Chain, Ernst Boris (1906-1979)

views updated Jun 27 2018

Chain, Ernst Boris (1906-1979)

Germanborn English biochemist

Ernst Chain was instrumental in the creation of penicillin , the first antibiotic drug. Although the Scottish bacteriologist Alexander Fleming discovered the penicillium notatum mold in 1928, it was Chain who, together with Howard Florey , isolated the breakthrough substance that has saved countless victims of infections. For their work, Chain, Florey, and Fleming were awarded the Nobel Prize in physiology or medicine in 1945.

Chain was born in Berlin to Michael Chain and Margarete Eisner Chain. His father was a Russian immigrant who became a chemical engineer and built a successful chemical plant. The death of Michael Chain in 1919, coupled with the collapse of the postWorld War I German economy, depleted the family's income so much that Margarete Chain had to open up her home as a guesthouse.

One of Chain's primary interests during his youth was music, and for a while it seemed that he would embark on a career as a concert pianist. He gave a number of recitals and for a while served as music critic for a Berlin newspaper. A cousin, whose brotherinlaw had been a failed conductor, gradually convinced Chain that a career in science would be more rewarding than one in music. Although he took lessons in conducting, Chain graduated from FriedrichWilhelm University in 1930 with a degree in chemistry and physiology.

Chain began work at the Charite Hospital in Berlin while also conducting research at the Kaiser Wilhelm Institute for Physical Chemistry and Electrochemistry. But the increasing pressures of life in Germany, including the growing strength of the Nazi party, convinced Chain that, as a Jew, he could not expect a notable professional future in Germany. Therefore, when Hitler came to power in January 1933, Chain decided to leave. Like many others, he mistakenly believed the Nazis would soon be ousted. His mother and sister chose not to leave, and both died in concentration camps.

Chain arrived in England in April 1933, and soon acquired a position at University College Hospital Medical School. He stayed there briefly and then went to Cambridge to work under the biochemist Frederick Gowland Hopkins. Chain spent much of his time at Cambridge conducting research on enzymes . In 1935, Howard Florey became head of the Sir William Dunn School of Pathology at Oxford. Florey, an Australianborn pathologist, wanted a topnotch biochemist to help him with his research, and asked Hopkins for advice. Without hesitation, Hopkins suggested Chain.

Florey was actively engaged in research on the bacteriolytic substance lysozyme, which had been identified by Fleming in his quest to eradicate infection. Chain came across Fleming's reports on the penicillin mold and was immediately intrigued. He and Florey both saw great potential in the further investigation of penicillin. With the help of a Rockefeller Foundation grant, the two scientists assembled a research team and set to work on isolating the active ingredient in Penicillium notatum.

Fleming, who had been unable to identify the antibacterial agent in the mold, had used the mold broth itself in his experiments to kill infections. Assisted in their research by fellow scientist Norman Heatley, Chain and Florey began their work by growing large quantities of the mold in the Oxford laboratory. Once there were adequate supplies of the mold, Chain began the tedious process of isolating the "miracle" substance. Succeeding after several months in isolating small amounts of a powder that he obtained by freezedrying the mold broth, Chain was ready for the first practical test. His experiments with laboratory mice were successful, and it was decided that more of the substance should be produced to try on humans. To do this, the scientists needed to ferment massive quantities of mold broth; it took 125 gallons of the broth to make enough penicillin powder for one tablet. By 1941, Chain and his colleagues had finally gathered enough penicillin to conduct experiments with patients. The first two of eight patients died from complications unrelated to their infections, but the remaining six, who had been on the verge of death, were completely cured.

One potential use for penicillin was the treatment of wounded soldiers, an increasingly significant issue during the Second World War. For penicillin to be widely effective, however, the researchers needed to devise a way to massproduce the substance. Florey and Heatley went to the United States in 1941 to enlist the aid of the government and of pharmaceutical houses. New ways were found to yield more and stronger penicillin from mold broth, and by 1943, the drug went into regular medical use for Allied troops. After the war, penicillin was made available for civilian use. The ethics of whether to make penicillin research universally available posed a particularly difficult problem for the scientific community during the war years. While some believed that the research should not be shared with the enemy, others felt that no one should be denied the benefits of penicillin. This added layers of political intrigue to the scientific pursuits of Chain and his colleagues. Even after the war, Chain experienced firsthand the results of this dilemma. As chairman of the World Health Organization in the late 1940s, Chain had gone to Czechoslovakia to supervise the operation of penicillin plants established there by the United Nations. He remained there until his work was done, even though the Communist coup occurred shortly after his arrival. When Chain applied for a visa to visit the United States in 1951, his request was denied by the State Department. Though no reason was given, many believed his stay in Czechoslovakia, however apolitical, was a major factor.

