Born in Manchester, England, Harden did his undergraduate work at a local school, Owens College, but went to the University of Erlangen in Germany for graduate studies. After obtaining his Ph.D. there in 1888, he returned home and spent ten years teaching at his alma mater. In 1898, he began studying fermentation simply because he thought it might help him differentiate between several varieties of bacteria. Although his original theory did not work out, Harden gradually became more and more interested in fermentation itself, the process by which a certain few agents seemed able to cause a number of organic compounds first to decompose, then to transform themselves into other compounds altogether.
The most commonly-seen example of the process--and the one that especially intrigued chemists during the mid-to-late 1800s--was alcoholic fermentation, the conversion of glucose and other sugars into alcohol apparently through the action of yeast preparations. For a long time, scientists had assumed that living cells in yeast contained a "vital force" that enabled yeast to transform other compounds. But in 1897, a German biochemist, Eduard Buchner, proved that a cell-free juice extracted from yeast could also act as a fermenting agent. Buchner named the active principle in his yeast juice zymase, which he assumed was an enzyme. It was Buchner's zymase-containing yeast juice that Harden used in his research studies for the next several years.
In 1904, working at the Jenner Institute of Preventive Medicine along with a student named William J. Young, Harden made an interesting discovery. He had already learned that boiling his yeast juice appeared to destroy its enzymatic activity, rendering it no longer able to ferment sugar. But during one particular experiment, he found that, if he added a little of the boiled and apparently "dead " yeast juice to an active batch, the addition seemed somehow to increase the yeast's fermentation powers. The boiled juice, then, must still contain some sort of active principle. But what could it be"
To find out, Harden decided to try dialysis, a filtering process often used in chemistry. Another batch of active yeast juice was poured into a semipermeable bag and the bag itself placed in a container of pure water. Gradually, some of the juice' s smaller molecules began filtering out through the bag's membrane-like sides and into the water. The rest, containing the larger molecules, remained behind.
After repeatedly testing both sections of juice--separately and once again combined--Harden reported that zymase, the yeast's enzyme, apparently consisted of two parts: a large-molecular part that could not survive boiling and was almost certainly a protein ; and a small-molecular part that could survive boiling and was probably not a protein. Neither part could ferment sugar by itself. Although Harden called the non-protein factor a coferment, it was clearly the first example of a coenzyme, the non-protein molecule--usually composed of vitamin s--that many enzymes needed as an attachment before they could do their work.
Harden studied the fermentation process for several more decades, discovering, among other things, that inorganic phosphate groups played an important but temporary role in fermentation. It was this discovery that helped arouse interest in an important new branch of biochemistry, intermediary metabolism. This branch of biochemistry concentrates on the study of certain intermediate compounds that come to life, sometimes very briefly, during the course of many biochemical reactions. Harden's discovery also caused later researchers, such as Carl and Gerty Cori and Fritz Lipmann, to realize the vital importance of the phosphates to biochemistry.
Harden became a professor of biochemistry at the University of London in 1912. With Hans Euler-Chelpin, he shared the 1929 Nobel Prize in chemistry for his work in fermentation. He was the Joint Editor of The Biochemical Journal with William Bayliss from 1913 to 1938 and received the Davy Medal in 1935. In 1936, four years before his death, he was knighted.
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