As World War I came to an end, one of the most deadly pandemics the world has know infected one fifth of the world's population, causing more deaths than the war had itself. Outbreaks occurred in North America, Europe, Asia, Africa, Brazil, and the South Pacific. People who contracted the disease where known to have muscle and joint pain, headaches, sore throats, a cough, and a fever. It was not uncommon to see someone collapse on the street or at work, because of the sudden onset of dizziness and weakness that were also symptoms of this killer. The deadly disease that stuck in pandemic form in 1918 was the Spanish influenza, although it would take the world many more decades to find the microbe which caused the disease, and still longer to understand it.
At the time of the outbreak, science was still relatively new in the medical field. Pasteur's germ theory was only recently considered to be correct, and although researchers could work to isolate the causes of disease, they still had a great deal to learn. In 1884 Robert Koch had developed a postulate, by which the cause of disease could be isolated. It stated that a microorganism: must be found in all cases of the disease, showing a relationship to damaged tissue; be isolated and grown in a pure culture outside of the host; be taken from this culture and infect a healthy animal with the same disease; and lastly should be recoverable from all experimentally infected animals. This was widely accepted, as an ideal measure in finding the cause of pathogens. Large government grants funding scientific research of pathogens were still far in the future, but there was more money and skilled scientists from around the world willing to work on the search for the cause and cure, than at any previous time.
Prior to the pandemic, Pfeiffer, a well respected scientist of the time, found a bacillus in the sputum of an influenza patient. A year after obtaining the sample he began work with the bacillus, testing it on monkeys and other lab animals. When the animals came down with symptoms of influenza, and the bacillus was recovered from the animals, he announced that he had isolated the microbe responsible for influenza, and named it the Pfeiffer bacillus. Studies done during the pandemic both supported and weakened Pfeiffer’s hypothesis. In one survey the bacillus was found present in 80% of the cases, but in some regions, it wasn’t present at all.
One of the first investigations occurred in November and December of 1918 at a Navy training base located on Deer Island. Sixteen sailors volunteered to be test subjects, in order to receive pardons for offenses they had committed. They were transferred to a Quarantine station, and exposed to blood and respiratory tract secretions taken from bodies of those who had recently died of the disease. Many strains of Pfeifer’s bacillus were included in these inoculations. All of the volunteers remained healthy. In another attempt 10 of the soldiers were taken to flu wards of a Navy hospital, and interacted with the patients, getting as close as to within two inches of the faces of the ill. Only one of the ten became ill, and his symptoms were so mild that it was probably not influenza.
Another investigation, performed at the military training camp, CampLewis, involved a novel test of the time, blood and sputum cultures. These tests were based on the germ theory of disease, and were commonly ordered by physicians for research purposes. They involved placing samples obtained from patients in blood agar in Petri dishes, and examining it to discover which organisms were present. In this study all soldiers who became ill had blood and sputum cultures taken. A vast number of microbes were found in all cases, with the most common being pneumoccus, streptococcus, and staphyloccus. Pfeiffer’s bacillus was found as well, but in a very small quantity. This led to a split among scientists.
Some scientists believed that the epidemic at Camp Lewis wasn’t influenza, but rather an acute respiratory infection. This however, didn’t explain other studies results, including the one performed on Deer Island. Others believed that believed that Pfeiffer’s bacillus produced such a strong poison, that only a few microbes were needed to cause symptoms. A more popular theory was that the bacillus attacked the body’s immune system, allowing many other types of microbes to infect the body, and overwhelm the primary cause of disease. Another group of scientists saw these test results as evidence against the theory that Pfeiffer’s bacillus was the cause of the pandemic.
William Park led a group of researchers from around the world to investigate whether Pfeiffer’s bacillus was really the microbe they were searching for. His team in New York took nine samples from a small community, increasing the likelihood that all would have come from the same original source. Each sample showed a different bacillus, suggesting to Park that the bacillus wasn’t the cause of disease, but perhaps part of an individual’s reaction to it. He went on to obtain over one hundred samples from New York City. These were tested, and the results showed variety between Pfeiffer’s bacilli. The London team’s results supported those of Park’s team. These results should have been enough to disprove Pfeiffer’s hypothesis, but it was only the beginning of the long journey to find the true microbe behind Spanish Influenza.
