Levene, Phoebus Aaron Theodor

(b. Sagor, Russia, 25 February 1869; d. New York, N. Y., 6 September 1940),

biochemistry.

An American biochemist who carried out extensive research on conjugated proteins, Levene was particularly noted for his pioneering work on nucleoproteins and their component nucleic acides. He was the second of eight children of a custom shirtmaker, Solom Michael Levene and the former Etta Brick. The family moved to St. Petersburg in 1873 so the children might attend private schools and the classical academy. Upon graduation from the latter in 1886, Phoebus was admitted to the Imperial Military Medical Academy in St. Petersburg, where chemistry was taught by Borodin and his son–in–law, Alexander Dianin. Because of growing anti–Semitism the Levene family emigrated to New York in 1891, but Phoebus returned to the medical academy and received his M.D. in the fall of that year.

He then undertook medical practice in New York’s Lower East Side but was concurrently enrolled as a special student in the chemistry department of the Columbia University School of Mines. In 1896 he became associate in physiological chemistry at the recently opened laboratories of the Pathological Institute of the New York State Hospitals. He soon contracted tuberculosis and, while recovering in a sanitarium at Saranac Lake, decided to abandon the practice of medicine and devote his life to biochemical research. At various times in the next decade he served at the Pathological Institute and at the Saranac Lake Laboratory for the Study of Tuberculosis, where he worked on the chemistry of the tubercle bacillus. Interspersed were periods of study with Edmund Drechsel in Bern, Albrecht Kossel in Marburg, and Emil Fischer in Berlin. At Marburg he became interested in nucleic acids, and at Berlin he applied Fischer’s new ester fractionation procedure to the determination of the amino acids in gelatin. In 1905 Simon Flexner selected him to head the biochemical studies at the newly created Rockefeller Institute for Medical Research, where he worked until his retirement in 1939.

Levene was an intense, hard–driving scientist. He was thin, of short stature, and had penetrating, darkbrown eyes, close–cropped mustache, and a stern expression. He liked to work in the laboratory and managed to do so while supervising a staff of postdoctoral students and assistants, many of them from foreign countries. He conferred daily with his associates, keeping in close touch with the progress of their research and making suggestions reflecting his broad familiarity with the literature. An accomplished linguist, he addressed his foreign students in their native tongues. He spoke excellent German and French, but his English always had a heavy Russian accent.

In 1919 he met Anna M. Erickson at Saranac Lake. She was born in Montana but was then a member of the Norwegian Lutheran Colony in Evanston, Illinois. They were married in 1920. There were no children. Their home reflected Levene’s interest in music (he played the violin), contemporary art, and literature. Although a gracious host in a social setting, Levene never permitted social affairs to interfere with his scientific activities. His political views were liberal; he supported the Kerensky government, but was unsympathetic to the Bolsheviks.

Of particular importance in his career was his pioneering work on the nucleic acids. Although discovered in 1871, little was known about them in 1900 except that they were present in nucleoproteins, and contained phosphoric acid groups associated with nitrogenous and nonnitrogenous material. Levene showed the presence in cells of two principal types. One, obtained readily from yeast, he showed to be composed of four nucleosides in which he identified the hitherto unknown sugar D–ribose. The optical isomer, L–ribose, had recently been synthesized in Europe, and Levene showed his sugar to be identical except for direction of optical rotation. He also synthesized the hypothetical hexose sugars, D–allose and D–altrose, from D–ribose.

In subsequent work Levene identified four nucleotides from yeast nucleic acid and showed the presence of phosphoric acid, ribose, and a nitrogenous base (either a purine or a Pyrimidine). He was able to show that nucleic acids are high polymers composed of the four nucleotides. Related work on thymus nucleic acid showed a similar composition, but the identity it in 1929, twenty years after the identification of ribose, as 2–deoxy–D–ribose. His laboratory established the sequence of units in the nucleotides, worked out the ring structures of the sugars, and established the position of attachment of the bases and phosphate units on the sugars. Levene died four years before RNA and DNA were recognized to play a principal role in transmission of hereditary information.

Besides his work on the ribose sugars, Levene undertook work on the glycoproteins in 1900, isolating nitrogenous sugars from the mucoids. The structures of these hexosamines could be established only after extensive synthetic studies on sugars and amino sugars. His identification of chondrosamine as 2–amino–2–deoxy–D–galactose and chitosamine as 2amino–2–deoxy–D–glucose was later confirmed by the work of Haworth and his associates. In his studies of sugar Levene made important contributions to the understanding of the Walden inversion.

Other research dealt with the lipids. Levene showed that lecithin isolated from different parts of the body contains different fatty acids; that sphingomyelins prepared from various organs are identical; and that “kerasinic acid” from the cerebroside, kerasin, is identical with lignoceric acid.

Levene was a skilled laboratory worker who utilized simple apparatus with great effectiveness. Because of his medical training he carried out animal experiments with unusual skill. His more than 700 publications reveal a great diversity of research interests, yet they reflect an integration revealing a deep understanding of the problems involved in unraveling the chemistry of living processes. His early work resulted in the isolation of specific proteins. It was necessary to develop improved analytical procedures to unravel their composition. He complemented analysis with synthesis in attacking such problems. Early work on the racemization of synthetic diketopiperazines led him to conclude that protein structure was explainable by classical valence theory. While his isolation of propylglycine anhydride from a gelatin hydrolysate challenged the new polypeptide theory of protein structure, the problem was ultimately resolved. His work on protein structure quickly led to studies of the nonprotein constituents of conjugated proteins (nucleoproteins, lipoproteins, glycoproteins) and thereby to the studies of sugars, lipids, and nucleic acids.

Levene was a charter member of the American Society of Biological Chemists, the National Academy of Sciences, and of numerous other American and foreign societies. In 1931 he received the Willard Gibbs Medal of the American Chemical Society and in 1938 was awarded the William H. Nichols medal of the New York section of the same society.

BIBLIOGRAPHY

I. Original Works. A bibliography of Levene’s publications is appended to the biography by D. D. Van Slyke and W.A. Jacobs (see below). Most appeared in the Journal of Biological Chemistry. Levene published fragmentary results rapidly, rather than waiting until a major area of research was completed. His books areHexosamines, their Derivatives, and Mucins and Mucoids (New York, 1922); Hexosamines and Mucoproteins (New York, 1925); and Nucleic Acids (New York), 1931).

II. Secondary Literature. There are no extensive biographies of Levene. The best short biography of him as a person is Melville L. Wolfram, “Phoebus Aaron Theodor Levene,” in Eduard Farber, ed., Great Chemists (New York, 1961), pp., 1313-1324. Wolfram served as a postdoctoral fellow in Levene’s laboratory and obtained personal information about the family background from Alexander, the younger brother of Phoebus. He gives Aaron as the father’s name and has much information on Levene’s Russian name and its transliteration. There is also some personal material in D.D. van Slyke and W.A. Jacobs, “Phoebus Aaron Theodor levene,” Biographical memoirs. National Academy of Sciences,23 (1945), 75-126. Other sketches are R. Stuart Tipson, “Phoebus Aaron Theodor Levene, 1869-1940,” in Advances in Carbohydrate Chemistry,12 (1957), 1-12; and Lawrence W. Bass, “American Contemporaries, P.A. Levene,” in Industrial and Engineering Chemistry. News edition,12 (1934), 105.

Aaron J. Ihde