In last week’s article, I covered the history behind the “new” mRNA vaccines. New is a relative term and was used in the media when talking about mRNA vaccines. It gave some the feeling that the technology was developed on the fly when their history goes back several decades in reality.

Projects with names like “Operation Warp Speed,” which focused on the creation and mass production of vaccines for SARS-Cov-2, made it seem like the process of testing the vaccines was rushed. Time was definitely pressing, but the vaccines went through all the standard steps in testing for safety and efficacy and on a massive worldwide scale. The story is a beautiful display of what our species can accomplish when pressed and lays a foundation for handling future pandemics.

It would be hard to pick a single year out that made the creation of the Pfizer and Moderna vaccines possible, but the year 2005 would be in the discussion. In that year, an article titled “A Scalable, Extrusion-Free Method for Efficient Liposomal Encapsulation of Plasmid DNA” was published in the journal Pharmaceutical Research. The paper demonstrated a novel technique for getting nucleic acids like DNA or RNA inside the already effective lipid nanoparticle delivery system Pieter Cullis worked on for decades. This showed that you could make vast amounts of these tiny fat bubbles that contained lab-engineered genetic codes and do so in a cost-effective way. Like many technologies, the main hurdle is often funding since investors tend to want a return.

That same year Katalin Karikó and Drew Weissman published an article in the journal Immunity titled “Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA.” This article showed that a modified component of RNA called pseudouridine could halt an immune reaction against lab-engineered RNA.

This pseudouridine is already very common in the human version of RNA but uncommon in bacterial RNA. Our immune systems have evolved mechanisms of detecting these tiny differences, allowing us to mount an immune reaction to the bacterial version and not our own. Suppose we simply engineered the RNA we wanted to deliver to have pseudouridine only. In that case, we could ensure it did not get detected and destroyed by our immune system.

The foundation for both effectiveness and mass production had been laid in 2005. The possibilities of this technology were now clear, and mRNA companies with the goals of revolutionizing vaccines and curing genetic diseases started popping up. BioNTech, the company behind the Pfizer vaccine, was formed in 2008, Moderna in 2010, and Defense Advanced Research Projects Agency began funding mRNA vaccine technologies in 2012. A technology over five decades in the making was now ready for the big-time, and research trials exploded.

Scientific advancements in our understanding of nucleic acids like RNA joined with chemical mass production advancements and finally with the almighty dollar to get us where we are today. Once the genome of SARS-CoV-2 was sequenced in early 2020, the ability to engineer and deliver a genetic vaccine to fight it was simple. Still, like all vaccines, it had to be put through the proper clinical trials first.

This Thanksgiving, I gave thanks to our not-so-new mRNA vaccines while remembering the family and friends I have lost to this tiny virus.

Dr. Jack Brown is the Paris Junior College Science Division chairman. 

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