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Saturday, December 2, 2023
Dr. Brown: Work on mRNA vaccines led to Nobel Prize in medicine
Dr. William Brown gets into the science and history of mRNA vaccines. RICHARD HARLEY/MIDJOURNEY

This year’s Nobel Prize was awarded to Katalin (Kati) Karikó and Drew Weissman for their key role in the development of mRNA vaccines in the two decades leading up to the COVID-19 pandemic.

Without that off-the-shelf work, mRNA vaccines would not have been available for the ensuing pandemic and many more millions would have died or developed persistent disabling post-infection symptoms – what’s been called Long COVID. But first a little history about mRNA.  

Single-stranded RNA probably appeared long before DNA in the evolutionary record because RNA offered a simpler, albeit more error prone tool for coding generation to generation genetic information.

In that role, RNA remains the sole tool for coding information in viruses such as COVID. 

For more complex lifeforms such as most cells, RNA was usurped by DNA as the primary tool for coding genetic complex information in genes.

In cells, genes play many roles of which the manufacture of thousands of different proteins is among the most important because they provide the building blocks for the cell’s internal skeleton, transport systems, communications systems, and several organelles in the cell. 

The steps between DNA and proteins form the “central dogma” of molecular biology. In the first, called transcription, a single stranded copy of the sequence of bases in the gene is made, called messenger RNA or mRNA.

In the last step, the base sequence in the mRNA is read by the cell’s ribosomes in the cytoplasm where the code is translated into a series of specific amino acids to create the precise protein specified by each gene. 

It’s more complicated than that but the essential point to grasp is the messenger-boy role played by mRNA in transcribing and translating specific genes into matching specific proteins.

That is the key to understanding the new science of employing mRNA to create tailor-made proteins including drugs for cancer and copies of the spike proteins of the COVID virus to provoke immune responses by the novel mRNA vaccines created and manufactured by Pfizer-BioNTech and Moderna.

Fortunately, hurdles to mRNA technologies, which would have stymied the development of mRNA vaccines, were overcome by Weissman and Karikó in the two preceding decades.

They helped make mRNA safe and effective for billions of recipients during the pandemic and later.

Another key obstacle to overcome with mRNA vaccines was how to protect fragile RNA from enzymes that would normally destroy it soon after it was injected.

The solution was to closet the mRNA in a lipid nanoshell to protect it from circulating enzymes in transit between the injection and insertion of the mRNA inside the host’s cells. 

Once inside, the mRNA co-ops the cell’s protein machinery (ribosomes) to create the desired proteins. Mission accomplished: the mRNA is then destroyed by the cell’s own enzymes, leaving nothing behind.

The latter is important because some anti-vaccine proponents continue to claim the mRNA (and DNA in other vaccines) becomes incorporated within the host’s genetic material. Not so.

The technology to create mRNA vaccines and protect them in nanoparticle-sized shells had been on the shelf of high-tech companies such as BioNTech and Moderna for several years where bio-engineered mRNA, for example, was explored as a possible tool for creating novel drugs to treat cancer. 

When, for example, Pfizer-BioNTech learned about the pandemic in China in January 2020, it launched “Project Lightspeed” to harness mRNA technology to rapidly develop an effective vaccine and get it ready for phase one trials within six months.

In a similar fashion, Moderna, working with the U.S. National Institutes of Health, developed and manufactured a  similar vaccine in the same timeframe using the science pioneered by Weissman’s and Karikó’s hard-won scientific advances of the previous two decades.

The whole program was an amazing success in preventing symptomatic COVID disease in the pandemic.

Given the uniqueness and effectiveness of mRNA vaccines, and the potential of mRNA technologies to revolutionize drug development, it was no surprise when the Nobel committee awarded the 2023 Nobel Prize in medicine to Weissman and Karikó for their pioneering work.

For their efforts, in 2021 the two won the Lasker-DeBakey Clinical Medical Research Award, which often heralds a Nobel Prize in the future – as it did here.

The whole field of mRNA technologies pioneered by the duo’s earlier studies has opened a new world for creating similar mRNA vaccines for influenza, tuberculosis, HIV, malaria and the respiratory syncytial virus (RSV). It also opens new avenues for treating cancer and perhaps autoimmune diseases. 

Dr. William Brown is a professor of neurology at McMaster University and co-founder of the InfoHealth series at the Niagara-on-the-Lake Public Library.  

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