A conversation with McGill’s ‘guru’ of mRNA

Nahum Sonenberg reflects on his career, the new Centre for RNA Sciences and basic science

Canada’s leading expert on mRNA, Nahum Sonenberg, PhD, is the Gilman Cheney Chair in Biochemistry at McGill University’s Rosalind and Morris Goodman Cancer Institute.

Prof. Sonenberg, who earned his PhD from the Weizmann Institute of Science in 1976, has dedicated more than 50 years to the study of RNA biology. His exploration of the mechanics of RNA translation and how it is regulated, both in normal conditions and in disease states, has improved science’s understanding of diseases including cancer, diabetes, autism and fragile X syndrome.

When he joined McGill in 1979, he had already made significant progress in determining how the genetic code from DNA is transmitted through mRNA. He discovered the mRNA 5' cap-binding protein, eIF4E, and identified the role the molecule plays in translating genetic information into proteins — transforming the scientific community’s understanding of protein synthesis.

“He worked out the molecular mechanisms that determine the efficiency of mRNA’s protein output,” says Jerry Pelletier, PhD, a Professor of Biochemistry and Prof. Sonenberg’s graduate student in the 1980s, quoted in an article for the McGill News. “He's the guru at McGill in terms of his contribution to mRNA technology.”

Prof. Sonenberg has been a fellow of the Royal Society of Canada since 1992. He was elected a Fellow of the Royal Society of London in 2006 and named to the Order of Canada in 2010. In 2012, he became a Fellow of the American Association for the Advancement of Science and in 2015 a foreign associate of the American National Academy of Sciences and National Academy of Medicine.

He is the recipient of the Robert L. Noble Prize of the National Cancer Institute of Canada, the Killam Prize for Health Sciences, the Gairdner Foundation International Award, and the Wolf Prize in Medicine, among other awards. More recently, he was included in the latest cohort of laureates to the Canadian Medical Hall of Fame.

In this interview, Prof. Sonenberg reflects on his storied career, the unique value of McGill’s Centre for RNA Sciences — and the urgent need for ongoing funds in support of basic scientific research.

Why is the Centre for RNA Sciences important?

Well, nobody can argue about its importance, because of the mRNA vaccines for COVID-19. The vaccines worked, and they saved the lives of millions of people. They saved about 300,000 people just in Canada. We know from the researchers working in the field that this technology will apply to many other diseases. Indeed, the companies that are now producing the mRNA vaccines started with cancer as their target. When I first consulted with Moderna [in 2013], that was the major idea. If we have the same success with cancer, it will be a huge breakthrough. But it’s not only cancer. There are so many applications for this RNA technology — not only mRNA, but other kinds of RNAs as well. Basically, this field is highly attractive for anybody who wants to work in medical research today. And because we have so much expertise at McGill in basic research, then of course we should apply it to saving lives.

The COVID-19 pandemic brought about so much misinformation and disinformation. What’s the one thing you would like to communicate to the general public?

The public gets so much information that is not scientifically correct. And this is a serious problem. So, this is more for the social sciences — how to get people to believe in the sciences and not in baseless ideas? There is no shred of evidence that the vaccines can cause the disease. Of course, you can have side effects. But they are rare, and scientists are addressing that. I want to point to the case of the polio virus vaccine from the 1950s. It saved the lives of millions of people. It’s known that one in a million vaccinees develops an allergic reaction and could die. So, you take the risk because you save the lives of millions of people. If there are side effects, then we scientists want to understand the cause and address them. And, of course, there is so much about how the body works that we still don’t know. We just need the funding to do the research.

Going back to earlier days, why did you choose to come to McGill in 1979?

I was an exchange student in the United States, doing a post-doc there. I had good friends in Montreal, working on the same virus. McGill has a fantastic reputation, so it wasn’t difficult for me to decide to come to McGill.

Looking back at your career, what has been the biggest challenge?

The biggest challenge is, of course, to get enough funds to do the research you plan to do. You have many ideas, but you know you cannot do it all. So, you must choose, because there is a short supply of money. The writing of grants takes 80 per cent of my time — instead of using the time to read the literature and speak to my team members. I have a large team of 25 talented people, a mix of research associates with experience, as well as post-docs and students. But the major challenge is always, as I said before the funding. If I had more money, I could have accomplished much more and better.

What has been the most rewarding part?

The most rewarding part is when you find something new. When I was a post-doc, I looked for the protein that binds the unique structure called “cap” at the end of the mRNA. People had tried and failed. And I found it. I was the first human being in the universe who discovered this protein. This is what provides great satisfaction — the discovery of new things.

What advice would you give emerging scientists?

Nothing is more stimulating than doing science with all its challenges and finding out how the universe works. Finding out how to minimize human suffering. The rewards are enormous. Despite the difficulties, you should keep doing what you like to do, and you will find your way.

Where do you see RNA therapeutics going in the next five or ten years?

If everything works well — and it is bound to work well — it is only a matter of being persistent, getting enough funding, and finding enough time to do the experiments. In the end, we will be able to cure many diseases. RNA is such a critical tool, and it is so promising. Proteins do most of the work in our cells. So, if you can replace them, add them, or modify them, we will advance medicine by leaps and bounds. So much has been discovered by serendipity. Perhaps tomorrow we will make another discovery. With all the scientific advancements that have been made up to now, combined with the emerging RNA technology, we are sure to see great progress.

Anything else to add?

The one thing I want to reiterate is very simple: The need for more money for basic research. We have the people, we have the brains, we have the abilities. But we don’t have sufficient resources. But science is the par excellence means to move humanity forward. Without science, we wouldn’t have been able to talk today on Zoom, for example! Everything that we take for granted in our world is here because of science. That is the quintessence of life.

Read more about Prof. Nahum Sonenberg’s contributions to mRNA biology.

 

 

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