unprecedented event that introduced trench warfare, submarines, the bloody battles of the Somme and Verdun, and the horrors of chemical warfare. Moreover, the epidemic had no obvious dramatic effect. It did not kill a world leader. It did not usher in a long period in which death from influenza was a new and constant threat. It did not leave behind legions of crippled and maimed or disfigured survivors who would serve as haunting reminders of the disease.

His latest hypothesis, he said in an interview in August 1998, is that in the fifty years preceding the 1918 flu, the world had been through one of the most profound revolutions ever to change the course of history: the germ theory of disease. “Every eighteen months, a new pathogen was identified, and it went on for years,” Crosby noted. Each discovery drove home the message that science was conquering disease. As the drumbeat of infectious agents continued, people “heaved a great sigh of relief. At last infectious disease was not important anymore,” Crosby concludes. Then came the flu epidemic, which made a mockery of the newfound optimism. And when it ended, Crosby posits, perhaps the most comforting reaction was to forget about it, to push it to the back of humanity’s collective consciousness as quickly as possible. To “see no evil, hear no evil.”

The health center’s report in December 1918 highlights the dilemma: “The outstanding fact, perhaps, is the extreme rapidity with which the epidemic spread after it attained the proportions of an epidemic in the first areas affected. The epidemic became nation-wide in the four or five weeks after it appeared in an epidemic stage in the first localities affected. A fact of scarcely less importance is that the disease reached an epidemic state in a number of localities in the central, northern, southern, and western sections at about the same time as it did in the area along the northeastern coast.”

As one scientist, Richard Edwin Shope, noted years later: “In many respects, the epidemiologist had an easier time getting the pandemic disease transferred from Boston to Chicago, for instance, than he did getting it the remaining thirty-eight miles from Chicago to Joliet.

“The present received opinion,” Johnson wrote, “is that this species of Catarrh [influenza] arises from contagion, which possibly may be true; yet to my mind it appears no easy matter to conceive how the disease can spread so far and wide in so short a space of time as we perceive it does, or how it can affect persons many miles apart, at the same time, where there had been no previous direct or indirect intercourse—if propagated only by a matter arising from the body of a man laboring under it.”

Such ideas also persisted after a flu pandemic of 1847. One doctor wrote: “What I wish to point out now is the fact that the Influenza pervades large tracts of country in a manner much too sudden or simultaneous to be consistent with the notion that its prevalence depends exclusively upon any contagious properties that it may possess.”

It looked like ‘flu,’ it presented the identical symptoms of ‘flu,’ and until proved it was not ‘flu,’ I shall stand by that diagnosis.”

Shope, with his upbringing on Iowa farms and his familiarity with pig diseases, was intrigued. He read Koen’s papers and could not dismiss the connection between swine flu and the human pandemic. Could it be, he wondered, that the long-lost 1918 flu organism was still extant, living on in pigs who had acquired the disease from people? If so, Shope and Lewis reasoned, if they focused on the new swine flu epidemic, they had a perfect opportunity to figure out what was causing the swine—and the human—disease.

there was no single cause of swine influenza. Both the virus and the bacteria needed to be present, acting in synergy to cause the disease.

Ferrets are small and sometimes vicious mammals, relatives of weasels, and not the usual laboratory animal. They had become an offbeat choice of some British scientists who found that they were uniquely susceptible to dog distemper.

British scientists had reasoned that the symptoms of dog distemper at least superficially resembled those of human influenza and decided that if they could understand distemper perhaps they could understand the flu.

They found the distemper virus, but their initial hypothesis proved wrong: the distemper virus turned out not to be related to whatever was causing influenza. Then again, since ferrets were so susceptible to distemper, Smith, Andrewes, and Laidlaw reasoned that it was worth a try to see if ferrets could also get the flu. The British scientists began modestly, inoculating two ferrets with the filtrate from human influenza patients. Within two days, both of the animals became ill, developing fevers and runny noses and all the outward symptoms of human influenza. It was a promising start, and demanded to be followed up, the investigators decided.

