Failure is the sturdiest foundation

How our inability to end one pandemic is saving us from another

In my last newsletter, I covered some of the issues around chasing the end of the pandemic with vaccines. Basically, it boils down to what Ralph Baric—the world’s greatest coronavirus researcher—describes as an inevitable flood of SARS-CoV-2 variants that will elude vaccines faster than we can produce and distribute new ones. Those variants emerge in places where the virus is replicating plentifully (the cool scientific term is ‘transmission cycles’), and they will continue to do so until there are no more pockets of susceptible hosts (read: non-immune humans) to infect and mutate within. Phew. If you want to read about Baric’s forty-year journey from outsider coronavirologist to one of the most consequential scientists alive, it’s all in my upcoming book The Invisible Siege: The Rise of Coronaviruses and the Search for a Cure.

Ralph Baric, coronavirus legend

That grim scenario wouldn’t hold, though, if the whole world got vaccinated. But between the pitifully low lack of access to vaccines in low- and middle-income countries and the hyped up anti-vax movement, we’re not going to get close to global herd immunity, which is what’s needed to stop the pandemic. So. What are the options?

Fury-inducing statistics courtesy of the New York Times

Hope. And no, that’s not a joke.

Well, this is where there is, actually some good news. And it’s not just about this pandemic: it’s good news about whatever future coronavirus pathogen next threatens humanity (and yes, there will undoubtedly be more). And like so many scientific successes, this one is rooted in abject failure.

Decades after its discovery, HIV remains one of the world’s most dangerous viruses. But, as we’ve all heard many times, it has been transformed from a killer into a chronic condition. What’s remarkable, though, is that this was all done without a vaccine. The HIV virus is so elusive (it turns the body’s own immune cells against itself) and so slippery (it mutates at a clip that makes SARS-CoV-2 look like its standing still) that every attempt to create a vaccine—and there have been many over the past forty years—have failed. And still, humanity somehow found a way to control the spread of HIV.

That we were able to do so in the absence of a vaccine is one of modern science’s greatest achievements. So how did it happen? The trick was, basically, to assume that the virus was going to burrow its way into human hosts, and that the focus should be on disrupting it once it did. In practical terms, that meant forgetting about vaccines and focusing on antiviral treatments that could stop the virus replicating. It’s a bit like trying to stop the snow from falling (and forgive the simile; I’m writing this from Toronto, where there’s been record snowfall), which is something nature decides, not us. That doesn’t mean, though, that we have to throw ourselves at the mercy of the elements. We can equip ourselves with multiple tools—a warm jacket, waterproof boots, and a shovel—to make sure that when the snow hits, we stay warm and protected.

Toronto. Nuff said. Fred Lum/Globe & Mail

So it goes with antivirals. They won’t help your immune system kill viruses before they find a reservoir inside your body, but they will protect us from the worst of an infection by hindering a virus’s capacity to replicate. In the case of HIV, a combination of antiviral medications (known collectively as highly active antiretroviral therapy) has become so effective that HIV-positive people who take them can have so little virus in their bloodstream that it can no longer be detected, let alone make them sick. It’s an incredible feat—the control of a deadly pandemic-level pathogen without a vaccine—but that’s only the beginning. Because HIV medications reduce the amount of virus in a person’s bloodstream to undetectable levels, they also make it essentially impossible for someone infected with HIV and on treatment to infect other people: there just simply isn’t enough virus in their bloodstream to be a threat. This technique—using medications designed to control AIDS-related illness to stop the spread of a vaccine-dodging pathogen—is known as Treatment as Prevention, and it’s revolutionized the way we think about elusive pathogens.

U=U is the newest clarion call in the long fight to end the AIDS pandemic

Antivirals got lost in the COVID vaccine frenzy, even though they might just be our way out…

There are clear lessons here for the future of COVID-19, and for once they’re uniformly positive. We now have multiple approved antiviral medications—Pfizer’s Paxlovid, Molnupiravir, and Remdesivir—that disrupt different stages of SARS-CoV-2 replication. What’s great about these is that they all target parts of the virus that aren’t prone to mutating, unlike the spike protein, which is the target of all current vaccines and which mutates at roughly three times the rate of rest of the virus.