After the war, Chain tried to convince his colleagues that penicillin and other antibiotic research should be expanded, and he pushed for more state-of-the-art facilities at Oxford. Little came of his efforts, however, and when the Italian State Institute of Public Health in Rome offered him the opportunity to organize a biochemical and microbiological department along with a pilot plant, Chain decided to leave Oxford.

Under Chain's direction, the facilities at the State Institute became known internationally as a center for advanced research. While in Rome, Chain worked to develop new strains of penicillin and to find more efficient ways to produce the drug. Work done by a number of scientists, with Chain's guidance, yielded isolation of the basic penicillin molecule in 1958, and hundreds of new penicillin strains were soon synthesized.

In 1963, Chain was persuaded to return to England. The University of London had just established the Wolfson Laboratories at the Imperial College of Science and Technology, and Chain was asked to direct them. Through his hard work the Wolfson Laboratories earned a reputation as a firstrate research center.

In 1948, Chain had married Anne Beloff, a fellow biochemist, and in the following years she assisted him with his research. She had received her Ph.D. from Oxford and had worked at Harvard in the 1940s. The couple had three children.

Chain retired from Imperial College in 1973, but continued to lecture. He cautioned against allowing the then-new field of molecular biology to downplay the importance of biochemistry to medical research. He still played the piano, for which he had always found time even during his busiest research years. Over the years, Chain also became increasingly active in Jewish affairs. He served on the Board of Governors of the Weizmann Institute in Israel, and was an out-spoken supporter of the importance of providing Jewish education for young Jewish children in England and abroadall three of his children received part of their education in Israel.

In addition to the Nobel Prize, Chain received the Berzelius Medal in 1946, and was made a commander of the Legion d'Honneur in 1947. In 1954, he was awarded the Paul Ehrlich Centenary Prize. Chain was knighted by Queen Elizabeth II in 1969. Chain died of heart failure at age 73.

See also Antibiotic resistance, tests for; Bacteria and responses to bacterial infection; Chronic bacterial disease; Staphylococci and staphylococcal infections

Chain, Ernst Boris

views updated Jun 11 2018

CHAIN, ERNST BORIS

(b. Berlin, Germany, 19 June 1906; d. Mulranny. Ireland, 12 August 1979)

biochemistry.

Chain was the son of Russian-born Michael Chain, an industrialist, and Margarete Eisner, both of Jewish descent. The Chains also had a daughter, Hedwig. Michael Chain studied chemistry in Berlin, where he later established a firm that produced sulfates Ernst Chain developed an early interest in chemistry. most likely because of this close industrial connection. Chain also had a strong interest in a career in music; he was an accomplished pianist and music critic for a Berlin paper.

Chain graduated in chemistry and physiology from the Friedrich-Wilhelm University in 1930 and received a D.Phil, degree from the chemical department of the Institute of Pathology at the Charité Hospital for his work on enzymes. Three months after Hitler assumed the chancellorship of Germany in January 1933, Chain immigrated to England, alone, and became a naturalized citizen six years later. His mother and sister remained in Germany, presumably for financial reasons, since the family had fallen into debt after Michael Chain’s death in 1919. Chain tried to assist them, although his own financial circumstances in England were difficult. Margarete and Hedwig eventually died in the Nazi holocaust Chain began work under Frederick Gowland Hopkins in the department of biochemistry at Cambridge in October 1933 and received a Ph.D. for research on phospholipids. In 1935 Howard W. Florey, professor of pathology at Oxford, invited Chain (on Hopkins’ recommendation) to organize a biochemical section in the Sir William Dunn School of Pathology,

Chain pursued a wide range of research topics during his career, from general enzymology during his early days in Berlin and England, to phytotoxins, carbohydrate metabolism, fermentation production of ergot alkaloids, and other subjects later in life. His most significant work—the research for which he received a Nobel Prize in medicine with Florey and bacteriologist Alexander Fleming in 1945— concerned penicillin. In the late 1930’s, Florey and Chain began their investigation of this mold broth filtrate from Penicillium notatum as part of their general interest in systemic antibacterial agents. Fleming had isolated penicillin in 1928. He found it was a promising external antiseptic against some pathogenic bacteria, but its chemical instability (among other reasons) soon led him to abandon penicillin as a therapeutic agent.

