The Great Influenza

The influenza also struck extremely quickly. Those who suffered slowly and did not survive usually died of pneumonia, resembling the deaths of typical influenza victims. But those who died quickly likely died from an extreme attack by the virus itself. And, strangely, their lungs looked nothing like the lungs of typical pneumonia victims.

The respiratory tract only does one thing: it moves oxygen taken in from air into red blood cells. The trachea carries air from outside into the body and into the lungs via bronchioles. Then, the heart pumps blood without oxygen into the lungs, and the blood picks up oxygen in the lungs before returning to the heart and spreading to the rest of the body. If the process fails, part of the body will turn blue, which causes cyanosis. And cyanosis will ultimately kill other organs in the body

Where healthy lung tissue is “light, spongy, and porous,” a congested lung will harden (244). In cases of pneumonia, typically the alveoli (the air sacs in the lungs that allow for gases to transfer) or the lung’s lobes are attacked. But in the quick-spreading cases of the 1918 influenza, pathologists noted something unusual: the space between alveoli was filled with blood. The lungs themselves were the site of the fight between the virus and the body.

That fight involved an immune system response, of course. Typically, the body defends from a virus or disease before it reaches the lungs by using enzymes in saliva to destroy the invaders or nasal hairs to filter them out. If something gets past those defense, the body will attack it by creating more mucus and forcing the virus or germ out by coughs and sneezes. These symptoms are not usually fatal to a person, but in more serious attacks the body will launch “more aggressive defenses” (246). These include inflammation and the release of cytokines, white blood cells that fight the invaders but also have noxious effects, causing headaches and body pain. If enough cytokines are released, the body will actually essentially be killed by its own immune system. This seems to be what happened to many of the victims of the 1918 influenza. Essentially, the virus attacked the lungs, creating viral pneumonia. Then, the body attacked the lungs with cytokines and created fibrous connective tissues that prevented blood from moving properly through the lungs, leaving it to pool inside them. Because young adults typically have the healthiest immune systems, they tended to have the strongest responses to the virus. And this ultimately killed them, as their bodies overreacted, which explains why so many people in their 20s and 30s died of influenza.

In the 1970s physicians discovered a process they named ARDS (acute respiratory distress syndrome). Given the symptoms of the 1918 influenza victims, most modern doctors would recognize that they were victims of ARDS. However, to this day there is no solution to the problem. ARDS will still kill, as people just stop being able to breathe. It is impossible to know how many people died of ARDS during the 1918 pandemic, but it was certainly enough to cause physicians to worry about another viral outbreak. While bacterial invaders can be fought with antibacterial treatments, ARDS cannot. To make matters worse, bacterial resistance is on the rise, so even bacterial pneumonia brought on by a pandemic might not be beatable.

As the virus rampaged across the world, scientists began a race to fight it. In the United States, Welch, Gorgas, Cole, their colleagues, and the people they trained would lead that fight. To fight it, they needed to know three things: the epidemiology of influenza, its pathology, and what the pathogen was. Put more simply, they needed to know how it spread, what it did in the body, and what it was. They learned the epidemiology and pathology fairly quickly, recognizing it immediately as a disease that spread in crowds and one that left people contagious for about three to six days after infection; they also recognized what the virus did to the lungs once a person was infected. But determining the pathogen proved to be much more challenging.

Welch himself contracted influenza sometime after visiting Devens. He went to Atlantic City alone to recover and realized he would not be playing any more of a role in fighting the pandemic. With Flexner and Gorgas both in Europe, the fight would have to be left to “their spiritual descendants” (259). These included Wolbach and Avery, who Welch had called, as well as several people fighting the pandemic independently: Park and Williams in New York, as well as Lewis in Philadelphia. These individuals knew they had to move quickly but could not let panic erode their process and lead to a disordered approach. They had to build on existing knowledge of the immune system as well as the scientific method (as much as they could, given the circumstances) to isolate and attack the pathogen.

At the time, the common belief among scientists was that influenza was caused by “Pfeiffer’s bacillus” (technically named Bacillus influenzae), a bacteria found by the German Richard Pfeiffer, a student of Robert Koch, who discovered the bacteria in several victims of the 1889–90 influenza epidemic. Given Pfeiffer’s reputation, there was no reason to doubt his discovery.

But in science there is no certainty. A good scientist exists on the edge between certainty and doubt, so all must ask a simple question: “How does one know when one knows?” (262). One cannot know truly. One can only test and retest and re-retest. A result is only as close to true as one can possibly get if it is reproducible but can also lead to another discovery. Thus, while Pfeiffer’s theory seemed correct, it had a problem. In many cases in the 1918 pandemic, “Pfeiffer’s bacillus” could not be found, leading some to conclude the disease was not influenza, since there supposedly could be no influenza if there were no influenza bacilli.

Laboratories around the world dedicated themselves to studying influenza, but by 1918, the laboratories could not function at full capacity as so much attention was being paid to fighting the war. Researchers dedicated themselves to fighting trench fever and gangrene or to creating or defending against poison gases. Still, many great minds were fighting influenza, including “the most important” ones in the United States: “Oswald Avery at Rockefeller, William Park and Anna Williams at the New York City Department of Public Health, and Paul Lewis in Philadelphia” (268).

