Call it the year of the jab. Between December 2020, when the first COVID- 19 vaccines were rolled out in North America, and December 2021, more than 8.3 billion doses were administered in 184 countries. Close to 90 per cent of the populations in countries like the United Arab Emirates, Portugal and Chile are now fully vaccinated, and, as of this writing, more than 83 per cent of Canadians have received at least one dose. All of these shots—created, manufactured and distributed with breathtaking, dizzying speed—will comprise the largest immunization campaign in human history.
Vaccines have become much more than needles in arms; they are a movement, a moment, a phenomenon, a vibe, a story of both astonishing scientific progress and vexing political calculus. When we weren’t talking about Succession or the Raptors, we were talking about vaccines—the good, the bad and the ugly. Vaccine mandates, certificates and passports transformed travel, work and leisure. We took selfies when we got our first doses and pictures of our kids when they finally got theirs. The decision to get vaccines tore some families apart, and some governments exploited this conflict for their own gain. “Vaccine” became Merriam-Webster’s word of the year. Now the year of the jab is turning into years. As I write this, the Omicron wave has capsized everything again, accelerating boosters and making complete global vaccination more urgent than ever.
One thing’s for certain, though: No matter what happens over the next several months, we’re still going to be talking about vaccines. And what we talk about when we talk about vaccines are the brand-new miracles known as messenger RNA, or mRNA, vaccines. Both the Moderna and the Pfizer-BioNTech vaccines are mRNA vaccines. To date, 95 per cent of the vaccines that Canadians have received were mRNA vaccines. These shots essentially turn your body into its own personal drug factory, and they have proven exceptionally effective against COVID. They have also transformed the pharmaceutical industry, dramatically cutting the speed with which vaccines can be produced.
COVID vaccines largely owe their existence to a visionary Canadian molecular biologist named Derrick Rossi, who’s notable as much for his alt-rock appearance—tousled hair, soul patch, Western shirts—as he is for his pioneering scientific discoveries. Rossi is ambitious and freewheeling. He loves punk music, he bombs around Boston on his bike, and his obsession with the Maple Leafs verges on fanatical. He is also a great evangelist for science and talks about his work with the infectious enthusiasm of a DJ raving about an obscure EP—the mind of Francis Crick in the body of Marc Maron.
He and his wife, the Finnish biologist Nina Korsisaari, have three teenaged daughters, all hockey players, and they live in the Boston suburb of Newton. Their large, sprawling house bustles with kids and pets—specifically, three corn snakes, a ball python and a dog named Chili. (In a nod to Stanley Kubrick’s 2001: A Space Odyssey, Rossi wanted to call him OpenthepodbaydoorHal; he was overruled.) In his library, Rossi keeps a large collection of butterflies—he’s an amateur lepidopterist too—and he has an entire bookshelf dedicated to editions of Moby Dick, his favourite novel.
In 2010, Rossi was a young professor at Harvard Medical School; he was working on stem cell research when he figured out how to chemically tweak mRNA so that it could be used to fight just about any disease or illness. Rossi’s discovery was nothing less than a scientific revolution, landing him on Time’s “People That Mattered” list in 2010 and the magazine’s “100 Most Influential People” the year after. That year, Rossi founded Moderna to commercialize his findings, and interest and investment poured in. Noubar Afeyan, CEO of the Cambridge venture-capital firm Flagship Pioneering, called Rossi’s idea the most promising thing he had ever seen.
While it took a decade—and a once-in-a-century pandemic—for Rossi’s ideas to be proven at scale, modified mRNA has completely reinvigorated and reoriented the vaccine industry. In the public imagination, Pfizer is no longer just the Viagra company or Johnson & Johnson just the maker of baby shampoo. Now they are synonymous with world-changing life-saving medicines. Rossi, meanwhile, is certain we’ll see another global outbreak in about 20 years. What it’ll be is anybody’s guess, but he knows that the only way to combat it is to keep innovating, to keep moving, to keep looking forward. “MRNA is great technology,” he says. “It’s fast, it’s versatile. But let’s not stop there. Let’s not rest on our laurels.”
Rossi was born in 1966 in Scarborough, Ont., the youngest son of immigrants from Malta. His father managed an auto body shop at a Ford dealership, and his mother ran a daycare centre out of their home. It was a tumultuous place—Rossi had four siblings, and his brother Steve kept a large, and exotic, collection of pets: snakes, piranhas, a horned owl, a squirrel, a raccoon. Rossi was into animals too and for a long time dreamed of becoming a veterinarian.
