McMaster researcher reflects on ‘interesting’ story behind 2 Nobel-prize-winning mRNA researchers

The story behind the two Nobel-prize winners whose work allowed for the development of mRNA COVID-19 vaccines is as interesting as their discovery itself, a researcher at McMaster University said Wednesday.

Speaking on CBC Radio’s Metro Morning, Dawn Bowdish, an immunologist and Canada Research Chair in Aging, said the two investigators had very different histories but found a common soul and a common curiosity about how RNA works in the immune system.

“They met at their institute, but their career trajectories could not have been more different,” Bowdish said.

This week, Katalin Kariko of Hungary and Drew Weissman of the United States won the 2023 Nobel Prize in Physiology or Medicine for their work.

Read an edited and abridged version of Bowdish’s interview with Jill Dempsey below.

For those who don’t know: What makes the mRNA vaccine worthy of a Nobel Prize?

mRNA is what we use to code proteins in our body. When we use it in a vaccine or a gene therapy, it looks a lot like RNA, which is what viruses use to infect us. So, the challenge that they had is: How do we get the mRNA to do its job making a protein, be it in a vaccine or in gene therapy, without the immune system overreacting, interpreting it as being a virus and then destroying it before it can do its job? 

The cleverness that accumulated in a paper in 2005 was they found out how to make little modifications to the mRNA to make it sort of invisible to the immune system to make it less likely to cause a strong immune reaction and by doing that, it was stable enough that it could be used for some of these technologies that we use it for today, including the vaccines, but not limited to the vaccines. 

Was it the curiosity that brought these two together? What’s their shared story? 

The story behind the story is as interesting as the story. These are two investigators who had very different histories but found a common soul and a common curiosity about how RNA works in the immune system. Doctor Kariko was a Hungarian born scientist who had immigrated to the U.S. to do some work. Doctor Weissman had what we call a standard pedigree, an excellent supervisor, a good physician. They met at their institute, but their career trajectories could not have been more different. 

Doctor Kariko had an experience which is so common to all the new Canadians listening to your radio show who came to Canada with a professional degree and people say, ‘I don’t know if I can trust that because it’s not from a university I understand.’ She struggled to get funding to the point where she had to shut down her lab and she was demoted and had to work for Doctor Weissman instead of as a colleague. After years of struggles and being told that her work was incremental, not very important, not really worthy of grant funding, that she was a supporting character in the cast — not a leader, she ended up leaving academia and going to work as the vice president for the company we generally call Pfizer BioNTech to develop these vaccines. 

In contrast, Doctor Weissman had a very storied career. He had the scientific pedigree, he had mentors and sponsors, he was promoted and he’s done very well in the academic system. And unfortunately there is a gendered aspect to this story because Dr. Kariko’s story is still something that occurs today with women in science. 

And why does that continue to happen given her level of success and recognition?

Ultimately, our funding agencies in Canada do a really good job at investigating why women scientists aren’t funded as much and why, when they are funded, they get less money. It’s this implicit bias that people who have different career trajectories maybe took time off to have babies or one of the things we really value in science is travelling to different parts of the world for your career but women often don’t do that because they’re not the primary breadwinner. 

We have to make it economically viable to be a scientist when you’re also at this stage in life where you’re going to become a parent. We need to have our institutions supporting child care so people can work the long hours that you need as a scientist. 

Again, often irrespective of gender in Canada we don’t do a great job of funding blue-sky, experimental, curiosity-based science. We always wanted to lead to something immediately. And the Nobel Prizes teach us again and again that we can’t predict which discoveries will end up being transformative and so we really do need to have a basis in curiosity-based science and let the science take us where it will. 

I want to bring it full circle and back to the mRNA vaccine. Where can it be applied next? Where do we go from here? 

I study older adults and I remember vividly the first days of of the long term care sector getting their mRNA vaccines and thinking, ‘I’m going to have to explain to people that if this behaves like the influenza vaccine, the best we can hope for is fewer deaths and maybe making the disease a little bit less bad in some people.’

These vaccines over-performed beyond my wildest dream in vulnerable populations. So the mRNA technology really does seem to work very well on older people, people who are immunocompromised much better than our current vaccines. 

They are good for those populations. They’re easily adapted so we can make them quickly to new variants and they’re adaptable to make combination vaccines. There are trials now of combining influenza and COVID or influenza, RSV and COVID. That’s something we wouldn’t be able to do with most conventional technologies. And they can also be used for gene therapy, but will no doubt expand to more. The future is bright, very, very bright.