By May 1940 Chain had produced enough penicillin for Florey to conduct tests on mice infected with deadly hemolytic streptococci. These early tests yielded very promising results, Chain, in collaboration with Edward Abraham, spent the rest of the year improving the extraction and purification of penicillin for clinical tests, which began early in 1941.

Serious problems with the fermentation production of penicillin led the British and American governments, by early 1944. to coordinate hundreds of scientists for the development of a commercially feasible synthesis of penicillin. Chain and his collaborators at Oxford, however, had shed much light on the chemistry of the drug by this time. They had determined the structures and syntheses of the two compounds produced by the acid hydrolysis of the penicillin molecule. Also, they had discovered the structure of the intermediate compound between these two degradation products and penicillin. By October 1943, they proposed what turned out to be the correct structure of penicillin. That the massive penicillin project failed to produce a practical synthesis of the drug was academic, because workers succeeded in producing penicillin by fermentation, on a mass scale. Yet this development did not diminish the significance of the contributions of Chain and his colleagues. They established a fundamental understanding of the chemistry of penicillin. This aided fermentation work on the drug in the 1940’s and served as the foundation for the development of semisynthetic penicillins from the mid 1950’s on.

In 1948 Chain left Oxford to organize the International Centre for Chemical Microbiology at the Istituto Superiore di Sanità in Rome. Before moving, he married biochemist Anne Beloff, with whom he collaborated on many projects during the remainder of his career. (They had two sons and a daughter.) The center developed into a training ground for researchers interested in production of antibiotics. Thus, a microbiologist and a biochemist from the British pharmaceutical firm Beecham spent a year at the center (1956–1957) to learn how to produce penicillin. Chain, who was a consultant to Beecham. had the visiting scientists acquaint themselves with the production of a penicillin that he believed would lend itself to chemical modification, so that new penicillin. could he tailored to meet specific therapeutic needs. Chain’s later involvement with this work is not clear, but by 1957 Beecham scientists in England identified the nucleus of the penicillin molecule in their fermentation broth. Beecham soon learned how to produce this compound in large quantities. The ability to produce the penicillin nucleus on a mass scale, coupled with the earlier discovery, by chemist John C. Sheehan at MIT, of a method to add chemical side chains to this nucleus, created the framework for a new era in the history of penicillin—the era of semisynthetic penicillins.

Chain contributed to a number of fields in addition to penicillin research. Soon after arriving in Rome, he and his colleagues at the center began a project on carbohydrate metabolism. This research illuminated the role of insulin in some metabolic pathways in various tissues. Chain also advanced fermentation methods to produce therapeutically useful alkaloids from the ergot fungus in high yield.

Chain continued this work and initiated some new projects after he moved back to England in 1964 to become chairman of the department of biochemistry at Imperial College of Science and Technology in London. He and associates in the biochemistry and chemistry departments investigated the action of fusicoccins, plant toxins that cause wilting, and they established the chemical structures of several of these toxins. Chain also helped clarify the biochemistry of the myocardium, particularly in cases where the heart was deprived of oxygen, as in cardiac arrest. He and his colleagues in the biochemistry department found that unless the arrested heart was perfused with a glucose solution, other cellular energy reserves, such as adenosine triphosphate and creatine phosphate, would be depleted to levels that would hamper the heart’s recovery. In the 1970’s Chain and a group of chemists and biochemists investigated a new antibiotic from the soil microorganism Pseu domonas fluorescens. which they called pseudomonic acid. The antibiotic was active against several pathogens, but it was too toxic for clinical application.

Chain was active in many fields, but his greatest contribution to science and medicine was the introduction and development of penicillin. For this work he received many honorary degrees, prestigious scientific prizes, and a knighthood.