That means that, even if the vaccines fail against future variants, antiviral medications almost certainly won’t. Multiple studies show that COVID-19 antivirals reduce moderate and severe illness by up to 90%, and that they could even protect hospitalized people from needing a ventilator. There’s even good evidence that they could even protect against infection if taken prior to exposure to virus; say, if someone in your family or social network tested positive. And that starts moving things into the realm of Treatment as Prevention: COVID-19 treatments that can stop people from getting sick while also stopping the spread of the SARS-CoV-2 virus itself.

PBS News Hour gets it.

This is ‘end of the pandemic’ stuff, for two reasons. First, because, as I mentioned, the COVID-19 antivirals target parts of the virus that don’t mutate rapidly, so they’ll likely remain effective over time. Second, because these treatments are cheap and easy to distribute, especially compared to the COVID-19 vaccines, which means that Treatment as Prevention campaigns could be deployed to places around the world where outbreaks are occurring and could stop them in their tracks. It’s an unbelievably effective public health approach, and it brings me unadulterated hope for the future.

I’ll end on one last piece of good news. The parts of the virus that these antiviral medications target haven’t only remained stable across all the SARS-CoV-2 variants. They’re also present in every single coronavirus that has ever been discovered. That means that, no matter what coronavirus pathogen shows up next—and SARS, MERS, and SARS-CoV-2 makes it three in thirty years—we can have a lot of confidence that the antivirals that work against COVID-19 will protect us from the next abomination nature sends our way. Does that spell the end of coronavirus pandemics? It just might.


Meanwhile, in Dan Werb News:

We are one (!) month away from the publication of The Invisible Siege: The Rise of Coronaviruses and the Search for a Cure. There have been some more really positive reviews filtering up, including in Library Journal (paywalled, but thank you librarians, anyway) and from some goodhearted early readers, which you can see on Goodreads. I’m getting pretty amped to have this book out in the world. As always, you can pre-order it here.

You might just love it.


Thanks for reading. You can find me at my website and on Twitter. If you want to go deep on my science, check out my one true love: Pubmed. If you haven’t yet signed up for this newsletter, or know someone who would like it, go ahead and do it here.

Walking slowly towards the outgoing tide

Why COVID-19 vaccines are both better than we could ever imagine and the wrong strategy to end the pandemic.

There’s a great deep dive in this past weekend’s New York Times about the decades-long journey that brought mRNA vaccines from concept to cure. It’s the kind of story that I love (and that my book Invisible Siege: The Rise of Coronaviruses and the Search for a Cure, chronicles extensively): a story about scientists working towards turning an esoteric dream into a reality, even (especially!) when nobody else cared. And what a reality: the COVID-19 vaccines developed by Pfizer and Moderna have now been injected into billions of arms and blanketed the world with some pretty serious protection to disease. That’s something that we take for granted, but it’s worth stopping, breathing deeply, and taking some perspective for a minute on what that really means.

Good hands, as the say in the basic science biz (courtesy of NYT)

While the Omicron wave has made everyone feel miserable, the scientific response to the pandemic has played out far better than anyone dared dream. It starts with those mRNA vaccines. For context, the US Food and Drug Administration (which has final say on whether a drug can be marketed in the US) set the threshold for COVID-19 vaccine effectiveness at 50%. Let that sink in. Fifty percent! That means, of course, that getting a vaccine would be a coin toss: half the people who got a shot would still get as sick as the people who didn’t. The rationale for the FDA was that this was the absolute minimum level of effectiveness to get a population to herd immunity (which is about 70% of a population that is immune to getting sick) through a combination of naturally-acquired immunity (by getting infected with the SARS-CoV-2 virus) and a kick ass inoculation campaign that managed to get close to 100% of the population vaccinated. The upshot is that each percentile increase in the effectiveness of a vaccine makes it that much easier to reach herd immunity and get through the pandemic.

The vaccines stay the same, but the virus keeps on getting smarter…

When Pfizer and Moderna shared the results from their mRNA vaccine trials, both were, stunningly, 95% effective against illness. What a relief: it meant that reaching that 70% herd immunity threshold would be way easier (read: would require getting fewer people vaccinated) than if the vaccines were 50% effective. What’s so damn frustrating, though, is that while humanity has been getting itself immune to COVID-19, the SARS-CoV-2 virus hasn’t been standing still. At this point, the vaccines are by and large made to stop the spread of a version of the virus that first spread through Wuhan, China. Since then, three major variants have spread. D614G, the first, was the version of the virus that first went global, replacing the ‘wild-type’ version of the virus that first emerged in Wuhan. Delta was the variant that ultimately outcompeted D614G (with honorable mentions to Alpha, Beta, and Gamma), and Omicron has now shown itself to be far more transmissible than anything that has come before. Each step of the way, the vaccines have seen their effectiveness degrade, and the rapid spread of Omicron (and its accompanying hospitalizations) proof of just howwily coronaviruses are in evolving to overcome our defenses.

