When Peter Kulis rolled up his sleeve last March to receive his first dose of a Pfizer-BioNtech vaccine for COVID-19, he couldn’t help but think about what the moment meant for him as a scientist .
“You know,” he told the nurse who was administering the jab, “I really had to do something about making this vaccine.”
He responded by shooting her with a look that was more strange than astonishment.
“Like I was from outer space,” Dr. Kulis remembered.
Now a professor at the University of British Columbia and co-founder of Acutas Therapeutics in Vancouver, he has earned a bit more recognition after being named a co-winner last week of the 2021 Prince Mahidol Prize for Medicine. The award, which comes with US$100,000, is one of the first high-profile international science awards to acknowledge the pioneers behind the mRNA vaccine – the most effective defense against COVID-19.
Dr. Kulis is sharing the prize with Katalin Kariko, senior vice president of BioNTech based in Mainz, Germany, and Drew Weisman, director of vaccine research at the University of Pennsylvania. His co-winners are credited with discovering how to engineer messenger RNA — a molecule that gives instructions for making proteins — for use as an active ingredient in vaccines. The COVID-19 vaccines developed by BioNTech and Moderna, based in Cambridge, Mass., both rely on discovery.
Dr. Kulis played a different role. It was through their work over many years that vaccine makers had a way to encapsulate delicate messenger RNA molecules inside a lipid bubble, or “nanoparticle,” that protects RNA from degradation and prevents it from entering cells. allows. The system is essential for vaccines to work.
Announcing the award, the Prince Mahidol Award Foundation in Thailand said that Dr. Kulis’s achievement has not only made vaccines possible, it has opened the door to “the prevention and treatment of many diseases in the future”.
Alan Bernstein, president of CIFAR, a Toronto-based research funding organization, and a member of Canada’s COVID-19 Vaccine Task Force, called Dr. Kulis’s contribution “a great example of the power of fundamental science in service to humanity.” In addition to enabling the mRNA revolution in vaccine development, he said, the technology will discover more applications in cancer research, among other areas.
For Dr. Kulis, such exciting possibilities were hardly on the horizon in the 1970s, when he completed his PhD in experimental physics at UBC, before deciding that the problems researchers were facing in the life sciences were elsewhere. seemed more stimulating.
During his postdoctoral work at Oxford University, he became fascinated by the characteristics of lipid membranes – the double-layered fatty sheaths that surround living cells and various cell components. He was particularly concerned with the fact that some membranes clearly differentiated on their inner and outer surfaces, containing a diverse array of lipids on either side.
“I’m interested in why there were so many different lipids and what they were all doing,” he said.
While studying the question, he learned to wrap lipid membranes around molecules in order to investigate the chemical properties of the membrane’s inner surfaces. From there it was a small conceptual step to thinking about packing a drug inside a lipid to help it get to where it’s needed in the body.
By then he was back at UBC and running his own laboratory. They had formed a team of young researchers and were figuring out how to design lipids for drug delivery. This is followed by more than two decades of basic research in the lab, combined with a succession of startup companies and partnerships to develop applications. At first, the team’s focus was on cancer drugs, but by 2000 the work had shifted toward a new medical frontier: gene therapy.
Dr. Kulis said a pivotal period began in 2005 when he and his colleagues, in collaboration with Massachusetts-based Alnylam Pharmaceuticals, developed an RNA drug that suppresses the action of a faulty gene in liver cells, known as amyloidosis. The cause of the condition is known. The size and chemical properties of the RNA are very different from those of the cancer drugs the team previously worked on. This meant that the lipid packaging system had to be rebuilt from the ground up.
The collaboration was successful and paved the way for an even greater challenge. If a small piece of RNA can be given to inhibit a biological process, why can’t a larger piece of messenger RNA be given to start a new biological process?
By this point Dr. Kulis had already co-founded Acutas to develop lipid nanoparticle pharmaceuticals. In 2014 the company received an e-mail from Dr. Weisman, who was working with BioNTech on messenger RNA vaccines and needed a delivery system. This was followed by years of work, and by the end of 2019 Pfizer also joined the project to create an mRNA influenza vaccine using lipid nanoparticles.
Then the pandemic struck. Almost overnight, the entire effort was redirected towards COVID-19. As of spring 2020, the Pfizer-BioNTech vaccine was in clinical trials. Meanwhile, Moderna, which had previously worked with Acutas, was using its own lipid nanoparticle at the same end. Despite playing such an important role in the story, Dr. Kulis said he was still stunned a year ago when trial results showed that mRNA vaccines had about 95 percent efficacy.
“It was really unbelievable,” Dr. said Kulis, who describes himself as a scientific entrepreneur. “I mean, you keep doing what you do, and then something like this happens. It’s just wonderful.”
Vaccines only scratch the surface when it comes to potential applications of the Canadian-made lipid nanoparticle technology, he said. In another direction Acutas is moving in partnership with an American company, Verve Therapeutics, to develop a gene-editing drug that may lower levels of bad cholesterol to help prevent heart disease.
Both university and federal programs supported the work on key points, Dr. Kulis said. And the key to its success was capturing the critical mass of expertise that was built around the effort.
“Keeping people local is important … and I think we should be doing more to keep our talent in Canada,” he said. “Countries that invest in their human capital are always going to do better.”
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