History of Medicine

FLU SHOTS 100 YEARS AGO

     Just for fun I decided recently to peek at the contents of the JAMA from 100 years ago. As you might expect several articles dealt with medical problems of WWI soldiers and several with the 1918 influenza epidemic, also roaring through the military. What caught my eye, though, was the attention paid to influenza vaccines.

     Influenza was believed by many to be caused by “Pfeiffer’s bacillus”, a small

Richard Pfeiffer (Wikipedia)

fastidious rod now considered to be the bacterium Hemophilus influenzae. However, because Pfeiffer, a protégé of the great bacteriologist Robert Koch, could not produce the illness in animals, and because the bacillus turned up in other conditions and in normal throats, proof of its causative role remained elusive. Brushing aside these uncertainties, however, influenza vaccines hit the market rapidly and were aggressively promoted.

     The power of vaccination was well known by then and several, such as smallpox, rabies, and typhoid, were available. William Park, director of New York City Health Dept’s

William Park (Wikipedia)

laboratories, who had already made diphtheria antitoxin and vaccine, made a three-dose influenza vaccine from Pfeiffer’s bacillus, widely used in the military and by industrial employees. A professor of bacteriology at Tufts Medical School, Timothy Leary (not the marijuana guy), made another one, used in state custodial institutions and on the private market. At the University of Pittsburg Medical School a vaccine was created from 13 different strains of Pfeiffer bacillus (employed by the Red Cross), at Tulane still another, and in New York a private physician, Horace Greeley, made his from a cocktail of 17 strains.

      But was Pfeiffer’s bacillus really the cause of influenza? More studies generated more uncertainty. Pneumococci and streptococci were now turning up in greater numbers in sputum and lung samples than Pfeiffer’s bacillus. Based on this, Edward Rosenow of the Mayo Clinic made a vaccine from five different respiratory tract bacteria, including

Preparing Rosenow vaccine at Chicago Public Health Lab (from A Report on
the Epidemic of Influenza in Chicago, 1918. Courtesy National Library of Medicine)

pneumococci and streptococci. It was distributed to the upper Midwest and manufactured by the City of Chicago, where over 500,000 doses were produced.

     Could all these vaccines be effective? Most reports said they were, but sensible readers realized that was impossible. Study design had been faulty in all but one case,

George McCoy (NIH Almanac)

said William Park of New York and George McCoy of the US Public Health Service in an important article. And that one exception failed to show any protective effect. The missteps, they said, were giving vaccines without randomization, using too few subjects, and starting the studies well after an epidemic begins. Park and McCoy each performed their own studies, Park with employees of the Metropolitan Life Insurance Co. and McCoy with inmates of a “state institution for the insane” in California. Both studies began before the flu hit their subjects, both ensured comparable study and control groups, and both employed the Rosenow vaccine. Neither study showed any protective effect, thus setting important precedents for future vaccine trials. (True randomization and blinding of experimenters were later developments. The first such trial was in 1943, evaluating a remedy for the common cold.)

     That a filterable agent might be the cause of influenza had occurred to only a few people during the pandemic. One was Charles Nicolle, winner of the Nobel Prize for his discovery of the louse as the vector of epidemic typhus. He reported transmission of flu to monkeys and humans with submicroscopic filtrates of sputum from flu sufferers. Eventually he and others with similar ideas were proven to be correct, paving the way for modern flu vaccines.

      

     HAPPY HOLIDAYS TO ALL, AND DON’T FORGET YOUR FLU SHOT!

    

SOURCES:

Eyler, John M. “The State of Science, Microbiology, and Vaccines Circa 1918”. Public Health Reports. 2010 suppl 3; 125: 27-36.

McCoy, G W. “Pitfalls in Determining the Prophylactic or Curative Value of Bacterial Vaccines” Public Health Reports 1919; 34(22): 1193-5.

Sholly, A I and Park, W H. “Report on the Vaccination of 1536 Persons Against Respirtory Diseases, 1919-20.” J Immunology1921; 6: 103-16.

McCoy, G W and Murray, V B. “The Failure of a Bacterial Vaccine as a Prophylactic Against Influenza” 1918; JAMA 71(24):1997.

Nicolle, Charles and Lebailly, Charles. “Recherches Expérimentales sur la Grippe” Annales de l’Institut Pasteur 1919; 33: 395-402.

Bhatt, Arun. “Evolution  of Clinical Research: A History Before and Beyond James Lind” Perspect Clin Res 2010; 1(1): 6-10.