In Grade 11, though, he discovered molecular biology and fell in love. He was simply astonished by what the human body can do. “I just thought it was really cool,” he says. “There were these little machines inside the cell and they were so precise. I found it amazing that evolution had built this technology to orchestrate life.” Molecular biology was having a moment—discoveries in genetic engineering in the early 1970s led to the birth of the modern biotech industry, and by the 1980s, the concept of gene-based therapies emerged.
Rossi’s fascination with the field took him all over the world. He did a couple of undergrad years at Western, then transferred to U of T, where he got his master’s degree. There followed stints, educational and otherwise, in Paris, Dallas, central Africa and Helsinki before Rossi completed a post-doctoral fellowship at Stanford. There was little rhyme or reason to his travels; he was mostly driven by chance and a spirit of adventure. “So many people calculate their lives into the future,” he says. “You know, young people who say they want to get something on their CV. I would never, in a million years, do it that way. You’ve got to let life unfold, and when some opportunity arises out of left field, you’ve got to have the balls to say ‘Yeah, I’m going to move to Finland.’”
When Rossi was hired at Harvard in 2007, he continued to be governed by a restless curiosity. He was an assistant professor in the stem cell and regenerative biology department but also worked as an investigator at the Immune Disease Institute and at Boston’s Children’s Hospital, considered the country’s finest pediatric hospital. He was proudly iconoclastic. He avoided conferences and meetings, preferring to stay in his lab rather than network. Where his colleagues typically paid close attention to their budgets and received funding for research they promised to do over the next five years, Rossi disdained both. He applied for, and received, lots of money but would often work on something other than what he was funded to do. “The science would lead the way,” he says. “Whatever inspiration, whatever data. It could be a shot off the crossbar, who knows?”
Just six months into his job at Harvard, Rossi followed such inspiration. In 2006, the Japanese stem cell researcher Shinya Yamanaka had figured out, essentially, how to reverse time, taking mature, specialized cells back to an undifferentiated embryonic state. Yamanaka’s discovery had the potential to create personalized treatments for disease, or even generate new body parts, and it would win him the Nobel Prize six years later. His process, which involved infecting cells with a virus that contained four specific genes, had its roadblocks—most notably, it could cause mutations in the genome and, possibly, cancer. Therapies derived from his research were extremely difficult to develop.
“We could build a better wheel, a racing wheel, but why not make a spaceship?”
Rossi thought he could perform the same reprogramming trick without touching the DNA. He turned instead to mRNA, or messenger ribonucleic acid. Messenger RNA delivers instructions to cells to create proteins that carry out designated functions in the cell or body. Working off of previously ignored research done by biologists at the University of Pennsylvania, Rossi figured he could alter the chemical building blocks of mRNA—essentially disguising them—so that synthetic mRNA could be introduced from outside a cell without tripping an antiviral response. Once inside the cell, an mRNA sequence would translate into a protein that had the potential to counteract rare genetic diseases, like cystic fibrosis, for example.
In one test, Rossi dosed himself with mRNA encoded for jellyfish protein, smearing it on his arm to see if it would penetrate his cells and make his skin glow green. That didn’t pan out. But in another experiment, his lab encoded mRNA for luciferase, the protein that causes fireflies to glow. Then they injected the mRNA into mice and placed them in a dark chamber with a light-sensitive camera. Sure enough, the mRNA expressed the protein—the mice lit up. “It could have taken us years to get it to work in animals,” Rossi says. “But it worked in the first experiment.”
Armed with such results, Rossi filed a patent application, published a landmark paper and in 2010 founded Moderna. (The term “modified mRNA” was itself tweaked to create the company’s name.) Rossi had intended to focus on genetic diseases until the subject of vaccines came up during a conversation with Tim Springer, a hugely influential colleague at Harvard. Rossi wasn’t so sure. Vaccines already existed; he wanted to make drugs for the 6,000-odd diseases for which there were no treatments. “There was already a wheel on the car,” he says. “We could build a better wheel, a racing wheel, but why not make a spaceship?”
But Moderna eventually recognized that vaccines, even if not the endgame, could be an excellent way to test and prove mRNA. The technical hurdles were very low—you didn’t have to repeat the dose more than once or twice. They could be made extraordinarily quickly.
