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Phoebus Levene

 
Scientist: Phoebus Aaron Theodor Levene

Russian–American biochemist (1869–1940)

Levene was born in Sagor, Russia, and gained his MD from St. Petersburg in 1891. He then emigrated with his family to America where he attended courses in chemistry at Columbia University, New York. He continued his chemical studies in Germany under Emil Fischer and Albrecht Kossel, who introduced him to the study of nucleic acids. In 1905 he joined the newly formed Rockefeller Institute for Medical Research where he remained for the rest of his career.

It was known that nucleic acid exists in two forms, one found in the thymus of animals and the other in yeast. Kossel had shown that thymus nucleic acid contained the four nitrogen compounds adenine, guanine, cytosine, and thymine, whereas yeast nucleic acid differed by containing uracil instead of thymine. Carbohydrate and phosphorus were also known to be present. Virtually nothing, however, was known about its structure and function. The work of Levene allowed some conclusions to be drawn on these issues.

In 1909 Levene found that the carbohydrate present in yeast nucleic acid is the pentose sugar ribose; it was not, however, until 1929 that he succeeded in identifying the carbohydrate in thymus nucleic acid. It is also a pentose sugar but lacks one oxygen atom of ribose and was therefore called deoxyribose.

These facts enabled Levene to suggest a simple tetranucleotide structure for the inevitably named ribonucleic and deoxyribonucleic acids (RNA and DNA). (A nucleotide is simply one of the four bases plus a sugar and a phosphate group.) According to Levene each of the four bases occurred just once in each DNA and RNA molecule and were joined together by the sugar and phosphate groups. This structure could then be repeated to form a polynucleotide with the bases occurring in the same order throughout.

Levene had succeeded in establishing the nucleic acids as genuine molecules existing independently of the proteins but the price he paid for this clarification was to impose on them an absurdly simple and repetitive structure. Consequently, when the search for biological individuality reached the molecular level, the far more complex and varied structure of the proteins was favored over the ‘monotonous’ form of the nucleic acids, and a generation of biochemists mistakenly sought for the structure of the gene among the inexhaustible potential of the amino acids.

When Levene was told, shortly before his death, of the classic work of Oswald Avery, which showed the crucial part played by DNA, he was reported to be skeptical. It took a further 13 years before James Watson and Francis Crick came up with their famous double helical structure and completed the revolution begun by Levene and other biochemists earlier in the century.

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Phoebus Levene
Molecular diagram of a proposed tetranucleotide, later shown to be incorrect. It was proposed by Phoebus Levene around 1910

Phoebus Aaron Theodore Levene, M.D. (25 February 18696 September 1940) was a Russian-American biochemist who studied the structure and function of nucleic acids. He characterized the different forms of nucleic acid, DNA from RNA, and found that DNA contained adenine, guanine, thymine, cytosine, deoxyribose, and a phosphate group.

He was born into a Jewish family as Fishel Aaronovich Levin in Sagor in Lithuania, Russia but grew up in St. Petersburg (Petrograd). There he studied medicine at the Imperial Military Medical Academy (M.D., 1891) and developed an interest in biochemistry. In 1893, because of anti-Semitic pogroms, he and his family emigrated to the United States and he practiced medicine in New York.

Levene enrolled at Columbia University and in his spare time conducted biochemical research, publishing papers on the chemical structure of sugars. In 1896 he was appointed as an Associate in the Pathological Institute of the New York State Hospitals, but he had to take time off to recuperate from tuberculosis. During this period, he worked with several chemists, including Albrecht Kossel and Emil Fischer, who were the experts in proteins.

In 1905, Levene was appointed as head of the biochemical laboratory at the Rockefeller Institute of Medical Research. He spent the rest of his career at this institute, and it was there that he identified the components of DNA. (He had discovered ribose in 1909 and deoxyribose in 1929.) Not only did Levene identify the components of DNA, he also showed that the components were linked together in the order phosphate-sugar-base to form units. He called each of these units a nucleotide, and stated that the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule. His ideas about the structure of DNA were wrong; he thought there were only four nucleotides per molecule. He even declared that it could not store the genetic code because it was chemically far too simple. However, his work was a key basis for the later work that determined the structure of DNA. Levene published over 700 original papers and articles on biochemical structures. Levene died in 1940, before the true significance of DNA became clear.

Levene is known for his "tetranucleotide hypothesis" (formulated around 1910) which first proposed that DNA was made up of equal amounts of adenine, guanine, cytosine, and thymine. Before the later work of Erwin Chargaff, it was widely thought that DNA was organized into repeating "tetranucleotides" in a way that could not carry genetic information. Instead, the protein component of chromosomes was thought to be the basis of heredity; most research on the physical nature of the gene focused on proteins, and particularly enzymes and viruses, before the 1940s.[1]

Notes

  1. ^ Lily E. Kay, The Molecular Vision of Life: Caltech, the Rockefeller Foundation, and the Rise of the New Biology, Oxford University Press, 1992. pp. 104-116

References

  • "Phoebus Aaron Theodor Levene, 1869-1940" by R. S. Tipson (1957) in Advances in Carbohydrate Chemistry Volume 12, pages 1–12. Entrez Pubmed 13617111.

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