When Drs. Katalin Karikó and Drew Weissman first met at the University of Pennsylvania, Dr. Karikó had been demoted and was moving from job to job because she lacked funding to support her research. Dr. Karikó’s research was in using messenger RNA (mRNA) to treat disease, however, her ideas were met with great skepticism by the scientific community. Fortunately, Dr. Weissman, an immunologist, also had an interest in this area. He welcomed Dr. Karikó into his lab in 1997, and the two have collaborated on synthetic mRNA treatments ever since.
Despite numerous rejections and setbacks, the two persisted in their mRNA research because they believed that this held the future for vaccinations that could bolster our immune system to fight numerous types of diseases. This approach was attractive because if this worked, it would mean people could gain immunity without having to be injected with an actual strain of a virus, which was the norm up until the Covid-19 pandemic. Drs. Karikó and Weissman’s decades of perseverance paved the way for the technology needed to combat and pull the world out of the Covid-19 pandemic.
The Covid-19 pandemic, caused by SARS-CoV-2, started in Wuhan, China in December 2019, and rapidly spread to infect 771 million people and contributed to 6.9 million deaths worldwide. Social distancing became the norm as countries went on lockdown and work from home became common for people not on the front lines. Despite the precautionary measures, it became clear that the only way out of the pandemic would be the introduction of an effective vaccine. Two vaccines received Emergency Use Authorization in the U.S. in December 2020, and both of those vaccines used the mRNA technology that Drs. Karikó and Weissman had spent more than two decades perfecting.
Both the Pfizer-BioNTech and Moderna vaccines contain mRNA that instructs the person’s cells to manufacture the Covid-19 spike protein, simulating infection with Covid-19. Because the immune system sees this protein as an invader, it mounts an immune response to the spike protein that is present on the coronavirus thereby giving the person robust immunity to Covid-19. So far 81 percent of the U.S. population has received at least one dose and 70 percent of the population is considered fully vaccinated.
Eyes On The Prize
The Nobel Assembly at Karolinska Institute decided Monday to award the 2023 Nobel Prize in Physiology or Medicine jointly to Drs. Katalin Karikó and Drew Weissman, who paved the way for the development of the mRNA vaccines that contributed immensely to ending the pandemic and saving countless lives. Both vaccines were 95 percent effective at preventing disease. What surprised the world was how fast these vaccines were developed and how well they worked. This was largely due to the innovative approach of these two newest Nobel laureates.
This was possible because the mRNA provides biological induction by delivering a DNA blueprint that the body can use to make proteins. When Drs. Karikó and Weissman first started collaborating, they began their experiments by injecting mice with mRNA, however many of the mice were getting sick and some even died. Eventually they packaged the mRNA into a lipid nanoparticle, which helped it to evade detection by the host immune system until it got to its target location. They also incorporated pseudouridine into the mRNA. Pseudouridine enhanced RNA stability inside the body and it decreases anti-RNA immune response. These modifications kept the animals from getting sick after the injections and allowed them to successfully create vaccines for mice.
However, success in mice does not always translate to success in humans. In order to create an mRNA vaccine for Covid-19, the scientists first needed to have the DNA template. The DNA template was provided on January 11, 2020 by Chinese scientists who had the earliest exposure to the virus. This mRNA technology worked so well that the time between the Chinese government providing their SARS-CoV-2 genetic structure and Moderna transporting its vaccine candidate to the National Institutes of Health (NIH) in the United States for phase one studies was just 44 days. It is notable that other vaccines that used the same technology without the pseudouridine were not as successful as the Pfizer-BioNTech and Moderna vaccines.
Dr. Katalin Karikó received her bachelor’s degree in biology in 1978 and her doctorate in biochemistry in 1982 from the University of Szeged in her native Hungary. Her lab in Hungary lacked funding, so she moved to the U.S. and started work as a postdoctoral fellow at Temple University and eventually transitioned to a position at the University of Pennsylvania. Dr. Karikó has been researching mRNA-based therapy since 1990, when she became an adjunct professor at Penn. Dr. Karikó research was met with great skepticism and resulted in grant rejections and her manuscripts not being accepted for publication by major journals. She was demoted and “kicked out from Penn,” which led to her pursuing an opportunity to work in Germany with BioNTech in 2013. There, she initially served as vice president and in 2019 she was promoted to senior vice president. She has since returned to Penn, where she is adjunct professor of neurosurgery.
Dr. Drew Weissman received his bachelor’s degree from Brandeis University and his M.D. and Ph.D. in 1987 from Boston University. He completed his residency at Beth Israel Deaconess Medical Center followed by a fellowship at the National Institutes of Health, under the supervision of Dr. Anthony Fauci, who at the time was director of the National Institute of Allergy and Infectious Diseases. Dr. Weissman is professor of medicine and director of the Institute for RNA Innovation at Penn Medicine.
In her interview with the Nobel Committee, Dr. Karikó’s message to female scientists was “you don’t have to choose between having a family, you can have it, you don’t have to over assist your child, your child will watch you and they will do, because that’s what counts, the example that you present.” Indeed, Dr. Karikó’s daughter followed her mom’s persistence and is a two-time Olympic champion and five-time world champion in rowing.
Drs. Karikó and Weissman marshalled in the technology to fight off this invisible enemy known as Covid-19. Indeed, by making visible the approach to successful immunization against this lethal disease, they too became visible to the world and have rightfully earned the honor of being called Nobel laureates. Like any great scientists, they have their eyes on what’s next. They are looking to cure other diseases with this technology, including sickle cell disease, various forms of cancer and also creating other vaccines to address other diseases like flu, malaria, leptospirosis and respiratory syncytial virus (RSV). Drs. Karikó and Weissman provide hope to scientists conducting research not yet appreciated by the scientific community and they also provide hope for humanity that collectively we have the talent to fight the most lethal of enemies, even when invisible, as was seen with the Covid-19 pandemic.