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Persistence Pays Off: Recognizing Katalin Karikó and Drew Weissman, the 2023 Nobel Prize Winners in Physiology or Medicine

Posted on by Lawrence Tabak, D.D.S., Ph.D.

Modified mRNA is inserted into a lipid nanoparticle. This is delivered via a vaccine. Cells read the instructions and make viral spike proteins which leads to antibody production.
Karikó and Weissman discovered how to slightly modify mRNA to avoid an inflammatory response making the mRNA vaccines possible. Credit: Donny Bliss/NIH

Last week, biochemist Katalin Karikó and immunologist Drew Weissman earned the Nobel Prize in Physiology or Medicine for their discoveries that enabled the development of effective messenger RNA (mRNA) vaccines against COVID-19. On behalf of the NIH community, I’d like to congratulate Karikó and Weissman and thank them for their persistence in pursuing their investigations. NIH is proud to have supported their seminal research, cited by the Nobel Assembly as key publications.1,2,3

While the lifesaving benefits of mRNA vaccines are now clearly realized, Karikó and Weissman’s breakthrough finding in 2005 was not fully appreciated at the time as to why it would be significant. However, their dogged dedication to gaining a better understanding of how RNA interacts with the immune system underscores the often-underappreciated importance of incremental research. Following where the science leads through step-by-step investigations often doesn’t appear to be flashy, but it can end up leading to major advances.

To best describe Karikó and Weissman’s discovery, I’ll first do a quick review of vaccine history. As many of you know, vaccines stimulate our immune systems to protect us from getting infected or from getting very sick from a specific pathogen. Since the late 1700s, scientists have used various approaches to design effective vaccines. Some vaccines introduce a weakened or noninfectious version of a virus to the body, while others present only a small part of the virus, like a protein. The immune system detects the weak or partial virus and develops specialized defenses against it. These defenses work to protect us if we are ever exposed to the real virus.  

In the early 1990s, scientists began exploring a different approach to vaccines that involved delivering genetic material, or instructions, so the body’s own cells could make the virus proteins that stimulate an immune response.4,5 Because this approach eliminates the step of growing virus or virus protein in the laboratory—which can be difficult to do in very large quantities and can require a lot of time and money—it had potential, in theory, to be a faster and cheaper way to manufacture vaccines.

Scientists were exploring two types of vaccines as part of this new approach: DNA vaccines and messenger RNA (mRNA) vaccines. DNA vaccines deliver an encoded protein recipe that the cell first copies or transcribes before it starts making protein. For mRNA vaccines, the transcription process is done in the laboratory, and the vaccine delivers the “readable” instructions to the cell for making protein. However, mRNA was not immediately a practical vaccine approach due to several scientific hurdles, including that it caused inflammatory reactions that could be unhealthy for people.

Unfazed by the challenges, Karikó and Weissman spent years pursuing research on RNA and the immune system. They had a brilliant idea that they turned into a significant discovery in 2005 when they proved that inserting subtle chemical modifications to lab-transcribed mRNA eliminated the unwanted inflammatory response.1 In later studies, the pair showed that these chemical modifications also increased protein production.2,3 Both discoveries would be critical to advancing the use of mRNA-based vaccines and therapies.

Earlier theories that mRNA could enable rapid vaccine development turned out to be true. By March 2020, the first clinical trial of an mRNA vaccine for COVID-19 had begun enrolling volunteers, and by December 2020, health care workers were receiving their first shots. This unprecedented timeline was only possible because of Karikó and Weissman’s decades of work, combined with the tireless efforts of many academic, industry and government scientists, including several from the NIH intramural program.  Now, researchers are exploring how mRNA could be used in vaccines for other infectious diseases and in cancer vaccines.

As an investigator myself, I’m fascinated by how science continues to build on itself—a process that is done out of the public eye. Luckily every year, the Nobel Prize briefly illuminates for the larger public this long arc of scientific discovery. The Nobel Assembly’s recognition of Karikó and Weissman is a tribute to all scientists who do the painstaking work of trying to understand how things work. Many of the tools we have today to better prevent and treat diseases would not have been possible without the brilliance, tenacity and grit of researchers like Karikó and Weissman.


  1. K Karikó, et al. Suppression of RNA Recognition by Toll-like Receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity DOI: 10.1016/j.immuni.2005.06.008 (2005).
  2. K Karikó, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stabilityMolecular Therapy DOI: 10.1038/mt.2008.200 (2008).
  3. BR Anderson, et al. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activationNucleic Acids Research DOI: 10.1093/nar/gkq347 (2010).
  4. DC Tang, et al. Genetic immunization is a simple method for eliciting an immune response. Nature DOI: 10.1038/356152a0 (1992).
  5. F Martinon, et al. Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. European Journal of Immunology DOI: 10.1002/eji.1830230749 (1993).

NIH Support:

Katalin Karikó: National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke

Drew Weissman: National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research; National Heart, Lung, and Blood Institute


  • Dear Dr Weissman

    Thank you for your fine article.

    But it could have been better.

    How about simply saying that the NIH, and the
    USA academic system made a mistake in not
    recognizing and finding someway to provide
    minimal support to Dr. Kariko?

    I refer specifically to a wealthy clinical
    department at the distinguished University of
    Pennsylvania Medical

    Only by recognizing mistakes can we begin to remedy them.
    That is a fundamental principle of science itself.
    It should be a principle of scientific administration, I hope
    you will accept, without being insulted by what I write.

    Ever yours
    Robert Eisenberg
    Prof. and Chairman emeritus Dept of Physiology and Biophysics, Rush University
    Adjunct Professor Illinois Institute of Technology (Chemistry and Mathematics)
    Adjunct Professor University of Illinois Chicago (Biomedical Engineering).

  • Mr Rudolph says:

    Congrats to Weissman and Kariko, keep up the great work. Persistence is the key and most definitely Faith! You guys Rock!

  • Vical King says:

    Great now you can all acknowledge Dr Malone for inventing the actual idea and patents in the first place

  • Manny Karos says:

    Congratulations on the Nobel prize in Physiology or Medicine. Your research has and always will benefit public health in an exemplary manner.
    Manuel Karos
    Retired FDA
    Consumer Safety Officer

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