From The Economist on the occasion of the award of the Nobel Prize for Medicine to Katalin Karikó and Drew Weissman for their work that led to the development of the Covid-19 mRNA vaccines, a lovely short appreciation of vaccines.
The World Health Organisation (WHO) says that vaccines have saved more from death than any other medical invention. It is a hard claim to gainsay. Vaccines protect people from disease cheaply, reliably and in remarkable numbers. And their capacity to do so continues to grow. In 2021 the who approved a first vaccine against malaria; this week it approved a second.
Vaccines are not only immensely useful; they also embody something beautifully human in their combination of care and communication. Vaccines do not trick the immune system, as is sometimes said; they educate and train it. As a resource of good public health, they allow doctors to whisper words of warning into the cells of their patients. In an age short of trust, this intimacy between government policy and an individual’s immune system is easily misconstrued as a threat. But vaccines are not conspiracies or tools of control: they are molecular loving-kindness.
The WHO says that vaccines currently prevent 4-5 million deaths per year. The CDC points to a paper that says that more than 50 million death can be prevented between 2021 and 2030. Vaccination is nothing short of a scientific miracle. (via eric topol)
From Kurzgesagt, an accessible explanation of what happens to the human body when you get sick.
Your brain activates sickness behavior and reorganizes your body’s priorities to defense. The first thing you notice is that your energy level drops and you get sleepy. You feel apathetic, often anxious or down and you lose your appetite. Your sensitivity to pain is heightened and you seek out rest. All of this serves to save your energy and reroute it into your immune response.
They also reveal the best way to boost your immune system to protect yourself against disease. I don’t want to spoil it but it’s vaccines. Vaccines are one of the best things humans have ever invented.
From Vox’s Joss Fong, a video essay on how conservatives turned against the Covid-19 vaccine in the US.
President Donald Trump presided over the fastest vaccine development process in history, leading to abundant, free vaccines in the US by the spring of 2021. Although the mRNA Covid-19 vaccines haven’t been able to stop transmission of the virus, they have been highly effective against hospitalization and death, saving hundreds of thousands of lives and rendering the majority of new Covid-19 deaths preventable.
Trump has received three doses of the vaccine. But many of his most dedicated supporters have refused, and many have died as a result. Why? Obvious culprits include misinformation on social media and Fox News and the election of Joe Biden, which placed a Democrat at the top of the US government throughout the vaccine distribution period. But if you look closely at the data, you’ll see that vaccine-hesitant conservatives largely made up their mind well before the vaccines were available and before Donald Trump lost the 2020 election.
Fong makes a compelling argument for the potential genesis of conservative vaccine denial: early on in the pandemic, in February and March 2020, prominent conservative leaders and media outlets (like Trump and Fox News) told their constituents that the threat of the pandemic and of SARS-CoV-2 has been exaggerated by journalists and liberal politicians. So, in the mind of a Fox News viewer, if the pandemic is not such a big deal, if it is “just the flu”, then why would you want to get vaccinated? Or wear a mask? Or take any precautions whatsoever? Or, most certainly, why wouldn’t you be angry at you and your kids (your kids!) being forced to do any of those things?
Historically, contracting the measles has been linked to subsequent illness (and possibly death) from other causes. In the past few years, scientists have discovered why this is: measles causes “immune amnesia”.
Enter “immune amnesia”, a mysterious phenomenon that’s been with us for millennia, though it was only discovered in 2012. Essentially, when you’re infected with measles, your immune system abruptly forgets every pathogen it’s ever encountered before — every cold, every bout of flu, every exposure to bacteria or viruses in the environment, every vaccination. The loss is near-total and permanent. Once the measles infection is over, current evidence suggests that your body has to re-learn what’s good and what’s bad almost from scratch.
“In a way, infection of the measles virus basically sets the immune system to default mode,” says Mansour Haeryfar, a professor of immunology at Western University, Canada, “as if it has never encountered any microbes in the past”.
This re-learning process takes up to three years, which “around the time it takes infants to acquire immunity to everyday pathogens in the first place”. In the meantime…
It’s not surprising, then, that measles doesn’t just increase the risk of illness, but also death. In fact, childhood mortality from other viruses is strongly linked to the incidence of measles. The 2015 study showed that when childhood mortality in the UK, US, or Denmark goes up, this is usually because measles has become more prevalent.
The findings explain why vaccinating children against measles has the unexpected, beneficial side-effect of reducing deaths among children, way beyond the numbers who were ever at risk of dying from measles itself.
Of course, an extremely effective and safe vaccine offers protection against both measles and the immune amnesia it causes. But with the steep rise in anti-vaccination sentiment during the pandemic and the increasing willingness of conservative leaders to disregard public health protections in favor of “individual freedom”, widely vaccinating against this dangerous pathogen in the US & elsewhere will be more difficult than in the past.
Science is the foundation for our success. 150 years ago nobody knew where diseases came from. Or more precisely, people thought they knew, but they were wrong. The widely accepted idea at the time was the ‘Miasma’ theory of disease. Miasma, the theory held, was a form of “bad air” that causes disease. The word malaria is testament to the idea that ‘mal aria’ — ‘bad air’ in medieval Italian — is the cause of the disease.
Thanks to the work of a number of doctors and chemists in the second half of the 19th century humanity learned that not noxious air, but specific germs cause infectious diseases. The germ theory of disease was the breakthrough in the fight against the microbe. Scientists identified the pathogens that cause the different diseases and thereby laid the foundation for perhaps the most important technical innovation in our fight against them: vaccines.
Here’s what vaccines did for us, in three charts:
Even among those who accept and understand how good vaccines are at stopping disease, it’s difficult to truly appreciate just how incredible and transformative they have been. By one estimate, vaccines saved between 150 & 200 million lives from 1980 & 2018…and that’s just for smallpox. Covid-19 vaccines have saved hundreds of thousands of lives in Europe and the US in the first year of their availability. Truly a miraculous invention.
