The 1918 pandemic mistake that changed medicine forever - National Geographic UK

Casting a long shadow

Despite the chaos it caused in 1918—or arguably because of it—Pfeiffer's bacillus had a lasting effect on medicine and microbiology.

Then as now, researchers trying to control the pandemic were publishing their findings about causes and treatments at a frantic pace. But in 1918 it was much harder to compare results, let alone understand the big picture. The public health community at the time had no standardised methods of research or testing, virtually no peer review, and no common protocols for clinical trials. Some of the vaccine trials for the 1918 flu were conducted on vulnerable populations, including mentally ill patients, orphans, and prisoners.

In response, the American Public Health Association issued the nation's first guidelines for conducting vaccine trials in January 1919. The guide included some of the most foundational practices used today, such as having a control group—a set of participants who don't get the experimental treatment and so serve as a baseline—and matching participants in the control and experimental groups by gender, age, and prior exposure.

In 1928 "a very bad year of seasonal influenza got Congress worried," so they created the National Institutes of Health, says historian John Barry, author of The Great Influenza. "Had 1918 not sensitised them, it wouldn't have happened."

Similarly spurred by the missteps of the 1918 pandemic, the World Health Organisation established a network of 26 laboratories around the world called the Global Influenza Surveillance and Response System in 1952. Taubenberger says scientists were thus better prepared when the H2N2 pandemic hit in 1957. They were ready with antibiotics to treat the secondary infections that had been so devastating in 1918, and they could quickly create effective vaccines for the specific strain.

Also, one upside of chasing down Pfeiffer's bacillus—also known as Haemophilus influenzae, or H. flu—was that researchers learned more about it. In 1929 a young bacteriologist named Margaret Pittman studied more than 500 mucus samples from Rockefeller Hospital patients. She was trying to definitively establish or completely sever the link between the bacterium and the flu, and she didn't do either. But she did discover six encapsulated strains of H. flu. Humans are H. flu's only host, and some strains live harmlessly in our noses and throats. But one strain, now known as Hib, is especially pathogenic.

Pittman's work revealed Hib as the cause of a variety of serious conditions, including influenzal meningitis, which can lead to death or lifelong disabilities. Soon after her discovery, Pittman developed a serum from horse blood that saved tens of thousands of children and made her internationally famous. Her insights were instrumental in the creation of the Hib vaccine 50 years later, which has since virtually eradicated Hib diseases wherever it's been introduced.

An historic coronavirus, too?

Recently scientists have found hints that Pfeiffer's mistake may not have been the only error associated with the 1889 pandemic. If they're right, the discovery could have implications for the COVID-19 pandemic.

In a 2005 paper Belgian researcher Leen Vijgen traced the most common ancestor of a bovine coronavirus and the human coronavirus CO43 to around 1890, when it seems to have leapt from cows to people. Other scientists have since argued that the disease seen in 1889 shares similar symptoms to those of COVID-19, including the loss of taste and smell, seizures, and long recovery periods.

Perhaps, they say, the 1889 pandemic was not caused by a flu virus at all, but by the CO43 coronavirus. Teasing out the truth may offer a window into the future of SARS-CoV-2; for one, the strain of CO43 circulating today causes only mild symptoms.

Taubenberger and his NIAID colleague David Morens have also set their sights on the 1889 pandemic. They're seeking tissue samples from the period, which have so far proven elusive.

"It's very, very hard to find autopsy samples from before 1918," Taubenberger says. "We have been working very hard with other collaborators around the world to find such cases, and we've been analysing autopsy cases going back to about 1907 or so. No one is aware of any tissues from the 1890s. But that's not to say they don't exist somewhere."

Taubenberger adds that it's a modern mistake to think the researchers working during past pandemics were missing the obvious: Despite having vastly better technology and improved understanding of how viruses cause disease, we're still in the dark about some aspects of COVID-19, including its origins, its long-term impacts on the body, and its ultimate evolutionary trajectory. Today's scientists have also had to navigate conflicting data about how COVID-19 spreads and how best to control it.

"If you don't know what the unknowns are, you can't look for them," Taubenberger says. "We don't know what our unknowns are. A hundred years from now, there are definitely going to be insights that should have been quote-unquote 'obvious' to us now. And that's perfectly fine. That's the way of science."

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