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 complexity and seemingly good ideas.

On complexity and seemingly good ideas.

Elizabeth Kolbert’s lovely essay in the New York Review of Books, “Chemical Warfare’s Home Front,” describes Fritz Haber’s contribution to the use of toxic gas in war.

Haber orchestrated the use of chlorine to suffocate all animal life – including soldiers – downwind of his nation’s troops. And his plan succeeded. After unleashing 300,000 pounds of chlorine gas, huge numbers of people died. Soldiers– some of whom suffocated, some whose lungs burned, some who committed suicide when enveloped by the gas – as well as horses, cows, chickens, wildlife.

Chemical warfare is horrible, but Haber’s battlefield “experiment” was considered a success. Military researchers then concocted more dangerous chemical agents, like DNA-crosslinking mustard gas and muscle-clenching Sarin nerve gas.

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Fritz Haber’s other ideas were seemingly more beneficial for humanity. Haber was awarded the Nobel Prize in chemistry for making synthetic fertilizer.

Synthetic fertilizer let us grow more crops.

We could feed billions more people!

The global population soared.

If we hadn’t invented synthetic fertilizer, the global population would still be under four billion people.

Climate change would still be a huge problem – the most outrageous polluters haven’t been the most populous nations. Climate change was caused primarily by the United States and other wealthy nations, whereas overpopulation will first devastate equatorial nations.

A seemingly good idea – more fertilizer! – has greatly exacerbated the scale of suffering.

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Kolbert discusses the invention of chlorofluorocarbons, which seemed like great coolants. With CFCs, Frigidaire could build cheaper refrigerators! Regular families could keep their ice cream cold without spending as much on electricity.

Unfortunately, CFCs also dissolve our ozone layer. More dangerous ultraviolet radiation began to reach us from the sun, causing horrible skin cancers.

CFCs seemed like a good idea — they do work great as coolants — but they caused awful problems as part of a bigger system.

Kolbert quotes the chemist F. Sherwood Rowland, who said, in reference to his studies of CFCs, “The work is going very well, but it looks like the end of the world.”

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Anthropologist Joseph Tainter argued civilizations collapse when overwhelmed by complexity.

Like the children’s nursery rhyme about the old lady who swallowed a fly — then a spider to catch the fly, then a cat to catch the spider — our complicated solutions can create new, perhaps worse, problems.

This is the theme of Jenny Kleeman’s Sex Robots and Vegan Meat. Kleeman investigates several industries that purport to solve our world’s problems – You can eat meat without killing animals! You can make a baby without a mother’s body! – without addressing the fundamental causes of these problems.

Describing her travels, Kleeman writes:

I head back to my hotel as the reassuring cloak of darkness falls on Las Vegas. I’m exhausted. Music is thumping out of huge speakers mounted on the building’s exterior: throbbing, pounding beats that are supposed to entice gamblers into the hotel’s casino. I wipe my key card and flop down on the giant bed.

On the bedside table, there’s a metal dish full of individually wrapped pairs of earplugs: wax ones, foam ones, silicone ones – a profusion of solutions supplied by the management to the noise pollution problem caused by the management.

They could just switch the music off, of course, but they have provided a little piece of technology instead so they don’t have to.

My head is full of Eva, [a prototype interactive sex doll] who has the body of a real woman, but can be beaten without feeling a thing. Rather than dealing with the cause of a problem, we invent something to try to cancel it out.

Perhaps we should eat different foods. Perhaps our attitudes about sex or the importance of a sociable community are making our lives worse. Perhaps if we addressed these issues directly, we wouldn’t need sex robots or vegan meat.

Clean meat is one of many possible futures of food, so long as we continue to eat meat. We will always have the power to not want it anymore, or to want it much less.

That is where the real power lies: in harnessing our desires, rather than in mastering technology. Until we do, we will be even further removed from where our food comes from, and will feel even less responsible for it.

We will be perpetuating the kind of thinking that caused the meat mess in the first place.

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In April 2020, I described two major drawbacks to our efforts to “slow the spread” of Covid-19 instead of providing targeted protection for the people at high risk of severe illness.

1.) Immunity to most coronaviruses lapses within a matter of months. Keeping the virus in circulation longer increases the total number of infections and makes it more difficult to shield people at high risk from eventual exposure.

2.) Each infection encompasses some number of viral replications and thus genetic drift. If a population of 20 people transfers a virus between themselves one by one, rather than all catching it from the same initial carrier, the virus has 20-fold more generations to mutate and better evade our immune systems.

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Admittedly, my April 2020 prediction about the timeline for vaccine development was quite wrong – I thought this might take three to five years. I’m thankful that I was wrong. I’m obviously grateful for the fantastic work done by vaccine developers so far.

For these vaccines to effectively staunch viral transmission, we’ll need to vaccinate large numbers of people – immunity from prior infections won’t necessarily help much because immunity to this particular virus lapses so quickly, and because people’s prior infections were staggered in time. (Indeed, we’ll probably need to vaccinate large numbers of people repeatedly, because some of our data suggests that vaccine-derived immunity to this also lapses on a timescale of months.)

Unfortunately, we live in a country where large numbers of people distrust the medical establishment. Even if we had sufficient doses of the vaccines available today, I don’t know what percentage of our population would choose to get them.

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Masks definitely reduce viral transmission. It was obviously a good idea for everyone to wear masks anywhere that high risk and lower risk people share the same space.

Cooperation definitely makes for a better place to live. In places that enacted mask orders, it’s obviously a good idea to follow them.

It’s worth remembering, though, that any fix – even something as simple as this piece of cloth covering my nose and mouth – can have unintentional consequences. New virus variants – which our current vaccines may be less effective against – are a predictable result of our effort to “slow the spread” with masks.

And yet.

I volunteer with Pages to Prisoners, an organization that sends free books to people who are incarcerated. We’ve included a sheet of information about Covid-19 with each package recently, helping to explain that Covid-19 is not a hoax, that it’s a dangerous respiratory disease, that masks and social distancing can help people reduce their risk.

I’m currently revising this information sheet – it was put together months ago, when we understood less about this virus – and I’m still recommend that everyone wear masks.

Not just because prisons are places where many low risk and high risk people are confined together — although, they are. Outrageous sentencing practices have led to a large number of elderly people being stuck in prison.

But also, anecdotal evidence suggests that people are more likely to develop severe illness from Covid-19 when they are exposed to a large number of viral particles at once.

Viruses reproduce exponentially – you can get sick if you inhale even one capsid. But you’re more likely to get seriously ill if you inhale a whole bunch of viral particles. If you’re initially exposed to a small number of particles, your body will have more time to fight off the infection before it makes you feel sick.