This is such an interesting article on vaccine avoidance in America by a primary care doctor & sociologist who have studied the phenomenon in America and other places. As more data has come in about the pandemic and vaccination program, the main differentiator in whether someone is willing to get a vaccine or not is class.
Over the past four decades, governments have slashed budgets and privatized basic services. This has two important consequences for public health. First, people are unlikely to trust institutions that do little for them. And second, public health is no longer viewed as a collective endeavor, based on the principle of social solidarity and mutual obligation. People are conditioned to believe they’re on their own and responsible only for themselves. That means an important source of vaccine hesitancy is the erosion of the idea of a common good.
Americans began thinking about health care decisions this way only recently; during the 1950s polio campaigns, for example, most people saw vaccination as a civic duty. But as the public purse shrunk in the 1980s, politicians insisted that it’s no longer the government’s job to ensure people’s well-being; instead, Americans were to be responsible only for themselves and their own bodies. Entire industries, such as self-help and health foods, have sprung up on the principle that the key to good health lies in individuals making the right choices.
Almost more than anything else, the pandemic has shown how damaged the US is from decades of neglect of the common good and how vulnerable we are to things like disease and political coups.
It may seem like sometimes that with the pandemic, we’re back to square one. With the much more contagious Delta variant in play and an increasing number of breakthrough infections, the efficacy of these vaccines that we thought were amazing maybe aren’t? (Or maybe we just need to readjust our expectations?) But in terms of what these vaccines were specifically developed for — reducing & preventing severe disease and death — they are still very much doing their job. Just take a look at this graph from a White House Covid-19 press briefing yesterday:
Even with Delta endemic in the country, the vaccines are providing extraordinary protection against infections severe enough to land folks in the hospital. In a recent CDC study of infections and hospitalizations in Los Angeles County, they report that on July 25, the hospitalization rate of unvaccinated people was 29.2 times that of fully vaccinated persons. 29 times the protection is astounding for a medical intervention. These vaccines work, we’re lucky to have them, and we need to get as many people worldwide as we can vaccinated as quickly as we can. Period.
You might want to take a deep breath or do a couple of laps around the house before watching this video about a community in the Ozarks with a very low Covid-19 vaccination rate. Here’s a sample. An ICU patient wearing an oxygen mask on why he didn’t get vaccinated:
I’m more of a libertarian and I don’t like being told what I have to do. I’m still not completely 100% sold on the inoculation.
Video narrator:
It was eerie to hear Christopher insist on his individual freedoms even as he struggled to breathe.
Can you hear me screaming all the way from my desk to wherever you are? I don’t like being told what I have to do?! Fucking hell. And this:
There’s no better place to see the impact of this political rhetoric than in the hospital. Only about 50 percent of the staff are vaccinated. None of the unvaccinated staffers were willing to talk.
Unfortunately, communal benefit is harder to define, harder to quantify, and harder to describe than individual protection, because “it’s not the way Americans are used to thinking about things,” Neil Lewis, a behavioral scientist and communications expert at Cornell, told me. That’s in part because communal risk isn’t characteristic of the health perils people in wealthy countries are accustomed to facing: heart disease, stroke, diabetes, cancer. Maybe that’s part of why we gravitate toward individual-focused comparisons. Slipping into a pandemic-compatible, population-based frame of mind is a big shift. In the age of COVID-19, “there’s been a lot of focus on the individual,” Lewis told me. That’s pretty at odds “with how infection works.”
As someone who has struggled with analogizing the virus & vaccines, I was nodding my head a lot while reading this. Something I’ve noticed in recent years that Wu didn’t get into is that readers desire precision in metaphors and analogies, even though metaphor is — by definition! — not supposed to be taken literally. People seem much more interested in taking analogies apart, identifying what doesn’t work, and discarding them rather than — more generously and constructively IMO — using them as the author intended to better understand the subject matter. The perfect metaphor doesn’t exist because then it wouldn’t be a metaphor.
The Panola Project is a short film by Rachael DeCruz and Jeremy Levine that follows the efforts of local convenience store owner Dorothy Oliver to get the people in her small Alabama community vaccinated against Covid-19. A trusted member of her community, Oliver teams up with county commissioner Drucilla Russ-Jackson to call & go door-to-door, talking with people one-on-one, cajoling and telling personal stories of loss to get folks signed up for a mobile vaccination clinic.
In the film, Oliver and Russ-Jackson arrange for a hospital to set up a pop-up site in Panola, but the site will only be established if they get at least forty people to sign up to take the vaccine. We follow Oliver as she goes door to door, talking people into signing up, lightly cajoling them about their fears and concerns. When I asked her how she does it, her answer was disarmingly simple: “I just be nice to them,” she said. “I don’t go at them saying, ‘You gotta do that.’” DeCruz, too, was struck by the way Oliver and Jackson talked to people who were on the fence about the vaccine, an issue more often discussed with stridency of various types. “There’s this very warm and kind of loving and caring way that Dorothy and Ms. Jackson approached those conversations, even when people aren’t in agreement. And it wasn’t done in a way that’s, like, ‘I know better than you.’ “
Oliver’s charm with the skeptics is remarkable, but so is her determination to bring the vaccine to her underserved town. Most of the women and men Oliver talked to leaped at the opportunity to sign up for the vaccine. On vaccine day, they rolled down their car windows to thank her. “We appreciate y’all giving it to us, because a lot of people don’t really know where to go to take these vaccines,” one woman tells her. Vaccine hesitancy in Black communities has been harped on in the media, but those conversations can gloss over questions of availability. Levine told me that they were struck by how many people had put off vaccination for logistical rather than ideological reasons. In Panola, he says, they regularly heard people say, “I want the shot. How do I get this? I don’t have a car; how am I going to get forty miles to the closest hospital and back?”
The result? In a state with one of the lowest vaccination rates in the country, 94% of adults in Panola have been vaccinated, due in part to Oliver’s and Russ-Jackson’s efforts.
