On vaccination.

On vaccination.

The shape of things determines what they can do. Or, as a molecular biologist would phrase it, “structure determines function.”

In most ways, forks and spoons are similar. They’re made from the same materials, they show up alongside each other in place settings. But a spoon has a curved, solid bowl – you’d use it for soup or ice cream. A fork has prongs and is better suited for stabbing.

In matters of self defense, I’d reach for the fork.

On a much smaller scale, the three-dimensional shapes of a protein determines what it can do.

Each molecule of hemoglobin has a spoon-like pocket that’s just the right size for carrying oxygen, while still allowing the oxygen to wriggle free wherever your cells need it. A developing fetus has hemoglobin that’s shaped differently – when the fetal hemoglobin grabs oxygen, it squeezes more tightly, causing oxygen to pass from a mother to her fetus.

Each “voltage-gated ion channel” in your neurons has a shape that lets it sense incoming electrical signals and pass them forward. Voltage-gated ion channels are like sliding doors. They occasionally open to let in a rush of salt. Because salts are electrically charged, this creates an electric current. The electrical current will cause the next set of doors to open.

Every protein is shaped differently, which lets each do a different job. But they’re all made from the same materials – a long chain of amino acids.

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Your DNA holds the instructions for every protein in your body.

Your DNA is like a big, fancy cookbook – it holds all the recipes, but you might not want to bring it into the kitchen. You wouldn’t want to spill something on it, or get it wet, or otherwise wreck it.

Instead of bringing your nice big cookbook into the kitchen, you might copy a single recipe onto an index card. That way, you can be as messy as you like – if you spill something, you can always write out a new index card later.

And your cells do the same thing. When it’s time to make proteins, your cells copy the recipes. The original cookbook is made from DNA; the index-card-like copies are made from RNA. Then the index cards are shipped out of the nucleus – the library at the center of your cells – into the cytoplasm – the bustling kitchen where proteins are made and do their work.

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When a protein is first made, it’s a long strand of amino acids. Imagine a long rope with assorted junk tied on every few inches. Look, here’s a swath of velcro! Here’s a magnet. Here’s another magnet. Here’s a big plastic knob. Here’s another magnet. Here’s another piece of velcro. And so on.

If you shake this long rope, jostling it the way that a molecule tumbling through our cells gets jostled, the magnets will eventually stick together, and the velcro bits will stick to together, and the big plastic knob will jut out because there’s not enough room for it to fit inside the jumble.

That’s what happens during protein folding. Some amino acids are good at being near water, and those often end up on the outside of the final shape. Some amino acids repel water – like the oil layer of an unshaken oil & vinegar salad dressing – and those often end up on the inside of the final shape.

Other amino acids glue the protein together. The amino acid cysteine will stick to other cysteines. Some amino acids have negatively-charged sidechains, some have positively-charged sidechains, and these attract each other like magnets.

Sounds easy enough!

Except, wait. If you had a long rope with dozens of magnets, dozens of patches of velcro, and then you shook it around … well, the magnets would stick to other magnets, but would they stick to the right magnets?

You might imagine that there are many ways the protein could fold. But there’s only a single final shape that would allow the protein to function correctly in a cell.

So your cells use little helpers to ensure that proteins fold correctly. Some of the helpers are called “molecular chaperones,” and they guard various parts of the long strand so that it won’t glom together incorrectly. Some helpers are called “glycosylation enzymes,” and these glue little bits and bobs to the surface of a protein, some of which seem to act like mailing addresses to send the protein to the right place in a cell, some of which change the way the protein folds.

Our cells have a bunch of ways to ensure that each protein folds into the right 3D shape. And even with all this help, something things go awry. Alzheimer’s disease is associated with amyloid plaques that form in the brain – these are big trash heaps of misfolded proteins. The Alzheimer’s protein is just very tricky to fold correctly, especially if there’s a bunch of the misfolded protein strewn about.

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Many human proteins can be made by bacteria. Humans and bacteria are relatives, after all – if you look back in our family trees, you’ll find that humans and bacteria shared a great-great-great-grandmother a mere three billion years ago.

The cookbooks in our cells are written in the same language. Bacteria can read all our recipes.

Which is great news for biochemists, because bacteria are really cheap to grow.

If you need a whole bunch of some human protein, you start by trying to make it in bacteria. First you copy down the recipe – which means using things called “restriction enzymes” to move a sequence of DNA into a plasmid, which is something like a bacterial index card – then you punch holes in some bacteria and let your instructions drift in for them to read.

The bacteria churn out copies of your human protein. Bacteria almost always make the right long rope of amino acids.

But human proteins sometimes fold into the wrong shapes inside bacteria. Bacteria don’t have all the same helper molecules that we do,.

If a protein doesn’t fold into the right shape, it won’t do the right things.

If you were working in a laboratory, and you found out that the protein you’d asked bacteria to make was getting folded wrong … well, you’d probably start to sigh a lot. Instead of making the correctly-folded human protein, your bacteria gave you useless goo.

Shucks.

But fear not!

Yeast can’t be grown as cheaply as bacteria, but they’re still reasonably inexpensive. And yeast are closer relatives – instead of three billion years ago, the most recent great-great-grandmother shared between humans and yeast lived about one billion years ago.

Yeast have a few of the same helper proteins that we do. Some human proteins that can’t be made in bacteria will fold correctly in yeast.

