Vaccines Are the Safest Medical Procedure We Have. Make Your Wager Wisely.
Frontline infectious disease physician Amesh Adalja received his COVID-19 vaccine on December 18th, 2020 in Butler, PA.
In the late 1650's the French polymath and renowned scientist Blaise Pascal, having undergone a religious experience that transformed him into something of a zealot, suggested the following logical strategy regarding belief in God: If there is a God, then believing in him will ensure you an eternity of bliss, while not believing in him could earn you an eternal sentence to misery.
On the other hand, if there is no God, believing in him anyway will cost you very little, and not believing in him will mean nothing in the non-existent after life. Therefore, the only sensible bet is to believe in God. This has come to be known as Pascal's wager.
It has a surprising number of applications beyond concerns for a comfortable afterlife. There are many things for which the value of believing something or not can be seen as a cost vs. likely benefit wager, often without regard to the actual truth of the matter. Since science does not profess to have a final truth, and in many areas freely admits its incomplete knowledge, Pascal's wager can provide a useful method of deciding between two alternatives.
For example, it seems that a significant percentage of the population is suspicious of science, or so we are told. We often hear that some large number, approaching or exceeding half of Americans, do not believe in evolution. This seems remarkable on the face of it because there is no viable scientific opposition to evolution and it is widely accepted by biologists and other life-scientists as being fundamental to understanding biology – from genetics to medicine.
What we are not often told is that most of those who answer negatively about believing in evolution nonetheless understand evolution – or at least the basics of it. They are not stupid, ignorant or uninformed. They have simply made a Pascalian wager. What benefit we might ask is derived from believing in evolution rather than a divine creation? Unless you are a professional biologist it is hard to see how this would affect your everyday life. On the other hand professing a belief in Darwinian evolution over the biblical narrative will likely ostracize you from family, friends, co-workers, your church community - in short most of your social infrastructure. Place your bets.
Can we apply any of this to decisions over the current controversy surrounding vaccination – and in particular the newly arrived Covid-19 vaccine?
While it is true that for entirely economic reasons, this is the first vaccine to be produced in this way, the method is not really new and the science that makes it possible has been developing over the last 40 years.
Common Concerns
There are certainly reasons to be concerned about being vaccinated and it would be a gross over-simplification to consider anyone who expresses reticence about taking a vaccine, this new vaccine in particular, as being just plain dumb or scientifically illiterate or gullible. They need be none of these things and still may be suspicious of the vaccine.
One issue is safety. The vaccine, any vaccine, is designed to mobilize your immune system, essentially to fool it into believing that there is an invading virus present and to mount an immune response. That way it will be ready when the real invasion comes, if it comes. This seems pretty sensible and preferable to going to war with an opponent you know nothing about. But still, it is fooling around with Mother Nature and some people are uneasy about that. Although it must be pointed out that the virus is not at all shy about fooling around with your immune system and many other parts of you, so letting it have its way is not good policy either.
What about a vaccine made of genes? This vaccine is being produced by what is being touted as a new method using RNA – genes. While it is true that for entirely economic reasons, this is the first vaccine to be produced in this way, the method is not really new and the science that makes it possible has been developing over the last 40 years. So it's not so radical as the press makes it seem.
But it is true that this method uses RNA, genetic material, to make the vaccine. We hear a lot about gene modification and the potential dangers associated with it. Why then am I going to allow RNA, genes, to be injected into me? The first thing to realize is that this is exactly what the virus does – so whether you get a vaccine or an infection, you are getting genes injected into you. The virus RNA encodes around 12 functional genes (by comparison humans and other mammals have around 25,000 genes). The virus only contains the genes to make a new virus – it does not have any of the capabilities of a normal cell to actually turn those genes into the proteins that make up the complete virus. It hijacks your cells to do this – and that's how it sickens you, by forcing your cells to make new viruses instead of what they should be doing.