As one commenter noted, all of the solidly “blue” states are above the vaxxed national average and all the solidly “red” states are below it. The picture is a little more muddy when you look at the rates at the county level:
The “conservatives are unvaxxed” trend is still there, but a lack of access and education around the vaccines in counties with large Black and Latino populations also plays a large role in whether people are vaccinated or not.
Dr. Brytney Cobia treats Covid-19 patients at the Grandview Medical Center in Birmingham, Alabama, a state that ranks last in the US in fully vaccinated adults. In a recent Facebook post, Cobia shares that people are willing to get vaccinated after having to watch an unvaccinated member of their family die from Covid.
I’ve made a LOT of progress encouraging people to get vaccinated lately!!! Do you want to know how? I’m admitting young healthy people to the hospital with very serious COVID infections. One of the last things they do before they’re intubated is beg me for the vaccine. I hold their hand and tell them that I’m sorry, but it’s too late. A few days later when I call time of death, I hug their family members and I tell them the best way to honor their loved one is to go get vaccinated and encourage everyone they know to do the same. They cry. And they tell me they didn’t know. They thought it was a hoax. They thought it was political. They thought because they had a certain blood type or a certain skin color they wouldn’t get as sick. They thought it was ‘just the flu’. But they were wrong. And they wish they could go back. But they can’t. So they thank me and they go get the vaccine. And I go back to my office, write their death note, and say a small prayer that this loss will save more lives.
Since yesterday’s announcement, I’d been feeling uneasy about the CDC’s decision to update its guidance to state that fully vaccinated people don’t need to wear masks in most situations indoors or out. Zeynep Tufekci’s piece in the Times nails why.
It’s difficult for officials to issue rules as conditions evolve and uncertainty continues. So I hesitate to question the agency’s approach. But it’s not clear whether it was responding to scientific evidence or public clamor to lift state and local mandates, which the C.D.C. said could remain in place.
It might have been better to have kept up indoor mask mandates to help suppress the virus for maybe as little as a few more weeks.
The C.D.C. could have set metrics to measure such progress, saying that guidelines would be maintained until the number of cases or the number vaccinations reached a certain level, determined by epidemiologists.
The vaccine is on its way to controlling Covid-19 in the US — but we’re not there yet. We’re not the UK or Israel…they’re further along in their vaccination campaigns and their daily cases and deaths are way down, warranting behavioral changes. In the US, over 600 people/day are still dying of Covid-19 and our case positivity rate is still above 3%. Too many people, including almost all children, are still vulnerable and as Tufekci says, the CDC could have waited a few more weeks to more quickly drive down the virus levels.
Update: The CDC’s move has been sharply condemned by National Nurses United, the nation’s largest union of registered nurses:
“The union noted that more than 35,000 new cases of coronavirus were being reported each day and that more than 600 people were dying each day. “Now is not the time to relax protective measures, and we are outraged that the C.D.C. has done just that while we are still in the midst of the deadliest pandemic in a century,” Ms. Castillo said.”
And Ken Schultz notes that the needle the CDC is trying to thread here might not work out the way that they’d hoped.
Imagine the social preference ordering is:
1. Unvaccinated wear masks, vaccinated don’t.
2. Everyone wears masks.
3. No one wears masks.
Selfish, short-sighted behavior and the inability to monitor vaccination status mean that, in trying to get #1, you can end up at #3.
So I trust the CDC’s position that #1 is socially desirable from a scientific perspective. But by undermining mask mandates, they have made it more likely that we end up in #3, which science says is still risky. Living with #2 for now respects both science and social science.
In 1955, epidemiologist Thomas Francis Jr. announced the results of a field trial of the polio vaccine that Jonas Salk had developed. America erupted in joy.
Now a phalanx of bulky television cameras focussed on Francis as he prepared to report on the efficacy of the vaccine. He had good news to share: to cheers from the audience, he explained that the Salk vaccine was sixty to seventy per cent effective against the most prevalent strain of poliovirus, and ninety per cent effective against the other, less common strains. All this had been shown through what was, at that time, the largest vaccine trial ever conducted.
All afternoon and evening, church bells rang out across America. People flooded into the streets, kissing and embracing; parents hugged their kids with joy and relief. Salk became an instant national hero, turning down the offer of a ticker-tape parade in New York City; President Dwight D. Eisenhower invited him to the White House and, later, asked Congress to award him a Congressional Gold Medal. That night, from the kitchen of a colleague’s house, Salk — whose name was being touted in newspapers, magazines, radio reports, and television news broadcasts around the world — gave his first network-TV interview to Edward R. Murrow, whose show “See It Now” had exposed the tactics of Senator Joseph McCarthy a year earlier. Blushing in admiration, Murrow asked the doctor, “Who owns the patent on this vaccine?” “The people,” Salk said, nobly. “There is no patent. Could you patent the sun?”
In the days that followed, schoolchildren were instructed by their teachers to write thank-you notes to Salk. Universities lined up to offer him honorary degrees. Millions of American doctors, nurses, and parents got down to the serious business of vaccinating their children against polio, using a shot they’d been anticipating for seventeen years.
But the polio vaccine rollout had its challenges, including a manufacturing negligence & oversight failure that resulted in tens of thousands of polio cases in otherwise healthy children.
In May, the polio vaccination drive was temporarily suspended. Leonard Scheele, the U.S. Surgeon General, inspected the facilities of all six vaccine companies and fired the government officials he considered to be culpable; the director of the N.I.H. and the Secretary of Health voluntarily resigned. New safety procedures were developed, including an improved means of filtering the viral mix just before the formaldehyde was added. Better tests were developed to detect live virus, and stricter record-keeping was instituted. The incident could have created a vaccine-hesitancy crisis. But, incredibly, the American public readily accepted the medical establishment’s explanation for the failure, and its pledges to right the situation. The nation’s trust in medical progress and in Dr. Salk was so resolute that, when it was announced that a new, safe polio vaccine was available, parents pushed their children back to the head of the line. It’s hard to imagine such an outcome today.
