Thousands of sick people stood in line, awaiting treatment in clinics. On their backs, women carried glassy-eyed children, who in turn carried the virus. Officials called it the “worst epidemic outbreak in years.” It was April 1957, half a lifetime after the 1918 flu, and at least 10 percent of Hong Kong’s 2.5 million people were sick. There was no end in sight—especially as an influx of 700,000 refugees from communist China congregated in overcrowded neighborhoods.
The world appeared on the brink of the first global influenza pandemic since 1918, although this outbreak was caused by a different strain of the flu virus. It was labeled H2N2, and contained the genes of both a human and an avian flu virus. The avian genes had likely leaped from ducks, which were (and continue to be) handled in great numbers in the bird markets of China. It was a textbook example of antigenic shift, which created a new virus not recognizable by our immune systems. The results could have been catastrophic, but the virus seemed capricious. True to its unpredictable nature, the flu hit people differently. Identical samples were found both in those who had died and in those who suffered mild symptoms and recovered.
This “Asian influenza” invaded Britain by the autumn, tripling the flu death rate. It killed about 68,000 people in the United States and perhaps 2 million worldwide. However, unlike the 1918 pandemic, the Asian flu did not overwhelm those who were otherwise healthy. Instead, it appeared to target people who were always at risk, like those with chronic underlying heart or lung diseases. In the U.S., Asian flu also quickly spread to schoolchildren; more than 60 percent became clinically ill.
The story of the twentieth century can be told through its wars or its technological leaps—or through its flu pandemics. The outbreaks were irregular in timing, as with all of recorded flu history, but they were familiar in progression: a point of origin, a rapid spread, sickness and death, and a furious public debate about how to respond. With each passing decade, from the Eisenhower years to the Gerald Ford interlude to the Obama era, we became more equipped to fight back, but the counterattack was never perfect and always fraught.
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Medically speaking, 1957 was very different from 1918. Physicians had two new weapons with which to fight the pandemic. The first was antibiotics, which were now available to fight any secondary bacterial infections. They changed everything. Deadly skin infections were easily treated. Rheumatic heart disease, a dreaded complication of strep throat, became a thing of the past. Perhaps most important of all, bacterial pneumonia could now be treated. In the pre-antibiotic era, pneumonia was called “the old man’s friend” because it caused a very rapid but blessedly painless death. Breathing became more and more difficult as the bacteria multiplied within the lungs, preventing the entry of life-sustaining oxygen. There was nothing to be done. The patient would drift off into unconsciousness and soon expire. These lethal bacterial pneumonias often followed an influenza infection, especially in the elderly. And now there were, at last, antibiotics that could save thousands of lives—which is exactly what they did in the 1957 influenza outbreak. Without them, the death toll would have been far greater.
The second new weapon was not a cure for those who had been stricken, but a prevention for those who were still healthy. For the first time there were vaccines that could protect those who were not yet infected. The American virologist Maurice Hilleman first learned of the 1957 outbreak from an article in the New York Times, which prompted him to get a head start on the production of an H2N2 vaccine. Working together with the pharmaceutical industry, he spent much of the summer of 1957 creating a vaccine that could thwart Asian flu. Growing enough influenza virus to produce the vaccine is challenging. For reasons that are not known, the virus is very picky about what it chooses to grow on. After a long process of trial and error, it became apparent that the only medium on which influenza would grow was fertilized chicken eggs. And so Hilleman went to work, and demanded that farmers keep enough chickens available to produce millions of eggs. Thanks to his leadership, there were about 40 million doses of the vaccine by the end of 1957. He recalled later, “That’s the only time we have ever averted a pandemic with a vaccine.”
The H2N2 influenza continued to circulate for the next decade, but it no longer caused significant outbreaks. Eventually it disappeared, only to be replaced by a new strain of avian flu, which in 1968 caused the third pandemic of the twentieth century. It originated in Hong Kong (again!), and like the 1918 influenza, its spread was accelerated by war.
The “Hong Kong influenza” was a descendant of the 1957 Asian flu. Hong Kong remained ground zero because chickens and ducks were handled in vast open markets, once again allowing the avian and human influenza viruses to mix and swap genes. It quickly spread to Southeast Asia, and in August 1968 soldiers returning from Vietnam brought the virus into the United States. It was reported in Australia and England by September, in Canada by December, and in France in January of 1969.
