- [In German only] Harro Albrecht, Ulrich Bahnsen, Jens Lubbadeh und Florian Schumann, ZEIT 2.Oktober 2023
- Katalin Karikó (Wikipedia)
- Drew Weissman (Wikipedia)
The decisive idea was her own initiative: Katalin Karikó, the daughter of a Hungarian butcher, and born in 1955, decided to study biology at the age of 14. She studied in Szeged, Hungary, from 1972 to 1982. Katalin Karikó first came into contact with mRNA during her doctoral thesis in Hungary in the 1970s. It is chemically different from DNA: with uridine instead of thymidine.
She obtained a degree in biology in Szeged in 1978 and a doctorate in biochemistry in 1982, both from the University of Szeged. She continued her postdoctoral research at the Institute of Biochemistry of the Hungarian Biological Research Centre. Sensitive, but not abnormal for Eastern Europe at the time: from 1978 to 1985, she worked as an agent for the Hungarian secret police, which she claims she was blackmailed into doing because she feared repercussions for her career or reprisals against her father.
In 1985, her laboratory lost its funding and Karikó left Hungary for the USA with her husband Béla Francia and their two-year-old daughter. She accepted an invitation to Temple University in Philadelphia. She worked there for three years, and then lived in Washington for a year.
From 1989, she worked at the Faculty of Medicine at the University of Pennsylvania. In 1998, she met immunologist Drew Weissman, professor at the same university by chance (in the queue in front of a photocopier, see below). She then researched the development of mRNA-based drugs with him.
Together they founded a company, which Karikó led as managing director. A specific drug development failed and the patent they obtained on the technology was sold by the university. Bitterly, Karikó's position as assistant professor was not extended by the university. She was downgraded to a temporary postdoc position.
She finally succeeded in modifying the mRNA molecules in such a way that they were no longer destroyed by the immune defence in human cells, but continued to have a stable immunogenic effect. Ingenious! Karikó published the results together with Weissman. Derrick Rossi from Harvard took up the technology and developed it further. In 2010, he and his colleagues founded the company Moderna.
In Germany, the busy founders of BioNTech, Uğur Şahin and Özlem Türeci, became aware of Karikó and offered her a job. Karikó has been Senior Vice President at BioNTech since 2013. She has been a professor at her home university in Szeged since the end of September 2022.
Karikó's goal was to create artificial mRNA that would stimulate the exact protein production needed to cure a specific disease. She found a way to modify the mRNA in such a way that it tricks the human immune system.
However, the scientific community was not particularly interested in their discovery. At that time, in the mid-2000s, most were focussing on DNA research. She was demoted at university and was unable to find research funding. The company she had set up with her colleague Weissman was unsuccessful. Where others would have given up long ago, Karikó fought on and believed in her research.
She told the "Washington Post" in an interview what drove her at the time:
"I want to live long enough to be able to help bring the RNA to the patient. I want to see at least one person who can be helped with this treatment."
And then came corona. The name mRNA was suddenly on everyone's lips. The fact that the vaccines were available so quickly was due to decades of basic research by many researchers. Karikó succeeded in further developing the work and making it applicable to humans. In doing so, she laid the foundation for the vaccines now being developed by BioNTech and Moderna against the coronavirus.
Their first dialogue at the photocopier must have gone something like this, as the two later recounted:
"I can produce RNA," said Karikó proudly.
"And I want to create a vaccine against HIV," said Weissman. "But DNA doesn't work, can I get RNA from you?"
"No problem."
With the rather quiet Weissman, Karikó found the solution to a complicated problem in 2005: giving the immune system a head start against invading pathogens. If the genetic code of a virus, for example, is known, this information could be injected into a person. In this way, the body's own defence system gets to know the virus like a profile and is prepared for an emergency. However, if left unchanged, foreign mRNA leads to violent inflammatory reactions in the human body. This is how the immune system recognises the mRNA of viruses and bacteria and tries to eliminate them.
Together with Weissman, Karikó succeeded in finding a solution. The mRNA of mammals is not recognised as foreign by the body because the bases are chemically slightly altered. So the scientists modify mRNA in the laboratory.
And it worked: the immune cells to which they present the modified mRNA no longer trigger an inflammatory reaction, the mRNA is not degraded, but it does induce antibodies.
Suddenly the mRNA can be used for medical purposes - for potential vaccines, cancer drugs and completely new and powerful gene therapies.
Karikó and Weissman recognised this potential and published their findings in 2005, 15 years before the outbreak of the coronavirus pandemic. The significance of this discovery also remained unclear to their (typically mainstream) US university for a long time (although they later made a lot of money from the patent):
The University of Pennsylvania never offered her researcher Karikó a professorship, which she naturally regrets today. Karikó even had to vacate her laboratory in 2013. She retired and continued her research privately.
But a stroke of luck unfolded: That same year, Karikó met Uğur Şahin in Mainz, who, together with his wife Özlem Türeci, had founded the then still inconspicuous company BioNTech in Goldgräbergasse, Germany. Alongside Türeci and Şahin, stem cell researcher Derrick Rossi recognised the potential of Weissman and Karikó's work early on. Their research also led him to success.
From 2006, Rossi was fascinated by a process developed by Shinya Yamanaka that transforms aged body cells back into very young embryo cells. However, this requires four genes to be introduced into the cells - a major risk. Instead of the four genes, Rossi uses the mRNA they produce. This made him the co-founder of a new start-up: Moderna.