This is a very good and bracing essay from David Roth for Defector about a certain type of knee-jerk libertarian response to the pandemic in the US.
In place of any actually ennobling liberty or more fundamental freedom, contemporary American life mostly offers choices. But since most of these are not really choices at all in any meaningful way, it might be more accurate to say that we’re offered selection. The choice between paying for health insurance and running up six figures of non-dischargeable debt because you got sick, for instance, is honestly less a choice than a hostage situation. But because the second outcome is still extremely possible even if you choose to pay for health insurance, it’s more correct to say that the choice is already made, and that the decision is more about choosing from an array of variously insufficient and predatory options the one whose name or price or risk you like most. Sometimes there isn’t even that, and the choice is a binary one between something and nothing. None of this is really what anyone would choose, but these ugly individuated choices are what we get.
And then:
The broader complacent and unreasoned acceptance that props up our otherwise untenable status quo is shot through all these facile “it’s a private matter and a personal choice” formulations; if you have accepted that mostly useless choices between dreary outcomes are all you could ever get as a citizen in the wealthiest and most powerful country on earth, then you have also accepted that these choices are actually very important, and that making them is the thing makes you free. None of these personal choices actually make anything better for the person making them. In the case of the vaccine, those choices have devastating downstream impacts for all the people who glance off the choice-maker as they carve their personal hero’s journeys through the world. None of this matters as much as the idea that the choice is theirs to make.
The NY Times has a profile of Dr. Katalin Kariko, who struggled for decades against a system unwilling to consider and fund her ideas about how messenger RNA could be used to instruct cells inside human bodies to “make their own medicines”. Her work has culminated in two highly effective vaccines for Covid-19 and is being extended to produce possible vaccines for HIV, the flu, tuberculosis, and malaria.
Now Katalin Kariko, 66, known to colleagues as Kati, has emerged as one of the heroes of Covid-19 vaccine development. Her work, with her close collaborator, Dr. Drew Weissman of the University of Pennsylvania, laid the foundation for the stunningly successful vaccines made by Pfizer-BioNTech and Moderna.
For her entire career, Dr. Kariko has focused on messenger RNA, or mRNA — the genetic script that carries DNA instructions to each cell’s protein-making machinery. She was convinced mRNA could be used to instruct cells to make their own medicines, including vaccines.
Stat also wrote a piece about Kariko and the development of the mRNA vaccines. It seems like Kariko will be strongly considered for a Nobel Prize in Chemistry for her achievements. The Covid vaccines will save hundreds of thousands of lives alone, and if mRNA can indeed be harnessed to protect against HIV and malaria, the effect on the world will be immense. Give Kariko all the prizes and whatever she wants to be happy in life — she’s earned it and more.
But mRNA’s story likely will not end with COVID-19: Its potential stretches far beyond this pandemic. This year, a team at Yale patented a similar RNA-based technology to vaccinate against malaria, perhaps the world’s most devastating disease. Because mRNA is so easy to edit, Pfizer says that it is planning to use it against seasonal flu, which mutates constantly and kills hundreds of thousands of people around the world every year. The company that partnered with Pfizer last year, BioNTech, is developing individualized therapies that would create on-demand proteins associated with specific tumors to teach the body to fight off advanced cancer. In mouse trials, synthetic-mRNA therapies have been shown to slow and reverse the effects of multiple sclerosis. “I’m fully convinced now even more than before that mRNA can be broadly transformational,” Özlem Türeci, BioNTech’s chief medical officer, told me. “In principle, everything you can do with protein can be substituted by mRNA.”
Related to my post from last month about what a 95% or 66% efficacy rate of a vaccine even means, Vox made a clear and concise video about why comparing vaccine efficacy rates is difficult — trials were done in different countries with different variants under different conditions with different levels of disease — and why protection against severe illness, hospitalization and death is a better way to compare and evaluate these vaccines. As this chart from Dr. Eric Topol shows, all of the major vaccines show strong protection against severe illness.
I thought this interview with Dr. Ashish K. Jha, dean of the Brown University School of Public Health, was really good and useful in terms of calibrating expectations with regard to the “end” of the pandemic, vaccines, and variants. On the guidance that vaccinated people should be getting:
I think it is essential that we give guidance to people. And I think we should give guidance to people on what they can do safely once they are vaccinated. People say, “Can your behavior change?” My answer is: absolutely! That’s a major motivation for getting vaccinated. First of all, what’s very clear to me is vaccinated people hanging out with other vaccinated people is pretty darn close to normal. You don’t have to wear a mask. You can share a meal. The chance that a fully vaccinated person will transmit the virus to another fully vaccinated person who then will get sick and die … I mean, sure, people get struck by lightning, too. But you don’t make policy based on that. And we need to remind people that there is a huge benefit to getting vaccinated, which is that you are safe enough to do the things you love with other vaccinated people.
After getting his second dose of the Covid-19 vaccine at a clinic at Berkshire Community College, Yo-Yo Ma got out his cello and performed a 15-minute impromptu concert for the others folks at the clinic.
When Ma had first visited the clinic for his first shot, he did so quietly, taking in the surroundings, staff said. But brought his cello when he returned for the second shot.
Staff described how a hush fell across the clinic as Ma began to play. “It was so weird how peaceful the whole building became, just having a little bit of music in the background,” said Leslie Drager, the lead clinical manager for the vaccination site, according to the Washington Post.
Why is it weird? Music is amazing. I know you could never get such a “frivolous” spending measure through an American deliberative body these days, but how awesome would it be for the government to commission out-of-work musicians to play at vaccination clinics? Ok maybe you couldn’t have anyone sing and the brass & woodwinds would probably have to sit this one out, but you could have strings, guitars, percussion, pianos, DJs, etc. there to play some relaxing, uplifting, or energetic music, according to local custom & culture. Bring back the WPA!
