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  • Writer's pictureP.K. Peterson

The 2023 Noble Prize in Physiology or Medicine: The Power of Persistence

- Katalin Karikó, Ph.D., Hungarian-American biochemist, winner of 2023 Nobel Prize for Physiology or Medicine

- Drew Weissman, M.D., Ph.D., professor of vaccine research, University of Pennsylvania School of Medicine, winner of 2023 Nobel Prize for Physiology or Medicine

The Nobel Prize for Physiology or Medicine is considered the highest honor in medical research. This year, the Nobel Assembly awarded the prize to Katalin Kariko and Drew Weissman for their transformative work that led to mRNA vaccines against SARS-CoV-2, the cause of the COVID-19 pandemic that’s wreaked havoc on mankind for nearly four years. In this week’s Germ Gems post, I provide a brief history of the Nobel Prize for Physiology or Medicine and an overview of the extraordinary nature not only of mRNA but also of this year’s two Nobel laureates.

The Nobel Prize in Physiology or Medicine. Swedish industrialist Alfred Nobel, known for his invention of dynamite, created the Nobel Prize. In his will, Nobel specified that the prizes were to be awarded in the following areas: Physiology or Medicine; Physics; Chemistry; Literature; and Peace. (The Nobel Prize for Economics was established in 1968 by an endowment from Sweden’s central bank.) The first Nobel Prizes were awarded in 1901. Since then, the Nobel Assembly, a group of 50 professors at Karolinska Institute in Stockholm, has awarded 114 prizes for groundbreaking discoveries in physiology or medicine.

Alfred Nobel intended that the prizes that carry his name be awarded for scientific discoveries that would be of greatest benefit to human kind. Over the course of the past 122 years there’s been occasional controversy over who received the prize in physiology or medicine, e.g., awarding the 1949 prize to Antonio Muniz for pre-frontal lobotomy to treat psychiatric disorders. But no one can argue about the paramount benefit to humankind of this year’s Nobel Prize for Physiology or Medicine, shared by the 13th woman to win the award, Katalin Kariko, and Drew Weisman—a team that led the way to mRNA vaccines that prevent COVID-19. (Of the 228 laureates for physiology or medicine, only 13 have been women.)

The SARS-CoV-2 mRNA vaccines have saved millions of lives. As Niek Sanders, a principal investigator at Ghent University’s Laboratory of Gene Therapy in Belgium, said: “Nobel Prizes with such a high impact on society are rare and occur only once in 25 or 50 years.”

What is mRNA? u (mRNA) is a type of single-stranded RNA molecule involved in protein synthesis. It’s made from a DNA template during a process called transcription. (While DNA garners more attention than RNA, it appears that RNA actually arose evolutionarily before DNA.) The role of mRNA is to carry protein information from DNA in a cell’s nucleus to the cell’s cytoplasm, where the protein-making machinery reads the mRNA sequence and translates it into amino acids in a growing chain resulting in the finished product—a protein. (Incredibly, our cells express more than 100,000 proteins.)

The SARS-CoV-2 virus bears a spike protein on its surface that allows the virus to bind to healthy cells. The SARS-CoV-2 mRNA vaccines work by coding for the spike protein the virus uses to enter cells. To put it simply, the mRNA in the vaccine teaches the cells in your body how to make copies of the SARS-CoV-2 spike protein. This enables your body’s immune system to recognize the virus and neutralize it if you are exposed to a future infection.

What did Katalin Kariko and Drew Weissman do? Kariko, a biochemist, and Weissman, an immunologist, began studying synthetic mRNA technology in the 1990s when they worked together at the University of Pennsylvania. Their seminal paper in 2005 described how they were able to successfully deliver modified mRNA into the body and trigger an immune response—the kind that trains the immune system for future viral infections. They found a way to modify mRNA to be less inflammatory by replacing uridine with a similar molecule called pseudouridine. And of critical importance, they worked out a way to deliver it into cells using lipid nanoparticles as the delivery vehicle.

Weissman and his colleagues were working on a mRNA vaccine for influenza when word spread of a mysterious pathogen causing pneumonia in people in Wuhan, China in late 2019. When the pathogen was identified as the coronavirus, SARS-CoV-2, they quickly realized it was a perfect target for a mRNA vaccine. Their insight was quickly followed by the biotechnology companies Pfizer-BioNTech and Moderna pivoting their work on mRNA vaccines to SARS-CoV-2.

Kariko, senior vice president and head of RNA protein replacement therapies at BioNTech, was working on using modified mRNA for cancer treatment when SARS-CoV-2 emerged in 2019. Previously, she had worked with colleagues at the University of Pennsylvania on mRNA vaccines against Zika virus, influenza virus, HIV, and herpes simplex virus. And while she didn’t know that this new infection would evolve into a full-scale pandemic, she thought the mRNA vaccine approach was a very good way to make a vaccine to fight it.

What spurred them on? Since the 1990s, Kariko and Weissman have worked on mRNA technology. Like many scientists working in academic institutions they faced numerous challenges. Yet, they persisted.

In 2013, Kariko left her position as a senior research investigator at the University of Pennsylvania’s School of Medicine because Penn refused to reinstate her to a tenure track position as it did not consider her research of faculty quality. She had been devoted to the institution for decades but had endured multiple professional setbacks—denied one grant after another, rejection of the paper that subsequently made her famous, and a demotion.

Reflecting on their work together at the University of Pennsylvania, Weissman recalls, “It was technical hurdles for 25 years. We couldn’t get funding, Kati [Kariko] kept getting demoted and pushed out.” He then sums up the driving force that kept them going, “It was very difficult to do this research, but we saw early on the potential and how important RNA was likely to be. And that kept us going. We never gave up.”

Creative thinking, hard work and luck are all important in achieving any worthwhile goal. But as President Calvin Coolidge (”Silent Cal”) wrote: “Nothing in this world can take the place of persistence. Talent will not: nothing is more common than unsuccessful men with talent. Genius will not; unrewarded genius is almost a proverb. Education will not: the world is full of educated derelicts. Persistence and determination alone are omnipotent.”

Indeed, persistence is the one personality trait that is critical for attaining anything worth having in life. Kariko and Weissman share this trait. And as beneficiaries of their hard work and persistence, we should thank them and congratulate them on their Nobel awards.

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Main Page images courtesy of Shuxian Hu, MD. Dr. Hu is a scientist in the Neuroimmunology Research Laboratory at the University of Minnesota.

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