Research studies from military bases have shown that Covid-19 will continue to spread even when everyone wears masks and tries to stay six feet away from each other. But we haven’t tested – an experiment like this would be totally unethical – whether we’re more likely to see asymptomatic or mild cases when people’s initial exposure is to a small number of viral particles.

It’s quite likely, though.

So, although I think our efforts to “slow the spread” weren’t the best plan last year, I’ll still be recommending masks.

On predictions and a scientific response to calamity.

On predictions and a scientific response to calamity.

We’re fast approaching flu season, which is especially harrowing this year.

We, as a people, have struggled to respond to this calamity. We have a lot of scientific data about Covid-19 now, but science is never value-neutral. The way we design experiments reflects our biases; the way we report our findings, even more so.

For example, many people know the history of Edward Jenner inventing the world’s first vaccine. Fewer are aware of the long history of inoculation in Africa (essentially, low-tech vaccination) that preceded Jenner’s work.

So it’s worthwhile taking a moment to consider the current data on Covid-19.

Data alone can’t tell us what to do – the course of action we choose will reflect our values as a society. But the data may surprise a lot of people – which is strange considering how much we all feel that we know about Covid-19.

Indeed, we may realize that our response so far goes against our professed values.

Spoiler: I think we shouldn’t close in-person school.

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Since April, I’ve written several essays about Covid-19. In these, I’ve made a number of predictions. It’s worthwhile to consider how accurate these predictions have been.

This, after all, is what science is. We use data to make an informed prediction, and then we collect more data to evaluate how good our prediction was.

Without the second step – a reckoning with our success or failure – we’re just slinging bullshit.

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I predicted that our PCR tests were missing most Covid-19 infections, that people’s immunity was likely to be short-lived (lasting for months, not years), and that Covid-19 was less dangerous than seasonal influenza for young people.

These predictions have turned out to be correct.

In my essays, I’ve tried to unpack the implications of each of these. From the vantage of the present, with much more data at our disposal, I still stand by what I’ve written.

But gloating’s no fun. So I’d rather start with what I got wrong.

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My initial predictions about Covid-19 were terrible.

I didn’t articulate my beliefs at the time, but they can be inferred from my actions. In December, January, and February, I made absolutely no changes to my usual life. I didn’t recommend that travelers be quarantined. I didn’t care enough to even follow the news, aside from a cursory glance at the headlines.

While volunteering with the high school running team, I was jogging with a young man who was finishing up his EMT training.

“That new coronavirus is really scary,” he said. “There’s no immunity, and there’s no cure for it.”

I shrugged. I didn’t know anything about the new coronavirus. I talked with him about the 1918 influenza epidemic instead.

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I didn’t make any change in my life until mid-March. And even then, what did I do?

I called my brother and talked to him about the pizza restaurant – he needed a plan in case there was no in-person dining for a few months.

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My next set of predictions were off, but in the other direction – I estimated that Covid-19 was about four-fold more dangerous than seasonal influenza. The current best estimate from the CDC is that Covid-19 is about twice as dangerous, with an infection fatality ratio of 0.25%.

But seasonal influenza typically infects a tenth of our population, or less.

We’re unlikely to see a significant disruption in the transmission of Covid-19 (this is the concept of “herd immunity”) until about 50% of our population has immunity from it, whether from vaccination or recovery. Or possibly higher – in some densely populated areas, Covid-19 has spread until 70% (in NYC) or even 90% (in prisons) of people have contracted the disease.

Population density is hugely important for the dynamics of Covid-19’s spread, so it’s difficult to predict a nation-wide threshold for herd immunity. For a ballpark estimate, we could calculate what we’d see with a herd immunity threshold of about 40% in rural areas and 60% in urban areas.

Plugging in some numbers, 330 million people, 80% urban population, 0.25% IFR, 60% herd immunity threshold in urban areas, we’d anticipate 450,000 deaths.

That’s about half of what I predicted. And you know what? That’s awful.

Each of those 450,000 is a person. Someone with friends and family. And “slow the spread” doesn’t help them, it just stretches our grieving to encompass a whole year of tragedy instead of a horrific month of tragedy.

If we don’t have a safe, effective vaccine soon enough, the only way to save some of those 450,000 people is to shift the demographics of exposure.

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Based on the initial data, I concluded that the age demographics for Covid-19 risk were skewed more heavily toward elderly people than influenza risk.

I may have been wrong.

It’s difficult to directly compare the dangers of influenza to the dangers of Covid-19. Both are deadly diseases. Both result in hospitalizations and death. Both are more dangerous for elderly or immunocompromised people, but both also kill young, healthy people.

Typically, we use an antigen test for influenza and a PCR-based test for Covid-19. The PCR test is significantly more sensitive, so it’s easier to determine whether Covid-19 is involved a person’s death. If there are any viral particles in a sample, PCR will detect them. Whereas antigen tests have a much higher “false negative” rate.

Instead of using data from these tests, I looked at the total set of pneumonia deaths. Many different viruses can cause pneumonia symptoms, but the biggest culprits are influenza and, in 2020, Covid-19.

So I used these data to ask a simple question – in 2020, are the people dying of pneumonia disproportionately more elderly than in other years?

I expected that they would be. That is, after all, the prediction from my claims about Covid-19 demographic risks.

I was wrong.

In a normal year (I used the data from 2013, 2014, and 2015, three years with “mild” seasonal influenza), 130,000 people die of flu-like symptoms.

In 2020 (at the time I checked), 330,000 people have died of flu-like symptoms. Almost three times as many people as in a “normal” year.

For people under the age of 18, we’ve seen the same number of deaths (or fewer) in 2020 as in other years. The introduction of Covid-19 appears to have caused no increased risk for these people.

But for people of all other ages, there have been almost three times as many people dying of these symptoms in 2020 compared to other years.

In most years, one thousand people aged 25-34 die of these symptoms; in 2020, three thousand have died. In most years, two thousand people aged 35-44 die of these symptoms; in 2020, six thousand have died. This same ratio holds for all ages above eighteen.

Younger people are at much less risk of harm from Covid-19 than older people are. But, aside from children under the age of eighteen, they don’t seem to be exceptionally protected.

Of course, my predictions about the age skew of risk might be less incorrect than I’m claiming here. If people’s dramatically altered behavior in 2020 has changed the demographics of exposure as compared to other years – which is what we should be doing to save the most lives – then we could see numbers like this even if Covid-19 had the risk skew that I initially predicted.

