1913 Nobel Prize in Physiology or Medicine — Charles Richet
What You Will Learn
Understand how it was discovered that there are moments when immunity, instead of protecting us, kills us, and why some people carry EpiPens today.
The Discovery That Immunity Can Work Against Itself
Richet gave a fitting name to his discovery. He created the opposite of the Greek word prophylaxis (prevention) and called it anaphylaxis (against protection). Against protection—the name itself encapsulates the essence of his discovery.
We learn that the immune system is a system that protects the body. Antibodies recognize pathogens, and then quickly respond when the same pathogen appears again—this is the principle of vaccination and a fundamental concept in immunology.
However, Richet discovered that this principle sometimes works in reverse. A dog, when first exposed to a substance, showed no ill effects. However, a few weeks later, when exposed to the same substance a second time, it died within seconds. This happened even when the second exposure involved a much smaller amount of the substance.
This observation overturned more than just a single fact. It challenged the entire assumption that “immunity is always a good thing.”
The Era: A Nobel Prize Experiment on a Yacht
In the summer of 1901, in the Mediterranean Sea, Prince Albert I of Monaco's yacht, the Princess Alice II, was sailing. This ship was the Prince's private oceanographic research vessel, and the Prince was an amateur scientist passionate about marine biology.
On board were French physiologists Charles Richet and Paul Portier. The Prince posed an intriguing question: “Why is the venom of the Portuguese man-of-war (Physalia physalis) that swims near our ship so painful?” His suggestion was to purify the toxins in the venom and study them.
After returning from the yacht, Richet and Portier conducted experiments in a Paris laboratory, repeatedly injecting the venom into dogs. Unexpected observations followed.
At the time, Europe was experiencing the last burst of the Belle Époque. The story of this discovery, born on the Prince's yacht and leading to a Nobel Prize, embodies the romance of that era. However, this tranquility was shattered a year later by World War I. The yacht research became a thing of the past, and the next generation's research shifted toward trenches and battlefields.
When compared to Korean history, 1913 was the fourth year of the Japanese colonial rule. The Governor-General's Office was being established (the predecessor of today's Seoul National University Hospital), and Koreans virtually had no opportunity to receive treatment in their own language at their own hospitals. While Europe enjoyed the luxury of discoveries leading to Nobel Prizes, Korea was in an era where it could not even imagine such a thing.
The Man: A Thinker and an Experimentalist
Richet was born in Paris in 1850. He came from a wealthy family of doctors and studied both medicine and physiology at the Sorbonne University. His areas of interest were unusually broad—digestive physiology, thermoregulation, hypnosis, psychology, poetry, and even parapsychology.
Particularly interesting is the fact that he was a mainstream scientist who had a serious interest in parapsychology. He believed that phenomena such as telepathy and ghosts should be scientifically investigated, and he even conducted related experiments. This aspect of his background is unrelated to his Nobel Prize, but it reveals his character: he was a person who did not dismiss observations that went against common sense.
This character was key to the discovery of anaphylaxis.
When Richet and Portier injected the Portuguese man-of-war venom into dogs, their goal was simple: “Determine the lethal dose and create an antiserum.” They were trying to apply the then-popular serum antiserum approach.
The first experiment went as expected. The dogs died after a certain dose, and lower doses were harmless. However, when they re-injected a low dose to the dogs that had survived a few weeks later, something that defied common sense happened.
The dogs experienced severe convulsions just seconds after the injection. They suffered from difficulty breathing, vomiting, incontinence, and died within minutes. They died from a small amount that had saved them during the first exposure. Richet’s reaction to this observation in the first experiment was different from that of other scientists of the time. He did not dismiss it as an experimental error. Instead, he concluded, “This is a new phenomenon.”
This judgment led him to the Nobel Prize. His research partner, Paul Portier, did not receive the Nobel Prize—this, along with the case of Karl and Gessner, remains a representative example of those who "should have received it together but didn't" in the early Nobel Prizes.
Key Achievement: The Discovery of a Self-Destructive Feedback Loop
Anaphylaxis: The Meaning of “Against Protection”
Richet’s name was accurate. He realized that this phenomenon was not a malfunction of the immune system, but rather a state in which immunity works against itself.
