Albrecht Kossel

Albrecht Kossel: The Chemist Who Named the Letters of Life

Asked in 1911 what he was actually doing in his laboratory, Albrecht Kossel gave a reporter from *The New York Times* one of the more honest descriptions of basic science ever offered: "The processes of life are like a drama, and I am studying the actors, not the plot. There are many actors, and it is their characters which make this drama. I seek to understand their habits, their peculiarities." The actors he identified were adenine, cytosine, guanine, thymine and uracil. Four decades later, other people worked out the plot.

A Merchant's Son in Rostock

Kossel was born on 16 September 1853 in Rostock, the son of Albrecht Karl Ludwig Enoch Kossel — a merchant and Prussian consul — and Clara Jeppe Kossel. At the Rostock Gymnasium he showed an early and decided taste for chemistry and botany, and in 1872 he enrolled at the University of Strassburg to read medicine.

The choice of Strassburg was really a choice of teacher. Felix Hoppe-Seyler headed what was then the only department of biochemistry in Germany, and it was under him that Kossel learned to treat the contents of a cell as chemistry rather than as biology. He also studied with Anton de Bary, Wilhelm von Waldeyer, August Kundt and Adolf von Baeyer — an extraordinary constellation of teachers — and completed his studies at the University of Rostock, passing his medical licensing examination in 1877.

Taking Nuclein Apart

He returned to Strassburg the same year as Hoppe-Seyler's research assistant, and there attacked the problem that would define him. In 1869 Friedrich Miescher had isolated a substance from cell nuclei that he called nuclein; nobody knew what it was. Kossel showed that nuclein consisted of a protein part and a non-protein part, and isolated the latter, establishing it as nucleic acid. This was the necessary first move: before anyone could ask what nucleic acid did, someone had to establish that it was a distinct chemical substance at all.

In 1883 he became Director of the Chemistry Division at the Physiological Institute of the University of Berlin, succeeding Eugen Baumann, and it was over the following two decades — from 1885 to 1901 — that he carried out the work for which he is remembered. One by one, Kossel isolated and identified the five organic compounds present in nucleic acids: adenine, cytosine, guanine, thymine and uracil. They are now called the nucleobases, and they are the alphabet in which DNA and RNA are written.

He could not have known what he was cataloguing. The idea that these five small molecules encoded heredity lay half a century in the future, and it took Rosalind Franklin's crystallography and Watson and Crick's 1953 model of the double helix to make sense of them. But Kossel had done the indispensable spadework: he had established what the components were and in what chemical terms they had to be described.

Marburg, and the Rest of the Cell

In 1895 Kossel was appointed professor of physiology and director of the Physiological Institute at the University of Marburg, and after Hoppe-Seyler's death he took over the editorship of the *Zeitschrift für Physiologische Chemie*, the journal at the centre of the discipline. In 1896 he discovered the amino acid histidine, developed methods for separating the so-called hexone bases, and became the first to isolate theophylline.

In 1901 he moved to Heidelberg as director of the Heidelberg Institute for Protein Investigation, and the emphasis of his work shifted to the other half of the nuclein problem: the proteins. His research on protein composition revealed the polypeptide nature of the protein molecule, and in his later years he concentrated on the protamines and histones — the proteins bound up with nucleic acid in the nucleus — introducing flavianic acid as a reagent for quantitative protein analysis.

The Nobel Prize, 1910

In 1910 Kossel received the Nobel Prize in Physiology or Medicine "for his discovery of histones and the other bases of nucleic acids" — recognition of his determination of the chemical composition of the nucleic acids of the cell. At the ceremony on 10 December 1910 the presentation speech placed his work in its wider frame: "The study of the living organism has more and more led to the view that its smallest independent units — the cells — also to a certain degree lead an independent life and are the real seats of the vital processes."

Other honours followed. In 1911 he travelled to the United States to give the Herter Lecture at Johns Hopkins University on "The Proteins" — the only visit he ever made to America. In 1923 he was chosen as Germany's representative to the Eleventh Physiological Congress in Edinburgh and received an honorary degree from the University of Edinburgh, a significant gesture towards a German scientist so soon after the war.

A Quiet Refusal

That gesture was not accidental. In 1914 Kossel declined to sign the manifesto of German professors defending their country's conduct in the war — a document nearly every prominent German academic put his name to. In 1917 he refused government pressure to declare publicly that Germany's food provisions were sufficient when they were not. He was not a political man, but on both occasions he declined to lend his authority to a lie.

Students, Collaborators, and a Physicist Son

Kossel's laboratory was a conduit as well as a workshop. With Henry Drysdale Dakin he investigated arginase and discovered agmatine in herring roe. Edwin B. Hart, who passed through his orbit, went on to the celebrated single-grain experiment of 1907–11 and to nutritional work on anaemia and goitre; another student, Otto Folin, discovered phosphocreatine.

In 1886 Kossel married Luise Holtzmann, daughter of the Heidelberg professor of German literature and Sanskrit Adolf Holtzmann. Of their three children, two survived to adulthood: Walther, born in 1888, and Gertrude, born in 1889. Luise died of acute pancreatitis in 1913. Walther Kossel became a distinguished physicist and professor of theoretical physics at Tübingen, formulating the theory of ionic chemical bonding and the octet rule and lending his name to the Sommerfeld–Kossel displacement law — an unusual case of a father and son each reshaping a different science.

Heidelberg, 1927

Kossel became professor emeritus in 1924 but went on lecturing at Heidelberg. In April 1927 he travelled to England for the Lister Centenary celebrations. Three months later, on 5 July 1927, he died in Heidelberg of angina pectoris, aged seventy-three.

The Albrecht Kossel Institute for Neuroregeneration at the University of Rostock carries his name. The more durable memorial is the four-letter alphabet he assembled without knowing it was one.