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I predicted that four or more years would pass before we’d be able to vaccinate significant numbers of people against Covid-19.

I sure hope that I was wrong!

We now know that it should be relatively easy to confer immunity to Covid-19. Infection with other coronaviruses, including those that cause common colds, induce the production of protective antibodies. This may partly explain the low risk for children – because they get exposed to common-cold-causing coronaviruses so often, they may have high levels of protective antibodies all the time.

Several pharmaceutical companies have reported great results for their vaccine trials. Protection rates over 90%.

So the problem facing us now is manufacturing and distributing enough doses. But, honestly, that’s the sort of engineering problem that can easily be addressed by throwing money at it. Totally unlike the problem with HIV vaccines, which is that the basic science isn’t there – we just don’t know how to make a vaccine against HIV. No amount of money thrown at that problem would guarantee wide distribution of an effective vaccine.

We will still have to overcome the (unfortunately significant) hurdle of convincing people to be vaccinated.

For any individual, the risk of Covid-19 is about twice the risk of seasonal influenza. But huge numbers of people choose not to get a flu vaccine each year. In the past, the United States has had a vaccination rate of about 50%. Here’s hoping that this year will be different.

Covid-19 spreads so fast – and so silently, with many cases of infected people who feel fine but are still able to spread the virus – that it will almost certainly be a permanent resident of the world we live in. We’re unlikely to eradicate Covid-19.

Which means that elderly people will always be at risk of dying from Covid-19.

The only way to protect people whose bodies have gone through “age-related immunosenence” – the inevitable weakening of an immune system after a person passes the evolutionarily-determined natural human lifespan of about 75 years – will be to vaccinate everybody else.

Depending on how long vaccine-conferred immunity lasts, we may need to vaccinate people annually. I worry, though, that it will become increasingly difficult to persuade people to get a Covid-19 vaccine once the yearly death toll drops to influenza-like levels – 50,000 to 100,000 deaths per year in the United States.

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I wrote, repeatedly, that immunity to Covid-19 is likely to be short-lived. Immunity to other coronaviruses fades within a few months.

(Note: you may have seen articles in the New York Times suggesting that we’ll have long-lasting protection. They’re addressing a different question — after recovery, or vaccination, are you likely to become severely ill with Covid-19? And the answer is “probably not,” although it’s possible. When I discuss immunity here, I mean “after recovery, or vaccination, are you likely to be able to spread the virus after re-infection?” And the answer is almost certainly “yes, within months.”)

And I wrote about the interplay between short-lived immunity and the transmission dynamics of an extremely virulent, air-born virus.

This is what the Harvard public health team got so wrong. When we slow transmission enough that a virus is still circulating after people’s immunity wanes, they can get sick again.

For this person, the consequences aren’t so dire – an individual is likely to get less sick with each subsequent infection by a virus. But the implications for those who have not yet been exposed are horrible. The virus circulates forever, and people with naive immune systems are always in danger.

It’s the same dynamics as when European voyagers traveled to the Americas. Because the European people’s ancestors lived in unsanitary conditions surrounded by farm animals, they’d cultivated a whole host of zoogenic pathogens (like influenza and this new coronavirus). The Europeans got sick from these viruses often – they’d cough and sneeze, have a runny nose, some inflammation, a headache.

In the Americas, there were fewer endemic diseases. Year by year, people wouldn’t spend much time sick. Which sounds great, honestly – I would love to go a whole year without headaches.

But then the disgusting Europeans reached the Americas. The Europeans coughed and sneezed. The Americans died.

And then the Europeans set about murdering anyone who recovered. Today, descendants of the few survivors are made to feel like second-class citizens in their ancestral homelands.

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In a world with endemic diseases, people who have never been exposed will always be at risk.

That’s why predictions made in venues such as the August New York Times editorial claiming that a six- to eight-week lockdown would stop Covid-19 were so clearly false. They wrote:

Six to eight weeks. That’s how long some of the nation’s leading public health experts say it would take to finally get the United States’ coronavirus epidemic under control.

For proof, look at Germany. Or Thailand. Or France.

Obviously, this didn’t work – in the presence of an endemic pathogen, the lockdowns preserved a large pool of people with naive immune systems, and they allowed enough time to pass that people who’d been sick lost their initial immunity. After a few months of seeming calm, case numbers rose again. For proof, look at Germany. Or France.

Case numbers are currently low in Thailand, but a new outbreak could be seeded at any time.

And the same thing is currently happening in NYC. Seven months after the initial outbreak, immunity has waned; case numbers are rising; people with mild second infections might be spreading the virus to friends or neighbors who weren’t infected previously.

All of which is why I initially thought that universal mask orders were a bad idea.

We’ve known for over a hundred years that masks would slow the spread of a virus. The only question was whether slowing the spread of Covid-19 would cause more people to die of Covid-19.

And it would – if a vaccine was years away.

But we may have vaccines within a year. Which means that I may have been wrong. Again, the dynamics of Covid-19 transmission are still poorly understood – I’ll try to explain some of this below.

In any case, I’ve always complied with our mask orders. I wear a mask – in stores, at school pickup, any time I pass within six feet of people while jogging.

To address global problems like Covid-19 and climate change, we need global consensus. One renegade polluting wantonly, or spewing viral particles into the air, could endanger the whole world. This is precisely the sort of circumstance where personal freedom is less important than community consensus.

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The transmission dynamics of Covid-19 are extremely sensitive to environment. Whether you’re indoors or outdoors. How fast the air is moving. The population density. How close people are standing. Whether they’re wearing masks. Whether they’re shouting or speaking quietly.

Because there are so many variable, we don’t have good data. My father attended a lecture and a colleague (whom he admires) said, “Covid-19 is three-fold more infectious than seasonal influenza.” Which is bullshit – the transmission dynamics are different, so the relative infectivity depends on our behaviors. You can’t make a claim like this.

It’s difficult to measure precisely how well masks are slowing the spread of this virus.

But here’s a good estimate: according to Hsiang et al., the number of cases of Covid-19, left unchecked, might have increased exponentially at a rate of about 34% per day in the United States.

That’s fast. If about 1% of the population was infected, it could spread to everyone within a week or two. In NYC, Covid-19 appear to spread to over 70% of the population within about a month.

(To estimate the number of infections in New York City, I’m looking at the number of people who died and dividing by 0.004 – this is much higher than the infection fatality rate eventually reported by the CDC, but early in the epidemic, we were treating people with hydroxychloraquine, an unhelpful poison, and rushing to put people on ventilators. We now know that ventilation is so dangerous that it should only be used as a last resort, and that a much more effective therapy is to ask people to lie on their stomachs – “proning” makes it easier to get enough oxygen even when the virus has weakened a person’s lungs.)

