Nobel Prize in Physiology/Medicine 2023: A New Way of Looking at Vaccines

Just three years ago, in December 2020, the first COVID-19 vaccine was given to a person outside of a clinical trial. Ninety-year-old Margaret Keenan received the vaccine at a hospital in Coventry, UK, and news of the event spread far and wide. At the time, many people were facing strict restrictions for the upcoming holidays, the Alpha, Beta, and Delta variants of the SARS-CoV-2 virus were identified as variants of concern, and an estimated 1.5 million people worldwide had died from the disease. That vaccination marked a turning point for many throughout the long months of quarantines, lockdowns and COVID-19 waves, particularly for healthcare workers. It also spurred the fastest vaccine rollout in history.

The first COVID-19 vaccine brought to market was based on the use of messenger RNA (mRNA) to induce an immune response to a pathogen, a different approach to developing vaccines, as opposed to using weakened or inactivated viruses, or viral vectors. It took many years to overcome the technical obstacles to enable mRNA vaccines to work, and for these efforts, the Nobel Prize in Physiology or Medicine 2023 was awarded to Katalin Karikó and Drew Weissman.

A Recipe for a Protein

mRNA is a single strand of genetic material that serves as a copy of one gene from a cell’s DNA. Once the information is copied onto mRNA, the molecule can travel from the cell’s nucleus, where the DNA is stored, to the cytoplasm, where the information is translated into a protein molecule. mRNA was discovered in 1961 and the concept of using it as a potential vaccine was envisioned in the late 1980s after in vitro transcription made it possible to synthesise RNA without a cell culture. But the problem was that mRNA induced inflammation in the organism. And even without that significant obstacle, mRNA was considered an unstable molecule, one that would be quickly degraded by the organism before it could perform its function.

Biochemistry and Immunology

In the early 1990s the development of mRNA into therapeutics became a central theme in Katalin Karikó’s research. The biochemist had recently emigrated to the U.S. from Hungary and for years faced many difficulties in getting grants. In 1997, she met the immunologist Drew Weissman, who had just been hired by the University of Pennsylvania, where Karikó had worked since 1989 and had recently been demoted. Weissmann was interested in dendritic cells, which can control adaptive immune responses. They began to work together to figure out how mRNA can be administered safely, without triggering a strong inflammatory response.

Success came in 2005, when Karikó and Weissman found that by modifying uridine, one of the four nucleosides of RNA, into pseudouridine, it was possible to suppress the capacity of mRNA to activate dendritic cells. Yet the time still wasn’t ripe for the scientific community to appreciate these findings. Despite many efforts and continued research, Karikó was refused a faculty position by the University of Pennsylvania in 2013 and for the next nine years commuted to Germany, where she was Senior Vice President of BioNTech. She had no idea that an mRNA vaccine would soon be one of the most sought-after therapeutics on the planet.

The Value of Perseverance

The story behind this year’s Nobel Prize in Physiology or Medicine isn’t only about excellence in scientific research, it’s also a story of remarkable resilience, fuelled by determination and a love of science. “Nothing distracts me from my work,” Weissman told Nobel Media’s Adam Smith soon after learning he had won the prize. Career trajectories can go awry even after reaching important milestones. Karikó was mostly dependent on the support and encouragement of her family to keep going, and remained optimistic by echoing the words of Hans Selye, the Hungarian-Canadian endocrinologist, “You have to focus on the things you can change.”

Recent studies have shown that mRNA-based vaccines against COVID-19 have the highest total efficacy and effectiveness compared to other vaccines. But the hurdles are still there in convincing people that the technology is safe. “As important as the vaccine is, if you don’t take it, it won’t work,” said Weissman. This is crucial for potential future applications of mRNA-based therapeutics, which aim to treat a wide range of illnesses, from genetic diseases to cancer.

A pandemic unexpectedly brought mRNA technology to the forefront of medical research, but as a knock-on effect, effective science communication became more important than ever. The abundance of Q&As, graphics and videos on how mRNA vaccines work is a good example for science communication with a comprehensive approach.