Katalin (Kati) Kariko
(January 17, 1955 -        )
Born in Kasujszallas, Hungary
Year of Discovery 2005
KarikoKatalin Kariko light corrected
Doggedness and Design Drive the Discovery of mRNA Vaccines

It is remarkable how fast the COVID-19 vaccine was produced. Vaccines, humanity’s great disease prevention tool, used to take years to develop. But the COVID-19 vaccine was developed in days and was available in months. Vaccines are medicines that make our immune system recognize germs before we catch them. That way, when the germ comes along, our immune system fights it off, usually completely. If not, we don’t get very sick. There are now vaccines to prevent more than 20 diseases and many of us will get as many as 70 vaccines in our lifetime, all preventing illness..

But the science behind the COVID-19 vaccine actually took over 30 years to develop, largely spurred on through the tireless efforts of Kati Kariko, a scientist who was somewhat obsessed with the idea of a new kind of medicine, using mRNA. 

Katalin (Kati) Kariko was born in Hungary, where she earned a PhD in Biochemistry and began doing research as a postdoctoral fellow. In 1985, the research money dried up and she was forced to look for another job. She moved to the United States and eventually landed at the University of Pennsylvania where she hoped to do groundbreaking research on mRNA. The m stands for messenger and messenger RNA carries instructions from your cell’s DNA to ribosomes, telling them to make proteins. Our bodies may produce as many as 400,000 different proteins and they are what keep us functioning and alive. Scientists hypothesized that it might be possible to make synthetic mRNA that tells the body to make medically useful proteins. The problem was no one could get it to work, so over time, most lost belief in it. But not Kariko.

In 1989 Kariko began working with Dr. Elliot Barnathan, planning to insert mRNA into cells to induce them to make new proteins. Other researchers laughed at the idea, but they persevered. Eventually they designed an experiment that instructed cells to make an enzyme – urokinase, (normally made in the kidney, it is involved in dissolving naturally occurring blood clots). With anticipation they watched the results of their experiment come in. It did produce urokinase! “I felt like a god,” Dr. Kariko recalled.  It was a proof of concept that mRNA could be used to direct a cell to manufacture a desired protein. But that is a long way from a working medicine. Dr. Barnathan left the university and Dr. Kariko was left without a grant or a lab to work in.

University research works like this. You come up with a great idea, then apply for a government grant to test your hypothesis. Get the grant and you fund a lab to do your research. Don’t get the grant and you may have to find another job.  “Every night I was working: grant, grant, grant,” Karikó remembered. “And they always came back no, no, no.” The university expected Kariko to quit, as most unfunded researchers do. 

But a neurosurgeon who had worked with her, Dr. David Langer urged his department to give her research a chance. They each think the other saved them.  She thinks he saved her from joblessness and the end of her research.  He credits her with saving his line of thinking.  He stated, “Kate’s genius was a willingness to accept failure and keep trying, and her ability to answer questions people were not smart enough to ask. She was an expert at experimental design, with the controls often giving the most crucial data.”  But again, the ups and downs of the research world struck, and within a couple of years Dr. Langer and his department head left the university and with them went her lab and her funding.

Then by chance, in 1998 she met Dr. Drew Weissman at a copy machine. Weissman’s area of research was HIV. Kariko confidently told him she could make a vaccine against HIV. In reality, she had hit a wall in her research. She could make the cells manufacture proteins in petri dishes but not in living mice. The mice got sick every time. 

The two spent years working to solve this problem and in 2005 finally succeeded.  In experiments, it is important to have controls to compare your experiment to; they provide a known result - what should happen. They performed an experiment where they used tRNA (transfer) as the control. When they compared the mice that received tRNA with the mice that received mRNA (messenger), they noticed that the tRNA mice didn’t get sick. Comparing the structures of tRNA and mRNA, they found that the key difference was one molecule. That molecule was uridine. Upon further investigation, they noticed that human mRNA also contains uridine. The mice didn’t get sick because it recognized tRNA as their own, while it recognized the mRNA without uridine as a foreign body, so the mice’s immune system attacked it. They substituted a very similar synthetic protein, pseudouridine in the mRNA they were making and suddenly the mice didn’t get sick anymore. The substitution allowed them to alter cell function without prompting the immune system to attack. They published their discovery and the university patented it.  