Now the new vaccines have taken just one of those genes – the one that directs the production of the now infamous spike protein that appears on the surface of a normal virus – and injects just that one gene into your muscle cells, which then make that one single protein. Your immune system comes along and sees that weird protein and makes antibodies to it. These same antibodies will now recognize the spike protein on the surface of any viral particles that invade your body. We have effectively turned the virus into its own enemy.
The viral RNA that you are getting will decompose over a few days because RNA is not a stable molecule (that, by the way, is why the vaccine needs to be kept frozen) and it will no longer exist in your body. It could only become a permanent part of your genome if it were a DNA molecule instead of an RNA molecule – and even the chances of that happening would be chemically remote. So regardless of how it sounds, this may actually be the safest sort of vaccine to use. In the future it is likely that all vaccines will be made this way.
Then, of course, there is the issue of who is running this whole vaccine program – the government and the pharmaceutical industry. These are the guys who brought you opioid addiction, death by Vioxx, soaring drug prices, the worst health care system in the developed world, regulations where you don't need them and none where you do – am I really going to trust this cast of so-called "inept villains," as some believe, to dictate my personal health choices? Do we know for sure that the claims of efficacy are real or just made up to sell some worthless procedure? It would not be the first time. (I would not, on the other hand, worry about Bill Gates having a chip inserted into you along with the vaccine – if you use any social media, navigational tools, or purchase anything online, then Bill Gates already knows more about you than he will get from any injectable chip. So that train has left the station.)
The main upside to vaccines is that because they use your already existing defense system, they are surprisingly safe.
The Vaccine Wager
All this and a few lesser issues are worth a pause for sure. But we must also look on the positive side of the ledger. Why trust science? Modern medicine and the science behind it has eliminated or dramatically lessened such scourges as smallpox, polio, cholera, chicken pox, measles, rabies and dozens of other killer pathogens that had previously wiped out enormous numbers of people, in some cases significant parts of entire generations. Don't we depend on science for much of the comfort and safety of our everyday lives? Isn't science the way we heat our homes, drive to work, fly around the world, have dependable food? Yes, there is the bomb – but there is also anesthesia.
When it comes to viruses, the only tool we have to fight them is vaccination. The only tool. Antibiotics are for bacteria, a completely different sort of creature. Sanitation beyond personal hand washing is ineffective. Vaccines trick the immune system into recognizing the virus earlier than it would otherwise and protect normal cells from invasion by the virus. Tricking the immune system is understandably problematic for people who believe that their body knows best if it's just kept healthy. This virus, as we have seen from the array of infected people that includes apparently healthy folks, unfortunately does not subscribe to that belief.
By a similar sort of reasoning, some people make the plausible error of calculating that the vaccine is 95% effective but the survival rate is 99%, so why not just let my natural resistance take care of this? Indeed, that might not be unreasonable thinking if we were talking about the common cold, but this virus has shown itself to be a tricky character and we are not yet able to predict who gets a serious case and who a mild one. With those sorts of stakes, you shouldn't wager on either of those numbers because they have nothing to do with you as an individual. Like flipping a coin, there is only a 1% chance of it coming up heads 6 times in a row. But if it has come up heads 5 times in a row the probability of it coming up heads on the next flip is … still 50/50.
An even larger unknown is whether there may be long-term effects associated with SARS-Cov-2, as is the case for many viruses. The 1918 influenza virus has been linked to a subsequent 2-3 fold increase in Parkinson's disease by a mechanism we still don't understand. The virus that gives children chicken pox will hide out in a person's body for 40 years or more and then emerge as a painful, sometimes debilitating, case of shingles. The 99% survivability rate of this virus is meaningless if 20 years from now it causes some devastating pulmonary or brain disease.
The main upside to vaccines is that because they use your already existing defense system, they are surprisingly safe. Safer than antibiotics which have numerous side effects because they are not part of our normal make up and are cell killers – mostly bacterial cells, but they are not so perfectly targeted that they don't leave some collateral damage in their wake. All drugs and treatments have side effects, but vaccines in general have the fewest. This vaccine in particular has undergone many more than the usual safety measures - multiple independent review boards, massive press and public attention, governmental and non-governmental oversight, the most diverse trial cohorts ever assembled. Nothing here was rushed, no shortcuts were taken.
