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From “Not Good Enough” to Nobel Prize Winner

Art Courtesy of Luna Aguilar

Early in her career, Katalin Karikó was confronted with a dilemma. As a researcher at the University of Pennsylvania, she had struggled to secure grant money and was faced with an ultimatum: either leave the university and abandon any hopes of becoming a tenured faculty member, or receive a demotion, setting her career back by years. It seemed that Karikó’s deep interest in mRNA would soon see its end. What followed, instead, is a story of incredible persistence, dedication, and brilliance.

Beginning in the 1960s, scientists had connected the dots of DNA’s role in protein synthesis—the process responsible for almost all cellular functions—and mRNA was the critical missing piece. Short for messenger RNA, this helical strand of molecules represents DNA in a portable manner, allowing for information from the nucleus of the cell to be delivered to ribosomes where protein synthesis can occur.

By the 1970s, the concept of synthetic mRNA—custom-created in the lab and introduced into the cells of patients—created the prospect of initiating healing processes from within cells. Immediately, the possible range of applications seemed endless: could mRNA revolutionize vaccine development by prompting cells to produce key antibodies against convoluted viral infections? Could mRNA therapy enhance the immune system’s abilities to detect and eliminate cancerous cells? Karikó’s fascination with the potential of mRNA therapy inspired her life’s research within the field, making the University of Pennsylvania’s disregard of her work absolutely crushing. To better understand why, we must start from the beginning.

Katalin Karikó’s career in science began at the University of Szeged in her native Hungary, where she first learned about viruses and mRNA. There, she found herself surrounded by peers who seemed more academically prepared, whether more experienced in the lab or more fluent in English. In her recently published autobiography, Breaking Through: My Life in Science, Karikó reflects on her time at university and playing catch-up with her peers. “If I have any superpower, it has always been this: a willingness to work hard and methodically, and refuse to stop,” she wrote. This superpower would prove to be indispensable throughout her life.

In 1985, the company that had funded Karikó’s postdoctoral research terminated her role. Following many fruitless attempts to secure a funded position across Europe, Karikó finally found an opportunity to continue her research at Temple University in Philadelphia. She arrived in America with her husband, her daughter, and $1,200 in cash sewn into the stuffing of her daughter’s teddy bear.

While Karikó’s work was going well, her supervisor proved to be hostile, threatening to revoke her visa if she left his lab. But Karikó was determined to stay in America, and where there’s a will, there’s a way. In 1989, she found a position in the cardiology clinic at the University of Pennsylvania’s medical school as a biochemist surrounded by doctors. “Working among MDs [gave me] the thing I valued most: a chance to learn,” Karikó wrote. “Besides, when hadn’t I been a fish out of water?”

At first, her experience at UPenn was very positive. Alongside her boss, Dr. Elliot Barnathan, Karikó worked on using mRNA to deliver proteins that would reduce the risk of blood clots in target areas, and she became even more convinced of the potential of her research.

Unfortunately, this conviction was not shared by many. A critical metric for scientific success was—and still is—attracting funding, and Karikó had been repeatedly rejected by grants that deemed her research too risky and slow. “I published more slowly than others,” she explained. “I didn’t want my scientific papers to be rushed. I didn’t want to be so eager to publish that I risked contaminating the scientific literature with dubious results.”

Karikó found UPenn to be increasingly impatient with her lack of funding and as a result, dismissive of her work. “I was learning that succeeding at a research institution like Penn required skills that had little to do with science,” she wrote. “You needed the ability to sell yourself and your work.”

In January 1995, Karikó was diagnosed with breast cancer. Soon after, her husband was forced to stay in Hungary due to visa complications. This time also marked five years since she joined UPenn, and per university policy, she must either be demoted or leave. Faced with a difficult decision at one of the most difficult points in her life, Karikó nonetheless stayed true to her scientific calling, taking the demotion in order to continue her mRNA research.

Two years later, Karikó met Dr. Drew Weissman, an immunologist who had just joined the university. Weissman was interested in vaccines, and Karikó had just the expertise he needed to deliver antigens—molecules that trigger an immune response against viruses—with mRNA. The pair discovered that, by slightly altering one base nucleotide, they could safely administer mRNA without causing a negative inflammatory reaction. When combined with Karikó’s previous work on mRNA delivery, the team had the final piece of the puzzle.

The pair excitedly submitted their mRNA vaccine research to Nature—but their paper was rejected as merely an “incremental contribution.” When they finally convinced another journal to publish their work, it gained little attention.

Meanwhile, UPenn was again getting impatient, citing Karikó’s continued inability to secure funding. “[All they cared about was] dollars per net square footage,” she wrote. “The fact was, I barely cost this department anything… my salary was laughable compared with the neurosurgeons who surrounded me… I had no staff, no postdocs… I wasn’t even a faculty member!” When she appealed for her faculty position to be reinstated, the department responded that she was “not of faculty quality.”

Fortunately, with their research finally published, Karikó and Weissman’s mRNA vaccines were recognized by a few. Realizing that UPenn was not going to support their work, the pair licensed their technology to the then-little-known BioNTech, where Karikó assumed the role of vice president in 2013. Working in industry was refreshing, Karikó explained. “It didn’t matter whether you spoke with an accent, or whether you’d attended an Ivy League school, or if you were good at schmoozing.” Science was science.

Then, in early 2020, all eyes turned towards the novel coronavirus. Suddenly, vaccine development was required at an unprecedented scale and speed, and BioNTech was at the forefront. The Pfizer-BioNTech vaccine’s phase III trials came back successful within a year, making Karikó a hero. After decades of obstacles, threats of deportation, demotions, and rejections, her superpower—a fierce belief in her research and refusal to stop at any cost—had finally helped her realize her dream.

On October 2, 2023, Katalin Karikó and Drew Weissman were awarded the Nobel Prize in Physiology or Medicine for their work on mRNA vaccines.

UPenn immediately acknowledged Karikó’s and Weissman’s Nobel Prize, coining them “Penn’s historic mRNA vaccine research team” in a social media post (later marked as “misleading” due to Karikó’s lack of affiliation with the university over the past decade), accompanied by a press release that failed to mention Karikó’s difficult history with the university. The post drew criticism from prominent members of the medical and scientific communities. One assistant professor from Stevenson University commented, “A woman winning the Nobel Prize for the same work Penn called ‘not faculty quality’ & Penn CLAIMING CREDIT is exactly how misogyny in academia works.”

Indeed, Karikó’s journey underlines prominent issues in academia. UPenn’s self-congratulatory post highlights their attempt to mask their poor treatment and lack of support, while exemplifying the institutional desire to prioritize profit over genuine, innovative research. Finally, Karikó’s narrative serves as an important reminder of the repeated undervaluation of women’s work in science. While Karikó’s story is one of triumph, it’s important to call attention to the many shortcomings present in academia and to create an environment supportive of scientific innovation. In Karikó’s words:

“We can do better. Science, at its best, is about asking questions, trying things, and going wherever that inquiry takes you. It requires walking into the unknown—the unknown is the very point!”