1926 Nobel Prize in Physiology or Medicine — Johannes Fibiger

What You Will Learn in This Article

You will understand that even the Nobel Prize can be wrong, and why this error teaches us about the essence of scientific verification.

The Most Famous Error in Nobel Prize History

The 1926 Nobel Prize in Physiology or Medicine was awarded to Johannes Fibiger of the University of Copenhagen for his “discovery of Spiroptera carcinoma,” meaning he was recognized for being the first to artificially induce cancer in experimental animals.

However, subsequent research over the following three decades reached a surprising conclusion: Fibiger’s experimental results were, in fact, misinterpreted. What he created was not real cancer, but rather vitamin A deficiency-induced squamous metaplasia, and the Spiroptera nematode was not the cause.

This became one of the most famous cases of a post-award reassessment in Nobel Prize history. What does this tell us? That even the most authoritative recognition systems judge within the limits of the knowledge of their time. And that science is the only system of knowledge that can correct its own errors. It was science itself that eventually revealed Fibiger’s error.

The Zeitgeist — The Roaring Twenties

In 1926, the world was still at the peak of the Roaring Twenties, but cracks were already forming:

• NBC’s first broadcast (November) — The beginning of the American radio network
• End of the Rif War in Morocco (May) — End of a large-scale rebellion against European colonial rule
• Birth of Elizabeth II (April) — The emergence of a figure who would live until the end of the century
• Death of Japanese Emperor Taisho (December) — Beginning of the Showa era. The next 30 years would be the era of Japanese militarism.

From a historical perspective of medicine, this period was when cancer research was becoming established as an academic discipline. Previously, cancer was the subject of individual clinical case reports and autopsy observations, but efforts were being made to create an experimentally reproducible model. Fibiger’s research was considered a representative work in this trend.

Here is an interesting fact from that era that is not well known. In 1915, Katsusaburo Yamagiwa of Japan successfully induced experimental squamous cell carcinoma by repeatedly applying coal tar to the ears of rabbits. This was the first historically reproducible chemical carcinogenesis model. However, he did not receive the Nobel Prize. There are several interpretations as to why, but it is believed that one of the main reasons was that Japanese science at the time was not sufficiently known in the Western academic community.

If we compare this to Korean history, 1926 was the year that the Keijo Imperial University Medical School was established. However, the proportion of Korean students was very low, and the conditions for Koreans to conduct science within their own language and cultural context were still not in place. While Japan was missing out on recognition in the world academic community for Yamagiwa’s cancer research, the situation in Korea was even more difficult.

The Man — A Diligent Pathologist’s Misjudgment

Fibiger was born in Silkeborg, Denmark, in 1867. He studied medicine at the University of Copenhagen and became a pathologist, later becoming a professor of pathological anatomy at the University of Copenhagen. He was known as a very diligent and careful scholar. His laboratory notebooks were meticulous, his observations were thorough, and his conclusions were not hasty.

Here is how he came to conduct the Spiroptera experiment. In 1907, while examining the pathological specimens of rats from a slaughterhouse in Copenhagen, he discovered lesions resembling tumors in the stomachs. He observed small nematodes within these lesions. He named this nematode Spiroptera neoplastica and hypothesized that it might be the cause of the tumors.

To verify this hypothesis, he conducted a large-scale experiment. He infected cockroaches (the intermediate host of Spiroptera) and fed them to rats, and then observed whether lesions developed in these rats. And indeed, lesions appeared in a significant number of rats. He concluded that this was the “first reproducible experimental carcinogenesis.”

This paper was published in 1913 and caused a sensation in the international academic community. If cancer could be created in the laboratory, its cause could be identified, and if the cause is known, prevention and treatment would be possible. The 1926 Nobel Prize was the culmination of this excitement.

The problem was that the lesions were not real cancer.

The Key Achievement — And Why It Was Wrong

The Original Claim

The lesions observed by Fibiger were squamous metaplasia and hyperplasia of the gastric epithelial cells. He diagnosed this as squamous cell carcinoma. Histologically, these two states are often difficult to distinguish, especially in the early stages of abnormal proliferation, which can appear very similar to early signs of squamous cell carcinoma.

To summarize with a CS analogy, this is a case of extrapolating observational data into a deterministic hypothesis. In software, we may be tempted to assume that a pattern we find in log data is evidence of a root cause. However, that pattern may be a byproduct of another underlying cause. Fibiger’s experiment fell into exactly this trap.

The Reality Revealed 30 Years Later

In the 1930s and 1950s, several researchers tried to reproduce Fibiger’s experiments, but they were not able to obtain accurate results. Some laboratories succeeded, and others failed. This reproducibility issue was present from the beginning, but at the time of the Nobel Prize, it was not considered a critical problem.

