STOCKHOLM -- Two scientists won the Nobel Prize in medicine Monday for discoveries that enabled the creation of mRNA vaccines against covid-19 that were critical in slowing the pandemic -- technology that's also being studied to fight cancer and other diseases.
Hungarian-American Katalin Kariko and American Drew Weissman were cited for contributing "to the unprecedented rate of vaccine development during one of the greatest threats to human health," according to the panel that awarded the prize in Stockholm.
The panel said the pair's "groundbreaking findings ... fundamentally changed our understanding of how mRNA interacts with our immune system."
Traditionally, making vaccines required growing viruses or pieces of viruses and then purifying them before the next steps. The messenger RNA approach starts with a snippet of genetic code carrying instructions for making proteins. Pick the right virus protein to target, and the body turns into a miniature vaccine factory.
In early experiments with animals, simply injecting lab-grown mRNA triggered a reaction that usually destroyed it. Those early challenges caused many to lose faith in the approach.
But Kariko, a professor at Szeged University in Hungary and an adjunct professor at the University of Pennsylvania, and Weissman, of the University of Pennsylvania, figured out a tiny modification to the building blocks of RNA that made it stealthy enough to slip past immune defenses.
Kariko, 68, is the 13th woman to win the Nobel Prize in medicine. She was a senior vice president at BioNTech, which partnered with Pfizer to make one of the covid-19 vaccines. Kariko and Weissman, 64, met by chance in the 1990s while photocopying research papers, Kariko told The Associated Press.
When they started chatting, Kariko bragged that she could make Weissman 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.
Dr. Paul Hunter, a professor of medicine at Britain's University of East Anglia, described the mRNA vaccines made by BioNTech-Pfizer and Moderna Inc. as a "game-changer" in shutting down the coronavirus pandemic, crediting the shots with saving millions of lives.
"We would likely only now be coming out of the depths of covid without the mRNA vaccines," Hunter said.
John Tregoning of Imperial College London, called Kariko "one of the most inspirational scientists I have met." Her work with Weissman "shows the importance of basic, fundamental research in the path to solutions to the most pressing societal needs," he said.
The duo's pivotal mRNA research was combined with two other earlier scientific discoveries to create the covid-19 vaccines. Researchers in Canada had developed a fatty coating to help mRNA get inside cells to do its work. Studies with prior vaccines at the U.S. National Institutes of Health showed how to stabilize the coronavirus spike protein that the new mRNA shots needed to deliver.
Dr. Bharat Pankhania, an infectious diseases expert at Exeter University, predicted that the technology used in the vaccines could be used to refine vaccines for other diseases like Ebola, malaria and dengue, and might also be used to create shots that immunize people against certain types of cancer or auto-immune diseases including lupus.
'NOW IT'S HERE'
"The future is just so incredible," Weissman said. "We've been thinking for years about everything that we could do with RNA, and now it's here."
Since 2021, Kariko and Weissman 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 he sleeps poorly, so he was awake early Monday morning at his home in Philadelphia.
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 daughter.
The two have collaborated for decades, with Kariko focusing on the RNA side and Weissman handling the immunology: "We educated each other," she said.
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.
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 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, Pa., to work for a little-known startup called BioNTech that was working on turning mRNA into medicine.
Eventually, that company would partner with Pfizer to create an mRNA vaccine against the coronavirus, and Kariko would become only 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 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.
Before covid-19, mRNA vaccines were already being tested for diseases like Zika, influenza and rabies -- but the pandemic brought more attention to this approach, Kariko said. Now, scientists are trying out mRNA approaches for cancer, allergies and other gene therapies, Weissman said.
"It's already been going on for many years, but this has just given RNA the recognition," he said.
The prize carries a cash award of $1 million from a bequest left by the prize's creator, Swedish inventor Alfred Nobel. The laureates are invited to receive their awards at ceremonies Dec. 10, the anniversary of Nobel's death.
Nobel announcements continue with the physics prize today, chemistry Wednesday and literature Thursday. The Nobel Peace Prize will be announced Friday and the economics award on Oct. 9.
Information for this article was contributed by David Keyton, Mike Corder, Maddie Burakoff, Maria Cheng and Lauran Neergaard of The Associated Press and by Carolyn Y. Johnson of The Washington Post.