The Next Plague Is Around the Corner

Disease experts are not worried about Ebola or Zika or even MERS—but instead with a disease that has killed millions in the 20th century.

Tony Fauci is the director of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH). It’s Fauci’s job to stop plagues before they start. Recently, Fauci was asked which infection scared him the most. The questioner assumed that he would say Ebola or Zika or MERS or SARS—all infections for which no vaccines and no anti-viral medicines are commercially available. But he didn’t. “Pandemic influenza,” he said.

Fauci isn’t the only one talking about pandemic flu these days. On April 7, 2017, Sanjay Gupta hosted a program on CNN titled “Unseen Enemy.” Gupta linked his program to an article titled, “The Big One Is Coming, and It’s Going to Be a Flu Pandemic”. On April 21, 2017, the Centers for Disease Control and Prevention (CDC) published a monograph titled, “Community Mitigation Guidelines to Prevent Pandemic Influenza—United States, 2017,” highlighting non-pharmaceutical interventions to stop the spread of flu like face masks, quarantine, and school closures.

Our fear of an influenza pandemic is best explained by the derivation of the word pandemic, meaning “all people.” Several times a century, influenza sweeps across the globe. For example:

• Between 1918 and 1919, Spanish influenza infected up to 40 percent of the world’s population, killing 50 million people. In the United States, between September 1918 and April 1919, 675,000 people died from the disease.    

• Between 1957 and 1958, Asian influenza killed 4 million people in the world and 70,000 in the United States. One reason that Asian flu wasn’t as deadly as Spanish flu was that an American scientist saw it coming and made a vaccine to prevent it—the first person in history to successfully predict and modify an influenza pandemic. His name was Maurice Hilleman. Decades later, Hilleman made a predication about the next great influenza pandemic.

On April 17, 1957, while sitting in his office at the Walter Reed Army Medical Research Institute, Hilleman read an article in the New York Times titled “Hong Kong Battling Influenza Epidemic.” “I saw an article that said that there were 20,000 people lined up being taken to the dispensaries,” he said. “And children with glassy-eyed stares, tied to their mother’s backs, were waiting to be seen.” Public health officials estimated that the virus had already infected 250,000 people, 10 percent of Hong Kong’s population. Hilleman put down the paper: “My God,” he said, “This is the pandemic. It’s here.”

One month later, Hilleman received throat washings from a navy serviceman infected with the virus. Hilleman tested sera from hundreds of civilians in the United States to see whether anyone had antibodies to the virus. No one did. The strain of virus circulating in Hong Kong was new. 

Hilleman then sent samples of what was later called Asian flu to six American-based vaccine manufacturers. He figured that if he were to have any hope of saving American lives, he would have to convince companies to make and distribute influenza vaccine in four months. He also knew that the production of millions of doses of influenza vaccine would require hundreds of thousands of eggs a day. He urged farmers not to kill their roosters, even though it was late in the hatching season. 

Pharmaceutical companies made the first lots of Asian influenza vaccine in June 1957. Vaccinations began in July. By late fall, companies had distributed 40 million doses. At the beginning of the school year, Asian influenza entered the United States. The National Health Survey estimated that during the week of October 13 alone, 12 million people were sick with influenza. Within a few months, influenza had infected 20 million Americans. Although the 1957 pandemic killed only a fraction of those killed during the 1918 pandemic, the two pandemics shared one sad feature: the disease disproportionately killed healthy young people. During the 1957 pandemic more than 50 percent of infections occurred in children and teenagers, at least a thousand of whom died from the disease—numbers that would have been far greater had it not been for Hilleman’s vaccine.  

Before he died in 2005, Maurice Hilleman believed that he had detected a pattern in influenza pandemics that allowed him to predict the next one. The father of modern vaccines, Maurice Hilleman had participated in either the primary research or development on 9 of the 14 vaccines currently given to young children. He had spent much of his career being right. So his prediction had to be taken seriously.  

Influenza viruses are defined in part by a protein that sits on the surface of the virus called the hemagglutinin or H protein. Antibodies directed against this H protein neutralize the virus. Although 17 different H proteins have been identified, only three have ever caused pandemics: H1, H2, and H3.  

Hilleman believed that future influenza pandemics could be predicted from the past: 

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H2 virus caused the pandemic of 1889. 

H3 virus caused the pandemic of 1900. 

H1 virus caused the pandemic of 1918. 

H2 virus caused the pandemic of 1957. 

H3 virus caused the pandemic of 1968. 

H1 virus caused the mini-pandemic of 1986. 

Hilleman saw two patterns in these outbreaks. First, the types of hemagglutinins occurred in order: H2, H3, H1, H2, H3, H1. Second, the intervals between pandemics of the same type were always 68 years—not approximately 68 years, but exactly 68 years. For example, an H3 pandemic occurred in 1900 and 1968; an H2 pandemic in 1889 and 1957; and an H1 pandemic in 1918 and 1986. Sixty-eight years was just enough time for an entire generation of people to be born, raised, and die. 

Using this logic, Hilleman predicted that an H2 influenza virus, similar to the ones that had caused disease in 1889 and 1957, would cause the next pandemic—a pandemic that would begin in 2025. As it turns out, Maurice Hilleman was wrong. The H1 pandemic of 2009, which affected 59 million Americans, causing 265,000 to be hospitalized and 12,000 to die, didn’t fit into Hilleman’s scheme. 

When Hilleman made his prediction in 2005, knowing that his death was imminent, he said, “We’ll soon know whether I was right or wrong. And I’ll be watching. I’ll be looking down—or up—to find out what happened.”


Paul A. Offit, MD, is the director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and the author of Vaccinated: One Man’s Quest to Defeat the World’s Deadliest Diseases (HarperCollins, 2007).