Howard Florey

Based on Wikipedia: Howard Florey

The Man Who Actually Made Penicillin Work

Here's a story about one of the greatest injustices in the history of science. Alexander Fleming gets the credit for penicillin. His name is the one schoolchildren learn. His face appeared on stamps. But Fleming abandoned penicillin after discovering it, convinced it was too unstable to be useful.

The man who actually turned penicillin from a laboratory curiosity into the most important drug in human history was an Australian named Howard Florey. His discoveries are estimated to have saved over eighty million lives. Australian Prime Minister Robert Menzies once said, "In terms of world well-being, Florey was the most important man ever born in Australia."

Yet most people have never heard of him.

From Adelaide to Oxford

Howard Walter Florey was born in 1898 in Malvern, a suburb of Adelaide in South Australia. His surname, incidentally, rhymes with "sorry"—a fact that becomes relevant only because people kept mispronouncing it throughout his career.

His father Joseph was a bootmaker who had emigrated from England, hoping the Australian climate would help his first wife's tuberculosis. It didn't—she died in 1886. Joseph remarried, and Howard became the only boy in a family of four sisters and half-sisters. One of those sisters, Hilda, became a bacteriologist herself, pioneering laboratory medicine in Australia. She would later provide crucial inspiration for her younger brother's career path.

Young Howard was brilliant but not obviously destined for scientific greatness. At St Peter's College in Adelaide, he excelled at chemistry, physics, mathematics, and history—a broad competence rather than a singular obsession. He played cricket, Australian football, tennis, and track athletics. He was head boy. When World War One broke out in 1914, he desperately wanted to enlist, but his parents refused to give the required permission.

So he went to medical school instead.

The Rhodes Scholar Who Wouldn't Be Pushed Around

In 1920, Florey won a Rhodes Scholarship to study at Oxford. This was, and remains, one of the most prestigious academic honors in the world—a full-ride scholarship to one of humanity's oldest universities, established by the diamond magnate Cecil Rhodes in his will.

But Florey immediately got into a bureaucratic battle. The Rhodes Committee wanted him to start in October, which would mean either postponing his scholarship for a year or leaving Australia without finishing his medical examinations. Florey refused both options. He would take his exams and start at Oxford when he was ready, in January.

This was not how things were done. Rhodes Scholars did not dictate terms to the Rhodes Committee.

Florey enlisted the Governor of South Australia to argue his case. He won. He passed his examinations with second-class honors, received his medical degree in absentia, and sailed for England on a ship called the Otira—traveling free as the ship's surgeon.

This stubbornness would define his entire career. Florey was not a warm man. He was demanding, exacting, and notoriously difficult to work with. His laboratory technicians rotated out regularly because few could tolerate his standards. But this same iron will would prove essential when he took on the seemingly impossible task of manufacturing penicillin.

The Wandering Scientist

Florey's twenties were a blur of institutions and countries. After Oxford, he went to Cambridge. Then to the United States on a Rockefeller Foundation fellowship. Then to London Hospital. Then back to Cambridge. Then to the University of Sheffield.

At each stop, he accumulated skills and frustrations in roughly equal measure.

In America, he studied under Alfred Newton Richards at the University of Pennsylvania and Robert Chambers at Cornell. These connections would prove crucial later—Richards would become the key American supporter of the penicillin project during World War Two.

In London, he was miserable. He hated his daily commute from the suburb of Chobham, which left his experimental work "at the mercy of the railway timetable." For a man as obsessive about his research as Florey, this was intolerable.

At Cambridge, he finally had proper laboratory facilities, but no prospect for promotion. He dreamed of leading an interdisciplinary research team—bringing together physiologists, biochemists, and pathologists to tackle major problems. This was an unusual vision for the time. Science in the 1920s and 1930s was organized around individual researchers working in disciplinary silos. Florey wanted something more like a modern research institute.

He wouldn't get the chance to build one until 1935.

The Mucus Man

Before penicillin, Florey was known—to the extent he was known at all—as an expert on mucus.

This sounds unglamorous because it is unglamorous. But mucus is one of the body's most important defense mechanisms, a slimy barrier that traps pathogens before they can invade. Florey wanted to understand how it worked at the cellular level.

His mucus research led him to lysozyme, an enzyme that Alexander Fleming had discovered in 1922. Lysozyme is found in tears, saliva, and mucus. It kills bacteria by breaking down their cell walls. Fleming had noticed it when his own nasal mucus dripped onto a bacterial culture and created a clear zone where the bacteria had died.