Masks dramatically slow the rate of transmission.

A study conducted at a military college – where full-time mask-wearing and social distancing were strictly enforced – showed that the number of cases increased from 1% to 3% of the population over the course of two weeks.

So, some math! Solve by taking ten to the power of (log 3)/14, which gives an exponential growth rate of 8% per day. Five-fold slower than without masks.

But 8% per day is still fast.

Even though we might be able to vaccinate large numbers of people by the end of next year, that’s not soon enough. Most of us will have been sick with this – at least once – before then.

I don’t mean to sound like a broken record, but the biggest benefit of wearing masks isn’t that we slow the rate of spread for everyone — exponential growth of 8% is still fast — but that we’re better able to protect the people who need to be protected. Covid-19 is deadly, and we really don’t want high-risk people to be infected with it.

I’ve tried to walk you through the reasoning here — the actual science behind mask policies — but also, in case it wasn’t absolutely clear: please comply with your local mask policy.

You should wear a mask around people who aren’t in your (small) network of close contacts.

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I’m writing this essay the day after New York City announced the end of in-person classes for school children.

This policy is terrible.

A major problem with our response to Covid-19 is that there’s a time lag between our actions and the consequences. Human brains are bad at understanding laggy data. It’s not our fault. Our ancestors lived in a world where they’d throw a spear at an antelope, see the antelope die, and then eat it. Immediate cause and effect makes intuitive sense.

Delayed cause and effect is tricky.

If somebody hosts a party, there might be an increase in the number of people who get sick in the community over the next three weeks. Which causes an increase in the number of hospitalizations about two weeks after that. Which causes people to die about three weeks after that.

There’s a two-month gap between the party and the death. The connection is difficult for our brains to grasp.

As a direct consequence, we’ve got ass-hats and hypocrites attending parties for, say, their newly appointed Supreme Court justice.

But the problem with school closures is worse. There’s a thirty year gap between the school closure and the death. The connection is even more difficult to spot.

Even if you have relatively limited experience reading scientific research papers, I think you could make your way through this excellent article from Chistakis et al.

The authors link two sets of existing data: the correlation between school closures and low educational achievement, and the correlation between low educational achievement and premature death.

The public debate has pitted “school closures” against “lives saved,” or the education of children against the health of the community. Presenting the tradeoffs in this way obscures the very real health consequences of interrupted education.

These consequences are especially dire for young children.

The authors calculate that elementary school closures in the United States might have (already!) caused 5.5 million years of life lost.

Hsiang et al. found that school closures probably gave us no benefit in terms of reducing the number of Covid-19 cases, because children under 18 aren’t significant vectors for transmission (elementary-aged children even less so), but even if school closures had reduced the number of Covid-19 cases, closing schools would have caused more total years of life to be lost than saved.

The problem – from a political standpoint – is that Covid-19 kills older people, who vote, whereas school closures kill young people, who are intentionally disenfranchised.

And, personally, as someone with far-left political views, it’s sickening for me to see “my” political party adopt policies that are so destructive to children and disadvantaged people.

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So, here’s what the scientific data can tell us so far:

  • We will eventually have effective vaccines for Covid-19. Probably within a year.
  • Covid-19 spreads even with social distancing and masks, but the spread is slower.
  • You have no way of knowing the risk status of people in a stranger’s bubble. (Please, follow your local mask orders!)
  • Schools – especially elementary schools – don’t contribute much to the spread of Covid-19.
  • School closures shorten children’s lives (and that’s not even accounting for their quality of life over the coming decades).
  • An individual case of Covid-19 is about twice as dangerous as a case of seasonal influenza (which is scary!).
  • Underlying immunity (from prior disease and vaccination) to Covid-19 is much lower than for seasonal influenza, so there will be many more cases.
  • Most people’s immunity to Covid-19 probably lasts several months, after which a person can be re-infected and spread the virus again.

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So, those are some data. But data don’t tell us what to do. Only our values can do that.

Personally, I value the lives of children.

I wouldn’t close schools.

On threat.

On threat.

At the end of “Just Use Your Thinking Pump!”, a lovely essay that discusses the evolution (and perhaps undue elevation) of a particular set of practices now known as the scientific method, Jessica Riskin writes:

Covid-19 has presented the world with a couple of powerful ultimatums that are also strikingly relevant to our subject here. The virus has said, essentially, Halt your economies, reconnect science to a whole understanding of yourself and the world, or die.

With much economic activity slowed or stopped to save lives, let us hope governments find means to sustain their people through the crisis.

Meanwhile, with the din of “innovation” partially silenced, perhaps we can also use the time to think our way past science’s branding, to see science once again as integral to a whole, evolving understanding of ourselves and the world.

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True, the world has presented us with an ultimatum. We must halt our economies, reconnect science to a whole understanding of ourselves and our world, or die.

Riskin is a professor at Stanford. Her skies are blackened with soot. In the words of Greta Thunberg, “Our house is on fire.

For many years, we’ve measured the success of our economy in terms of growth. The idea that we can maintain perpetual growth is a delusion. It’s simple mathematics. If the amount of stuff we manufacture – telephones, televisions, air conditioners – rises by 3% each and every year, we’ll eventually reach stratospheric, absurd levels.

In the game “Universal Paperclips,” you’re put in control of a capitalist system that seeks perpetual growth. If you succeed, you’ll make a lot of paperclips! And you will destroy the planet.

Here in the real world, our reckless pursuit of growth has (as yet) wrought less harm, but we’ve driven many species to extinction, destroyed ancient forests, and are teetering at the precipice of cataclysmic climate change. All while producing rampant inequality with its attendant abundance of human misery.

We must reconnect science to a whole understanding of ourselves and the world, or die.

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We are in danger. But Covid-19 isn’t the major threat we’re facing.

I consider myself to be more cautious than average – I would never ride a bicycle without a helmet – and I’m especially cautious as regards global pandemic. Antibiotic resistance is about to be a horrific problem for us. Zoogenic diseases like Covid-19 will become much more common due to climate change and increased human population.

I’m flabbergasted that these impending calamities haven’t caused more people to choose to be vegan. It seems trivial – it’s just food – but a vegan diet is one of our best hopes for staving off antibiotic resistant plagues.

A vegan diet would have prevented Covid-19. Not that eating plants will somehow turbocharge your immune system – it won’t – but this pandemic originated from a meat market.

