Influenza: The Hundred-Year Hunt to Cure the 1918 Spanish Flu Pandemic

by Dr Jeremy Brown

We tend to shrug off the flu as just a nasty cold, but in the United States alone it kills between 36,000 and 50,000 people each year.

if a pandemic strain of influenza as deadly as the 1918 virus were to infect the United States today, more than 2 million people could die.

Flu is certainly not “the emperor of all maladies,” as cancer was described by the oncologist Siddhartha Mukherjee, but it is the malady of all empires.

Because it was given in highly toxic doses, it may have been the aspirin that killed so many during the pandemic, and not the influenza itself. This is an unsettling thought, but it might help explain the deaths of a disproportionate number of otherwise healthy young adults—the very population that today rarely suffers from serious flu infections.

The treatment is really expectant, symptomatic and individualistic.

That last sentence is gold. It should be ingrained in the brain of every medical student in every medical school in the country. Wait and see what happens, treat the symptoms, and think about your patient and the individual profile she fits.

A rock is not alive, but a bacterium is. Viruses lie somewhere between the two.

virus is a box of chemicals, without the structures of a basic cell. It cannot metabolize or replicate on its own. In order to reproduce, it must invade living cells. Viruses infect bacteria and plants, reptiles, fish, birds, and mammals.

The most useful definition we have is that an epidemic is a severe local outbreak, while a pandemic is a global outbreak that makes people very sick, and spreads rapidly from a point of origin.

Was it the virus itself—perhaps a super version of the flu—or were there other reasons for its lethality? We’ve settled on four different explanations for why so many people died. Each is supported by some evidence, yet none is wholly satisfying.

The first explanation is that the virus had a protein on its surface that prevented the production of interferons, which signal to our immune system that our defenses have been penetrated. Healthy lung cells that transfer oxygen into the bloodstream are hijacked by the virus and destroyed by its replication process. Once dead, these cells are replaced with dull fibrous ones that are incapable of transporting oxygen, just like a scar that forms at the site of a cut and never looks the same as the surrounding healthy skin. An autopsy performed within hours on a U.S. Army private named Roscoe Vaughan in South Carolina showed that one of his lungs had this type of pneumonia. It’s possible that the sabotage of interferons allowed the 1918 virus to trigger a lethal viral pneumonia. Second, if the 1918 virus itself didn’t kill you, then secondary bacterial pneumonia probably did. Victims of the pandemic, their bodies weakened and their lungs already ravaged, caught bacterial infections like streptococcus and staphylococcus, which were deadly in this era before antibiotics. We now think that the majority of deaths in the 1918 pandemic resulted from these secondary infections, not from the flu virus itself. The South Carolina soldier’s other lung showed evidence of this kind of infection. He was killed by the one-two punch of the virus and a bacterial infection that swept in as his defenses crumbled. The third explanation for 1918’s lethality is that the flu virus triggered an over...

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.

The FDA also authorized the release of an experimental drug called peramivir.

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.

HA, remember, is a critical part of the weaponry of the influenza virus because it allows the particle to recognize the victim’s cell, like a radar acquiring its target.

The relationship between mental health and the moon made its way into our language long ago. The word lunatic is derived from the Latin lunaticus, meaning “struck by the moon.”

The vitamin D theory has to do with a loss of our immune function over the winter months. In winter in the Northern Hemisphere, the sun is at a lower angle in the sky, resulting in fewer hours of daylight. This leads to less melatonin and less vitamin D production, which leads to immune suppression. That makes us more prone to illness, and more likely to catch the flu.

In 2007 a group from New York’s Mount Sinai School of Medicine had looked at the role of cold air and humidity in the transmission of the flu virus. They used guinea pigs as their guinea pigs. These animals are very susceptible to infection by the human influenza virus. After placing cages of infected guinea pigs next to cages of uninfected ones, the researchers blew air from the former to the latter, while varying both the temperature and the humidity. They found that when the temperature and humidity were both low, there was a high rate of transmission. The virus became less transmissible, however, as the humidity and temperature increased. In fact, once the temperature reached a balmy 86 degrees Fahrenheit (or 30 degrees Celsius) there was no transmission of the influenza virus at all. The uninfected animals remained happy and healthy.

