Medical History

Medical History

In March of 1942, Anne Miller lay dying at New Haven Hospital. A nursing school graduate married to Yale’s athletic director, Miller was suffering from streptococcal septicemia, a common and life-threatening infection of the blood, following a miscarriage. “During four weeks of treatment her temperature soared above 106 degrees, and no medications, not even sulfa drugs, had broken the fever,” John Curtis wrote in a 1999 article for the Yale School of Medicine.

No one had thought to try it yet, but there was a brand new drug, never before tested in the United States, that had the ability save her life: penicillin.

This mold with strange antibacterial qualities had been discovered 14 years earlier by Alexander Fleming, a professor of bacteriology at St. Mary’s Hospital in London. Returning from a vacation, Fleming had found mold in some of his lab’s Petri dishes. Around it, Fleming noted a strange phenomenon: no staphylococcus bacteria was growing. Fleming suspected he was on to something, but his efforts to isolate and purify the penicillin for further research were unsuccessful.

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A decade later, a team at Oxford University led by researcher Howard Florey, with the help of Ernst Chain and Norman Heatley, was getting close to testing penicillin on human subjects. But it took an astounding “2,000 liters of mold culture fluid to obtain enough pure penicillin to treat a single case of sepsis in a person,” according to a PBS News Hour article by physician Howard Markel. As the American Chemical Society tells it, Heatley began growing penicillin in a strange array of culture vessels including baths, bedpans, milk churns and food tins in order to produce enough mold for the research.

Then World War II slammed the brakes on Florey, Chain and Heatley’s plans. Hoping to keep their work moving, Heatley and Florey came to the United States. Heatley headed to Peoria, Illinois, to work with colleagues at a US Department of Agriculture lab; Florey came to Connecticut, hoping to interest the pharmaceutical industry in undertaking more penicillin research.

Before penicillin, there was no treatment for major infections like pneumonia, and small cuts and scratches could lead to life-threatening blood poisoning. Some people recovered on their own; many did not. According to Curtis, by the time Anne Miller was fighting for her life in New Haven, only six patients in England had received penicillin; four of them had recovered. The brand new medication wasn’t part of any medical protocol, and only a tiny usable amount existed.

But Miller had an amazing stroke of good luck. Two Yale colleagues simultaneously carried the latest information about penicillin to her doctor, John H. Bumstead. Her gynecologist, Orvan Hess, had just read an article about penicillin and mentioned it to Bumstead in a meeting they happened to have that week. And just down the hall from Miller, in another room, Bumstead was treating his colleague, Dr. John F. Fulton, a close friend of researcher Florey. Fulton also “had close ties at the National Research Council,” where he had already “play a key role in establishing a program to produce penicillin in the United States in 1941,” according to Kerry L. Falvey’s Medicine at Yale: The First 200 Years (2010).

Bumstead mentioned Miller’s case to Fulton, and Fulton agreed to help. After a series of phone calls, he managed to secure 5.5 grams of penicillin—according to Falvey, “half the total supply of penicillin then available in America.” No one knew how large or how frequent the dose should be. Curtis’s article recounts what happened next:

A sample was flown to New Haven from Washington and delivered to the hospital by a state trooper… Miller began receiving her first dose via intravenous drip at 3:30 p.m. on a Saturday. The next morning her temperature, which had hovered between 103 and 106.5 degrees, dropped to normal for the first time in four weeks. By Monday her appetite had returned and she had eaten four full meals. Her bacteria count dropped.

The drug was so rare that, according to Curtis, the intern with primary responsibility for injecting it was also tasked with saving Miller’s urine and sending it to Merck & Company pharmaceuticals, where up to 70 percent of the penicillin administered to the patient could be recovered and reused. The treatment was successful, and Miller became the first person whose life was saved by penicillin in the United States. She lived another 57 years and died in 1999 at the age of 90.

Within three months of Miller’s seemingly miraculous recovery, 10 more patients had been treated, according to the American Chemical Society. The following year, the U.S. War Production Board took on oversight of the drug, working with 21 private companies to ramp up production for use by the military. According to Falvey, more than 200 patients at New Haven Hospital were part of penicillin’s clinical trials, and by 1945, US manufacturers were producing 646 billion “units” of the new wonder drug—a standard dose today is between 200,000 and 500,000 units for an adult, according to the Mayo Clinic—every month. One of the major goals, says the American Chemical Society, was to have an adequate supply on hand for the planned invasion of Europe. Tens of thousands of lives are believed to have been saved by the end of the war as a result.

In 1945, Alexander Fleming, Howard Florey and Ernst Chain were awarded the Nobel Prize for their penicillin research. That same year, Anne Miller met Fleming in person. “There was an unusual expression on his face as he stood and looked at a woman who had made a remarkable recovery,” she told the New Haven Register in a 1972 interview. “It was a look of more than average interest, I would say.”

Written by Kathy Leonard Czepiel. Image, of bottles of penicillin produced in 1944, courtesy of the Science Museum Group. This story was originally published on March 28, 2019.

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