COVID-19 mRNA vaccines have Oak Ridge roots

The COVID-19 pandemic has added a lot of new terms to daily conversation. Phrases like “mask mandate” and “social distancing” will probably fall into disuse when COVID-19 passes from the scene. However, the term “mRNA vaccine” is likely to have more staying power.

Messenger RNA — mRNA — vaccines, such as the highly effective COVID-19 jabs developed by Pfizer and Moderna, are the first inoculations of their kind to be approved by the FDA for use against any disease, and they have had a profound effect in curtailing infections.

mRNA is a specialized type of RNA — a molecule that’s similar to its cousin, DNA, the molecule that carries genetic information in all known forms of life.

Early studies

Studies on the structure of RNA were done at ORNL in the early 1950s by biologist Elliot “Ken” Volkin and biochemist Waldo Cohn. They used radioisotope and chromatography techniques that were originally developed for plutonium production at the laboratory’s Graphite Reactor during World War II.

In 1956, further research by Volkin and ORNL biologist Lazarus Astrachan enabled them to observe the role that RNA plays when a virus infects a bacterium. This interaction proved to be critical to understanding the role that RNA plays in viral infections.

Paul Berg, winner of the 1980 Nobel Prize in Chemistry, said Volkin and Astrachan discovered that, when a bacteriophage virus infects a bacterium, the virus takes over the cell’s protein-making machinery and instructs it to make viral proteins. The coding sequences of the virus’s genes are copied from its DNA into short-lived RNAs that are transported out of the nucleus into the cytoplasm, where the proteins are assembled. Because these RNAs transport information from genes in the nucleus to the cytoplasm, they are called messenger RNAs.

Former ORNL director Alvin Weinberg said that Berg described these studies on mRNA as an “unsung but momentous discovery of a fundamental mechanism in genetic chemistry” and a “seminal discovery [that] has never received its proper due.”

DNA-like RNA

Volkin and Astrachan called this new kind of RNA “DNA-like RNA” and spent several years investigating its behavior. Their findings, published in 1956, received a less-than-enthusiastic reception in the biology community. Volkin reportedly thought that the findings weren’t widely accepted because they didn’t agree with theory at the time — even though he and Astrachan repeated the studies several times with the same results.

Five years later, French scientists François Jacob and Jacques Monod published a paper that further illuminated the function of mRNA, an accomplishment for which they received the 1965 Nobel Prize in Medicine and Physiology.

Special delivery

The mRNA vaccines developed over the last two years to combat COVID-19 take advantage of mRNA’s knack for delivering instructions by telling cells to build a piece of the COVID-19 spike protein that enables the virus to attach itself to human cells.

Once this fragment of the COVID-19 protein appears on the surface of cells, the body’s immune system recognizes it as a threat and starts making antibodies to eliminate it. Later, when a COVID-19 virus sporting the same spike protein appears, antibodies are already on hand to defend against it.

The success of mRNA vaccines in slowing the COVID-19 pandemic makes it likely that we will soon see efforts to apply similar technology to the task of warding off a range of infectious diseases. It also illustrates the importance of basic scientific research — like Volkin and Astrachan’s findings — which, although they were dismissed at the time, ultimately helped to pave the way for a new class of pandemic-beating vaccines.