Introduction by Professor John F. Cryan for Dr Katalin Karikó

26 Apr 2023

A Sheansailéir agus a mhuintir uilig na hOllscoile, Chancellor of the NUI, Registrar of the NUI, President of UCC, Distinguished Guests, Ladies and Gentlemen.

‘If one takes the path of success, then one ends up either successful or unsuccessful, there is no third alternative’.

These are the words of the Hungarian writer Imre Kertész - winner of the Nobel Prize in Literature in 2002.

Katalin “Kati’ Karikó’s lifework has been dedicated to the understanding of how to create messenger RNA (mRNA) that human bodies can exploit and tolerate, she has laid the bedrock for SARS-CoV-2 vaccines that have saved millions of lives. Her work also promises to be at the forefront of treatments for a variety of other conditions not only infections but cancers and rare diseases that were previously thought undruggable. She has enabled future medicines to arrive today. 

The story of an immigrant from a modest background in rural Hungary- who moves to the US to follow her scientific dreams and makes one of the most important discoveries that has enabled the world to respond to the pandemic- it sounds like a movie pitch- the American dream, Alexander Hamilton eat your heart out…

And whilst all of this is indeed true, unlike Kertesz’s view, the pathway to success in science can lay in between successful or unsuccessful for so long. Kariko, throughout her career, has triumphed over various technical, scientific, and professional challenges. And tonight, we honour her as an inspirational role model for her tenacity, for advancing innovation from basic science to clinical translation and for encompassing the joy of discovery & creativity throughout her career. 

I’m reminded of the line from Magda Szabó’s The Door

“Creativity requires a state of grace. So many things are required for it to succeed—stimulus and composure, inner peace and a kind of bitter-sweet excitement.” 

Kati Karko’s journey is one of bitter-sweet excitement full of fascinating anecdotes all which speak to her determination and self-belief from an early age. She was born the daughter of a butcher in a small rural town Kisújszállás in Eastern Hungary. Until she was ten years old, they all lived in a one-room cottage with no running water and spotty electricity. She decided she wanted to be a scientist from early-on and was hell-bent on following this dream. There is a wonderful story of her at 13 setting out solo across Hungary to a science summer camp, her parents only learned that the trip had gone smoothly after she returned a week later. The following year, she travelled again solo to a national science contest in Budapest. She won third place nationally! 

Her outstanding academic results opened to her the doors of the University of Szeged, which has one of the strongest biological training programs in the country at the time and it was here that the medical potential of RNA began to capture her imagination. Unlike DNA, mRNA would not cause mutations by inserting into chromosomes and it would disappear—like a drug—rather than take up permanent residence in people’s cells. 

However, many practical barriers stood between this therapeutic fantasy and its applications. Scientists would need to make the specific mRNAs of interest in the laboratory, in test tube situations, something that did not become feasible until the mid 1980s. They also needed to deliver the molecules to specific cells within the body. To accomplish this task, the mRNA required packaging to protect it from destructive enzymes and at the same time get across the cell’s lipid bilayer, which repels mRNAs. As an undergraduate, Karikó began tackling the delivery step. She wrapped DNA inside lipid carriers called liposomes. This involved the onerous task of harvesting phoshoplipids as raw material from the brains of slaughtered cattle.

During her Ph.D., she learned how to manipulate RNA and hasn’t stopped since. After graduation, and as a new mother she continued the project as a postdoctoral fellow, but funding dried up. Kariko never wanted to leave Hungary; but she knew that in order to pursue her scientific objectives she had to leave. She sent out letters to labs in Europe and the United States and settled on a postdoc at Temple University in Philadelphia. 

She took her engineer husband and two-year-old daughter with her, along with a teddy bear that had the equivalent of $1200 sewn into it – the proceeds from the sale of their car, exchanged on the black market. Because Hungary limited exportable foreign cash, smuggling it out was the best option. I believe she still has the Teddy Bear with its surgical scars to this day. She spent 3 years at Temple, and then moved to the Uniformed Services University of Health Sciences in Bethesda to learn basic molecular biology and immunology, and was introduced to a new product, lipofectin, a lipid that could carry nucleic acids into cells. It sure beat harvesting cow brain. In 1989 she accepted a Research Assistant Professor position—a nontenured faculty position—at the University of Pennsylvania in Philadelphia, thanks to a cardiologist Elliot Barnathan, who had the grants to pay her salary. 