Stéphane Bancel became Moderna’s first CEO in 2011, when it was just a little start-up. Under his leadership, the company became an economic powerhouse, raising the largest IPO in biotech history (US$600 million) in 2018. It had a valuation of nearly US$8 billion. In 2013, it forged a lucrative research partnership with AstraZeneca (and a few years later would do the same with Merck). Bancel and Rossi frequently clashed, with Rossi concerned that Moderna’s leadership was more focused on money than science. Rossi, ever the renegade, felt that he didn’t fit into the company culture, and, in 2014, he decided to leave. While he sat on Moderna’s board of directors, as well as its scientific advisory board, he had kept his day job at Harvard and had never been an employee of the company. But when he left, he retained a significant share in the business. Rossi doesn’t like to talk about how much he’s earned from those shares. “I have done well,” he says, noting that the company’s market cap is now around US$89 billion.
Bancel and Rossi had agreed on one thing: Vaccines were the perfect vehicle for mRNA. After struggling for years to bring other therapies to market, the company shifted its research focus in 2017. But in order to prove that a medication works, it needs to be tested on an existing disease. To that end, COVID-19 came along at just the right time. “If you don’t have disease, you can’t do clinical trials,” says Mark Lievonen, the co-chair of Canada’s COVID-19 Vaccine Task Force and former president of the pharmaceutical company Sanofi Pasteur. Moderna had created experimental mRNA vaccines for SARS and Zika, but those diseases retreated before the company could get to large-scale clinical trials.
In December 2019, COVID broke out in Wuhan, China. On January 10, 2020, the Chinese media reported the first death from the virus. That same day, Chinese scientists posted online the virus’s genetic sequence. Within hours, researchers at the U.S.’s National Institutes of Health, which had long been collaborating with Moderna on other vaccines, reconfigured their work.
Modified mRNA made it all so simple. Once injected into the body, it told the cells to generate a specific part of the virus—the now familiar spike protein—and the immune system then produced antibodies that were trained to bind to the protein to block infection. The body was then able to identify the new virus and could fight it before it replicated. Forty-two days after the virus sequence was published, Moderna started making its COVID-19 vaccine. “Modified mRNA turned out to be the exact right technology for the challenge,” Rossi says. “You couldn’t have imagined a better one.”
Pre-pandemic, vaccines were considered a lousy business model. Unlike other medications, which are often taken daily, many vaccines are administered only once in a lifetime or, as with the flu shot, once a year. A vaccine can sell for $10 a shot while a genetic therapy, say, can sell for thousands or even tens of thousands of dollars per treatment. Clinical trials can be complex and can take a decade or more, and for many companies, the ROI is simply not worth it. When Mark Lievonen, of the COVID task force, started work at Toronto’s Connaught Laboratories (which eventually became part of Sanofi Pasteur, Sanofi’s vaccine arm) in 1983, the global vaccine market was only worth about a billion dollars. “For many years, vaccines were the poor cousins of pharmaceuticals,” says Lievonen.
COVID completely changed this, at least for the foreseeable future. For the pharmaceutical companies producing an effective vaccine, those vaccines became enormous money-makers. As part of Operation Warp Speed, the U.S.’s accelerated vaccine development project, American taxpayers handed over US$2.5 billion to Moderna, US$1.25 billion to AstraZeneca and US$500 million to Johnson & Johnson. (Pfizer didn’t take any of the OWS money, but it did sign a US$1.95 billion deal to sell 100 million doses to the States.) Clinical trials usually run consecutively—phase one, phase two and so on. Because of the emergency of the pandemic, phase two trials were run before the data from phase one was complete, an overlapping system generally considered too financially risky to be the normal order of things.
In COVID’s case, however, the expedited timeline was a literal lifesaver. “One thing that will become the norm is that to develop a new mRNA drug will literally take weeks, tops,” says Rossi. “The front end of making the medicines will really be reduced in time.” The pandemic also served, temporarily at least, as inadvertent PR for Big Pharma, long pilloried for making enormous profits off of human suffering. Thanks to COVID vaccines, the industry was credited with, even celebrated for, saving the world from certain ruin. Not bad for a bad business model.
While the COVID vaccine was an undeniable arms race, there was also, in many ways, an unprecedented spirit of cooperation. Giants like Pfizer and BioNTech teamed up, and GSK joined forces with both Sanofi and AstraZeneca. Two-thirds of the world’s countries joined COVAX, a coalition designed to accelerate the development and distribution of vaccines. By last December, there were 1,400 COVID vaccines and treatments in development.
