Influenza is a potentially devastating infectious disease, commonly spread through coughing and sneezing in humans. The disease is also spread through contact with the infected droppings of birds and other animals. Initial symptoms include fever, headache, tiredness, cough, sore throat, runny or stuffy nose, body aches, diarrhea and vomiting. More serious cases may lead to pneumonia, which may be fatal, especially when contracted by young children or frail, older adults. Prior to Francis’ development of the vaccine to fight against it, influenza claimed millions of lives worldwide. Descriptions of human influenza date back over 2,000 years, and it has been responsible for several pandemics or worldwide outbreaks. Francis had seen one such outbreak in his lifetime, the 1918 flu pandemic that infected a third of the world's population and killed over 20 million people. 

In 1941 Francis was appointed director of of the commission on influenza of the Armed Forces Epidemiological Board. He worked closely with the military as the human influenza virus had dealt the armed forces a huge blow during World War I, and the military was determined not to let it happen again. That year, Francis also joined the newly formed School of Public Health at the University of Michigan. It was here that the “magic” began. Francis and his team not only isolated the influenza virus, he also showed that more than one strain of the virus existed. This is particularly relevant today, as year-by-year new flu vaccines are reformulated to fight against the most dominant strains. Francis also developed the first effective vaccine to fight against influenza. Previous efforts at a vaccine had been with a live, attenuated vaccine, that had not proven very effective. His was a “killed-virus” vaccine. This type of vaccine uses a dead influenza virus. Since the virus is dead, it can’t give the disease, but it still causes the body to react and develop immunity. Getting a virus to the point of going into a vaccine is a complicated adaptation process. In Francis's time, one batch involved 77 passages in  mice; 717 passages in cell culture; 30 passages in chick embryos; 5 passages in ferrets; and 50 passages in chick embryos.  This killed-virus vaccine continues to be the method used in influenza vaccines today.  Francis developed a bivalent vaccine, covering two strains of influenza. It was tested in 1943 where it was found that 2% of the vaccinated came down with the flu, while 7% of the unvaccinated got sick with the flu. It was distributed to the armed forces in 1944 and to civilians  in 1945.

Today's flu vaccine changes yearly because the influenza virus constantly mutates. There is a worldwide surveillance system in place, constantly testing what virus is sickening people. Flu is seasonal, so its prevalence rotates back and forth between the northern hemisphere and the southern hemisphere as the seasons change. So, every year a norther hemisphere and a southern hemisphere vaccine is developed based on the latest strains of the continually evolving virus.

Scientists have constantly been working to improve the vaccine. Through the years the vaccine has changed from Francis' bivalent (two strain) vaccine to a trivalent and now a quadrivalent vaccine in science's never ending quest to keep us safe.  In the past 10 years scientists have developed ways to culture the virus used for the vaccine only in cells, skipping the chicken eggs.  If a pandemic occurs like 1918, this method might allow quicker development of the vaccine and of getting the vaccine to the public.   

Written by science writer, Tim Anderson