According to a study conducted by the Pew Research Center, among those people who said they probably or definitely won’t get a Covid-19 vaccine, the top two reasons given were “concern about side effects” and “the vaccines were developed and tested too quickly”. For our purposes here, I’m going to ignore the first concern — the data is pretty conclusive that, on average, the vaccine side effects are minimal when compared to the effects of actually contracting Covid-19 — and focus on the quick development timeline. If you’re among those who are apprehensive about the unprecedented speed at which the world’s governments and scientific community mobilized to create several effective Covid-19 vaccines, I hope the following will help you make a good decision.
In reading a bunch of different resources (linked below throughout), I identified six main reasons why the Covid-19 vaccines were developed so quickly compared to past efforts.
1. The need was urgent. Covid-19 changed the entire world in a very short span of time and it was evident in the absence of an effective vaccine, tens of millions more people would unnecessarily die and/or suffer and the rest of us would be living in fear of disease and death. This urgency drove several of the other factors here: the availability of funding, resources, and collaboration.
2. Funding & focus. Companies and governments threw billions and billions of dollars at this. Companies, research centers, and scientists dropped other stuff they were working on to study SARS-CoV-2 and Covid-19. Governments prioritized regulatory approval for trials, etc. From a thread by Dr. Kat Arney:
Relatively few in the scientific, pharma & policy worlds care about vaccines compared w/ drugs. Most vaccine programmes are underfunded as they’re perceived as not profitable, only relevant to LMICs, & have few research groups/companies working on them. Getting funding & research capacity for vax usually takes months/years. COVID-19 vaccine was a massive global research effort w/ $millions for multiple groups/projects in weeks. Years of funding cycles & lab research happened in months, huge amount of time saved.
We proceeded at risk. So people say, what do you mean by “at risk”? Are you risking safety? Are you risking scientific integrity? No, it’s a financial risk. In other words, you invest in things that cost a lot of money before you even have an answer to whether the prior step worked.
And a classic example is the production of large scale amounts of clinical lots, which have been produced and are being produced before you even know that your vaccine works, so that you have hundreds of millions of doses ready to go. If the vaccine works, you’ve saved many months. If the vaccine doesn’t, you lost a lot of money, to the tune of hundreds of millions if not billions of dollars. But it was felt it was worth that investment and that risk financially in order to save time.
3. Availability of volunteers & high incidence of disease. In order to statistically show the vaccine works, you need people to test it on and you need enough people in the studies to get sick. Kat Arney again:
To show vax effectiveness, you need a high number of people with the disease in the population — big problem with the Ebola vax is that it took so long to develop the outbreak was over & the couldn’t get enough numbers to conclusively show it worked
We’re in a global pandemic — the vaccine is being tested in places with very high community prevalence, so trials can hit pre-determined statistical milestones very quickly. Huge amount of time saved.
Hundreds of thousands of people around the world volunteered to test these vaccines — without them, we’d be months and years away from a safe, tested vaccine.
4. International & corporate collaboration. Countries and companies shared research, data, and resources because the primary goal was to develop effective vaccines and save lives, not make a profit. For instance, Chinese researchers posted the genome for SARS-CoV-2 on January 11, 2020, allowing the effort to develop a vaccine to begin.
5. We knew a lot about coronaviruses from previous work. This wasn’t an effort that started from scratch. From Bloomberg:
The Pfizer-BioNTech and Moderna vaccines may seem brand new, but they are the culmination of more than a decade of work that started during the SARS and MERS outbreaks. Vaccines were even developed against MERS but were never needed. Nevertheless, scientists learned a huge amount from working with that virus, which is from the same family as the one that causes Covid-19.
Really, most of the vaccine platform development work is already done. You just have to do the remaining part, which is adding the right viral antigens to the already-proven platform and making sure it’s safe and effective in humans. Even in just the last five to 10 years, we’ve made big leaps in developing new kinds of vaccine platforms like those being tested for SARS-CoV-2.
6. Scientific and technological capability. Ok, we know a lot about coronaviruses but humanity’s general scientific and technological abilities have never been stronger or more powerful. Again from Bloomberg:
Remember also that technology has evolved rapidly — for example, we’re now about able to sequence the genomes of every mutant version of the virus in less than a day. That helps in speeding up vaccine development.
However we have collectively now shown that with money no object, some clever and highly motivated people, an unlimited pool of altruistic volunteers, and sensible regulators that we can do amazing things.
Conditions may be ripe for a better summer, however. Vaccine supplies should be flowing more freely, at least in the U.S.; the Biden administration now expects enough vaccine doses in hand for all adults by the end of May. With most vulnerable populations protected, there should be fewer hospitalizations and deaths. And with warmer weather, people can return to outdoor life.
Widespread transmission of the virus could be replaced by more sporadic and localized outbreaks. There’s also growing evidence that vaccines don’t just protect people from getting symptomatic Covid-19, but can reduce transmission.
And in the long-term, well, SARS-CoV-2 will be around for years and even decades to come:
Years from now, SARS-CoV-2 could join the ranks of OC43, 229E, NL63, and HKU1 — the four endemic, seasonal coronaviruses that cause a chunk of common colds every year. Essentially, our immune systems — primed by vaccines, boosters, and previous encounters with the coronavirus — will be ready to knock back SARS-2 when we see it again, potentially blocking an infection or leading to one that causes no symptoms or maybe just the sniffles.
It’s good to read stuff like this — it provides a basis to use when calibrating your optimism or pessimism for future activities and desires.
In the 70s, the US government enlisted the droids of Star Wars to encourage parents to immunize their kids against childhood diseases like whooping cough and measles.
American parents weren’t getting their kids vaccinated. Measles, polio and whooping cough were taking a toll on young lives. Just as it is today, the message was important but the spot itself was horrible — a sludgy, if informative script. We shot it in a faux sci-fi control room. Most memorable was the way R2 appeared to pay no attention to the laws of physics.
