Katalin Karikó is awarded the Nobel Prize in Physiology or Medicine

Katalin Karikó and Drew Weissman have been awarded the Nobel Prize in Physiology or Medicine in Stockholm. According to the citation, the microbiologist born in Szolnok, Hungary, and her research partner played a key role in the development of new types of mRNA-based vaccines, in fighting the biggest pandemic in the past hundred years and in opening new paths for future medicine. This is the third time that a Hungarian citizen has been awarded the world's most prestigious prize: in 1937 Albert Szent-Györgyi received the Nobel Prize in Physiology or Medicine, and in 2002 Imre Kertész was awarded the Nobel Prize in Literature. They are now joined by Katalin Karikó, whose name has become known around the world in the past few years.

The Royal Swedish Academy's announcement of Karikó's prize can be watched here:

Nobel Committee Secretary Thomas Perlmann said he was able to speak to both researchers by phone before the announcement. Both Karikó and Weismann were overwhelmed with emotion and were very happy to receive the prize. During the conversation, Karikó recalled that she had also had some dramatic moments in her research career, one of which was when she relocated from the United States to Germany in 2013.

Rickard Sandberg, a member of the Nobel Prize's medical committee, said that more than 13 billion mRNA-based vaccines have been administered, saving the lives of millions of people or reducing the chances of serious diseases, which also kept societies functioning.

"This year's Nobel Prize is in recognition of their fundamental scientific discovery that has radically changed our understanding of the interaction between mRNA and the immune system," said Sandberg.

Many were already expecting Karikó's award

A few years ago, Karikó's name was unknown outside her narrow profession even in Hungary, but by 2021 she had become a global icon and has since been awarded a string of prestigious scientific prizes. Among them are a series of what are often referred to as the precursors to the Nobel Prize: the Horwitz Prize from Columbia University; the Albany Prize, the most prestigious US scientific award; the Breakthrough Prize, the prize with the largest prize money; and the Lasker Prize for clinical development.

Based on these, Katalin Karikó and her former research colleague Drew Weissman of the US were already mentioned among the contenders for two Nobel Prizes, in Physiology or Medicine as well as in Chemistry, in the year of the spread of mRNA-based coronavirus vaccines. However, there was some question as to whether the usually rather conservative Nobel committee would make an exception for them. Although Alfred Nobel's original idea was to recognise the greatest scientific achievements of the previous year, they actually tend to wait decades rather than award the greatest prize in science too quickly. It was not known whether an exception would be made, given the huge social impact made during the pandemic and the huge scientific prospects that opened up.

That didn't work out that year in the end, with the Prize in Physiology and Medicine going to David Julius and Ardem Patapoutian for their fundamental discoveries in skin sensation, and the Prize in Chemistry going to Benjamin List and David W.C. MacMillan for their work on asymmetric organocatalysis.

This year's top contenders for the Nobel Prize in Medicine were researchers in two fields. One was the study of sleep. Here the focus was on research into the relationship between narcolepsy and a neuropeptide called orexin.

Kevan Shokat was also shortlisted for his achievements in cancer research. The American biologist developed a method to block the KRAS gene, which is responsible for a third of cancers. Another type of cancer therapy, T-cell therapy, is another scientific work that could win a Nobel Prize, several researchers said in advance.

Not just because of the vaccine

The pandemic years were also an unprecedented challenge for the international scientific community, and the rapid development of vaccines against the coronavirus was an unprecedented success, even though it did not, of course, bring the epidemic to an end overnight. At stake – alongside such 'trivialities' as global health and the restoration of normal life – was the prestige of science in an age that is in many ways anti-science, and the world watched with bated breath as news of vaccines broke like probably no innovation before. Katalin Karikó's research laid the foundation for a new type of vaccine, which then brought the scientific breakthrough.

Although Karikó's award was clearly motivated by the COVID-19 vaccine, it was not solely for the vaccine that she was honoured, but for laying the foundations for the widespread pharmaceutical application of mRNA technology. Katalin Karikó herself, although she was awarded the Prize in Physiology or Medicine, considers herself primarily a chemist:

"Suddenly everyone is an epidemiologist now, but I'm not. I'm a biochemist who understands RNA."

– she said in an interview with Telex in May 2021.

Tamás Freund, President of the Hungarian Academy of Sciences, spoke to Telex ahead of the 2021 awards about what Katalin Karikó's Nobel Prize would mean for Hungary. As he said at the time, Karikó's "Nobel Prize, which many of us are hoping for, would put the international spotlight on the strength of Hungarian science and education, the creativity of the Hungarian scientific mind, and at the same time provide further convincing evidence to Hungarian policymakers of the importance of supporting basic research.

Katalin Karikó's Nobel Prize would also be a special joy because she would be the first female Nobel Prize winner from Hungary! Her success would draw attention to the outstanding achievements of Hungarian women researchers, who are among the international leaders, especially in fields related to Katalin Karikó's."

A long and hard road to the Nobel Prize

Karikó first heard about the medical use of mRNA in 1976, when she was a student at the University of Szeged. At the beginning of her studies, she was not particularly interested in microbiology, preferring plants, but under the guidance of Jenő Tomasz, an organic chemist, she soon found her future field of specialisation.

After graduation, she was employed in the Biological Research Centre in Szeged. She had to leave the research centre a few years later, at the age of 30, because of downsizing. She sought opportunities abroad and moved to America with her family in 1985. She first joined Temple University in Philadelphia, but after a few years there she fell out with her boss, who threatened to have her expelled from the United States. She transferred to another university in the city, the University of Pennsylvania, but they didn't really believe in her project.