Florey systematically tested which animals produced lysozyme. Dogs, rabbits, and guinea pigs all had it in their secretions. Cats had very little. Goats had none at all, except in their tears. By 1930, he had concluded that lysozyme played only a minor role in natural immunity—interesting, but not a breakthrough.

The lysozyme work, however, established a pattern. Florey was interested in how the body defends itself against infection. He was building expertise in antibacterial substances. And he was learning to work at the intersection of physiology and biochemistry.

All of this would come together spectacularly in the next decade.

A Marriage Under Strain

In 1926, Florey married Ethel Reed, a fellow medical student from Adelaide. She had followed him to England, and they were married at Holy Trinity Church in Paddington, London.

Ethel was intelligent and capable. She collaborated on two scientific papers in the late 1920s. But her health was poor—she suffered from respiratory problems and progressive hearing loss—and she found it increasingly difficult to keep up with her husband's relentless work schedule.

Florey cycled to his laboratory every day, including Sundays, arriving at ten in the morning (earlier on teaching days). He expected similar dedication from everyone around him. Ethel eventually stopped coming to the laboratory after she became pregnant with their daughter Paquita in 1929.

Their marriage would become increasingly strained over the years. Florey was obsessive about his work and emotionally distant. Ethel was isolated and unwell. The relationship survived, barely, but it was not a happy one.

Building the Team

In 1935, at the age of thirty-seven, Florey became director of the Sir William Dunn School of Pathology at Oxford. This was the opportunity he had been waiting for.

The school was well-funded but underperforming. Florey immediately set about assembling the interdisciplinary team he had long envisioned. The most important recruit was Ernst Boris Chain, a brilliant and volatile German-Jewish biochemist who had fled Nazi Germany in 1933.

Chain was everything Florey was not: emotional, dramatic, prone to tantrums and grandiose claims. Their relationship was productive but difficult. Chain would later complain bitterly that he hadn't received enough credit for the penicillin work. But in 1935, he was simply grateful for the position, and he brought exactly the biochemical expertise that Florey's team needed.

The other key members included Norman Heatley, a quiet, methodical biochemist who would solve the crucial problem of how to purify penicillin; Margaret Jennings, who would become Florey's close collaborator (and, after Ethel's death, his second wife); and Edward Abraham, who would later make his own fortune discovering the cephalosporin antibiotics.

This was the team that would change medicine forever.

Picking Up Where Fleming Left Off

Alexander Fleming had discovered penicillin in 1928, entirely by accident. A mold spore had contaminated one of his bacterial cultures, and he noticed that the bacteria near the mold had died. He identified the mold as Penicillium notatum and named the antibacterial substance it produced "penicillin."

Fleming published his findings and then... stopped. He made a few desultory attempts to purify penicillin, but the substance was unstable and difficult to work with. By the early 1930s, he had moved on to other projects. Penicillin sat in the scientific literature as a curiosity—known to exist, assumed to be impractical.

In 1938, Florey and Chain were looking for a new research project. Chain came across Fleming's old papers on penicillin while reviewing the literature on antibacterial substances. He thought the chemical structure might be interesting. Florey thought the therapeutic potential might be worth investigating.

Neither of them initially grasped what they were getting into.

The Impossible Manufacturing Problem

Penicillin presented an almost absurd set of challenges. The mold produced it in tiny quantities. The substance broke down rapidly when heated. It was destroyed by acid and alkali. It dissolved in water but not in most organic solvents.

To test penicillin on a single human patient, Florey's team would need to process hundreds of liters of mold culture. To treat the casualties of a world war—which is what Florey had in mind from the beginning—they would need to scale up production by a factor of millions.

Norman Heatley became the hero of this phase. He was the kind of scientist who could build anything out of anything. When commercial equipment proved unsuitable, he improvised. He constructed an extraction system using old milk churns, biscuit tins, and ceramic bedpans. He developed a method for transferring penicillin between water and a solvent called amyl acetate, which allowed for continuous purification.

The work was tedious beyond description. Growing the mold. Harvesting the broth. Extracting the penicillin. Losing most of it in each step. Starting over.

By early 1941, they had produced enough penicillin to test on a human being.

The Policeman Who Almost Survived

Albert Alexander was a forty-three-year-old police constable from Oxford. In December 1940, he had scratched his face on a rose thorn. The scratch became infected. The infection spread to his eyes and scalp. By February 1941, he was dying.

Alexander became the first patient to receive systemic penicillin treatment. The results were dramatic. Within twenty-four hours, his temperature dropped. His appetite returned. The infection began to clear.