There are many reasons researchers could not quickly discover the cause of and treatment for the Spanish Influenza. The largest of these obstacles was the division of the scientific community on Pfeiffer’s bacillus. Those who believed it to be the cause were chasing a dead end, and those who doubted it spent much of their time either trying to prove it false. Those who went on to search for another cause had some other major obstacles in their path as well.
The first problem being the shear number of microbes found in sputum samples from patients. There were so many microbes in the samples it would take an immense amount of time to consider each as a possible cause until the true cause was found. Complicating this further was the fact that technology of the time did not allow researchers to see or culture even smaller possible causes, viruses.
Virology was a relatively new science. Yellow fever, the first human virus to be discovered, had been found within the last twenty years. In 1914 the cold virus was found by exposing the noses of healthy people to filtrates from secretions of people contaminated with the common cold. Many researchers didn’t consider the possibly that a virus was behind the flu, because of the number of bacterial microbes found in the secretions of the lungs of the victims. Those who did ended up spending a lot of time breaking the ground in this field, discovering the basics and publishing materials on what went wrong, so that others could avoid it.
Another major problem facing researchers was that of finding a laboratory animal to use in experiments. It was not known whether any animals besides humans could contract the disease, and humans made the worst test subjects. Controls that can be set for other lab animals like genetics, diet, and other environmental conditions, can not be enforced when working with humans. Also many experiments that can be performed on other lab animals cannot be performed on humans, such as the testing of potentially dangerous drugs and vivisection.
Some scientists moved on to study canine distemper. This disease showed many of the same symptoms, and appeared to quite similar clinically to influenza, with the exception of the species which it infected. They hoped that discoveries made while working with canine distemper could be used to provide clues as to where to look next when working with influenza. The investigation went very well, yielding an isolation of the virus and a vaccine within five years. In the year 1933 an influenza epidemic occurred in England. Three scientists, Smith, Andrews, and Laidlaw took the opportunity to investigate the virus theory. They collected throat washings from a great number of patients, directly after the onset of symptoms. These were then filtered, and a variety of species of lab animals were exposed to the filtrates. One of these animals, the ferret, was a fairly uncommon choice of animal, but had been selected because of it’s usefulness in the research of distemper. The ferret ended up being the only animal that was successfully infected by the filtrate, developing fevers, muscle weakness, and running noses within three days. All other tested animals remained healthy.
Due to the promising results with the ferrets in the open trial, another trial was made which included much higher investments. A great deal of money went into making the lab facility sterile, guaranteeing control over the microbes that were present. The experiments performed in this facility showed that infection occurred after exposing the noses of the ferrets to the filtrate, or by placing healthy and sick animals together. Other methods, such as injects of the filtrate under the skin, did not work. Although unable to culture the virus, as Koch’s postulate suggested was nessacary for isolating the cause of infection, it was passed successfully through 26 ferrets by means of filtrate. When Pfeiffer’s bacillus was introduced to the animals, it produced a disease that closely resembled that of the filtrate. After recovery it was found that the ferrets were immune for several months, offering an explanation for why the soldiers at Camp Lewis did not develop disease when exposed to many microbes.
Due to the discovery that ferrets developed immunity after contracting the disease, the team of scientists investigated possible prevention methods. It was found that the blood of humans who had recovered form influenza contained antibodies against the infective agent found in the ferrets. These experiments provided more support for the theory that the virus, rather than Pfeiffer’s bacillus was the cause of the Spanish influenza. However, some doubts remained, because Koch’s Postulates had not been fulfilled.
Over time more support has come from many other experiments. An occurrence that provided some of the strongest support happened by accident in 1936. A ferret who was infected by the virus sneezed on a lab worker. The lab worker developed influenza, even though there was no epidemic in that region that year. Despite the gain of knowledge across the decades, there are still many mysteries about influenza that remain today. The changing nature of the surface proteins, resulting in different strains, requires that new vaccines be developed every year. Scientists are still in search of potential patterns in these mutations, so that they can develop a single vaccine that would prevent all strains.
