"I had a little bird, and its name was Enza,
I opened the window, and in-flew-Enza."
— Children's rhyme during the 1918 influenza pandemic
Influenza viruses are constantly mutating. Because of these mutations, natural infection or immunization one year doesn't protect against disease the following year. For this reason, the Centers for Disease Control and Prevention recommends that everyone more than 6 months old should receive a yearly influenza vaccine.
Worse: Several times every century, the change is so dramatic that very few people living on the planet are immune. This can result in a worldwide epidemic, or pandemic.
The first person to successfully predict an influenza pandemic and make a vaccine in advance of its entry into the United States was Maurice Hilleman.
Hilleman was born Aug. 30, 1919, in eastern Montana, during the worst influenza pandemic in history.
During the 1918 pandemic, influenza infected 500 million people, half the world's population. In a single month, October 1918, 400,000 Americans died from influenza. In one year, the average lifespan of Americans in their 20s and 30s decreased by 25 percent.
When it was over, the 1918 pandemic — the most devastating outbreak of an infectious disease in medical history — had killed between 50 and 100 million people worldwide; all within a single year.
Hilleman went on to become a microbiologist at the Walter Reed Army Medical Institute in Washington. On April 17, 1957, while sitting in his office, he 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. And children with glassy-eyed stares, tied to their mother's backs, were waiting to be seen," Hilleman recalled in an interview I conducted while writing a book on the topic.
Public health officials estimated that the virus had infected 250,000 people — 10 percent of Hong Kong's population. Hilleman recognized that the people of Hong Kong weren't just suffering from a yearly epidemic.
"My God. This is the pandemic. It's here," Hilleman recalled saying.
The next day, Hilleman cabled the army's 406th Medical General Laboratory in Zama, Japan, and asked for throat washings from any serviceman in the area who was infected. He received a specimen on May 17, 1957.
For five days and nights Hilleman worked to determine whether the influenza virus circulating in Hong Kong could be a pandemic strain. Using banked blood samples obtained from the World Health Organization, the U.S. Public Health Service, and the Armed Forces Epidemiological Board, Hilleman found that only a handful of people — in the Netherlands and the United States — had antibodies to the virus. All were men and women in their 70s and 80s who had survived the influenza pandemic of 1889-1890 that had killed six million people.
The virus that had caused the 1889 pandemic was back. And virtually no one had antibodies to stop it.
Under Hilleman's direction, U.S. pharmaceutical companies made the first lots of Asian influenza vaccine in June 1957. By late fall, companies had distributed 40 million doses. When it was over, the influenza pandemic of 1957 killed 70,000 Americans and four million people worldwide. But Hilleman's quick actions saved tens of thousands of American lives. For his efforts, Hilleman won the Distinguished Service Medal from the U.S. military.
In 1960, Hilleman moved to Chestnut Hill in Philadelphia. For the next 45 years, he worked for the pharmaceutical company Merck, where he conducted the primary research or development on most of the vaccines given to infants and young children today. Because of his work on vaccines, we live, on average, 30 years longer than we did 100 years ago.
In the months before his death in 2005, Hilleman made a prediction regarding the next pandemic. Understanding this prediction depends on understanding why influenza is so elusive.
Influenza got its name from Italian astrologers, who blamed the disease's periodic occurrence on the influence — in Italian, influenza — of the heavenly bodies. The most important part of the virus sits on its surface. Called the hemagglutinin, this protein is responsible for attaching to cells that line the windpipe and lungs. Antibodies to the hemagglutinin prevent the virus from binding to cells and, therefore, prevent infection.
Influenza virus doesn't have only one type of hemagglutinin; it has 17. Hilleman noted, however, that only three types of hemagglutinins had ever caused pandemics: H1, H2, and H3.
Hilleman believed that future influenza pandemics could be predicted from the past:
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 observed two patterns in these outbreaks. First, the types of hemagglutinins occurred in this order: H2, H3, H1, H2, H3, H1. Second, the intervals between pandemics of the same type were exactly 68 years. For example, an H3 pandemic occurred in 1900 and 1968, and an H2 pandemic occurred in 1889 and 1957. 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 virus, similar to the ones that had caused pandemics in 1889 and 1957, would cause the next pandemic, which would begin in 2025.
Hilleman made his prediction in 2005, months before his death. As it turned out, his pattern didn't hold up. In 2009, the world suffered an influenza pandemic caused by H1 virus, just 23 years after the last H1 pandemic.
Paul A. Offit, MD, is a professor of pediatrics at the Children's Hospital of Philadelphia and the author of the forthcoming book "Bad Advice: Or Why Celebrities, Politicians, and Activists Aren't Your Best Source of Health Information" (Columbia University Press, June 2018).