Harden, Arthur

(b. Manchester, England, 12 October 1865; d. Bourne End, Buckinghamshire, England, 17 June 1940)

biochemistry.

Harden was the third child and only son of Albert Tyas Harden, a Manchester businessman, and Eliza MacAlister of Paisley; there were eight daughters. The family was nonconformist and their values were austere, a characteristic which Harden maintained throughout his life. He studied under Henry Roscoe at Owens College, University of Manchester, from which he graduated in 1885 with first-class honors in chemistry.

Having been awarded the Dalton scholarship in 1886, Harden undertook graduate study under Otto Fischer at the University of Erlangen. He received the Ph.D. in 1888 with a dissertation on the preparation and properties of β-nitrosonaphthylamine. He then became junior lecturer at the University of Manchester, where he soon advanced to senior lecturer and demonstrator. He was heavily involved in teaching and writing and published a paper (1897) on the composition of some bronze and iron tools discovered by Flinders Petrie.

In 1897 Harden became head of the chemistry department at the British Institute of Preventive Medicine (renamed the Jenner Institute in 1898 and the Lister Institute in 1903) and began research in microbiological chemistry. After 1905 the biochemistry department merged with Harden’s department under his leadership.

In 1898 Harden began studies on the fermentation of sugars by coliform bacteria, hoping to discover a chemical means to distinguish varieties of Escherichia coli (then termed Bacterium coli). He discovered several compounds formed in the bacterial decomposition of sugars and developed a scheme for the breakdown process. He showed that acetylmethylcarbinol produced by Bacterium coli aerogenes was responsible for the Voges-Proskauer color reaction which was used empirically by bacteriologists for diagnostic purposes. Although he continued his work in bacterial chemistry until 1912, his major attention after 1900 was given to alcoholic fermentation by yeasts.

In 1897 Eduard Buchner had discovered that alcoholic fermentation could be carried out by a cell-free juice extracted from yeast, and he named the active enzyme present in the extract zymase. The first crude zymase preparations produced carbon dioxide and alcohol—even without the presence of added sugar. Harden investigated this reaction and found that glycogen was expressed from yeast cells when zymase was prepared, thus furnishing a source of sugar. Harden also investigated the fact that the yeast juice quickly lost its power to ferment sugar and discovered that a proteinase expressed from yeast cells destroyed the zymase in a short time.

Continuing his studies on alcoholic fermentation with his student William John Young (later professor of biochemistry at the University of Melbourne), Harden learned in 1904 that the capacity of yeast juice to ferment glucose was stimulated by the addition of boiled yeast juice. He and Young showed that by dialysis or filtration through a Martin gelatin filter it was possible to separate yeast juice into two fractions, neither of which had the capacity to ferment glucose. Combination of the fractions led to normal fermentation. The dialyzable, filterable portion was a low molecular weight substance, stable to boiling, and easily precipitated by 75 percent alcohol. Harden called this substance a coferment although the names coenzyme I, cozymase, and (after its constitution was fully established by Euler-Chelpin, H. Schlenk, and co-workers) diphosphopyridine nucleotide (DPN) came to be used. Harden showed that the coferment contained phosphate but failed to make further progress in clarifying its chemical nature.

Harden and Young also observed that phosphate salts stimulated yeast juice to produce carbon dioxide. They found that phosphate combined with glucose, fructose, or mannose to form a hexose diphosphate which Young later isolated and identified. They showed this compound to be hydrolyzed by a phosphatase present in the juice. In 1914 Robert Robison, working in Harden’s laboratory, discovered hexose monophosphate as an intermediate in the fermentation process. Although Harden continued his studies on fermentation, he failed to make further major contributions toward understanding the nature of the process. However, his recognition of the presence of phosphate esters in fermentation liquors was important in directing the attention of other workers to phosphorus compounds as intermediates in fermentation and muscular respiration.

During World War I Harden abandoned fermentation studies and directed his attention toward vitamin problems. With S. S. Zilva he studied problems connected with the substances which prevented beriberi and scurvy. He established the synthesis of the antiberiberi factor by yeast and disproved the claims for the reported activity of α-hydroxypyridine and adenine. By removal of sugars, organic acids, and proteins from lemon juice he prepared a concentrate with enhanced antiscorbutic activity which was useful in treating infant scurvy.

Harden’s postwar researches were concentrated on the nature of the enzymes in yeast and their mode of action. He confirmed Carl Neuberg’s discovery of carboxylase in yeast and studied peroxidase and invertase. He also studied the role of inorganic salts in fermentation.

In 1929 Harden shared the Nobel Prize for chemistry with Euler-Chelpin for their studies of alcoholic fermentation. He was elected to the Royal Society in 1909, received the society’s Davy Medal in 1935, and was knighted the next year.

Throughout his career, Harden wrote and edited many warks. In addition to several early chemistry textbooks, he collaborated with Roscoe in a study of Dalton’s notebooks, which led to the publication of A New View of the Origin of Dalton’s Atomic Theory (1896). From 1913 to 1937 he was largely responsible for editing the Biochemical Journal.

Harden was married to Georgina Bridge of Christchurch, New Zealand, in 1890; they had no children. His wife died in 1928, two years before Harden retired from his professorship at the Lister Institute. A progressive nervous disease was responsible for his death.

BIBLIOGRAPHY

I. Original Works. There is no collected bibliography of Harden’s publications. Most of his research papers were published in the Proceedings of the Royal Society, Journal of the Chemical Society, and Biochemical Journal. For the studies of Dalton’s notebooks, see A New View of the Origin of Dalton’s Atomic Theory (London, 1896), written with H. E. Roscoe; and a later work, “John Dalton’s Lectures and Lecture Illustrations. Part III. The Lecture Sheets Illustrating the Atomic Theory,” in Memoirs and Proceedings of the Manchester Literary and Philosophical Society, 59 (1915), 41–66, written with H. F. Coward.

Harden’s other works include “The Composition of Some Ancient Iron and a Bronze Found at Thebes,” in Transactions of the Manchester Literary and Philosophical Society, 41 (1897), 1-3; Practical Organic Chemistry (London, 1897), written with F. C. Garrett; Inorganic Chemistry for Advanced Students (London, 1899), written with H. E. Roscoe; “The Alcoholic Ferment of Yeast Juice,” in Proceedings of the Royal Society, 77B (1907), 405-420, written with W. J. Young; and Alcoholic Fermentations (London, 1911; rev. ed., 1914, 1923, 1932). His Nobel Prize address, “The Function of Phosphate in Alcoholic Fermentation,” is in Nobel Lectures, Including Presentation Speeches and Laureates’ Biographies, Chemistry, 1922–1941 (Amsterdam, 1966), pp. 131-141.

II. Secondary Sources. The best biography is the obituary sketch by Ida Smedley-Maclean, “Arthur Harden (1865-1940),” in Biochemical Journal, 35 (1941), 107-1081. See also F. G. Hopkins and C. J. Martin, “Arthur Harden, 1865-1940,” in Obituary Notices of Fellows of the Royal Society of London, 4 (1942-1944), 3-14; C. J. Martin, in Dictionary of National Biography, 1931-1940, pp. 395-397; and Nobel Lectures, cited above, pp. 142-143.

Aaron J. Ihde