A biochemist, Severo Ochoa received the Nobel Prize in Physiology or Medicine in 1959 for his “discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.”
Severo Ochoa de Albornoz was born on 24 September 1905, in Luarca, Spain, the youngest of seven children. His father, Severo Manuel Ochoa, was a lawyer and businessman who died when Ochoa was 7 years old. His mother, Carmen de Albornoz, moved the family from Luarca, in Asturias, to Málaga, on the southern coast. Ochoa attended a private Jesuit school where a chemistry teacher inspired him to study the natural sciences. Inspired by the career of Ramón y Cajal, Ochoa chose to study biology. In 1923, he was admitted to the Medical School of the Universidad de Madrid (University of Madrid). As Ramón y Cajal already had retired, Ochoa studied under Juan Negrin, who encouraged him and a fellow student, José Valdecasas, to conduct laboratory experiments to isolate creatinine from urine. The two developed a method to measure creatinine levels in muscle. During the summer of 1927, Ochoa worked with Dr. Noel Paton in Glasgow, Scotland, to learn more about creatinine metabolism and to improve his skills in English. After he returned to Madrid, he and Valdecasas submitted a paper on their work to the Journal of Biological Chemistry, among the first of hundreds of papers Ochoa was to write over the course of his career.
In 1929, Ochoa completed his undergraduate degree in medicine and went to study with Otto Meyerhof in Berlin-Dahlem. Meyerhof had received the Nobel Prize in 1922 for work on muscle metabolism and glycolysis (the splitting of sugars), processes by which cells obtain energy. His laboratory in the Kaiser Wilhelm Institut für Medizinische Forshung (Kaiser Wilhelm Institute for Medical Research) was widely recognized in the field of biochemistry. While in Berlin, Ochoa became interested in the chemical processes involved in muscle contraction, the metabolic role of phosphocreatinine, and the enzymatic mechanisms of metabolic reactions, specifically looking into the sources of energy in muscular contraction in frogs. Still focusing on muscle contraction, Ochoa completed his doctoral thesis in Madrid, writing about the role of adrenal glands on the chemistry of muscular contraction. He was awarded his MD degree in 1931. In the same year, he married Carmen Cobián.
For his post-doctoral work, Ochoa went to London to study enzymes at the National Institute for Medical Research for 2 years. In particular, he conducted research involving the enzyme glyoxalase, which is involved in the oxidation of glucose to lactic acid.
When Ochoa returned to Madrid, a bright career stretched before him at the Instituto de Investigaciones Medicales (Institute for Medical Research) at the medical school of the Universidad de Madrid (University of Madrid). He started off as a lecturer in physiology and biochemistry, then as the director of the physiology section. His stable path at the Instituto was cut off, however, when the Spanish Civil War began.
In 1936, Ochoa embarked on a series of temporary positions during a period he referred to as “the wander years.” He returned to Meyerhof’s laboratory, which had moved to Heidelberg, as a research assistant working on enzymatic steps involved in glycolysis and fermentation. Before too long, however, the unrest preceding the Second World War prompted both Meyerhof and Ochoa to leave Heidelberg. Ochoa found a fellowship at the Marine Biological laboratory in Plymouth, England, in July 1937. As staff at the lab were limited, Ochoa’s wife Carmen assisted him in his work to isolate what came to be known as nicotinamide adenine dinucleotide (NAD). As the fellowship in Plymouth was only for 6 months, Ochoa found another fellowship in December 1937, this time in Oxford, England, to work with Rudolf Albert Peters on the role of thiamine (Vitamin B1) in enzyme action, and of thiamine and adenosine triphosphate (ATP) in cellular respiration.
