1910 Nobel Prize in Physiology or Medicine — Albrecht Kossel
What You Will Learn in This Article
You will understand that even 43 years before the discovery of the DNA double helix, someone had already identified its “alphabet,” and that this alphabet is the A·G·C·T·U we know today.
A·G·C·T·U Existed Before DNA
We remember DNA as a “double helix.” The story of Watson and Crick elucidating its structure in 1953 is so famous that it is difficult to imagine anything before that.
But let's ask this question: How did Watson and Crick know what the double helix was made of? What they saw in the X-ray images was a “pattern,” not an “ingredient list.” The list of ingredients—adenine, guanine, cytosine, thymine, and uracil—was already created by someone else half a century earlier.
That person is Kossel. In his 1910 Nobel Prize lecture, he said: "I have identified the chemical components of the cell nucleus. The next generation will figure out what they are used for."
This statement is chilling. It is because it is the statement of someone who knows how to pass on the true meaning of his discovery to the next generation.
The Zeitgeist: The Year the Korean Empire Disappeared
1910 is a significant year. On August 29th, the Korean Empire ceased to exist. The Japan-Korea Annexation Treaty was signed, erasing the 500-year-old dynasty and the name "Korean Empire" from the map.
At the same time, Kossel was receiving the Nobel Prize in Europe for his work on "the chemistry within the cell nucleus." At a time when Korean history was losing its nation, German chemistry was mapping the universe inside cells. This disparity became one of the roots of the Korean-Japanese relationship and the attitude that Korea would develop towards science and technology in the following decades.
Looking at the broader historical context, 1910 was the last year of the Belle Époque in European chemistry. The Golden Age came to an abrupt end four years later with the outbreak of World War I. Haber's invention of nitrogen fixation was in 1908, Einstein's special relativity in 1905, and Rutherford's discovery of the atomic nucleus in 1911. It was a time when the entire microscopic world, from atoms to cell nuclei, began to be described for the first time in the language of chemistry.
From the perspective of medical history, the characteristic of this era is the shift “from clinical to laboratory.” Following Pasteur and Koch's establishment of bacteriology, the next generation of scientists ventured deeper into the cell. Kossel was one of the pioneers.
Biographical Narrative: A Chemist Who Organized His Mentor's Legacy
The story of Kossel must begin with his mentor, Friedrich Miescher.
In 1869, Miescher removed bandages from pus in a hospital, isolated white blood cell nuclei, and extracted a new substance from them. It was an acidic substance with an unusually high phosphorus content that was unknown at the time. Miescher named it "nuclein." This was the first discovery of what we know today as nucleic acid.
The problem was that Miescher didn't know what it was. He only determined that this substance "exists within the cell nucleus and contains a lot of phosphorus" before he died. Nuclein remained an unidentified black box.
This is where Kossel enters the picture. He was born in 1853 in Rostock, Germany, studied chemistry at the University of Strasbourg, and then worked under Felix Hoppe-Seyler—Miescher's mentor—at the Physiological Institute in Strasbourg. He naturally inherited the nuclein problem.
His approach was different from his mentors. If Miescher stopped at "this substance exists," Kossel set a goal to "break down this substance into its components." In terms of software, Miescher was the person who discovered the compiled binary file, and Kossel was the person who tried to disassemble it.
His laboratory was a place that required extreme patience. Obtaining a few grams of nuclein required kilograms of calf thymus. He repeated the process of gradually hydrolyzing the substance with acid and alkali for more than 20 years, observing the crystals produced, performing elemental analysis, and recording the characteristics.
Key Achievements: Defining the Alphabet of the Cell Nucleus
Five Bases: A·G·C·T·U
The crystals that Kossel extracted from nuclein were as follows:
- Adenine (1885) — Derived from the Greek word "aden" (gland). He named it.
- Guanine (previously known → Kossel proved it was a component of nuclein)
- Cytosine (1894) — Derived from "cell." Named by Kossel.
- Thymine (1893) — Derived from "thymus." Named by Kossel.
- Uracil (1900) — His student, Ascher, participated in the discovery.
These five substances are the five bases of nucleic acid that we know today. The alphabet of DNA is A·G·C·T, and the alphabet of RNA is A·G·C·U. Kossel is the answer to the question of who first introduced this alphabet to the world.
Here, the CS analogy fits naturally. What Kossel did was like reverse-engineering an unknown file format. He took a binary lump called nuclein, separated the repeating patterns within it one by one, and defined the character set of the format. He didn't yet know what grammar the letters were combined into, or what program they would execute, but he confirmed that "this language consists of five letters."
However, this analogy breaks down here. Software reverse engineering is about reconstructing something when the original design document exists somewhere. But Kossel had no design document at all. What he discovered was the character set of a system that nature had "accidentally" evolved. This is closer to writing the first specification document than reverse engineering. It was an event in which humans first documented a language that nature had been using.
Proteins as well: Histones and Protamines
Kossel's achievements are not limited to nucleic acids. He also isolated two types of basic proteins within the cell nucleus:
- Histone — A protein that wraps DNA. Today, it is a key component of gene expression regulation.
- Protamine — A protein that compresses DNA extremely tightly in sperm nuclei.
At the time, he didn't know why these proteins were in the nucleus. He simply recorded that they "are found together with nucleic acid." However, this observation became the root of epigenetics a century later. Histone acetylation and methylation—the histones that we see in papers every day—were first introduced to the world in Kossel's laboratory.
"The Next Generation Will Figure Out What They Are Used For"
Kossel's Nobel Prize lecture contains remarkable humility. He acknowledged that he had identified all the chemical components of nuclein, but he admitted that he didn't know what they do in the cell. And he said, "the next generation will figure it out."
This statement becomes a prophecy. Indeed, the next generation—Griffith's transformation experiment in 1928, Avery's proof of DNA as the genetic material in 1944, and Watson and Crick's discovery of the double helix in 1953—gave meaning to Kossel's alphabet. They discovered that A and T pair with each other, and that G and C pair with each other, and that the sequence contains genetic information.
To conclude with a CS analogy, Kossel is a linguist who defined the character set and left the grammar to future generations. It is similar to the Unicode Consortium assigning code points and leaving the design of programming language syntax to language designers.
Why is it Important?
Without Kossel's discovery, there would be no Watson and Crick. Or, more accurately, there would be no vocabulary to understand the double helix.
"Adenine forms two hydrogen bonds with thymine, and guanine forms three hydrogen bonds with cytosine" — This sentence was written by Watson and Crick, but of the five nouns in this sentence (adenine, thymine, guanine, cytosine, hydrogen bond), the first four are all Kossel's inventions.
More importantly, it was an event that marked the beginning of molecular biology as a discipline. Before Kossel, biology was the study of form. What it looks like, how it grows, how it moves. After Kossel, biology becomes the study of molecules. What it is made of, how the molecules interact. The first step in this transformation was the ingredient list of nuclein.
And it leaves us with a lesson: "Knowing the ingredients is different from knowing the function." Kossel took 40 years to identify the ingredients, and it took humanity another 40 years to discover the function of those ingredients. This is why we cannot say that we understand life just because we have sequenced all the genes. The sequence is the alphabet, not the literature.
Summary of the five bases discovered in the nuclein decomposition and their lineage: Kossel hydrolyzed nuclein from calf thymus with acid, separating purines (adenine and guanine) and pyrimidines (cytosine, thymine, and uracil). These five letters become the DNA (A, G, C, T) and RNA (A, G, C, U) of today.
→ Experience it with Coding: DevBench — Character Sets and Encoding → Learn about CS Concepts: DryBench — Reverse Engineering