Dr. Karikó, the 13th woman to win the prize, languished for many long years without funding or a permanent academic position, keeping her research afloat only by latching on to more senior scientists at the University of Pennsylvania who let her work with them. Unable to get a grant, she said she was told she was “not faculty quality” and was forced to retire from the university a decade ago. She remains only an adjunct professor there while she pursues plans to start a company with her daughter, Susan Francia, who has an M.B.A. and was a two-time Olympic gold medalist in rowing.
The mRNA work was especially frustrating, she said, because it was met with indifference and a lack of funds. She said she was motivated by more than not being called a quitter; as the work progressed, she saw small signs that her project could lead to better vaccines. “You don’t persevere and repeat and repeat just to say, ‘I am not giving up,’” she said.
She and Dr. Weissman had their first chance meeting over a copy machine at the University of Pennsylvania in 1998.
Dr. Karikó, the daughter of a butcher who had come to the United States from Hungary two decades earlier when her research program there ran out of money, was preoccupied by mRNA, which provides instructions to cells to make proteins. Defying the decades-old orthodoxy that mRNA was clinically unusable, she believed that it would spur medical innovations.
At the time, Dr. Weissman was desperate for new approaches to a vaccine against H.I.V., which had long proved impossible to defend against. A physician and virologist who had tried and failed for years to develop a treatment for AIDS, he wondered if he and Dr. Karikó could team up to make an H.I.V. vaccine.
It was a fringe idea that, when they began their research, seemed unlikely to work. The mRNA was delicate, so much so that when it was introduced to cells, the cells instantly destroyed it. Grant reviewers were not impressed. Dr. Weissman’s lab instead relied on seed money that the university gives new faculty members to get started.
“We saw the potential and we weren’t willing to give up,” Dr. Weissman said.
For years, Dr. Weissman and Dr. Karikó were flummoxed. Mice injected with mRNA became lethargic. Countless experiments failed. They wandered down one dead end after another. Their problem was that the immune system interprets mRNA as an invading pathogen and attacks it, sickening the animals while destroying the mRNA.
But eventually, the scientists discovered that cells protect their own mRNA with a specific chemical modification. So they tried making the same change to mRNA synthesized in the lab before injecting it into cells. It worked: The mRNA was taken up by cells without provoking an immune response.
The discovery “fundamentally changed our understanding of how mRNA interacts with our immune system,” the panel that awarded the prize said, adding that the work “contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.”
At first, other scientists were largely uninterested in taking up that new approach to vaccination. Their paper, published in 2005, was rejected by the journals Nature and Science, Dr. Weissman said. The study was eventually accepted by a niche publication called Immunity.
But two biotech companies soon took notice: Moderna, in the United States, and BioNTech, in Germany, where Dr. Karikó eventually became a senior vice president. The companies studied the use of mRNA vaccines for flu, cytomegalovirus and other illnesses. None moved out of clinical trials for years.
Then the coronavirus emerged.
Almost instantly, Drs. Karikó and Weissman’s work came together with several strands of disparate research to put vaccine makers ahead of the game in developing shots. That included research done in Canada that allowed fragile mRNA molecules to be safely delivered to human cells, and studies in the United States that pointed the way toward stabilizing the spike protein that coronaviruses used to invade cells.
By late 2020, less than a year into a pandemic that would eventually kill at least seven million people globally, regulators had authorized strikingly effective vaccines made by Moderna and by BioNTech, which partnered with Pfizer to produce its vaccine. Both used the modification Dr. Karikó and Dr. Weissman discovered.
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