Polly Matzinger’s unique path to science

Few, if any, internationally renowned scientists came into their fields of expertise in such a roundabout way as Polly Matzinger.

In recounting her story, the danger lies in appearing to make light her achievements, in view of her personal history. Nothing could be further from the truth. Indeed, many people could find inspiration in her journey.

In 2002, Discover magazine included Matzinger in its list of “The 50 most important women in science”, for her pioneering research into the workings of the human immune system.

Matzinger was born on 21 July 1947 in La Seyne, southeastern France. The family moved to the US in 1954, finding their way to southern California.

In a detailed account of her early life, the Famous Scientists website says she was described in her senior-class high school yearbook as someone “most likely to not succeed”.

She began a science major at the Irvine campus of the University of California in 1965, it says, but quit before earning a degree.

What followed were a string of jobs, including chipping mortar off used bricks, working as a dog trainer, playing bass in jazz bands and “her best-earning job of all, as a Playboy bunny in Boulder, Colorado”.

She finally settled on work as a cocktail waitress because it allowed her ample free time to write and play music and continue her animal training.

The article describes how, in 1972, Matzinger was working in a bar near the campus of the University of California, Davis, a school noted for its medical research facilities, and where some of the regulars were science professors. 

Lively conversations ensued, Matzinger was inspired to return to school and, in 1976, she completed her Bachelor of Science.

In 1979 she earned a PhD in biology from UC San Diego, followed by four years of postdoctoral work in Britain at Cambridge University, then six years at the Basel Institute for Immunology in Switzerland. She returned to the US and went to work for the National Institutes of Health in Bethesda, Maryland.

The research for which Matzinger is best known is her “danger theory” of immunology, which she published in the Annual Review of Immunology in 1994.

In it, she says “the primary driving force of the immune system is the need to detect and protect against danger… it does not do the job alone, but receives positive and negative communications from an extended network of other bodily tissues.”

A 2012 article published in the journal Frontiers in Immunology, headlined “The danger theory: 20 years later”, describes how the dominant thinking in immunology for 60 years had been the “self-non-self theory”.

It says Matzinger’s theory “claims that immune responses are triggered by ‘danger signals’, or ‘alarm signals’, released by the body’s own cells. According to the danger theory, every immune response is not due to the presence of ‘nonself’ (i.e., genetically foreign entities), but to the emission, within the organism, of ‘danger signals’.”

The self-non-self theory, the article explains, holds that “an immune response is triggered against all foreign (‘nonself’) entities, whereas no immune response is triggered against the organism’s own constituents. For Matzinger, despite the evolution of the self-non-self theory between the 1960s and the 1990s, today’s immunologists still think of the immune system within this framework, even though this theory may be interpreted as fundamentally flawed.”

The article concludes that although Matzinger’s theory retains its validity, it has lost some support over the years, that doubts have been cast on its function “as a general, unified framework for immunity”.