PROVIDENCE, R.I. [Brown University] — In October 2023, the two scientists whose breakthrough discoveries made possible the SARS-CoV-2 vaccines received the Nobel Prize in Physiology or Medicine.

Their finding, in 2005, was deceptively small: a modification to a messenger RNA molecule, which let the molecule elude the body’s immune system, enter a cell and prompt it to produce antibodies. That tweak proved the viability of mRNA vaccines, and 15 years later saved millions of lives worldwide.

Prior to the COVID-19 pandemic, mRNA vaccines were developed for rabies and several cancers; clinical trials are still underway. But many experts believe RNA — ribonucleic acid — is poised to do so much more.

“COVID was just the tip of the iceberg,” says Dr. Mukesh K. Jain, dean of medicine and biological sciences at Brown University.    

Jain is referring not just to the diseases that scientists know are related in some way to RNA — several cancers, flu, Huntington’s disease, spinal muscular atrophy, Alzheimer’s disease and ALS, to name just a few — but to the ones scientists don’t yet know. And that number is vast: due to shortcomings in available technology, they know the function of, at most, 5% of all RNAs. The rest, says Brown Professor of Molecular Biology, Cell Biology and Biochemistry Juan Alfonzo, is “dark matter.”

Alfonzo, a world-renowned RNA biologist, sums up the fundamental quandary confronting his field: “What the heck is going on?”

He is determined to get to the bottom of the mystery, as director of the new Brown RNA Center and a leader in a global effort to identify and sequence all human RNA, in all of its forms — a project that Jain says would be “one of the largest scientific endeavors since the Human Genome Project.”

If the endeavor succeeds, Alfonzo adds, the outcome will be no less than “a new understanding of medicine and biology.”

This piece was adapted from a Medicine@Brown story by Phoebe Hall. Read the full feature on the magazine’s website.