The drug that helped win the war
Every day, men, women and children are rescued from dangerous infections by drugs that began -- in the words of author Eric Lax -- as “a blue-green moon of mold [that] shone over a sea of islets of staphylococci.” The fuzzy trespasser on the culture plate of bacteria was the fungus that makes penicillin. It was Alexander Fleming, a shy and eccentric microbiologist, who first spotted it in his laboratory at St. Mary’s Hospital, London. The year was 1928.
After all the recent doom and gloom over the so-called demise of antibiotics, it’s refreshing to read Lax’s book about the dawn of the antibiotic era and some of the impassioned scientists who would help usher it in a decade and a half after Fleming’s initial discovery. Did they realize their work would change medicine forever? Roughly 50 miles north of Fleming’s lab, three Oxford researchers -- Howard Florey, Ernst Chain and Norman Heatley -- at least knew this: If they extracted and produced penicillin in quantity, it could greatly benefit the Allied war effort. But first they had to overcome financial and technical challenges. They also feared that penicillin might fall into enemy hands. Lax’s title, “The Mold in Dr. Florey’s Coat,” reveals their worst-case strategy. If the Nazis invaded, the Oxford team decided they would hide Penicillium notatum spores in the fabric of their clothes.
Most popular accounts of penicillin begin and end with Fleming, who always seems to get the lion’s share of credit despite sharing the 1945 Nobel Prize for Physiology or Medicine with Florey and Chain. Not that Fleming is undeserving. His first great discovery was lysozyme, a natural antibiotic substance that he found in mucus from his own runny nose. But lysozyme killed only harmless bacteria. The next serendipity was the wafting of fungal spores into Fleming’s laboratory while he and his family summered in Suffolk. When he returned to his lab, he found that mold had invaded his cultures, leaving clear, germ-free rings on carpets of staphylococci. This time, he struck gold. Staph bacteria -- then and now -- cause a host of ills, from boils and abscesses to life-threatening infections of the heart, lungs and blood.
To Fleming’s credit, he stuck with penicillin research for several years, even after a mortifying talk at London’s Medical Research Club drew not one question, and his first penicillin paper in the British Journal of Experimental Pathology was roundly ignored. By the mid-1930s, however, he had moved on. Penicillin was an elusive compound, and Fleming lacked the fire in the belly to continue trying to unlock its secrets. As a result, he failed to purify the active ingredient in “mold juice” and never once tested his Penicillium culture filtrate on infected animals. Looking back, one wonders whether he fully appreciated penicillin’s immense therapeutic promise.
The tale of its wartime journey from laboratory curiosity to 20th century miracle drug, in Lax’s hands, makes for a marvelous read. His account is also the first to contain more than 60-year-old diary entries, as well as modern musings by Heatley, until recently the sole survivor of the inner circle of Oxford researchers who picked up the work where Fleming left off.
The penicillin quest began in earnest in 1940 when the Oxford team, led by pathology Chairman Florey, started detailed studies. Florey had a clear agenda: to sort out penicillin’s chemical structure and mechanism of action, to prove its safety and efficacy in animals and people and, finally, to launch the extraction process. The excitement of watching a dark brown drop of penicillin-infused urine from a test mouse demolish germs was just the beginning. Soon, Heatley had enough penicillin to launch a trial in a handful of white mice infected with virulent streptococci. As Lax recounts, around midnight one of the control mice “got up and staggered about for a few seconds, then fell down, twitched once or twice and was dead,” while the others appeared “very seedy.” By 4 a.m., the last control mouse had died. Nearby, the penicillin-treated mice napped and nibbled biscuit crumbs.
After recording these findings, an elated Heatley pedaled home only to be stopped en route by a vigilant Home Guardsman with a rifle. After all, about 350,000 Allied troops were stranded on the beaches of northern France and tensions were running high. Much of the book’s success lies in this braiding of intimate wartime details with lucid descriptions of the evolving science. In 1940 and 1941, everything in Britain was scarce. Nonetheless, the penicillin work progressed, with Heatley using Huntley & Palmers biscuit tins, pie plates and finally a porcelain vessel (dubbed the bedpan) to extract penicillin from mold and establish the world’s first penicillin factory. Meanwhile, Florey tested precious drams of the drug in a nearby septic ward. Albert Alexander, a constable racked with staph from a rose thorn scratch was an early recipient. Although his initial improvement was dramatic, to the anguish of all, he died when treatment doses simply ran out.
The author is best known for his definitive biography of director Woody Allen, as well as other books including “Life and Death on Ten West,” a chronicle of UCLA’s leukemia and bone marrow transplant ward. “The Mold in Dr. Florey’s Coat” combines his biographer’s skill with an intelligent sympathy for medicine, science and the polar personalities that sometimes produce brilliant collaborations. As he points out, organizing individual scientists to each solve a piece of a larger puzzle was rare at that time in British academia. Thanks to Florey, oil and water mixed at Oxford. Chain, a gifted but volatile Belorussian immigrant, tackled penicillin’s tricky chemistry, while Heatley, a courtly, meticulous man, exercised his talent for operational research and technical improvisation.
Florey was also coolly pragmatic when it came to funding. Although the sums he gleaned early on were certainly humble by today’s standards (his first Medical Research Council award for penicillin was 25 pounds, or roughly $100), he knew that sizable grants were crucial to the work. Eventually, he found generous patronage at the Rockefeller Foundation.
The Rockefeller connection, in turn, facilitated technology transfer to the United States, where penicillin production became the War Department’s No. 2 priority after the Manhattan Project. U.S. pharmaceutical companies signed on, working together with unprecedented cooperation. By D-day 1944, Lax writes, U.S. penicillin production had reached 100 billion units per month, enough to treat 40,000 war-wounded and civilian patients -- a far cry from the days when Heatley had to process 2,000 liters of mold filtrate for a single patient.
So, what do readers and modern infectious disease doctors and readers take away from this saga? First, gratitude that the ubiquitous septic wards that preceded antibiotics -- where hospitalized patients used to linger for weeks or months with rotting wounds stuffed with carbolic-acid-soaked rags -- are no longer, at least in many countries. Second, faith in the passion that fueled penicillin’s wartime development. That passion for continued medical progress is alive and well today. Yes, Fleming’s 1945 prediction that penicillin, used improperly, would ultimately turn ineffective has largely come true. With our current, expanded arsenal of antibiotics, however, we still win far more often than we lose.
There is also a lesson in “Dr. Florey’s Coat.” The unsung hero had the happiest life. Perhaps Heatley should have shared in Nobel glory, but, as Lax reveals, the perennial tinkerer never paid it much mind. He lived with his wife, Mercy, in the same modest cottagefor more than 50 years, outlasting his collaborators by decades. He died Jan. 5 at the age of 92, presumably with a measure of quiet satisfaction in having helped make one of the greatest medical breakthroughs of the 20th century.
Beautifully researched and written, alive with scientific and human insight, Lax’s fine book likely will become the classic account of penicillin’s true medical beginnings. *
