Nobel Prize Winners in Physiology or Medicine---Katalin Kariko and Drew Weissman


American scientists Katalin Kariko and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their discovery of nucleoside base modifications that enable the development of effective mRNA vaccines against COVID-19.

Katalin Kariko, an American female scientist, suffered from cancer, her job was once in jeopardy, and she was in trouble many times. But regardless, she has been focusing on studying messenger RNA (mRNA), which she believes can be used to instruct cells to produce drugs, including vaccines.

Katalin's father is a butcher in a small town with a population of only 10,000 (the Hungarian town of Novosaráš). Since she was a child, Katalin has watched her father work and study the structure of living things under the butcher's knife. Her interest in biology began from then on.

Twenty-seven years later, Katalin received her Ph.D. But the good times did not last long. Due to lack of research funds, she had to find another way out. Since there are more research opportunities and funding in the United States, I am eager to embrace the American dream.

In 1985, after she received an invitation for a postdoctoral research opportunity at Temple University in Philadelphia, Pennsylvania, Katalin came to Philadelphia, the United States, with her husband and two-year-old daughter to work as a postdoctoral fellow at Temple University.

Because according to Hungarian government regulations, they were only allowed to exchange $100 in cash, Katalin told the Hungarian news website G7 that they sold the car on the black market, sewed $900 into their daughter's teddy bear, and traveled from Hungary to the United States. This was all she owned at the time.

Four years later, by chance, she went to the University of Pennsylvania as a "research assistant professor." Although she had the title of assistant professor, there was no promotion path. How long you can stay in the laboratory depends entirely on whether there are sufficient scientific research funds. At this time, the concept of gene therapy began to emerge. It is thought that if we could correct the disease-causing genetic mutations in our bodies, many genetic diseases could be cured. The most effective way to correct these genes is to go straight to Huanglong and achieve it through DNA. But Katalin doesn’t think so. She studied the use of mRNA to treat viral infections during her PhD, and believes that mRNA, which is responsible for converting DNA signals into proteins, has more potential.

But at that time, the field of mRNA was dead. The idea that mRNA could be used to fight diseases was so radical that the first application for research funding in 1990 was rejected, and several subsequent applications were still frustrated. Katalin has spent his entire career studying messenger RNA (mRNA), the genetic script that delivers deoxyribonucleic acid (DNA) instructions to a cell's protein-making machinery. She determined that mRNA could be used to instruct cells to produce drugs, including vaccines. But for many years, her job at Penn was in jeopardy. She moved from lab to lab, relying on one senior scientist after another to add her to the team. Her annual income never exceeded $60,000.

At that time, Katalin and another scientist, Professor Barnathan, were studying the unpopular field of mRNA in a cramped laboratory. But fate then played a joke on her. Soon, Professor Barnathan left the school and went to work in a biotechnology company, but he did not take Katalin with him. There were only two ways before her, either to find a laboratory to work in, or to apply for scientific research funding on her own. Katalin was not good at applying for funding, and mRNA technology was not yet mature at the time. A colleague who had worked with her briefly offered a lifeline. He recommended Katalin to the chairman of the Department of Neurosurgery and secured her a position. This new team tried to use mRNA technology to direct blood vessels to synthesize molecules that can dilate blood vessels, but multiple rounds of experiments ended in failure. Later, colleagues themselves and even the chairman of the Department of Neurosurgery left the school. Katalin is once again left alone. This was the darkest moment in her life. In 1995, she experienced a low point in her life and was demoted at the University of Pennsylvania. She was demoted from a research assistant professor to a senior researcher. She had cancer and her husband was stuck in Hungary due to visa issues. And the mRNA technology for which she had devoted countless efforts has also reached a dead end.

In 1997, Katalin, who was still working hard for her ideals at the University of Pennsylvania, was trying to make a photocopy of a document. But he met Drew Weissman, an immunology guru who also wanted to use a copy machine. Weissman graduated from Boston University and later worked at the National Institute of Allergy and Infectious Diseases under the tutelage of the famous infectious disease scientist Dr. Anthony Fauci.

Katalin recalled: "I am an RNA scientist, and I can make everything with mRNA." Weissman told her that he wanted to develop a vaccine to prevent AIDS.Katalin said: "Yes, I can do it." Their common interest in mRNA technology made the two hit it off and became a long-term scientific research partner. Drew Weissman soon discovered that this very low-level scholar had the same views on mRNA therapy as he did, and the two immediately began collaborating.

After several years of long research, Katalin and Weissman finally discovered that through methylation of nucleic acids, the response of immune recognition receptors to mRNA can be effectively avoided and the side effects caused by mRNA can be greatly reduced. This study was published in Immunity in 2005 and directly made the application of mRNA therapy possible.

In order to achieve clinical translation, Katalin and Weissman had frequent contacts with pharmaceutical companies and investment companies, but rarely attracted interest. Fortunately, Huangtian's efforts paid off, and eventually two biotechnology companies took notice of their work: Moderna in the United States and BioNTech in Germany. Pfizer has a partnership with Bayerntech, which currently provides funding for Weissman's lab. Soon, clinical trials of mRNA influenza vaccines began, and new vaccines have been developed to deal with cytomegalovirus and Zika viruses.

Then, the new coronavirus came, and mRNA technology became an important tool for the rapid development of new coronavirus vaccines. A number of mRNA new coronavirus vaccines obtained positive data in clinical trials. The mRNA COVID-19 vaccine launched by Baytech in cooperation with Pfizer has also successfully obtained authorization from the European Union and the United States. In 2020, when the results of the Phase III clinical trial of the BioNTech vaccine were announced, it was shown that the mRNA vaccine has strong protective efficacy against the new coronavirus.

Katalin, who has been on the bench in the field of mRNA therapy for 40 years, is not ecstatic about the effectiveness of the vaccine because she has been mentally preparing for this moment of success for 40 years. After that, the accolades came pouring in. On September 25, 2021, Katalin and Weissman received the Lasker Clinical Medical Research Award together. In June 2022, Katalin won the 2022 "World Outstanding Female Scientist Award". On August 4, 2023, the Chinese University of Hong Kong awarded Professor Katalin an honorary Doctor of Science degree in recognition of her contribution to the development of vaccines and treatment of human diseases.