Through years of creative work and dogged persistence, Katalin Karikó and Drew Weissman forged a scientific partnership that overturned conventional wisdom about using mRNA as a vaccine platform. Their work laid the essential foundation for the mRNA-based COVID-19 vaccines, making it possible to develop and manufacture them with unprecedented speed in the midst of a global pandemic.
In the early months of 2020, as the singular threat of SARS-CoV-2 was establishing itself as the worst pandemic in a century, the immediate prospects seemed bleak. Although the genome of the virus was sequenced quickly, its virulence and rapid spread led many to despair that it could not be controlled and stopped before COVID-19 claimed an enormous toll of lives. It was clear that, as with communicable diseases of the past, a safe and effective vaccine would be the ultimate weapon against the virus, but how to find a vaccine for a brand new version of a pathogen only seen in different forms previously? Fortunately, scientists did not have to start from scratch. Katalin Karikó and Drew Weissman had been among a cadre of inventive and creative researchers who had already spent years laying the groundwork for an entirely new approach to vaccines—one based on messenger RNA (mRNA).
The potential of mRNA for vaccines or disease therapies was considered little more than an interesting but highly unlikely prospect for many years. A vital component of the cellular protein production pathway, mRNA was simply thought to be too unstable to be used outside the cell. It was also shown to trigger a severe and sometimes fatal inflammatory response in test animals, with the body's own immune system attacking mRNA as if it were a foreign intruder. There appeared to be no practical way to overcome these obstacles, and RNA therapy seemed a scientific dead end.
Karikó and Weissman thought differently. They were both fascinated by RNA, and in more than the basics: they wanted to explore how RNA in its various forms could fight disease. After a chance meeting while both faculty at the University of Pennsylvania, they joined scientific forces to explore RNA vaccines and therapies. The challenges they faced were more than simply scientific. Because the idea of an mRNA-based vaccine was widely dismissed, funding for such research was hard to obtain. Still, they pressed on, convinced their research could blaze a new path in vaccine development. Finally, three biotech companies already keenly interested in the potential of mRNA, CureVac, Moderna, and BioNTech, agreed to support the research.
Karikó and Weissman devised a way to allow mRNA to evade the immune system response by altering one of its nucleotides. The modified version of mRNA could safely slip into a host cell and direct the synthesis of the encoded protein. To solve the stability problem, they found a way to package the mRNA molecule inside a lipid nanoparticle to protect and preserve it until it reached its final destination inside a cell. These fundamental breakthroughs, realized several years before anyone ever heard of COVID-19, formed the basis of the revolutionary vaccines manufactured by Pfizer-BioNTech and Moderna. When SARS-CoV-2 blindsided the world, the scientific tools were already in place to quickly create a remarkably effective vaccine that, slowly but surely, is enabling humanity to come to terms with this deadly disease.
Karikó and Weissman hail from very different backgrounds. Weissman was raised in comfortable middle-class surroundings in Massachusetts and schooled at Brandeis University and Boston University, later working with Dr. Anthony Fauci through a fellowship at the National Institutes of Health. Meanwhile Karikó spent the early part of her life in politically repressive and economically-deprived Hungary, then still part of the Soviet Bloc. She earned her Ph.D. in biochemistry at the University of Szeged and then chose to pursue science in the U.S., emigrating in 1985.
Karikó and Weissman’s tenacious and determined work has also opened up a new range of exciting possibilities to battle AIDS, cancer, and cardiovascular disease through the application and further development of the mRNA technology that the COVID vaccines have vindicated so spectacularly. And as the SARS-CoV-2 virus continues to challenge science with new variants, they are in the forefront of efforts to develop a universal vaccine to protect against all existing COVID variants and any that might arise in the future. It is hardly an easy task, and one that some think is not possible or practical. But as Katalin Karikó, now a senior vice president of BioNTech, and Drew Weissman, who remains a professor of medicine at the University of Pennsylvania’s Perelman School of Medicine, can attest, the same thing was once said about mRNA vaccines—before they showed how it could be done.