But Florey didn't have enough penicillin. The team had thrown everything they had at Alexander's case—200 milligrams on the first day, 300 the next—and it still wasn't enough for a full course of treatment. They resorted to extracting penicillin from Alexander's own urine and re-injecting it. Even this wasn't enough.

Five days into treatment, the penicillin ran out. Alexander relapsed. He died on March 15, 1941.

The case was simultaneously a triumph and a tragedy. The penicillin had clearly worked—Alexander had been recovering until the supply ran out. But it had also exposed the brutal mathematics of the situation. Treating one patient required all the penicillin that Florey's entire team could produce in months of work. Treating thousands would require industrial-scale manufacturing that simply didn't exist.

The American Expedition

By mid-1941, Britain was fighting for its survival. German bombs were falling on English cities. The country's industrial capacity was devoted to aircraft, tanks, and ammunition. There was no possibility of scaling up penicillin production domestically.

Florey and Heatley flew to the United States in July 1941, carrying the precious Penicillium mold in their coat pockets. Their mission was to convince the American government and pharmaceutical industry to take on penicillin production.

It worked—spectacularly. The Americans threw their industrial might at the problem. Agricultural researchers in Peoria, Illinois, discovered that a different species of Penicillium, found on a moldy cantaloupe from a local market, produced far more penicillin than the original strain. Chemical engineers developed deep-tank fermentation methods that could produce penicillin by the ton.

By D-Day in June 1944, there was enough penicillin to treat every wounded Allied soldier. A substance that had killed a policeman through scarcity in 1941 was saving thousands of lives by 1944.

The Nobel and the Myth

In 1945, Florey, Chain, and Fleming shared the Nobel Prize in Physiology or Medicine "for the discovery of penicillin and its curative effect in various infectious diseases."

Fleming was the public face of the triumph. He was charming and quotable. He gave good interviews. The story of the accidental discovery—the contaminated petri dish, the moment of insight—was irresistibly romantic.

Florey, by contrast, was awkward with journalists. He disliked publicity and refused to promote himself. When reporters asked about penicillin, he gave credit to his team. When they pushed for a heroic narrative, he deflected.

The result was one of the great myths of medical history: Fleming the lone genius, penicillin the serendipitous discovery. The decade of painstaking work at Oxford—the biochemistry, the purification, the animal trials, the clinical tests, the manufacturing breakthroughs—all of this faded into the background.

Florey never publicly complained, but privately he was bitter. He had spent years solving problems that Fleming had abandoned. His team had done the actual work of turning a laboratory curiosity into a life-saving drug. And Fleming got the credit.

Life After Penicillin

Florey spent the remainder of his career as a scientific statesman. He became provost of Queen's College, Oxford, in 1962. He served as president of the Royal Society—Britain's premier scientific organization, founded in 1660—from 1960 to 1965. He was instrumental in founding the Australian National University in Canberra and served as its chancellor from 1965 until his death.

He never stopped researching. After penicillin, he worked on cephalosporins—another class of antibiotics, which would become crucial as bacteria developed resistance to penicillin. He studied atherosclerosis, the buildup of fatty plaques in arteries. He even did work on contraception.

But nothing matched the penicillin achievement. How could it? He had helped save eighty million lives. Everything else was an anticlimax.

The Difficult Genius

Florey was not an easy man to like. He was demanding, impatient, and emotionally cold. His first marriage was unhappy, though he and Ethel stayed together until her death in 1966. He remarried Margaret Jennings, his longtime collaborator, the following year—less than eighteen months before his own death.

He was also capable of great loyalty. Jim Kent, the fourteen-year-old boy he had recruited as a laboratory assistant at Cambridge in 1927, remained with him for forty years. Norman Heatley, who had done so much of the crucial purification work, became a lifelong friend.

And he was scrupulously honest. When journalists wanted to make him a hero, he refused. When the Nobel Committee came calling, he insisted that Chain and Fleming share the prize. When the British government offered him a peerage, he accepted it—but he never stopped insisting that penicillin was a team achievement.

The Lesson

Howard Florey died on February 21, 1968, at the age of sixty-nine. He had a heart attack in Oxford, the city where he had done his greatest work.

His story contains a lesson about how science actually works. Discovery is necessary but not sufficient. Fleming discovered penicillin, but he didn't make it useful. That required a different kind of work: systematic, unglamorous, collaborative. It required growing mold in bedpans and extracting antibiotics from urine. It required convincing governments and corporations to invest in manufacturing. It required years of failure before success.

Fleming saw the mold and recognized something interesting. Florey saw the same thing and asked: how do we make this work?

Both questions matter. But only one of them saved eighty million lives.