Fleming announced his find in February 1929 at the prestigious Medical Research Club, but none of his colleagues showed much interest. His June 1929 article on penicillin, published in the British Journal of Experimental Pathology, met with similar apathy. Painfully shy, Fleming didn’t push the topic and eventually immersed himself in other projects.
Almost a decade later, England was bracing for war and British scientists urgently sought out new treatments for battlefield infections, which they knew from past conflicts often killed more troops than bombs and bullets combined. Thirty-three-year-old Dr. Ernst Chain, a Jewish refugee from Hitler’s Germany who resembled a young Albert Einstein, stumbled across Fleming’s 1929 article by “sheer luck,” he later said, and showed it to Dr. Howard Florey, his boss at Oxford University’s Sir William Dunn School of Pathology. Florey agreed that it warranted more study, and the two men, along with Dr. Norman Heatley and Dr. Margaret Jennings, secured a Rockefeller Foundation grant to research penicillin’s medical applications. Funding appeals to their own government’s Medical Research Council, British pharmaceutical companies, and Oxford University were all rejected.
Time was running short. In July 1940 the Luftwaffe launched a ferocious six-month bombing campaign over England that ultimately killed more than twenty thousand civilians. Like many parents who had the means, Florey sent his children overseas, and they ended up staying in Connecticut with his friend Dr. John Fulton. Aside from possibly losing their own lives, Florey and his team feared that a direct strike on their lab would wipe out irreplaceable research; a single batch of Fleming’s original Penicillium notatum was all they had to work with. In case of a full-on German invasion, they planned to rub the penicillin spores, which were extremely resilient, into their coat pockets and flee to a neutral country.
On February 12, 1941, police constable Albert Alexander became the first person treated with penicillin. Alexander had scratched his face on a rose thorn, causing an infection to flare across his cheeks and into his eyeballs, which started to swell up hideously. The right eye had to be lanced right away before bursting, and the left one was extracted entirely. Soon Alexander’s entire body was under attack. “He was oozing pus everywhere,” Heatley recorded in his diary. Then, less than twenty-four hours after Alexander received penicillin, his condition improved noticeably, and by February 22 he had rebounded almost completely.
Almost. Just as he was on the verge of a full recovery, doctors exhausted their penicillin stock. Despite his dramatic turnaround, Alexander’s now defenseless body was unable to repel the last lingering microbes, and they multiplied with a vengeance. Within days he was dead.
Florey and Heatley had frantically tried to grow penicillin in anything they could get their hands on—Petri dishes, bedpans, pie tins, cafeteria trays—but purifying the low-yield mold was maddeningly slow. If one patient could so rapidly drain their supplies, they realized, there was no hope of providing mass quantities for injured troops and civilians in the years to come.
Still unable to persuade the British government or private companies to underwrite their efforts, Florey decided he would have to approach a partner outside of war-torn Europe, a partner with the resources, manpower, and scientific wherewithal to produce this new wonder drug on a massive scale. He knew just whom to call.
· · ·
“Good morning, USDA, how may I help you?” a lovely Scottish voice asked when I first contacted the Department of Agriculture’s National Center for Agricultural Utilization Research (NCAUR) in Peoria. I told the receptionist, Jackie Shepherd, what I was doing and briefly recapped my understanding of NCAUR’s role in manufacturing penicillin after English doctors had discovered it. Jackie verified that, yes, I had the right place, and connected me to their communications officer, Katherine O’Hara, to schedule a visit. But before patching me through, Jackie playfully admonished me. “I don’t believe that Fleming was English,” she said, her native lilt sounding stronger than before. “He was a Scotsman.”
When I arrive weeks later at 1815 North University Street I’m pleased to find Jackie manning the front desk, and she’s as gracious in person as on the phone. Jackie buzzes Katherine O’Hara, and while I’m waiting, I peruse the lobby display cases about NCAUR and its three sister labs in Louisiana, California, and Pennsylvania. They were all built during the Depression to devise new ways of putting surplus crops to good use, and their accomplishments are both impressive and eclectic. They’ve created frozen concentrated orange juice, lactose-free milk, dehydrated potato flakes, biodegradable plastics, and a silicone emulsion that preserves antique books. Peoria, specifically, came up with the idea of using infrared lamps to make french fries crispy, designed an ingenious method of cleaning Navy warplanes by air blasting them with ground corncobs, and produced the blood plasma substitute dextran.
