The University of Pennsylvania is basking in the glow of two researchers who this week were awarded the Nobel Prize in medicine for their pioneering work on messenger RNA.
Until recently, the school and its faculty largely disdained one of those scientists.
Penn demoted Katalin Kariko, shunting her to a lab on the outskirts of campus while cutting her pay. Kariko's colleagues denigrated her mRNA research, and some wouldn't work with her, according to her and people at the school. Eventually, Kariko persuaded another Penn researcher, Drew Weissman, to work with her on modifying mRNA for vaccines and drugs, though most others at the school remained skeptical, pushing other approaches.
Kariko hasn't only proved her detractors wrong but also reached the pinnacle of science. Her research with Weissman helped lead to the mRNA vaccines that protected people worldwide during the Covid-19 pandemic and now shows promise for flu, cancer and other diseases.
Penn, which patented their mRNA technology, has made millions of dollars from drugmakers that licensed it. And on Monday, when Kariko and Weissman were awarded the Nobel, on top of prestigious science prizes in recent years, the school expressed a different perspective on their work.
The reversal offers a glimpse of the clubby, hothouse world of academia and science, where winning financial funding is a constant burden, securing publication is a frustrating challenge and those with unconventional or ambitious approaches can struggle to gain support and acceptance.
"It's a flawed system," said David Langer, who is chair of neurosurgery at Lenox Hill Hospital, spent 18 years studying and working at Penn and was Kariko's student and collaborator.
Penn wasn't the only institution to doubt Kariko's belief in mRNA when many other scientists pursued a different gene-based technology. In a reflection of how radical her ideas were at the time, she had difficulty publishing her research and obtaining big grants.
Another reason her relationship with the school frayed: Kariko could antagonize colleagues. In presentations, she often was the first to point out mistakes in their work. Kariko didn't intend to offend, she just felt the need to call out mistakes, she later said.
A native of Hungary, Kariko came to the university in 1989 as a research assistant professor in the cardiology department of the medical school. Her job, which wasn't a tenure-track position, was to do research and deliver lectures for graduate students.
Kariko was thrilled at the chance to pursue her mRNA research and became a friendly presence in the department. Yet she felt like something of a second-class citizen. Once, she was reprimanded for using deionized water belonging to a senior member of her lab, rather than climb five flights of stairs to get some from a different laboratory, she later recalled.
After long days in the lab, Kariko returned home to write grant applications, proposing to use mRNA to develop various treatments. She rarely found success. Reviewers sometimes questioned her proposals, noting her title at the school.
Penn professors and others had good reasons for their skepticism. Most everyone else was becoming enamored with using DNA, a different molecule. DNA has two strands of nucleotides that wind around each other like a twisted ladder, making it durable. By contrast, mRNA is single-stranded and notoriously unstable and hard to work with.
To Kariko, mRNA was the perfect molecule -- it only needed to get inside the cell's walls to create proteins, not all the way into the nucleus, like DNA.
In 1995, after Kariko turned 40, she received an ultimatum: Leave Penn or agree to a demotion. Kariko accepted a new, lower-paid position. It left her feeling liberated, she later said, while giving her time to keep improving her mRNA techniques.
Then she and Weissman achieved a breakthrough. They modified the base components, or nucleosides, of mRNA, to avert an inflammatory response. Now, the molecule could get into cells to create ample proteins, the key to producing vaccines and drugs.
Penn patented their mRNA technology. Kariko and Weissman tried to license it for their biotech company but couldn't afford the price the school demanded, Weissman recalled.
Penn eventually licensed it to another company. During the past few years, Penn made tens of millions of dollars licensing the technology to various companies including BioNTech and Moderna that produced Covid vaccines.
Today, Kariko is an adjunct professor in the school's department of neurosurgery.
"Katalin Kariko and Drew Weissman are brilliant researchers who represent the epitome of scientific inspiration and determination," Penn's president, Liz Magill, said this week." [1]
Katalin Kariko was just very lucky. Drew Weissman is so taciturn and gloomy that no one wants to work with him. Because of that loneliness, he agreed to help her.
1. U.S. News: Penn Toasts Winning Scientist After Shunning Her for Years. Zuckerman, Gregory. Wall Street Journal, Eastern edition; New York, N.Y.. 05 Oct 2023: A.2.
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