She grew up in Hungary, daughter of a butcher. She wanted to be a scientist. She moved to the US but for decades never found a permanent position, instead clinging to the fringes of academia.

Now Katalin Kariko, 66, known to colleagues as Kati, has emerged as one of the heroes of Covid-19 vaccine development. Her work, with her close collaborator, Dr Drew Weissman of the University of Pennsylvania, US, laid the foundation for the stunningly successful vaccines by Pfizer-BioNTech and Moderna.

For her entire career, Kariko has focussed on messenger RNA, or mRNA — the genetic script that carries DNA instructions to each cell’s protein-making machinery. She was convinced mRNA could be used to instruct cells to make their own medicines, including vaccines.

But for many years her career at the University of Pennsylvania was fragile. She migrated from lab to lab, relying on one senior scientist after another to take her in. She never made more than $60,000 a year.

“When your idea is against the conventional wisdom that makes sense to the star chamber, it is very hard to break out,” said Dr David Langer, a neurosurgeon who has worked with Kariko.

In 1989, she landed a job with Dr Elliot Barnathan, then a cardiologist at the University of Pennsylvania. It was a low-level position, research assistant professor, and never meant to lead to a permanent tenured position. She was supposed to be supported by grant money, but none came in.

She and Barnathan planned to insert mRNA into cells, inducing them to make new proteins. In one of the first experiments, they hoped to use the strategy to instruct cells to make a protein called the urokinase receptor. If the experiment worked, they would detect the new protein with a radioactive molecule that would be drawn to the receptor.

One fateful day, the two scientists hovered over a dot-matrix printer in a narrow room at the end of a long hall. A gamma counter, needed to track the radioactive molecule, was attached to a printer. It began to spew data. Their detector had found new proteins produced by cells that were never supposed to make them — suggesting that mRNA could be used to direct any cell to make any protein at will. “I felt like a god,” Kariko recalled.

Barnathan, though, soon left the university, accepting a position at a biotech firm, and Kariko was left without a lab or financial support.

Universities only support low-level PhDs for a limited amount of time, Langer said, “If they don’t get a grant, they will let them go.” Kariko “was not a great grant writer”, and at that point “mRNA was more of an idea”, he said. Langer urged the head of the neurosurgery department to give Kariko’s research a chance. “He saved me,” she said.

Langer hoped to use mRNA to treat patients who developed blood clots following brain surgery, often resulting in strokes. His idea was to get cells in blood vessels to make nitric oxide, a substance that dilates blood vessels but has a half-life of milliseconds. Doctors cannot just inject patients with it.

He and Kariko tried their mRNA on isolated blood vessels used to study strokes. It failed. They trudged through snow in Buffalo, New York, US, to try it in a laboratory with rabbits prone to strokes. Failure again.

And then Langer left the university, and the department chair said he was leaving as well. Kariko again was without a lab and without funds. A meeting at a photocopying machine changed that. Weissman happened by, and she struck up a conversation. “I said, ‘I am an RNA scientist; I can make anything with mRNA’,” Kariko recalled. Weissman told her he wanted to make a vaccine against HIV. “I said, ‘Yeah, yeah, I can do it’,” Kariko said.

Despite her bravado, her research on mRNA had stalled. A control in an experiment finally provided a clue. Kariko and Weissman noticed their mRNA caused an immune overreaction. But the control molecules, another form of RNA in the human body — so-called transfer RNA, or tRNA — did not.

A molecule called pseudouridine in tRNA allowed it to evade the immune response. As it turned out, naturally occurring human mRNA also contains the molecule.

Added to the mRNA made by Kariko and Weissman, the molecule did the same — and also made the mRNA much more powerful, directing the synthesis of 10 times as much protein in each cell.

The idea that adding pseudouridine to mRNA protected it from the body’s immune system was a basic scientific discovery with a wide range of thrilling applications.

Leading scientific journals rejected their work. When the research was finally published, in Immunity, it got little attention. “We talked to pharmaceutical companies and venture capitalists. No one cared,” Weissman said.

Eventually, though, two biotech companies took notice of the work: Moderna, in the US, and BioNTech, in Germany. Pfizer partnered with BioNTech, and the two now help fund Weissman’s lab.

Soon clinical trials of an mRNA flu vaccine were underway, and there were efforts to build new vaccines against cytomegalovirus and the Zika virus, among others.

Then came the coronavirus. Chinese scientists posted the genetic sequence of the virus ravaging Wuhan in January 2020, and researchers everywhere went to work. BioNTech designed its mRNA vaccine in hours; Moderna did it it in two days.

On November 8, the first results of the Pfizer-BioNTech study came in, showing the mRNA vaccine offered powerful immunity. Kariko turned to her husband. “Oh, it works,” she said. “I thought so.”

To celebrate, she ate an entire box of Goobers chocolate-covered peanuts — by herself.

NYTNS