Pre-pandemic, Canada’s vaccine-production industry was largely dominated by two foreign pharma giants: the French Sanofi and the British GlaxoSmithKline, which maintain large production facilities in Toronto and Ste-Foy, Que., respectively. GSK produces flu vaccines, while Sanofi makes vaccines for a diverse range of diseases including diphtheria and polio. And yet neither company had idle capacity that could be easily or quickly switched over to produce COVID vaccines, especially the new mRNA ones. A deal between Canada and the Chinese firm CanSino to quickly co-produce a local vaccine fell apart seemingly because of worsening diplomatic relations.
Without a homegrown vaccine or the infrastructure to immediately manufacture one, we were at the mercy of foreign suppliers. Which meant we were at the mercy of unreliable supply chains. Which meant, most significantly, we were at the mercy of the companies that quickly established a monopoly, were able to set their own prices and so far have refused to share their intellectual property. According to the People’s Vaccine Alliance, a coalition of international NGOs demanding equal access to COVID vaccines, Pfizer-BioNTech and Moderna are charging governments as much as US$41 billion above the estimated cost of production.
“Canada is far more prepared now for future variants and future pandemics”
Of course, for-profit companies deserve to earn reasonable profits. But when their research and products have largely been paid for by public money—all in the name of public health—there should also be reasonable restrictions on that profit. At the very least, those companies should be expected to share their vaccine patents and technological know-how with countries and organizations that are unable to afford their prices. As we’ve seen with Omicron, such thinking is neither selfless nor socialist: lopsided vaccine distribution has contributed to the emergence of variants that are still wreaking havoc in wealthy countries with high vaccination rates.
Faced with a lack of domestic vaccine, Canada nonetheless embarked on its own form of vaccine nationalism, buying up as many doses as it could. In February, it even plundered COVAX, taking 1.9 million AstraZeneca doses that had been earmarked for low-income countries. By the end of May 2021, Canada had spent more than $14 billion on COVID vaccines and therapeutics and an additional $1 billion on an immunization plan. We had more vaccines per capita than any other country in the world, enough to protect a country four times our size.
But what about the next pandemic? Most experts think it will be caused by another respiratory illness, like swine or avian flu. Deadlier pathogens, like, say, Ebola, kill their hosts before they can spread very far. Accordingly, the federal government gave Sanofi Pasteur $415 million to build a new end-to-end influenza-vaccine-production facility in Toronto (with Sanofi kicking in an additional $455 million and promising to create 1,225 new jobs). The National Research Council of Canada built another facility, the Biologics Manufacturing Centre in Montreal, to the tune of $126 million. It is scheduled to start producing the Novavax protein subunit COVID vaccine sometime this year. In May, the Government of Canada invested almost $200 million in Resilience Biotechnologies so it could expand its mRNA vaccine manufacturing capability in Mississauga, Ont. And in August, it announced that Moderna would be building a production operation somewhere in Canada in the next two years.
But Resilience, Novavax and Moderna are all American companies. Where are our own biotech firms? In March of 2020, the feds invested $792 million in 10 Canadian companies developing vaccines and production capacity. One of these, the Quebec City-based Medicago, has been creating plant-based vaccines and therapeutics for decades and just completed phase three trials of its own COVID vaccine. It could be approved by the time you read this, making it the first Canadian-made vaccine. Medicago received $173 million in October 2020 from the federal government, and since the pandemic began the company has grown by 100 employees. (It currently has about 500.) Nathalie Charland, Medicago’s senior director of scientific and medical affairs, feels that Canada, while perhaps not prepared for this particular pandemic, has made great strides. She takes comfort, she says, in how competitors and countries came together during this crisis to share knowledge and resources. “The pandemic has drawn attention not only to domestic capacity but also beyond that to domestic research and development,” she says. “There are smaller groups across Canada that are working hard to make the next generation of vaccines and to make sure we’re prepared as a country.”
“After vaccines, I think we’re going to see a boom— a big boom—in anti-tumour mRNA”
One of those groups is Providence Therapeutics in Calgary, which has been researching mRNA-based cancer vaccines since 2015. When the novel coronavirus emerged, Providence immediately pivoted to develop its own COVID vaccine, successfully doing so, its CEO Brad Sorenson says, just a month after Moderna. Like Medicago, it grew throughout the pandemic, from 11 to 65 employees. But unlike Medicago, Providence hasn’t received nearly the same financial support at either the federal or the provincial level. To get his vaccine through clinical trials, Sorenson says, he needed about $100 million, but to date, Providence has received only $13 million in support (from the National Research Council and NGen). He repeatedly asked the federal government for a no-interest loan or a vaccine order and has received neither. Understandably perplexed and angry about the situation, Sorenson finally stopped knocking on doors in Ottawa. In September, Providence secured that $100 million from Everest Medicines in China, licensing its mRNA technology so it can make and sell its mRNA vaccines in China and Southeast Asia.