The new flu virus replaced the H2 protein on its surface with a different one, called H3, but the rest of the virus was pretty much unchanged. Because of these similarities, the old vaccine to the Asian H2N2 influenza provided some immunity against the Hong Kong flu. Similarly, those who had caught the 1957 Asian flu retained a degree of immunity to the new infection. This explains why the Hong Kong flu, which caused a million deaths worldwide, was still less deadly than the Asian flu. The Hong Kong flu strain still causes influenza today, although not on an epidemic scale. Our immune system has learned to fight this flu virus as it would any other.
The twentieth century had witnessed the mass death caused by the Spanish flu, and was now facing new influenza viruses. The virus was never wholly vanquished. It was always changing shape. And it next struck almost two decades later, when an army private collapsed at Fort Dix, outside of Trenton, New Jersey.
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When new recruits arrived at Fort Dix in the fall of 1975 they were given the most current flu vaccination, which contained weakened versions of common flu strains. After the Christmas break, soldiers returned to base during an especially cold winter. In short order there was an outbreak of a flu-like illness causing fevers, sore throats, and fatigue. Throat swabs of the patients showed not influenza but another microbe, adenovirus, which causes an influenza-like illness. The patients were also tested for the flu virus by the New Jersey Department of Health, and the results were puzzling. Some men had a known strain of influenza, but several had a mystery strain. Two of these mystery swabs were sent to the Center for Disease Control, which identified the virus as a descendant of the 1918 virus.
All the recruits recovered, but then, on February 4, 1976, a private named David Lewis collapsed after a routine five-mile march and was taken to the Fort Dix hospital. There, a few hours later, he died from what appeared to be a fast-acting pneumonia. Lewis’s death was initially reported as having been caused by a disease of unknown origin. But within two weeks the CDC identified the virus: it was a strain of pig influenza.
This prompted more questions than answers. None of the men who were sick at Fort Dix had been in contact with swine. The virus must have mutated, allowing it to spread directly between people, without going through its original host species. The CDC also identified the virus as an H1N1 type—like the one in 1918.
The Fort Dix outbreak was caused by a new strain of influenza, but it was most certainly not an epidemic. Only one person died. Nonetheless, it was of pivotal importance. To this day, the way the government responded to the 1976 outbreak is a topic of considerable controversy. Some experts believed then that the potential for a pandemic demanded a massive vaccination program. Others said the risks of such a program outweighed the benefits.
Because the strain originated from a virus that infected pigs, that 1976 flu was called swine flu, and it became a public health emergency. No one knew if it would spread like its 1918 ancestor and become a pandemic, or remain a local outbreak that caused only a single death. In the midst of the initial effort to identify the Fort Dix virus, Edwin Kilbourne, a virologist at the Mount Sinai School of Medicine in New York, published an op-ed piece in the New York Times with a gripping headline: “Flu to the Starboard! Man the Harpoons!” Kilbourne was not aware of the Fort Dix outbreak when he wrote the piece, which makes his observations all the more poignant.
Kilbourne looked back at the frequency of previous flu pandemics and discovered that they occurred at intervals of eleven years or less. The next pandemic, he wrote, was due sometime before 1979. It could be minimized by vaccinating the 45 million Americans who were most at risk. He also called on the CDC, the Food and Drug Administration, and the National Institutes of Health to work together to provide flu vaccines for the public, and called on health officials to plan for “an imminent natural disaster.”
The day after Kilbourne’s prescient publication, federal officials gathered in Atlanta at the CDC headquarters. How should they respond to the Fort Dix swine flu? At a quiet and understated press briefing, they released some details of the outbreak, though they were careful never to mention the 1918 pandemic. Swine flu remained confined to Fort Dix and had not spread to the surrounding civilian population. But officials were concerned that the virus would reappear the following fall and spark a global pandemic. The only way to prevent this was to quickly produce a vaccine, and they decided that the best scientist to lead the project was Kilbourne himself.
In March, less than a month after Private Lewis died, officials decided to turbo-charge the production of a vaccine and inoculate all Americans by the autumn. While the risk of a pandemic was very small, the consequences would have been devastating. “Better a vaccine without an epidemic,” Kilbourne said, “than an epidemic without a vaccine.”
A massive vaccination program was also a massive gamble. If no swine flu outbreaks occurred in the fall, health officials could be accused of waste and overreach. But there was another concern: in a letter to the New York Times, Dr. Hans Neumann from the New Haven Department of Health noted that based on the projected scale of the immunizations, within two days of getting a flu shot, about 2,300 people would have a stroke and 7,000 would have a heart attack. “Why?” he asked. “Because that is the number statistically expected, flu shots or no flu shots.”