The disruption of WWII reached Ochoa in England, as well. In 1939, the laboratory in Oxford had to redirect its focus to the war effort. In addition, because Ochoa was not a British citizen, he had to leave. Ochoa contacted Drs. Carl and Gerty Cori and joined them in 1941 as an instructor and research associate in pharmacology at the University of Washington in St. Louis, MO, in the United States. Although his time in St. Louis was short lived, he found stability in New York. In 1942, he became a research associate in medicine at the New York University School of Medicine, working his way up to assistant professor of biochemistry (1945), professor of pharmacology (1946), and professor of biochemistry as well as chair of that department (1954), a position he held for 20 years.
While at NYU and with the assistance of his graduate and post-doctoral students, Ochoa continued to work on metabolism and cellular respiration, especially on the steps involving oxidative phosphorylation (also known as electron transport), CO2 fixation in green plants, and the tricarboxylic acid (TCA) cycle (also known as citric acid cycle or Krebs cycle). In 1946, one of his first post-doctoral students, Arthur Kornberg, assisted Ochoa in the discovery of malic enzyme. Another post-doctoral student, Marianne Grunberg-Manago, joined Ochoa’s team in 1953 and worked on bacterial cells in which they found an enzyme, polynucleotide phosphorylase, which enabled them to synthesize ribonucleic acid (RNA) from ribonucleoside diphosphates in vitro.
Ochoa published the results of this work in 1955, in the J of Am Chem Society. In 1959, Ochoa received the Nobel Prize for Physiology or Medicine for his work contributing to the “discovery of the mechanisms in the biological synthesis or ribonucleic acid and deoxyribonucleic acid.” His co-recipient was his former student, Arthur Kornberg, for his discovery of DNA polymerase in bacteria.
The polynucleotide phosphorylase Ochoa discovered plays a role in the mechanism that converts DNA nucleotides of the genetic code into the functional sequence of amino acids to form a protein. In 1959, Marshall Nirenberg at the National Institutes of Health (NIH) developed a procedure using synthesized mRNA molecules containing amino acids with radioactive labels to determine how DNA information is expressed as protein function. Beginning in 1961, staff at Ochoa’s laboratory at NYU also were working on this topic. Using polynucleotide phosphorylase to generate polyribonucleotides of a known base composition, they experimented to see if amino acids would be incorporated into proteins depending on the specific base composition of polyribonucleotides. The two laboratories entered into friendly competition and, between 1961 and 1963, published a series of papers that fully defined all aspects of the genetic code. Nirenberg and others (but not Ochoa) received the Nobel Prize in 1968 for interpreting the genetic code and its function in protein synthesis. Ochoa continued to work on the mechanisms of protein synthesis.
In 1974, Ochoa retired from NYU and accepted a position at the Roche Institute of Molecular Biology in New Jersey. After 1975, he concurrently held a position at the newly established Instituto de Biología Molecular in Madrid. In Spain, he led a research group including former students César de Haro and José Manuel Sierra, still focused on the mechanisms of protein synthesis.
In 1985, Ochoa retired from the position in New Jersey and returned to live in Madrid. Unfortunately, his wife Carmen died of pneumonia in 1986. After her death, Ochoa refrained from writing for publication. He did, however, continue to participate in conferences and to work with students at the Centro de Biología Molecular in Madrid. In June 1993, the journalist Mariano Gómez Sanchez published a biography of Ochoa entitled “La Emoción de Descubrir” (The Thrill of Discovery). Later that year, Ochoa also died of pneumonia, at the age of 88.
Sources:
en.wikipedia.org “Severo Ochoa”
http://www.britannica.com “Severo Ochoa: Spanish-American Biochemist”
http://www.nobelprize.org “Severo Ochoa: Biographical”
http://www.encyclopedia.com/people/medicine/medicine-briographies/severo-ochoa
Ruiza, M., Fernández, T., Tamaro, E. (2004). http://www.biografiasyvidas.com “Severo Ochoa”
http://www.thefamouspeople.com “Severo Ochoa Biography”
Newton, D. E. (2007). “Ochoa, Severo” in Latinos in Science, Math, and the Professions. New York, NY: Facts on File.
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