Two start up medical companies, Moderna and BioNTech, saw the potential and licensed the new technique. Both companies began working on making vaccines with the technique six to seven years before COVID-19 came along, so they were ready to create a vaccine for it. One of the revolutionary aspects of these new vaccines, is that they can create the vaccine in the lab in literally hours. Afterward, there is a long period of testing for months before the vaccines are ready for humans, but creating the vaccines themselves with this method is revolutionarily fast.

A simplified version of how a mRNA vaccine works goes like this. The vaccine is injected into the muscle in your arm. The mRNA in the vaccine acts as the instructor for the cells to make a protein for a little while. In this case the protein is a piece of the spike protein that is on the surface of the SARS-COV-2 virus that causes covid.  Then the body’s immune system sees the spike protein and recognizes it as something that should not be there. This signals the body to produce antibodies and memorize what that invader looks like. The mRNA in the vaccine soon disintegrates, the immune system clears the spike protein that was made and the person is left with working antibodies to the virus that causes COVID-19, ready to spring into action if it invades the body. 

By August of 2021 the two companies’ mRNA vaccines had been given to more than 200 million people in the U.S. and Europe, cutting the sickness and death rate amongst those vaccinated dramatically. The companies have contracted to produce another 1 billion doses for the rest of the world.  And that is just the start of Kariko and Weissman’s revolutionary mRNA medicine.


                                                                                                                    Written by science writer, Martha Pat Kinney


Lives Saved:  Over 1,000,000


Snippets
When Kati Kariko emigrated from Hungary, they were only allowed to take $100 out of the country so they sewed $1,200 they had saved into their daughter's teddy bear.

After six years, her bosses at Penn were reportedly so frustrated by the lack of momentum from her research that they cut her salary and demoted her. “I thought of going somewhere else, or doing something else,” Karikó told Stat News. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”

When the first results of the Pfizer-BioNTech study came in, showing that the mRNA COVID-19 vaccine offered powerful immunity to the pandemic virus, Dr. Kariko turned to her husband and said, “Oh, it works - I thought so." She celebrated the good results by eating an entire box of Goober's chocolate-covered peanuts by herself. 

Kariko and Weissman were vaccinated with the new COVID-19 vaccine on December 18, 2020 at the University of Pennsylvania’s hospital along with the doctors and nurses. When an administrator told everyone that the scientists whose research made the vaccine possible were there, everyone clapped. Kati Kariko wept.

She attributes her parents with her work ethic and perseverance, which she passed on to her own daughter, Susan, who is a two-time Olympic gold medal winner in rowing.    


Key Contributors
Kati Kariko
Drew Weissman
WeissmanKariko













Vaccines are Ubiquitous & Omnipresent Throughout Our Lives
It is bizarre that vaccines are controversial, when virtually everyone has had vaccines. The average person born today may get 70+ vaccines in their lifetime. 

  • There are 31 childhood vaccines (counting booster shots). Over 90% of people have received some of these vaccines.

Virtually everyone constantly benefits from vaccines

  • Did you know that all beef, poultry, and pork you eat comes from vaccinated animals?
  • And that all horses, dogs, cats, and zoo animals are vaccinated?
  • Who wants to live in a world where you can’t pet your friends’ dog because it may not have been vaccinated, and may have rabies?

Links to More About the Scientist And Science
Kariko's Wikipedia Page
https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3 
Interview and Article
https://www.statnews.com/2021/07/19/katalin-kariko-messenger-rna-vaccine-pioneer/