After the Biden administration announced they will have enough Covid-19 vaccine supply to cover every single adult in the country by the end of May, I got to wondering about what they were going to do with the tens & hundreds of millions of surplus doses already procured for the remainder of the year. “Oh,” I thought, naively, “We’ll be able to distribute it to countries that can’t easily procure or manufacture vaccines of their own!” And I’m sure some of that will happen, if only for PR purposes. But it’s perhaps more likely that America will practice vaccine diplomacy and use the stockpile to reestablish its global leadership.
The United States has backed away from the world. This isn’t a Clinton thing or a W Bush thing or an Obama thing or a Trump thing or a Biden thing, but instead a United States thing. The American people lost interest in playing a constructive role in the world three decades ago, and America’s political leadership has molded itself around that fact. Trump may have been instinctually and publicly hostile to all things international, but Biden is only different in tone. Biden’s Buy-American program is actually more anti-globalization than Trump’s America-First rhetoric as it is an express violation of most of America’s international trade commitments. TeamBiden says it wants to reestablish America’s global leadership…but it plans to do so without any troops or money. Sorry, but that’s not how it works.
Which makes the possibilities for vaccine diplomacy wildly interesting. The United States has no responsibility to provide COVID vaccines to the world. It can — it will — distribute them, but it will want something in return.
Even if you disagree with some of the analysis here, it will be interesting to watch where America’s stockpile ends up. Given Biden’s rhetoric of “listening to the science” when it comes to the pandemic, I hope that at least some of that supply goes to places that need it most to make certain the pandemic doesn’t sputter on for years, generating potentially dangerous new variants, even if it’s politically disadvantageous.
Like three dozen other countries, the United States contracted with multiple vaccine companies for several times the number of doses needed to cover its population. No one knew at the time which, if any, of the candidate vaccines would work or when they might prove safe and effective. But by now, most of the prepurchased vaccines appear to offer solid protection — which means many countries will receive far more vaccine than they need. The excess doses the United States alone may have by July would vaccinate at least 200 million people.
A chart in the article notes that the US has procured enough vaccine to cover almost 1.5 billion people after fully vaccinating its entire population.
In popular press and social media, there’s been a misunderstanding of what is actually meant when scientists say that the Pfizer and Moderna Covid-19 vaccines have an efficacy of 94-95%. It does not mean that 95% of vaccinated people are protected from infection — these vaccines are better than that. Dr. Piero Olliaro explains in a letter to The Lancet:
The mRNA-based Pfizer and Moderna vaccines were shown to have 94-95% efficacy in preventing symptomatic COVID-19, calculated as 100 x (1 minus the attack rate with vaccine divided by the attack rate with placebo). It means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0.05% of vaccinated people would get diseased.
Another way to put it: you’re 20 times less likely to get Covid-19 with a vaccine than without. (And again, data indicates these are safe vaccines.) Olliaro explains with some simple math:
If we vaccinated a population of 100,000 and protected 95% of them, that would leave 5000 individuals diseased over 3 months, which is almost the current overall COVID-19 case rate in the UK. Rather, a 95% vaccine efficacy means that instead of 1000 COVID-19 cases in a population of 100,000 without vaccine (from the placebo arm of the abovementioned trials, approximately 1% would be ill with COVID-19 and 99% would not) we would expect 50 cases (99.95% of the population is disease-free, at least for 3 months).
And of course if you vaccinate widely, it becomes a compounding situation because the virus just runs out of people to infect.
In an opinion piece for the NY Times, Zeynep Tufekci and epidemiologist Michael Mina are urging for new trials of the Moderna and Pfizer/BioNTech Covid-19 vaccines to begin immediately to see how effective a single dose might be in preventing new infections. If the trials do indicate that a single dose works, that would effectively double the number of people we could vaccinate within a certain time period, saving countless lives in the US and worldwide.
Both vaccines are supposed to be administered in two doses, a prime and a booster, 21 days apart for Pfizer and 28 days for Moderna. However, in data provided to the F.D.A., there are clues for a tantalizing possibility: that even a single dose may provide significant levels of protection against the disease.
If that’s shown to be the case, this would be a game changer, allowing us to vaccinate up to twice the number of people and greatly alleviating the suffering not just in the United States, but also in countries where vaccine shortages may take years to resolve.
But to get there — to test this possibility — we must act fast and must quickly acquire more data.
For both vaccines, the sharp drop in disease in the vaccinated group started about 10 to 14 days after the first dose, before receiving the second. Moderna reported the initial dose to be 92.1 percent efficacious in preventing Covid-19 starting two weeks after the initial shot, when the immune system effects from the vaccine kick in, before the second injection on the 28th day
That raises the question of whether we should already be administrating only a single dose. But while the data is suggestive, it is also limited; important questions remain, and approval would require high standards and more trials.
The piece concludes: “The possibility of adding hundreds of millions to those who can be vaccinated immediately in the coming year is not something to be dismissed.”
The vaccine structure is highly idealized, with spike mRNA in magenta, lipids in blue, and PEG-lipid in green. The background is blood serum or lymph.
Both the Pfizer/BioNTech and the Moderna Covid-19 vaccines are based on mRNA — you can brush up on how they work at Stat or the CDC.
mRNA vaccines are a new type of vaccine to protect against infectious diseases. To trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, they teach our cells how to make a protein — or even just a piece of a protein — that triggers an immune response inside our bodies. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies.
With the first approved Covid-19 vaccines set to roll out in the US soon, some of the focus has shifted to how the vaccine will be distributed and its equitable allocation. Part of the distribution logistics puzzle is making sure there are enough glass vials to hold and transport the vaccine around the nation to those waiting to be vaccinated. For the New Yorker, Christopher Payne took some photos of two Corning factories that are manufacturing vials as fast as they can.