The animals lived in complete isolation in a special building. And no scientists or visitors were allowed in, unless they were disinfected, their clothing along with them. The disinfectant was the acrid-smelling household cleaner known as Lysol. To come into the research building, you had to wear rubber boots and an overcoat, which was hosed with Lysol as you walked by. Then you sloshed through a passageway that was three inches deep in the liquid. By the time you reached the ferrets, you reeked of Lysol but, presumably, were germ-free.

The flu virus they used was isolated from Wilson Smith himself, who had gotten the flu when a sick ferret sneezed in his face. That strain, called “WS” after Smith, still exists.

Even when the scientists inoculated ferrets with a combination of Pfeiffer’s bacillus and the filtrate, the bacteria seemed unimportant. The animals had essentially the same disease as they had when they were inoculated with only the filtrate. So Shope’s troubling findings did not seem to hold up. Pfeiffer’s bacillus did not seem to be amplifying the symptoms of flu.

Moreover, the British scientists discovered, they could protect ferrets from influenza by first mixing the filtrate with serum from people or ferrets who had already had the flu and then dripping it into a healthy ferret’s nose. The immunity that builds up after an influenza infection was in the blood and could block the flu virus.

To complete the picture, the British scientists found a connection between human flu and swine flu. The ferrets were susceptible to both diseases. Smith, Andrewes, and Laidlaw could give ferrets influenza by inoculati...

The snarly animals with sharp teeth did not want to sit still while Shope dripped flu-containing liquid into their noses. Shope decided to anesthetize the ferrets before inoculating them with swine flu. To his surprise, he discovered that when he did the experiments this way, the flu virus caused not just influenza but also a severe pneumonia, one that caused the lungs to swell with watery blood and that sometimes even killed the animals. It looked for all the world like a typical case of the 1918 flu.

American scientist Francis found that they could give white mice the flu if they took the flu viruses from sick ferrets. The virus, apparently, changed somewhat while it was growing in ferrets so that now mice were susceptible to it. And mice were not just susceptible—they developed the worst sort of flu. It was accompanied by an often fatal pneumonia.

Shope asked the next obvious question: Were the human flu virus and the swine flu virus one and the same? With the discovery that mice and ferrets could get flu from both human and swine viruses, the pieces were in place to get an answer.

Shope gave ferrets and mice influenza by inoculating them with a human flu virus. When the animals recovered, he tried giving them swine flu. They were immune to it. Then he tried the opposite experiment, giving ferrets and mice s...

The serum completely inactivated the human influenza virus, he discovered, but only partially inactivated the swine flu virus. At least the flu strains that were around a decade after the 1918 epidemic were slightly different from swine flu.

The results were unequivocal. Both in London and in the United States, people who had survived the 1918 flu had antibodies that completely blocked Shope’s swine flu virus. People who were born after 1918 did not have those antibodies.

The 1918 influenza virus, it seemed, may have survived after all, in the bodies of pigs.

The mysteries of the 1918 flu were beginning to be solved. There was a swine flu connection—probably people had given the flu to pigs, scientists proposed, and the virus may have remained in pigs, lying dormant until, one day, it might strike back at people. But there remained the question of when, and whether, the deadly flu virus might come back to infect the human race. And if it did, how could we get advance warning?

The 1918 epidemic came in two waves, a mild flu in the spring of 1918 followed by the killer flu in the fall. And it seemed that the two flu strains were closely related. Infection with the first strain protected against the second

“The conclusion is that mild attacks earlier in the year, as a rule, conferred immunity against the more fatal type of disease which prevailed subsequently.”

Not only the 2,000 who had had the disease in April but the 24,000 who apparently were not affected escaped the fall epidemic. It appears from this that the mild influenza of April gave a marked degree of immunity against the virulent form in October.”

It began to seem that the flu virus had gone somewhere between the first and second waves of the 1918 flu where it mutated into a killer strain. Perhaps, some thought, it had gone into animals.

he said, the difference between the first and second wave of the flu was not the virus but a hanger-on, the old nemesis of flu researchers, Pfeiffer’s bacillus. Shope was convinced that people were dying of influenza in the second wave of the 1918 flu because they were infected with both the virus and the bacterium, which amplified the virus’s effects.

These theories today are largely discarded, remnants of another time. Hemophilus influenzae is now known to cause a bacterial meningitis in children, and there is a vaccine to protect them against it.