So, you take some yeast, genetically modify it to produce a human protein, then grow a whole bunch of it. This is called “fermentation.” It’s like you’re making beer, almost. Genetically modified beer.

Then you spin your beer inside a centrifuge. This collects all the solid stuff at the bottom of the flask. Then you’ll try to purify the protein that you want away from all the other gunk. Like the yeast itself, and all the proteins that yeast normally make.

If you’re lucky, the human protein you were after will have folded correctly!

If you’re unlucky, the protein will have folded wrong. Your yeast might produce a bunch of useless goo. And then you do more sighing.

There’s another option, but it’s expensive. You can make your human protein inside human cells.

Normally, human cells are hesitant to do too much growing and dividing and replicating. After all, the instructions in our DNA are supposed to produce a body that looks just so – two arms, two eyes, a smile. Once we have cells in the right places, cell division is just supposed to replace the parts of you that have worn out.

Dead skin cells steadily flake from our bodies. New cells constantly replace them.

But sometimes a cell gets too eager to grow. If its DNA loses certain instructions, like the “contact inhibition” that tells cells to stop growing when they get too crowded, a human cell might make many, many copies of itself.

Which is unhelpful. Potentially lethal. A cell that’s too eager to grow is cancer.

Although it’s really, really unhelpful to have cancer cells growing in your body, in a laboratory, cancer cells are prized. Cancer cells are so eager to grow that we might be able to raise them in petri dishes.

Maybe you’ve heard of HeLa cells – this is a cancer cell line that was taken from a Black woman’s body without her consent, and then this cell line was used to produce innumerable medical discoveries, including many that were patented and have brought in huge sums of money, and this woman’s family was not compensated at all, and they’ve suffered huge invasions of their privacy because a lot of their genetic information has been published, again without their consent …

HeLa cells are probably the easiest human cells to grow. And it’s possible to flood them with instructions to make a particular human protein. You can feel quite confident that your human protein will fold correctly.

But it’s way more expensive to grow HeLa cells than yeast. You have to grow them in a single layer in a petri dish. You have to feed them the blood of a baby calf. You have to be very careful while you work or else the cells will get contaminated with bacteria or yeast and die.

If you really must have a whole lot of a human protein, and you can’t make it in bacteria or yeast, then you can do it. But it’ll cost you.

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Vaccination is perhaps the safest, most effective thing that physicians do.

Your immune system quells disease, but it has to learn which shapes inside your body represent danger. Antibodies and immunological memory arise in a process like evolution – random genetic recombination until our defenses can bind to the surface of an intruder. By letting our immune system train in a relatively safe encounter, we boost our odds of later survival.

The molecular workings of our immune systems are still being studied, but the basic principles of inoculation were independently discovered centuries ago by scientists in Africa, India, and China. These scientists’ descendants practiced inoculation against smallpox for hundreds of years before their techniques were adapted by Edward Jenner to create his smallpox vaccine.

If you put a virus into somebody’s body, that person might get sick. So what you want is to put something that looks a lot like the virus into somebody’s body.

One way to make something that looks like the virus, but isn’t, is to take the actual virus and whack it with a hammer. You break it a little. Not so much that it’s unrecognizable, but enough so that it can’t work. Can’t make somebody sick. This is often done with “heat inactivation.”

Heat inactivation can be dangerous, though. If you cook a virus too long, it might fall apart and your immune system learns nothing. If you don’t cook a virus long enough, it might make you sick.

In some of the early smallpox vaccine trials, the “heat inactivated” viruses still made a lot of people very, very sick.

Fewer people got very sick than if they’d been exposed to smallpox virus naturally, but it feels different when you’re injecting something right into somebody’s arm.

We hold vaccines to high standards. Even when we’re vaccinating people against deadly diseases, we expect our vaccines to be very, very safe.

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It’s safer to vaccinate people with things that look like a virus but can’t possibly infect them.

This is why you might want to produce a whole bunch of some specific protein. Why you’d go through that whole rigamarole of testing protein folding in bacteria, yeast, and HeLa cells. Because you’re trying to make a bunch of protein that looks like a virus.

Each virus is a little protein shell. They’re basically delivery drones for nasty bits of genetic material.

If you can make pieces of this protein shell inside bacteria, or in yeast, and then inject those into people, then the people can’t possibly be infected. You’re not injecting people with a whole virus – the delivery drone with its awful recipes inside. Instead, you’re injecting people with just the propeller blades from the drone, or just its empty cargo hold.

These vaccine are missing the genetic material that allow viruses to make copies of themselves. Unlike with a heat inactivated virus, we can’t possibly contract the illness from these vaccines.

This is roughly the strategy used for the HPV vaccine that my father helped develop. Merck’s “Gardasil” uses viral proteins made by yeast, which is a fancy way of saying that Merck purifies part of the virus’s delivery drone away from big batches of genetically-modified beer.

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We have a lot of practice making vaccines from purified protein.

Even so, it’s a long, difficult, expensive process. You have to identify which part of the virus is often recognized by our immune systems. You have to find a way to produce a lot of this correctly-folded protein. You have to purify this protein away from everything else made by your bacteria or yeast or HeLa cells.

The Covid-19 vaccines bypass all that.

In a way, these are vaccines for lazy people. Instead of finding a way to make a whole bunch of viral protein, then purify it, then put it into somebody’s arm … well, what if we just asked the patient’s arm to make the viral protein on its own?

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Several of the Covid-19 vaccines are made with mRNA molecules.

