Chain, EB

NAME: Chain, Sir Ernst Boris

ACHIEVEMENT(S): Penicillin

NICKNAME/ALIAS: None

DATE/PLACE OF BIRTH: 19 June 1906, at Berlin, Germany

DATE/PLACE/AGE AT DEATH: 12 August 1979, in Mulranny, Co. Mayo, Ireland.  Aged 73

DISCIPLINE: Biochemist

FIELD: Medicine

LANGUAGE: English and German

PARENTS: Michael Chain (d. 1919) and Margarete Eisner

SIBLINGS: Hedwig

SPOUSE: Anne Beloff, married 1948

CHILDREN: Two sons and a daughter

EDUCATION: Luisengymnasium, Berlin, 1918-24; Friedrich Wilhelm University,

Berlin, 1924-30

MAJOR WORK: "Pencillin as a Chemotherapeutic Agent" (with H.W. Florey and

others, in 'The Lancet'), 1940

LIFE AND TIMES: Soon after graduating Chain began work in the chemical department of the Institute of Pathology at the Charite Hospital in Berlin, while also conducting research at the Kaiser Wilhelm Institute for Physical Chemistry and Electrochemistry.

In April 1933, after receiving a D.Phil. for his work on enzymes from the

Institute of Pathology. 

When Hitler took power three months earlier, Chain decided to move temporarily to England, mistakenly assuming that Hitler would soon be ousted.  His mother and sister remained, and later died in concentration camps.

Soon after his arrival in England, Chain first got a job at University College Hospital Medical School in London, but in October 1933 moved to the University of Cambridge, where he began work in the department of biochemistry under Frederick Gowland Hopkins*.  At Cambridge, Chain spent the next 18 months conducting research on enzymes, and received a Ph.D. for his research on phospholipids.

In 1935, he was recommended by Hopkins to the new head of the School of Pathology at the University of Oxford, Florey*, who believed that experimental pathology would greatly benefit from the collaboration of pathologists with chemists, and was looking for a talented biochemist to join his staff. As a result, in 1935 Chain became University Demonstrator and Lecturer in Chemical Pathology at Oxford, and began to assist Florey in his research on the bacteriolytic substance lysozyme, which is present in tears, nasal secretion and egg white, and which was first identified in 1920 by the bacteriologist Alexander Fleming.

In 1937, while investigating the bacteria-digesting properties of lysozyme,

Chain found Alexander Fleming's* note (1928) that the mold  'penicillium

notatum' inhibits bacterial growth. Chain and Florey were immediately intrigued by the potential of this mold, and the following year, with the aid of a Rockefeller Foundation grant, they assembled a research team and began to try and isolate and identify the antibacterial agent.

With the aid of fellow scientist Norman Heatley, Chain and Florey began their work by growing large quantities of the mold in the Oxford laboratory from which, over a period of several months, Chain then painstakingly isolated small amounts of powder which he

obtained by freeze-drying the mold broth. In the spring of 1940 Chain had sufficient powder to do the first practical test, which showed that preparations of penicillin that were no more than 1 per cent pure would protect laboratory mice from infections with streptococci and staphylococci when introduced into the blood stream.

This dramatic result provoked Florey to place the highest priority on the  production of sufficient penicillin in the laboratory to allow for a small clinical trial. To do this, massive quantities of mold broth had to be fermented (it took 125 gallons of the broth to make enough penicillin powder for one tablet), while Chain, in collaboration with Edward Abraham, concentrated on improving the extraction and purification of penicillin for clinical testing. 

Chain discovered that the optimum time for extraction of the penicillin is when the mold is one week old, and that free penicillin is acidic and more soluble in certain organic solvents than it is in water. The process he then developed involved agitating the penicillin broth with acidified ether or amyl acetate, then reducing the acidity of the solution until it was almost neutral, removing all impurities, and then evaporating the purified solution at a low temperature in order to give a stable form of the active substance.

Chain and Abraham then found that 1mg of the active substance they had obtained contained between 40 and 50  units of penicillin and that, in a concentration of only 1 part per million, it was still able to destroy staphylococcus bacteria.   They also showed that their purified penicillin was only minimally toxic, and that its antibacterial effect was not diminished by the presence of blood or pus.

Clinical tests began early in 1941, with penicillin given to eight seriously-ill patients.  Two died from complications unrelated to their infections, but the remaining six, who had been on the verge of death, were completely cured. One immediate use for penicillin was the treatment of wounded soldiers in World War II but, for penicillin to be widely effective, the researchers needed to mass-produce the substance.

Florey and Heatley went to the United States in 1941 and by 1943 hundreds of scientists in Britain and America had been coordinated for the development of a commercially feasible synthesis of penicillin.  Although these efforts failed to produce a practical synthesis of the drug (which was not achieved until the mid-1950s), new ways were found to yield more and stronger penicillin from the mold broth, and by 1943 the drug went into regular medical use for Allied troops.

After the war, Chain worked hard to convince his colleagues that penicillin and other antibiotic research should be expanded, and he pushed for more investment in the facilities at Oxford. However, he was largely unsuccessful, and when in 1948 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 International Research Centre for Chemical Microbiology became internationally renowned as a centre for advanced research, and here during the 1950s Chain worked to develop new strains of penicillin and to find more efficient ways to produce the drug. His research team eventually isolated the basic penicillin molecule in 1958, and hundreds of new penicillin strains were soon synthesized in large

quantities.

ASSESSMENT: For their pioneering work on penicillin Chain, Florey, and Fleming shared the 1945 Nobel Prize for Physiology or Medicine.

EXTRA CONNECTIONS: None

ONELINER: Ernst Chain, penicillin pioneer

BIBLIOGRAPHY:

EB, DSB, DNB

Clark, Ronald W., The Life of Ernst Chain: Penicillin and Beyond, New  York & London: St. Martin's, 1985

Milite, George A., "Ernst Boris Chain", in Notable 20th Century  Scientists, ed. Emily J. McMurray, New York & London:  Gale Research Inc., 1995