Simple Biography, Early year of Phoebus Levene
In February 25, 1869, Phoebus Levene was born in Žagarė Lithuania. At the time, this region was Sagor that belong to Russian Empire. On September 6, 1940, he passed away in New York, USA.
Phoebus Levene completed his medical PhD in the Imperial Military Medical Academy in 1891.Two years later, the entire family emigrated to New York, USA, to escape the growing antisemitism in Russia. He made a living as a doctor on the lower East Side of New York until 1896. In his spare time, Phoebus Levene studied chemistry at Columbia University, and worked in the lab of John G. Curtis for physiological chemistry. An important turning point in his career came in 1896, as he left the medical field to become a full-time biochemist: the New York State Hospitals hired him as a physiological chemistry assistant in pathological Institute. However, before he could celebrate, tuberculosis struck him down in November. His life and career were delayed for two years by disease and cure.
In the last years of 19th century, he worked as a visiting scholar in several European laboratories. Nobel Prize winner Albrecht Kossel imparted knowledge of nucleic acids and protein to him. In 1905, Levene was invited to take up the position of assistant researcher at the Rockefeller institution. His talent in biochemistry was quickly revealed, and in 1907, he was appointed director of the chemistry department, a position he held until retirement. More than 700 papers on nucleic acids, proteins, carbohydrates, and lipids were published.
Phoebus Levene proposed composition and structure of nucleic acids, nucleotides
His mentor Albrecht Kossel had already identified that nucleic acids contain bases, phosphates, and monosaccharides. The nucleic acid extracted from yeast (RNA) contained pentose, but the nucleic acid from thymus (DNA) was mistakenly believed to have hexose. In 1910, Phoebus Levene demonstrated that pentose extracted from the hydrolysate of yeast nucleic acid was D-ribose. This nucleic acid was termed by him as ribonucleic acid, or abbreviated as RNA. In 1929 in Levin's laboratory, thymus nucleic acids were hydrolyzed by enzymes and then treated with dilute acid. Levene extracted another type of pentose that was named as deoxyribose, because hydroxyl group on the second carbon was replaced by a hydrogen, and the other parts are identical to ribose. This nucleic acid was termed by him as deoxyribonucleic acid, or abbreviated as DNA.
Because, in early experiments, RNA was separated from yeast and wheat germ, while DNA was obtained from animal tissues such as thymus, people long believed that RNA existed only in plant cells, while DNA was present only in animal cells. Thus, they were called plant or animal nucleic acids respectively. Levene corrected this early misconception. Both types of nucleic acids are actually fundamental components of cells, whether they are animal, plant, or microbial. Levene also pointed out that nucleic acids contain only two purines, A and G, while other purines are by-products of nucleic acid extraction. The bases are different in RNA and DNA. The former contains A, G, C, U, while the latter contains A, G, C, T.
Tetranucleotide hypothesis
Years of hydrolysis experiments provided Levene with a comprehensive understanding of structure and chemical composition in nucleic acids. A nucleotide contains a base (purine or pyrimidine), a pentose (ribose or deoxyribose), and a phosphate. The base and phosphate are attached to the pentose. Nucleotides are the fundamental units of nucleic acids. However, Levine proposed a false tetranucleotide hypothesis to elaborate how nucleotides form nucleic acids.
DNA was hydrolyzed by acid, so the extract was actually fragments. Their molecular weight was around 1500D and closest to four nucleotides. In nucleic acids, the quantity of A and T, C and G are equal. Although A ≠ G, their ratio is close to 1. However. Researchers could only obtain an extremely little of impure DNA each time, and the task of hydrolyzing nucleic acids was technically unwieldy. Thus, it was almost impossible to get accurate information. Having been aware of these difficulties, researchers in the first half of the 20th century were tolerant of the vastly diverse bases ratios in different laboratories. The experimental data was false in a long time: the four bases in DNA are almost equal in quantity. This directly indicated that DNA is a small molecule containing only four different nucleotides. In 1938, new techniques such as ultracentrifugation demonstrated that nucleic acids have enormous molecular weights between 1 million D and 2 million D. He simply made a slight modification to the tetranucleotide hypothesis: DNA is organized by repeating tetranucleotide. Although he admitted that DNA was a macromolecular compound, its structure still remained extremely simple.