1934 Nobel Prize in Physiology or Medicine β Whipple, Minot, and Murphy
What You Will Learn in This Article
This article explores the story of three American physicians who, without knowing the identity of a mysterious substance, used it to treat a previously 100% fatal disease and achieve complete recovery. It also examines the process by which the identity of this mysterious substance was revealed 20 years later.
Curing Diseases with the Unknown
At the time, pernicious anemia was a 100% fatal disease. The name itself, "pernicious," reflected its deadly nature. Patients became extremely pale, their tongues turned bright red and swollen, they developed neurological symptoms, and eventually died within a few years.
Given that it was a type of anemia, it seemed logical to treat it with iron supplements. However, iron supplementation proved ineffective. This was a case of anemia with a different cause. Unfortunately, no one knew what that cause was.
In 1926, two physicians in Boston made a surprising announcement: feeding patients liver daily cured the disease. And it did so dramatically, within a few weeks. Within months of this therapy being announced, mortality rates for the disease plummeted in hospitals across the United States and Europe.
Here lies a fascinating irony: they did not know what component of the liver was responsible for the cure. Nevertheless, this therapy clearly worked and saved countless lives. The identity of this component was later revealed to be vitamin B12, 14 years after this Nobel Prize, in 1948. This is a case of a disease being cured using an unknown substance, and the Nobel Prize being awarded before its identity was known.
The World in 1934: Hitlerβs Rise and Nazi Ideology
The year 1934 marked a period in which the character of Nazi Germany was fully solidified. On June 30th, the "Night of the Long Knives" occurred. Hitler, in a single night, murdered his longtime comrade RΓΆhm, the leader of the Nazi paramilitary organization (SA), along with other political rivals. In August, after the death of President Hindenburg, Hitler combined the roles of Chancellor and President, becoming the "FΓΌhrer." This was the moment when Nazi Germany became a fully realized dictatorship.
During this period, the purge of Jews from German academia was in full swing. A significant number of Jewish scientists had already emigrated or were preparing to do so. The American Rockefeller Foundation operated a large-scale program to resettle them in American universities. The explosive growth of American science in the latter half of the 20th century was greatly facilitated by this program.
In the Far East, the Long March of the Chinese Communist Party began in October of that year. Pursued by Nationalist forces, they traveled over 8,000 kilometers, a journey that later became a legend in the leadership of Mao Zedong. Manchuria solidified its position as a formal state, becoming a stepping stone for Japan's expansion into the mainland.
In the United States, the New Deal was gaining momentum. The Great Depression was beginning to bottom out, and various reforms, including the preparation of the Social Security Act and the strengthening of labor unions, were underway during that year. The universities of Rochester and Boston, where Whipple, Minot, and Murphy worked, were among the beneficiaries of this period of American academic expansion.
In the context of Korean history, 1934 was the year in which the Japanese colonial forced savings campaign was launched on a large scale. This was a coercive policy aimed at mobilizing the assets of Koreans for war funds. While in Europe, the discovery of a treatment for a disease using an unknown substance was being recognized with a Nobel Prize, in Korea, assets were being forcibly confiscated under an unknown pretext. It was an era in which different forms of "the unknown" yielded different results in the two worlds.
The Individuals: Different Contributions
The three Nobel laureates made different contributions from different universities.
Whipple: The Foundation of Animal Experiments
George Whipple was born in 1878 in New Hampshire, USA. He was a pathologist at the University of Rochester Medical School. His contribution, however, was not directly related to pernicious anemia itself. He was conducting experiments on "bleeding anemia."
His experimental model was the dog. He periodically drew blood from dogs to induce artificial anemia and then fed them various diets to quantitatively determine which foods most rapidly restored hemoglobin levels.
The results were clear: liver was overwhelmingly effective. The recovery of dogs from bleeding anemia was fastest when they were fed liver. He repeated and quantified these observations between 1920 and 1925, concluding that "there is something in liver that helps with hematopoiesis."
Here lies the irony. Whipple's experiments were on bleeding anemia, not pernicious anemia. The two diseases have completely different causes. However, his observations ultimately provided a crucial clue to Minot and Murphy.
Minot and Murphy: The Leap in Clinical Application
George Minot was born in 1885 in Boston. He was a physician at Harvard Medical School. William Murphy was his colleague and a young collaborator.
Minot himself was a diabetic. In that year, he was barely surviving by taking insulin. This young physician, who often thought about death, desperately sought a way to prevent the deaths of others.
He read Whipple's paper on dog experiments and decided to take a bold leap. "If liver is effective in bleeding anemia, wouldn't it be worth trying in pernicious anemia?" Although the two diseases have different causes, they both involve problems with hematopoiesis.
He and Murphy began an experiment in which they fed 45 patients with pernicious anemia 240-360 grams of cooked liver daily. This was a significant amount β about one large steak's worth of liver per day. It was a quantity that patients found difficult to swallow.
The results were immediate. Within weeks, the patients' hemoglobin levels returned to normal, their paleness disappeared, and they returned to their normal lives. This was the moment when the first effective treatment for a disease that had previously been 100% fatal was established.
