Pennsylvania, 1997, a couple of scientists talk at the photocopy machine. They do not know at this moment but they are forging the science behind the invention that years later would affect the lives of many people —the development of effective mRNA vaccines against COVID-19. They were Dr. Katalin Karikó and Dr. Drew Weissman.

Abington Township, Philadelphia, 2023, 3:40 a.m. The phone rang in the house of Katalin Karikó. It was a call from Stockholm, she has won the nobel prize in Medicine.

“The Second Scientist” is a series of articles which aims to introduce the reader to some remarkable female scientists who played a leading role in advancing science and shaping the world. This article delves into the life of the biochemist Katalin Karikó with the purpose of making her figure and her career known and to arouse curiosity. In addition to the recognition of her research resulting in the Nobel Prize, the scientific career of Dr. Katalin Karikó stands as a compelling testament to the power of resilience and determination. Her commitment made her persevere in working on a technology that initially faced skepticism, yet ultimately resulted in her receiving the 2023 Nobel Prize in Physiology or Medicine along with Dr. Drew Weissman for their groundbreaking discoveries that enabled the development of effective mRNA vaccines against COVID-19. 

Katalin Karikó was born in 1955 in Sznolnok, Hungary. She grew up in Kisújszállása, a small town about 150 km east from Budapest, where there was no running water or television. Her father worked as a butcher, her mother was a bookkeeper, and together they lived in a “very simple” home [1]. She recalls a very joyful childhood marked by a fascination with the anatomy of the animals slaughtered by her father.  By the age of 14, excelling in a national biology contest and ranking third in the country, she already realized she wanted to become a scientist. 

Karikó began her academic journey in Hungary, but within a few years, she was compelled to depart her home country due to insufficient funding, a sad scenario faced by many scientists worldwide, a phenomenon known as brain drain [3,4]. In her early academic years, she already developed  the vision that messenger RNA (mRNA) could be used to instruct cells to make their own therapeutic compounds, including vaccines, although she was also aware of the challenges involved.

In 1985 Karikó was offered  a position in Temple University in Philadelphia. Back then, the Hungarian government only allowed people to leave the country with just $100, so she smuggled some extra cash in her daughter’s teddy bear and set off for Philadelphia with her family. During her post doctoral research, she continued working on her unorthodox idea of developing an antiviral therapy based on mRNA, although at that point she had limited background in immunology. She moved from lab to lab and struggled to get funding as her ideas seemed wild and fanciful. In the early 90’s, mRNA therapeutics and vaccines were still in their early stages, and only a few research groups were exploring the field. However, Karikó consistently recognized their potential. Eventually, in 1989, she got a nontenured research assistant professor position at the University of Pennsylvania in Philadelphia. 

One day, while photocopying some papers, she met Drew Weissman, another newly-arrived assistant professor who mentioned  he was interested in developing an AIDS vaccine.  They realized their expertise complemented each other perfectly —Karikó contributed her extensive knowledge on RNA technology, and Weissman brought the immunology background for its application. Together they embarked on pioneering research in mRNA vaccines, albeit with little funding since gene therapy was dominating scientific attention at the time and scientists were still not taking the RNA therapeutic technology seriously [5]. 

Initially, Kariko and Weissman’ s multiple attempts were unsuccessful as the mRNA used was triggering a strong immune reaction in immune cells. The mRNA was being recognized by the immune system as an intruder, leading to the production of inflammatory proteins, rendering it unsuitable for therapeutic purposes. In fact, under normal conditions, mRNA never gets outside the cells or encounters immune cells in the body. Therefore, the primary challenge laid in effectively delivering the mRNA inside the body [6]. 

However, after additional research they could show that with a few modifications, the mRNA could go undetected by the immune system [6]. Karikó and Weissman recognized the profound implications of their discovery for mRNA-based therapy. Despite initial rejection as an incremental contribution by the scientific journal Nature, their work, which years later will grant them a Nobel Prize, was eventually published in the journal Immunity [7]. For more technical information about the biology behind mRNA vaccines and different types of RNA-based technologies, you can read our previous articles on the topic.

With hindsight, It is easy to see that their discovery of the mRNA modifications was groundbreaking and very promising. However, back then, neither the university nor the pharmaceutical companies of the time were willing to finance Kariko’s work, which was written off as unrealistic. After repeated unsuccessful attempts to secure funding to pursue her unconventional ideas, she was demoted from her faculty position and forced to retire from Pennsylvania University [8]. 

At the age of 58 and after living in the USA for 28 years, she faced a setback in her career. However, in a display of determination, in 2013 Karikó left for Mainz (Germany), joining the company BioNTech, where she continued to work on mRNA. BioNTech, at that time, was a small and little-known biotech firm specializing in RNA pharmaceuticals. At the beginning of the COVID-19 pandemic, she was tasked with designing a vaccine for SARS-CoV-2. The rest is history. Thanks to the work she and Weissman laid down in the previous years, the vaccine could be developed very rapidly. Now, BioNtech is a worldwide-known company due to the development of their COVID-19 vaccine, in collaboration with the pharmaceutical company Pfizer. On the date of publication of this article more than 13 billion doses of COVID-19 vaccines have been administered globally [9]. Karikó is vice president of Biontech since 2019 and she is also an adjunct professor of Neurosurgery at the University of Pennsylvania.

Despite being demoted several times in her career, she never dwelled on self-pity or the question “why me?”, neither did she take these obstacles personally, as she has explained in several interviews. She rather always shifted the focus to “what’s next?” and embraced a stoic approach [8]. Her resilience and perseverance led her to never giving up, and handling adversity by turning the stress into positive changes. Her own daughter learned from her example of determination and has become a two-time Olympic champion in rowing.

There are many small and significant decisions that lead to a discovery of this caliber which impacts the life of thousands of people around the world. Countless “what ifs” that might not have occurred. If she hadn’t left Hungary for Pennsylvania. If she had never joined BioNTech. If she and Weissman had never randomly met at the photocopier and talked. From this, there is certainly a lesson to be learned. Talk to your colleagues, greet them in the hallways, never stop asking questions. You never know.