Likewise, in the week following a flu vaccine, another 9,000 people would contract pneumonia, of whom 900 would die. These would certainly occur after a flu shot, but not as a consequence of it.
“Yet,” wrote Neumann, “can one expect a person who received a flu shot at noon and who that same night had a stroke not to associate somehow the two in his mind?”
Grandma got the flu vaccine in the morning, and she was dead in the afternoon. Although association does not equal causation, this thinking could lead to a public backlash against vaccinations that would threaten future programs. (More recently we have seen the mistaken identification of association with causation produce a backlash against vaccinations, which are mistakenly blamed for autism.) As a preventive measure, some health experts advised against the vaccine, and said it should be stockpiled instead. If the swine flu returned in the fall, then—and only then—would the vaccine be released to the public.
The decision made it all the way to the White House. President Gerald Ford accepted the advice of his health care advisers, who wanted to err on the side of action rather than inaction. Flanked by Jonas Salk and Albert Sabin, the discoverers of the polio vaccine, Ford announced a request for emergency funds to inoculate every man, woman, and child against the impending threat of pandemic swine flu. Discarding the caution of doctors at the meeting in Atlanta, the president mentioned the 1918 pandemic.
“Some older Americans today will remember that 548,000 people died in this country during that tragic period,” Ford said in the White House briefing room. “Let me state clearly at this time: No one knows exactly how serious this threat could be. Nevertheless, we cannot afford to take a chance with the health of our nation.”
His decision would have far-reaching implications. There were complexities for industry too. Drug companies faced the challenge of producing enough vaccines in short order, and of obtaining insurance in case anything should go wrong. After the manufacturers threatened to cease all production of the vaccine unless they were adequately protected, President Ford signed a bill in August to indemnify them. The vaccine program started in early October, and was quickly followed by precisely the kind of frightening media reports that officials had feared. It became a public relations nightmare.
Three elderly people died after receiving the flu vaccination at the same clinic, and people panicked about a connection that didn’t exist. Walter Cronkite appeared on the evening news to reassure the public, and to caution against sensationalist reporting. His pleas went unheeded. The media blamed the vaccine for all manner of illnesses and deaths. The New York Post even claimed that it had been used as a deadly weapon to kill the head of the Gambino crime family. The CDC reminded the public that in truth there was no increase in the death rate among elderly Americans receiving the vaccine. President Ford got his flu shot on television. But public opinion was swayed not by logic or evidence but by emotion and anxiety.
People doubted the vaccine or, worse still, feared it. There were reports of an increase in the number of cases of a rare neurological disease called Guillain-Barré syndrome (GBS), which causes a range of symptoms including difficulty swallowing, weakness in the arms and legs, and muscle paralysis. In the fall the CDC recorded an unusual number of GBS cases following vaccination. Although there was no known relationship between flu vaccines and GBS, the CDC asked doctors to report any new cases to them. This added to the uproar. Some doctors who couldn’t diagnose the source of a patient’s weakness were now attributing it to GBS, especially if the patient had recently been vaccinated. By December the CDC was so concerned about the confusion that it ended the vaccination program. There had not been a single case of swine flu, but there were dozens of cases of GBS attributed to the flu vaccine. A “sorry debacle,” the New York Times wrote in an editorial. The newspaper faulted “the excessive confidence of the Government medical bureaucracy” led by the CDC, which had taken advantage of the outbreak to multiply its budget. Newsweek was more direct. This was “the swine flu snafu,” and David Sencer, the CDC’s director, was forced to resign.
And then the lawsuits began (after all, this is America). Vaccine manufacturers had been indemnified by Congress, which left the federal government liable for any damages. By 1980 more than 3,900 claims had been filed, seeking a total of at least $3.5 billion in compensation. By then over 500 cases of GBS following a flu shot had been reported, and 23 of those people had died.
Despite more than forty years of analysis and debate, it is still unclear if there really was a link between GBS and the swine flu vaccine. In the military, where almost 2 million people received a double dose of the influenza vaccine, there was actually a decrease in cases of GBS. Today, on its seasonal influenza website, the CDC states that data on the association between GBS and seasonal flu vaccination are “variable and inconsistent” across flu seasons. But even if there had been a causal association, it was, for some, a small price to pay for avoiding catastrophe. Thirty years later, Sencer, the fired CDC director, reflected on the decision. “Public health leaders must be willing to take risks on behalf of the public,” he wrote. And even with 20/20 hindsight, Sencer stood by the decision to release the vaccine, because “when lives are at stake, it is better to err on the side of overreaction than underreaction.”
