Katalin Karikó and the mRNA Vaccine
Thanks to the COVID-19 pandemic, infectious disease jargon has become a global lingua franca. For over two years, nearly every news headline and Zoom chat room conversation has contained phrases like PCR tests, R value, spike protein, and mRNA vaccine. Whether working from home or spending too much time on TikTok in quarantine, we’ve thought about COVID constantly. Yet, this technical language has slowly lost its significance. We’ve stopped caring about the scientific details of the pandemic and started getting back to our lives. We’ve forgotten just how extraordinary it is that we produced a safe and effective vaccine using a novel biological mechanism in under a year. Who were the scientists behind this feat? Who was it that made the extraordinary ordinary?
One scientist in particular carried the torch for the mRNA vaccine field for over four decades—through lab closures, career obstacles, and a move across the Atlantic. Dr. Katalin Karikò graduated from the University of Szeged with her Ph.D. in 1978. She began studying antiviral activity in synthetic mRNA at the Biological Research Centre in Szeged, Hungary. In 1985, her lab lost funding and was shut down. Karikò and her young family immigrated to the United States in search of better career opportunities, where she found a position at Temple University in Philadelphia. There, she worked on a clinical trial that successfully treated patients with HIV/AIDS and other hematologic diseases with an early RNA vaccine technology. This project established her career’s focus on mRNA-based therapies.
Seen Right: Dr. Katalin Karikò, the award-winning mRNA vaccine researcher. Courtesy of Csilla Cseke/EPA in Encyclopædia Britannica.
In 1989, Karikò accepted a position at the University of Pennsylvania, where she again faced difficulties funding her research and publishing in major journals. Though Karikò was originally on track to become a full professor, the university demoted her due to lack of funding. She persisted even without the benefits of full professorship, publishing breakthrough discoveries about synthetic nucleotide modifications of mRNA that enabled its use in human vaccines. These modifications made the virally-derived mRNA non-toxic to humans and safe to administer. She also demonstrated that synthetic mRNA could direct protein synthesis when injected into cells, constituting the basis of mRNA vaccine technology. In the 2000’s, Karikò filed patents on the nucleotide modifications she designed: her first venture into the biotechnology industry. In 2013, she left her academic career to become senior vice president of the German biotechnology start-up BioNTech, where she could finally apply her expertise in therapeutic mRNA technology. Here, Karikó further improved the design of synthetic mRNA for non-toxic delivery to humans and studied the use of mRNA vaccines to treat influenza. Her work set the company up for lucrative success: under her leadership, BioNTech developed the mRNA COVID-19 vaccine that was globally distributed by Pfizer. To date, this COVID-19 vaccine is the most administered vaccine in the United States and is second only to the Oxford-AstraZeneca vaccine in doses delivered worldwide.
mRNA vaccine technology is ultimately responsible for the unbelievably quick turnaround on the COVID-19 vaccine development. Traditional vaccines introduce our bodies to an inactive foreign protein known as an antigen. Our immune cells then recognize this antigen as dangerous and mount an immune response against it. After a few weeks, the immune system learns how to fight this antigen. It creates specialized memory cells that circulate the bloodstream, watching for anything resembling the weak antigen delivered by the vaccine. The COVID-19 mRNA vaccine uses a different molecule to get the same result. It makes use of synthetic mRNA, which can be translated into proteins by machinery native to our cells. The vaccine supplies our bodies with a strand of mRNA encoding the coronavirus spike protein. The protein is manufactured by our cells and then presented for immune cells to recognize. The immune system then learns how to fight any kind of virus expressing the spike protein, retaining this knowledge in specialized memory cells.
Seen Above: Major companies developed four COVID-19 vaccines used around the world. Karikò and her team at BioNTech partnered with Pfizer to engineer the United States’ most popular option. Courtesy of Reuters.
Never before has the development of a vaccine been so rapid, and never before has an mRNA-based vaccine been distributed with such ubiquity and reliability. This endeavor was an extraordinary feat of human engineering and determination—determination that has lasted far longer than the year it took to develop the COVID-19 mRNA vaccines. Indeed, scientists like Dr. Karikò were studying the antiviral effects of mRNA for years before COVID-19 pushed mRNA vaccines to the top of the scientific to-do list. Researchers dreamed of mRNA vaccines being used to prevent viral infections ranging from the common flu to HIV. However, as Karikò’s story shows us, these projects proved difficult to fund. Virology was dominated by research into traditional weak antigen-based vaccines, and grant-providing institutions like universities and governments didn’t want to gamble on a new, poorly-understood type of vaccine—until about two and a half years ago.
Thanks in large part to Karikò’s work and leadership in the field, mRNA vaccines became the hero of the global COVID-19 response. In 2021 and 2022, Karikò received over 50 awards including Time’s Hero of the Year and the German Future Prize. After years of sacrifice and struggling to fund and publish her work, Karikò’s research has proven to be some of the most relevant science in recent history. In light of her enormous contributions to vaccine technology and global health, many in the scientific community expect her to be nominated for a Nobel Prize in Medicine in the coming years.
Karikò’s story is an inspiration as well as a portent for the scientific community. Her research will impact every person on the planet. The development of a safe and effective COVID-19 vaccine will doubtless lead to the development of mRNA vaccines against viruses that have plagued the world for centuries. And, as a woman and an immigrant scientist, she is a role model for underrepresented groups in STEM.
Yet, Karikò’s story also forces us to confront the flawed system by which academic research is conducted in the modern day. Funding controls research, and the institutions that grant funding are more concerned with immediate financial reward for their investment than with the expansion of knowledge that will lead to future advancement in medical care and technology. Even the academic institutions that exist to support researchers often encourage only ‘publishable’ research, investing more resources in labs focused on trending therapeutic techniques or profitable diseases.
Academia as an institution often fails to realize that the greatest scientific advancements usually come from undervalued basic science research. Indeed, the infamous CRISPR gene-editing system was accidentally discovered by microbiologists studying bacterial osmosis—and further researched by a scientist interested in developing yogurt cultures. Today, work by geneticists Feng Zheng, Emmanuelle Charpentier, and Jennifer Doudna has made CRISPR one of the most important tools in biological research. Similarly, some of the most fundamental knowledge about the cell cycle was discovered in 1982 by Tim Hunt, who spent his summer collecting and experimenting on sea urchins at a Massachusetts marine lab. Likewise, Green Fluorescent Protein (GFP) was discovered in bioluminescent jellyfish by Japanese chemist and marine biologist Osamu Shimomura. GFP was the first fluorophore discovered and purified and is now an essential imaging tool for researchers everywhere. All three of these discoveries received Nobel Prizes. Despite popular belief, conducting ‘unprofitable’ research seems to be the best way to discover something monumental.
Karikò’s four tumultuous decades of research established the basis of mRNA vaccine technology and enabled virologists to engineer and distribute a safe and effective COVID-19 vaccine within a year. This demonstration of a successful mRNA vaccine will surely lead to the emergence of a fascinating subfield of virology and the development of even more mRNA vaccines in the coming decades. We’re entering an exciting era in the field of vaccine development and infectious disease research. Yet, one can’t help but imagine where mRNA vaccine technology would be today had it received greater institutional support. Katalin Karikò’s story is a moving and vital reminder to the scientific world that the greatest discoveries come from the strangest places: from tiny bacteria engineering their own immunity, from strange-looking sea creatures—and, just maybe, from a young scientist with unorthodox ideas and the tenacity to match.