After attending the Eliot Grammar School, Sumner spent six years at the Roxbury Latin School, where he became interested in physics and chemistry. His formal chemical training was received at Harvard, where he earned the B. A. in chemistry (1910) and the M. A. (1913) and Ph. D. (1914) in biochemistry.
Between his undergraduate and graduate study, Sumner taught chemistry and physiology at Mt. Allison College in Sackville, New Brunswick (1910), and held a research assistantship in chemistry at Worcester Polytechnic Institute, Worcester, Massachussets (1911 - 1912).
Sumner's post-doctoral European tour continued the grand academic tradition he had established for himself, as did the news - which caught up with him in Switzerland - that he had been offered an assistant professorship of biochemistry at the Ithaca division of Cornell University Medical College. He was affiliated with Cornell for the rest of his life, becoming a full professor in 1929.
Sumner's early research was directed toward the development of analytical techniques for biochemical samples, but it was neither very productive nor personally rewarding.
In 1917, directed by both his interests and circumstances, he elected a more daring project: the isolation of an enzyme. Enzyme purification seemed the research best suited to his limitations of time, facilities, and finances (he had a heavy teaching load, a poorly equipped and poorly staffed laboratory, and no research funds). Moreover, his doctoral dissertation had required much work with a preparation containing the enzyme urease, so Sumner easily settled upon urease as the enzyme he would try to isolate.
Yet if the purification of urease, or any enzyme, seemed tailored to Sumner's experience and situation, it must also have appeared exceedingly ambitious. Although enzyme-catalyzed fermentations had been familiar chemical phenomena for centuries, the specific nature of the "ferment" had been a question for both wonder and warm debate.
The term "enzyme" was less than half a century old, and the realization that a large number of enzymes exist to catalyze the specific chemical transformations within cells was even newer. Theoretical novelty was compounded, furthermore, by practical complexity. Enzymes, which are present in plant and animal tissues in small amounts and are easily destroyed by heat and chemicals, were difficult to obtain in any form more pure than a concentrated juice extracted from an organic source.
Sumner later acknowledged that a number of experts counseled him against wasting his time trying to purify an enzyme, and that during the years he pursued the project he several times became so discouraged that he temporarily abandoned the work. Nevertheless he recognized that a full chemical characterization of enzymes was impossible without purification; and his nine years of working with urease, an enzyme that catalyzes the decomposition of urea into ammonium carbonate, were rewarded by the discovery in 1926 that apparently pure crystals of a protein exhibiting high urease activity could be obtained from the jack bean (Canavalia ensiformis).
The reception of Sumner's announcement that urease is a purifiable protein, however, was no warmer than that given his earlier proposal to attempt the isolation of urease. The recognized leader in enzyme investigations during the period, Richard Willstetter, had been futilely attempting to purify an enzyme (invertase) for years, and had become convinced that enzymes did not fit into any of the traditional biochemical groups of lipid, carbohydrate, and protein. Any protein in Sumner's preparation, he felt assured, must be a "carrier, " a compound on which the enzyme was adsorbed, and not the enzyme itself. Equally confident of his findings, Sumner stood his ground and contended vigorously with Willstetter and his supporters for several years.
His argument for the protein nature of enzymes received reinforcement in 1930, when John Northrop of the Rockefeller Institute reported the isolation of pepsin, a digestive enzyme and a protein. By the end of the decade, more than a dozen other enzymes had been crystallized and identified as proteins; and Sumner's position had been established.
His isolation of urease (and similar investigations of a number of other enzymes) not only began the clarification of the chemical nature of enzymes but also contributed to the progress of the chemistry of proteins in general, progress that drew freely from researchers on crystalline enzymes. Sumner's interest in enzymes lasted until the end of his career and resulted in more than 100 scientific papers.
Also in 1943 Sumner published The Chemistry and Methods of Enzymes, written with G. F. Somers; it went through several editions and was popular as a standard introduction to the subject.
He retired from Cornell in July 1955, and died in Buffalo, New York.
Sumner was elected to the National Academy of Science in 1948. In 1949, he was elected a Fellow of the American Academy of Arts and Sciences.
A hunting accident at the age of seventeen required the amputation of his left arm above the elbow, but with the determination that marked his whole career, the originally left-handed Sumner so completely overcame his handicap that in later years he amazed colleagues with his one-handed manipulations of chemical apparatus.
Sumner married Bertha Louise Ricketts; they had five children and were divorced in 1930. In 1931 Sumner married Agnes Paulina Lundkvist; they were divorced in 1943. That same year he married Mary Morrison Beyer; they had two sons.