Robert Austrian dies

Robert Austrian, a clinician and pioneer in vaccine research, who helped to develop the first multivalent vaccine against the pneumococcus bacteria in 1977, died from a stroke on March 25th. He was 90 years old.

Austrian devoted more than six decades of his life to researching the organism Streptococcus pneumonia. With what his colleagues call gentlemen-like tenacity, he repeatedly asserted that, despite the advent of penicillin, pneumonia remained a significant cause of death among the elderly, and the vaccine he developed and licensed to Merck in 1977 could significantly reduce cases of infection in patients. Over the course of his life he went "from the bench to the bedside to lobbying the medical community" about the importance of the pneumococcal vaccine, Harvey Friedman, chief of infectious diseases at University of Pennsylvania, told The Scientist. "He did the lobbying by just being right."


Friedman and Austrian became friends in 1973, when Friedman began as a trainee in infectious disease and Austrian was in his 11th year as Chair of Medical Research at University of Pennsylvania.

The son of Charles Robert Austrian, an infectious disease scientist at Johns Hopkins, Austrian focused on pneumococcal pneumonia as a practicing physician after most of the medical community turned to other areas, assuming the disease had been eradicated by penicillin, synthetically produced since the 1940s. However, Austrian continued to see patients die from pneumonia, and was convinced that there was more science could do.

Austrian established his own microbiology lab at the former New York King's County Hospital (now known as SUNY Downstate). He taught his residents and interns to take samples from pneumonia patients and quickly plate them, right on the ward levels. In 1964, after gathering 10 years' worth of patient records, he and Jerome Gold, from New York King's County Hospital, published a report showing that, despite antibiotic treatment, hundreds of patients had died from the disease.

Next, Austrian began typing the different strains of the organism, a difficult task because the bacteria are easily overwhelmed by other bacteria in culture and missed by the untrained eye. Although it was the polysaccharide outer layers associated with each of the different strains that became crucial in developing an immunogenically successful vaccine, Austrian started his search by identifying the different strains by the way they bound different antigens.

By the time he became the Chair of Medical Research at the University of Pennsylvania, he had identified dozens of serotypes, particularly the capsular types most associated with fatalities from pnemococcal blood stream infections. He developed a vaccine under the sponsorship of the National Institute of Allergy and Infectious Diseases and conducted clinical trials in South African gold miners, reporting in 1976 that his vaccine was safe and effective. In 1977, Austrian licensed a vaccine containing antigens to 14 serotypes to Merck, and then, in 1983, the vaccine was expanded to include 23 strains -- accounting for 85 % of pneumococcal blood stream infections. There are now more than 90 known strains of the bacteria. The vaccine is currently given to people over 65. In 2000, researchers released a childhood pneumonia vaccine, followed by a conjugate meningococcal vaccine in 2005 -- products that would have not been possible without Austrian's body of work, according to his colleagues.

"The fact that he had produced that vaccine was a revelation," Leonard Hayflick from the University of California at San Francisco, who was a colleague of Austrian's at UPenn in the 1960s, told The Scientist. "I don't think there's anything comparable to it in respect to multivalent capacity."

Comparatively speaking, other vaccines target far fewer strains. For example, the vaccine for human papillomavirus targets only four strains, and the polio vaccine targets only three strains.

Skepticism in the medical community prevailed throughout Austrian's early career. After he developed the first vaccine and ran clinical trials in South Africa, many doubted that Austrian's results would be applicable to U.S. cases of pneumonia, said Friedman. However, a 1991 report by Austrian showed the vaccine was in the range of 70% effective, meaning that the individual efficacy of each component of the vaccine had to be on the order of 95% -- largely putting an end to much of the debate over the vaccine's efficacy.

Austrian continued to run clinical trials to prove the vaccine's efficacy and typing samples that labs and hospitals from around the world had sent him. More than 150 of Austrian's scientific papers have now collectively been cited nearly 7,000 times, and in 1978 he earned the Albert Lasker Award for Clinical Medical Research.

Indeed, Austrian kept typing isolates through his last days. "He worked up until two days before he died," Jeffrey Weiser, infectious disease researcher at UPenn and colleague of Austrian's, told The Scientist. "He was an incredibly hard working, dedicated person who had great focus. How many people have worked on the same problem for six decades?"

Andrea Gawrylewski
mail@the-scientist.com

Image: Robert Austrian, courtesy of the University of Pennsylvania.

Links within this article:

Robert Austrian
http://www.uphs.upenn.edu/idd/Austrian.html

Harvey Friedman
http://www.med.upenn.edu/camb/faculty/mv/friedman.html

Charles Robert Austrian
http://www.medicalarchives.jhmi.edu/sgml/austrian.html

J. Weitzman, "Pneumococcus genome," The Scientist, July 23, 2001.
http://www.the-scientist.com/article/display/19790/

R. Austrian and J Gold, "Pneumococcal bacterium with especial reference to bacteremic pneumococcal pneumonia," Annals of Internal Medicine, 60: 759, 1964.
http://www.the-scientist/pubmed/14156606

R. Austrian et al, "Prevention of pneumococcal pneumonia by vaccination," Trans Assoc Am Physicians, 89:184-94, 1976.
http://www.the-scientist.com/pubmed/14433

T. Sharrer, "Leitz inverted microscope, circa 1958," The Scientist, March 2007.
http://www.the-scientist.com/article/display/52900

ED Shapiro et al. "The protective efficacy of polyvalent pneumococcal polysaccharide vaccine,"
N Engl J Med, 325:1453-60, Nov 1991.
http://www.the-scientist.com/pubmed/1944423

S. Black et al. "Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children," Pediatr Infect Dis J. 19(3):187-95, March, 2000.
http://www.the-scientist.com/pubmed/10749457

Jeffrey Weiser
http://www.med.upenn.edu/camb/faculty/mv/weiser.html