From Penicillin to Phages: Yale’s Century-Long Fight Against Infection

Before the discovery of antibiotics, even minor infections—from a paper cut to complications following childbirth—could be fatal. In the early 20th century, bacterial disease claimed countless lives, often despite the best efforts of physicians.

Although Scottish bacteriologist Alexander Fleming observed the antibacterial effects of Penicillium mold in 1928, it was more than a decade before the power of the first antibiotic became fully apparent.

In 1942, a patient named Harry Lambert was admitted to a hospital in England for a life-threatening infection of the nervous system. Fleming administered a sample of penicillin into Lambert's spinal canal and he showed improvement the next day.

Across the Atlantic, New Haven resident Anne S. Miller developed a severe bacterial infection following a miscarriage. Her internist, Yale’s John H. Bumstead, MD, could do little to stop the infection.

While waiting to discuss her case with Bumstead, Miller’s obstetrician/gynecologist, Orvan W. Hess, MD, read an article about how a bacterium was being used to treat similar infections in animals. He remarked to Bumstead that an effective treatment for their patient might be possible if a similar approach could be applied in humans—an observation that prompted Bumstead to consider an unconventional option.

As it happened, another of his patients, John F. Fulton, MD, professor of physiology and chair of the Department of Physiology at Yale School of Medicine, was also in the hospital with a pulmonology infection. Fulton was acquainted with Norman Heatley, an Oxford University researcher who was working to increase penicillin production. Bumstead asked Fulton to contact Heatley and request a dose to treat Miller.

His outreach was rewarded. Heatley was able to provide 5.5 grams of the drug, half the existing supply of penicillin in the U.S. at the time. The drug was flown in and delivered to the hospital by a state trooper on March 14, 1942.

Miller received her first dose that same day. By the next morning, her temperature—elevated for weeks—had returned to normal. She was pronounced cured several weeks later, becoming the first patient in the United States whose life was saved by penicillin.

Miller died at the age of 90 in 2000.

Miller’s recovery offered compelling evidence of penicillin’s promise, but a single case was not enough to change medical practice.

With the efficacy of penicillin proven, Francis G. Blake, MD, professor of medicine, chair of the Department of Internal Medicine, and dean of Yale School of Medicine, went on to oversee some of the first clinical trials of penicillin in the United States.

These early trials confirmed penicillin’s extraordinary ability to treat bacterial infections. Given its potential to save civilian lives and protect soldiers during wartime, the U.S. government prioritized large-scale production, working with pharmaceutical companies to expand supply.

The impact was dramatic. Historically, infections killed more soldiers than battlefield injuries. During World War I, bacterial pneumonia alone carried an 18% fatality rate. By World War II, that figure had dropped to less than 1%—a change attributed largely to penicillin.

By 1945, production had expanded enough to meet the needs of both military and civilian populations, ushering in the antibiotic era.

Yale’s role in penicillin’s early clinical use and validation positioned the institution as a leader in translating laboratory discoveries into life-saving therapies. That legacy extends well beyond antibiotics themselves, shaping how modern medicine approaches infectious disease, clinical trials, and therapeutic innovation.

Nearly a century later, Yale scientists are tackling a new crisis—one that echoes the pre-penicillin era in troubling ways.

Bacteria are evolving faster than the antibiotics created to treat them. Antimicrobial resistance is now considered one of the top global public health threats, contributing an estimated 4.71 million deaths worldwide in 2021, with a significant increase in resistant organisms after the COVID-19 pandemic.

Just as Yale physicians once helped usher penicillin from experimental compound to clinical reality, Yale scientists today are working to confront this next challenge.

One of the most promising strategies involves bacteriophages (phages for short)—viruses that infect and destroy bacteria. Unlike broad-spectrum antibiotics, phages can be tailored to target specific bacterial strains, including those resistant to multiple drugs.

Since 2013, researchers at Yale’s Center for Phage Biology & Therapy at Yale led by Paul E. Turner, PhD, Rachel Carson Professor of Ecology and Evolutionary Biology, have been using phages to treat infections caused by multidrug-resistant bacteria.

Yale School of Medicine researchers are also exploring complementary strategies to meet the growing threat of antimicrobial resistance. Teams are building extensive “phage libraries” and tailoring phages to specific bacterial infections, with early work showing promise in treating challenging conditions such as drug-resistant infections in people with cystic fibrosis.

These efforts reflect an integrated approach—combining basic science, clinical innovation, and personalized therapy—that mirrors Yale’s historic role in bringing penicillin from laboratory discovery to life-saving use and now extends that legacy into the post-antibiotic era.