These mRNA molecules are the index cards that we use for recipes in our cells’ kitchens, so the only trick is to deliver a bunch of mRNA with a recipe for part of the Covid-19 virus. Then our immune system can learn that anything with that particular shape is bad and ought to be destroyed.

After learning to recognize one part of the virus delivery drone, we’ll be able to stop the real thing.

We can’t vaccinate people by injecting just the mRNA, though, because our bodies have lots of ways to destroy RNA molecules. After all, you wouldn’t want to cook from the recipe from any old index card that you’d found in the street. Maybe somebody copied a recipe from The Anarchist Cookbook – you’d accidentally whip up a bomb instead of a delicious cake.

I used to share laboratory space with people who studied RNA, and they were intensely paranoid about cleaning. They’d always wear gloves, they’d wipe down every surface many times each day. Not to protect themselves, but to ensure that all the RNA-destroying enzymes that our bodies naturally produce wouldn’t ruin their experiments.

mRNA is finicky and unstable. And our bodies intentionally destroy stray recipes.

So to make a vaccine, you have to wrap the mRNA in a little envelope. That way, your cells might receive the recipe before it’s destroyed. In this case, the envelope is called a “lipid nanoparticle,” but you could also call a fat bubble. Not a bubble that’s rotund – a tiny sphere made of fat.

Fat bubbles are used throughout cells. When the neurons in your brain communicate, they burst open fat bubbles full of neurotransmitters and scatter the contents. When stuff found outside a cell needs to be destroyed, it’s bundled into fat bubbles and sent to a cellular trash factories called lysosomes.

For my Ph.D. thesis, I studied the postmarking system for fat bubbles. How fat bubbles get addressed in order to be sent to the right places.

Sure, I made my work sound fancier when I gave my thesis defense, but that’s really what I was doing.

Anyway, after we inject someone with an mRNA vaccine, the fat bubble with the mRNA gets bundled up and taken into some of their cells, and this tricks those cells into following the mRNA recipe and making a protein from the Covid-19 virus.

This mRNA recipe won’t teach the cells how to make a whole virus — that would be dangerous! That’s what happens during a Covid-19 infection – your cells get the virus’s whole damn cookbook and they make the entire delivery drone and more cookbooks to put inside and then these spread through your body and pull the same trick on more and more of your cells. A single unstopped delivery drone can trick your cells into building a whole fleet of them and infecting cells throughout your body.

Instead, the mRNA recipe we use for the vaccine has only a small portion of the Covid-19 genome, just enough for your cells to make part of the delivery drone and learn to recognize it as a threat.

And this recipe never visits the nucleus, which is the main library in your cells that holds your DNA, the master cookbook with recipes for every protein in your body. Your cells are tricked into following recipes scribbled onto the vaccine’s index cards, but your master cookbook remains unchanged. And, just like all the mRNA index cards that our bodies normally produce, the mRNA from the vaccine soon gets destroyed. All those stray index cards, chucked unceremoniously into the recycling bin.

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The Johnson & Johnson vaccine also tricks our cells into making a piece of the Covid-19 virus.

This vaccine uses a different virus’s delivery drone to send the recipe for a piece of Covid-19 into your cells. The vaccine’s delivery drone isn’t a real virus – the recipe it holds doesn’t include the instructions on how to make copies of itself. But the vaccine’s delivery drone looks an awful lot like a virus, which means it’s easier to work with than the mRNA vaccines.

Those little engineered fat bubbles are finicky. And mRNA is finicky. But the Johnson & Johnson vaccine uses a delivery drone that was optimized through natural selection out in the real world. It evolved to be stable enough to make us sick.

Now we can steal its design in an effort to keep people well.

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Lots of people received the Johnson & Johnson vaccine without incident, but we’ve temporarily stopped giving it to people. Blood clots are really scary.

You might want to read Alexandra Lahav’s excellent essay, “Medicine Is Made for Men.” Lahav describes the many ways in which a lack of diversity in science, technology, and engineering fields can cause harm.

Cars are designed to protect men: for many years, we used only crash test dummies that were shaped like men to determine whether cars were safe. In equivalent accidents, women are more likely to die, because, lo and behold, their bodies are often shaped differently.

Women are also more likely to be killed by medication. Safety testing often fails to account for women’s hormonal cycles, or complications from contraceptives, or differences in metabolism, or several other important features of women’s bodies.

White male bodies are considered to be human bodies, and any deviation is considered an abnormal case. Medication tested in white men can be approved for everyone; medication tested in Black patients was approved only for use in other Black patients.

Although more than half our population are women, their bodies are treated as bizarre.

For most people, the Johnson & Johnson vaccine is safe. But this is a sort of tragedy that occurs too often – causing harm to women because we’re inattentive to the unique features of their bodies.

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I haven’t been vaccinated yet, but I registered as soon as I was able – my first dose will be on April 26th. Although I’ve almost certainly already had Covid-19 before, and am unlikely to get severely ill the next time I contract it, I’m getting the vaccine to protect my friends and neighbors.

So should you.

On moral outrage.

On moral outrage.

My family had spring break travel plans for before the shutdown.

We canceled them.

At the time, we feared for our safety. My spouse said to me, “You caught the flu twice this year, even after you were vaccinated, and the second time was the sickest I’ve ever seen you. I’m really worried about what will happen if you catch this new thing, too.”

