From Fired and “Crazy” to Nobel Prize: The Unlikely Triumph of Katalin Karikó, the Unsung Hero of mRNA Vaccines

  Was fired 5 times, never received tenure, found it difficult to obtain research funding, and did not even have a stable laboratory – this is how Katarin Corico, the 2023 Nobel Prize winner in Physiology or Medicine, turns 65 professional life.
  Perhaps the only thing she is proud of is raising her only daughter, Susan Francia, a two-time Olympic gold medalist in rowing.
  Throughout her long academic career, Katalin endured failure, contempt, and humiliation. This is related to her research direction. mRNA (messenger ribonucleic acid) has never been favored by the academic community, and few people are interested in it. But Katalin is convinced it can change the world.
  In 2020, the COVID-19 epidemic broke out, and Katalin’s research became the basis for the advent of the mRNA vaccine.
  The advent of the vaccine was not the result of Katalin alone, but the joint effort of many scientists, but Katalin played a great role in it.
  In the eyes of many people, this is a story of hardships and triumphs, but in Katalin’s view, her persistence has nothing to do with external evaluations. This is just a journey of love.
Two roads diverged in the yellow woods

  Katalin was born in 1955 in a small town with a population of about 10,000 in eastern Hungary. Her father was a butcher but could play the violin and knew mental arithmetic; her mother was an accountant and also liked music.
  When Katalin was 2 years old, her father Janos unfortunately lost his job. Since then, he could only do odd jobs in bars, construction sites and farms. The family lives in an adobe house with a reed roof and no running water, television or refrigerator.
  As a child, Katalin witnessed the birth of a neighbor’s cow and often went hiking deep in the forest. She was curious about birds and plants.
  When Katalin was 14, she placed third in a national biology competition and determined to become a scientist when she was 16.
  At that time, Katalin read a book by Hungarian scientist Hans Scheyer on the effects of stress and anxiety on physical health. Scheye believes that negative emotions are also a kind of energy, and people should transform them into positive emotions and live a life free from resentment and regret and without inner pressure. Little Katalin resonated strongly with this and vowed to live up to it throughout her life.
  She took Sheyer’s words to heart, “You have to focus on the things you can change,” and adopted that as her motto.
  Katalin was subsequently admitted to the University of Szeged, a top research university with a long history in Hungary, where the Nobel Prize winner in Physiology or Medicine, St. Györgyz Albert, was educated. Katalin studied at this university until she graduated with a PhD. At a disco party in the Department of Biology, she met Bello Francia, who was five years younger than her. The two subsequently married and soon had a daughter.
  While studying at university, Katalin one day listened to a lecture about the underestimated potential of mRNA. From then on, she was fascinated by mRNA. At the time, scientists were excited about using gene editing to treat disease, but mainstream research was focused on using DNA molecules.
  mRNA is not a popular molecule; it is difficult to make and extremely unstable.
  But Katalin was fascinated by mRNA. Compared with DNA, which has to enter the cell nucleus to exert its effects and have a permanent impact on the human body, mRNA can exert its effects as long as it enters the cytoplasm and is safer for the human body.
  Two roads diverged in a yellow forest, and Katalin chose the one less traveled by, even though she would be impoverished for many years to come.
Second-class citizens

  Having determined her research direction, Katalin soon encountered her first setback. In 1985, Katalin was fired from the Institute of Biology at the University of Szeged due to lack of funds. In order to find a new job, Katalin sent her resume everywhere and finally received a postdoctoral invitation letter from Temple University in the United States.
  Katalin only started learning English when she was in college. Both her husband and she had poor English proficiency, but in order to continue studying mRNA, they decided to immigrate to the United States.
  At that time, the Hungarian government implemented restrictions, and Katalin and his wife were required to carry only $100 out of the country. They sold their car on the black market, sewed the 900 pounds they got into a stuffed teddy bear for their two-and-a-half-year-old daughter, and boarded the plane to the United States with trepidation.
  The first days were difficult. Katalin’s annual salary was US$17,000. Her mother later came to the United States, and the family of four lived on this money.
  Her husband, Bello, failed to continue his career as an engineer. He then worked as a maintenance manager in an apartment building, fixing heating and sewers, and his income was similar to Katalin’s.
  In the summer of 1989, Katalin found a better job and entered the Ivy League University of Pennsylvania.
  At Penn, Katalin’s title is “Assistant Research Professor.” Many of the people who do this kind of work are immigrants. They are called “aliens”. They earn meager wages and work for the professors who control the laboratories, just so that they can work in the laboratories of world-class universities and get green cards. .
  Life is not easy for “second-class citizens”. Once, Katalin was scolded because she did not climb five floors to another laboratory, but directly used experimental water prepared by a senior researcher in the same laboratory.
  For assistant research professors, the “end of the tunnel” is to produce results as soon as possible, apply for funding, have their own laboratory, and become professors. However, Katalin did not make it to this day.
mRNA crazy woman