But back in the early 19th century, for a colonial empire dealing with overseas smallpox epidemics, glass vials were not an option. Smallpox vaccination at that time was most reliably accomplished by transferring material from cowpox blisters on one person (or cow) to another person. The freshly inoculated person got a little sick but later proved to be immune to the much deadlier smallpox. So when Spain’s Royal Philanthropic Vaccine Expedition set sail in 1803 to inoculate the inhabitants of their overseas colonies for smallpox, they used the bodies of human beings to transport the vaccine. To be more specific, they used “twenty-two orphan boys, ages three to nine”.1
And so it was that, “in the era before refrigeration, freeze-dried vaccines, and jet aircraft,” writes medical historian John Bowers, “the successful circumnavigation of the globe with the vaccine…rested on a single medium — little boys.” During the long crossing, approximately twenty-two orphans who had not previously contracted smallpox or cowpox were “vaccinated in pairs every ninth or tenth day,” via arm-to-arm inoculation (taking lymph from an unbroken pustule on a recently vaccinated boy and introducing it under the skin of another). This created a vaccine chain — the vaccine remained active and viable for the entire journey.
The three-year expedition was success and an early & effective example of philanthropic healthcare, but you also have to note here that the reason the Americas were ravaged by smallpox was because Spain brought it there in the first place.
Given the era, it’s likely that no one asked the orphans whether they wanted to participate — and some seemed too young to consent anyway. They’d been abandoned by their parents, were living in institutions, and had no power to resist. But the Spanish king, Carlos IV, decided to make them a few promises: They would be stuffed with food on the voyage over to make sure they looked hearty and hale upon arrival. After all, no one would want lymph from the arm of a sickly child. Appearance mattered. And they’d get a free education in the colonies, plus the chance at a new life there with an adoptive family. It was a far better shake than they’d get in Spain.
The article describes these children as “orphaned” but I wonder if it’s not more accurate to describe them as “enslaved”. Surely these kids didn’t have a real choice in whether they wanted to be infected with cowpox and carried overseas in a cramped ship.↩
In an incredible effort, science has provided the world with what looks like an incredibly effective vaccine for Covid-19. For Stat, Helen Braswell writes about the challenges of turning that vaccine into vaccinations. In the US, despite heroic work from individuals and individual groups, our public health system has proved unequal to the challenge of addressing the pandemic, and we’re now turning, in part, to that system to distribute and administer the vaccines, as well as to educate the public and drum up support for vaccination. The people that we’re counting on are public officials and healthcare workers worn out from what is essentially one 9-month-long wave of illness, hospitalizations, and death across the country. Misinformation and skepticism of science and government has sowed “justified distrust” about vaccines in many people:
Concern about the vaccines, however, cuts across ethnic and socioeconomic groups. President Trump’s overt efforts to pressure the FDA to issue EUAs before the Nov. 3 election — before the vaccine trials were finished — has deepened the sense of unease. The CDC’s early pandemic testing fiasco, coupled with its sidelining by the Trump administration, has eroded its standing as a trusted source of information.
Alison Buttenheim, an associate professor of nursing and health policy at the University of Pennsylvania, refers to the current situation as a perfect storm of “justified distrust.”
“People who don’t think twice about vaccinating their kids totally on time, who get their flu shot every year, are in the sort of, ‘Hmmm. Might wait six months on this one,’” Buttenheim, who works on vaccine acceptance, told STAT. “I’ve heard people say, ‘I’ll get the European one,’” she said, adding other people have said they would get vaccinated after Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, gets vaccinated.
And it’s not just the general public. A recent survey of 2,000 doctors and nurses in New Jersey found that 60% of doctors planned to take a Covid vaccine, but only 40% of nurses intended to, Health Commissioner Judith Persichilli said in a recent “60 Minutes” segment about Operation Warp Speed.
Fauci, along with other respected public health officials and workers, should get vaccinated live on CNN. Stream it on YouTube and Twitch. It won’t convert the anti-vax, anti-mask, QAnon wingnuts (nothing will) but if you can at least get healthcare workers and at-risk folks on board, it would be time well spent.
But that’s only one small piece of the puzzle. Braswell’s piece is long and comprehensive look at the challenges regarding the Covid-19 vaccines and is worth reading all the way through.
Now that the preliminary results of various Covid-19 vaccine trials are coming out (and looking promising), attention is turning to the eventual distribution of the vaccines. The logistics of getting the doses out to hospitals, clinics, and doctor’s offices is one concern but so is the question of who should get vaccinated first. Supplies of the vaccines will be limited at first, so we’ll need to decide as a society what distribution method is most fair and is of the most benefit to the greatest number of people.
In addition several recommendations — including that the vaccine be distributed to everyone free of charge — a central feature of the report is a four-phase system of vaccine distribution, summarized in this graphic:
I’d like to stress that this graphic does not show all groups of people included in each phase — please consult the text of the report for that before you go sharing that graphic on social media without context. For example, here’s the full description for “high-risk health workers” in Phase 1a:
This group includes frontline health care workers (who are in hospitals, nursing homes, or providing home care) who either (1) work in situations where the risk of SARS-CoV-2 transmission is higher, or (2) are at an elevated risk of transmitting the infection to patients at higher risk of mortality and severe morbidity. These individuals — who are themselves unable to avoid exposure to the virus — play a critical role in ensuring that the health system can care for COVID-19 patients.
These groups include not only clinicians (e.g., nurses, physicians, respiratory technicians, dentists and hygienists) but also other workers in health care settings who meet the Phase 1a risk criteria (e.g., nursing assistants, environmental services staff, assisted living facility staff, long-term care facility staff, group home staff, and home caregivers). The health care settings employing these workers who are at increased risk of exposure to the virus may also include ambulatory and urgent care clinics; dialysis centers; blood, organ, and tissue donation facilities; and other non-hospital health care facilities. Finally, there are community and family settings where care for infected patients occurs. Not all the workers in these settings are paid for their labor, but, while they are caring for infected people, they all need to be protected from the virus.