And a vegan diet will mitigate your contribution to climate change, which has the potential to cause the full extinction of the human race.

Make our planet uninhabitable? We all die. Make our planet even a little less habitable, which leads to violent unrest, culminating in warring nations that decide to use nukes? Yup, that’s another situation where we all die.

By way of contrast, if we had made no changes in our lives during the Covid-19 pandemic – no shutdown, no masks, no social distancing, no PCR tests, no contact tracing, no quarantines – 99.8% of our population would have survived.

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Indeed, we often discuss the Covid-19 crisis in a very imprecise way. We say that Covid-19 is causing disruptions to learning, that it’s causing domestic violence or evictions. On the front page of Sunday’s New York Times business section, the headline reads, “The Other Way that Covid Kills: Hunger.

Covid-19 is a serious disease. We need to do our best to avoid exposing high-risk people to this virus, and we should feel ashamed that we didn’t prioritize the development of coronavirus vaccines years ago.

But there’s a clear distinction between the harms caused by Covid-19 (hallucinogenic fevers, cardiac inflammation, lungs filling up with liquid until a person drowns, death) and the harms caused by our response to Covid-19 (domestic violence, educational disruption, starvation, reduced vaccination, delayed hospital visits, death).

Indeed, if the harms caused by our response to Covid-19 are worse than the harms caused by Covid-19 itself, we’re doing the wrong thing.

In that New York Times business article, Satbir Singh Jatain, a third-generation farmer in northern India, is quoted: “The lockdowns have destroyed farmers. Now, we have no money to buy seeds or pay for fuel. …. soon they will come for my land. There is nothing left for us.

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Covid-19 is awful. It’s a nasty disease. I’m fairly confident that I contracted it in February (before PCR tests were available in the United States), and my spouse says it’s the sickest she’s ever seen me.

Yes, I’d done something foolish – I was feeling a little ill but still ran a kilometer repeat workout with the high school varsity track team that I volunteer with. High intensity workouts are known to cause temporary immunosuppression, usually lasting from 3 to 72 hours.

My whole family got sick, but I fared far worse than the others.

It was horrible. I could barely breathe. Having been through that, it’s easy to understand how Covid-19 could kill so many people. I wouldn’t wish that experience on anyone.

And I have very low risk. I don’t smoke. I don’t have diabetes. I’m thirty-seven.

I wish it were possible to protect people from this.

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Obviously, we should have quarantined all international travelers beginning in December 2019. Actually, ten days probably would have been enough. We needed to diecitine all international travelers.

By February, we had probably allowed Covid-19 to spread too much to stop it.

By February, there were probably enough cases that there will always be a reservoir of this virus among the human species. 80% of people with Covid-19 feel totally fine and don’t realize they might be spreading it. By talking and breathing, they put viral particles into the air.

By the end of March, we were much, much too late. If you look at the numbers from New York City, it’s pretty clear that the preventative measures, once enacted, did little. Given that the case fatality rate is around 0.4%, there were probably about 6 million cases in New York City – most of the population.

Yes, it’s possible that New York City had a somewhat higher case fatality rate. The case fatality rate depends on population demographics and standard of care – the state of New York had an idiotic policy of shunting Covid-19 patients into nursing homes, while banning nursing homes from using Covid-19 PCR tests for these patients, and many New York doctors were prescribing hydroxychloroquine during these months, which increases mortality – but even if the case fatality rate in New York City was as high as 0.6%, a majority of residents have already cleared the virus by now.

The belated public health measures probably didn’t help. And these health measures have caused harm – kids’ schooling was disrupted. Wealthy people got to work from home; poor people lost their jobs. Or were deemed “essential” and had to work anyway, which is why the toll of Covid-19 has been so heavily concentrated among poor communities.

The pandemic won’t end until about half of all people have immunity, but a shutdown in which rich people get to isolate themselves while poor people go to work is a pretty shitty way to select which half of the population bears the burden of disease.

I am very liberal. And it’s painful to see that “my” political party has been advocating for policies that hurt poor people and children during the Covid-19 pandemic.

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Because we did not act soon enough, Covid-19 won’t end until an appreciable portion of the population has immunity – at the same time.

As predicted, immunity to Covid-19 lasts for a few months. Because our public health measures have caused the pandemic to last longer than individual immunity, there will be more infections than if we’d done nothing.

The shutdowns, in addition to causing harm on their own, will increase the total death toll of Covid-19.

Unless – yes, there is a small glimmer of hope here – unless we soon have a safe, effective vaccine that most people choose to get.

This seems unlikely, though. Making vaccines is difficult. And we already know that most people don’t get the influenza vaccine, even though, for younger people, influenza is more dangerous than Covid-19.

Look – this is shitty. I get an influenza vaccine every year. It’s not just for me – vaccination protects whole communities.

Economist Gregory Mankiw believes that we should pay people for getting a Covid-19 vaccine.

Yes, there are clear positive externalities to vaccination, but I think this sounds like a terrible idea. Ethically, it’s grim – the Covid-19 vaccines being tested now are a novel type, so they’re inherently more risky than other vaccines. By paying people to get vaccinated, we shift this burden of uncertainty onto poor communities.

We already do this, of course. Drug trials use paid “volunteers.” Especially phase 1 trials – in which drugs are given to people with no chance of medical benefit, only to see how severe the side effects are – the only enrollees are people so poor that the piddling amounts of money offered seem reasonable in exchange for scarfing an unknown, possibly poisonous medication.

Just because we already do an awful thing doesn’t mean we should make the problem worse.

And, as a practical matter, paying people to do the right thing often backfires.

In An Uncertain Glory, Jean Dreze and Amartya Sen write:

To illustrate, consider the recent introduction, in many Indian states, of schemes of cash incentives to curb sex-selective abortion. The schemes typically involve cash rewards for the registered birth of a girl child, and further rewards if the girl is vaccinated, sent to school, and so on, as she gets older.

These schemes can undoubtedly tilt economic incentives in favor of girl children. But a cash reward for the birth of a girl could also reinforce people’s tendency to think about family planning in economic terms, and also their perception, in the economic calculus of family planning, that girls are a burden (for which cash rewards are supposed to compensate).

Further, cash rewards are likely to affect people’s non-economic motives. For instance, they could reduce the social stigma attached to sex-selective abortion, by making it look like some sort of ‘fair deal’ — no girl, no cash.

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What happens if it takes a few years before there are sufficient doses of an effective vaccine that people trust enough to actually get?

