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The drive to develop Covid-19 vaccines as quickly as possible was conducted at warp speed and involved a huge array of contributors, all of whom deserve recognition for the vital life-saving work they carried out, but the vast majority of them agree that if one person should be singled out for special praise it’s Katalin Karikó. The vaccines would not exist without her groundbreaking research which was carried out despite, not because of, the wishes of her university employers, and now that she has become famous for her work she is using the spotlight to highlight other innovators in her field, rather than bask in accolades for herself. What could be more superheroic than that?

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The humble origins of a True Superhero 

Katalin was born in 1955 in Kisújszállás, a small town in eastern Hungary, in humble circumstances. Her father was a butcher and her mother a bookkeeper.d They lived in an adobe house with a reed roof and a sawdust oven, with just one room that was heated through the winter and no running water or refrigeration. Despite her rudimentary surroundings, Katalin quickly demonstrated that she had a tremendous gift for learning, competing in national academic contests as a schoolgirl and placing in the top three in Hungary in her specialist subject of biology.

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Biology was always her passion and she was particularly interested in the potential applications of messenger RNA (also known as mRNA), which the body uses to generate specific proteins. If you can synthesize mRNA that is tailored to your purposes, you can control the proteins being produced by the body, and the potential to develop new therapies and treatments using the body's own genetic systems was tremendously exciting to Katalin. She earned a Bachelor's Degree in biology in 1978 at the University of Szeged and a doctorate in biochemistry four years later, before going on to begin her postdoctoral studies of mRNA at the Hungarian Academy of Sciences. Sadly, in the first of many setbacks in her career, the Biological Research Center’s lab had its funding cut in 1985, and Katalin was left with nowhere to carry out her research. 

Mockery, rejection, and demotion

Her solution was typically radical; she emigrated to the US, along with her husband and their two-year-old daughter, future two-time US Olympic rowing gold medallist Susan Francia, who also had a brief career as an international currency smuggler. At that time, Hungarian citizens were only allowed to take the equivalent of $50 out of the country, but as the family went through customs at Budapest’s airport Susan was clutching a teddy bear stuffed with $1,200 worth of banknotes, the proceeds from the sale of the family car. She passed through the border guards without incident, and Katalin and her family were able to move to Philadelphia, where she resumed her postdoctoral work at the University of Pennsylvania. 

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Unfortunately, academic life did not become any more stable for Katalin. Nobody saw any great future in synthetic mRNA research and Karikó’s ideas were not taken seriously, and even mocked. The major stumbling block was that while she was able to create synthesized mRNA that would create desired proteins in a petri dish, when she introduced it to animal subjects their immune systems would recognize the synthetic mRNA as foreign and an aggressive immune response would be provoked. Consequently, she was unable to obtain funding grants for her research and eventually the University of Pennsylvania demoted her. She had been on track to become a full professor with tenure at the university, but her superiors could see no future for her research and attempted to pull the plug in 1995. 

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Katalin was undeterred by this rejection. As she later put it, “Usually, at that point, people just say goodbye and leave because it’s so horrible.” Despite the humiliation, Karikó stayed on at the university. “I thought of going somewhere else, or doing something else. I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here and I just have to do better experiments.” She would soon find an opportunity to do just that, thanks to a chance meeting with the man who would help solve the mRNA conundrum, Drew Weissman.

Patently ridiculous

Katalin would spend a lot of time at the University photocopier, talking to anyone who would listen about mRNA, and offering to synthesize it for other photocopier users. This continued for two years until she encountered Weissman, an immunologist who was looking to make HIV vaccines, and saw promise in Karikó’s approach. The two began working together on a fix to the immune response problem, and while progress was slow they eventually hit on a solution in 2005, modifying nucleosides in the mRNA to remove the receptors that provoked the body’s immune responses. The technique worked like a charm, and the pair believed that the phone would be ringing off the hook with scientists demanding to know more about their breakthrough discovery; instead, their paper outlining the technique was rejected by the major journals, and only carried by Immunity, a niche publication. Consequently their discovery received minimal attention in the wider scientific community. 

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There were some shrewd observers who saw the potential in the duo’s discovery, but unfortunately their superiors at the University of Pennsylvania were not among them. Under the terms of their contracts, the patents on Karikó and Weismann’s techniques belonged to UPenn, but their employers were skeptical that the technology had any long-term benefits and ultimately sold the exclusive licensing rights for the patent in 2010 to a small firm from Wisconsin called Cellscript, for just $300,000. Karikó’s share of the profits was a paltry $38,250; UPenn also offered her an untenured adjunct professor position with a salary of just $50,000 a year. Seven years later, Moderna and BioNTech paid $75m each to Cellscript for licensing rights; Karikó finally received $2m from each of these deals, but her goal was never to make a profit from her discoveries; she was determined to see new vaccines and treatments that utilized her mRNA breakthrough, and the sub-licensing of the patents to major drug producers meant that goal was finally going to be realized.

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Covid-19 took a terrible toll, but it also provided a proving ground for mRNA vaccine technology, and the results were spectacular. Moderna had devised a prototype vaccine within two days of the genome sequence being released in 2020, and Pfizer’s eight-month turnaround from first human tests to emergency approval was a record. Many figures deserve credit for their contributions to the research that made these incredible life-saving treatments possible so quickly, but the consensus is that Katalin Karikó in particular deserves special recognition, not just for her groundbreaking research, but also for the relentless enthusiasm with which she pursued her goals, in the face of incredible adversity. 

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She continues to be a leading light in the mRNA research community, praised by her contemporaries for the work she does promoting other up-and-coming RNA bioengineers. As one such scientist, Anna Blakney, told Nature, Karikó “is actively trying to lift other people up in a time when she’s been so under-recognized her whole career”. It is also a time when many major players in the biotech industry are filing patent lawsuits against each other, but Karikó’s focus is on aiding, rather than arresting, further mRNA treatments, and with work ongoing in vaccines for HIV, malaria, ebola, tuberculosis, and many more diseases, it’s clear that she intends to continue being a True Superhero for some time yet. 

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