Polly Matzinger Revolutionized Immunology Similarly to How Einstein Revolutionized Physics.

Social Media questions and answers are often too short and too shallow to be of much worth when trying to understand the world. A foundational mistake prevalent in all social media is the conflation of image with reality. This question from a web site called Quora (Quora.com) caught my attention: “Why hasn't the world had another Einstein? It's been over a hundred years since the theory of relativity and the closest we have had is Hawking.” This question is seemingly a question about the existence of geniuses in the world, but it is stated with at least three false opinions and conflates fame in the media with actual revolution in scientific understanding. It also ignores the reality that a subject like physics is a human creation made for convenience, which expresses the false opinion that physics is the most important science.

When seeing this question about another Einstein, the first person I think of is Polly Matzinger. Matzinger, in terms of scientific achievement, is very much like Einstein. But for many reasons, Matzinger did not reach the fame and media attention given to Einstein or to Hawking. Matzinger revolutionized the field of immunology by thinking. Matzinger, alone at first, and later with appreciative colleagues, proved that the first principle of immunology is the danger signal model, overthrowing the previous self / not self model. Immunology is a very import field in biotech and the core of new therapies in virology, cancer, and auto-immune disease.

Matzinger is not as famous as Einstein (or Hawking) for a number of reasons unrelated to her scientific achievements and profile. She is a woman and worked as a cocktail waitress and a playboy bunny. She did not fit in with the academic elites and was an independent thinker. She was an immigrant to the United States. She worked for the US government and so never became a millionaire or billionaire. But wait: very similar circumstances can be said of Einstein. Einstein was a member of a discriminated class; he was Jewish, and even until the 1950’s and beyond, places like Columbia University had quotas to not let in too many Jews. (This quota being why Richard Feynman went to MIT and not Columbia even though he was famous for winning New York area mathematical contests in high school.) His early academic career did not fit with expected norms. Einstein did not answer questions as quickly as his teachers desired and was thought to be slow. Einstein had to work in a patent office after graduation. Einstein immigrated to the United States. He never became rich in the way Thomas Edison did and stayed in academia supported by government grants. Given the similarity of circumstances, the excuses used to ignore Polly Matzinger are not the reason she is not as famous as Albert Einstein. I conclude that despite superficial progress, academia and media are more misogynist and elitist than in the time of Einstein.

The web site, Famous Scientists (https://www.famousscientists.org/polly-matzinger/), relates concisely stories of some of the obstacles Polly Matzinger overcame in life. Immigrating at age 11, she was barred from New York public schools because she did not speak English. The family moved to Hollywood, California. She was described in her senior class yearbook as “Most Likely Not to Succeed.” Working as a cocktail waitress, she became friends with Professor Robert Schwab, a regular at B’s Bar in Davis, California. The famous scientist web site summarizes well “The Case of the Inquisitive Waitress”:

In 1972, age 25, Matzinger was working in Mrs. B’s bar in Davis, California. Two of the regulars were biology professors. With her interest in animal behavior – particularly dog behavior – she enjoyed listening to them talking shop over their beers.

One day the professors began talking about mimicry in the animal kingdom, such as how a hoverfly dresses itself as a wasp to deter predators. Suddenly their waitress posed questions they couldn’t answer.

Why, she asked, didn’t any animals mimic the skunk? For example, why are there no black and white striped raccoons? Intrigued, Professor Robert Schwab started having regular conversations with Matzinger about science. He told her that her questioning mind was the mind of a true scientist. He brought science articles into the bar for her to read and encouraged her to study biology.

If she became a biologist, he insisted her work would never bore her.

When Polly Matzinger submitted a paper to the Journal of Experimental Immunology in 1978, the editor would not accept the paper with her as a solitary author. While the famous scientist web site gives an explanation, including Matzinger using the words “we” in the paper, an immunology colleague who knew Polly personally told me that the paper was not accepted because the editor could not believe a woman with a less than stellar academic background and no elite mentor could write an important paper by herself. Needing another author, and having heard comments like, “You must have talked to someone (some already prestigious immunologist), she thought: “I talk to my dog.” The paper was published with co-author Galadriel Mirkwood, Polly Matzinger’s dog. After publication the editor found out the species of Galadriel Mirkwood and refused to publish any more of Matzinger’s work up until the day of his death.

At the NIH, the Matzinger lab was known as the “Ghost Lab.” This was because most of her work was done by thinking, not by experimenting and generating data. Her character as an inquisitive waitress asking questions was more illuminating than the expected profile of an NIH scientist. Having a ghost lab also reduced the number of photo ops that may have promoted her image in the eyes of the media. Charles Janeway, a professor at Yale who collaborated with Matzinger in the field of innate immunity, often retold at conferences the funny story of how he had to put on a lab coat and held an electrophoretic gel upside down when a magazine wanted a photo of him for an article. Being less amenable than Janeway to the reporters’ games, Matzinger is more often pictured petting a dog than wearing a lab coat.

The stories about Matzinger provide evident evidence of the prejudice and elitism that she had to overcome. But also contained in the stories are the characteristics that she shares with Einstein.

Matzinger asked the fundamental question: “How does the body’s immune system know that this bacteria or cancer cell is “not self”? And she thought about this for years, ignoring what “most scientists think.” Einstein asked the fundamental question: “What do you really mean when you say two events separated in space happened at the same time”? Einstein thought about this question for years and explains its importance in his book, The Evolution of Physics.

Matzinger had a ghost lab. She read experiments done by others and solved problems by thinking about them. Einstein did not build photoelectric cells, but he thought out the consequences of the photo-electric effect. In my opinion, Einstein was the only person in world smart enough to understand Max Planck’s paper on black body radiation and how this introduced the whole idea of quantum mechanics. Scientists should give this a try. Go read Planck’s paper and then ask yourself: would this paper make me say, “Oh my, Newton was wrong!”

Back around 1900, in an Encyclopedia Britannica article titled “Atom,” Max Planck wrote “And the slowness of the development of scientific ideas may be estimated from the fact that Bayle does not see any force in this statement by Aristotle, but continues to admire the paradox of Zeno.” Similarly, Matzinger’s danger signal theories are widely ignored in favor of the self / not self model. Humira, a “humanized” antibody, is thought to be less immunogenic because it has a “human” sequence. Humira is estimated to stop working in about 40% of patients because of blocking antibodies from an immune response. Wim Jiskoot has shown that one danger signal, aggregation, is correlated to immunogenicity while having a human or non-human sequence is uncorrelated. A key experimental finding is that the 100% human sequenced protein, Erythropoietin, has different immunogenicity rates when delivered in different buffers. Also, some camelid antibody based biotherapeutics displayed greater pre-existing immunogenicity only after being humanized in sequence. There are many people who refuse to believe in Einstein’s theory of relativity and stick to Newton’s invalidated idea that time is absolute.

Why hasn't the world had another Einstein? If you think that the nebulous, everchanging mishmash of social media gossip, talking points, and tweets is the world, the answer is simple: the ‘world’ has not decided that it was useful to raise a scientist to the level of Einstein’s fame. If you think that the word world refers to this planet where living, inquisitive, thinking human beings discover revolutionary principles leading to amazing advances in science that are very slowly accepted by the public, then there are many people similar to Einstein, and Polly Matzinger is one of the most similar.