Well, by then the pandemic will have run its course anyway. Masks reduce viral transmission, but they don’t cut transmission to zero. Even in places where everyone wears masks, Covid-19 is spreading, just slower.

I’ve been wearing one – I always liked the Mortal Kombat aesthetic. But I’ve been wearing one with the unfortunate knowledge that masks, by prolonging the pandemic, are increasing the death toll of Covid-19. Which is crummy. I’ve chosen to behave in a way that makes people feel better, even though the science doesn’t support it.

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We, as a people, are in an awful situation right now. Many of us are confronting the risk of death in ways that we have not previously.

In The Rise and Fall of American Growth, Robert Gordon writes:

More than 37 percent of deaths in 1900 were caused by infectious diseases, but by 1955, this had declined to less than 5 percent and to only 2 percent by 2009.

Of course, this trend will still hold true in 2020. In the United States, there have been about 200,000 Covid-19 deaths so far, out of 2,000,000 deaths total this year. Even during this pandemic, less than 1% of deaths are caused by Covid-19.

And I’m afraid. Poverty is a major risk factor for death of all causes in this country. Low educational attainment is another risk factor.

My kids am lucky to live in a school district that has mostly re-opened. But many children are not so fortunate. If we shutter schools, we will cause many more deaths – not this year, but down the road – than we could possibly prevent from Covid-19.

Indeed, school closures, by prolonging the pandemic (allowing people to be infected twice and spread the infection further), will increase the death toll from Covid-19.

School closures wouldn’t just cause harm for no benefit. School closures would increase the harm caused by Covid-19 and by everything else.

On ants and infection.

On ants and infection.

I live in a college town. Last week, students returned.

Yesterday’s paper explains that dire punishment awaits the students who attended a Wednesday night party. In bold letters atop the front page, “IU plans to suspend students over party.

In the decade that I’ve lived here, many parties have led to sexual assaults, racist hate speech, and violence. The offending students were rarely punished. But this party was egregious because “there were about 100 people there.

IU officials “have seen a photothat shows a large group of young people standing close together outside a house at night, many of them not wearing masks.

I’ve seen the images – someone filmed a video while driving by. There they are – a group of young people, standing outside.

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Science magazine recently interviewed biologist Dana Hawley about social distancing in the animal kingdom.

When spiny lobsters are sick, their urine smells different. Healthy lobsters will flee the shared den. Leaving is dangerous, since the lobsters will be exposed to predators until they find a new home, but staying would be dangerous, too – they might get sick. To survive, lobsters have to balance all the risks they face.

My favorite example of social distancing in the animal kingdom wasn’t discussed. When an ant is infected with the cordyceps fungus, it becomes a sleeper agent. Jennifer Lu writes in National Geographic that “as in zombie lore, there’s an incubation period where infected ants appear perfectly normal and go about their business undetected by the rest of the colony.

Then the fungus spreads through the ants body, secreting mind control chemicals. Eventually, the fungus will command the infected ant to climb to a high place. A fruiting body bursts from the ant’s head and rains spores over the colony.

Infection is almost always lethal.

If an ant notices that a colony member has been infected, the healthy ant will carry the infected ant away from the colony and hurl it from a cliff.

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The FDA will approve any Covid-19 vaccine that cuts risk by half. It’s very unlikely that a Covid-19 vaccine will cut the risk by more than about two-thirds, and the vaccine will work least well for people who need protection most.

Most likely, the Covid-19 epidemic will end before there’s vaccine. The herd immunity threshold seems to be much lower than some researchers feared – our current data suggest that the epidemic will end after about 40% of the population has immunity.

The herd immunity threshold isn’t an inherent property of a virus – it depends upon our environment and behaviors. In prisons, we’ve seen Covid-19 spread until nearly 90% of people were infected. In parts of New York City where many essential workers live in crowded housing, Covid-19 spread until 50% of people were infected.

In a culture where everyone kissed a sacred statue in the center of town each morning, the herd immunity threshold would be higher. If people wear masks while interacting with strangers, the herd immunity threshold will be lower.

In a world that maintains a reservoir of the virus, though, someone who hasn’t yet been exposed will always be at risk.

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The New York Times recently discussed some of the challenges that colleges face when trying to reopen during the epidemic.

Most schools ban socializing outside “social pods” – the small groups of students that some colleges are assigning students to, usually based on their dorms.

Most administrators seem to believe that a rule banning sex is unrealistic, and are quietly hoping that students will use common sense and refrain from, say, having it with people outside their pod.

In 2012, The Huffington Post published a list of the “Top 10 sex tips for college freshmen.” Their fourth piece of advice (#1 and #2 were condoms, #3 was not having sex while drunk) is to avoid having sex with people who live too close to you. “Students in other dorms = fair game. Students in same dorm = proceed with caution.

I had a big group of friends for my first two years of college. After a breakup, I lost most of those friends.

This is crummy, but it would be much worse if I’d lost my friendships with the only people whom the administrators allowed me to spend time with.

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We can slow the spread of Covid-19, but slowing the spread won’t prevent deaths, not unless we can stave off infection until there is a highly effective vaccine. That might take years. We might never have a highly effective vaccine – our influenza vaccines range in efficacy from about 20% to 80%, and we have much more experience making these.

Our only way to reduce the eventual number of deaths is to shift the demographics of exposure. If we reach the herd immunity threshold without many vulnerable people being exposed, we’ll save lives.

A college would best protect vulnerable students and faculty by allowing the students who are going to socialize to host dense parties for a few weeks before mingling with others. This would allow the virus to spread and be cleared before there was a risk of transferring infections to vulnerable people.

I’d draft a waiver. Are you planning to socialize this semester? If so, come do it now! By doing so, you will increase your risk of contracting Covid-19. This is a serious disease – it’s possible for young, healthy people to die from it. But, look, if you’re gonna socialize eventually, please just get it over with so that you don’t endanger other people.

With this plan, some young people might die of Covid-19. But some young people will die of Covid-19 even if everyone practices social distancing – slowing the spread of infections doesn’t save lives, it delays deaths. And fewer young people would die of Covid-19 than die of influenza each year.

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When confronting cordyceps, which is almost always fatal, ants throw sick colony members off cliffs.

When ants confront less lethal fungal infections, they protect the colony by shifting the demographics of exposure and by ramping up to the herd immunity threshold as quickly as possible.

Malagocka et al. discuss demographics in their review article, “Social immunity behavior among ants infected by specialist and generalist fungi.”

Outside-nest foragers, who have the highest risks of acquiring pathogens from the environment, have limited access to the brood area with the most valuable groups, and are recruited from older individuals, who are less valuable from the colony survival perspective.

