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Discovery & Development Drug Discovery, COVID-19, Small Molecules, Vaccines, Profession

The Nobel Prize for mRNA Vaccines Against COVID-19

Photography, courtesy Penn Medicine

The 2023 Nobel Prize in Physiology or Medicine has been awarded jointly to Katalin Karikó and Drew Weissman “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.”

Their technology – now recognized by the most prestigious prize in science and medicine – is used in both the Pfizer/BioNTech and Moderna COVID-19 vaccines.

“Thomas called”

Speaking at a press conference at the University of Pennsylvania (UPenn), Karikó explained that she received “the news” via a phone call at around 3.40 am, but confessed that she didn’t know if it was real or a prank. She was also concerned that the caller did not have the correct phone number for Weissman, so Karikó sent him a message.

Weissman explained, “I just got a cryptic message at 4 in the morning: ‘Thomas called’. So I texted her back and said ‘Who’s Thomas?’ And she says: ‘Nobel Prize.’”

But still they were unsure – partly wondering if it might be an anti-vaxxer or some other nefarious player toying with them. Weissman says he watched the formal announcement from bed with his wife and cat (if you’re interested, the cat at the time was begging for food). And then it all became very real.

“The phrase Nobel Prize elicits images of individuals whose work has, without exaggeration, changed the world,” said J. Larry Jameson, executive vice president of the UPenn Health System and Dean of the Perelman School of Medicine. “During the biggest public health crisis of our lifetimes, vaccine developers relied upon the discoveries by Dr. Weissman and Dr. Karikó, which saved innumerable lives and paved a path out of the pandemic. Now, the same approach is being tested for other diseases and conditions. More than 15 years after their visionary laboratory partnership, Kati and Drew have made an everlasting imprint on medicine.” 

An uphill battle

Karikó and Weissman initially met in 1997 – at a coffee machine at UPenn – where they found they had a shared interest in mRNA. The chance meeting led to a research partnership, but the world around them was not ready for their work. In fact, prior to their meeting, in 1995, Karikó had already been demoted from tenure track and received a pay cut because she was unable to secure financial grants for work with synthetic mRNA. At the time, synthetic mRNA was considered too unstable to be of use. However, Weissman was interested. Speaking to Bostonia, Weissman said, “I never say no to anything. RNA had been tried by others and didn’t work very well, but I wanted to try it.” 

In their early work together, Karikó and Weissman injected mice with mRNA, but discovered that this triggered an aggressive inflammatory immune response. They persevered. In 2005, they found a way to modify a nucleoside to evade the immune response. They believed that the findings would be groundbreaking, leading to countless vaccines and therapeutics. But the world was not interested.

“We couldn’t get funding. We couldn’t get publications. We couldn’t get people to notice mRNA as something interesting,” Weissman recalled at the press conference. “It had failed clinical trials and pretty much everyone gave up on it, but Kati lit the match. And we spent the rest of our 20+ years working together figuring out how to get it to work; how to get a vaccine to function well. And COVID hit and the vaccines were recognized for 95 percent efficacy, which was really a turning point in RNA therapeutics.”

Commenting on the prize, John Tregoning, Professor in vaccine immunology within the Department of Infectious Disease at Imperial College London, said, “Kati Karikó is one of the most inspirational scientists I have met. The ideas that she and Drew Weismann developed were critical for the success of RNA vaccines. They demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it. This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA. This was a vital building block of the success of the RNA vaccines in reducing disease and death during the pandemic. Their work shows the importance of basic, fundamental research in the path to solutions to the most pressing societal needs.”

Eventually, the technology was licensed to BioNTech and Moderna. While Weissman remained at UPenn, Karikó departed in 2013 (in her Nobel Prize interview, she describes it as being “kicked out”) and joined BioNTech – after meeting BioNTech scientists during a trip to Europe, when she accompanied her daughter to a rowing tournament (her daughter, Susan Francia, is today a two time Olympic gold medalist). When meeting BioNTech, Karikó said, “This was the first time in my life that I didn’t have to explain that RNA is good, because all of the people who were there, were believers.”

Some controversy…

The University of Pennsylvania has showered both Karikó and Weissman with praise. Today, Karikó is a professor at Szeged University, Hungary, and an adjunct professor of Neurosurgery at UPenn’s Perelman School of medicine. Weissman is the Roberts Family Professor of Vaccine Research, also at the Perelman School of Medicine. Penn President Liz Magill said, “Katalin Karikó and Drew Weissman are brilliant researchers who represent the epitome of scientific inspiration and determination. Day after day, Dr. Weissman, Dr. Karikó and their teams worked tirelessly to unlock the power of mRNA as a therapeutic platform, not knowing the way in which their work could serve to meet a big challenge the world would one day face. With the truest devotion to their field, they’ve already promised they will not stop here, and that is the greatest inspiration of all. Our Penn community is enormously proud of their groundbreaking achievements and this well-deserved recognition.” 

However, some have pointed out that UPenn has not acknowledged the difficulties that Karikó encountered in her early career. Others are also pointing to a 2020 interview with Karikó published by Wired. In 2013, UPenn refused to reinstate Karikó to the faculty position she had lost in 1995. She said, “They told me that they’d had a meeting and concluded that I was not of faculty quality. When I told them I was leaving, they laughed at me and said, ‘BioNTech doesn’t even have a website.’”

On the social media platform X (formerly known as Twitter), the university is taking a beating in response to its social media posts congratulating the winners. Here are just two examples:

  • Founder of Siren Biotechnology Nicole Paulk posted: “You shunned her and put roadblocks in the way of her and her research when she was at Penn. You should feel immense shame, not pride, today. You played no role in this. This win is hers and Drew's.”
  • The Kulkarni Lab at Harvard Medical School posted, “Wait, didn't @PennMedicine fire her 10 years ago and not support her when she needed them? Fact that they are now using her to gloat about how wonderful they are proves one of Simon's Maxims. "Institutions Don’t Love You Back"

The university will have to deal with the press storm, and the research community as a whole should take note of the significant issue highlighted by Karikó’s experience: good or even groundbreaking research does not always get funded. 

Biologist Michael Eisen at UC Berkeley added further fuel to the X fire: “Not to be a crankypuss, but awarding a Nobel for work that suffered from not being taken seriously for decades only *after* it proved to be of incredible value is not a triumph of prizemaking - it's a complete condemnation of it and the entire culture of modern academic science.”

Immeasurable impact

The world is fortunate that Weissman and Karikó believed so passionately in the potential of their work and persevered for so long. COVID-19 vaccines have been estimated to have prevented almost 20 million COVID-19 deaths worldwide.

The whole team at The Medicine Maker offers sincere congratulations to Katalin Karikó and Drew Weissman. I’d like to finish with a press conference quote from Weissman: “We would sit together in 1997 after work and talk about all of the things that we thought RNA could do, all of the vaccines, and therapeutics and gene therapies, and realized how important it had the potential to be. And that’s why we never gave up.”

Again, huge congratulations – and thank you for not giving up!

If you’d like to read more about the winners, check out their Nobel Prize Interviews. 

Weissman interview

Karikó interview

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About the Author
Stephanie Vine

Making great scientific magazines isn’t just about delivering knowledge and high quality content; it’s also about packaging these in the right words to ensure that someone is truly inspired by a topic. My passion is ensuring that our authors’ expertise is presented as a seamless and enjoyable reading experience, whether in print, in digital or on social media. I’ve spent fourteen years writing and editing features for scientific and manufacturing publications, and in making this content engaging and accessible without sacrificing its scientific integrity. There is nothing better than a magazine with great content that feels great to read.

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