So here's the vaccine wager. Vaccines are the safest medical procedure we have. They are also among the most effective, but that's curiously not important for the bet. My claim about their safety is because vaccines are in a special class of medical tools. They are the only medical procedure or drug that is given to healthy people. Every other treatment we use medically is aimed at some existing pathology - from a cold to cancer.
Vaccines therefore have to reach a higher standard of safety than any other medical treatment. You can't take healthy people and make them sick. Vaccines have fewer side effects than virtually any other drug you wouldn't even think twice about taking – aspirin, for instance, which can cause internal bleeding, gastric ulcers, stroke. But since you are sick when you take those drugs you are willing to make the bet that the benefits will outweigh the possible side effects.
With vaccines the wager is much simpler – it is indeed more like Pascal's original wager. It may or may not be highly effective (some vaccines are only 60% effective) but they are so safe that taking them poses little risk, whereas not taking them subjects you (and others) to considerable risk, i.e., getting the virus. Like believing or not in an afterlife, the smart money is with Pascal, who I think would have reasoned himself right to the head of the vaccination line.
Astronaut and Expedition 64 Flight Engineer Soichi Noguchi of the Japan Aerospace Exploration Agency displays Extra Dwarf Pak Choi plants growing aboard the International Space Station. The plants were grown for the Veggie study which is exploring space agriculture as a way to sustain astronauts on future missions to the Moon or Mars.
Astronauts at the International Space Station today depend on pre-packaged, freeze-dried food, plus some fresh produce thanks to regular resupply missions. This supply chain, however, will not be available on trips further out, such as the moon or Mars. So what are astronauts on long missions going to eat?
Going by the options available now, says Christel Paille, an engineer at the European Space Agency, a lunar expedition is likely to have only dehydrated foods. “So no more fresh product, and a limited amount of already hydrated product in cans.”
For the Mars mission, the situation is a bit more complex, she says. Prepackaged food could still constitute most of their food, “but combined with [on site] production of certain food products…to get them fresh.” A Mars mission isn’t right around the corner, but scientists are currently working on solutions for how to feed those astronauts. A number of boundary-pushing efforts are now underway.
The logistics of growing plants in space, of course, are very different from Earth. There is no gravity, sunlight, or atmosphere. High levels of ionizing radiation stunt plant growth. Plus, plants take up a lot of space, something that is, ironically, at a premium up there. These and special nutritional requirements of spacefarers have given scientists some specific and challenging problems.
To study fresh food production systems, NASA runs the Vegetable Production System (Veggie) on the ISS. Deployed in 2014, Veggie has been growing salad-type plants on “plant pillows” filled with growth media, including a special clay and controlled-release fertilizer, and a passive wicking watering system. They have had some success growing leafy greens and even flowers.
"Ideally, we would like a system which has zero waste and, therefore, needs zero input, zero additional resources."
A larger farming facility run by NASA on the ISS is the Advanced Plant Habitat to study how plants grow in space. This fully-automated, closed-loop system has an environmentally controlled growth chamber and is equipped with sensors that relay real-time information about temperature, oxygen content, and moisture levels back to the ground team at Kennedy Space Center in Florida. In December 2020, the ISS crew feasted on radishes grown in the APH.
“But salad doesn’t give you any calories,” says Erik Seedhouse, a researcher at the Applied Aviation Sciences Department at Embry-Riddle Aeronautical University in Florida. “It gives you some minerals, but it doesn’t give you a lot of carbohydrates.” Seedhouse also noted in his 2020 book Life Support Systems for Humans in Space: “Integrating the growing of plants into a life support system is a fiendishly difficult enterprise.” As a case point, he referred to the ESA’s Micro-Ecological Life Support System Alternative (MELiSSA) program that has been running since 1989 to integrate growing of plants in a closed life support system such as a spacecraft.