Konrad et al. discuss intentional exposure in their research article, “Social transfer of pathogenic fungus promotes active immunization in ant colonies.”

When worker ants encounter an infected colony member, they intentionally inoculate themselves. “Social immunization leads to faster elimination of the disease and lower death rates.

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It feels disquieting for me to defend the behavior of frat guys. Personally, I’d like to see the whole fraternity system abolished. And in March, when we knew less about Covid-19, I was appalled that people went out partying over spring break. But I was wrong. Perhaps inadvertently, those young people were behaving in the way that would save most lives.

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Erika Meitner’s 2006 poem “Pediatric Eschatology” begins

the nurse called back and told us to use bleach
on anything we touch, she said wash everything
in hot water
, insisted we won’t treat you if
you’re asymptomatic, we won’t
, and made us
an appointment anyway. so we waited and waited
with the dog-eared magazines and recall posters

It’s horrible to face the end. It’s almost worse to know that the things you fear are harmless to others. All the asymptomatic cases are like a slap in the face to those whose friends and family have died.

Braun et al. recently published a study in Nature showing that a large number of people who’ve never encountered Covid-19 may already have significant immunity. Parts of the Covid-19 virus are similar to the viruses that cause common colds, and exposure to those viruses might provide the immunity that lets people recover without ever feeling sick.

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I believe we should be doing more to protect young people. Gun control, ending farm subsidies, fighting climate change. Enacting privacy laws to reign in the surveillance capitalists. Breaking up monopolies. Providing good careers despite automation. Making sure that everyone has clean air to breathe and clean water to drink. Getting nutritious food into our nation’s many food deserts. Providing equitable access to health care.

But, punishing young people for socializing?

We’re not making them safer. And we’re not making ourselves safer, either.

Seriously, I know we humans are selfish, but we have to be able to handle an epidemic better than ants.

Red ant: photograph by William Cho

On hydroxychloroquine, expertise, and the power of persuasion.

On hydroxychloroquine, expertise, and the power of persuasion.

Recently, a friend who works in the ER wrote to ask me about hydroxychloroquine.

Yes, I know. I was shocked, too. But my friend was sincere. Although most reputable news outlets have publicized that hydroxychloroquine doesn’t work against Covid-19, my friend read an article from Harvey Risch in Newsweek that seemed really compelling.

Risch has impeccable credentials – he’s an M.D. Ph.D. and a professor of epidemiology at Yale’s School of Public Health. And a lot of what he wrote for his July 23rd article is quite sensible:

Why has hydroxychloroquine been disregarded?

First, as all know, the medication has become highly politicized. For many, it is viewed as a marker of political identity, on both sides of the political spectrum. Nobody needs me to remind them that this is not how medicine should proceed.

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Medical data isn’t perfect, and confirmation bias is very real. So there’s a chance that medical doctors really could hoodwink themselves into discounting a helpful medication, the same way that so many medical doctors get suckered into overprescribing drugs after pharmaceutical companies bribe them with gifts. Yup, medical doctors are human, too.

I know that I’m so dismayed by our current president that I’m inclined to distrust hydroxychloroquine just because he says the drug is great.

So it was a shock for me to read Risch’s article. He wrote that there was data showing that hydroxychloroquine, when used in a combination therapy early during a high-risk person’s Covid-19 infection, could dramatically reduce the risk of serious complications. If more people took hydroxychloroquine, he wrote, fewer would die.

Risch acknowledges that hydroxychloroquine is dangerous – it might kill 1 out of each 10,000 people who take it – but Covid-19 is obviously dangerous, too – it kills 3 out of each 1,000 people who contract it:

In the future, I believe this misbegotten episode regarding hydroxychloroquine will be studied by sociologists of medicine as a classic example of how extra-scientific factors overrode clear-cut medical evidence.

But for now, reality demands a clear, scientific eye of the evidence and where it points. For the sake of high-risk patients, for the same of our parents and grandparents, for the sake of the unemployed, for our economy and for our polity, especially those disproportionately affected, we must start treating immediately.

Those are strong words. And, really, the Newsweek article felt persuasive to me. And so I looked up Risch’s research in the American Journal of Epidemiology, hoping to see the actual data in support of his claims.

I’m lucky, that way. I’m a scientist, so I don’t have to trust the words of a supposed expert. I’m an expert. I get to look at the data.

The data are much less compelling than Risch’s words.

Risch discusses the results of an uncontrolled study by Vladimir Zelenko, a medical doctor in Monroe, New York: “For example, among Connecticut cases 60 years of age or older, at present the mortality is 20%. Thus it would be ballpark to estimate that some 20% of the 1466 treated high-risk patients in the Zelenko cohort would have died without outpatient hydroxychloroquine plus antibiotic.

This is an egregiously inaccurate statement. The high death rate cited – 20 – is for older patients who test positive for Covid-19 and have such severe symptoms that they need to be hospitalized.

As described in the short statement released by Zelenko, he treated 405 people who visited his office complaining of mild cough, fever, headache, sore throat, or diarrhea. His patients were not given a Covid-19 test. Presumably, many were never infected with Covid-19.

It is not a surprise to see that a 60-year-old patient who takes hydroxychloroquine after developing a sore throat from seasonal allergies is less likely to die than a 60-year-old patient who is diagnosed with Covid-19 in the hospital.

Of Zelenko’s 405 patients, at least two 2 died. This is lower than the expected 1% mortality rate of high-risk patients who contract Covid-19. But this set of 405 patients included low-risk patients experiencing shortness of breath and high-risk patients experiencing mild headache, many of whom never had Covid-19.

Zelenko’s report is two pages long and written in extremely lucid prose. Risch either totally misread it, which is galling, or intentionally mis-described it, which is worse.

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So, why was Zelenko giving people hydroxychloroquine in the first place?

Well, I’d heard that an in vitro study – which means “inside a test tube or petri dish, not a person” – showed that hydroxychloroquine reduced Covid-19 viral replication. But I hadn’t read the original paper. So I looked it up.

It should have taken me less than a minute to find this paper. Unfortunately, people have been pretty sloppy with their references. I get it. Covid-19 is scary, and it’s urgent, so people are publishing faster than usual.

I assumed that I could pull up almost any paper on hydroxychloroquine and Covid-19 and quickly find the citation for the original study. Indeed, most purport to be citing it. But in this, the citation that ought to have pointed to that study instead sent me to a paper on the differentiation of lung stem cells, and in this, the relevant citation incorrectly points to a paper on the drug lopinavir.

