Arthur Harden

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Arthur Harden (October 12, 1865, to June 17, 1940) was a British biochemist who made significant progress in the study of glycolysis and fermentation. Born in Manchester, Harden attended Victoria University and, after almost a decade of teaching, began to research yeast fermentation. With colleague William John Young, the researchers discovered the compoundNicotinamide adenine dinucleotide (NAD+) in 1906.

For this and his later work on sugar, yeast, and enzymes, he was awarded the 1929 Nobel Prize in chemistry along with Hans von Euler. Harden received many other prizes for his work and continued to research this subject for the rest of his life. [1][2] [3]

Early life and interests

Brought up with his sisters in Manchester, England, Arthur Harden had parents who were “austere non-conformists,” not going to plays at the theatre or celebrating Christmas.[3] Harden attended Tettenhall College in Staffordshire until the age of sixteen. He went on to Victoria University, where he achieved “first-class” honors in chemistry.[3] The following year, 1886, he received the Dalton Scholarship.[3]

Harden loved to travel, visiting Greece and South Africa, as well as being an excellent skater, golfer, and later gardener.[1] He was known as a man of middling temper, well-liked by both colleagues and students, and was married in 1907 to Georgina Sydney.[1]

Career

Teaching

Until the tutelage of his teacher J.B. Cohen, Harden produced his first paper on silicon tetrachloride, published in 1886 for the journal “Transactions of the Chemical Society.”[3] After obtaining his Ph.D., Harden became a senior demonstrator and lecturer in Manchester, doing research and teaching the history of chemistry to honors students.[3] Working with a colleague, he also wrote a paper and a book on the diffusion of gases and even helped write textbooks on chemistry.[3]

Early research

In 1897, after nine years lecturing and demonstrating at Manchester, Harden joined the British Institute of Preventative Medicine at the suggestion of his long time colleague Sir Henry Roscoe.[1] A year later, the institute changed its name to the Jenner Institue of Preventative Medicine.[1] One of Harden’s new colleagues, Doctor Allan Macfadyen, encouraged him to study the bacterial fermentation of sugars.[1]

NAD+

Eduard Buchner’s momentous discovery in 1897 of cell-free fermentation opened up a whole new area of study for biochemists, and much work began exploring yeast fermentation.[1] Harden was one such chemist, and published a book on alcoholic fermentation and wrote papers on vitamins.[4] In 1901, William John Young, a fellow British chemist, became Hardens’ assistant.[5] Harden and Young thus began a decade long collaboration, mostly on yeast fermentation.[6] Two years later, the Jenner Institute, where they worked, changed its name again, this time to the Lister Institute.[1] Harden and Young studied yeast glycogen and where and under what conditions “yeast juice” would lose or redouble its fermentation ability. [6] While others often solely studied the effects of experiments, Arthur and Young studied every part, such as the amount of CO2 and the rate of reaction throughout the process.[6]

In 1906, the duo made a significant discovery when they uncovered a compound they named Nicotinamide adenine dinucleotide (NAD+).[7] This “co-factor” was found by adding boiled yeast extract to non-boiled extracts, which significantly amplified the alcoholic fermentation process.[7] This effect implied that something new was in the boiled mixture; this; this was called a “cozymase.”[7] Harden found that this biotic factor, along with phosphate, were responsible for creating zymase.[8] The revelation that at least three compounds were involved in the creation of zymase, and that it was not an uncomplicated enzyme, was a significant discovery.[8] Some attempted to argue the finding, but the work of Harden and Young was not able to be discredited.[8]

From 1906-1911, Young and Harden contributed six papers to the journal “The Proceedings of the Royal Society” about yeast fermentation and carbohydrate metabolism.[5][6] In 1907, the two researchers further studied “co-fermentation,” and the interactions of the phosphate radical and a then yet unknown structure that moved the radical to a sugar molecule.[5] The duo’s partnership ended in 1912 when Young moved to Australia to work in a Lectureship at the Institute of Tropical Medicine.[6]

While Harden was working on his research, his professional career was not standing still. Harden became head of the Biochemistry Department at the Lister Institute in 1907, and in 1909 Harden was elected to the Fellowship of the Royal Society.[4][5] Harden was also involved in the founding of the Biochemical Society in 1911, later called the Biochemical Journal in 1912, and was its editor for twenty-five years.[1][9] Harden also became a professor of biochemistry at the University of London in 1912.[4]