Key observations:
- First exposure: harmless or mild reaction
- Latency period: the body "remembers" the substance for 2-3 weeks
- Re-exposure: an explosive reaction to a much smaller amount than the first exposure
- Result: rapid drop in blood pressure, constriction of the airways, circulatory collapse, and death
This pattern creates exactly the opposite result on the same mechanism as the principle of vaccination. In vaccination, the first exposure creates antibodies, and the second exposure causes those antibodies to quickly eliminate the pathogen. In anaphylaxis, the first exposure creates IgE antibodies, and the second exposure causes the IgE to explosively activate mast cells, releasing mediators such as histamine into the entire circulatory system. The same recognition system produces exactly the opposite result.
A CS analogy fits naturally here. Anaphylaxis is like a normally functioning intrusion detection system (IDS) shutting down the entire system due to a false positive. This is a common problem in today’s cloud infrastructure: if the automatic defense system mistakes normal traffic for an attack and shuts down the firewall, the service itself dies as a result. Defense becomes self-destruction.
Or, it can also be seen as an overshoot of a positive feedback loop. In a normal immune response, activated cells are inhibited when they complete their task. In anaphylaxis, the inhibitory signal does not catch up with the activation signal, and mediators are released explosively. This is similar to a recursive call in software that causes a stack overflow without a base case.
However, this analogy breaks down here. Software recursion crashes immediately, but anaphylaxis is an extremely complex cascade in which hundreds of different mediators act sequentially at the molecular level. It is not a single function call stack, but a state in which hundreds of interconnected signaling pathways go haywire simultaneously.
Anaphylaxis Overturned Immunological Common Sense
Before Richet's discovery, immunology was based on the assumption that “antibodies are good.” The achievements of Behring, Koch, and Ehrlich were all antibody-based therapies, and antibodies were always on our side.
Richet showed that antibodies can be both allies and enemies. This realization fundamentally changed the direction of immunology. Autoimmune diseases (rheumatism, lupus, Hashimoto’s), allergic diseases (pollen, food, drugs), and transplant rejection—all are rooted in the concept of “disease caused by immune system malfunction,” and anaphylaxis was the prototype of that concept.
Clinical Application: Epinephrine and EpiPens
Richet’s discovery did not immediately lead to clinical applications. It was known that anaphylaxis occurred, but there was no way to prevent it. It took 20 to 30 years after his Nobel Prize to solve this problem.
The key was the discovery that epinephrine (adrenaline) can immediately reverse anaphylactic shock. Epinephrine constricts blood vessels, opens the airways, and increases heart rate to reverse circulatory collapse. The EpiPen that we prescribe today to patients with severe allergies works on this exact principle. And the existence of that prescription is due to the pathological condition that Richet discovered.
Why It Matters
Richet's Nobel Prize was the recognition of the concept that “immunity is a double-edged sword.” Before that, immunology was a simple story: pathogen vs. antibody. After Richet, immunology becomes a much more complex story: self vs. non-self, tolerance vs. response, regulation vs. malfunction.
The larger significance is the establishment of the concept that “the body can attack itself.” In an era when the term autoimmune disease did not yet exist, Richet showed its prototype. Today, autoimmune diseases are common, affecting 5-8% of the population. The first step in understanding and treating them was the discovery of anaphylaxis.
And there is a lesson for us. “Observations that go against common sense are the seeds of discovery.” If Richet's partner, Portier, had dismissed the deaths of the first dogs as experimental errors, anaphylaxis would have been discovered much later. Like Richet, who seriously investigated the controversial topic of parapsychology, he was a person who knew how to confront uncomfortable observations head-on. That attitude was his true qualification for the Nobel Prize.
Even as you read this sentence, someone in the world is being rushed to the emergency room with a nut or bee sting allergy. The epinephrine injection placed in that emergency room is a testament to Richet's discovery.
Anaphylaxis Cascade Summary: In the first exposure, the antigen induces IgE antibody production. These IgE antibodies bind to the surface of mast cells and basophils and wait. During re-exposure, when the antigen binds to the surface IgE, the mast cells explode, releasing mediators such as histamine in large quantities, rapidly causing vasodilation, airway constriction, and circulatory collapse.
→ Experience it with coding: DevBench — False Positives and Self-Destruction Prevention → Learn about CS concepts: DryBench — Positive Feedback and System Failure