BIBLIOGRAPHY

I. Original Works. On the contributions of Chain and his Oxford colleagues to the introduction of penicillin, see “Penicillin as a Chemotherapeutic Agent,” in Lancet (1940), 2 , 226–228. with H. W. Florey et al, ;“Further Observations on Penicillin,” ibid., (1941), 2, 177–189, with E. P. Abraham et al; “Purification and Some Physical and Chemical Properties of Penicillin,” in British Journal of Experimental Pathology, 23 (1942). 103–115, with E. P. Abraham: and “The Earlier Investigations Relating to 2-Pentenylpenicillin,” in Hans T. Clarke. John K Johnson. and Robert Robinson, eds. The Chemistry of Penicillin (Princeton, 1949), 10–37. with E. P. Abraham et.al. Chain coauthored several papers with scientists from Beecham Laboratories on the isolation of the nucleus of penicillin and its conversion to new penicillins, including “Penicillin Derivatives of p Aminobenzylpenicillin,” in Nuture. 183 (1959), 180–181, with A. Ballio et al, ; and a series of six articles in Proceedings of the Royal Society of London, B154 (1961) 478–531.

Among Chain’s principal publications on carbohydrate metabolism and the action of insulin are two series of papers that he published with his associates at the Istituto Superiore di Sanità in. Selected Scientific Papers from the Istituto Superiore di Sanità. 1 (1956), 293–535, and 2 (1959), 109–149; and “Recent Studies on Carbohydrate Metabolism,” in British Medical Journal (1959). 2, 709–719, He reported his work on the production of ergot alkaloids in “Production of a New Lysergic Acid Derivative in Submerged Culture by a Strain of Claviceps paspali Stevens & Hall,” in Proceedings of the Royal Society of London, B155 (1962), 26–54, with F. Arcamone et al: and Biosynthesis of Ergotamine by Claviceps purpurea (Fr.) Tul.,” in Biochemical Journal. 134 (1973). 1–10, with R. A. Bassetl and K. Corbett.

Chain’s research on the production and chemical resolution of phytotoxins from Fusicoccum appeared in “Fusicoccin: A New Wilting Toxin Produced by Fusi coccum amygdale Del.,” in Nature, 203 (1964), 297. with A. Ballio et al: and a series of four articles he published with his colleagues in chemistry and biochemistry at Imperial College in Journal of the Chemical Sciety. Section C (1971), 1259–1274: and Journal of the Chemical Society: Perkin Transactions I (1973). 1590–1599. and (1975). 877–883.

Signal publications by Chain on cardiac metabolism include “Effects of Insulin on the Pattern of Glucose Metabolism in the Perfused Working and Langendorff Heart of Normal and Insulin-Deficient Rats,” in Biochemical Journal, 115 (1969). 537–546. with K. R. L. Mansford and L. H. Opie; “The Role of Glucose in the Survival and ‘Recovery’ of the Anoxic Isolated Perfused Rat Heart,” ibid., 128 (1972), 1125–1133 with D. J Hearse; and “Recovery from Cardiac Bypass and Elective Cardiac Arrest; The Metabolic Consequences of Various Cardioplegic Procedures in the Isolated Rat Heart,” in Circulation Research. 35 (1974). 448–457. with David J. Hearse and David A. Stewart.

On Chain’s pseudomonic acid research, see “Pseudomonic Acid: An Antibiotic Produced by Pseudomonas fluorescens.” in Nature234 (1971) 416 -417. with A. T. Fuller et al; and a series of three papers that he published with co-workers from Imperial College in Journal of the Chemical Society: Perkin Transactions I (1977) 294–322.

Also useful are “Penicillinase-Resistant Penicillins and the Problem of the Penicillin-Resistant Staphylococci”in Anthony V. S, de Rueck and Margaret Cameron, eds., Resistance of Bacteria to the Penicillins (Buston. 1962). 3–24; and “A Short History of the Penicillin Discovery from Fleming’s Early Observations in 1929 to the Present Time,” in John Parascandola ed. The History of Antibiotics: A Symposium (Madison, Wis. 19801, 15–29.

II. Secondary Literature. The most comprehensive biography of Chain is Ronald W. Clark, The Life of Ernst Chain: Penicillin and Beyond (New York. 1985). More useful on Chain’s scientific work is Edward Abraham, “Ernst Boris Chain”in Biographical Memoirs of Fellows of the Royal Society. 29 (1983), 43–91. Several sources discuss Chains work on penicillin, the most detailed of which is Howard W. Florey et al., Antibiotics 2 vols. (London, 1949). Also useful is John Patrick Swann, “The Search for Synthetic Penicillin During World War 11.” British Journal for the History of Science 16 (1983). 154 190. John C. Sheehan. The Enchanted Ring: The Untold Story of Penicillin (Cambridge. Mass. 1982), discusses the emergence of the semisynthetic penicillins.

