Nobel Prize in Medicine Honors Two Scientists Who Enabled mRNA Vaccines

Katalin Karikó and Drew Weissman discovered a way to edit mRNA so it could be used in vaccines without getting attacked and destroyed by the body

A screen with a picture of the Nobel laureates behind a panel making the announcement
A photo from the announcemnent of this year's Nobel Prize in Physiology or Medicine. The researchers discovered a way to edit synthetic mRNA so that it could pass by cells' defense mechanisms, allowing it to be used in Covid-19 vaccines. Jonathan Nackstrand / AFP via Getty Images

Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine on Monday for their discoveries that contributed to the development of mRNA vaccines against Covid-19.

In 2005, the pair of researchers found a way to manipulate mRNA so that it could be used in vaccines, a puzzle that had blocked scientists’ efforts to create mRNA-based shots for decades. Fifteen years later, this breakthrough enabled Moderna and Pfizer-BioNTech to rapidly develop immunizations to fight the Covid-19 pandemic. Covid-19 vaccines, both with and without mRNA, saved an estimated tens of millions of lives around the world.

“What’s important here I think is that vaccines can be developed so fast, and this was as we just heard, largely due to ... improvements in technology and this basic discovery,” Gunilla Karlsson Hedestam, a member of the Nobel Committee, said at the prize’s announcement, per Scientific American’s Lauren J. Young.

Messenger RNA, or mRNA, is a single-stranded molecule that carries instructions for making proteins from DNA in the cell’s nucleus to the building machinery in the cytoplasm. These proteins conduct nearly all of the cell’s work.

Scientists hypothesized they could design mRNA in the lab that would direct cells to make viral proteins, training the immune system to fight a specific virus, writes Quanta magazine’s Yasemin Saplakoglu.

Prior to Covid-19, vaccines typically included killed or weakened viruses to trigger an immune response, or they contained parts of a virus, sometimes transmitted to cells through a harmless carrier called a “vector.” But these techniques required cells to be grown in controlled lab conditions, a resource-intensive process that slowed down vaccine production, according to a statement from the Nobel Committee.

In theory, mRNA vaccines could be made faster. But, in experiments, human cells always attacked the mRNA as though it were an invader. There didn’t seem to be a way around the fact that cells would destroy the foreign mRNA.

But Karikó, a biochemist who grew up in Hungary, chose to study the subject anyway. In the 1990s, she worked on the mRNA problem for years, even though her requests for grant funding were repeatedly denied. She even got demoted from the track to full professorship at the University of Pennsylvania, wrote Stat News’ Damian Garde and the Boston Globe’s Jonathan Saltzman in 2020.

“I thought of going somewhere else, or doing something else,” she told the publication. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”

In the late 1990s, Karikó started collaborating with Weissman, an immunologist also at the University of Pennsylvania who was searching for an HIV vaccine, per the New York Times’ Benjamin Mueller and Gina Kolata.

In 2005, the pair finally found a way to alter mRNA so that it evaded cells’ defenses. Just like DNA, RNA has four types of bases that attach to its backbone. In mammals’ cells, RNA bases are often modified, while those of synthetic mRNA are not. Altering the mRNA’s bases almost completely eliminated the cells’ inflammatory response, Karikó and Weissman discovered. In later studies, the researchers showed that edits to the bases also increased protein production.

This breakthrough aided the rapid development of two mRNA-based Covid-19 vaccines—Pfizer’s and Moderna’s—which were approved only a year after the first cases of the disease were reported. Now, about 650 million doses of the two vaccines have been given in the United States, with hundreds of millions more administered around the globe, per the New York Times. All Covid-19 vaccines combined prevented an estimated 14.4 million to 19.8 million deaths worldwide in the first year of their use.

“I think she should be given credit for saving the world,” Jean Bennett, a gene-therapy scientist also at the University of Pennsylvania, said of Karikó to the Washington Post’s Carolyn Y. Johnson in 2021. Her ideas were “so ahead of her time, she had a hard time convincing people that they would actually work. They seemed too science fiction-y to people and too challenging.”

Karikó is the 13th woman to receive the Physiology or Medicine Nobel since it was first awarded in 1901. She and Weissman will split the prize of 11 million Swedish kronor, about $1 million.

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