Katalin Karikó, from ignored immigrant to “mother” of the Covid-19 vaccine

“Redemption! … I started to breathe very hard, I got so excited that I was afraid of dying or something like that.” This is how biochemist Katalin Karikó recalls that it was her reaction to the news that the vaccine developed by the American pharmaceutical company Pfizer and its German partner BioNTech, which is based on research in which she was pioneering and for which she risked her career, had been 90% effective against the Sars-CoV-2 coronavirus.

Considered today as a “superstar” and the “mother of the vaccine” for her precursors studies on the technology of messenger ribonucleic acid (mRNA) -also used in the vaccine of the Modern American laboratory-, the work of this scientist was not always so recognized. Now it seems incredible, but for a whole decade, that of the 90s, nobody supported Karikó’s research. “I would get one rejection letter after another from institutions and pharmaceutical companies when I asked them for money to develop this idea,” he explains.

“It was demoted, questioned and rejected. Now, her work is the basis of the vaccine against Covid-19 ”, the CNN chain recently highlighted about this woman born 65 years ago in Hungary, during the communist era. Raised in a one-room house, without running water or a refrigerator in Szolnok, a small town outside Budapest, Karikó’s adolescence later passed in Kisújszállás, where her father worked as a butcher. “I was a happy girl. My father was a butcher and I liked to watch him work, to observe the viscera, the hearts of the animals, perhaps that’s where my scientific vein came from, ”the biochemist told the Spanish newspaper El País from his home on the outskirts of Philadelphia, in the USA. USA

Passionate about science, Karikó began taking her first steps in science at the age of 23, at the Center for Biological Research of the University of Szeged, where she also obtained her doctorate. But “communist Hungary made things very difficult,” said the biochemist. For this reason he did not hesitate to leave the country when in 1985 he received an invitation from Temple University in Philadelphia to take a postdoctoral position. She and her husband and young daughter left for the United States after selling their car, the scientist revealed to The Guardian. They put the money, the equivalent of about US $ 1,200, in their daughter’s teddy bear to keep it. “It was going to be a one-way trip. We didn’t know anybody, “he told Business Insider.

At Temple he continued his research, and then at the University of Pennsylvania School of Medicine (UPenn). “(Molecular biologist) Pierre Meulien and colleagues in France first used liposome-encapsulated mRNA to vaccinate mice against influenza and published their results in the European Journal of Immunology in 1993. In the early 1990s, my plan was to use the mRNA that encodes therapeutic proteins to treat diseases, instead of vaccinating, “Karikó told La Tercera by email.

But by then, the scientist’s idea that mRNA could be used to fight disease was deemed too radical, too financially risky to fund. She applied for grant after grant, but continued to receive rejections, and in 1995 was demoted to the rank of simple researcher at UPenn. He was also diagnosed with cancer around the same time. “Usually at this point, people say goodbye and walk away, because it’s so awful,” he told STAT, a health news site, in November. “I thought about going somewhere else or doing something else. I also thought that maybe she wasn’t good enough, not smart enough, ”she confessed. At the time, Karikó was not a US citizen and needed a job to renew her visa. For this reason, she decided to continue as a researcher in a lower rank and with a low salary.

The Hungarian biochemist was determined to carry out her research. And the momentum came to an end in 1997, when a simple encounter in front of a photocopier changed Karikó’s fate. Together with the machine, he met the immunologist from the University of Pennsylvania, Drew Weissman, a newcomer scientist who came from the team of Anthony Fauci, an eminence in HIV and who currently directs the public institute that has developed the vaccine together with Moderna . Weissman wanted the AIDS virus vaccine and took Karikó into his lab to try messenger RNA.

“When I met Drew Weissman we started to focus on vaccine development. We used conventional mRNA that encodes viral antigens for vaccination, but it was causing inflammation. Starting in 2005, we used nucleoside modified mRNA, which was a very powerful vaccine that did not cause inflammation and generated a very strong immune response that protected animals from infection, ”Karikó explained to La Tercera.

In 2010, a group of US researchers founded a company that bought the rights to the Karikó and Weissman patents. Its name was an acronym for “modified RNA”: ModeRNA. The company promised to be able to treat infectious diseases with messenger RNA. Around the same time, another small German company founded by two scientists of Turkish origin, BioNTech, acquired several of the patents on modified RNA from both researchers to develop cancer vaccines. In 2013, after almost 40 years of practically anonymous work, Karikó was hired by BioNTech, of which she is now Senior Vice President.

Karikó and Weissman’s next step was to place the RNA in “lipid nanoparticles”, a coating that prevents them from degrading too quickly and facilitates their entry into cells. Its results were made public in 2015. Five years later, when science tries to fight against a coronavirus that is invading the planet, its advances in this field have been the pillar on which the vaccines have been developed that have restored hope to the humanity. “Nucleoside-modified mRNAs were used to create the anti-Sars-CoV-2 mRNA vaccines, BioNTech / Pfizer’s BNT162b2 and Moderna / NIH (US National Institutes of Health) mRNA-1273,” says the researcher. to this medium. “This is something incredible, because it means that all the work that I was doing for years, during the 90’s, and convincing people that maybe mRNA would be good, it was worth it,” he celebrates.

How do you feel knowing that the Pfizer / BioNTech vaccine against Covid-19 will save so many lives?

I’m glad the vaccine is very powerful and protects vaccinated people. I hope that many people get vaccinated and life can return to normal.

Several countries in the world have already started inoculation against Covid-19. Do you think that the messenger RNA vaccine can be more effective than the classic ones?

Yes, the mRNA vaccine is more effective and safer than classical vaccines that contain attenuated or inactivated viruses.

The richest countries have bought a large part of the stock of available vaccines. Considering this situation, when do you think the world will be able to defeat the pandemic?

The United States and the European Union gave their taxpayers’ money to different companies to accelerate the development of the vaccine, assuming the financial risk in case the vaccine fails. In this way, companies could prepare the vaccine for the next stages of clinical trials without knowing if their vaccine is effective. With the help of this strategy, vaccines were prepared very quickly without taking shortcuts considering safety evaluations. Therefore, all countries benefit from this strategy, because the distribution of the vaccine started much earlier and will reach all citizens of the world sooner.

The WHO director general has warned that the coronavirus pandemic “will not be the last.” Will it be easier and faster to develop a vaccine against new diseases in the future?

I am sure that the development of the next mRNA vaccine will be much faster, since all the companies involved gained a lot of experience, especially in how to increase production.

Could this technology be used in the future to develop vaccines against cancer or HIV?

Several companies are developing cancer vaccines based on mRNAs that encode cancer antigens, some of which target shared tumor antigens, while others generate individualized cancer vaccines designed to specifically target a patient’s own tumor. Generating HIV vaccines is more complicated. Long-term survivors of HIV-infected people can suppress the virus because they have different genetic backgrounds, rather than generating a special immune response against the virus. Therefore, more research is needed to find a solution.

A few weeks ago, Derrick Rossi, one of the founders of Moderna, told STAT that Karikó and Weissman should receive the Nobel Prize in Chemistry. Kenneth Chien, a cardiovascular biologist at the Karolinska Institute in Sweden and also a co-founder of Moderna, agrees: “All messenger RNA companies, Moderna included, exist thanks to the original work of Karikó and Weissman. They deserve the lion’s share, because without their discoveries RNA vaccines would not be as advanced as to be able to face this pandemic ”.

For Karikó it is inevitable to remember the time when she was a young scientist still in her native Hungary and her mother told her that one day she would win the Nobel. “I would answer him, but if I can’t even get a scholarship, I don’t even have a permanent position at the university!”