Like Philadelphia, New York was run by a corrupt political machine, as Tammany Hall had regained control of the city’s politics in January 1918. The new mayor, John Hylan, replaced the existing head of the health department, which had been the best citywide health department in the world, with Royal Copeland, who was not even a medical doctor. Copeland, like Krusen in Philadelphia, denied the existence of influenza in New York for weeks until making a public statement that the incidence of the virus was decreasing, which, of course, it was not.

Park and Williams could not do anything to change Copeland’s views, but they were able to work diligently in the lab. They had worked together for more than 20 years by 1918 and “complemented each other perfectly” (271). Park had an aristocratic background and believed that the work he did in the laboratory served god. He was a master bureaucrat and was extremely methodical in exploring existing medical knowledge more deeply and exhaustively. He and Park had collaborated, for instance, not on a new cure for diphtheria but on a way to mass produce a cheaper version of it. Williams was the opposite of Park: wild where Park was stolid, creative where Park was stubborn. They created a laboratory that was among the best in the world and perhaps the only one capable of mass producing a vaccine or serum for influenza—if one could be found.

The National Research Council divided the study of influenza into pieces, and it asked Park and Williams to focus on identifying the organism causing the virus. Park approached the task with confidence and planned on testing a large sample of people and then monitoring the ones who got ill using sophisticated laboratory techniques. But the virus spread too quickly, infecting even people in Parks and Williams’s laboratory. New York announced but did not implement a quarantine, despite hundreds of thousands of people suffering from influenza (more than 30,000 of whom died). Park adjusted his plans, knowing the laboratory had two constants: the laboratory routine and the unceasing supply of blood, sputum, urine, and organs of dead patients.

For the samples, they used the same tedious method of washing their own hands, extracting a sample, washing it, washing it again, and washing it still one more time, then transferring it to various loops into a test tube. All day, they would do this same process over and over. And for days, they found the same result: no influenza bacillus. Frustrated, Park asked Williams to concentrate efforts on finding it, and she eventually proved adept at finding it in over 80% of cases. Park and Williams turned to the question of whether that bacteria was a cause of the virus or a symptom. The only way to determine that was to isolate it, inject it into a lab animal, and re-isolate the pathogen in that animal. Pfeiffer’s bacillus did kill rats, but it did not create the same symptoms in rats as it did in humans. They would have to use humans as subjects to fully test it. In Boston, such human experiments began, but they were not conclusive. No volunteer subject got sick from the injection of Pfeiffer’s. A doctor conducting the experiment did get influenza from a different source, but that proved nothing.

Meanwhile, in Philadelphia, Paul Lewis was also searching for the cause of influenza. Lewis grew up in Milwaukee before attending the University of Wisconsin and then Penn. He then worked under Welch and Osler at various points in his career, and eventually under Flexner at Rockefeller. Lewis loved laboratory research and had worked with Flexner on polio, first proving it was a viral disease and then creating a vaccine. By 1918, Lewis was one of the world’s foremost virus experts.

Lewis began experimenting on various sera based on the blood of those who survived influenza. To his dismay, he had to abandon the scientific method at times, as he was making “blunt-force” efforts in “desperate attempts to save lives” (283). The science could follow if he found something successful. Thus, he chose to work on multiple strands of research at the same time rather than in succession. His first efforts involved trying to develop a vaccine using the same methods he used to develop the polio vaccine. Then, he focused on isolating Pfeiffer’s bacillus. Then, he attempted to grow his own bacteria using beef proteins and attempting to kill pneumococci instead of the influenza bacillus. Then, he turned back to killing the bacillus, trying to figure out where Flexner had gone wrong in his own attempts to kill pneumonia a decade earlier. Lewis hoped Flexner had failed because of technical error, so he became obsessed with correcting any problems with technique, hoping he could apply his advanced knowledge of Pfeiffer’s bacillus to the same experiments and make some progress.

When Welch called Oswald Avery to investigate at Devens, Avery immediately left his lab in New York. In Massachusetts he immediately tried to isolate the influenza bacillus that Park, Williams, and Lewis were also trying to find. He struggled at first but eventually found it in more than two-thirds of the dead soldiers. Avery told Welch the news, which confirmed the news Wolbach had given him of the presence of Pfeiffer’s in the autopsies he performed. Welch, Cole, and Vaughan wired the surgeon general to say, “It is established that the influenza at Camp Devens is caused by the bacillus of Pfeiffer” (290). But Avery was not so sure.

Back at the Rockefeller Institute in New York, he continued to dwell on the subject, wondering why he and many others were struggling to find the bacteria in patients. While it was true that Pfeiffer’s bacillus was notoriously hard to grow in the lab, and therefore it would be easy to dismiss the inability to locate it as a technical error, Avery felt there might be something missing.

While Park, Williams, and Lewis struggled to stick to the rigors of the scientific method during the crisis, Avery did not. He was always in control of every experiment, every aspect of his life. He had a virtually unadorned office and kept his workspace similarly clean and bare. Avery was a narrow thinker, but narrow in a focused way, not a small way. He did not spend much time with social interactions, instead preferring the isolation of the lab. He was also extremely patient. As the pandemic raged on, he obsessively devoted his focus to growing lab strains of Pfeiffer’s bacillus and figured out still better ways to find it in a patient. Thus, if it did not show up in a patient, it would be definitively known that it was because the bacillus was not there, not because the researcher failed in technique. Because of Avery’s work, Cole suspected that the primary infectant might not actually be Pfeiffer’s bacillus, since it did not seem to appear in every victim.