Katalin Karikó kept building the case anyway, and in 1995 the University of Pennsylvania demoted her after her grant applications were turned down again and again.
She and immunologist Drew Weissman found that swapping one building block of synthetic mRNA, uridine, for a related molecule called pseudouridine let the RNA slip past the immune system instead of triggering inflammation. The finding, published in 2005 after being turned down by several top journals, led to the modified building block later used in mRNA vaccines.
That fix sat mostly unnoticed for years outside a small circle of researchers, until it became the basis for the COVID-19 mRNA vaccines, authorized within a year of the pandemic's start and later given in billions of doses. In October 2023 the Nobel Assembly gave Karikó and Weissman the Prize in Physiology or Medicine, nearly three decades after her university judged the work not worth funding.
Read the original study
Karikó and Weissman, Nobel Prize, 2023 · doi.org/10.1016/j.immuni.2005.06.008
The idea they almost defunded won.
Source
- Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005). Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity, 23(2), 165–75. https://doi.org/10.1016/j.immuni.2005.06.008