Hungarian-American scientist Katalin Kariko’s obsession with researching a substance called mRNA to fight disease once cost her a faculty position at a prestigious university, dismissing the idea as a dead end.
Now her seminal work – paving the way for the Pfizer and Moderna Covid-19 vaccines – could save the world from a 100-year pandemic.
“This is just incredible,” she told AFP in a video call from her home in Philadelphia, adding that she was not used to the attention after years of toil in obscurity.
It shows why “it is important for science to be supported on many levels”.
Kariko, 65, spent much of the 1990s writing grant applications to fund her research on “messenger ribonucleic acid” – genetic molecules that tell cells which proteins to make, essential to keep our bodies alive and healthy.
She believed that mRNA was key to treating diseases where having more of the right kind of protein can help, such as recovering the brain after a stroke.
But the University of Pennsylvania, where Kariko was on her way to a professorship, decided to pull the plug after scholarship rejections piled up.
“I was for promotion, and then they just demoted me and expected me to walk out the door,” she said.
Kariko was not a US citizen at the time and needed a job to renew her visa. She also knew she wouldn’t be able to send her daughter to college without the hefty staff discount.
She decided to continue as a researcher on the lower rung, scraping around with a meager salary.
It was a low point in her life and career, but “I just thought … you know, the (lab) bench is here, I just need to do better experiments,” she said.
The experience formed her philosophy for dealing with adversity in every aspect of life.
“Think carefully and at the end you have to say, ‘What can I do?’
“Because then you don’t waste your life.”
Determination runs in the family – her daughter Susan Francia did go to Penn where she earned a master’s degree and won gold medals with the US Olympic rowing team in 2008 and 2012.
Double breakthroughs –
In the body, mRNA provides cells with the instructions stored in DNA, the molecules that contain all of our genetic code.
By the late 1980s, much of the scientific community was focused on using DNA for gene therapy, but Kariko believed that mRNA also showed promise because most diseases are not hereditary and don’t need solutions that permanently alter our genetics.
But first, she had to overcome a major problem: In animal experiments, synthetic mRNA triggered a massive inflammatory response when the immune system sensed an intruder and rushed to fight it.
Kariko, along with her chief collaborator Drew Weissman, discovered that one of the four building blocks of the synthetic mRNA had gone wrong – and they were able to solve the problem by replacing it with a modified version.
They published a paper on the breakthrough in 2005. Then, in 2015, they found a new way to deliver mRNA to mice, using a greasy coating called ‘lipid nanoparticles’ that prevent the mRNA from being broken down and put it in the right way. part helps places. of cells.
Both innovations were key to the Covid-19 vaccines developed by Pfizer and its German partner BioNTech, where Kariko is now senior vice president, as well as the injections made by Moderna.
Both work by instructing human cells to make a surface protein from the coronavirus, which simulates infection and trains the immune system for when it encounters the real virus.
New treatments
The mRNA breaks down quickly and the instructions it gives the body are not permanent, making the technology an ideal platform for a variety of applications, Kariko said.
These can range from new flu vaccines, which are faster to develop and more effective than the current generation, to new disease treatments.
For example, AstraZeneca is currently working on an mRNA treatment for heart failure patients that supplies signaling proteins that stimulate the production of new blood vessels.
While she doesn’t want to make too much of it, as a foreign-born woman in a male-dominated field, she felt undervalued at times – she said people would come after class and ask, “Who’s your supervisor?”
“They always thought, ‘That woman with the accent, there must be someone behind her who’s smarter or something,’” she said.
Should all go well with the Pfizer and Moderna vaccines, it’s not hard to imagine the Nobel Prize Committee rewarding Kariko and fellow mRNA researchers.
That would be bittersweet for Kariko, whose late mother would call her every year after the announcements to ask why she wasn’t elected.
“I said to her, ‘I never get any (federal) scholarships in my life, I am nobody, not even a faculty,’ ‘she laughed. To which her mother would reply,” But you work so hard! “