Innovation thrives in the spotlight
By Tom Culman
As Engagement Associate at RA Capital Management, Tom Culman manages a variety of educational, outreach, and advocacy-oriented projects.
September 29, 2021
The story of Alexander Fleming is a popular one. As it should be — it’s a good story about one of the most important discoveries in medical history, penicillin. But most people only know the first act of the play: that Fleming left his lab in a mess while on vacation, just to come back to find mold growing on his petri dishes that seemed to repel Staphylococcus bacteria. Stories like that inspire young scientists.
That was in 1928. For about a decade, penicillin was little more than a curiosity used to separate different types of bacteria. Howard Walter Florey and Ernst Boris Chain of Oxford (who shared in Fleming’s Nobel prize) wouldn’t begin testing it in people until the ‘40s, and even then they could hardly produce enough to treat infections in a single person. Scaling production of the drug would prove impossible with the strain Fleming discovered.
Does that make penicillin’s origin story — or Fleming’s contribution — worthless? Hell no! Science is iterative, and stories like that help us understand the struggles, mistakes, and successes of history’s innovations.
A War of Innovation
At the outset of World War 2, Axis and Allied powers had essentially the same antibiotic capabilities: sulfonamides, or sulfa drugs, which weren’t great. Any general can tell you how dangerous infection is in wartime. The development of new antibiotics became an international priority.
WW2 accelerated the era of modern antibiotics. But at the same time, the war created supply shortages that became a major obstacle for the penicillin team in England. Oxford needed help, and so Florey and his colleague, Norman Heatley, turned to America. Heatley worked with the U.S. Department of Agriculture to solve the scientific riddles necessary to scale production while Florey tackled financial concerns.
The Cantaloupe of Fate
Mary Hunt was constantly on the lookout for interesting molds.
In 1943, as a bacteriologist at the Department of Agriculture’s Northern Regional Research Laboratory (NRRL), she noticed an important one. It was growing on a cantaloupe in a grocery store in Peoria, Illinois. That mold — the ancestor of today’s penicillium molds — could produce a penicillin yield many times greater than Fleming’s strain. Hunt’s team irradiated the mold, mutating it to produce even more penicillin. (Supposedly, they also ate the cantaloupe.)
… At least that’s how the story goes. Among historians, Hunt’s exact role is a bit more controversial, but as this article from Peoria Magazine lays out, she clearly played a part. Supervisors at her lab wrote in their 1944 paper, “We are likewise indebted to Miss Mary K. Hunt for collecting samples of moldy materials and for assisting in the isolation and preliminary testing of many strains.”
Hunt’s story, like Fleming’s, is important. Scientific stories create a lens through which we can see how many people were involved in a landmark finding, how seriously they took their work, and the roles of nature and chance. The pride the city of Peoria feels at having brought such an important discovery into the world is important. That feeling is part of what inspires future discoveries and our greatest accomplishments as individuals, communities, and a society.
Money Matters
But ingenuity and determination can only get you so far, as Florey came to understand. While Heatley was zapping molds and eating questionable fruit at the NRRL, Florey was shopping penicillin around to the biggest pharmaceutical companies in America. He would be disappointed in their responses, mostly because many of them were already running into the same scaling problem that stalled progress in Oxford.
Florey then visited Alfred Newton Richards, chair of the medical branch of the OSRD — the US agency responsible for coordinating research that could help Allied powers. The agency designed better guns and ships and developed new technologies like RADAR and the atomic bomb.
Richards got the big names in WW2-era pharma around a table along with Robert Coghill of the NRRL. If Florey and his team were ever going to scale penicillin production, they would need the supply chains and manufacturing capabilities of Merck, Squibb, Pfizer, and Lederle. So the industry would need to be convinced penicillin was scalable. And to move as quickly as possible, information would need to be shared.
In just their second meeting, 10 days after the attack on Pearl Harbor, the executives agreed to share their research through the OSRD. With new techniques from the NRRL and war raging to push demand, penicillin suddenly became a scalable and lucrative innovation.
Allied governments, pharmaceutical companies, nonprofits like the Red Cross, and countless hospitals and clinics each played key parts in penicillin’s story. Even everyday citizens made their contribution, as the cutting-edge antibiotic had to be rationed among the public to be saved for troops.
The wartime mentality spurred on the production of penicillin. The War Production Board invested in some 175 companies working on the drug and appointed Albert Elder as their “Penicillin Czar.” Elder wrote to manufacturers, “You are urged to impress upon every worker in your plant that penicillin produced today will be saving the life of someone in a few days or curing the disease of someone now incapacitated. Put up slogans in your plant! Place notices in pay envelopes! Create an enthusiasm for the job down to the lowest worker in your plant.”
Simplified tales like Fleming stumbling upon penicillin can inspire. But they can also fool people into thinking that’s how drugs are actually discovered. Why invest billions when scientists can change the course of history accidentally, right? Well that’s not how it worked then, and it’s certainly not how it works now.
80 Years Later, History Repeats Itself
The mRNA technology underpinning the Moderna and Pfizer/BioNTech’s COVID-19 vaccines has been around in nascent form for decades. Back in the ‘90s, investors, governments, and granting organizations dismissed the tech while scientist Katalin Karikó fought to develop it.
Adverse immune reactions to mRNA led to years of failure and Karikó’s demotion at UPenn. But eventually, with the help of her colleague Drew Weissman, she discovered a way to protect synthetic mRNA from the body’s immune system, using a hybrid of synthetic and natural mRNA to sneak past the body’s defenses and instruct the body to do…well, potentially, a lot.
In 2005, Karikó and Weissman started publishing their findings on this hybrid mRNA. Their papers caught the attention of two teams of researchers that would eventually become Moderna and BioNTech. At first, neither company was very interested in infectious disease or vaccines. Those weren’t “hot spaces,” financially speaking. Both companies set their sights on oncology instead, where vast amounts of money were and are being invested. By 2019, though, both companies had dipped their toes into mRNA vaccines, partially due to the same immune response problems Karikó had observed. These side effects grew worse with the larger numbers of doses needed to treat cancer.
Then a pandemic came, priorities changed, and vaccines became the center of attention. With private and public money being thrown at the problem from every direction, most companies pursued tried-and-true methods of vaccine development. BioNTech (partnered with Pfizer) and Moderna launched ahead of the competition with mRNA vaccines.
As with penicillin, a wartime mentality had again come to the biotech sector. We should be glad it did. Without it, could we have developed COVID vaccines so quickly? There was even a brief, beautiful moment where it felt like every American was doing their part and getting vaccinated. Or at least I let myself believe that for a minute.
We were fortunate with penicillin and mRNA vaccines as people were working on those problems before they became crucial. Then, instead of squandering previous work, society spent public and private funds on those technologies to bring them to the world, fast. These inventions — the ones used inside our own bodies — rely on some of the most complicated mechanisms known to science. We have stories like Fleming’s, Hunt’s, and Karikó’s to simplify them, inspire us, and teach broader lessons about the scientific process. But we cannot allow simple stories to fuel the public misconception that science runs on simple developments. No drug was ever developed in a day.
