The prize is awarded to Katalin Karikó and Drew Weissman for research that led to the development of mRNA vaccines
The Nobel Prize in Physiology or Medicine this year is awarded to Katalin Karikó and Drew Weissman for their research that led to the development of mRNA vaccines, serving as the foundation for the development of COVID-19 vaccines
The collaboration that led to the mRNA vaccines. Weissman and Karikó | Nobelprize.org.
Understanding mRNA vaccines
While traditional vaccines rely on introducing actual disease-causing agents or parts of them such as weakened or dead viruses, or in some cases certain proteins of these viruses, which are injected to elicit an immune response against them, mRNA vaccines take a different approach. Rather than using the virus or its proteins, these vaccines use messenger RNA - a copy of the gene, which is essentially a set of instructions for cells to produce the virus's protein. Once this mRNA is injected and taken up by cells, they begin to produce the virus's protein in large quantities. This protein is then presented to the immune system, stimulating an immune response.
Weissman and Karikó played pivotal roles in advancing mRNA vaccine research. While as early as 1990, researchers demonstrated that mRNA could be injected into mice, leading their cells to produce the corresponding protein, there were significant challenges. Regular mRNA degrades rapidly within the body upon injection and often triggers cellular defense mechanisms that cause local inflammation without necessarily stimulating the sought-after immune response against the target protein.
Traditional vaccines involve the actual disease-causing agents or parts of them. Illustration of the various types of vaccines that preceded mRNA vaccines | Illustration: Nobelprize.org
Stabilizing the Molecule
In 2005, and in subsequent research studies, Weissman and Karikó found a solution. RNA consists of four types of building blocks known as bases. The sequence of these bases along the RNA molecule dictates the amino acid sequence that a cell will utilize to construct the protein.Weissman and Karikó knew that in mammalian cells, which continually produce their own RNA as part of the process of protein synthesis, these bases frequently undergo chemical modifications. Naturally, the RNA produced by these cells does not trigger an immune response. Is there a correlation?
The researchers modified the regular RNA by replacing uridine with the very similar molecule pseudouridine. This subtle change did not impact the cell's ability to interpret the information stored in the RNA but dramatically altered the body’s response - the mechanisms causing inflammation were not activated. Additionally, the RNA exhibited greater stability, allowing cells to produce the desired protein in sufficient quantities to trigger an immune response. Concurrently, other researchers trying a treatment in mice with short RNA molecules against hepatitis B virus inflammation showed in a 2005 study that it's possible to encapsulate RNA molecules in lipid nanoparticles facilitating the RNA's entry into cells. This method was later adapted for messenger RNA.
The coronavirus vaccines have demonstrated that this technology enables the development of a safe vaccine against a new and unfamiliar pathogen in a matter of mere months, while also eliciting a remarkably efficient immune response.
Today, companies such as Pfizer and Moderna are developing mRNA vaccines against other diseases, including viral illnesses and cancer.
Karikó and Weissman discovered that if you produce an RNA molecule with specific chemical changes, the mechanisms causing inflammation are not activated. Illustration that delves into the changes and their effects | Nobelprize.org
Research Without BudgetKatalin Karikó was born in 1955 in Szolnok, Hungary, and completed a PhD in biology at the University of Szeged. She had been engaged in RNA research in a lab in her country since 1978, but in 1985 the lab lost its funding and she moved to the United States. Following brief postdoctoral training, she joined the University of Pennsylvania as a researcher. In 1990, she began exploring the field of mRNA-based therapies. In 1995 she once again lost funding for her lab but remained at the university nonetheless.
Drew Weissman was born in the United States in 1959. In 1987, he earned both an MD and a PhD from Boston University, specializing in immunology. He completed clinical training in hospitals and at the National Institutes of Health (NIH), working under Anthony Fauci, who would later become the scientific advisor to the U.S. president during the COVID-19 pandemic. In 1997, he secured a research position at the University of Pennsylvania, where he was later joined by Karikó.
In their joint work, they solved the primary challenge of RNA vaccine technology, laying the foundation for modern vaccines. In 2013, Karikó helped establish the BioNTech company, which was later acquired by Pfizer and formed the basis for the company's mRNA vaccine development. Weissman and Karikó received awards for their work, including the Canada Gairdner International Award, the Lasker Award, the Louisa Gross Horwitz Prize, and the Breakthrough Prize for their development of coronavirus vaccines.
ראיון טלפוני עם קטלין קריקו, מיד לאחר ההכרזה על הזכייה (באנגלית):
Last year, the Nobel Prize in Physiology or Medicine prize was awarded to Swedish researcher Svante Pääbo, who developed methods for sequencing the DNA of ancient humans, especially the Neanderthals, and is considered the father of paleogenetics. His research shed light on the origin and evolution of humans.
The 2021 Nobel Prize was awarded to David Julius from the University of California, San Francisco, and Ardem Patapoutian from the Scripps Institute in California for discoveries that helped understand the activities of cells responsible for sensing heat and touch and transmitting this information to the brain. In 2020, the prize was awarded to three researchers from the United States and Canada, Harvey J. Alter, Michael Houghton, and Charles Rice, for the discovery of the Hepatitis C virus.
The last woman to win the Nobel Prize in Medicine was Chinese researcher Tu Youyou, who received the award in 2015 for her contribution to the development of malaria drugs. Since then, only male scientists have received the prize.