Edwin Kilbourne, the virologist who had written that prescient op-ed piece in the first days of the 1976 outbreak, also defended his decisions. He declared an “unyielding position on the need for vaccine production and immediate vaccination.” Even though the outbreak was confined to Fort Dix, the swine flu was transmissible from person to person and was in the same family as the 1918 virus. That the virus disappeared over the summer of 1976 meant nothing. Viruses can vanish, only to return as an even greater threat. That had happened after the first wave of the 1918 epidemic. It was likely to happen again. “None of these facts,” he wrote, “was noted by critics of the program.” Kilbourne called for better influenza preparation, “but with the realization that no amount of hand washing, hand wringing, public education, or gauze masks will do the trick.”
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The impulse to do something, to react in the face of a catastrophe, is a common theme in our fight against influenza. In 1918 Chicago’s public health commissioner noted that “worry kills more people than the epidemic,” and so every step should be taken to assuage the public. In 1976 we stockpiled vaccines for every single American, at great cost, even though there was no certainty that a pandemic was coming. It was a high price to keep the public from worrying.
The next “pandemic” broke out in 2009, in the era of social media and the twenty-four-hour news cycle, and it was also caused by a swine flu strain. It invaded a world that had already endured, minute by minute, the traumas of the 9/11 terrorist attacks, the Indian Ocean tsunami, and Hurricane Katrina. But now there were regular planning exercises and heightened cooperation between federal, state, and local health agencies. Life was different. And there was Twitter.
In March 2009 the virus was first detected in Mexico, where it killed about sixty people. Acting quickly, the Mexican government closed schools, banned public gatherings, and ordered troops to hand out face masks at subway stations. By April the strain had reached the United States, and some students in New York tested positive for the disease. This time the strain contained genes from four ancestors: an American swine flu, a European swine flu, an avian flu, and a human flu. It was still an H1N1 strain, similar to the 1918 and 1976 strains. By June there were more than 30,000 cases across seventy-four countries, and the director-general of the World Health Organization (WHO) declared it a pandemic. Over half the cases of influenza in the United States were caused by the new strain. While most of the deaths occurred in children and adults, there were very few in those over the age of sixty-five, who appeared to be immune; perhaps they had been infected by a similar virus years prior. By June, all fifty states had reported cases of H1N1, and the CDC reported that at least a million people had been infected. Thankfully nearly all of them recovered without needing medical treatment.
Once again, the latest flu outbreak bore eerie similarities to the 1918 pandemic. Cases were first reported in late spring and early summer. Next, the virus went into hiding. Then, at the end of August, just like in 1918, there was a sudden surge in cases. But for the first time in history, there were now drugs that could target the influenza virus itself. These medications were available by prescription to the public, and were also part of the country’s Strategic National Stockpile (SNS), a mother lode of medications and equipment that could be released in a medical emergency that overwhelmed the health care system. To meet the demand in 2009, the SNS released some of its store of antiviral medications as well as almost 60 million face masks.
The FDA also authorized the release of an experimental drug called peramivir. It was part of the SNS but was still undergoing clinical trials, and there was very limited data on its safety and efficacy. As a result, it could be used only under extraordinary conditions, and the 2009 outbreak qualified. The FDA received 1,371 requests for the drug between October 2009 and June 2010. After the pandemic subsided, doctors went back to look at the success of peramivir, but were unable to draw any definitive conclusions. About 15 percent of the patients who received it died, but they were already critically ill when the request for the drug was made. Three years later the FDA approved peramivir, even though there was little evidence of its healing magic.
Over the summer of 2009, vaccine production kicked into gear. Following Gerald Ford’s example, President Barack Obama was photographed that December rolling up the sleeve of his sweater in the White House to receive his influenza vaccine. Again, a U.S. president was assuring the public, through the media, that the vaccine was both safe and necessary.
“People need to understand that this vaccine is safe,” Obama said during a radio interview in the Oval Office, before noting the low rate of vaccination among African Americans. “If I had the two people that are most important in my life, my two daughters, get it right away—and they’ve been just fine with it and in fact haven’t gotten sick this entire flu season—then you need to know that you need to make sure your children get it as well.”