These were the early days of mRNA… in the 1990s when there were a handful of groups working on mRNA vaccines. Soon enthusiasm for RNA medicines floundered. mRNA instability presented an insurmountable hurdle. mRNA research, and Karikó’s idea that it could be used to fight disease was deemed too radical, too financially risky, and too complex to fund. She applied for grant after grant, but kept getting rejections. Institutional support waivered and there was also the question of how could a basic-science investigator in a clinical department succeed on projects that large and experienced mRNA groups didn’t even dare try. Then in 1995, she was demoted from her position at UPenn. 

Most others would give up but again she persisted – a chance meeting with Drew Weissman around a xerox machine 1997, when he had just been hired as an Assistant Prof. at Penn Medicine changed things forever. Kariko had now been working with mRNA for almost 10 years, and Weissman told her he’d been working in Tony Fauci’s lab and was interested in mRNA technologies for HIV so they joined forces. In the mid 2000s, they made a major discoverys that the mRNA stimulated the immune system & they sent their paper a Nature journal, and within 24 h it was rejected for being incremental. They then showed how modifications to the mRNA allowed it to avoid immune activation in mice. In the modified mRNA molecules, the nucleoside uridine is replaced with pseudouridine, which solved the problem of immune activation and, additionally, improved the stability of the mRNA. The following year 2009, Karikó asked to be reinstated as a research assistant professor. She was told that she was “not faculty quality,” she says. 

Meanwhile, Derrick Rossi, tat Harvard Medical School, grasped the significance of the modified mRNAs & deployed them to convert mammalian cells into embryonic stem cells. This high-profile result, published in 2010, helped launch the company ModeRNA. In 2013, Karikó joined the small biotech company in Germany BioNTech. Biontech was set up by two inspirational physician-scientists and children of Turkish immigrants Ugur Sahin and Ozlem Tureci in 2008. When Kariko joined it didn’t even have a website today it employs > 4500 people. 

She and Weissman—now separated by the Atlantic Ocean—continued to improve the modified mRNA-based strategy. Crucially, they sought a packaging system devoid of downsides—toxicity, lability, or other characteristics that would compromise use in humans. Using so-called lipid nanoparticles, Karikó and Weissman’s group produced a promising vaccine against Zika virus that conferred rapid and lasting immunity in mice and monkeys. When the SARS-CoV2 pandemic hit in 2020, the technology was ready. BioNTech/Pfizer and Moderna made safe and powerful vaccines with unprecedented speed. To date, hundreds of millions of people across the globe have received these life-saving interventions. 

When I look back upon the past, I can only dispel the sadness which falls upon me by gazing into that happy future when the infection will be banished.

Who said this?, Well it was a very famous Hungarian physician & scientist Ignaz Semmelweis. He discovered in the 19 Century that washing the physician’s hands in a solution of chlorinated lime prevented the transmission of purpureal fever. Whilst Semmelweiss’s mantra ‘Wash your hands’ gained a greater significance once again in recent times- the rapid discovery and deployment of vaccines based on the work of another Hungarian, Kariko has epitomised societies journey out of the pandemic. The very fact we are here together in this room today is due to the effectiveness of these vaccines. 

Karikó’s relentless allegiance to her goal prompted a medical revolution. Researchers are exploiting modified mRNAs to develop vaccines for many different disorders ranging from cancers, infectious diseases, autoimmune disorders, heart failure, and inherited illnesses. Now retired from Biointech, Kariko is back in USA enjoying time with her grandchildren Her hard work ethic and endurance has passed onto the next generation. Her daughter, Susan Francia, has rowed for the US, winning two Olympic gold medals in Beijing and London!. The tides have now turned from Kati being asked for autographs of her daughter to the other way around!

She’s been feted by the World Health Organization, painted onto the side of a building in Budapest, was in Time magazine’s Top 100 list and even made Glamour Magazine’s Women of the Year. She has won over 100 prestigious awards including the Lasker Prize, Breakthrough Science Prize, and the Horwitz Prize. Stay tuned as I’m sure there is a certain Swedish Prize on the Horizon….

She has received Honorary Doctorates from her alma mater University of Szeged, from Duke University, Humanitas University of Milan, Eötvös Loránd University Budapest, Radboud University Nijmegen, Rockefeller University, Tel Aviv University, Université libre de Bruxelles, University of Geneva and Yale University. In December she received the Semmelweis Budapest Award- the most prestigious international scientific recognition from the University now named after one Ignaz Semmelweis.

