From nowhere to Nobel

Katalin Karikó, the 13th woman to be awarded the Nobel Prize in Physiology or Medicine, was initially demoted from her position at the University of Pennsylvania for the same research on messenger RNA (mRNA) that won her the achievement in 2023.

Katalin Karikó and Drew Weissman jointly received the award in October for their chemical modifications to mRNA that prevent the immune system from sending an inflammatory response when it enters the body. Their research laid the foundation for the development of mRNA vaccines, which later became critical to fight the COVID-19 pandemic. However, until recently, their decades-long research was met with skepticism, and it was an arduous journey to receive support and funding for them to continue their work.

Before the pair began their research, mRNA was not believed to be a viable avenue for vaccines because it triggered a harmful immune response. When Karikó and Weissman started collaborating in the 1990s to address this issue, they discovered that natural mRNA formed within cells displayed additional chemical modifications that lab-manufactured mRNA lacked. They experimented with different modifications to lab-made mRNA and injected immune cells to observe their behavior, and they were successful in reducing the inflammatory response. However, their 2005 paper detailing their findings was dismissed by the majority of the scientific community, including Nature and Science. It was finally published in the small journal Immunity before being recognized by Moderna and BioNTech years later.

Karikó had been pursuing mRNA research long before meeting Weissman at UPenn, fully believing in its potential even though many around her did not share the same sentiment. Because she struggled to secure grants and resources, UPenn demoted her multiple times and cut her pay, regardless of any progress she showed. Undeterred, she hopped from lab to lab to continue her work until she landed in Weissman’s lab, which initially wanted to develop a vaccine against HIV. Karikó’s higher-ups at UPenn remained skeptical of her mRNA vaccine research throughout her entire employment and forced her to retire in 2013, citing that she was not “faculty quality.” At the same time, Karikó and Weissman’s work on mRNA modification was taken up by Moderna and BioNTech in the early 2010s to focus on creating vaccines for MERS-CoV, the Zika virus, and others. Karikó left UPenn to become the vice president of BioNTech and later found herself at the forefront of the COVID-19 vaccine development.

When the need for a COVID vaccine became apparent, BioNTech, who partnered with Pfizer, and Moderna were able to hit the ground running thanks to the mRNA vaccine research they already had in progress. All strains of coronavirus are known for the spike protein on their surfaces, which helps the virus enter human cells. The mRNA vaccines from Moderna and BioNTech-Pfizer targeted that spike protein so that cells could build an immune response to prevent the virus from entering, and both vaccines contained the modification that Karikó and Weissman had discovered over a decade ago. Without their pivotal work and perseverance, the pandemic response could have taken an extremely different route.

“After the efficacy of mRNA vaccines was demonstrated with COVID, the concept has since gained popularity and transformed the biotech industry.”

After the efficacy of mRNA vaccines was demonstrated with COVID, the concept has since gained popularity and transformed the biotech industry. Companies are currently trying to develop treatments with mRNA technology that target a variety of diseases, including cancer, and Karikó and Weissman’s research lies at the core. Karikó’s Nobel Prize is a symbol of recognition for decades of groundbreaking work that was constantly dismissed. However, it has prompted the discussion that her struggle to be heard likely stemmed from being a woman and a foreigner in a male-dominated field. When people learned of Karikó’s backstory after the Nobel Prize was announced, UPenn received backlash for its past treatment of her. Instead of responding to that criticism, the university released a statement of celebration, emphasizing its association with Karikó and Weissman while they worked on their research.

Being one of the handful of women awarded the Nobel Prize in Physiology or Medicine in its entire history after an uphill battle is an inspiring story. However, it also serves as a reminder that there are many scientists in similar situations working on important research that may get swept under the rug because people are unwilling to understand their visions. Their research may also, one day, prove to change the landscape of a field, just as Karikó shifted biotech with mRNA therapeutics.