Katherine, a warm and welcoming host, takes me up to her office, where she hands me a packet of penicillin-related materials from NCAUR’s archives.
“Here’s what started it all,” she says, pulling out the historic July 9, 1941, telegram from Department of Agriculture administrator Dr.
Percy Wells to NCAUR director Dr. Orville E. May:
HEATLEY AND FLOREY OF OXFORD, ENGLAND, [ARE] HERE TO INVESTIGATE PILOT SCALE PRODUCTION OF BACTERIOSTATIC MATERIAL FROM FLEMING’S PENICILLIUM IN CONNECTION WITH MEDICAL DEFENSE PLANS. CAN YOU ARRANGE IMMEDIATELY FOR SHALLOW PAN SETUP TO ESTABLISH LABORATORY RESULTS IN METAL [CONTAINERS].
Heatley and Florey’s journey to the United States was exhausting and dangerous, requiring cloak-and-dagger measures to get them from London to Lisbon, where they scurried onto a Pan Am Clipper with blacked-out windows. From Portugal they flew directly to New York City. America wasn’t yet at war, but with the Luftwaffe patrolling the skies over Europe and German warships prowling the Atlantic, no mode of transportation to the States was safe. (Before leaving, Heatley and Florey went out for a much-needed night of entertainment and decided to catch the new Alfred Hitchcock thriller Foreign Correspondent. They were unaware that in the movie’s climactic scene, a plane identical to theirs is shot by a German destroyer and plunges into the ocean. “The sinking of the ‘Clipper’ in the film struck [Florey] & me as rather a bad thing to see,” Heatley noted dryly in his diary.) Throughout the entire trip, Florey held on tightly to a briefcase packed with notebooks and carefully wrapped vials of freeze-dried penicillin.
They landed at LaGuardia Field on July 2 wearing thick wool suits more appropriate for England’s cooler climate than Manhattan’s sweltering heat. But summer humidity or not, neither man let go of his jacket; smeared into the coat pockets were the “backup” spores they would use in the event that Florey’s briefcase was heisted.
From the East Coast, the doctors made their way to Peoria, and on July 14 they met with Dr. Robert Coghill, director of NCAUR’s fermentation division, and Dr. Andrew Moyer, an expert on the nutrition of molds.
“Clete here is going to take you to Moyer and Coghill’s old labs,” Katherine says as she introduces me to Dr. Cletus Kurtzman, one of Moyer’s successors. Clete’s been working at NCAUR for forty-two years and oversees a collection of 100,000 different microbes. After we talk for several minutes I can sense that his passion is undiminished, and I ask him what first got him interested in science.
“I’ve been fascinated since I was a child. I’d go down to the pharmacy and buy powdered sulfur, potassium nitrate, and sulfuric acid, then come home and do experiments. Looking back on it, I’m surprised they’d sell those things to a boy, but it sure was fun.” He adds wistfully, “Those were the good old days.”
“And you never got hurt or anything?” I ask, thinking of how a young Robert Goddard nearly blew himself to pieces playing with similar chemicals.
“Let’s just say I’m very lucky to have all ten digits and a face.”
Clete and I start walking over to the building’s center section, and along the way he tells me, “I’m afraid the laboratories won’t look like they did origina
lly.”
“No worries,” I say. “I just want to see where it all happened.”
Within forty-eight hours of Heatley and Florey’s arrival at NCAUR, Moyer and his team were hard at work cultivating the samples smuggled over from Oxford. After an initial scare, when the spores that had blossomed so quickly in England didn’t take to NCAUR’s balmy, 80-degree-plus temperatures (the new air-conditioning system wasn’t operational until that September), the Peoria scientists were finally able to grow the first tiny batch of mold by July’s end.
To mass-produce penicillin, which was the whole reason the Oxford doctors had come to Illinois, Moyer first suggested utilizing corn-steep liquor in the fermentation process. The idea was as much practical as it was scientific; the thick, syrupy liquid was rich in nitrogen, and it could be acquired easily because nobody wanted the stuff. A by-product of cornstarch, it was often just dumped into the Illinois River.