The following facts were revealed:

1. Vitamin A Deficiency Factor: The diet given to the rats in Fibiger’s experiment was deficient in vitamin A. This deficiency itself induces squamous metaplasia in the epithelial cells.
2. The Secondary Effect of Spiroptera Infection: The nematode infection created local irritation, but this irritation alone could not cause cancer. The combination of infection and vitamin A deficiency resulted in the lesions he observed.
3. Not Real Cancer: The lesions he created did not actually show metastasis or invasion. It was squamous metaplasia and hyperplasia, but not cancer.

In other words, his experiment was not an artificial cancer model, but rather an observation of nutritional deficiency pathology. This is, in itself, an interesting discovery, but the claim that it “established experimental carcinogenesis,” which was the basis for the Nobel Prize, is not valid.

The Real Experimental Carcinogenesis: Yamagiwa’s Coal Tar

At the same time that Fibiger’s experiment was receiving so much attention, Katsusaburo Yamagiwa in Tokyo was inducing real squamous cell carcinoma in rabbits’ ears with coal tar. His method was simple and reproducible: if you apply coal tar daily, a real cancer will develop in the area after a few months. This lesion also metastasizes and is clearly cancer histologically.

There are several theories as to why Yamagiwa did not receive the Nobel Prize, but two things are certain:

1. At the time, the Western academic community had limited access to Japanese papers, and his research was not sufficiently recognized.
2. Fibiger’s story was more dramatic (nematodes cause cancer!) and captured the imagination of the Western academic community.

Today, Yamagiwa is recognized as the pioneer of chemical carcinogenesis research, but this is a posthumous recognition. At the time, Fibiger received the Nobel Prize.

To summarize with a CS analogy, this is similar to a case where a band-aid commit is deployed to production before finding the real root cause commit. The real cause was elsewhere, but a plausible explanation was first widely accepted. It would take a long time before the real cause was revealed.

Why This Error Is Important

The Nobel Prize awarded to Fibiger is a representative case of a scientific award that turned out to be an error. The lessons we can learn from this case are multifaceted.

First, the importance of reproducibility. Fibiger’s experiment was not perfectly reproducible in other laboratories from the beginning. When we talk today about the “reproducibility crisis” in psychological and medical research, this problem is the prototype. Results that cannot be reproduced eventually turn out to be errors.

Second, the danger of confounding variables. Fibiger interpreted the correlation between Spiroptera infection and gastric lesions as a causal relationship, but the real cause was the third variable, vitamin A deficiency. This is why we carefully consider confounding variables in statistical analysis today.

Third, cultural and linguistic bias. The fact that Yamagiwa’s real discovery was not recognized in the Western academic community was not due to the lack of his papers, but rather to the barriers of language and culture. When we talk about diversity in the international academic community today, it is worth remembering what this bias led to 100 years ago.

Fourth, the limitations of recognition systems. The Nobel Prize is a great recognition system, but it is also done by human beings. It judges within the limits of the knowledge and biases of the time. This fact teaches us that we should not accept theories that have been awarded prizes uncritically, but should verify them through reproduction and verification.

Even as you read this sentence, research teams are verifying newly discovered results. Some of these will be reinterpreted over time. This is not a failure of science, but rather the normal functioning of science. The Fibiger case reminds us of this.

What the Error Left Behind

Despite the error in Fibiger’s work, there were valuable follow-ups.

• It stimulated interest in the pathology of vitamin A deficiency, and subsequently contributed to the understanding of vitamin deficiency diseases.
• It clarified the methodological requirements for experimental cancer models (reproducibility, control groups, histological rigor).
• It provided an understanding of the pathological effects of Spiroptera infection and local irritation — one of the origins of our understanding today of the link between chronic infection and cancer risk.

Yamagiwa’s coal tar carcinogenesis model became the standard, and this led to the discovery of polycyclic aromatic hydrocarbons (PAHs), a group of carcinogenic substances. Today, we associate smoking with lung cancer and grilled meat with stomach cancer, and Yamagiwa is at the root of this understanding.

The Nobel Prize went to Fibiger, but Yamagiwa is now recognized as the father of experimental carcinogenesis. Time eventually corrects itself.

Summary of the Structure of the Fibiger Error: Observation of a correlation between Spiroptera infection and squamous metaplasia in gastric lesions was interpreted as a causal relationship, but the real cause was a third variable, vitamin A deficiency. After 30 years, the error was revealed through reproduction failure and subsequent investigation, and Yamagiwa was posthumously recognized as the father of experimental carcinogenesis.

→ Experience with Coding: DevBench — Confounding Variables and Misinterpreting Causation → Learn About CS Concepts: DryBench — Reproducibility and Result Verification