The seasonality of the flu is less of a mystery than it once was thanks to the work of Jeff Shaman and others. Humidity, sunlight, and temperature each seem to play a role,

From 1962 to 1987 most Japanese schoolchildren were vaccinated against influenza; at one point the vaccine was mandatory for a solid decade. The vaccination rate grew to around 85 percent, but the mandatory vaccination program was discontinued in 1994. Over the next several years, there was an increase in the number of deaths in the elderly during the flu seasons. In the U.S., where there had been no change in the vaccination policy, deaths of the elderly over the same flu seasons remained unchanged. Vaccinating one part of the population, in other words, benefits another.

leaving parents to pay for their children. Across Europe, the childhood vaccination rate is 15 percent, compared to almost 60 percent in the U.S.

this is on the home page of the CDC’s flu site: It can cause mild to severe illness. Serious outcomes of flu infection can result in hospitalization or death. Some people, such as older people, young children, and people with certain health conditions, are at high risk of serious flu complications. The best way to prevent the flu is by getting vaccinated each year. The CDC’s approach to flu is that it is a potentially deadly disease that can be prevented with a vaccine. The British take another approach. Here is the advice about the flu from their National Health Service: Flu is a common infectious viral illness spread by coughs and sneezes. It can be very unpleasant, but you’ll usually begin to feel better within about a week. . . . [If you are an otherwise healthy adult] there’s usually no need to see a doctor if you have flu-like symptoms. The best remedy is to rest at home, keep warm and drink plenty of water to avoid dehydration. There’s no mention of death as a complication. It’s all very “keep calm and carry on,” just like it was during the 1918 pandemic. At most, according to the British, influenza can be a bit of a nuisance: Most people will make a full recovery and won’t experience any further problems, but elderly people and people with certain long-term medical conditions are more likely to have a bad case of flu or develop a serious complication, such as a chest infection.

We give more chemotherapy to cancer patients near the ends of their disease, even though it improves neither the quality nor the length of their lives. We do these things because we can, because to do otherwise would be considered giving up—even if doing less would be an extremely sensible and kind decision.

The entwining of business and health during the great flu pandemic was vividly demonstrated at the Strand Theatre in New York. In October 1918, with the pandemic now plainly in the public eye, a new Charlie Chaplin movie opened. Shoulder Arms was a Great War comedy that took place on the battlefields of France, and audiences loved it. Perhaps they wanted a distraction, and a reason to leave their homes. The crowds were so large that the Strand extended the film’s run. Harold Edel, its twenty-nine-year-old manager, took out a full-page ad in the weekly Moving Picture World. Some theaters were shunned by “panic-stricken people,” Edel wrote, so he wanted to congratulate those who “take their lives in their hands to see it.” At the bottom of the ad, double-underlined and in a huge font, was the recommendation of the Board of Health to “AVOID CROWDS.” Edel’s ad continued: “New Yorkers took their life in their hands and Packed the Strand Theatre all week.” It was splendid news for the business during a period of dark turmoil. Edel, alas, never got to see his ad in print. He died of influenza a week before it went to press.

Airlines would suffer from a pandemic, but air travel might have helped cause it. Just as passenger ships brought the 1918 virus to vulnerable communities, the confined metal tubes that carry us through the skies are perfect flu incubators. We had no idea of just how big a part they played in the spread of influenza until another devastation occurred: the terrorist attacks on 9/11. There was a dramatic reduction in flights following the attacks, and a decrease in air travel persisted for some time. That year, the peak activity of the influenza virus came two weeks later than usual.

The title of his paper was “Success Is Something to Sneeze At”; sending a local team to the Super Bowl, he found, causes an 18 percent increase in influenza deaths in the elderly in the team’s hometown. In the years in which the Super Bowl was scheduled closer to peak flu activity, the effect was even greater; there was a sevenfold increase in influenza deaths back home.

focus my thoughts for the future in three broad categories: our knowledge about the virus, our response to it, and our preparation for the next outbreak. First, there has been no greater achievement in our battle against influenza than our knowledge about its cause.

Equally impressive is the way we can now respond to the virus. The most important new tools in our war chest have nothing to do with the virus itself. Those tools include antibiotics, which allow us to treat the complications that may follow influenza, as well as intensive care units, respirators ready to take over for beleaguered lungs, and specialists standing by who know the ins and outs of emergency care and infectious diseases.

But we still don’t have a drug that reliably attacks the influenza virus itself. What we have instead are antiviral medications whose benefits are at best controversial, and at worst nonexistent. We urgently need to develop a safe and effective drug that can destroy the virus.

There have been two approaches to this question: the pessimistic and the optimistic. For the pessimist, the next flu epidemic looks deadly and inevitable.

I’d like to see a memorial in our nation’s capital to the flu pandemic of 1918, to honor our losses, to reflect on how far we have come, and to remind us how much more there is yet to do.