The 2023 Nobel Prize for physiology or medicine has been awarded to the Hungarian biochemist Katalin Karikó and the American physician-scientist Drew Weissman. According to the Royal Swedish Academy of Science, they have been feted for “discoveries concerning nucleoside base modification that enabled the development of effective mRNA vaccines against COVID-19”.
Dr. Karikó is only the thirteenth woman to win the prize.
That the citation mentions the pandemic is testament to the effect mRNA vaccines had on its evolution as well as how the global disaster became an opportunity for these vaccines’ technology to showcase its potential.
mRNA stands for messenger RNA, a type of molecule that carries instructions from the DNA to a cell’s cytoplasm, where those messages are ‘read’ to produce various proteins. In the late 1980s, scientists realised that mRNA could become the basis for a new kind of vaccines if some hurdles could be overcome.
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The idea was to inject the body with a modified mRNA that would instruct cells to build a certain protein, which could then provoke the body’s immune system to ‘attack’ it as well as prepare itself to encounters with the same protein in future. This protein could be something produced by a virus – such as the spike protein of SARS-CoV-2. But the mRNA would have to survive its journey inside the body and be able to enter a cell.
Dr. Karikó and Dr. Weissman began to collaborate in the late 1990s. They and other scientists published many studies until 2004 elucidating the steps from delivering mRNA into a body (such as of a rat) to the immune system responding. But one problem remained. The immune system sensed the synthetic mRNA to be a foreign substance that needed to be eliminated but not the cells’ mRNA. Why?
A study the duo published in 2005, with Michael Buckstein and Houping Ni, had the answer: the cells’ mRNA underwent chemical reactions that modified it in certain ways, whereas the synthetic mRNA remained unchanged.
RNA is made up of smaller molecules called bases. Dr. Karikó and Dr. Weissman reported that when they modified some of these bases in the synthetic mRNA and delivered it to cells, the cells produced more provocative proteins than they did without the modifications. They had found out how foreign mRNA could enter a body and then its cells without setting off alarm bells.
They published two more studies that set the stage for the use of an mRNA platform for a new kind of vaccine. In 2020, the COVID-19 pandemic dawned on the world, and mRNA vaccines played a pivotal role – if also one overtaken by the dubious virtues of vaccine nationalism – in lowering its death toll.
“You can start a production cycle in the morning and by evening have enough for tests,” former Indian Institute of Science, Bengaluru, director Govindarajan Padmanabhan told The Hindu in October 2022 about the advantage of mRNA vaccines. Currently, scientists are exploring their use against influenza, dengue, and some cancers and auto-immune diseases.
