Stopping progress and happy accidents: how the mRNA vaccine was made

“I said,’I’m an RNA scientist. You can do anything with RNA,” Dr. Kariko recalled telling Dr. Weissman. He asked her: can you make an HIV vaccine?

“Oh yeah yeah yeah I can do that,” said Dr. Kariko. Said.

Until that point, over-the-counter vaccines had carried modified viruses or fragments thereof into the body to train the immune system to attack invading microorganisms. Instead, mRNA vaccines carry mRNA-encoded instructions that allow cells in the body to shed their viral proteins. Dr. Weissman believed that this approach would better mimic the actual infection and promote a stronger immune response than traditional vaccines.

Few scientists thought it would work. Molecules as fragile as mRNA seemed unlikely vaccine candidates. The grant reviewers were also unimpressed. His lab had to be run with seed money offered to new faculty to start the university.

By that time, it was easy to synthesize mRNA in the lab and encode any protein. Dr. Weissman and Kariko inserted the mRNA molecule into a human cell growing in a Petri dish, and as expected, the mRNA instructed the cell to make a specific protein. However, when they injected the mRNA into the mice, the animals became ill.

“Their fur was ruffled, crouched, stopped eating, and stopped running,” said Dr. Weissman. “No one knew why.”

The pair studied the workings of mRNA for seven years. Countless experiments have failed. They wandered one after another in the blind alleys. Their problem was that the immune system considered it part of the pathogen that invaded the mRNA and attacked it, destroying the mRNA and making the animal sick.

Eventually, they solved the mystery. Researchers have discovered that cells protect their mRNAs with certain chemical modifications. So scientists tried to make the same changes to the mRNA made in the lab before injecting it into the cells. It worked: mRNA was taken up by cells without eliciting an immune response.

Stopping progress and happy accidents: how the mRNA vaccine was made

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