Nearly 70 years ago, a team of doctors entered a state mental colony and injected extracts from mice lungs into the arms of nearly 250 "feebleminded males." The liquid was teeming with influenza virus, a tiny infectious agent that had been discovered just three years earlier.
Some of the boys and men got sore arms. Others developed rashes. As a flu epidemic swept through the nearby city of Philadelphia in the winter of 1936, the scientists crossed their fingers and hoped that what they had already seen in pigs and ferrets would prove true for people -- that a shot of crude virus into the muscle would protect the patients from getting sick.
That is just what happened. Fully 200 of the colony's 800 residents became ill -- but those who had received the shot succumbed at one-fourth the rate of those who had not.
It was the first demonstration that a vaccine against influenza was in reach, and it created keen medical interest in a world still reeling from the 1918 flu that had killed more than 20 million people.
Today, nearly 70 years later, mental institutions no longer offer up their patients for human experimentation. Influenza vaccine is manufactured not in mouse lungs but in gleaming, automated factories.
But the production of vaccine remains a never-ending headache -- and, by some measures, primitive.
One of the reasons is biology.
Influenza has proved a stealthier foe than those 1930s scientists imagined, for a central reason: The virus is constantly changing its shape. Anyone who would thwart it with medicine must play an endless game of catch-up -- making fresh vaccine every year to match the viral strains most likely to circulate in the next flu season.
"The problem with the influenza vaccine is influenza itself," says Dr. Edwin Kilbourne, retired emeritus professor of microbiology and immunology at New York Medical College and a veteran flu researcher.
It is also a problem of economics. Because making flu vaccine isn't lucrative, very few companies in the world manufacture it.
But the headaches of today are also tied to history and the early creation of the vaccine.
If the flu shot had been developed a little bit later (in the 1950s, say, like the polio vaccine) its manufacture would not remain enmeshed in early 20th century technology. It wouldn't depend on the ready supply of millions and millions of freshly fertilized chicken eggs trucked en masse from farms to pharmaceutical plants -- one egg, on average, for every vaccine shot into an arm.