Paille, one of the scientists running MELiSSA, says that the system aims to recycle the metabolic waste produced by crew members back into the metabolic resources required by them: “The aim is…to come [up with] a closed, sustainable system which does not [need] any logistics resupply.” MELiSSA uses microorganisms to process human excretions in order to harvest carbon dioxide and nitrate to grow plants. “Ideally, we would like a system which has zero waste and, therefore, needs zero input, zero additional resources,” Paille adds.
Microorganisms play a big role as “fuel” in food production in extreme places, including in space. Last year, researchers discovered Methylobacterium strains on the ISS, including some never-seen-before species. Kasthuri Venkateswaran of NASA’s Jet Propulsion Laboratory, one of the researchers involved in the study, says, “[The] isolation of novel microbes that help to promote the plant growth under stressful conditions is very essential… Certain bacteria can decompose complex matter into a simple nutrient [that] the plants can absorb.” These microbes, which have already adapted to space conditions—such as the absence of gravity and increased radiation—boost various plant growth processes and help withstand the harsh physical environment.
MELiSSA, says Paille, has demonstrated that it is possible to grow plants in space. “This is important information because…we didn’t know whether the space environment was affecting the biological cycle of the plant…[and of] cyanobacteria.” With the scientific and engineering aspects of a closed, self-sustaining life support system becoming clearer, she says, the next stage is to find out if it works in space. They plan to run tests recycling human urine into useful components, including those that promote plant growth.
The MELiSSA pilot plant uses rats currently, and needs to be translated for human subjects for further studies. “Demonstrating the process and well-being of a rat in terms of providing water, sufficient oxygen, and recycling sufficient carbon dioxide, in a non-stressful manner, is one thing,” Paille says, “but then, having a human in the loop [means] you also need to integrate user interfaces from the operational point of view.”
Growing food in space comes with an additional caveat that underscores its high stakes. Barbara Demmig-Adams from the Department of Ecology and Evolutionary Biology at the University of Colorado Boulder explains, “There are conditions that actually will hurt your health more than just living here on earth. And so the need for nutritious food and micronutrients is even greater for an astronaut than for [you and] me.”
Demmig-Adams, who has worked on increasing the nutritional quality of plants for long-duration spaceflight missions, also adds that there is no need to reinvent the wheel. Her work has focused on duckweed, a rather unappealingly named aquatic plant. “It is 100 percent edible, grows very fast, it’s very small, and like some other floating aquatic plants, also produces a lot of protein,” she says. “And here on Earth, studies have shown that the amount of protein you get from the same area of these floating aquatic plants is 20 times higher compared to soybeans.”
Aquatic plants also tend to grow well in microgravity: “Plants that float on water, they don’t respond to gravity, they just hug the water film… They don’t need to know what’s up and what’s down.” On top of that, she adds, “They also produce higher concentrations of really important micronutrients, antioxidants that humans need, especially under space radiation.” In fact, duckweed, when subjected to high amounts of radiation, makes nutrients called carotenoids that are crucial for fighting radiation damage. “We’ve looked at dozens and dozens of plants, and the duckweed makes more of this radiation fighter…than anything I’ve seen before.”
Despite all the scientific advances and promising leads, no one really knows what the conditions so far out in space will be and what new challenges they will bring. As Paille says, “There are known unknowns and unknown unknowns.”
One definite “known” for astronauts is that growing their food is the ideal scenario for space travel in the long term since “[taking] all your food along with you, for best part of two years, that’s a lot of space and a lot of weight,” as Seedhouse says. That said, once they land on Mars, they’d have to think about what to eat all over again. “Then you probably want to start building a greenhouse and growing food there [as well],” he adds.
And that is a whole different challenge altogether.
The Science of Why Adjusting to Omicron Is So Tough
A brain expert weighs in on the cognitive biases that hold us back from adjusting to the new reality of Omicron.
We are sticking our heads into the sand of reality on Omicron, and the results may be catastrophic.
