While the name of Sir Alexander Fleming will always be synonymous with the discovery of penicillin, Norman Heatley, who has died aged 92, worked on the purification and extraction of sufficient quantities of penicillin to perform the first clinical trials. Heatley was the last surviving member of the team of Oxford scientists who eventually recognised the potential of Fleming's discovery and, with great difficulty, managed to produce enough penicillin to conduct the trials that established it as the miracle drug of the 20th century. Without this work, it is unlikely that the commercial potential of penicillin would ever have been realised.
Heatley was born in Woodbridge, Suffolk, where, as a boy, his great passion was sailing on the River Deben in a small boat. He attended Tonbridge School, where, inspired by a chemistry teacher who, he said, had the "skills of a conjuror", he developed an interest in biochemistry.
After graduating in natural sciences at St John's College, Cambridge, in 1933 he obtained his PhD from Cambridge in 1936, and was invited to join a team of scientists in Oxford working under the dynamic Australian pathologist Howard Florey. The team, unusually for those days, brought together a group of scientists with very different backgrounds, including the flamboyant east European chemist Ernst Chain, and Heatley, the young, taciturn biochemist.
Alexander Fleming's discovery of penicillin in 1929 had largely been by accident. A forgotten culture plate had grown a big blob of green mould. In between the mould and clumps of yellow bacteria lay a host of dead microbes. Something emanating from the mould had apparently killed them. Fleming named his discovery penicillin, but concluded that it had little use or application. After publishing a vague academic paper about its laboratory properties, he soon moved on. For 10 years penicillin was forgotten.
When Heatley and the other members of Florey's team recognised the potential of Fleming's discovery, it proved, however, extremely difficult to reproduce the mould Fleming had discovered by accident. Not only was the right mould terribly elusive, it also proved very difficult to get the active ingredient out of the liquid which the mould produced. Only one part in two million is penicillin, and separating penicillin from the impurities was to prove a highly complex procedure. It was also wartime, which meant that research funds were scarce, equipment difficult to get hold of, and air raids a constant threat.
The breakthrough finally occurred when Heatley came up with the ingenious suggestion of transferring the penicillin back into water by changing the acidity. Even then, the penicillin produced still contained masses of impurities. Having extracted a small amount, the team then set about cultivating sufficient quantities to conduct trials on animals. Then, in May 1940, trials were conducted on eight mice. In meticulous handwriting, Heatley recorded the process in his diary: "After supper with some friends, I returned to the lab and met the professor to give a final dose of penicillin to two of the mice. The 'controls' were looking very sick, but the two treated mice seemed very well. I stayed at the lab until 3.45am, by which time all four control animals were dead." Typically low key, Heatley's diary entry notes merely that when he got home he discovered that he had put his underpants on back to front in the dark, merely adding: "It really looks as if penicillin may be of practical importance."
The team were all delighted with the results of the trial, and began looking ahead to testing penicillin on man; but a man is 3,000 times bigger than a mouse, and this meant dramatically increasing production of penicillin. The first problem was what to grow the mould in. Once again Heatley's Heath Robinson skills came crucially into play.
Always inventive, he pressed into service all kinds of lab glass, bottles and containers - some of which he found on Oxford rubbish dumps - but the most effective vessel proved to be porcelain bedpans from the Radcliffe Infirmary. However, only 16 were available, so Heatley set about designing his own version, which became known as the "penicillin bedpan". Made in slipware in the Potteries, 170 of these vessels, stacked on top of each other, turned the Oxford laboratory into a virtual penicillin factory.
Within a year of the mouse trials, sufficient penicillin was being harvested to treat a few human beings. The first patient was a 43-year old policeman who was dying of septicaemia. The drug was so scarce that a doctor would cycle from the hospital to the lab every day with the patient's urine, so that the excreted penicillin could be extracted and reused.
The supplies of penicillin ran out before the patient was cured and sadly he died. But there was no doubt from the dramatic initial results that penicillin was a new and potent cure for bacterial infections.
Florey, however, hated any publicity, and feared that Heatley and the other team members would be plagued by desperate relatives of dying patients if news got out of the progress they were making. For generations brought up post-penicillin, it is hard to remember that before antibiotics many infections were lethal. They were feared as cancer and heart disease are today. But Professor Fleming, backed by the press baron and sometime cabinet minister Lord Beaverbrook, welcomed the media attention at St Mary's Hospital Paddington, the site of his 1928 observation. The association of Fleming's name with penicillin was now permanently established.
Florey and his team soon realised that penicillin could have an effect on the outcome of the war, and made plans to increase production as rapidly as possible. Mind ful of the threat of a German invasion, Heatley always enjoyed describing how he hid penicillin spores in his clothes, in case the tanks came rolling down Headington Hill.
However, with British drug companies showing little interest or support, Heatley and Florey set sail from Lisbon to New York in 1941, taking samples of their mould with them.
The journey was to alter the course of penicillin's development. Heatley and Florey went to Peoria, Illinois, the heart of America's corn belt. A lab had been set up there during the depression to find ways of using agricultural waste products like corn steep, and its scientists knew a lot about growing moulds and microbes using fermentation techniques similar to those used in brewing. Heatley and Florey freely shared their knowledge with the big pharmaceutical firms. They also considered it unethical to take out a patent on penicillin.
The war gave added urgency to the search for the right kind of mould that would be the key to mass production of penicillin. The aim was to produce thousands of kilos of penicillin for allied troops. Florey has sometimes been blamed for giving away to the United States a valuable invention, but Heatley later said that they had no alternative but to seek commercial help from the US, believing that otherwise penicillin would not have been developed as quickly.
Heatley stayed on in Illinois for several months, supposedly to work in collaboration with his American counterpart Dr Andrew Moyer on the project, but relations between the two men were rather strained at times, since Heatley found Moyer secretive and uncommunicative. Moulds from all over the world were tested, but the breakthrough, when it came, was found closer to home, on a mouldy old melon.
While Heatley persevered with Moyer, back in Oxford, Florey was still trying to produce enough penicillin using discarded junk, increasingly bitter about the credit Fleming was getting for discovering penicillin. In May 1943, Florey travelled to north Africa with just enough penicillin to put the drug through the most demanding test so far, the treatment of war wounds. The results were dramatic and there was no doubt that a new miracle cure had been found. The results made headline news.
When Alexander Fleming was awarded the Nobel prize for medicine in 1945, he acknowledged that "Nature makes penicillin. I just discovered it." Florey and Chain also received Nobel prizes for their work, but it took more than 50 years for Heatley's contribution to be fully recognised. Without Heatley's ingenuity and inventiveness, Fleming's chance discovery might have remained forever lost.
Described by one of his friends as a "generous puritan", Heatley could never bring himself to throw anything away. Even in his last decade, as his health and memory faded, he never lost his inventive flair. He delighted in making wonderfully delicate miniature furniture from birds' quills, and after an operation, he insisted on bringing home from hospital the plastic drip containers, cutting them down to make food containers for the fridge.
In 1991 Heatley was awarded an honorary doctorate of medicine from Oxford University, one of only two such doctorates to be awarded to non-medical people in the university's history. There is now also an annual Heatley lecture at Oxford and a scholarship awarded in his name.
He is survived by Mercy, his devoted wife of 59 years, their four children, Rose, Tamsin, Jonathan and Chris, and his white cat Leah, who also shared his passion for bird watching.
· Norman George Heatley, scientist, born January 10 1911; died January 6 2004
