Severo Ochoa

Spanish-born biochemist Severo Ochoa (1905-1993) spent his life engaged in research into the workings of the human body. In the 1950s, he was one of the first scientists to synthesize the newly discovered ribonucleic acid (RNA) in the laboratory.

Severo Ochoa's ability to synthesize RNA in the laboratory marked the first time that scientists managed to combine molecules together in a chain outside a living organism, knowledge that would later prove to be an essential step in enabling scientists to create life in a test tube. For this work, Ochoa received the Nobel Prize in 1959. In addition to his laboratory work, Ochoa, who was trained as a physician in Spain, taught biochemistry and pharmacology to many generations of New York University medical students.

Severo Ochoa was born on September 24, 1905, in Luarca, a small town in the north of Spain. Named after his father, a lawyer, Ochoa was the youngest son in the family. He lived in this mountain town until the age of seven, when his parents decided to move to Málaga, Spain. The move gave young Severo access to a private school education that prepared him for entrance into Málaga College, which is comparable to an American high school. By this time, Ochoa knew that he eventually would enter a career in the sciences; the only question in his mind was in which field he would specialize. Because Ochoa found mathematics at Málaga College very taxing, he decided against pursuing an engineering career, in which such skills would be essential. Instead, he planned to enter biology. After Ochoa received his B.A. from Málaga in 1921, he spent a year studying the prerequisite courses for medical school, at that time physics, chemistry, biology, and geology. In 1923 he matriculated at the University of Madrid's Medical School.

At Madrid, Ochoa had dreams of studying under the Spanish neurohistologist Santiago Rámon y Cajal, but these were quickly dashed when he discovered that the 70-year-old histology professor had retired from teaching, although he still ran a laboratory in Madrid. Ochoa hesitated to approach Cajal even at the lab, however, because he thought the older man would be too busy to be bothered by an unimportant student. Nonetheless, by the end of his second year in medical school, Ochoa had confirmed his desire to do biological research and jumped at one of his professor's offers of a job in a nearby laboratory.

The Medical School itself housed no research facilities, but Ochoa's physiology teacher ran a small research laboratory under the aegis of the Council for Scientific Research a short distance away. Working with a classmate, Ochoa first mastered the relatively routine laboratory task of isolating creatinine—a white, crystalline compound—from urine. From there he moved to the more demanding task of studying the function and metabolism of creatine, a nitrogenous substance, in muscle. The summer after his fourth year of medical school he spent in a Glasgow laboratory, continuing work on this problem. Ochoa received his medical degree in 1929.

In an attempt to further his scientific education, Ochoa applied for a postdoctoral fellowship working under Otto Meyerhof at the Kaiser-Wilhelm Institute in a suburb of Berlin. Although the Council for Scientific Research had offered him a fellowship to pursue these studies, Ochoa turned down their offer of support because he could afford to pay his own way. He felt the money should be given to someone more needy to himself. Ochoa enjoyed his work under Meyerhof, remaining in Germany for a year.

On July 8, 1931, he married Carmen García Cobian, a daughter of a Spanish lawyer and businessman, and moved with his newlywed wife to England, where he had a fellowship from the University of Madrid to study at London's National Institute for Medical Research. In England Ochoa met Sir Henry Hallett Dale, who would later win the 1936 Nobel in medicine for his discovery of the chemical transmission of nerve impulses. During his first year at the Institute, Ochoa studied the enzyme glyoxalase, and the following year he started working directly under Dale, investigating how the adrenal glands affected the chemistry of muscular contraction. In 1933 he returned to his alma mater, the University of Madrid, where he was appointed a lecturer in physiology and biochemistry.

Within two years, Ochoa accepted a new position. One of the heads of the Department of Medicine was planning to start an Institute for Medical Research with sections on biochemistry, physiology, microbiology, and experimental medicine. The institute would be partially supported by the University of Madrid, which offered it space in one its new medical school buildings, and partially supported by wealthy patrons, who planned to provide a substantial budget for equipment, salaries, and supplies. The director of the new institute offered the young Ochoa the directorship of the section on physiology, which he accepted, and provided him with a staff of three. However, a few months after Ochoa began work, civil war broke out in Spain. In order to continue his work, Ochoa decided to leave the country in September, 1936. He and his wife immigrated to Germany, hardly a stable country itself in late 1936.

When Ochoa arrived, he found that his mentor Meyerhof, who was Jewish, was under considerable political and personal pressure. The German scientist had not allowed this to interfere with his work, though Ochoa did find to his surprise that the type of research Meyerhof conducted had changed dramatically in the six years since he had seen him last. As he wrote of the laboratory in a retrospective piece for the Annual Review of Biochemistry: "When I left it in 1930 it was basically a physiology laboratory; one could see muscles twitching everywhere. In 1936 it was a biochemistry laboratory. Glycolysis and fermentation in muscle or yeast extracts or partial reactions of these processes catalyzed by purified enzymes, were the main subjects of study." Meyerhof's change in research emphasis influenced Ochoa's own work, even though he studied in the laboratory for less than a year before Meyerhof fled to France.