  Katalin has always worried about funding for research. It always took her a long time to write applications in broken English, and they usually came to nothing. She didn’t even apply for the National Institutes of Health’s most common R01 research grant.
  mRNA is so unpopular that few people in the laboratory are willing to touch it. But Katalin was trying to get into trouble. For her, if she wanted to get tenure, it was best to change her direction rather than stick to mRNA. Katalin had this idea, but was stopped by her husband Bello. He said: “In this case, you are not doing what you like.”
  In order to continue to use research funds, Katalin worked at Barnassin and She worked in Professor Lange’s laboratory, but due to changes such as the dissolution of the laboratory, she was repeatedly unemployed.
  Department chair Judy Swain did not like this researcher who could not bring in funds and thought she had a bad personality. In 1995, Swain gave Katalin an ultimatum: Leave or be demoted.
  It was actually a pink slip, since no one wanted to accept a demotion, but Katalin agreed. Her title became “senior research associate,” a new position at Penn that had never existed before.
  One reason Katalin accepted the demotion was that her daughter Susan was going to college. If she resigns at this time, Susan will not be able to enjoy the benefits of paying only 1/4 of the tuition for the children of Penn faculty and staff, and Katalin’s family cannot afford the full tuition.
  At that time, Katalin’s annual salary was 40,000 US dollars, and her life was very difficult. She drove in and out of school in an old car that her husband had restored from a junkyard. In the memory of her daughter Susan, her vacation consisted of hanging around in her mother’s laboratory all day long, because Katalin’s family had no money to go on vacation.
  It’s not that Katalin doesn’t like money. Sometimes she sheds tears when she thinks about her family’s poverty.
  After wiping away her tears, Katalin continued her Quixotic behavior. She kept recommending mRNA to her colleagues, hoping to get into other people’s laboratories. “Do you need mRNA? I can make it for you.” Colleagues looked at Katalin with an increasingly strange expression, and some called her “that crazy mRNA woman” behind her back.
  It wasn’t until she met Drew Weisman at the printer that Katalin was able to escape.
An unheralded victory

  Weisman is a taciturn man who loves cats. He once almost missed a plane to an important meeting because he chased an anemic stray cat to give him erythropoietin.
  Weisman and Katalin met at a printer in 1997. After a few silences, Katalin took the initiative to chat with Weisman: “Are you new here? I am Katalin Corico, and I can synthesize mRNA. If you need it, I can help you synthesize it. ”
  No one thought that this encounter would become the beginning of one of the great collaborations in the history of science. Weissmann was trying to use DNA molecules to create an AIDS vaccine, and Katalin suggested that he try using mRNA.
  The next year, the two began working together. They injected the mRNA into the cells of mice and unexpectedly found that the mice became sickly and some even died. After artificial mRNA enters cells, it unexpectedly triggers an immune system response, killing these invaders at the cost of self-injury.
  Katalin decided to “modify” her own mRNA so that they could “deceive” the immune system. This was her main research direction during her Ph.D. After hundreds of failed attempts, they finally found the right solution.
  Katalin and Weisman’s research results were published in the famous journal “Immunity” in 2005. Weisman realized the significance of this discovery to medicine and happily waited for pharmaceutical companies to call his home, but no call came.
  The scientific community still lacks confidence in mRNA, and more importantly, Catalin and Weisman have not used this important discovery to make a resounding product.
  Katalin and Weisman used patents to establish a research and development company in 2006, but converting scientific research results into commercial products was a costly endeavor that they could not afford.
  Even though the small company later went bankrupt, Catalin and Weisman still believed in mRNA, but their research results were gradually forgotten.
  In 2013, Katalin was fired for the last time. She was deemed by the University of Pennsylvania as “not possessing the qualities of a teacher” and was forced to retire. In order to continue studying mRNA, Katalin accepted an invitation to serve as vice president of the German biopharmaceutical company Byrne Technologies, which did not even have a website at the time.
  Katalin was forced to leave her elderly mother and supportive husband and move to Germany, where she worked 10 months a year. For a full week after making this decision, Katalin cried herself to sleep every night.
  Her mother, Goz, who was very supportive of Katalin’s work, passed away in 2018. During her lifetime, her mother would pay attention to the announcements of Nobel Prize winners every year and said to Katalin: “Maybe your name will be pronounced, you work very hard.” Katalin explained to her mother with a wry smile: “It’s impossible. I’m not even a professor and I don’t have a team. All scientists work hard.”
Focus on what can be changed

  Katalin eventually won the Nobel Prize. When the COVID-19 epidemic broke out in 2020, the mRNA vaccine was widely used. Katalin, who made a key contribution to this, also came into the spotlight, and wealth and honors poured in.
  But she’s not working for money, honor, or status; she’s not even working.
  Katalin goes to the lab at 6 o’clock every day and stays there most weekends. Her husband Bello teased her, saying that based on Katalin’s working hours, her hourly wage might be only $1. Every time Katalin went out to work, Bello would laugh at her: “You don’t go to work at all, you go to have fun.” At the
  age of 16, Katalin read Scheyer’s “You have to focus on what you can change.” “Things”, she did this during her half-century scientific journey.

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