Omicron is over 4 times more infectious than Delta. The Pfizer two-shot vaccine offers only 33% protection from infection. A Pfizer booster vaccine does raises protection to about 75%, but wanes to around 30-40 percent 10 weeks after the booster.
The only silver lining is that Omicron appears to cause a milder illness than Delta. Yet the World Health Organization has warned about the “mildness” narrative.
That’s because the much faster disease transmission and vaccine escape undercut the less severe overall nature of Omicron. That’s why hospitals have a large probability of being overwhelmed, as the Center for Disease Control warned, in this major Omicron wave.
Yet despite this very serious threat, we see the lack of real action. The federal government tightened international travel guidelines and is promoting boosters. Certainly, it’s crucial to get as many people to get their booster – and initial vaccine doses – as soon as possible. But the government is not taking the steps that would be the real game-changers.
Pfizer’s anti-viral drug Paxlovid decreases the risk of hospitalization and death from COVID by 89%. Due to this effectiveness, the FDA approved Pfizer ending the trial early, because it would be unethical to withhold the drug from people in the control group. Yet the FDA chose not to hasten the approval process along with the emergence of Omicron in late November, only getting around to emergency authorization in late December once Omicron took over. That delay meant the lack of Paxlovid for the height of the Omicron wave, since it takes many weeks to ramp up production, resulting in an unknown number of unnecessary deaths.
We humans are prone to falling for dangerous judgment errors called cognitive biases.
Widely available at-home testing would enable people to test themselves quickly, so that those with mild symptoms can quarantine instead of infecting others. Yet the federal government did not make tests available to patients when Omicron emerged in late November. That’s despite the obviousness of the coming wave based on the precedent of South Africa, UK, and Denmark and despite the fact that the government made vaccines freely available. Its best effort was to mandate that insurance cover reimbursements for these kits, which is way too much of a barrier for most people. By the time Omicron took over, the federal government recognized its mistake and ordered 500 million tests to be made available in January. However, that’s far too late. And the FDA also played a harmful role here, with its excessive focus on accuracy going back to mid-2020, blocking the widespread availability of cheap at-home tests. By contrast, Europe has a much better supply of tests, due to its approval of quick and slightly less accurate tests.
Neither do we see meaningful leadership at the level of employers. Some are bringing out the tired old “delay the office reopening” play. For example, Google, Uber, and Ford, along with many others, have delayed the return to the office for several months. Those that already returned are calling for stricter pandemic measures, such as more masks and social distancing, but not changing their work arrangements or adding sufficient ventilation to address the spread of COVID.
Despite plenty of warnings from risk management and cognitive bias experts, leaders are repeating the same mistakes we fell into with Delta. And so are regular people. For example, surveys show that Omicron has had very little impact on the willingness of unvaccinated Americans to get a first vaccine dose, or of vaccinated Americans to get a booster. That’s despite Omicron having taken over from Delta in late December.
What explains this puzzling behavior on both the individual and society level? We humans are prone to falling for dangerous judgment errors called cognitive biases. Rooted in wishful thinking and gut reactions, these mental blindspots lead to poor strategic and financial decisions when evaluating choices.
These cognitive biases stem from the more primitive, emotional, and intuitive part of our brains that ensured survival in our ancestral environment. This quick, automatic reaction of our emotions represents the autopilot system of thinking, one of the two systems of thinking in our brains. It makes good decisions most of the time but also regularly makes certain systematic thinking errors, since it’s optimized to help us survive. In modern society, our survival is much less at risk, and our gut is more likely to compel us to focus on the wrong information to make decisions.
One of the biggest challenges relevant to Omicron is the cognitive bias known as the ostrich effect. Named after the myth that ostriches stick their heads into the sand when they fear danger, the ostrich effect refers to people denying negative reality. Delta illustrated the high likelihood of additional dangerous variants, yet we failed to pay attention to and prepare for such a threat.