Before Meyerhof left, however, he ensured that his protege was not stranded, arranging for Ochoa to receive a six-month fellowship at the Marine Biological Laboratory in Plymouth, England. Although this fellowship lasted only half a year, Ochoa enjoyed his time there, not the least because his wife Carmen started working with him in the laboratory. Their collaboration later led to the publication of a joint paper in Nature. At the end of six months, though, Ochoa had to move on, and friends at the lab found him a post as a research assistant at Oxford University. Two years later, when England entered the war, Oxford's Biochemistry Department shifted all its efforts to war research in which Ochoa, an alien, could not take part. So in 1940 the Ochoas picked up stakes again, this time to cross the Atlantic to work in the laboratory of Carl Ferdinand Cori and Gerty T. Cori in St. Louis. Part of the Washington University School of Medicine, the Cori lab was renowned for its cutting edge research on enzymes and work with intermediary metabolism of carbohydrates. This work involved studying the biochemical reactions in which carbohydrates produce energy for cellular operations. Ochoa worked there for a year before New York University persuaded him to move east to take a job as a research associate in medicine at the Bellevue Psychiatric Hospital, where he would for the first time have graduate and postdoctoral students working beneath him.

In 1945, Ochoa was promoted to assistant professor of biochemistry at the medical school. Two years later when the pharmacology chair retired, Ochoa was offered the opportunity to succeed him and, lured by the promise of new laboratory space, he accepted. He remained chairperson for nine years, taking a sabbatical in 1949 to serve as a visiting professor at the University of California. His administrative work did not deter him from pursuing his research interests in biochemistry, however. In the early 1950s, he isolated one of the chemical compounds necessary for photosynthesis to occur, triphosphopyridine nucleotide, known as TPN. Ochoa continued his interest in intermediary metabolism, expanding the work of Hans Adolf Krebs, who posited the idea of a cycle through which food is metabolized into adenosine triphosphate, or ATP, the molecule that provides energy to the cell. The Spanish scientist discovered that one molecule of glucose when burned with oxygen produced 36 ATP molecules. When the chairman of the biochemistry department resigned in 1954, Ochoa accepted this opportunity to return to the department full-time as chair and full professor.

Once more ensconced in biochemistry research, Ochoa turned his attentions to a new field: the rapidly growing area of deoxyribonucleic acid (DNA) research. Earlier in his career, enzymes had been the hot new molecules for biochemists to study; now, after the critical work of James Watson and Francis Crick in 1953, nucleic acids were fascinating scientists in the field. Ochoa was no exception. Drawing on his earlier work with enzymes, Ochoa began investigating which enzymes played roles in the creation of nucleic acids in the body. Although most enzymes assist in breaking down materials, Ochoa knew that he was looking for an enzyme that helped combine nucleotides into the long chains that were nucleic acids. Once he isolated these molecules, he hoped, he would be able to synthesize RNA and DNA in the lab. In 1955, he found a bacterial enzyme in sewage that appeared to play just such a role. When he added this enzyme to a solution of nucleotides, he discovered that the solution became viscous, like jelly, indicating that RNA had indeed formed in the dish. The following year, Arthur Kornberg, who had studied with Ochoa in 1946, applied these methods to synthesize DNA.

In 1959, five years after he assumed the directorship of the biochemistry department, Ochoa shared the Nobel Prize for Physiology or Medicine with Kornberg, for their work in discovering the enzymes that help produce nucleic acids. While Ochoa was particularly delighted to share the prize with his old colleague, by this time he was no stranger to academic plaudits. The holder of several honorary degrees from both American and foreign universities, including Oxford, Ochoa had also been the recipient of the Carl Neuberg Medal in biochemistry in 1951 and the Charles Leopold Mayer Prize in 1955. Ochoa served as chairperson of NYU's biochemistry department for 20 years, until the summer of 1974, just before his seventieth birthday. When he retired from this post, he rejected the department's offer to make him an emeritus professor, preferring to remain on staff as a full professor. But even that could not keep Ochoa sufficiently occupied. In 1974, he joined the Roche Institute of Molecular Biology in New Jersey.

In 1985 he returned to his native Spain as a professor of biology at the University Autonoma in Madrid to continue his lifelong fascination with biochemical research. At the age of 75 Ochoa wrote a retrospective of his life, which he titled "Pursuit of a Hobby." In the introduction to this piece, he explained his choice of title: at a party given in the forties in honor of two Nobel laureate chemists Ochoa listed his hobby in the guest register as biochemistry, although he was professor of pharmacology at New York University. Sir Henry Dale, one of the party's honorees, joked, "now that he is a pharmacologist, he has biochemistry as a hobby." Ochoa concluded this tale with the statement, "In my life biochemistry has been my only and real hobby."

Severo Ochoa died in Madrid on November 1, 1993.

Further Reading on Severo Ochoa

Nobel Prize Internet Archive, "http://www.almaz.com/nobel/medicine/1959a.html," Almaz Enterprises, July 22, 1997.

Nobel Prize Winners, H. W. Wilson, 1987.

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