Scary-looking variants, courtesy of CTV News

This matters because, as we’re seeing now, vaccines will become less effective over time, necessitating boosters and updated formulations to match the most recent variant. As long as herd immunity is elusive, new variants will inevitably arise, spread, and weaken vaccines.

Vaccines and the end of the pandemic

That brings us to a darker truth that rarely gets coverage: variants are going to keep showing up as long as the world—not a single country, but the entire world—doesn’t have access to vaccines. It’s not enough to protect people in wealthy countries. That might keep us in a sort-of mid-pandemic limbo, with breaks between waves followed by escalating case numbers and deaths, and lockdowns and restrictions, the whole thing continuing ad nauseum. But hoarding vaccines is only going to treat symptoms of the pandemic. If we’re serious about ending the threat of COVID-19, everybody everywhere needs access to a vaccine. That way, herd immunity can be reached across the world, which would then stop the virus from being able to replicate and mutate at will, which would reduce the chances of horrible new variants emerging, which would end the pandemic once and for all.

It’s a simple formula and one of the rare moments when the ethical path (vaccines for everyone) fully lines up with the most selfish one (I want the pandemic to end for me).

While the dream of vaccine equity has a ways to go, there are some really hopeful signs that we might just get there. The mRNA vaccines weren’t designed to be especially cheap or easy to transport globally. But new vaccine candidates like Corbevax (dubbed ‘The World’s COVID-19 Vaccine’) and HexaPro are specifically being developed as inexpensive, easily distributable options for global scale-up. Let’s hope they get there.

Until they do, worry not (there’s already enough anxiety out there). Vaccines are still an incredibly effective way to protect yourself. They just aren’t likely to end the pandemic. In my next newsletter, I’ll tell you about the secret weapon that 19 might just make COVID-19 the last coronavirus pandemic to wreak havoc on humanity. Hint: it doesn’t have anything to do with vaccines…

Meanwhile, in Dan Werb news:

Publishers Weekly named The Invisible Siege: The Rise of Coronaviruses and the Search for a Cure one of the top ten science books of the upcoming season. In their starred review, they called it “a page-turning and unsettling look at the history of coronaviruses”, and that “the light he sheds on scientists whose work has gone largely under the radar makes for a moving account.” Well, damn. That’s nice. You can pre-order the book here.

Join me, won’t you?


Thanks for reading. You can find me at my website and on Twitter. If you want to go deep on my science, check out my one true love: Pubmed.


A story about hope, science, viruses, the pandemic, and the long way through the darkness

Well I damn did it. Behold the last 18 months of my life. The Invisible Siege: The Rise of Coronaviruses and the Search for a Cure. This is the story of how science saved the day, starting in the 1980s and running through to the COVID-19 vaccines and treatments that came online last year. This was such a joy to write in the midst of the pandemic shittiness. As things looked grimmer and grimmer, I spent hundreds of hours talking to scientists who had spent decades studying coronaviruses and making the scientific discoveries that would deliver us vaccines and treatments. There’s so much in this book that is thrilling, earth-shattering, and at times frankly unbelievable. But it is all true, I swear.

What I didn’t know before writing this book – and what I’m so excited to share with readers – is the backstory of the cures that are seeing us through the COVID-19 pandemic. And I don’t just mean vaccines: the antiviral treatments like molnupiravir and remdesivir, which are both protective against COVID-19 disease, have their roots in scientific discoveries that happened decades before SARS-CoV-2 ever emerged. How? Well, it took an amazing amount of sheer will on the part of a really small group of coronavirologists to keep pushing towards their development. How they designed a strategy to counter a virus that didn’t yet exist is one of the great stories of the pandemic, and unlike many of the others, it’s a story of hope and optimism.

Beyond that, this book is about camels, bats, patents, profits, authoritarian governments, minks, mice, and some incredible human beings. I think you will like it, whoever you are. (And yes, before you mention it, I am schooled in the role of bias in informing self-serving opinions.)

You can preorder this beautiful book here:

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I’m so excited to share this with you all ?