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The Hungarian-born biochemist who helped pioneer the research behind the mRNA technology used in the two Covid-19 vaccines that showed positive results, believes it has always been child’s play.
“I never doubted it would work,” Katalin Karikó told the Guardian. “I had seen the data from animal studies and I expected it. I’ve always wanted to live long enough to see something I’ve worked on approved. “
This month was the culmination of Karikó’s lifelong work on researching mRNA, or messenger ribonucleic acid.
The 65-year-old, who left Hungary in 1985 to pursue an academic career in the United States with her husband, baby and just £ 900 hidden in a teddy bear, has now been proposed as a possible Nobel Prize winner.
His work helped pave the way for Pfizer / BioNTech and Moderna vaccines against the coronavirus. Both showed approximately 95% efficacy in late-stage clinical trials. They are expected to receive emergency approval and be provided to the first patients in the coming weeks.
The key to both is mRNA, a single-stranded messenger molecule that provides genetic instructions from DNA, wrapped inside the cell nucleus, to the cell’s protein factories outside the nucleus. In the case of vaccines, the molecule instructs cells to start churning out the harmless spike protein as a warning for the immune system to mobilize against the coronavirus.
The adaptability of mRNA has opened up a new field of therapy, not only for vaccines but also for drugs in areas ranging from cancer to stroke and cystic fibrosis.
Karikó joined BioNTech seven years ago, but for the past four decades she has been stubborn in pursuing her work. He left Hungary, where he had synthesized RNA at the University of Szeged, after receiving an invitation from Temple University in Philadelphia. She brought her engineer husband and two-year-old daughter with her, along with a teddy bear that was sewn onto £ 900 – the proceeds from the sale of their car, traded on the black market.
His daughter, Susan Francia, continued to row for the United States, winning two Olympic gold medals in Beijing and London. “She always said our work ethic was guiding her,” said Karikó. The biochemist recalled how one year she realized in May that she had worked every day until then, including New Year’s, and from time to time she also slept in the office.
In 1989 she joined the University of Pennsylvania School of Medicine, and it was there that she and her colleagues first saw that mRNA worked. “It was then that I knew it was going to be something,” he said. But the team fell apart due to lack of funds. “Then we couldn’t get any money because it was too new.”
He wanted to use mRNA to treat cystic fibrosis and strokes, but he didn’t have the funds to develop the ideas.
In 1998, Drew Weissman, who was working on an HIV vaccine at the National Institutes of Health, joined the university. “I met him at the Xerox machine and told him I could produce any RNA,” recalled Karikó.
They ended up working together and, in 2005, they took a major step forward. The problem with the mRNA was that it triggered an inflammatory reaction when injected. The two researchers, however, found a way to avert this response by modifying one of the four building blocks of mRNA, called nucleosides.
They published their discovery, but it received little attention at the time. Some – including Derrick Rossi, one of Moderna’s founders – now say the duo should receive the Nobel Prize in Chemistry for their breakthrough.
The following year, Karikó and Weissman founded a company to develop mRNA drugs, led by Karikó as CEO. But they never made it to clinical trials, and the university sold the exclusive license of their patent to a third party, CellScript. Meanwhile, Rossi, a Canadian stem cell biologist who had read their groundbreaking 2005 paper, found strong financial backers and in 2010 founded Moderna in Cambridge, Massachusetts.
In 2013, Karikó joined BioNTech – she also had a job offer from Moderna – which was based on the Mainz university campus in Germany and didn’t even have a website at the time.
It has been a busy seven years. BioNtech now has 1,500 employees and its market value hit a record $ 25 billion (£ 19 million) when the first positive test results of the Covid-19 vaccine it developed with Pfizer were released last week.
Karikó is senior vice president of biotechnology and chief of RNA protein replacement therapies and is also an adjunct associate professor at the University of Pennsylvania. Weissman, a university professor of medicine, has continued to develop RNA vaccine candidates against influenza, herpes and HIV.
Both BioNTech and Moderna have licensed the modified mRNA technology developed by Karikó and Weissman for their vaccines.
Karikó has high hopes for mRNA as a “universal platform”, for example as a treatment for epidermolysis bullosa, a serious skin disease that causes painful blisters. And he already has great ideas on how it might work: “How about making mRNAs that the family can keep in the refrigerator and apply when their baby’s skin peels off?”
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