Adding corn-steep liquor alone, they discovered, upped the yield a stunning 1,000 percent.
Florey left Peoria to embark on a hat-in-hand tour of America’s pharmaceutical giants, begging them to mobilize their resources behind penicillin. Drug companies were familiar with its potential but also its production-related drawbacks and, like their British counterparts, doubted they could make a profit. Cultivation tanks the size of swimming pools, some scientists estimated, would be needed in order to skim off enough mold from the culture fluid’s surface, and that investment alone was calculated to be prohibitively expensive.
The Peoria crew was working to tackle this very problem, and they believed that “submerged growth” was the solution. If penicillin were brewed up in large drums—not just on the surface but throughout the mixture—production could be boosted exponentially. Moyer recommended adding lactose to the corn-steep liquor and aerating the broth with a constant supply of sterile oxygen in ten-thousand-gallon vats.
This, too, increased yields substantially.
Moyer realized, however, that to truly maximize results they needed a more resilient mold. Leading the hunt for this new, tougher strain was another NCAUR mycologist, the unfortunately named Kenneth Raper, who instructed members of the U.S. Army Transport Command to bring him mold extracts and soil samples from wherever they traveled around the world.
Any reluctance the pharmaceutical industry had initially shown in the summer of 1941 vanished on December 7. After the attack on Pearl Harbor, Lederle Laboratories, Merck, E. R. Squibb, and Charles Pfizer (more companies came aboard later) all agreed to join forces to mass-produce penicillin, and they received special dispensation from the government to work together without violating antitrust laws.
Having been on the sidelines for so long, the drug corporations struggled initially. By the early spring of 1942, they had collectively whipped up a mere 5.5 grams—barely more than a teaspoon’s worth—of pure penicillin, which at best could treat only a single individual.
The opportunity to do just that came in mid-March at Connecticut’s New Haven Hospital, where thirty-one-year-old Anne Miller was dying of blood poisoning brought on by a severe bacterial infection. Doctors had tried transfusions, surgery, and sulfanomides (the first antimicrobial drugs), but nothing worked, and Miller was deteriorating fast. Coincidentally, Miller’s doctor, John Bumstead, was also caring for a fellow physician, John Fulton, who had mentioned in passing that his English friend Dr. Howard Florey had developed a powerful new antibiotic called penicillin. Bumstead implored Fulton to get a dose for Miller, and Fulton was able to pull a few strings. The medicine was rushed to New Haven on Saturday, March 14, and Miller recuperated fully. She was the first American treated with penicillin and, it is believed, the first person anywhere saved by it.
At NCAUR there was further cause for celebration. After working seventy-hour weeks sifting through a malodorous array of decaying fruits, old cheeses, breads, meats, and clumps of dirt contributed by U.S. aircrews and scientists from around the globe, Raper had finally isolated the “super” mold he’d been searching for. Approximately fifty times more potent than anything previously tested, the strain eventually became the primogenitor for almost all of the world’s penicillin. And it was found, by chance, on an overripe cantaloupe purchased at a Peoria grocery store. (The exact location, alas, isn’t recorded. Robert Coghill only noted the source in NCAUR’s records as a “fruit market” near the lab.) The miracle melon itself was neither preserved for posterity nor disposed of with any kind of ceremonial pomp befitting its historic significance. After cutting the mold off the rind, staff members sliced up the cantaloupe and ate it.
By June 1944, right in time for the D-Day landings at Normandy, drug companies were churning out an estimated 100 billion units of penicillin per month, enough for an estimated forty thousand U.S. and British combatants. Hitler’s forces had to rely on less effective sulfa drugs and, consequently, experienced higher fatality rates, more amputations, and longer recovery times for injuries, diminishing their overall troop strength. Thousands of German soldiers were also incapacitated by sexually transmitted diseases such as syphilis and gonorrhea, which penicillin would have easily treated. On and off the battlefield, penicillin cured an ever expanding range of afflictions—pneumonia, strep throat, gas gangrene, septicemia, spinal meningitis, scarlet fever, puerperal sepsis, to name just a few—and with virtually no side effects. It became as indispensable to the Allied war effort as any weapon.