“Canada is far more prepared now for future variants and future pandemics,” Sorenson says. “Because of Providence. Because of what we did as a company and what we continue to do, despite the lack of federal funding.” Sorenson expects his vaccine, which goes into phase three trials early this year, to be approved by summer.
COVID isn’t going away any time soon, and neither are vaccines. While the virus may eventually become endemic, that won’t happen until almost everyone has been vaccinated or infected or both. There are still millions of kids to immunize, and then kids under five. In North America, even as we’re still ramping up the first boosters, we’re considering fourth shots and annual boosters—at least for a while. Moderna is developing a modified-mRNA-based combination booster and flu shot, which, depending on clinical trials, may be ready by the next flu season. And there’s still the spectre of other variants, which could require the production and distribution of more or other vaccines.
Rossi is still on the hunt for the next thing too. While he didn’t always agree with Moderna’s leadership, his experience there taught him the value of entrepreneurship. It was one thing to make discoveries in his own lab, but as a biotech entrepreneur, he could push forward many more discoveries in many more labs at the same time. In 2014, he co-founded Intellia Therapeutics, followed by Magenta Therapeutics and Stelexis Therapeutics, with each company centred around a different cutting-edge scientific idea, from CRISPR, the renowned targeted gene-editing technology, to the stem cell origins of cancer. In 2018, he became CEO of Convelo Therapeutics, a firm co-founded by Paul Tesar, a Cleveland scientist who has developed new regenerative therapies for multiple sclerosis and cerebral palsy. “Derrick is committed to making the world a better place through the companies he’s developed and founded,” says Tesar. “There are so many scientific advancements being made every day. He has this golden touch.”
At the moment, Rossi is most passionate about a new small-molecule therapeutic for snakebite, something that kills 125,000 people a year and maims 450,000 more. “Year in, year out, and the most impoverished, most marginalized people on the planet,” Rossi says. “It’s a neglected global health crisis and something needs to be done.”
In his search for the next scientific frontier, Rossi hasn’t abandoned modified mRNA. It’s still a singular technology. “You know, you can make vaccines in other ways,” he says. “But there are many, many therapies that will emerge, with time, from the mRNA technology that can’t be done with other technologies.” He remembers reading an article by Bill Gates raving about CRISPR, calling it the greatest contemporary innovation in biomedicine. Rossi chuckles to himself. “My first thought was ‘Close, but not quite.’ Bill got it wrong. First-grade modified mRNA is 100 times more powerful.”
These days, Rossi is most excited about mRNA in oncology. It’s the same basic principle—detect a malignant tumour, inject that tumour with mRNA, then get the mRNA to express something that the tumour doesn’t like. The mRNA can secrete beacons for the immune system to go in and take care of it. Or you can inject direct cytotoxic messages that essentially put the brakes on tumour cells or cause apoptosis, programmed cell death. “After vaccines, I think we’re going to see a boom— a big boom—in anti-tumour mRNA,” Rossi says.
For an iconoclast who’s helped change the world, Rossi is surprisingly modest. He answers emails speedily, spends hours on the phone with me, patiently answers the same questions he’s been asked a million times. He’s most excited to talk about hockey, specifically the Leafs’ goal song—Hall and Oates’ “You Make My Dreams”—which he loathes. His preference would be the decidedly more obscure David Bowie anthem “Chant of the Ever Circling Skeletal Family.” “Put that on after every goal,” Rossi says, “and it would be a big energy boost for everybody.” When I tell him I know a lighting technician at Scotiabank Arena who could put in the recommendation, he says to have my friend call him directly.
Ultimately Rossi gives credit to science—capital “S” science, as in all the researchers that came before and after him, his lab technicians, the vaccinologists, Anthony Fauci…the list goes on. His discovery was built on the work of others, he insists, and the work he does now is in collaboration with many other scientists and investors. But he’s thrilled that, after years in the Trumpian wilderness, by and large science is at last receiving the respect it’s due. “The good news is that people do recognize the importance of science,” he says. “That’s cool and good to see. And that’s the way it should be.”