There are some nice parallels between Dr. Kariko’s journey & my own. Like Dr. Kariko I studied originally as a biochemist-in a University city that was the country’s third city. As a postdoc in the late 1990s I moved to Philadelphia and was at the University of Pennsylvania, at the same time Dr. Kariko was there. Then I transitioned to the pharmaceutical industry in early 2000s just as the power of RNA was emerging and when I took my first academic post in the School of Pharmacy here in UCC my early research programme was all about the delivery of such molecules. Now in UCC as Vice President for Research & Innovation we have launched UCC Futures our ambitious new programme of research prioritisation coupled with an innovative academic recruitment strategy across ten indicative areas of strategic importance that will build a foundation for economic, societal and cultural resilience and prosperity. UCC Futures - Future Medicines, led by my wonderful collaborator Prof. Caitriona O’Driscoll from the School of Pharmacy combines a multidisciplinary team of renowned world leading scientists, engineers and clinician investigators at UCC and its affiliated hospitals to deliver high-impact, transformational, next generation medicines and medical technologies. It is creating step-change advancements in earlier detection, faster prognosis and targeted treatments to reduce the global health burden and improve quality-of-life for patients with chronic conditions, such as cancer, cardiovascular, gastrointestinal, neurological, and inflammatory diseases.

It is probably no surprise that RNA Medicines is a key strand to these ambitions. UCC has a longstanding heritage in RNA research. Most notably the work of Prof. John Atkins and more recently Pasha Baranov & colleagues in the School of Biochemistry & Cell Biology that has been focused on key elements of mRNA decoding. The pioneering work of Prof. O’Driscoll who has been joined by Dr. Piotr Kowalski to focus on developing innovative solutions to deliver RNA-based therapeutics will see Future Medicines develop even further. This is the first Honorary Conferring explicitly linked to the UCC Futures initiatives and I cannot think of a better recipient than Dr. Kariko.

There are many things that I find inspirational in Dr. Kariko’s journey. Most notably, the ability to thrive in face of adversity. I feel strongly that we need to acknowledge and perhaps even celebrate the in-between spaces between Kertesz’s Successful and unsuccessful more than we do. The importance of collaboration is key, mentors, allies, diversity of thought and background is weaved throughout her story. The power of working closely & co-creating solutions with industry in driving innovation. Her journey is a global one, showing benefits of mobility and the crucial role that immigrant researchers can have in advancing discovery. UCC brings researchers from every corner of the globe to Cork and with our UCC Futures programme this will be further augmented. Here in UCC we also have a major focus on increasing female entrepreneurship initiatives and encouraging more women into the enterprise sector. Likewise, we want to see not only increased female participation in STEM but to keep women engaged in research throughout their career and strive for equity in all areas of research. I hope Dr. Kariko’s story will inspire many young scientists. Indeed, this is a topic she is passionate about and a strong advocate for removing obstacles for mother’s in research. There is now a kids book on her life called “Never Give up”.

What the mRNA vaccine story tells us and what hopefully our funding agencies hear is that we must continue to support unconventional ideas, to support blue-skies research and the importance of funding people throughout their careers. It reveals blind spots in the scientific reward system — an avoidance of ideas that can be perceived to be so risky and out of the box

that they look impossible. It also highlights the importance of having strong commercialisation links with industry. The pandemic has spotlighted the power of science from both a societal and industrial perspective and we cannot be complacent on reinforcing the need to call for increased investment. We need to continue to embed this Future-focused innovation within our curriculum. UCC is the University where students get taught by world-class researchers. Because of Dr. Kariko, my colleagues in the School of Medicine will now have no problem in getting a first-year medical student to listen to their mRNA lecture…

The pandemic has also illuminated that the public understand the value of investment in science and innovation, and we need to engage more with them to shape our research questions and policies moving forward. When President O’Halloran launched our strategic plan a few months ago he spoke of the importance of securing our future- Through the excellent impactful research of Dr. Kariko we can be assured that our future is better secured.

Returning to Ignaz Semmelweis, he spent his last days condemned to an asylum at 47 with mucj of the medical establishment not believing his words on the importance of handwashing in infection control. Dr. Kariko has said she too has often felt like Cassandra, the mythological Trojan princess cursed to prophesy and never to be believed. We are so glad that the scientific world in academia and industry has finally listened to her that has enabled such an accelerated response out of the darkness of the pandemic.

The great Irish poet Eavan Boland has said “Our future will become the past of other women” We are thrilled that Future Medicines will become the past of this great women.

Kati Kariko: biochemist, innovator, and inspirational scientific role model, it gives me great pleasure to invite you to receive the Degree of Doctor of Science, honoris causa.

Praehonorabilis Cancellarie, totaque universitas! 

Praesento vobis hunc meum filiam, quam scio tam moribus quam doctrina habilem et idoneum esse quae admittatur, honoris causa, ad Gradum Doctoratus Scientia, idque tibi fide mea testor ac spondeo totique Academiae.