A Penn official once told Katalin Karikó she was ‘not of faculty quality.’ Her work there just won a Nobel Prize.

Every year, Katalin Karikó met with her University of Pennsylvania department chair to update him on her quest to treat disease with messenger RNA — fragile, inflammatory genetic molecules that were so difficult to work with that most scientists thought it was a waste of time.

Every year, he listened to her passionate description of the science for a few minutes, then chastised her for not contributing to the department’s all-important metric: “dollars per net square footage” of lab space.

The bottom line: Penn had rejected Karikó for a tenure-track position years earlier because she failed to secure funds for her research, and she still hadn’t managed to come up with any.

As the world now knows, Karikó proved her naysayers wrong. She and Penn colleague Drew Weissman won the Nobel Prize in medicine Monday for their research, which paved the way for COVID-19 vaccines that are credited with saving millions of lives. The school has reaped more than $1 billion in royalties from licensing patents it took out on their discoveries.

“We are bursting with pride,” university president Liz Magill said at a news conference with the two scientists.

But in an autobiography that comes out Tuesday, Karikó describes years of struggle to get her ideas accepted by Penn colleagues and the broader scientific community. Even after 2005, when she and Weissman published the first of several studies showing how mRNA could be used in a vaccine, she was rebuffed in her attempts to seek a tenured position, she says in Breaking Through: My Life in Science, published by Crown.

“I was told that I was ‘not of faculty quality,’” she wrote, describing a conversation with an unidentified administrator at Penn’s Perelman School of Medicine.

Her account illustrates the competitive, constantly churning treadmill of academic science, where success is defined by money and the publication of studies in scientific journals — neither of which occurs without the other. Scientists can’t conduct their experiments without money for chemicals, lab animals, and other supplies, yet in order to secure that funding, they have to provide the results of experiments. Which requires money.

The result is that many successful scientists learn to practice what is called grantsmanship, namely publishing safe, incremental advances to keep the funds coming.

Karikó chafed under that system, instead aiming for a high-risk target — using mRNA to fight disease — that most of her peers thought was unattainable. She did it working in lowly, non-tenured positions for more than two decades, finding a home in the labs of a few sympathetic colleagues who could spare the funds. Frustrated, she finally left Penn in 2013 for a German start-up called BioNTech, which would one day collaborate with Pfizer to make the first COVID vaccine.

Asked whether Karikó should have been granted tenure, the university responded with this statement:

“Dr. Katalin Karikó and Dr. Drew Weissman are outstanding scientists, whose discoveries helped pave the way for developing the life-saving vaccines deployed in the global fight against COVID-19. The recognition of their important work with the Nobel Prize is deeply deserved. We acknowledge and are grateful for the valuable contributions Dr. Karikó has made to science and to Penn throughout her time with the university.”

In interviews, two former Penn physicians said her account of repeated rejection was spot-on.

David Langer, now the chair of neurosurgery at Lenox Hill Hospital in New York, said it took a pandemic for others — both at Penn and beyond — to realize Karikó’s ideas held merit.

“Of course, hindsight is 20/20,” he said. “They should’ve promoted her.”

Former Penn cardiologist Elliot Barnathan, who hired Karikó to work in his lab in 1989, said the buzz at the time was all about gene therapy, which sought to harness the power of RNA’s more stable cousin, DNA.

RNA, on the other hand, is a temporary copy of DNA that degrades easily, and most academics dismissed Karikó’s idea of using it to treat disease.

“It was completely heretical at the time,” he said.

Barnathan rejected Karikó at first, too. When she sent in her application for a vacancy in his lab and did not hear back, she called his secretary to ask why. Barnathan believed that he had not found the right person, and planned to readvertise the position, the secretary said.

Karikó, who had previously worked at a lab at Temple University and was then working at a hospital in Maryland, was unsatisfied.

“She asked my secretary if I could please look at it again,” he recalled.

Barnathan hired Karikó after all, collaborating with her to study RNA in cardiovascular cells. When he left for a job in industry, she found another supporter in Langer, who was then a resident in Penn’s neurosurgery department. The pair studied mRNA in the brain.

In interviews, Barnathan and Langer said Karikó was not naive. She knew full well that her ideas meant nothing without money, whether at Penn or anywhere else. They said that at times, she may have hurt her cause with her blunt-spoken manner.

In the book, Karikó acknowledges that she was a tough taskmaster. She described one such instance from when she first met Langer, back when he was a medical student at Penn. He and a classmate bungled one of the steps in preparing a batch of RNA, and Karikó scolded them and threw out their samples.

“What were you thinking?” she said. “It’s useless, garbage!”

Karikó also stood out because of her background. The daughter of a butcher who’d completed the equivalent of sixth grade, she grew up in communist Hungary in a modest home with no running water, heated by burning sawdust left over from a nearby toy factory. As a scientist, she often sensed she was an outlier in the clubby world of medicine, whose leaders often were men whose fathers had been physicians before them.

In the book, Karikó describes one such episode when she traveled to a stroke center in Buffalo to perform an mRNA experiment in the brains of rabbits. She told her Buffalo counterpart that the experience reminded her of her father’s profession.

“No kidding!” he said. “My father is also a neurosurgeon. And my grandfather, too!”

She laughed, explaining that her upbringing was very different.

For decades, Karikó continued to publish what she considered to be high-quality research, but discovered it was not enough to gain acceptance by academia’s elite.

“I was learning that succeeding at a research institution like Penn required skills that had little to do with science,” she wrote. “You needed to know how to do things in which I have never had any interest (flattering people, schmoozing, being agreeable when you disagree, even when you are 100% certain that you are correct).”

She also found that for her career to advance, the studies also needed to be cited by others. Even when she started to collaborate with Weissman, the immunologist with whom she would share the Nobel, the work attracted little notice at first. For a long time, their initial 2005 study was cited by others just a few times a year.

But the pair were confident that the transient nature of mRNA, long seen by others as a flaw, would be a plus when used in a vaccine. They and others figured out how to deliver the delicate genetic molecules inside human cells by encapsulating them in millions of oily droplets, called lipid nanoparticles.

Once there, the mRNA served as a temporary blueprint, enabling the recipient’s cells to make a useful protein without any permanent changes to the person’s genetic makeup.

That’s how the COVID vaccines work. The mRNA carries the recipe for a spike-like protein on the surface of the coronavirus, giving the recipient a safe sneak preview of the virus so the immune system can prepare to fight the real thing.

On Dec 10, she and Weissman are due in Stockholm to receive the Nobel, the ultimate recognition that they were right.

Staff writer Susan Snyder contributed to this article.