Today, the power of messenger RNA is obvious: It is the backbone of coronavirus vaccines that were developed in record time, providing a crucial shield of protection that helped save millions of lives and allowed people to reunite safely with loved ones. But for decades, the idea this fragile genetic material could be a medicine was a tantalizing, unlikely possibility dangling at the margins of mainstream science.

Kariko and Weissman’s complementary knowledge helped to unravel a way to chemically tweak messenger RNA, turning basic biology into a useful medical technology ready to change the world when the pandemic struck. Their discovery is incorporated into the coronavirus vaccines made by Moderna and Pfizer and its German partner, BioNTech, which have now been administered billions of times.

For Kariko, awe-inspiring ideas, unnoticed successes and repeated rejections

Since 2021, the pair have been showered with many of the most prestigious prizes in science, leading to the expectation that it was a matter of when, not if, they would win a Nobel. In an interview, Weissman said that he sleeps poorly, so he was awake early Monday morning at his home in Philadelphia. But he wasn’t expecting a call from Stockholm this year, figuring it would be at least another six years until the work would be recognized.

He learned of the prize not from the Nobel committee initially, but from Kariko, who sent him a 4 a.m. text asking him if Thomas Perlmann had called him yet. He asked who that was, and she replied: Nobel Prize. They congratulated each other in disbelief, still wondering if it was a prank before they saw the official announcement online.

“It was a wonderful moment,” Weissman said, who celebrated with his wife and on FaceTime with his older daughter.

Perlmann, secretary general of the Nobel Assembly, said that when he spoke to Kariko early Monday, she reflected on her abrupt change in circumstances.

Kariko grew up in a small Hungarian village. Her father was a butcher, her mother a bookkeeper. She moved to the United States with her husband and toddler daughter in the mid-1980s and worked in a few different research jobs before landing a junior position at the University of Pennsylvania. Her track was an unlikely one for a future Nobel laureate — she struggled for years to raise the grant funding essential for a scientific career and never secured tenure.

Elliot Barnathan, a cardiologist who hired Kariko at Penn in 1989, said that he was overjoyed by the news and shared his elation Monday with a circle of people who had worked closely with Kariko, knew how she had struggled, and were cheering her on.

“She is really the embodiment of perseverance and what it takes to be a great researcher,” Barnathan said. Kariko’s ideas were radical in the late 1980s and early 1990s, he noted, but she relentlessly chipped away at problems, many of them incremental, always with the goal of making mRNA into a therapy.

In an interview for the Nobel Prize website, Kariko recalled that she “was kicked out and forced to retire” from Penn exactly 10 years ago. In a news conference held at Penn on Monday, where Kariko conducted much of her important scientific work but struggled for traditional success, she encouraged young scientists to love learning to solve problems and to be prepared for failure.

“You have to learn how to handle the failure, because most of the time, we don’t understand — we make [an] experiment and the outcome is not what we want,” Kariko said. “After failure … you move on.”

That is what Kariko did in her own life. In her late 50s, she moved away from her family, commuting to work in Germany from her home in Jenkintown, Penn. to work for a little-known start-up called BioNTech that was working on turning mRNA into medicine.

“I decided to go to Germany, to a biotech company that didn’t have a website, leaving my husband and my family behind. What the hell am I doing? For one week, every night, I cried myself to sleep,” Kariko said in a 2021 interview with The Washington Post.

Weissman helped make ‘hugs and closeness possible again’

Eventually, that company would partner with Pfizer to create an mRNA vaccine against the coronavirus, and Kariko would become the 13th woman to win the Nobel Prize in medicine.

“Every once in a while, you get a discovery that is transformative in that it’s not only for a specific discovery itself, but it essentially impacts multiple areas of science — and that’s what mRNA technology is,” said Anthony S. Fauci, a professor at Georgetown University and the former director of the National Institute of Allergy and Infectious Diseases.

Weissman was a fellow in Fauci’s lab for several years early in his career, and Fauci said he was a “very serious, committed, brilliant mind who was very creative.” He added that Weissman and Kariko brought different skill sets to a difficult scientific problem, and he praised their “persistent, dogged” work over decades.

“There was a great deal of skepticism early on. They didn’t have a lot of support, but they persisted,” Fauci said. “It was an amazingly productive collaboration.”

Decades of research helped launch a vaccine in record time

Messenger RNA is a code written in four letters that spell out the genetic instructions for building proteins in cells. Harnessing the ability to use the body’s own machinery to build proteins had vast therapeutic potential in theory, and Kariko had devoted her scientific life to trying to turn it into a medicine.

Weissman was focused on immune cells called dendritic cells and creating an HIV vaccine. When they started chatting at the photocopier in the late 1990s, Kariko bragged that she could make him messenger RNA for his experiments. “Kati lit the match,” he recalled at a news conference Monday. But they soon discovered a fundamental problem: By itself, messenger RNA triggered an inflammatory response.

In 2005, the pair discovered how to chemically modify one of the letters of RNA to nearly eliminate the inflammatory response. The Nobel committee recognized that fundamental work, but at the time the researchers were disappointed when it attracted little scientific notice.

“We couldn’t get funding, we couldn’t get publications, we couldn’t get people to really notice RNA as something interesting,” Weissman said. “It had failed clinical trials, and pretty much everybody gave up.”

Eventually, biotechnology companies became interested in the technology, but it was not until the pandemic — and the need to build vaccines at unprecedented speed — that its power became clear to the general public.

Weissman said he is most excited about extending messenger RNA to fight new diseases — a slew of vaccines are being tested against other infectious diseases, alongside cancer immunotherapies and rare disease treatments.

He hopes to use messenger RNA to develop a gene therapy to treat sickle cell disease that could be given as a single shot, opening up a cure to the less wealthy areas of the world where the disease is more common, including in Africa and India.

Cutting-edge experimental therapies for sickle cell are on the horizon, but they require patients’ own bone marrow cells to be removed, modified in a specialized laboratory and returned to them, a laborious and expensive process that isn’t practical to be administered in countries without vast medical resources.

The work is still in the early stages of development.

“Their approach costs a few million dollars per person, and in my view will never be useful worldwide,” Weissman said. “Ours is: You line people up, give them an IV injection and they’re cured. That can be done anywhere in the world easily.”

The Nobel Assembly cited the importance of the work for contributing to “the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.”