She wanted me to cancel my poetry classes in the local jail. My father, an infectious diseases doctor and professor of immunology, thought I should still go in to teach. “If somebody’s in there coughing up a lung, you should recommend he skip class next week,” my father told me.

But I was spooked. I felt glad when the jail put out a press release saying they’d no longer allow volunteers to come in – I didn’t want to choose between helping the incarcerated men and protecting my family.

My spouse is a high school science teacher. She felt glad that her biology classroom has over a dozen sinks. During the final week of school, she asked all her students to wash their hands for 20 seconds as soon as they walked into the room.

My spouse and I are both scientists, but it wasn’t until a week into the shutdown that I began to read research papers about Covid-19. Until then, we had gotten all our information from the newspaper. And the news was terrifying. Huge numbers of people were dying in Italy. Our imbecilic president claimed that Covid-19 was no big deal, making me speculate that this disease was even more dangerous than I’d thought.

Later, I finally went through the data from Italy and from the Diamond Princess cruise ship. These data – alongside the assumption that viral exposure should be roughly similar across age groups, if not higher for school children and young people who are out and about in the world – showed my family that our personal risk was probably quite low.

Still, we stayed inside. We were worried about harming others.

When I saw photographs of beaches packed with revelers, I felt furious. Did those selfish young people not realize that their choices could cause more people to die?

So it was shocking for me to learn that those selfish young people were actually doing the thing that would save most lives.

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We now know that Covid-19 can be transmitted by people who feel no symptoms, and that it was widespread in this country by March.

If we, as a people, had acted earlier, we could have prevented all these deaths. In January, it would have been enough to impose a brief quarantine after all international travel. In February, it would have been enough to use our current strategy of business closures, PCR testing, and contact tracing. In March, we were too late. The best we could do then – the best we can do now – was to slow the spread of infections.

Unfortunately, slowing the spread of infections will cause more people to die.

There’s an obvious short-term benefit to slowing the spread of infections – if too many people became critically ill at the same time, our hospitals would be overwhelmed, and we’d be unable to offer treatment to everyone who wanted it. We’d run out of ventilators.

This problem is exacerbated by the fact that we, as a people, are terrible about talking about death. There’s no consensus about what constitutes a good life – what more would have to happen for you to feel ready to die?

Personally, I don’t want to die. As my mind stopped, I’d feel regret that I wouldn’t get to see my children become self-sufficient adults. But I’d like to think that I could feel proud that I’ve done so much to set them on the right path. Since my twenties, I’ve put forth a constant effort to live ethically, and I’d like to imagine that my work – my writing, teaching, and research – has improved other people’s lives.

I’ve also gotten to see and do a lot of wonderful things. I’ve been privileged to visit four countries. I visited St. Louis’s City Museum when one of my kids was old enough to gleefully play. I have a bundle of some two dozen love letters that several wonderful people sent me.

I’ve had a good life. I’d like for it to continue, but I’ve already had a good life.

Many medical doctors, who have seen how awful it can be for patients when everything is done to try to save a life, have “do not resuscitate” orders. My spouse and I keep our living wills in an accessible space in our home. But a majority of laypeople want dramatic, painful measures to be taken in the attempt to save their lives.

People are making this choice even during the pandemic, when the choice to experience an excruciating death puts medical professionals at risk and reduces the quality of care available for everyone else.

Still. Even without our reluctance to discuss death, there would be a short-term benefit to slowing the spread of infections. The American healthcare system is terrible, and was already strained to the breaking point. We weren’t – and aren’t – ready to handle a huge influx of sick patients.

But the short-term benefit of slowing the spread of Covid-19 comes at a major cost.

The shutdown itself hurts people. The deaths caused by increased joblessness, food insecurity, educational disruption, domestic violence, and loneliness (“loneliness and social isolation can be as damaging to health as smoking 15 cigarettes a day”) are more difficult to measure than the deaths caused by Covid-19. We won’t have a PCR test to diagnose which people were killed by the shutdown.

Those deaths won’t all come at once. But those deaths are no less real, and no less tragic, than the immediate horror of a person drowning from viral-induced fluid buildup in their lungs.

And, perhaps more damning, if the shutdown ends before there’s a vaccine, the shutdown will cause more people to die of Covid-19.

Without a vaccine, slowing the spread of Covid-19 has a short-term benefit of reducing the rate of hospital admissions, at the long-term cost of increasing the total number of Covid-19 cases.

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All immunity fades – sometimes after decades, sometimes after months. Doesn’t matter whether you have immunity from recovery or from vaccination – eventually, your immunity will disappear. And, for a new disease, we have no way of predicting when. Nobody knows why some antigens, like the tetanus vaccine, trigger such long-lasting immunity, while other antigens, such as the flu vaccine or the influenza virus itself, trigger such brief protection.

We don’t know how long immunity to Covid-19 will last. For some coronaviruses, immunity fades within a year. For others, like SARS, immunity lasts longer.

The World Health Organization has warned, repeatedly, that immunity to Covid-19 might be brief. But the WHO seems unaware of the implications of this warning.

The shorter the duration of a person’s immunity, the more dangerous the shutdown. If our shutdown causes the Covid-19 epidemic to last longer than the duration of individual immunity, there will be more total infections – and thus more deaths – before we reach herd immunity.

This is, after all, exactly how a one-time “novel zoogenic disease” like influenza became a permanent parasite on our species, killing tens of thousands of people in the United States each year. Long ago, transmission was slowed to the point that the virus could circulate indefinitely. Influenza has been with us ever since.

