TORONTO -- The story of how the groundbreaking mRNA vaccines were developed to help the world fight COVID-19 is a fascinating one — but it’s been missing a key part, according to a scientist who says a fundamental aspect of these vaccines was originally developed by a small team in Canada.
How the mRNA vaccines produced by companies such as Moderna and Pfizer-BioNTech work is that the mRNA itself is wrapped in a protective shell made of lipid nanoparticles to allow it to enter the body and teach the immune system how to fight the novel coronavirus.
Without this crucial delivery system provided by the lipid nanoparticles, called LNP, the vaccines would not work.
But the question of where this system was developed — and by who — isn’t a straightforward one.
Canadian scientist Ian MacLachlan has been watching the vaccine rollout with awe, knowing he and his team played a vital role in their development, which began decades ago.
“There's a part of me that is almost overwhelmed, how effective and powerful these vaccines have been,†MacLachlan told Â鶹´«Ã½ in an interview.
“There would be no mRNA vaccines without the LNP system that was developed right here in Canada.â€
which dove into the tangled web of scientific work, patents, companies and lawsuits that surround the issue of who deserves credit for LNP, and specifically, the LNP used in COVID-19 vaccines.
MacLachlan said that many people believe the mRNA vaccines came out of nowhere, but this technology has been in the works for years.
“I've had conversations with folks that imagine that they were developed within the last 12 to 18 months,†he said. “But in reality, very soon after they discovered nucleic acids and their role in biology, people began thinking of ways of using nucleic acids as medicine.
“The idea of using RNA as a vaccine is something that's been around for 20 or 30 years.â€
A team of dedicated scientists in Vancouver were part of this. They knew that the world was going to need new tools for fighting diseases, and were determined to develop some.
“We wrote the screenplay for this movie,†MacLachlan said. "We saw this coming. We know that there are these emerging infectious diseases that are out there. And we as a society need to prepare for them. And one of the ways that we can prepare for them is to develop these types of technologies and to make them as broadly available as possible, so that when that time comes, they're there for our societies to use.â€
In the early 2000s, scientists were honing in on the therapeutical potential of RNA. But for RNA-based drugs to work, they need to be delivered in a way that allows it to enter a cell.
Over the coming decade, MacLachlan and a team at Protiva, a company he founded, worked on that problem, and came up with a way to safely deliver RNA. They found that a specific ratio of four lipids created the delivery system necessary to cover, protect RNA, and get it into the cell.
Mark Kay, a professor of genetics at Stanford University, became aware of MacLachlan and his team’s work in the field when he was looking into siRNA, a therapeutical method that uses RNA to turn off certain genes.
“It was clear from the work that he was doing that they had really made some extremely important discoveries that would allow for these RNAs to be delivered in a way that were therapeutic, as well as safe, and ultimately in humans,†Kay told Â鶹´«Ã½.
He explained that while other scientists were working in that field at the time, when it came to delivery systems that could be used safely in humans, MacLachlan and his team’s method stood out.
“Clearly the innovation that went into these lipid nanoparticles […] I think is a game changer,†he said.
“The contribution that he and his colleagues made is a very substantial, important breakthrough that ultimately led to the very early successes of the delivery of RNA into humans.â€
But this Canadian contribution hasn’t been highlighted since the start of the pandemic, and throughout the whirlwind race to develop these innovative new vaccines.
In a recent article that called MacLachlan “COVID's forgotten hero,†Forbes revealed the Canadian side of the story after finding MacLachlan’s name at the heart of patents involving the genesis of the LNP delivery technology.
“I think it's great that he's getting the recognition that he is for this, because it was important,†Kay said.
Looking back on it now, MacLachlan said that there’s a number of reasons why the Canadian contribution to LNP, and to the mRNA vaccines, is under appreciated.
Part of it is that when scientists tackle a problem, their new discoveries build on existing data and the discoveries of those who came before them, meaning that sometimes the attention is focused only on the most recent developments.
“There's a phenomenon whereby [the] last person holding the data wins,†he said.
“In part, I think this is by accident. But, as well, there are some, shall we say, disputes regarding the ownership of this technology, and that may be playing a role.â€
The legal tangle of who owns a technology, or can claim credit for it, make the story of the mRNA vaccines complicated.
For instance, Moderna tried to challenge a patent for LNP technology filed by a Canadian company — a patent with MacLachlan’s name on it — but then, after the existing patent was upheld, Moderna said their own technology had evolved far beyond the technology described in the patent.
Preclinical data released by Moderna appeared to show that their delivery system was made up of the same ratios of the same four lipids that MacLachlan and team had used, but Moderna stated that the preclinical formulation was not the same as the final vaccine.
Moderna maintains that their mRNA vaccine contains their own LNP technology.
But the legal questions around LNP began long before the pandemic had even started.
MISSED OPPORTUNITIES AND LEGAL EXHAUSTION
Kay wasn’t the only scientist who noticed MacLachlan and his team’s work at the time.
In 2006, MacLachlan’s work caught the eye of a talented biochemist — Katalin Karikó, a Hungarian scientist who is now a frontrunner for a Nobel Prize for her revolutionary work with mRNA.
Kariko has worked with BioNTech since 2013, but long before that, she proposed to MacLachlan that they partner to use her messenger RNA with his delivery system.
In an email to Â鶹´«Ã½, Kariko explained that she asked him constantly in 2006 to consider using his LNP with mRNA.
“I [knew] that he was formulating the siRNA, and I wanted him to try the mRNA as well,†she said. “Why did I want to formulate the mRNA with LNP? The mRNA product needed shelf-life. We need[ed] formulated mRNA that can be stored in the freezer for extended time.â€
However, MacLachlan was embroiled in legal conflicts over the technology, and so he declined Kariko’s idea.
“We were a small company at the time, and very much focused on the siRNA drugs, as opposed to the mRNA drugs,†he added.
The legal battles played a role, and after around a decade of “legal wrangling over the ownership of [LNP],†MacLachlan was drained.
He said as the company expanded and there were partners who “weren’t necessarily very well behaved,†leading to legal disputes with them over the ownership of the delivery system.
“That was a very unfortunate distraction, and something that I didn't want to spend the rest of my life having to deal with,†MacLachlan said.
So in 2014 he ended up walking away from it all, leaving his job to travel in a motor home with his family.
MacLachlan is now an independent scientist, consulting with a variety of pharma companies. He has no financial stake in his former company, and gets no royalties from his LNP work which he says is part of some 10 other vaccines and drug products.
But he is hoping to set the record straight, and is coming forward now that his story is out.
“I don't have a financial horse in this race, so to speak,†he said. “But I'm happy to, from time to time, help people understand this technology, and encourage people to do what they can to make it available to as many people who might choose to use it.â€
One of MacLachlan’s main reasons for agreeing to talk to media about developing LNP is that he wanted to uplift, not his own work, but his team’s.
“As an independent scientist now I no longer have a platform from which to advertise my team's accomplishments,†he said. “It’s an opportunity for me to acknowledge that team and make sure that their work is predominant.â€
These vaccines had roots in Canada long ago, he said.
“We started this wanting to help people, and it feels wonderful to know that we have been able to do that,†MacLachlan said.
Some people may distrust COVID-19 vaccines because they appear to come from huge corporations, but there are countless human beings behind these life-saving shots, he said.
MacLachlan urges Canadians to get their shot.
“At the end of the day, this technology was developed by young men and women scientists who really wanted to do what they could to help people,†he said.
“That's where it comes from. It doesn't come from some faceless multinational corporation. It's from the hearts and minds of people like myself, and hopefully that might help some Canadians.â€
