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Nov. 30, 2021 | Tuesday
Editorials and Opinions
Dr. Brown--Will mRNA vaccines someday win a Nobel Prize?
Dr. William Brown.

In 1953, a Nobel Prize was awarded to James Watson and Francis Crick for their model of DNA whose double-stranded helical structure hinted at how genes might be faithfully passed on from one generation to the next.

In what was little more than a one-page article in the journal Nature incorporating a single, simple illustration of the double-helix model for DNA, Watson and Crick provided the structural underpinnings for heredity and evolution – and launched the whole field of molecular biology.

Single-stranded RNA probably appeared well before DNA in the evolutionary record because RNA offered a simpler, albeit more error prone, tool for coding genetic information. In that role, RNA remains the sole tool for coding information in some viruses such as the SARS-CoV-2 virus, which causes COVID.

But for more complex lifeforms, RNA was usurped by DNA as the primary tool for coding genetic information in genes. Genes have many functions 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 step, called transcription, a single-stranded copy of the sequence of bases in the gene is made, called messenger RNA or mRNA, for short.

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 is to grasp the messenger-boy-like 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 tailormade proteins, including designer drugs for cancer and most recently, 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, had been overcome almost two decades ago by Drew Weissman and Katalin Kariko. They devised clever ways to modify mRNA to circumvent the body’s immune system, and within the cell, to thwart processes, which would otherwise shut down instructions from the inserted mRNA to make proteins.

But there was another challenge with mRNA – how to protect the mRNA from enzymes that would normally destroy it soon after it is injected into the host’s body. The solution was to hide the mRNA in a lipid shell to protect it from circulating enzymes in transit between injection and insertion inside the host’s cells.

Once inside, the mRNA co-ops the cell’s ribosomes to create the desired proteins. Mission accomplished, the mRNA is destroyed by the cell’s own enzymes, leaving nothing behind to be incorporated into the cell’s own genetic material.

The latter is an important point because some anti-vaccine proponents claim that the mRNA or DNA in some 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 for several years where bio-engineered mRNA, for example, was explored as a possible tool for creating novel drugs to treat cancer.

When BioNTech’s leaders, the husband-and-wife team of Özlem Türeci and her husband Ugur Sahin, learned about the pandemic in China in January 2020, they launched what they called, Project Lightspeed to harness mRNA technology to quickly develop a vaccine.

Looking ahead to manufacturing the vaccine on a large scale, they partnered early on with Pfizer, a large pharmaceutical company in the United States.

Moderna, another American company, partnered with the U.S. National Institutes of Health to develop a similar mRNA vaccine, both of which proved to be very effective in preventing symptomatic COVID in this pandemic.

Given the uniqueness and effectiveness of mRNA vaccines, and the potential of mRNA technologies to revolutionize drug development, it would not surprise me if the Nobel nominating committee choose to award a Nobel prize to Weissman and Kariko sometime in the future for their pioneering roles in developing mRNA technologies. For their efforts, the two recently won the 2021 Lasker-DeBakey Clinical Medical Research Award.

Other possible candidates for a future Nobel include BioNTech’s team of Türeci and Sahin, and perhaps even the pharmaceutical companies directly involved, for their rapid response and leadership during this pandemic.

So many people played important roles in the development of mRNA technology and these vaccines specifically, that the Nobel committee will need the wisdom of Solomon with this award. In the past, they’ve often waited to let the dust settle before awarding prizes like this. That’s what may happen here.

Our fifth annual review of the Nobel prizes begins on Monday, Nov. 8 at 11 a.m. and continues for the following five weeks. Like last year, each session will use Zoom and be recorded on YouTube. If interested, please sign up with the Niagara-on-the-Lake Public Library. I look forward to seeing you on Nov. 8.

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.