During this flu season, we commemorate the 100th anniversary of the Great Influenza Pandemic of 1918. It swept the world leaving 100 million dead, making it the most devastating infectious disease outbreak of all time. After a century, how has our knowledge changed, and what is there still to be done in order to conquer the flu?

Perhaps the most frightening aspect of the 1918 influenza pandemic was the mystery of what was causing it. The word “influenza” comes from the Italian word meaning “influence,” which attests to the astrological theory of its origin. We once thought the illness was caused by the conjunction of Jupiter and Saturn. Other theories included rotting animal carcasses, earthquakes, volcanic eruptions and “effluvia” discharged into the air from the bowels of the earth. “We may as well admit it and call it the ‘x’ germ,” wrote a public health official in the midst of the onslaught. People had no idea.

In 1892 two microbiologists working in Berlin had discovered a new bacterium called Bacillus influenza, and they claimed that caused influenza. But they were wrong. The bacteria were certainly present in flu victims, but they were not the cause of the flu. Instead, they were a secondary pathogen that invaded a body whose immune system was overwhelmed by what we now know to be viral influenza. The bacteria didn’t cause influenza any more than circling vultures caused the death of a deer felled by wolves.

But it soon became clear the cause of influenza was something far smaller than a bacterium, and in 1939 the newly invented electron microscope captured the first pictures of a virus. Soon after, scientists isolated influenza; today we know its genetic code, what its outer protein structure looks like, and how it invades healthy lung cells and reproduces. These advances in our knowledge of the virus have been nothing short of incredible. 

Without knowing the cause of flu, it was impossible to create a flu vaccine. But this didn’t stop scientists and doctors from doing something, anything, to combat the outbreak. In 1919 Edward Rosenow from the Mayo Clinic formulated a vaccine that contained five different kinds of bacteria isolated from the sputum and lungs of flu patients in Rochester, and doled it out to 100,000 people. At Tufts College Medical School in Boston, pathologist Timothy Leary (whose nephew and namesake would become a famous psychologist and experiment with psychedelics) produced his own blended vaccine using strains from the Chelsea Naval Hospital, a nurse’s nose at Carney Hospital, and the infected wards of Camp Devens. Leary mixed these samples together, grew them on plates of agar, and then sterilized the mixture. His vaccine was sent to San Francisco, where at least 18,000 people were inoculated with it. Of course, none of these vaccines actually worked, because they were targeting the wrong culprit.

Today we do have a vaccine for influenza, but it is far from perfect. It needs to be updated each season, and even in a good year it works no more than 50 percent of the time. Its effectiveness varies from patient to patient, from population to population and from year to year. There are certain groups who are at an increased risk of complications from influenza and should get vaccinated each year: children, the elderly, those with chronic medical conditions or a weakened immune system, and pregnant women.

But the vaccine does not seem to do much for otherwise healthy adults. At best it reduces their risk of influenza from 2 percent to just under 1 percent. So the quest for a better influenza vaccine continues. The holy grail would be a vaccine that covers all possible strains of influenza and that needs to be given only once and not every year as is now the case. Dozens of research labs across the world are working to create this so-called universal vaccine, so far without success. The influenza virus is just too adept at changing its disguise, remaining one step ahead of our efforts to neutralize it with a one-shot-fits-all vaccine.

Enemas. Mercury. Tree bark. Bloodletting. These were some of the medical interventions doctors used during the 1918 flu pandemic. Methods to boggle your mind and turn your stomach. Bloodletting, the practice of draining the body of blood—and therefore, in theory, of toxins and disease—was mainstream medical practice for more than 2,000 years. Remarkably, it was still used to treat patients with flu. British doctors bled patients when influenza swept through their army camps with catastrophic results. “So far,” they wrote, “we have been unable to find anything that has any real influence on the course of the disease.”

And then this: “Venesection has likewise failed to benefit the patient for more than a very short time, though possibly we have not resorted to this treatment sufficiently early.” The British physicians had tried venesection, the medical term for bloodletting, and it had not worked—perhaps, they thought, because they tried it too late in the course of the disease.

For nausea and vomiting, which are common symptoms of the flu, physician Arthur Hopkirk recommended small doses of dry champagne. “There is no finer pick-me-up after an attack of influenza” he wrote, “than good fiz.”  For fevers, the good doctor recommended a laxative, such as the delightfully named “effervescent magnesia.” Severe cases of flu required a severe laxative like calomel, which is made with mercury chloride. Mercury, of course, is highly toxic.

We have come a long way. We now have antibiotics, which do not target the influenza virus but can treat the secondary bacterial pneumonias that sometimes follow. It is these pneumonias that are thought to have caused the majority of deaths during the 1918 epidemic.  For the very sick we have ICUs, and there are heavily advertised antiviral drugs like oseltamivir, better known as Tamiflu. These target a protein on the surface of the flu virus to prevent it from spreading, and are part of the Strategic National Stockpile, standing ready to be deployed in the event of a pandemic.

But they are far from effective. The best evidence we have is that it shortens the symptoms of the flu by about one day, and the FDA-required package information states that Tamiflu hasn’t been shown to reduce flu-related bacterial infections or hospitalizations.

After a century of medical and scientific breakthroughs, influenza still taunts us. We now have a deep understanding of the virus but still lack both a truly effective vaccine and anti-viral drugs. The question is: will we have them in time for the next, inevitable pandemic?