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The first flu shot

Young man in a hurry

Early in 1941, a medical scientist named Thomas Francis relocated his young family from New York to Ann Arbor. He moved in a big hurry, as he did everything.

Recently he had turned down job offers from Harvard and Columbia. But when Michigan came calling, he’d said yes. His mission would be to start a brand-new department devoted to the prevention of epidemic diseases. It was a rare chance to make a major mark in his field.

He got straight to work on a dozen tasks at once — hiring faculty, organizing labs, seeking funding, planning courses, pushing his research along.

Then another call came, this one from the Department of War in Washington, D.C.

Americans were facing the growing prospect of a new world war against Germany, Italy, and Japan. Isolationists were against it, but the possibility of staying at peace was dwindling by the week. President Franklin Roosevelt’s call for a military draft had been approved by the margin of one vote in the House of Representatives, and now some 16 million young men were registering for service.

In Washington, graying men with advanced degrees in medicine and microbiology were meeting in hushed rooms hidden away from the press. Their business was quieter but no less urgent than turning out weapons and training soldiers.

The ghosts of 1918

U.S. Army soldiers with influenza at Camp Funston, Kansas, during the great influenza epidemic of 1918-19. Image: Otis Historical Archives, National Museum of Health and Medicine.

U.S. Army soldiers with influenza at Camp Funston, Kansas, during the great influenza epidemic of 1918-19. (Image: Otis Historical Archives, National Museum of Health and Medicine.)

In their minds were memories of overcrowded hospital wards in the winter of 1918-19, when the deadliest epidemic in history had circled the globe. In those months, lethal strains of influenza killed at least 50 million people, perhaps 100 million, more than the medieval Black Death killed in a century.

No one then had known exactly what caused it, still less how to prevent a recurrence. The Italian word influenza derived from a Latin word for the influence of the stars on human affairs — a grim visitation beyond anyone’s control.

Before 1918, it had come and gone in cycles, a severe illness, especially for the elderly, but nowhere near as deadly as smallpox, yellow fever, or cholera. The 1918 variant was far worse. The usual symptoms of headache, fever, and muscle aches swiftly turned to severe pneumonia. Patients coughed up blood and suffocated. Autopsies revealed lungs turned blue from lack of oxygen. Especially vulnerable were adults in their late teens and early 20s — the age of soldiers.

In the 1918-19 pandemic, influenza and its related illnesses killed nearly 50,000 American service members, almost as many as had died on the European battlefields. A similar infection in this new war would find millions of young Americans crammed into barracks and troopships. The impact would be unthinkable.

So Henry L. Stimson, the U.S. secretary of war, appointed major figures in medical science to a Board for the Investigation and Control of Influenza and Other Epidemic Diseases in the Army. They, in turn, authorized a specialized Commission on Influenza.

The board’s task was of the highest urgency. They must find a physician capable of preventing a recurrence of 1918-19.

The president of the board, Dr. Francis G. Blake, dean of the Yale School of Medicine, gave his colleagues the name of a student he had come to know well 20 years earlier: Tommy Francis.

Microbe hunter

U-M students —members of the Army Specialized Training Program —were among thousands who received the trial flu vaccine in 1943. Image: Bentley Historical Library.

U-M students — members of the Army Specialized Training Program — were among thousands who received the trial flu vaccine in 1943. (Image: U-M’s Bentley Historical Library.)

Born in 1900 in Gas City, Ind., Francis was the son of Welsh immigrants. His father was a pious steelworker, his mother a Salvation Army nurse. The Christian duty to help the poor and the sick ran strong in the family.

In New Castle, Pa., where the Francises moved for a steel-mill job, Tommy went around town with the local doctor, who showed him the structure of blood cells through the lens of a microscope. He was fascinated.

Outgoing, tough, and stocky, Francis was a boxer at Allegheny College. In 1921, he started at Yale Medical School, which had recently revamped its curriculum. It was now one of the nation’s best, paying close attention to scientific research and fully embracing clinical education — that is, placing students in direct daily contact with professors as they treated patients.

At Yale, Francis was so good at basic research that a professor urged him to get further training at the prestigious Rockefeller Institute in New York. Arriving on a Sunday, Francis found the gates locked. He threw his bag over the fence and climbed in after it.

For 10 years at Rockefeller, he hunted microbes in the lab. He became an expert on pneumococcus, the bug that triggers bacterial pneumonia. At the same time, he was so adept at treating patients that he became the favorite doctor of the Rockefeller family.

Healer vs. scientist

The competing instincts of the healer and the scientist warred inside him. One of his mentors, Dr. Oswald Avery, a brilliant molecular biologist, once found Francis with his head down on his research bench.

“What’s the matter, boy?” Avery asked. Francis said he was sorry another pneumonia season was about to start. He would have to abandon his test tubes to care for patients. “What’s in these flasks is much more exciting,” he said.

Avery brought him up short. Francis must be a physician first, a scientist second, the older man said. He must not forget that the only reason for the flasks was “to lick the pants off the pneumococcus.”

