“I said, ‘I am an RNA scientist. I can do anything with RNA,’” Dr. Karikó recalled telling Dr. Weissman. He requested her: Could you make an H.I.V. vaccine?
“Oh yeah, oh yeah, I can do it,” Dr. Karikó mentioned.
Up to that time, industrial vaccines had carried modified viruses or items of them into the physique to coach the immune system to assault invading microbes. An mRNA vaccine would as a substitute carry directions — encoded in mRNA — that will permit the physique’s cells to pump out their very own viral proteins. This method, Dr. Weissman thought, would higher mimic an actual an infection and immediate a extra strong immune response than conventional vaccines did.
It was a fringe concept that few scientists thought would work. A molecule as fragile as mRNA appeared an unlikely vaccine candidate. Grant reviewers weren’t impressed, both. His lab needed to run on seed cash that the college provides new school members to get began.
By that point, it was straightforward to synthesize mRNA within the lab to encode any protein. Drs. Weissman and Karikó inserted mRNA molecules into human cells rising in petri dishes and, as anticipated, the mRNA instructed the cells to make particular proteins. But after they injected mRNA into mice, the animals obtained sick.
“Their fur got ruffled, they hunched up, they stopped eating, they stopped running,” Dr. Weissman mentioned. “Nobody knew why.”
For seven years, the pair studied the workings of mRNA. Countless experiments failed. They wandered down one blind alley after one other. Their downside was that the immune system sees mRNA as a bit of an invading pathogen and assaults it, making the animals sick whereas destroying the mRNA.
Eventually, they solved the thriller. The researchers found that cells defend their very own mRNA with a selected chemical modification. So the scientists tried making the identical change to mRNA made within the lab earlier than injecting it into cells. It labored: The mRNA was taken up by cells with out frightening an immune response.