This announcement in 1926 immediately shook the world. Within months, hospitals in the United States and Europe adopted this therapy, and the mortality rate for pernicious anemia plummeted.
Key Achievement: Tracing Undefined Dependencies
"Effective, Even Without Knowing the Mechanism"
The common characteristic of the three Nobel laureates was that they demonstrated the possibility of treatment without fully understanding the mechanism of action. This attitude is now the foundation of modern clinical trial culture.
A CS analogy naturally applies here. This is similar to tracing an unknown dependency.
When a program crashes, we don't initially know the exact cause. What we do is experimentally find out "what changes will stop the crash."
- Reverting the library version to A stops the crash β There is a problem with the recent library update
- Setting environment variable X stops the crash β That variable is a required dependency
- Adding a specific file stops the crash β The crash occurred because that file was missing
In this approach, we can solve the problem even without knowing the exact cause. As long as we know "this fixes it," we don't need to understand the internal workings of the library, variable, or file.
Minot and Murphy did exactly this. They did not know what component of the liver was responsible for curing the disease. They only demonstrated that "eating liver cures it." This demonstration saved countless lives, and 20 years later, chemists gradually identified what that unknown substance was.
However, this analogy breaks down at this point. In software, unknown dependencies can eventually be identified by reading the source code or examining the logs in detail. We can fully identify the cause within a finite amount of time. However, in biomedical research, unknown factors are much more difficult to identify. In this case, it took 22 years (1948) to identify vitamin B12, and it took decades after that to fully elucidate its biosynthetic pathway.
The 20-Year Delay: Until the Identity Was Revealed
This Nobel Prize was awarded in 1934, and the identity of vitamin B12 was confirmed in 1948 (including Dorothy Hodgkin's X-ray crystallography in 1955). It took 22 years after the therapy was established for the identity of the therapeutic agent to be revealed.
This delay is one of the major themes in the history of medicine. The gap between "it works" and "we know why it works." This gap is often very large in medicine. For example, aspirin has been used since 1897, but its exact mechanism of action (COX enzyme inhibition) was not elucidated until 1971. That is a delay of 74 years.
The reason for this delay is understandable because the core question in clinical medicine is "does the patient recover?" rather than "by what mechanism does the patient recover?" The latter is an interesting scientific question, but it is of lower priority than the former.
The Discovery in Patients with Gastrectomy
A surprising observation emerged from the follow-up to the Minot-Murphy therapy: patients who had undergone total gastrectomy invariably developed pernicious anemia. This observation provided a crucial clue: something in the stomach is necessary to absorb this factor.
Following this discovery, Castle (William Castle) established the concept of the "intrinsic factor" in 1929. This protein, secreted by the gastric mucosa, is essential for the absorption of vitamin B12 in the small intestine. It was revealed that the true cause of pernicious anemia is a deficiency of this intrinsic factor in the stomach, which prevents the absorption of vitamin B12.
Following this discovery, the therapy evolved. Instead of eating large amounts of liver daily, it was replaced with purified liver extracts administered by injection, and eventually with vitamin B12 injections. Today, patients with pernicious anemia are fully managed with a monthly B12 injection.
Why It Matters
The Nobel Prize awarded to Whipple, Minot, and Murphy remains relevant today on three levels.
Clinical Level: Today, pernicious anemia is a completely manageable disease. Every year, millions of patients worldwide are treated with B12 injections or oral supplements. This Nobel Prize marks the beginning of a lineage that has transformed a disease that was 100% fatal into a chronic disease that can be managed.
Clinical Trial Culture Level: The principle of "demonstrating the effectiveness of treatment through controlled observation, even without knowing the mechanism" is now the philosophical basis of modern randomized controlled trials (RCTs). The principle that a new drug can be approved for use if it shows statistically significant efficacy under controlled conditions, even if we do not fully understand how it works.
Expansion of the Vitamin Concept Level: This discovery expanded the concept of vitamins to a new level. It identified not only deficiency itself but also "absorption deficiency" as a distinct type. Subsequently, various diseases related to absorption disorders began to be understood within the same frameworkβfat malabsorption, lactose intolerance, celiac disease, etc.
We are left with a lesson: "knowing that it works is different from knowing why it works." Both types of knowledge are important, but in urgent situations, the former must be established first. If a program is crashing and there is no time to find the root cause, we must first create a workaround to protect the service. Minot and Murphy adopted exactly this attitude and saved millions of lives.
Even as you read this sentence, patients with pernicious anemia around the world will be receiving B12 injections and living normal lives. The roots of this treatment lie in the dog laboratory in Rochester and the plates of cooked liver in Boston 100 years ago.
Summary of the demonstration of treatment with an unknown substance: Whipple's animal experiments on bleeding anemia quantified the hematopoietic effect of liver, and Minot and Murphy boldly applied this observation to patients with pernicious anemia, establishing the first effective treatment for a previously 100% fatal disease. It took 22 more years to identify the unknown substance as vitamin B12, but the treatment had already saved countless lives.
β Experience it with coding: DevBench β Tracing Unknown Dependencies and Workarounds β Learn about CS concepts: DryBench β Understanding Working Principles and Workarounds