Katalin Karikó’s initial disbelief in winning the 2023 Nobel Prize for Physiology or Medicine alongside her partner, American immunologist, Drew Weissman, reflects her humility and modesty, despite the significant impact of her contributions on global health. While you may not recognize her name, you are undoubtedly aware of her accomplishments.
Karikó and Weissman pioneered research on therapeutic applications of messenger RNA (mRNA) for over two decades, laying the groundwork for its eventual commercial use in COVID-19 vaccines. It is worth noting the irony that Karikó, who previously worked as a research assistant at the University of Pennsylvania, was denied tenure, grant funding, and had her work laughed at by colleagues, is now prominently featured on the front page of the school’s website for her well-deserved prize win. Her story is a reminder of the importance of unwavering perseverance in the face of skepticism.
Karikó dedicated her career to the study of lab-produced mRNA, which is a genetic molecule that plays a role in the process of protein synthesis within cells and acts as a “messenger” between genetic instructions stored in DNA and the production of proteins. Critically, mRNA can be produced without cell cultures, a slow and resource-intensive limitation of traditional vaccines. Karikó believed that mRNA was a viable means of producing vaccines rapidly, but the academic world disagreed, convinced that mRNA is too unstable and challenging to deliver on top of creating inflammatory reactions in initial testing. People hardly paid attention to her research, she made a modest income and frequently had to jump from lab to lab. Regardless, that did not alter her belief in mRNA. Her research, while initially rejected by leading scientific journals, was eventually published in 2005 in Immunity, but that led to hardly any interest from the scientific community.
Karikó’s research eventually led to methods of reducing inflammation and increasing protein production, and interest in mRNA technology began to pick up. By 2010, several companies were working on developing the method. Vaccines against Zika virus and MERS-CoV were pursued; the latter being closely related to SARS-CoV-2.
When the COVID pandemic hit, Pfizer and Moderna used the research conducted by Karikó and Weissman, amongst other scientists, to create vaccines that saved millions of lives. These two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed. Protective effects of around 95% were reported, and both vaccines were approved as early as December 2020, shortly after the World Health Organization declared the pandemic in March 2020.
The revolutionary idea of mRNA is that it allows rapid vaccine development against disease by providing genetic instructions. With the case of COVID-19, the mRNA vaccine contained genetic instructions to build one component, a protein, from the coronavirus.
Unsurprisingly, this same mRNA technology is now being researched for other diseases such as cancer. A new approach to treat pancreatic cancer is now underway in a phase 2 clinical trial to test the effectiveness of using an mRNA vaccine. This secondary phase follows a phase 1 trial in which the vaccine may have prevented or delayed relapses in half the patients who received it. This trial is promising for individuals affected by this form of cancer, as pancreatic cancer sadly results in death of approximately 95% of its patients, even when diagnosed early on. In the study’s initial phase, the researchers were able to take samples from 19 volunteers who had removed their pancreatic tumors. Scientists at BioNTech made mRNA cancer vaccines that were customized to each patient and had genetic instructions unique to the person’s tumors in hopes that it would trigger the immune system to attack the cancer cells. One and a half years after treatment, eight people remain cancer free.
Karikó’s journey is undoubtedly inspiring: she went from being dismissed and even laughed at from much of the scientific community to receiving the Nobel prize. Her unwavering commitment to her research despite the initial skepticism has ultimately saved thousands of lives all over the world and will continue to do so with her setting the foundation for mRNA research, making her an exceptionally deserving recipient of the prize.