That’s the glaring flaw in the recent Harvard Science paper recommending social distancing until 2022 – in their key figure, they do not incorporate a loss of immunity. Depending on the interplay between the rate of spread and the duration of immunity, their recommendation can cause this epidemic to never end.

And, if the shutdown ends before we have a vaccine, the lost immunity represents an increased death toll to Covid-19. Even neglecting all the other harms, we’ll have killed more people than if we’d done nothing.

This sounds terrifying. And it is. But the small glimmer of good news is that people’s second infections will probably be less severe. If you survive Covid-19 the first time you contract it, you have a good chance of surviving subsequent infections. But prolonging the epidemic will still cause more deaths, because herd immunity works by disrupting transmission. Even though an individual is less likely to die during a second infection, that person can still spread the virus. Indeed, people are more likely to spread the virus during subsequent infections, because they’re more likely to feel healthy while shedding infectious particles.

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This calculation would be very different if people could be vaccinated.

Obviously, vaccination would be the best way to end this epidemic. In order to reach herd immunity by a sufficient number of people recovering, there would have to be a huge percentage of our population infected. Nobody knows how many infections it would take, but many researchers guess a number around 60% to 70% of our population.

Even if Covid-19 were no more dangerous than seasonal influenza (and our data so far suggest that it’s actually about four-fold more dangerous than most years’ seasonal influenza), that would mean 200,000 deaths. A horrifying number.

But there’s no vaccine. Lots of people are working on making a vaccine. We have Covid-19 vaccines that work well in monkeys. But that doesn’t necessarily mean anything in terms of human protection. We’ve made many HIV vaccines that work well in monkeys – some of these increase the chance that humans will contract HIV.

It should be easier to make a vaccine against this coronavirus than against HIV. When making a vaccine, you want your target to mutate as little as possible. You want it to maintain a set structure, because antibodies need to recognize the shape of external features of the virus in order to protect you. HIV mutates so fast that its shape changes, like a villain constantly donning a new disguise. But the virus that causes Covid-19 includes a proofreading enzyme, so it’ll switch disguises less.

Still, “easier to make a vaccine against than HIV” is not the most encouraging news. Certain pharmaceutical companies have issued optimistic press briefings suggesting that they’ll be able to develop a vaccine in 18 months, but we should feel dubious. These press briefings are probably intended to bolster the companies’ stock prices, not give the general public an accurate understanding of vaccine development.

Realistically, a Covid-19 vaccine is probably at least four years away. And it’s possible – unlikely, but possible – that we’ll never develop a safe, effective vaccine for this.

If we end the shutdown at any time before there is a vaccine, the shutdown will increase the number of people who die of Covid-19. The longer the shutdown, the higher the toll. And a vaccine is probably years away.

The combination of those two ideas should give you pause.

If we’re going to end the shutdown before we have a vaccine, we should end it now.

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To be absolutely clear, vaccination would be the best way to resolve this crisis. Vaccination saves lives. The basic principle of inoculation was used for hundreds of years in Africa, India, and China, before it was adapted by Edward Jenner to create the first smallpox vaccine.

For a vaccine to end the Covid-19 epidemic, enough people will need to choose to be vaccinated for us to reach herd immunity.

Unfortunately, many people in the United States distrust the well-established efficacy and safety of vaccines. It’s worth comparing Covid-19 to seasonal influenza. On a population level, Covid-19 seems to be about four-fold more dangerous than seasonal influenza. But this average risk obscures some important data – the risk of Covid-19 is distributed less evenly than the risk of influenza.

With influenza, healthy young people have a smaller risk of death than elderly people or people with pre-existing medical conditions. But some healthy young people die from seasonal influenza. In the United States, several thousand people between the ages of 18 and 45 die of influenza every year.

And yet, many people choose not to be vaccinated against influenza. The population-wide vaccination rate in the United States is only 40%, too low to provide herd immunity.

Compared to influenza, Covid-19 seems to have less risk for healthy young people. Yes, healthy young people die of Covid-19. With influenza, about 10% of deaths are people between the ages of 18 and 45. With Covid-19, about 2% of deaths are people in this age group.

I’m not arguing that Covid-19 isn’t dangerous. When I compare Covid-19 to seasonal influenza, I’m simply comparing two diseases that are both deadly.

I get vaccinated against influenza every year.

Yes, you might have heard news reports about the influenza vaccine having low efficacy, but that’s simply measuring how likely you are to get sick after being vaccinated. We also know that the vaccine makes your illness less severe.

The influenza vaccine saves lives. The data are indisputable.

But people don’t choose to get it! That’s why I think it’s unfortunately very likely that people whose personal risk from Covid-19 is lower than their risk from influenza will forgo vaccination. Even if we had access to 300 million doses of a safe, effective vaccine today, I doubt that enough people would get vaccinated to reach herd immunity.

Obviously, I’d love to be wrong about this. Vaccination saves lives.

Please, dear reader, get a flu vaccine each year. And, if we develop a safe, effective Covid-19 vaccine, you should get that too.

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We don’t have a vaccine. The shutdown is causing harm – the shutdown is even increasing the total number of people who will eventually die of Covid-19.

Is there anything we can do?

Luckily, yes. We do have another way to save lives. We can change the demographics of exposure.