Situations associated with higher risk of transmission include caring for COVID-19 patients, cleaning areas where COVID-19 patients are admitted, treated, and housed, and performing procedures with higher risk of aerosolization such as endotracheal intubation, bronchoscopy, suctioning, turning the patient to the prone position, disconnecting the patient from the ventilator, invasive dental procedures and exams, invasive specimen collection, and cardiopulmonary resuscitation. In addition, there are other frontline health care workers who, if they have uncontrolled exposure to the patients or the public in the course of their work, should be in this initial phase. This group includes those individuals distributing or administering the vaccine — especially in areas of higher community transmission — such as pharmacists, plasma and blood donation workers, public health nurses, and other public health and emergency preparedness workers. The committee also includes morticians, funeral home workers, and other death care professionals involved in handling bodies as part of this high-risk group.
The report declines to list specific industries which would be covered in Phase 2’s “critical workers in high-risk settings” but generally says:
The industries in which these critical workers are employed are essential to keeping society and the economy functioning. Since the beginning of the pandemic, millions of people have been going to work and risking exposure to the virus to ensure that markets have food; drug stores have pharmaceutical products; public safety and order are maintained; mail and packages are delivered; and buses, trains, and planes are operating.
Note also the text at the bottom of the graphic: they recommend that within each phase, priority be given to geographic areas where folks are more socially vulnerable in situations like these (e.g. as represented in the CDC’s Social Vulnerability Index).
In developing this phased approach, the committee focused on those who are at the most risk of exposure, severe illness or death, and passing along the virus to others as well as critical workers:
Risk of acquiring infection: Individuals have higher priority to the extent that they have a greater probability of being in settings where SARS-CoV-2 is circulating and of being exposed to a sufficient dose of the virus.
Risk of severe morbidity and mortality: Individuals have higher priority to the extent that they have a greater probability of severe disease or death if they acquire infection.
Risk of negative societal impact: Individuals have higher priority to the extent that societal function and other individuals’ lives and livelihood depend on them directly and would be imperiled if they fell ill.
Risk of transmitting infection to others: Individuals have higher priority to the extent that there is a higher probability of their transmitting the infection to others.
You should read (or at least skim) the full report for more information about the plan and the rationale behind it.
On a personal parting note, as someone who is squarely in the 5-15% of Americans covered in Phase 4 — more specifically: as a 40-something straight white man who non-essentially works from home, isn’t low-income, doesn’t socialize widely even under normal circumstances, and should probably be the very last person on this whole Earth scheduled to be vaccinated under an equitable framework — I am content to wait my turn should the US adopt this framework or something like it.1 Distributing vaccines to those who need them most is absolutely the right thing to do, both ethically and from the standpoint of getting society “back to normal” as quickly as possible and with as little additional death and suffering as possible.
Being that equity often isn’t America’s thing, especially during the pandemic, I could see this going either way. And even if this framework is adopted, those who can afford it will undoubtably be able to procure themselves a dose right alongside those medical workers in Phase 1a.↩
The preliminary results on the AstraZeneca vaccine were based on a total of 131 Covid-19 cases in a study involving 11,363 participants. The findings were perplexing. Two full doses of the vaccine appeared to be only 62% effective at preventing disease, while a half dose, followed by a full dose, was about 90% effective. That latter analysis was conducted on a small subset of the study participants, only 2,741.
Hopefully more study will be done on that dosage question. From the AP:
“The report that an initial half-dose is better than a full dose seems counterintuitive for those of us thinking of vaccines as normal drugs: With drugs, we expect that higher doses have bigger effects, and more side-effects,” he said. “But the immune system does not work like that.”
The seemingly lower efficacy comes with some perhaps significant benefits: this vaccine is cheaper to produce and doesn’t require any special refrigeration.
The vaccine can be transported under “normal refrigerated conditions” of 2 to 8 degrees Celsius (36 to 46 degrees Fahrenheit), AstraZeneca said. By comparison, Pfizer plans to distribute its vaccine using specially designed “thermal shippers” that use dry ice to maintain temperatures of minus-70 degrees Celsius (minus-94 degrees Fahrenheit).
The Pfizer and Moderna vaccines were pretty similar in many respects and this one seems quite different. These results were just released a few hours ago, so it will be interesting to follow the debate and expert commentary on this. Stay tuned…
Update: This is amazing: the seemingly more effective 1/2 dose + full dose regimen was a mistake.
Around the time when Astra was initiating its partnership with Oxford at the end of April, university researchers were administering doses to trial participants in Britain.
They soon noticed expected side effects such as fatigue, headaches or arm aches were milder than expected, he said.
“So we went back and checked … and we found out that they had underpredicted the dose of the vaccine by half,” said Pangalos.
A far smaller number of participants was given the initial half-dose, so more research will need to be done to determine if this mistake will be added to the long list of scientific discoveries made because of errors. There’s a good piece in Nature that talks about what we know and don’t know about the vaccine results so far along with some informed speculation.
But, if the differences are bona fide, researchers are eager to understand why. “I don’t think it’s an anomaly,” says Katie Ewer, an immunologist at Oxford’s Jenner Institute who is working on the vaccine. “I’m keen to get into the lab and start thinking about how we address that question.” She has two leading theories for why a lower first dose might have led to better protection against COVID. It’s possible that lower doses of vaccine do a better job at stimulating the subset of immune cells called T cells that support the production of antibodies, she says.
Another potential explanation is the immune system’s response against the chimpanzee virus. The vaccine triggers an immune response not only to the SARS-CoV-2 spike protein, but also to components of the viral vector. It’s possible that the full first dose blunted this reaction, says Ewer. She plans to look at antibody responses against the chimpanzee virus to help address this question.
Update:A short thread by Dr. Natalie Dean, which leads with “AstraZeneca/Oxford get a poor grade for transparency and rigor when it comes to the vaccine trial results they have reported”.
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