John Patrick Swann

Ernst Boris Chain

views updated May 14 2018

Ernst Boris Chain

Ernst Boris Chain (1906-1979) was instrumental in the creation of penicillin, the first antibiotic drug.

Ernst Boris Chain was instrumental in the creation of penicillin, the first antibiotic drug. Although the Scottish bacteriologist Alexander Fleming discovered the penicillium notatum mold in 1928, it was Chain who, together with Howard Florey, isolated the breakthrough substance that has saved countless victims of infections. For their work, Chain, Florey, and Fleming were awarded the Nobel Prize in physiology or medicine in 1945.

Chain was born in Berlin on June 19, 1906 to Michael Chain and Margarete Eisner Chain. His father was a Russian immigrant who became a chemical engineer and built a successful chemical plant. The death of Michael Chain in 1919, coupled with the collapse of the post-World War I German economy, depleted the family's income so much that Margarete Chain had to open up her home as a guesthouse.

One of Chain's primary interests during his youth was music, and for a while it seemed that he would embark on a career as a concert pianist. He gave a number of recitals and for a while served as music critic for a Berlin newspaper. A cousin, whose brother-in-law had been a failed conductor, gradually convinced Chain that a career in science would be more rewarding than one in music. Although he took lessons in conducting, Chain graduated from Friedrich-Wilhelm University in 1930 with a degree in chemistry and physiology.

Chain began work at the Charite Hospital in Berlin while also conducting research at the Kaiser Wilhelm Institute for Physical Chemistry and Electrochemistry. But the increasing pressures of life in Germany, including the growing strength of the Nazi party, convinced Chain that, as a Jew, he could not expect a notable professional future in Germany. Therefore, when Hitler came to power in January 1933, Chain decided to leave. Like many others, he mistakenly believed the Nazis would soon be ousted. His mother and sister chose not to leave, and both died in concentration camps.

Chain arrived in England in April 1933, and soon acquired a position at University College Hospital Medical School. He stayed there briefly and then went to Cambridge to work under the biochemist Frederick Gowland Hopkins. Chain spent much of his time at Cambridge conducting research on enzymes. In 1935, Howard Florey became head of the Sir William Dunn School of Pathology at Oxford. Florey, an Australian-born pathologist, wanted a top-notch biochemist to help him with his research, and asked Hopkins for advice. Without hesitation, Hopkins suggested Chain.

Florey was actively engaged in research on the bacteriolytic substance lysozyme, which had been identified by Fleming in his quest to eradicate infection. Chain came across Fleming's reports on the penicillin mold and was immediately intrigued. He and Florey both saw great potential in the further investigation of penicillin. With the help of a Rockefeller Foundation grant, the two scientists assembled a research team and set to work on isolating the active ingredient in penicillium notatum.

Fleming, who had been unable to identify the antibacterial agent in the mold, had used the mold broth itself in his experiments to kill infections. Assisted in their research by fellow scientist Norman Heatley, Chain and Florey began their work by growing large quantities of the mold in the Oxford laboratory. Once there were adequate supplies of the mold, Chain began the tedious process of isolating the "miracle" substance. Succeeding after several months in isolating small amounts of a powder which he obtained by freeze-drying the mold broth, Chain was ready for the first practical test. His experiments with laboratory mice were successful, and it was decided that more of the substance should be produced to try on humans. To do this, the scientists needed to ferment massive quantities of mold broth; it took 125 gallons of the broth to make enough penicillin powder for one tablet. By 1941 Chain and his colleagues had finally gathered enough penicillin to conduct experiments with patients. The first two of eight patients died from complications unrelated to their infections, but the remaining six, who had been on the verge of death, were completely cured.

One potential use for penicillin was the treatment of wounded soldiers, an increasingly significant issue during the Second World War. However, for penicillin to be widely effective, the researchers needed to devise a way to mass-produce the substance. Florey and Heatley went to the United States in 1941 to enlist the aid of the government and of pharmaceutical houses. New ways were found to yield more and stronger penicillin from mold broth, and by 1943 the drug went into regular medical use for Allied troops. After the war, penicillin was made available for civilian use. The ethics of whether to make penicillin research universally available posed a particularly difficult problem for the scientific community during the war years. While some believed that the research should not be shared with the enemy, others felt that no one should be denied the benefits of penicillin. This added layers of political intrigue to the scientific pursuits of Chain and his colleagues. Even after the war, Chain experienced firsthand the results of this dilemma. As chairman of the World Health Organization in the late 1940s, Chain had gone to Czechoslovakia to supervise the operation of penicillin plants established there by the United Nations. He remained there until his work was done, even though the Communist coup occurred shortly after his arrival. When Chain applied for a visa to visit the United States in 1951, his request was denied by the State Department. Though no reason was given, many believed his stay in Czechoslovakia, however apolitical, was a major factor.