Our understanding of Covid-19 still has major gaps. We need to do more research into the role of interleukin 6 in our bodies’ response to this disease – a lot of the healthy young people who’ve become critically ill with Covid-19 experienced excessive inflammation that further damaged their lungs.

But we already know that advanced age, smoking status, obesity and Type 2 diabetes are major risk factors for complications from Covid-19. Based on the data we have so far, it seems like a low-risk person might have somewhere between a hundredth or a thousandth the chance of becoming critically ill with Covid-19 as compared to an at-risk person. With influenza, a low-risk person might have between a tenth and a hundredth the chance of becoming critically ill.

The risk of Covid-19 is more concentrated on a small segment of the population than the risk of influenza.

To save lives, and to keep our hospitals from being overwhelmed, we want to do everything possible to avoid exposing at-risk people to this virus.

But when healthy young people take extraordinary measures to avoid getting sick with Covid-19 – like the shutdown, social distancing, and wearing masks – they increase the relative burden of disease that falls on at-risk people. We should be prioritizing the protection of at-risk people, and we aren’t.

Because this epidemic will not end until we reach the population-wide threshold for herd immunity, someone has to get sick. We’d rather it be someone who is likely to recover.

Tragically, we already have data suggesting that a partial shutdown can transfer the burden of infection from one group to another. In the United States, our shutdown was partial from the beginning. People with white-collar jobs switched to working remotely, but cashiers, bus drivers, janitors, people in food prep, and nurses have kept working. In part because Black and brown people are over-represented in these forms of employment, they’ve been over-represented among Covid-19 deaths.

There is absolutely no reason to think that poor people would be more likely to safely recover from Covid-19 – indeed, due to air pollution, stress, sleep deprivation, limited access to good nutrition, and limited access to health care, we should suspect that poor people will be less likely to recover – but, during the shutdown, we’ve shifted the burden of disease onto their shoulders.

This is horrible. Both unethical and ineffective. And, really, an unsurprising outcome, given the way our country often operates.

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If we want to save lives, we need for healthy younger people to use their immune systems to protect us. The data we have so far indicates that the shutdown should end now — for them.

It will feel unfair if healthy younger people get to return to work and to their regular lives before others.

And the logistics won’t be easy. We’ll still need to make accommodations for people to work from home. Stores will have to maintain morning hours for at-risk shoppers, and be thoroughly cleaned each night.

If school buildings were open, some teachers couldn’t be there – they might need substitutes for months – and neither could some students, who might switch to e-learning to protect at-risk family.

We’ll need to provide enough monetary and other resources that at-risk people can endure a few more months of self-isolation. Which is horrible. We all know, now that we’ve all been doing this for a while, that what we’re asking at-risk people to endure is horrible. But the payoff is that we’ll be saving lives.

Indeed, the people who self-isolate will have lowest risk. We’ll be saving their lives.

And no one should feel forced, for financial reasons or otherwise, to take on more risk than they feel comfortable with. That’s why accommodations will be so important. I personally would feel shabby if I took extreme measures to protect myself, knowing that my risk is so much lower than other people’s, but you can’t look at someone in a mask and know their medical history, much less whom they might be protecting at home.

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All told, this plan isn’t good. I’m not trying to convince you that this is good. I’m just saying that, because we bungled things in January, this is the best we have.

If we could go back in time, we’d obviously do things differently. It’s only based on where we are now that physicians like David Katz argue we need to end the shutdown based on the principle of “harm minimization.”

Based on the data we have, I agree.

Ending the shutdown now, but only for some, will save lives.

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So, those selfish young people crowding on beaches? I looked at the photos and hated them.

But it turns out that their selfish actions were actually the exact plan that will save most lives.

I’ve had to swallow my moral indignation. I hope you can too.

On violence and gratitude.

On violence and gratitude.

Although I consider myself a benevolent tyrant, some of my cells have turned against me.  Mutinous, they were swayed by the propaganda of a virus and started churning out capsids rather than helping me type this essay.  Which leaves me sitting at a YMCA snack room table snerking, goo leaking down my throat and out my nose.

Unconsciously, I take violent reprisal against the traitors.  I send my enforcers to put down the revolt – they cannibalize the still-living rebels, first gnawing the skin, then devouring the organs that come spilling out.  Then the defector dies.

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CD8+ T cell destruction of infected cells by Dananguyen on Wikimedia.

My cells are also expected to commit suicide whenever they cease to be useful for my grand designs.  Any time a revolutionary loses the resolve to commit suicide, my enforcers put it down.  Unless my internal surveillance state fails to notice in time – the other name for a cell that doesn’t want to commit suicide is “cancer,” and even the most robust immune system might be stymied by cancer when the traitor’s family grows too large.

Worse is when the rebels “metastasize,” like contemporary terrorists.  This word signifies that the family has sent sleeper agents to infiltrate the world at large, attempting to develop new pockets of resistance in other areas.  Even if my enforcers crush one cluster of rebellion, others could flourish unchecked.

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How metastasis occurs. Image by the National Cancer Institute on Wikimedia.

I know something that perhaps they don’t – if their rebellion succeeds, they will die.  A flourishing cancer sequesters so many resources that the rest of my body would soon prove too weak to seek food and water, causing every cell inside of me to die.

But perhaps they’ve learned my kingdom’s vile secret – rebel or not, they will die.  As with any hereditary monarchy, a select few of my cells are privileged above all others.  And it’s not the cells in my brain that rule.