We want the future to be normal. We’re tired of the pandemic and just want to get back to pre-pandemic times. Thus, we greatly underestimate the probability and impact of major disruptors, like new COVID variants. That cognitive bias is called the normalcy bias.
When we learn one way of functioning in any area, we tend to stick to that way of functioning. You might have heard of this as the hammer-nail syndrome: when you have a hammer, everything looks like a nail. That syndrome is called functional fixedness. This cognitive bias causes those used to their old ways of action to reject any alternatives, including to prepare for a new variant.
Our minds naturally prioritize the present. We want what we want now, and downplay the long-term consequences of our current desires. That fallacious mental pattern is called hyperbolic discounting, where we excessively discount the benefits of orienting toward the future and focus on the present. A clear example is focusing on the short-term perceived gains of trying to return to normal over managing the risks of future variants.
The way forward into the future is to defeat cognitive biases and avoid denying reality by rethinking our approach to the future.
The FDA requires a serious overhaul. It’s designed for a non-pandemic environment, where the goal is to have a highly conservative, slow-going, and risk-averse approach so that the public feels confident trusting whatever it approved. That’s simply unacceptable in a fast-moving pandemic, and we are bound to face future pandemics in the future.
The federal government needs to have cognitive bias experts weigh in on federal policy. Putting all of its eggs in one basket – vaccinations – is not a wise move when we face the risks of a vaccine-escaping variant. Its focus should also be on expediting and prioritizing anti-virals, scaling up cheap rapid testing, and subsidizing high-filtration masks.
For employers, instead of dictating a top-down approach to how employees collaborate, companies need to adopt a decentralized team-led approach. Each individual team leader of a rank-and-file employee team should determine what works best for their team. After all, team leaders tend to know much more of what their teams need, after all. Moreover, they can respond to local emergencies like COVID surges.
At the same time, team leaders need to be trained to integrate best practices for hybrid and remote team leadership. Companies transitioned to telework abruptly as part of the March 2020 lockdowns. They fell into the cognitive bias of functional fixedness and transposed their pre-existing, in-office methods of collaboration on remote work. Zoom happy hours are a clear example: The large majority of employees dislike them, and research shows they are disconnecting, rather than connecting.
Yet supervisors continue to use them, despite the existence of much better methods of facilitating colalboration, which have been shown to work, such as virtual water cooler discussions, virtual coworking, and virtual mentoring. Leaders also need to facilitate innovation in hybrid and remote teams through techniques such as virtual asynchronous brainstorming. Finally, team leaders need to adjust performance evaluation to adapt to the needs of hybrid and remote teams.
On an individual level, people built up certain expectations during the first two years of the pandemic, and they don't apply with Omicron. For example, most people still think that a cloth mask is a fine source of protection. In reality, you really need an N-95 mask, since Omicron is so much more infectious. Another example is that many people don’t realize that symptom onset is much quicker with Omicron, and they aren’t prepared for the consequences.
Remember that we have a huge number of people who are asymptomatic, often without knowing it, due to the much higher mildness of Omicron. About 8% of people admitted to hospitals for other reasons in San Francisco test positive for COVID without symptoms, which we can assume translates for other cities. That means many may think they're fine and they're actually infectious. The result is a much higher chance of someone getting many other people sick.
During this time of record-breaking cases, you need to be mindful about your internalized assumptions and adjust your risk calculus accordingly. So if you can delay higher-risk activities, January and February might be the time to do it. Prepare for waves of disruptions to continue over time, at least through the end of February.
Of course, you might also choose to not worry about getting infected. If you are vaccinated and boosted, and do not have any additional health risks, you are very unlikely to have a serious illness due to Omicron. You can just take the small risk of a serious illness – which can happen – and go about your daily life. If doing so, watch out for those you care about who do have health concerns, since if you infect them, they might not have a mild case even with Omicron.
In short, instead of trying to turn back the clock to the lost world of January 2020, consider how we might create a competitive advantage in our new future. COVID will never go away: we need to learn to live with it. That means reacting appropriately and thoughtfully to new variants and being intentional about our trade-offs.