After the war, Chain tried to convince his colleagues that penicillin and other antibiotic research should be expanded, and he pushed for more state-of-the-art facilities at Oxford. Little came of his efforts, however, and when the Italian State Institute of Public Health in Rome offered him the opportunity to organize a biochemical and microbiological department along with a pilot plant, Chain decided to leave Oxford.

Under Chain's direction, the facilities at the State Institute became known internationally as a center for advanced research. While in Rome, Chain worked to develop new strains of penicillin and to find more efficient ways to produce the drug. Work done by a number of scientists, with Chain's guidance, yielded isolation of the basic penicillin molecule in 1958, and hundreds of new penicillin strains were soon synthesized.

In 1963 Chain was persuaded to return to England. The University of London had just established the Wolfson Laboratories at the Imperial College of Science and Technology, and Chain was asked to direct them. Through his hard work the Wolfson Laboratories earned a reputation as a first-rate research center.

In 1948, Chain had married Anne Beloff, a fellow biochemist, and in the following years she assisted him with his research. She had received her Ph.D. from Oxford and had worked at Harvard in the 1940s. The couple had three children.

Chain retired from Imperial College in 1973 but continued to lecture. He cautioned against allowing the then-new field of molecular biology to downplay the importance of biochemistry to medical research. He still played the piano, for which he had always found time even during his busiest research years. Over the years, Chain also became increasingly active in Jewish affairs. He served on the Board of Governors of the Weizmann Institute in Israel, and was an outspoken supporter of the importance of providing Jewish education for young Jewish children in England and abroad—all three of his children received part of their education in Israel.

In addition to the Nobel Prize, Chain received the Berzelius Medal in 1946 and was made a commander of the Legion d'Honneur in 1947. In 1954 he was awarded the Paul Ehrlich Centenary Prize. Chain was knighted by Queen Elizabeth II in 1969. Increasing ill health did not slow Chain down initially, but he finally died of heart failure on August 12, 1979.

Further Reading

Clark, Ronald, The Life of Ernst Chain, St. Martin's, 1985.

Curtis, Robert H., Great Lives: Medicine, Scribner, 1993, pp. 77-90.

Chain, Benjamin, "Penicillin and Beyond," Nature, October 10, 1991, pp. 492-94. □

Ernst Boris Chain

views updated May 23 2018

Ernst Boris Chain

1906-1979

German Biochemist

In 1945 Ernst Boris Chain shared the Nobel Prize in physiology or medicine for 1945 with Alexander Fleming and Howard Walter Florey "for the discovery of penicillin and its curative effect in various infectious diseases." Fleming had discovered the antibacterial action of the penicillium mold in 1928, but Chain and Florey recognized its therapeutic powers in 1940 and went on to isolate and purify penicillin. Although Fleming noted that his crude penicillin preparation was nontoxic when injected into mice, he did not carry out experiments to determine whether it would actually cure mice that had been infected with a virulent bacterium, such as streptococcus.

Chain, the son of Michael Chain, a chemist and industrialist, was born in Berlin. Chain became interested in chemistry while he was a student at the Luisengymnasium in Berlin. Both his teachers and his visits to his father's workplace stimulated his interest in chemistry and biochemistry. He graduated from the Friedrich-Wilhelm University in 1930 and spent the next three years carrying out research on enzymes at the Charité Hospital in Berlin. In 1933, when the Nazi regime assumed power in Germany, he immigrated to England. (Unfortunately, his mother and sister were not able to follow him and both died in concentration camps.) He worked on phospholipids at the School of Biochemistry at Cambridge University under the direction of Sir Frederick Gowland Hopkins for two years before transferring to Oxford University in 1935. Here, he worked as a demonstrator and lecturer in chemical pathology at the Sir William Dunn School of Pathology. In 1948 he was appointed the scientific director of the International Research Center for Chemical Microbiology at the Superior Institute of Health (Istituto Superiore di Sanità) in Rome. In 1961 he became a professor of biochemistry at Imperial College in London.

