Pioneers of mRNA Find Redemption in Nobel Prize
Katalin Karikó and Drew Weissman won the Nobel Prize in medicine on Monday for an idea that pushed them to the fringes of the scientific establishment before it saved millions of lives during the pandemic. Karikó, a molecular biologist, and Weissman, an immunologist, realized during a chance encounter at a University of Pennsylvania photocopy machine in the 1990s that they could combine their work to explore how messenger RNA might produce effective drugs or vaccines.
Their collaboration was met with skepticism by their colleagues and indifference in the scientific community. Karikó struggled to secure funding for her work. Penn demoted her and sent her to work in an office on the outskirts of campus.
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Years later, as drugmakers raced to develop vaccines against Covid-19, it was mRNA technology that powered widely used shots from Pfizer–BioNTech and Moderna. The Nobel committee credited Karikó’s and Weissman’s work with saving millions of lives. Karikó, a gregarious and outspoken scientist with a Ph.D. in biochemistry, had tried for nearly a decade to convince colleagues that mRNA could deliver desired proteins to the body. Then she met Weissman. Weissman, a medical doctor with a Ph.D. in immunology and microbiology, hardly smiled around campus, even for photos. His wife once joked that he was so taciturn he set a self-imposed word limit each day. He was eager to help other researchers, though.
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In the 1980s, researchers discovered a method of producing mRNA without cell culture called in vitro transcription. But mRNA made by that method triggered immune responses that caused inflammation and it didn’t result in efficient protein production in the body. Discoveries by Karikó and Weissman helped overcome those roadblocks. They proved they could modify mRNA, a kind of molecular worker bee that carries instructions encoded in DNA, so it could be used safely and effectively. Researchers are now testing mRNA vaccines to target other diseases including influenza and some cancers.
Weissman had been working with part of the immune system called dendritic cells, and Karikó had been experimenting with injecting mRNA into cancer cells. The two decided to inject mRNA into dendritic cells to see if the mRNA would cause the production of certain proteins. It did. The results were “off the wall,” Weissman once said. But the mRNA triggered an inflammatory response because the cells treated it as a foreign intruder, negating any benefit.
The duo figured out that if they modified the base components, or nucleosides, of mRNA, they could avert the inflammatory response. The modifications effectively rendered mRNA “immune silent,” allowing it to get into cells to do its work. The scientists also discovered that modified mRNA significantly increased protein production.
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https://archive.ph/YieOC
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This is why the vaccines were developed so fast - a criticism by many - the basic studies were already done.
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