But the number of cases had already peaked back in October. By January the flu season returned to its baseline. The swine flu crisis fizzled out. Experts had predicted it would cause up to 1.9 million deaths in the United States, but the estimated toll was 12,500, an unusually low figure for an influenza outbreak. Worldwide, deaths from the pandemic also did not exceed the number during a usual flu season.
The most lasting side effect of the 2009 swine flu pandemic was confusion among the public. Officials warned us repeatedly to brace for a deadly winter. The media reported flu deaths and advice on how to avoid getting sick. In an interview with the Washington Post, a fourteen-year-old from Maryland described her fears as she developed a high fever. “I went to the doctor when it hit 103,” she said. “He did a rapid test. He said he was pretty sure it was swine flu. It was not the regular flu season, and he had six cases that day. . . . When he said that I had swine flu, my mom and I laughed. ‘Okay, what do I really have?’ He said, ‘Yeah, I think that’s what you have.’ Oh, my God. At first I thought, ‘Am I gonna die?’ ”
Her fears were not surprising, given the mixed messaging from the top. In April 2009 President Obama had said that there was no cause for alarm. Then in October he declared the H1N1 outbreak to be a national emergency. The public didn’t know what to think.
To complicate matters, there was another kind of viral outbreak, on Twitter and other social media. For the first time in a public health emergency, misinformation and fear were spreading faster than the virus. There were almost 3 million tweets about the flu. It now had its own hashtag: #swineflu. A CDC spokesman thought that the online buzz about swine flu was a good sign, showing that the public was engaged and ready to fight back with knowledge and prevention measures. But Twitter feeds were infected with fearmongering, and cable news outlets like CNN and Fox News were criticized for exaggerating the story and stoking public worry. If the public believed that scientists were “crying wolf,” they would disregard future warnings.
In Washington, D.C., my emergency department was inundated with incoming patients who had flu-like symptoms. The ones with the flu were easy to spot. They wore blue disposable face masks handed out by the nurse when they checked in. Had we tested them for it, many would have been positive for H1N1. But it didn’t matter whether they were ill with swine flu or seasonal flu or just another viral infection, because almost all were well enough to be discharged. The 2009 swine flu season turned out to be no more and no less deadly than any other flu season.
Then came the fallout. There were claims that the death estimates were exaggerated. Fiona Godlee, editor of the influential British Medical Journal, reported that some of the experts advising the World Health Organization had not disclosed their financial ties to the pharmaceutical industry. This raised ethical questions about conflicts of interest.
The real problem was the WHO’s use of the word “pandemic.” Most people think of a pandemic as a disease that spreads and kills thousands of people. That description is echoed in the WHO’s official definition of the word as an infectious disease that causes “enormous numbers of deaths and illness.” But in talking about the 2009 outbreak, the WHO used a more academic and narrow definition that focused only on prevalence, not severity. After this was pointed out by an astute CNN reporter, a WHO spokeswoman announced that the organization had erred in using the more apocalyptic definition. “It was a mistake, and we apologize for the confusion,” she said, noting that the word painted “a rather bleak picture and could be very scary.”
The H1N1 outbreak was just another kind of seasonal influenza, and no more dangerous than usual. One word had elevated its stature in the minds of the media and the public. The 2009 “pandemic,” which was not really a pandemic at all, taught us that language is both a weapon and a handicap when waging a campaign against influenza. The public took the WHO and the CDC at their words, imagining that a lethal 1918-style outbreak was about to be unleashed.
This was not the first time that the description of a pandemic did not match its severity. The 1957 Asian flu was confusingly described by the WHO as both “comparatively mild” and “substantial.” The 1968 Hong Kong flu outbreak was called “mild” by the WHO, and “moderate” by the CDC. Either way, the influenza historian John Barry noted that few people who lived through the 1968 pandemic “even knew that it occurred.”
After the devastation of 1918, the flu spent the rest of the twentieth century stalking us without delivering another gut punch to the global population. But as our knowledge of influenza accumulated, the virus found new weaknesses in our systems. It revealed inadequacies in policy, preparedness, response, and media reaction. And we still didn’t have a genetic profile of the 1918 virus itself. But that was about to change. The hunt for a sample of the original 1918 virus involved a medical student working in the Arctic, a young pathologist trying to save his job from Congress, and bodies dug up from the frozen tundra.