Hungarian and American biochemists Katalin Karikó and Drew Weissman have won the 2023 Nobel Prize in Physiology or Medicine. They were awarded for developing the technology that forms the basis of mRNA vaccines against Covid-19. Their names were: presented At a ceremony organized by the Nobel Committee at the Karolinska Medical Institute in Stockholm.
tricking the immune system
In 2019, when the coronavirus pandemic began, few people would have thought that a vaccine against a new pathogen could be developed in record time. But it happened. The two Western vaccines created by Pfizer and Moderna were produced using new mRNA synthesis technology, which won the Nobel Prize in Medicine in 2023. In total, these vaccines have been administered nearly 13 million times, helping save the lives of millions of people around the world.
The technology makes it possible to create artificial mRNA with specific properties. If you give this to the human body, the cells will begin to produce the necessary proteins, including antibodies against pathogens. However, initial experiments showed that mRNA transcribed in vitro stimulated undesirable inflammatory responses and inefficient protein production in cells and tissues.
The turning point was Kariko and Weissman’s discovery that mRNA produced with altered bases evaded recognition by the innate immune system. This discovery of immune deception was critical to the creation of a vaccine suitable for clinical use during a pandemic.
“The main problem these scientists are trying to solve is that when nucleic acids are added, a cytotoxic effect occurs. That is, sensors in the cells see DNA or RNA nucleic acids where they should not be, and the cell signals that there is a virus-like infection inside it. As a result, the immune system is triggered.” and the cell begins to die. To prevent this, biochemists began to develop technologies in which some nucleotides are replaced with analogues, in particular pseudouridine. Pavel Volchkov, virologist and head of the MIPT genome engineering laboratory, told socialbites.ca: “Masking the RNA so that the cells do not turn on the antiviral alarm they wanted.”
mRNA revolution
The Pfizer and Moderna vaccines were the first signs. But the direction continues to gain momentum. Today, mRNA synthesis technology is also used in cancer treatment.
Pioneers in this direction in Russia are specialists from the Institute of Chemical Biology and Fundamental Medicine of the SB RAS. Even before the pandemic, they created the technological element base for mRNA synthesis. With such a foundation, it is possible to develop an analogue of the Pfizer and Moderna COVID-19 vaccines within a few weeks. Scientists are currently conducting research to create a flu vaccine.
“We are developing an mRNA vaccine for influenza. We have started an experiment on mice, we want to check whether the structure of the mRNA is assembled correctly, whether it is delivered to the cells correctly. Development director of the Biosan and Biolabmix group of companies SB RAS Institute of Chemical Biology and Fundamental Medicine genome editing We have another year of tests ahead of us, the head of the laboratory, Grigory Stepanov, told socialbites.ca.
However, according to experts, the Covid-19 vaccines produced by Pfizer and Moderna are not ideal. According to the head of the center. Gamaleya, academician Alexander Ginzburg, said mRNA vaccines have serious side effects that can be life-threatening.
“mRNA technologies have numerous side effects, including myocarditis on both the outer and inner lining of the heart chamber. They occur because our immune system perceives the lipids in which the mRNA is packaged as foreign. Also, when mRNA enters the body in the amounts of vaccination, it is evolutionary nonsense and the body absorbs them.” “They perceive it as foreign. As a result, serious inflammation occurs in the body,” Gunzburg explained.
However, there is also a scientific group at the Gamaleya Center that supports the direction of mRNA technology. When the patient no longer had any other options, they decided to use these technologies to develop a vaccine against cancer.
“We continue to create an mRNA vaccine against cancer. In this case there is no selection window. For example, the use of mRNA drugs in melanoma makes it possible to create a very strong immunity,” said Gunzburg.
Having mastered the technology to deceive the immune system invented by Catalin Kariko and Drew Weissman, mRNA drugs have a great future. mRNA technologies are not limited to infectious diseases, but can also be applied in the treatment of cancer and gene diseases.