Although the therapeutic application of messenger RNA, or simply mRNA, was considered one of the most promising areas of experimental medicine in the 1970s, its practical application seemed to many to be very distant or even hopeless, not worth the capital invested. It was only in 1961 that the mRNA molecule, which carries genetic information stored in DNA to the ribosomes that produce proteins, was discovered (it also earned a Nobel Prize at the time), and Katalin Karikó was one of those who hoped that it, or more precisely the use of artificial mRNA, would lead to a renewal of medicine. The idea was that by injecting the right RNA in nanoparticles into human cells, they could "teach" the immune system to recognise tumour cells or produce the right antibodies with a vaccine against viral infection.

By the 1990s, however, enthusiasm for mRNA in applied science had waned, mainly because it could not be stably delivered to the target organism. Karikó kept applying for grants, but her research wasn't bringing in much money for the university, and they began to see her efforts as a waste of time. She faced numerous unfairnesses, including being moved out of her lab and then being given a choice: either give up her research or take a pay cut. She chose the latter, continuing her decade-long quest, gradually becoming the only one in her environment who believed in it – for less than she would have gotten at a fast-food restaurant.

"I got about a dollar an hour, based on the time I spent in the lab and then worked at home, writing applications and articles"

– she recalled this period in an interview.

The way out was a chance meeting in the university photocopying room with Drew Weissman, now jointly Nobel laureate with Karikó, with whom they then worked on a solution that would not trigger an inflammatory immune response which made it impossible to deliver mRNA to the target organism. The solution was the replacement of one of the nucleosides that make up mRNA, which paved the way for practical applications. When the first mouse experiments were finally successful in 2005, hope awakened. "At that moment, we understood that this was a very important discovery that could be used in vaccines and therapies. We published a paper, filed a patent, and founded a company – and still nobody cared. Nobody invited us to talk about it, nothing happened," said the Hungarian researcher.

She and Weissman didn't give up, however, and within a few years, the revolutionary mRNA technology became exciting and less distant again in the field of medical research. In 2010, a company called Moderna was founded to apply modified mRNA to medicine, with the participation of several Harvard and MIT professors, and it was already building on Karikó and her colleague's research. The Hungarian researcher and Weissman also went their own way: they sold a licence based on their own development to BioNTech, a German company that was then counted as small. Today, the names of both companies are known practically all over the world. BioNTech created the first mRNA vaccine against the COVID-19, together with Pfizer, based on Karikó's decades of research, and this was followed shortly afterwards by Moderna's vaccine. (The latter has since sued the other two companies, accusing them of patent infringement.)

Many people would not have bet on that even a few years ago. In 2013, when Katalin Karikó tried to reapply for the Philadelphia professorship from which she had previously been removed, she was rejected and told she was not up to university standards. Then she announced that she was going to BioNTech and she was laughed at because the obscure company, run by Turkish immunologist Uğur Şahin from Germany, didn't even have a proper website.

"Recognition has been famously absent in my life, but it didn't bother me that much. I have done very well without my work being recognised as important. I was like Cassandra, I could see the future but I couldn't convince others of it. Even now, I don't feel like, ‘Oh well, I told you so’."

– said the Hungarian researcher in an interview with former classmate János Géczi last March.

The technology, based on the encoding of messenger RNA, has now reached a critical point, with many in a wide range of medical fields expecting much from it in the very near future. It took COVID-19 and the pandemic to show the potential for successful application on a global scale. The two new Nobel laureates, Katalin Karikó and Drew Weissman, were among the first to receive the vaccine together, based on their own development, and when tests on 8 November 2020 proved that the vaccine, which is a joint development with Pfizer, worked against the coronavirus, Karikó celebrated with a bag of chocolate peanuts.

The next mRNA vaccine will be against influenza, according to Katalin Karikó. It won't take long – she said in an interview with Telex in 2021 – for a universal vaccine to be developed against all coronaviruses, following the SARS-CoV-2 vaccine responsible for the current pandemic. But in addition to vaccine development, mRNA-based therapies are also expected to have a major impact on immunotherapy, cancer, cardiovascular and digestive diseases.

The Royal Swedish Academy of Sciences has now recognised Katalin Karikó and her fellow researcher, who were laughed at just a few years ago, for the latest revolution in medicine. Like the majority of Nobel Prize winners of Hungarian origin, the researcher from the small town of Kisújszállás spent half her life abroad – only at the lower rungs of the scientific hierarchy, and for a long time she was not only not rewarded, but her superiors sometimes tried to make her work impossible. As she said in an interview about moving, “If we had stayed, we would probably have been complaining, mediocre researchers. Perhaps we created more because we were in a constant struggle to survive, to succeed.”

Her message: Always focus on what you can change, don't worry about others

About half an hour after the Nobel Prize announcement, Karikó shared some of her thoughts with friends and journalists present in an online video chat.

The Nobel Prize-winning scientist was asked what message she would give to young researchers who are still at the beginning of their careers.

"The most important thing is to have physical and mental health, to learn to manage stress. The most important thing is that if they enjoy what they do, if they are happy doing it, they will get better and better," she said.

She then quoted another world-famous Hungarian scientist, János Selye, who laid the foundations for stress research. "We should always focus on what we can change, not on other people, because that's not the way forward."

When asked what her parents would say to her after she won the Nobel Prize, she became emotional and recalled her mother telling her repeatedly, "Maybe they will call your name, darling." Her mother was convinced that she would win a Nobel Prize one day, after all her hard work. Karikó used to explain to her that other researchers also work hard and that in itself is not enough for scientific recognition.