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Chain, Ernst Boris (1906-1979)

World of Microbiology and Immunology | 2003 | Copyright 2003 Gale, Cengage Learning. All rights reserved. (Hide copyright information) Copyright

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

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