Friedrich Miescher.
1879 picture of the laboratory where Miescher isolated nuclein. The lab was run by Felix Hoppe-Seyler, and located in the vaults of an old castle.
Phoebus Aaron Theodor Levene, 1915.
Levene working in the lab.
(1 of 4) Levene's laboratory at the Rockefeller Institute, 1922. Levene had a large lab space; note the type of equipment used at the time.
(2 of 4) Levene's laboratory at the Rockefeller Institute, 1922.
(3 of 4) Levene's laboratory at the Rockefeller Institute.
(4 of 4) Levene's laboratory at the Rockefeller Institute--used for distillation purposes.
Audio Glossary
Base pair, Chromosome, Deoxyribonucleic acid (DNA), Genome, NucleotideVideo Interviews
Thomas Sakmar is a professor at Rockefeller University. His lab works on the role of several proteins involved in photochemistry, specifically how protein structure is related to function. Dr. Sakmar has a personal interest in the work done by Phoebus Levene.
Clip 1 (2:14)
Comments on some of the prevailing theories of the time and Phoebus Levene's basic hypothesis.
Clip 2 (1:30)
Phoebus Levene's contributions -- the distinction between DNA and RNA.
Clip 3 (0:55)
The work of Erwin Chargaff and how it contributed to the downfall of Levene's tetranucleotide theory.
Clip 4 (2:00)
Did Levene's tetranucleotide theory affect the development of ideas in the field of nucleic acid research?
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In 1869, Friedrich Miescher isolated "nuclein," DNA with associated proteins, from cell nuclei. He was the first to identify DNA as a distinct molecule. Phoebus Levene was an organic chemist in the early 1900's. He is perhaps best known for his incorrect tetranucleotide hypothesis of DNA.
FRIEDRICH MIESCHER (1844-1895)
Friedrich (Fritz) Miescher was born in Basel, Switzerland. The Miescher family was well-respected and part of the intellectual elite in Basel. Friedrich's father was a physician and taught pathological anatomy; Friedrich's uncle, Wilhelm His, was a well-known embryologist. Miescher was an excellent student despite his shyness and a hearing handicap. Miescher initially wanted to be a priest, but his father opposed the idea and Miescher entered medical school. When he graduated in 1868, Miescher ruled out specialties where patient interactions were necessary because of his hearing problem. He decided to base his career on medical research. He went to the University of Tübingen to study under Felix Hoppe-Seyler in the newly established faculty of natural science. Hoppe-Seyler's laboratory was one of the first in Germany to focus on tissue chemistry. At a time when scientists were still debating the concept of "cell," Hoppe-Seyler and his lab were isolating the molecules that made up cells. Miescher was given the task of researching the composition of lymphoid cells -- white blood cells. These cells were difficult to extract from the lymph glands, but they were found in great quantities in the pus from infections. Miescher collected bandages from a nearby clinic and washed off the pus. He experimented and isolated a new molecule - nuclein - from the cell nucleus. He determined that nuclein was made up of hydrogen, oxygen, nitrogen and phosphorus and there was an unique ratio of phosphorus to nitrogen. He was able to isolate nuclein from other cells and later used salmon sperm (as opposed to pus) as a source. Although Miescher did most of his work in 1869, his paper on nuclein wasn't published until 1871. Nuclein was such a unique molecule that Hoppe-Seyler was skeptical and wanted to confirm Miescher's results before publication. Miescher continued to work on nuclein for the rest of his career. He also examined the metabolic changes that occur in salmon when they spawn. In 1872, Miescher was appointed the professor of physiology at the University of Basel, a position previously held by his father and then his uncle. The appointment meant more funds and equipment for research, but it also meant that Miescher had to teach. Although he put in a lot of time and effort, Miescher was not a good teacher. His shyness and preoccupation with his research made it difficult for him to relate to his students. He was a perfectionist and a workaholic, and often worked very long hours to do the nuclein isolations. It would be years before the role of nucleic acids were recognized. Miescher, himself, believed that proteins were the molecules of heredity. However, Miescher laid the groundwork for the molecular discoveries that followed. Miescher died in 1895 from tuberculosis. PHOEBUS AARON THEODOR LEVENE (1869-1940)
Phoebus Levene was born in Sagor in Russia. He grew up in St. Petersburg and studied medicine at the Imperial Military Medical Academy. As a student he worked in the laboratory of his organic chemistry professor where he likely developed an interest in biochemistry. In 1891, because of growing anti-Semitism in Russia, Levene and his family emigrated to the U.S. They arrived on the symbolic day of July 4. Levene went back to Russia almost immediately to finish his medical degree, but by 1892, he was in New York and practicing medicine on the Lower East Side. Levene did not give up research. He enrolled as a special student at Columbia University and he split his time between his medical practice and research in the department of physiology. By 1894, he began publishing papers on the chemical structure of sugars. Two years later, Levene received his first appointment as an Associate in the Pathological Institute of the New York State Hospitals. Unfortunately, around this time, Levene contracted tuberculosis and was forced to take time off to recuperate. Levene used the time between 1896 and 1905 to regain his health and to work with a number of well-known chemists, including Albrecht Kossel and Emil Fischer, the nucleic acid and protein experts of the time. In 1905, Levene was hired by the newly established Rockefeller Institute of Medical Research to head the biochemical laboratory. Levene did most of his nucleic acid work at the Rockefeller and stayed there until his death. Levene was a cultured man, an art lover and a collector. The walls of his house were lined with either prints and paintings or overflowing bookshelves. Levene was extremely well-read and was fluent in Russian, English, French and German. He also spoke passable Spanish and Italian. His experience, knowledge and his generosity made him a favorite with colleagues and friends. He was also said to be a great teacher, enthusiastic and supportive. Although mostly remembered now for his incorrect tetranucleotide theory of DNA, Levene published over 700 original papers and articles on the chemical structures of many biochemicals. Levene died in 1940, before the true significance of DNA became clear. |
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LinksThe Friedrich Miescher InstituteLocated in Basel, Switzerland, the FMI was founded in 1970 and named in honor of Friedrich Miescher. Bibliography
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