Don’t shoot the messenger. . . RNA !

I hate to say it (actually I love to say it), but the 1960s strikes again!

Last week, two companies reported great success with vaccines that could bring the world back to normal after many months of struggling to manage the Covid-19 virus. Even more companies may report good news, and the results have come astonishingly soon after President Trump developed Operation Warp Speed  to find therapeutics to fight the disease just seven months ago. How is this possible? Has something changed?


Fast vaccine development was the result of up-until-now unproven gene-based technology that promises new and targeted treatments for heart disease, cancer, diabetes, as well as other infectious diseases besides Covid. For many of you, this technology is connected to a familiar name from high school biology: messenger RNA or, simply, “mRNA.”

After the double helix shape of DNA discovery of James Watson,  Francis Crick, and Maurice Wilkins in 1953, researchers determined the mechanism by which amino acids were synthesized; the relationships between DNA, different kinds of RNA, and the central function of the cellular factory called a ribosome. This flurry of activity involved all sorts of biologists, physicists, chemists, and medical specialists in the early 1960s, and laid down the basic irreversible sequencing of how proteins were manufactured, and continues under the umbrella phrase of molecular medicine today.

Between 1960 and 1968 or so, we find names – virtually unknown – like Howard Dintzis, Francois Jacob, Sydney Brenner, Leslie Barnett, Matthew Meselson, Jacob Monod, Marshall Nirenberg, J.H. Mitthei, Robert Holley, Hans Khorana, and Sol Spiegelman, among others, who confirmed and began to explain the role of mRNA as a kind of molecular courier sent out from DNA with a quite a mission . . .

. . . to provide genetic instructions for cells to follow to make proteins whose myriad functions provide the foundation of life. Once scientists knew the genetic sequence of a pathogen – like a virus – the challenge was to program this master intermediary, mRNA, in a way that would trigger the production of disease-fighting proteins !

Hinted at in 1958, what is known as the “Central Dogma of Biology,” that illustrated the ordered flow of genetic information.

Winners of the 1968 Nobel Prize for Medicine and Physiology who, among others, helped to confirm “The Dogma” of biological systems.


This tinkering with the workings of genes differs from traditional virus vaccine production, which is miraculous to behold, but usually take years to develop. Examples include measles and shingles which use weakened or inactive strains to prompt an immune response from the body; and involve a complicated manufacturing and culturing process – often in eggs or large bioreactors.

By contrast, working with mRNA, researchers take advantage of the body’s molecular machinery so that vaccines become a kind of engineering issue instead of a scientific one.

The lure to repurpose cells into miniature drug factories to fight a disease hit a milestone with the complete mapping of the genome (the base pairs of nucleic acids that make up human DNA) in 2003. Hand in hand with advances in genetics came powerful computers that enabled researchers to vividly image problems to be solved, and render possibilities of tinkering at the cellular level.

In fact, companies such as Germany’s BioNTech in 2008 and Moderna in 2010 were created specifically to focus exclusively on mRNA, and carry out the promise that started when this ancient courier molecule was discovered in 1961. In 2018 the pharmaceutical giant Pfizer joined with BioNTech and, along with Moderna, quickly demonstrated that through mRNA mechanisms, the body can generate an immune response by stimulating disease-fighting T-cells – white blood cells that recognize and eliminate infected cells.

However efficient or facile these companies’ efforts, we don’t know how this will work in the intermediate to longer term since the vaccines have limitations that non-RNA manufactured vaccines don’t have. They must be stored at sub-zero temperatures. They require two doses three to four weeks apart to create an immune response. And the length of the induced immunity is unknown, and may be temporary.

Still, a virtue of this new “engineering” method is that it is highly adaptable if human immunity declines or the virus mutates, which happens routinely with the seasonal flu.

“The mRNA platform is essentially fully synthetic,” says Katherin Janson, who leads Pfizer’s vaccine research [The Wall Street Journal, Nov. 18, 2020]. “It’s a defined molecule that can be made very, very quickly, so you don’t need anything live – no live virus, no live cell culture, no eggs, no anything.”

It’s a new frontier, and, with frontiers come unknowns. We are on the threshold of programmable medicines of all sorts – from cancer to heart disease – with all the good, bad, and unexpected things that will inevitably come. In this case, we’re talking about “programming” to defeat an infectious disease, and if regulators approve applications now in the pipeline for emergency use to fight the coronavirus, it will be the first mRNA vaccine ever done.

And then we’ll be on our way . . . to the new frontier.

This Thanksgiving Day, let’s be thankful to those who brought us a vaccine for this bug in 2020 – those who built on the pioneering work of men and women in the 1960s who helped make it possible.

Until next time,

Thursday, November 26, 2020




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