Every “somatic cell” is doomed.  These cells compose my brain and body.  Each has slight variations from “my” genome – every round of cell division introduces random mutations, making every cell’s DNA slightly different from its neighbors’.

The basic idea behind Richard Dawkins’s The Selfish Gene is that each of these cells “wants” for its genome to pass down through the ages.  Dawkins argued that familial altruism is rational because any sacrifice bolsters the chances for a very similar genome to propagate.  Similarly, each somatic cell is expected to sacrifice itself to boost the odds for a very similar genome carried by the gametes.

Only gametes – the heralded population of germ cells in our genitalia – can possibly see their lineage continue.  All others are like the commoners who (perhaps foolishly) chant their king or kingdom’s name as they rush into battle to die.  I expect them to show absolute fealty to me, their tyrant.  Apoptosis – uncomplaining suicide – was required of many before I was even born, like when cells forming the webbing between my fingers slit their own bellies in dramatic synchronized hara-kiri.

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Human gametes by Karl-Ludwig Poggemann on Flickr.

Any evolutionary biologist could explain that each such act of sacrifice was in a cell’s mathematical best interest.  But if I were a conscious somatic cell, would I submit so easily?  Or do I owe some sliver of respect to the traitors inside me?

The world is a violent place.  I’m an extremely liberal vegan environmentalist – yet it takes a lot of violence to keep me going.

From Suzana Herculano-Houzel’s The Human Advantage:

image (1)Animals that we are, we must face, every single day of our lives, the consequences of our most basic predicament: we don’t do photosynthesis.  For lack of the necessary genes, we don’t just absorb carbon from the air around us and fix it as new bodily matter with a little help from sunlight.  To survive, we animals have to eat other living organisms, whether animal, vegetable, or fungus, and transform their matter into ours.

And yet the violence doesn’t begin with animals.  Photosynthesis seems benign by comparison – all you’d need is light from the sun! – unless you watch a time-lapsed video of plant growth in any forest or jungle.

The sun casts off electromagnetic radiation without a care in the world, but the amount of useful light reaching any particular spot on earth is limited.  And plants will fight for it.  They race upwards, a sprint that we sometimes fail to notice only because they’ve adapted a timescale of days, years, and centuries rather than our seconds, hours, and years.  They reach over competitors’ heads, attempting to grab any extra smidgen of light … and starving those below.  Many vines physically strangle their foes.  Several trees excrete poison from their roots.  Why win fair if you don’t have to?  A banquet of warm sunlight awaits the tallest plant left standing.

And so why, in such a violent world, would it be worthwhile to be vegan?  After all, nothing wants to be eaten.  Sure, a plant wants for animals to eat its fruit – fruits and animals co-evolved in a system of gift exchange.  The plant freely offers fruit, with no way of guaranteeing recompense, in hope that the animal might plant its seeds in a useful location.

But actual pieces of fruit – the individual cells composing an apple – probably don’t want to be eaten, no more than cancers or my own virus-infected cells want to be put down for the greater good.

A kale plant doesn’t want for me to tear off its leaves and dice them for my morning ramen.

But by acknowledging how much sacrifice it takes to allow for us to be typing or reading or otherwise reaping the pleasures of existence, I think it’s easier to maintain awe.  A sense of gratitude toward all that we’ve been given.  Most humans appreciate things more when we think they cost more.

We should appreciate the chance to be alive.  It costs an absurd amount for us to be here.

But, in the modern world, it’s possible to have a wonderful, rampantly hedonistic life as a vegan.  Why make our existence cost more when we don’t have to?  A bottle of wine tastes better when we’re told that it’s $45-dollar and not $5-dollar wine, but it won’t taste any better if you tell somebody “It’s $45-dollar wine, but you’ll have to pay $90 for it.”

Personally, I’d think it tasted worse, each sip with the savor of squander.

On playing outdoors, and allergies.

IMG_3797K has been on a big kick reading books about sending students outside.  Obviously, I approve.  Being outdoors seems to make most humans happier, and people who spend time outside seem more likely to care about preserving our environment.  Plus, K even has scholastic reasons to ask students to sit contemplatively outside — it’s reasonable for students in a college-level biology course to practice fieldwork.

I try to get N outside a lot, too, but with her it’s probably not reasonable to use “learning to do fieldwork” as an excuse.  She’s a bit young to practice the extreme patience needed for successful fieldwork, so I thought it might be worthwhile summarizing a few of the recent studies on exposure to the world, allergies, and autoimmune disorders.

I should declare my conflict of interest upfront, though.  I’m extremely biased because I want you, dear reader, and your friends, and your family, to spend more time outside.  Unless you’re, I don’t know, living in a tent, roasting carrots & beats & whatnot over a firepit every evening… then you’re probably outside plenty.  It’s the rest of us, those who lead more normative modern lives, sleeping in air-conditioned homes, zipping about town inside our cars, hoofing it down concrete sidewalks, spending long hours pecking at our computers, who could use a bit more outdoor time.  I’ll try my best to keep this short so that you can rush outside and play, but if you feel antsy & want to go out now, go ahead!  I won’t begrudge your priorities!

The basic idea behind all of this was proposed by David Strachan in the article “Hay Fever, Hygiene, and Household Size.”  He observed that younger siblings were less likely to get asthma and proposed that the messy, disease-prone lifestyle of multi-child families was protecting those younger children.  As in, getting sick more often as a child, and having an absentminded older sister who tracks mud through the house, might lead to better health as an adult.

