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We wouldn't have tried to fire you if we knew! Nobel Prize?

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After Shunning Scientist, University of Pennsylvania Celebrates Her Nobel Prize

School that once demoted Katalin Karikó and cut her pay has made millions of dollars from patenting her work

Katalin Karikó stuck with her mRNA research despite a struggle to publish her work and obtain big grants.

By Gregory Zuckerman, WSJ

Oct. 4, 2023 1:50 pm ET

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 Karikó, shunting her to a lab on the outskirts of campus while cutting her pay. Karikó’s colleagues denigrated her mRNA research and some wouldn’t work with her, according to her and people at the school. Eventually, Karikó 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.

Karikó hasn’t only proven 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 Karikó 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 Karikó’s student and collaborator.

Penn wasn’t the only institution to doubt Karikó’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—prerequisites for those hoping to get ahead in science and gain academic promotions.

Another reason her relationship with the school frayed: Karikó could antagonize colleagues. In presentations, she often was the first to point out mistakes in their work. Karikó didn’t intend to offend, she just felt the need to call out mistakes, she later said.

Once, she saw that cells two colleagues had worked on for weeks had degraded and were no longer viable and discarded them without asking for permission, startling her colleagues.

“This is trash,” Karikó told them.

The relationship between Karikó and Penn became strained over many years. A native of Hungary, she 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.

Karikó was thrilled at the chance to pursue her mRNA research and became a friendly presence in the department, lugging Hungarian dishes to the office that she shared with colleagues.

Yet Karikó also was sensitive to perceived affronts. Once, while chatting with colleagues at a department Christmas party, a professor mentioned that Karikó was working for him on a project.

“You think I’m working for you?” Karikó asked him, livid, according to someone who witnessed the episode. “I’m here to advance science, I’m never, ever, working for you.”

Research-assistant professors usually were foreign-born scientists—some faculty members referred to them as “the aliens”—willing to overlook meager salaries for the experience of working in the Ivy League university’s world-class labs and because Penn promised to support their green-card applications.

Karikó 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, Karikó 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. Researchers had to wear gloves just to touch equipment coming in contact with the molecule; just breathing on the instruments made them unusable for mRNA. Inside the cell, mRNA only sticks around a short while before it is eliminated. And the body has developed elaborate methods to ward off the molecule.

An infectious disease expert who helped develop the mRNA vaccine being used by Moderna and Pfizer BioNTech explains how Covid-19 has transformed vaccine development. Illustration: Preston Jessee for the Wall Street Journal

To Karikó, 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.

Karikó’s grant proposals met little success and she had to rely on faculty members to pay her salary.

In 1995, after Karikó turned 40, she received an ultimatum: Leave Penn or agree to a demotion. Karikó accepted a new, lower-paid position. It left her feeling liberated, she later said, while giving her time to keep improving her mRNA techniques.

“It’s like Fight Club, when you lose everything you are fearless,” she said in an interview in 2020 for the book “A Shot to Save the World.”

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. Karikó 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. Over 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, Karikó is an adjunct professor in the school’s department of Neurosurgery.

“Katalin Karikó and Drew Weissman are brilliant researchers who represent the epitome of scientific inspiration and determination,” Penn’s president, Liz Magill, said this week. Added Penn’s director of media relations, Ron Ozio, in a statement: “We acknowledge and are grateful for the valuable contributions Dr. Kariko has made to science and to Penn throughout her time with the University.”

Some other scientists called out the school for its treatment of Karikó. “UPenn needs to apologize to #NobelPrize2023 winner Dr. Karikó,” said epidemiologist and health economist Eric Feigl-Ding on X, formerly known as Twitter. Professor Florian Krammer added: “Didn’t you fire Katalin? Just asking……”

Resistance by Penn and others to Karikó’s work reflects how modern science works, Langer said. Her research with Weissman was a risky bet. It took them years to achieve their mRNA breakthrough and there was always a good chance their unconventional approach would prove fruitless.

“It begs the question of how many others aren’t being recognized for their work,” Langer said.

At the same time, talented people are overlooked in most every field.

“Michael Jordan was drafted third, Tom Brady was drafted 199th, you can say ‘how did people miss them’, too,” Langer said. “The story is that she persevered.”

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