Katalin Karikó and Drew Weissman, two scientists credited with discoveries leading to the development of mRNA vaccines against the Wuhan coronavirus, received the Nobel Prize in Physiology or Medicine on Monday.
Karikó, from Hungary, and Weissman, from Massachusetts, collaborated on research that ultimately led to breakthroughs in using mRNA technology to prompt human immune responses. The research was published nearly two decades ago, the Nobel Assembly detailed in its announcement of the award, and was initially considered to have potential in fighting viruses such as Zika, which had spread rapidly in South America in 2016, causing significant birth defects in children born to infected mothers. Experimentation with a potential mRNA vaccine against the coronavirus that causes Middle Eastern Respiratory Syndrome (MERS) ultimately led to the rapid development of the Wuhan coronavirus vaccine products – distributed by the corporations Moderna and Pfizer in America – debuting in 2021.
The onset of the ongoing Wuhan coronavirus pandemic prompted a flurry of scientific work pursuing the development of vaccines against the alpha variant of the virus, the version initially infecting people in Wuhan, China, in late 2019. The Pfizer and Moderna vaccines competed with several other vaccine products based on older technology. The most prominent competitors to the mRNA vaccines were developed using virus vectors. The two most widely used in the West, the Johnson & Johnson and AstraZeneca vector vaccines, ultimately lost medical approval in several countries after the documentation of a heightened risk of blood clots in women.
A growing volume of scientific studies indicates that the mRNA vaccines are not without their risks – prominently a link between the Wuhan coronavirus mRNA vaccines and myocarditis, a condition causing heart inflammation in young men – but pharmaceutical researchers continue exploring new applications for the technology to combat other viruses and non-viral conditions such as cancer.
Karikó and Weissman’s discoveries, the Nobel Assembly said, were “critical for developing effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020.”
“Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times,” the organization stated.
The two scientists studied how dendritic cells, which help mammalian bodies identify invading pathogens, respond to modified mRNA.
“Karikó and Weissman noticed that dendritic cells recognize in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signaling molecules,” the Nobel Assembly narrated. “They wondered why the in vitro transcribed mRNA was recognized as foreign while mRNA from mammalian cells did not give rise to the same reaction. Karikó and Weissman realized that some critical properties must distinguish the different types of mRNA.”
Their experiments in 2005 revealed that “the inflammatory response was almost abolished when base modifications were included in the mRNA. This was a paradigm change in our understanding of how cells recognize and respond to different forms of mRNA.”
These revelations led to pharmaceutical companies modifying mRNA in attempts to get the human body to efficiently resist viral infections. Years of research based on the initial 2005 discovery, the Nobel Assembly explained, came into rapid action in response to the Wuhan coronavirus pandemic.
“After the outbreak of the [Wuhan coronavirus] pandemic, two base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed,” the Assembly said. “Protective effects of around 95% were reported, and both vaccines were approved as early as December 2020.”
“The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform also for vaccines against other infectious diseases,” the Assembly continued. “In the future, the technology may also be used to deliver therapeutic proteins and treat some cancer types,” it predicted, crediting the technology with saving “millions of lives and prevent[ing] severe disease in many more, allowing societies to open and return to normal conditions.”
Millions of people around the world have now received one or multiple doses of coronavirus mRNA vaccine products and the shots have been the subject of much praise, speculation, and controversy. Both the Pfizer and Moderna vaccines originated in America, though Pfizer collaborated with the European corporation BioNTech and the Chinese company Fosun Pharmaceuticals to develop its product. The presence of Fosun Pharma on the list of developers did not stop the Communist Party of China, which was fiercely campaigning to blame the United States for the pandemic, from attempting to discredit the vaccines. Chinese state media outlets complained that mRNA technology was too “high-priced” and “complicated” – requiring more care to preserve than vaccines using inactivated viral material or vectors – for poor countries and promoted its homemade products by corporations Sinovac and Sinopharm.
As dictator Xi Jinping vowed to distribute Chinese traditional technology vaccines around the world as a “global public good,” the head of the Chinese Centers for Disease Control (CDC) at the time, Gao Fu (George Gao), openly stated that China’s products were inferior to the West’s mRNA technology.
“Everyone should consider the benefits mRNA vaccines can bring for humanity. We must follow it carefully and not ignore it just because we already have several types of vaccines already,” Gao said in April 2021, adding that Chinese vaccine’s “don’t have very high protection rates.”
Gao mysteriously “retired” a year later, allegedly as a result of his age, though his replacement was only two years younger.
China approved its first mRNA-technology vaccine product against the Wuhan coronavirus in March 2023, a product made by the local company CSPC Pharmaceutical Group.
American mRNA vaccine products have also prompted concerns at home in light of evidence suggesting a correlation between their use and incidents of myocarditis in young men.
“Individuals with preexisting cardiac conditions, such as myocarditis and pericarditis, should take particular caution when considering vaccination and discuss with their health care provider,” medical guidance published by the surgeon general of Florida in October 2022 read, suggesting men between the ages of 18 and 39 should avoid the products.
A study published in June 2022 by the U.S. Centers for Disease Control (CDC) found “a causal association between mRNA COVID-19 vaccination and myocarditis and pericarditis,” particularly in men.
“Risk is greatest in adolescents and young adults, higher after dose 2 compared to dose 1 of the primary series, and higher in males compared to females,” the study detailed.
The CDC said in an updated coronavirus vaccination guideline publication that the risk exists, but is less than the risk of myocarditis being triggered by a Wuhan coronavirus infection.
“In one study, the risk of cardiac complications, including myocarditis, in males 12-17 years old was 1.8 – 5.6 times higher after COVID-19 infection than after COVID-19 vaccination,” the CDC said in September.
BioNTech announced in January that it is developing mRNA-based cancer therapy.
“Up to 10,000 people will receive the immunotherapy tailored to individual tumours by the end of 2030, either in trials or as an approved treatment,” the Agence France-Presse (AFP) reported at the time.