Later works

In 1914, Harden began working with a new partner, Robert Robinson, and research on fermentation continued.[1] When World War I started, the Director of the Lister Institute left, and Harden became Deputy-Director.[1] In 1917, Harden and colleague Zilva established that vitamin deficiency caused scurvy, not an “unwholesome diet.”[1] Harden also helped with the Accessory Food Factors Committee created by the Medical Research Committee.[1] Harden continued his work on understanding the process of glycolysis, as well as its co-factors and intermediates.[4] He also advanced the work on cell-free fermentation originally started by Eduard Buchner.[4]

Later life, awards, and legacy

In 1929, he and his colleague Hans von Euler won the Nobel Prize for Chemistry for their work on yeast, sugars, and enzymes over many years.[4] Harden presented a lecture on the topic of phosphates and their role in alcoholic fermentation to the Nobel Prize committee on the day of his award on December 12, 1929.[10] Harden retired in 1930.[2] He received further awards for his work, including the Davy Medal of the Royal Society in 1935, and a knighthood from the United Kingdom in 1936.[1] The Institute of Brewing made him an honorary member, and he received several honorary degrees.[1]

For years he continued to teach and write articles and was the editor of the Committee of the Biochemical Society.[1] In 1938 he was presented a silver salver by the Biochemical Journal for his long years of work and contribution.[1] Until a year or two before he died, Harden came to the lab every day, still working on experiments.[1]

His role and memory continue to be honored by annual Harden conferences, and his work eventually led to further discoveries about the role of NAD+, a compound critical to the function of living cells. [11][9]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 Arthur Harden Written for the Biochemical Journal. Published November 1941, Volume 35; Accessed April 6, 2020
  2. 2.0 2.1 Sir Arthur Harden, F.R.S Written by J.C.G. Ledingham for Nature, Volume 146, Issue 122. Published July 1, 1940; Accessed April 13, 2020
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Arthur Harden. 1865-1940 Written by F. G. Hopkins and C. J. for the Royal Society, Volume 4, Number 11, Pages 2-14. Published November 1, 1942; Accessed April 13, 2020
  4. 4.0 4.1 4.2 4.3 4.4 4.5 THE NOBEL PRIZE MEN Written for Science, Volume 70, Issue 1821. Published November 22, 1929; Accessed April 13, 2020
  5. 5.0 5.1 5.2 5.3 Obituary: William John Young Written for Biochemistry Journal, Accessed from United States National Library of Medicine & the National Institutes of Health. Published July 1943, Volume 37; Accessed April 9, 2020
  6. 6.0 6.1 6.2 6.3 6.4 Arthur Harden Written by Ida Smedley-Maclean for the Biochemical Journal, Volume 35, Issues 10-11, Pages 1071-1081. Written November 1, 1941; Accessed April 13, 2020
  7. 7.0 7.1 7.2 Modulating NAD+ metabolism, from bench to bedside Written by Elena Katsyuba and Johan Auwerx for The Embo Journal, Volume 36, Issue 18. Published September 15, 2017; Accessed April 13, 2020
  8. 8.0 8.1 8.2 THE BACKGROUND TO ARTHUR HARDEN'S DISCOVERY OF COZYMASE Written by Robert E. Koehler Jr. for Bulletin of the History of Medicine, Volume 48, Number 1. Published Spring 1974; Accessed April 22, 2020
  9. 9.0 9.1 Arthur Harden: an unwitting pioneer of metabolic control analysis Written by Keith L. Manchester for Trends in Biochemical Sciences, Volume 25, Issue 2, Pages 89-92. Published February 1, 2000; Accessed April 13, 2020
  10. The Function of Phosphate in Alcoholic Fermentation Written by Arthur Harden for Nature, Volume 125, Pages 277-279. Published January 1, 1930; Accessed April 13, 2020
  11. Exploring the therapeutic space around NAD+ Written by Riekelt H. Houtkooper and Johan Auwerx for the Journal of Cellular Biology, Volume 199, Issue 2, Pages 205-209. Published October 15, 2012; Accessed April 13, 2020