Then, in 1933, British microbiologists discovered the virus that causes influenza. This was big. Memories of the 1918-19 pandemic were still raw. Viruses, far smaller than bacteria, were barely understood, and virology was a new science. But if Francis could help to uncover the secrets of this scourge, the cause of so much sorrow, he might light a path toward the ultimate goal — a vaccine.

The vaccine idea

Flu virus graphic

A globular influenza virus bumps into a respiratory cell in the nasal passages. Tiny branches reaching upward from the cell bind with proteins on the virus’ surface like a key in a lock. Next the virus will burrow inside the cell and make copies of itself. The copies will spread through the host’s system, and a flu infection will be underway. (Image: U.S. Centers for Disease Control.)

Medical scientists grasped that the most potent weapon against infection was the human immune system, the army of cells that are provoked into action by invading germs. Against the most lethal diseases, immune cells often lost the battle and the human host died. But if the host survived, the immune cells triggered by that battle remained in the bloodstream, ready to ward off any new attack by the same germ.

The vaccine idea was this: If you gave a person a weakened form of a particular germ, you could spark the immune system into action without threatening the patient. Then those immune cells would stay active in the person’s body, ready to fight off any new infection by that particular germ if it got into the body at its full strength.

So far, vaccines had been tried against only a few infectious diseases — smallpox, diphtheria, tetanus, and pertussis (whooping cough) — and not in large numbers. But Francis and a few other medical scientists were pondering the possibilities of vaccination on a massive scale against a broader array of pathogens.

Because of 1918-19, influenza led the list.

To have any chance at a vaccine, medical scientists had to know everything about the invading microbe — its structure; its life cycle; where it lived outside the human body; how it was transmitted from one body to another; how it flourished once it got inside; and how it fought with immune cells.

Viruses were many times smaller than bacteria, so they were harder to study. Scientists didn’t even know if viruses were living organisms or more like tiny machines. (The answer, even now, is: Both, sort of.)

The shapeshifter virus

Francis and Salk

Ten years to the day after the death of President Franklin Roosevelt, whose struggle against polio had inspired the drive for a polio vaccine, Thomas Francis, Jr. and Jonas Salk announced that field trials designed by Francis had proven the effectiveness of Salk’s polio vaccine. (Image: U-M’s Bentley HistoricalLibrary.)

Still just in his 30s, Francis became the country’s leading authority on influenza. He was the first to show that flu viruses changed in their chemical structure, deceiving the human immune system. In other words, the virus was not a stationary target. It was a shapeshifter. A person who had already had the flu would carry an immunity to the strain that had made them sick. But a new strain could be just different enough in its chemical makeup that the person’s immune cells — the ones stimulated by the original infection — wouldn’t recognize this new intruder.

The implication for medical sleuths like Francis was daunting. They would not be able to curb influenza with a single vaccine because it was not really a single virus. Any effective vaccine would have to carry weapons against more than one strain. Not that a vaccine against even one strain would be easy. Francis had developed a primitive vaccine that worked in the lab, but it was nowhere near ready for general testing.

That was where things stood in 1939 and 1940, as Americans faced the prospect of being drawn into war.

Francis had recently left the Rockefeller Institute to become chair of microbiology at New York University.

Then, early in 1941, he was contacted by Henry Frieze Vaughan, an epidemiologist who had just left his post as Detroit’s public health commissioner to become dean of U-M’s new School of Public Health. He soon had Francis’ agreement to start a Department of Epidemiology.

With funding from the National Foundation for Infantile Paralysis, Francis was getting ready to study the possibilities of a vaccine for polio. That was when the Army tapped him to direct its Commission on Influenza.

When the Japanese attacked the Pacific fleet at Pearl Harbor in December 1941, his assignment took on the highest urgency. Besides running his department at U-M, he must now advise the Army on healthy housing and sanitation at military camps across the country and overseas; watch out for and treat flu outbreaks; and see to his main task — to devise, develop, test, manufacture and administer the means of preventing a recurrence of the 1918-19 pandemic.

He would need a lab staffed by the best young microbiologists he could find.

… Continue reading at heritage.umich.edu

 

Top image: Pictured in the years after World War II, Thomas Francis continued his investigations of epidemic diseases at U-M. Image courtesy of U-M’s Bentley Historial Library. Sources included Myron E. Wegman, “Thomas Francis, Jr.: An Appreciation;” Jonas Salk, “The Restless Spirit of Thomas Francis, Jr., Still Lives;” John R. Paul, “Thomas Francis, Jr., as a Clinician, 1900-1969;” Colin M. Macleod, “Thomas Francis, Jr., M.D. 1900-1969,” in Archives of Environmental Health, 21:3 (1970); Charlotte Decroes Jacobs, Jonas Salk: A Life (2015); Richard Carter, Breakthrough: The Saga of Jonas Salk (1966); John R. Paul, Thomas Francis, Jr., 1900-1969: A Biographical Memoir (National Academy of Sciences, 1974); John M. Eyler, “DeKruif’s Boast: Vaccine Trials and the Construction of a Virus,” Bulletin of the History of Medicine (2006); Kendall Hoyt, “Vaccine Innovation in World War II,” Journal of Public Health 27:1 (2006). 

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