“One of the points of our work is the development of a universal artificial mRNA structure, which in the future will make it possible to change the part responsible for which virus the vaccine will work against and direct the mRNA to other viruses. We are building just such a platform,” said Grigory Stepanov.
The second fundamental problem that scientists are working on is how to properly organize the delivery of drugs into the cell. “There are different ways, for example lipid nanoparticles were used in Covid-19 vaccines. “We are also developing other distribution structures,” he said.
Stepanov emphasized that in their work, SB RAS scientists are guided by fundamental principles. articleIt was written by Katalin Kariko and Drew Weissman in 2005.
He hid the money in a teddy bear and fled to the USA
Now about the laureates themselves.
asks Katalin Kariko Call Known simply as “Katie”, she grew up in the small town of Kishuyszallas, Hungary. His mother worked as an accountant and his father was a butcher. While still at school, Katalin excelled in her natural science education and even placed third in the country at the Biology Olympiad.
As a student at the University of Szeged, he worked at the Center for Biological Research, a laboratory specializing in liposomes and vesicles that can be used to encapsulate genetic material. It wasn’t easy to order laboratory supplies at the time, so scientists obtained them themselves: The head of the laboratory even biked to the slaughterhouse to collect cow brains for experiments.
“This is how I’ve always understood science. In fact, there is no problem that cannot be solved. Can’t buy anything? You do”, – aforementioned Kariko Washington Post.
In 1985, the laboratory where Kariko worked was defunded. Then the biologist bought a one-way ticket from Hungary to the United States with her husband and two-year-old daughter. To achieve this, the family sold their car and hid the money inside a large teddy bear. He is currently hiding in Kariko’s daughter’s room.
But the most difficult moment in Kariko’s career was approaching: At the age of 58, he dropped out of the University of Pennsylvania and moved to Germany to work as a vice president at Biontech.
“I left my wife and our home in the USA, then I was left alone in a small apartment in Germany. The first week I thought: “I have a house on an acre of woods and a husband waiting in the USA, and now I’m living out of a suitcase here.” There was a washing machine in the basement and it was so dirty it took me half a day to clean it. For the first week, I cried myself to sleep every night and thought I had made a big mistake. But after that week, I was so busy that I didn’t have time to cry anymore.” memories scientist.
The news that the Covid-19 vaccine developed by Katalin Kariko worked caught the scientist’s attention on November 8, 2020, her daughter’s birthday.
“Yes, I remember, it was Sunday, my daughter’s birthday. We were celebrating when they called me and told me that the vaccine worked according to the test results. “Based on previous clinical trials, we were confident that the vaccine would be effective,” he said. shared Kariko.
Catalin Carico’s daughter, Susan Francia, won two Olympic medals as a rower and a member of Team USA.
“Have you noticed that you are rowing with your back in the direction of travel? Just like science. You don’t see the finish line. You don’t even know there’s a finish line. You don’t even know you’re going in the right direction. But you keep working,” Kariko said. newspaper El País.
born at 40
Drew Weissman grew up in Lexington, Massachusetts, USA. After completing his fellowship at the National Institute of Allergy and Infectious Diseases in 1997, he began working at the University of Pennsylvania, where he met Kariko.
Weissman played sports and studied martial arts in his youth, and while in high school he worked for his father’s company, which produced optical mirrors for satellites.
According to Stephanie Weissman, Drew Weissman’s younger sister, her brother was distinguished by endurance and discipline since childhood. He mastered sailing on his own when he was still a child. Stephanie Weissman noted that her brother “was born at 40.”
When scientists first found a way to safely use mRNA in vaccines and realized they had made major progress, no one paid much attention to the discovery. Contrary to expectations, no one called them, Weissman recalls.
“Our phones were silent. Nobody cared. But we knew the potential and never stopped working on it,” said Weissmann. report Washington post.
Now Katalin Kariko and Drew Weissman’s phones are ringing with thousands of calls: The whole world wants to congratulate them on being awarded the Nobel Prize in Physiology or Medicine.