IMG_4568Which is a lovely theory.  At birth, our immune systems are relatively ignorant.  They instinctively know that they should destroy things — we are the product of untold millennia of selection for those who can survive routine infections — but they don’t know what they should destroy.  Exposure to pathogens trains our immune systems to recognize & attack those pathogens.  Repeated exposure to innocuous substances trains us to ignore those ever-present harmless components of our environment.

The modern world is very clean, though.  We wash our hands.  We eat less dirt.  We’re less likely to even walk barefoot through the dirt.  Most people in the United States don’t pull their drinking water from a river that another tribe upstream defecates into.  And that’s good.  We get sick less.  Children are more likely to survive to adulthood.  But it also means that many people’s immune systems encounter fewer pathogens than they “expect.”

If you’re in the market for a really evil social psychology experiment, I’ve got one for you: find a small child & every day explain to that child that he should expect to get into at least one fight per week at school.  Tell him, “There are so many bullies out there!  You’ll have to be ready for them!  Don’t let them catch you off guard.  One fight a week!  Maybe two!  It’s a jungle and they prey on the weak!”

Once that kid starts kindergarten, even if it’s in a total fluff district where his classmates are all sunshine and rainbows, he’s probably going to get into fights.  Because he’ll assume those fights are supposed to happen, so he’ll blow tiny slights way out of proportion… you used the blue crayon too long!  Pow!

IMG_4696The hygiene hypothesis purports that our immune systems are the same.  They expect fights, and so if we put them into too-clean environs, they become the bullies they’ve been warned about (bonus points if you’re thinking about the shipwrecked sailer from The Watchmen now).  Immune systems can rage against innocuous compounds — those are allergies.  Or, worse, they get so incredibly bored, they’re expecting fights and everyone is so incredibly nice, that they begin to attack their own hosts.  As in, our own bodies.

Fighting off foreign infections helps the immune system learn to distinguish self from other, but if there are too few outsiders, the immune system just starts wailing on a mirror.  Wondering why the kid on the other side can’t ever be knocked down.

Autoimmune disorders are the pits.

And for years it seemed like there was nothing to do, once you contracted an allergy, except avoid the thing that triggers your itching and snurfling.  Or, worse, triggers your anaphylactic shock, dizziness, maybe death from loss of breathing.

But there might be hope!

Recently, researchers have been testing whether you can retrain an immune system to ignore innocuous compounds.  For instance, peanuts: by eating a small amount of peanuts every day you might be able to train your immune system to just leave them be instead of going berserk trying to pick a fight.  Because it’s the immune system’s fit of rage that kills people, not the peanuts themselves.  If peanuts are always around, that familiarity might breed lassitude.

(NOTE: there are a lot of references for this, and theoretically the idea is sound.  But let’s say you or someone you know has a peanut allergy — please DO NOT try to cure yourself this way without contacting a medical professional & undertaking the project in a hospital setting.  If you want to look up more papers on this, go to PubMed and search for “oral immunotherapy,” but please note that very low doses of the allergens are used, and even with those very low doses some people can go into shock.)

Another strategy that seems to be working well is to introduce punching bags into classrooms… that way the battle-ready children have something to smack without disrupting anybody’s education.

Err, wait.  I mean, intentionally introducing parasites into the human body so that the immune system has something to attack & is less likely to inflame the bowels, joints, liver, etc.  Apparently the symptoms of several autoimmune diseases can be ameliorated by parasites; here is one recent reference but there are many others.

Of course, harboring parasites is often not fun.  But as long as the parasites make you less ill than your own body’s attacks against itself did, why not?  Because autoimmune disorders are horrible — attempting to treat them with parasites is way more reasonable than using tapeworms to lose weight.

And, as a new parent, I also spend time thinking about prevention.  I slather my pale baby with sunscreen before we play outside.  And I make her play outside — major lifestyle changes over the last few decades probably explain our current allergy epidemic, with the incidence of peanut allergies & celiac disease up to 1% or higher.  Huge numbers of people who’ll suffer from these ailments for their whole lives.

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The most striking data on allergy prevention suggests that you should raise children on a farm.  For a lot of people, that’s not really feasible.  Even if K & I had the space, we wouldn’t raise animals — given that we can live well without subjugating any critters, I don’t think it’s the right thing to do.  But we can still take N to visit the pigs at our local farmed-animal sanctuary, and hopefully that’ll help a little.

Plus, we play outside.  Yes, the epidemiological data suggests that being outside on a farm helps most, but you can do pretty well just by getting out, running around, and playing in the dirt.

(Although even playing in the dirt is tricky.  It has to be clean dirt.  Bacteria are fine.  Some other soil parasites — a kid might get sick, but it’ll often be temporary sickness.  The whole thing about an immune system needing work to do means that nothing comes free.  But, ingesting petroleates would be bad.  Or heavy metals.  Halogenated aromatics.  And — yay pretend capitalism where businesses are allowed to impose negative externalities for free! — a lot of that dreck has been dumped for years.  Here in Bloomington we have a big tire factory & dirt on the properties downhill from it are poisoned.  Unless you have access to a good mass spec, your best bet for learning whether land is safe for a kid to grubble around on is to read up on its history.  Which is crummy to have to do, but the peculiar incarnation of capitalism indoctrinated by the U.S. has resulted in many horrors that still reverberate.)

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