In late October 1945, Alexander Fleming, Howard Florey, and Ernst Chain jointly won the Nobel Prize for Physiology or Medicine. Only three people, at most, can receive the award for the same discovery, and fairly or not, Heatley was shut out. (Moyer wasn’t even in the running, but he was the second microbiologist inducted into the National Inventors Hall of Fame. The first was Louis Pasteur.) That same fall NCAUR stopped manufacturing penicillin and licensed all production to private pharmaceutical firms. After the war, demand shifted from military to civilian applications, and penicillin became wildly profitable. In 1951 drug companies were producing approximately 30 trillion units a month, and within three decades that number skyrocketed to 385 trillion units.
Clete opens the stairwell door to the third floor, and we walk into a bright fluorescent-lit hallway.
“All of this has been newly renovated since the 1940s, and even the walls have been offset by the new construction, but Moyer’s lab would have been around here,” he says in front of Room 3118.
We peek inside, and Clete explains that this is where they now store NCAUR’s one hundred thousand cultures. “About eighty thousand of the microbes are fungi,” he says, “and the other twenty thousand are bacteria.” Large double-door steel refrigerators, like those found in any modern household kitchen, line both sides of the laboratory, and down the middle are liquid-nitrogen containers the size of industrial drum barrels.
We step back into the corridor, and before we return to Katherine’s office, Clete starts talking about a medical innovation developed during the early 1950s by Dr. Allene Jeanes in the lab right across from Room 3118. As Clete goes into detail about its chemical properties—something about polysaccharides and carbohydrate structures—my scientifically challenged brain begins to shut down, and I stand there nodding reflexively.
Then he mentions the word dextran and I realize he’s describing the blood plasma substitute I’d read about in the lobby. Originally intended for U.S. troops fighting on the front lines in Korea, it’s commonly used in hospitals today and has prevented countless patients from bleeding to death.
The lifesaving blood extender was created out of a “slimy bacterium,” Clete tells me, that wasn’t exactly drawn from the lab’s official collection of microbes. Another NCAUR scientist had shown the mold to Dr. Jeanes after spotting it inside a half-empty bottle of old root beer that someone, fortuitously, had neglected to throw away.
DR. MAURICE HILLEMAN’S BIRTHPLACE
If I had to name a person who has done more for the benefit of human health, with less recognition than anyone else, it
would be Maurice Hilleman.
—Dr. Robert Gallo, director of the Institute of Human Virology and the codiscoverer of the human immunodeficiency virus (HIV)
When my birth was registered at the County Court House, it was spelled Hilleman. The second “n” had been deleted because of anti-German sentiment in which our Church had been smeared with yellow paint.
Nothing else happened on August 30, 1919, except that on that day, Charles Guiteau was hanged for the murder of President James E. Garfield.
—From Dr. Maurice Hilleman’s unfinished autobiography, “Out of the Kingdom.” (Guiteau was actually executed thirty-seven years earlier.)
DR. MAURICE HILLEMAN’S widow, Lorraine, generously shared with me a copy of the autobiography her husband was struggling to complete while dying of cancer. Before meeting with his nephew Art Larson, here in Miles City, Montana, I was curious to read what Hilleman had written about his birthplace and its influence, if any, on his later achievements. “I consider it fortunate to have been born into modest means without a silver spoon in the mouth,” Hilleman recalled in rushed and uncorrected prose (understandable, considering the circumstances). “Work on the farm began at age 5 years of age [sic] where working with plants, animals, soil, mechanics and electricity gave a practical introduction into the workings of the biological and physical sciences.” Sadly, Hilleman had only made it up to the section about his high school years when he passed away at the age of eighty-five on April 11, 2005.
After he died, every major obituary echoed Dr. Robert Gallo’s sentiments about Hilleman’s contributions to global health and also noted that his research has possibly saved more lives than any other scientist’s. Some dropped the “possibly” altogether. “Among scientists, he is a legend,” Dr. Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases, said of Hilleman. “But to the general public, he is the world’s best-kept secret.” He’s a bit of a secret in Miles City, too.
Here Is Where: Discovering America's Great Forgotten History Page 30