In 1939 Chain and Florey began a systematic study of antibacterial substances produced by microorganisms. This work led to the discovery of the chemotherapeutic action of penicillin. Chain's work was critical to the next stage of this research, the isolation and elucidation of the chemical structure of penicillin and other natural antibiotics. Chain and Florey began their work on penicillin in order to find out whether penicillin preparations contained enzymes that could break down (lyse) bacterial walls. They thought that penicillin might actually be similar to lysozyme, a lytic enzyme that Fleming had discovered before he discovered penicillin. Chain and Florey later said that they had not considered the possibility that penicillin could have practical uses in clinical medicine when they began to work on penicillin. Their research on penicillin began in 1938, before the outbreak of World War II. Although penicillin proved to be a valuable chemotherapeutic agent for the treatment of infected war wounds and venereal disease, Chain emphasized that only purely scientific curiosity had motivated him to begin studying penicillin.

Although he is primarily remembered for his landmark work on penicillin, his research interests were very broad and he made significant contributions to the knowledge of snake venoms, tumor metabolism, the mechanism of lysozyme action, the carbohydrate-amino acid relationship in nervous tissue, the mode of action of insulin, fermentation technology, 6-aminopenicillanic acid and penicillinase-stable penicillins, lysergic acid production in submerged culture, the isolation of new fungal metabolites, and biochemical microanalysis.

Chain was author or co-author of many scientific papers and classic monographs on penicillin and antibiotics. In addition to the Nobel Prize, he received many honorary degrees and awards, including the Silver Berzelius Medal of the Swedish Medical Society, the Pasteur Medal of the Pasteur Institute and the Societé de Chimie Biologique, the Paul Ehrlich Centenary Prize, and the Gold Medal for Therapeutics of the Worshipful Society of Apothecaries of London. He was also a member or fellow of many learned societies in various countries. Chain married Anne Beloff in 1948. They had a long and happy marriage that was productive both in terms of collaborative research in biochemistry and a supportive family life.

LOIS N. MAGNER

Chain, Ernst Boris

views updated May 21 2018

Chain, Ernst Boris

Ernst Boris Chain (1906-1979) was one of three men (Australian biochemist Howard Walter Florey and Scottish chemist Alexander Fleming completed the trio) who discovered and developed the first antibiotic, penicillin. Chain's parents were Russian Jews who had emigrated to Berlin, Germany. He was educated at a Gernan university, but emigrated to Britain in 1933 to work at Cambridge University, where he studied enzymes and molds. His first discovery was about the behavior of bacteria. Chain found that they helped to spread infections by excreting an enzyme.

Chain began his collaboration with Florey (1898-1968) in 1939. Chain had noticed Fleming's (1881-1955) writings about how molds, essential to the development of penicillin, had killed bacteria in one of his sample dishes. Unfortunately, Fleming had not found a way to purify or concentrate his discovery. By 1941 Chain and Florey had accomplished what Fleming had not be able to do: isolate and test penicillin on humans. The results of the tests were outstanding, and mass production of penicillin soon followed. Chain also discovered that bacteria could develop a resistance to penicillin, so he worked on the development of other antibiotics as well.

After he shared the 1945 Nobel Prize with Florey and Fleming, Chain noticed that many post-war universities had gone back to an atmosphere of competitive, secretive research, which he did not like. In response he started two new research institutions, one in Rome and one in London, which maintained an atmosphere of cooperation and openness, thus setting the trend for our international research collaborations of today.

[See also Enzyme ]

Chain, Sir Ernst Boris

views updated May 17 2018

Chain, Sir Ernst Boris (1906–79) German-born British biochemist, who began his research career at Cambridge University in 1933. Two years later he joined Florey at Oxford, where they isolated and purified penicillin. They also developed a method of producing the drug in large quantities and carried out its first clinical trials. The two men shared the 1945 Nobel Prize for physiology or medicine with penicillin's discoverer, Alexander Fleming.

Chain, Sir Ernst Boris

views updated Jun 11 2018

Chain, Sir Ernst Boris (1906–79) British biochemist, b. Germany. He shared the 1945 Nobel Prize in physiology or medicine with Howard Florey and Alexander Fleming for the isolation and development of penicillin as an antibiotic. He also studied spreading factor, an enzyme that aids the dispersal of fluids in tissue.