Ugh. I mean, these bungled citations aren’t that big a deal for me, personally – just means I had to give up on piggybacking and instead search Pubmed. But it undermines trust when you can’t get the little things right.

Anyway, the earliest reference that I found was from Liu et al., their study “Hydroxychloroquine, a less toxic derivative of chloroquine, is effective at inhibiting SARS-CoV-2 infection in vitro.” And, yes, I’ll admit – I thought about putting in the wrong link just to mess with you. But, if I did that, would you still trust me about the rest of this?

Liu et al. used Vero cells – a cell line derived from a kidney cancer in African green monkeys – and for Figure 1, they measured both how much hydroxychloroquine it takes to kill cells (about 200 micromolar is a cytotoxic dose) and how much hydroxychloroquine it takes to inhibit viral infection (about a 10 micromolar dose).

Okay. To me, that’s already sounding a little spooky. The bigger the difference between an effective dose and a lethal dose, the safer you are.

That’s why a bunch of hippies died after The Teachings of Don Juan was published. That book touted jimsomweed as a psychedelic. Indeed, the plant contains a high concentration of scopolamine, which can give people nightmarish visions of flying. It’s a powerful hallucinogen. But the effective dose is quite close to the lethal dose – when curious kids try to get high off it, they’re flirting with death.

Everyone’s body is a little different from everyone else’s. Maybe a dose that’s safe for you would kill me. The odds of disaster are worse when the effective dose and lethal dose are similar.

So, Liu et al. saw cytotoxicity kick in at around 100 micromolar hydroxychloroquine, getting pretty high by 200 micromolar. And for their visual assay of viral infection, they bathed their Vero cells in 50 micromolar hydroxychloroquine.

To block viral entry, they were coming pretty close to just killing these cells with the drug.

And the problem is even worse inside a human body. You take a drug and it gets into your bloodstream. It’ll reach some concentration there. This is the concentration that matters most for toxicity.

But the drug will only be effective against Covid-19 when it reaches your lungs. When Marzolini et al. used mass spectrometry to measure how much of hydroxychloroquine was actually getting from a patient’s blood to their lungs, they found that it wasn’t at a high enough concentration to reproduce any effects seen in vitro.

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Indeed, a randomized clinical study showed that hydroxychloroquine fails as a post-exposure prophylaxis. The drug was given to people who were worried about exposure because they’d spent time with someone who tested positive for Covid-19. The drug didn’t help – these people contracted the infection at the same rate as people who were given a placebo.

A randomized clinical study also showed that hydroxychloroquine fails as a cure. People who visited a hospital and tested positive for Covid-19 but had mild symptoms were given the drug. Their disease was just as likely to progress as people who received a placebo.

Hydroxychloroquine doesn’t work, and it’s toxic.

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I was left wondering: why would Risch write these things? Why would he write that article for Newsweek? He’s clearly intelligent, and, from the tone of his writing, I feel confident that he wants to help people.

He might even believe wholeheartedly in the conclusion he’s presenting.

That’s generally true among scientists. Confirmation bias is insidious.

That paper from the team at Harvard? They did some modeling and argued that, if Covid-19 is seasonal, we will save most lives by periodically shutting down. But their model left out the waning immunity that would cause Covid-19 to be seasonal! Whoops. That’s why they reached the wrong conclusion.

Or the recent New York Times editorial from Iwasaki and Medzhitov, both professors of immunobiology at Yale, reassuring readers that they won’t get Covid-19 twice. Well, that’s not correct.

Some antigens confer immunity that lasts about as long as our lives. Most don’t. Influenza immunity lasts months, not years. The paper that Iwasaki and Medzhitov cited in their article, a study in which people were intentionally infected with a less dangerous coronavirus, found that immunity to that virus lasted months, not years.

Covid-19 immunity will not last forever. The relevant question isn’t whether you can be infected again, it’s how soon you can be re-infected. With the data we have so far, it’s reasonable to expect that the answer will be measured in months, not years.

There’s some good news – the second time you contract Covid-19, it’ll probably be less severe than the first. In addition to antibodies, your immune system has “T cell memory” to help you fight off subsequent infections. But, as is also described in the paper cited by Iwasaki and Medzhitov, even people who felt fine were shedding virus again the second time they were infected.

During the second infection, the research subjects were shedding viral particles for a shorter period of time. But, especially with Covid-19 – a virus that can be transmitted simply by talking – a person who sheds virus for a short time while feeling fine is probably more likely to transmit the disease than somebody who sheds virus for a whole week while feeling like garbage.

The person who feels like garbage will stay home. The person who feels fine won’t.

Still, though, I was left wondering – what underlying beliefs would sway Risch enough that he’d make these blunders?

Eventually, I decided to lump his motivation in with mine. Maybe that’s fair, maybe it’s not. Really, I have no idea what he was thinking, so this is just my best guess.

But I imagine that many of these people – Risch, Iwasaki, Medzhitov, John Ioannidis, David Katz, all of whom are very smart, and all of whom mean well – understand that the strategies we’re using against Covid-19 are both ineffectual and are causing harm.

No shutdown will eliminate Covid-19 – the best we can do is to delay it. And we can delay it only as long as we maintain the shutdown. Maybe that seems fine if you’re an older, wealthy person brimming with optimism about vaccine development, like Anthony Fauci who thinks we’ll have a working vaccine early next year, but it’s unconscionable if you think a working vaccine might be five or more years away.

I don’t think we should try to pause children’s development for five years.

Still, there’s no mathematical or logical way to prove what we should do. School closures definitely slow the spread of Covid-19. How do you balance the good of delaying an elderly person’s infection by three months (which is equivalent to a drug that extends a patient’s life by three months) with the harms we’re causing?

I know what I’d do, but other people have different priorities than me. And that’s okay!

I’d like to think, though, that I’m not trying to hoodwink anybody about the science in order to deceptively get them to do the thing I think is right.

Like, yes, I think schools should be open. I think we owe it to children. Right now, children are suffering, but this is our fault, the fault of grown-ups.

We have known for over a decade that we ought to make coronavirus vaccines – we didn’t devote enough resources to it, and now we don’t have one. We’ve known for decades that eating animals – both those sold in meat markets like in Wuhan and the ones raised in “concentrated animal feeding operations” throughout the U.S. – will create more zoogenic diseases, and we kept doing it. We know that a guaranteed basic income would’ve given people the resources they needed to self-isolate during an epidemic – we don’t have one. We know that guaranteed access to health care would keep our death rate down.

Climate change will make pandemics more frequent, in addition to making our world unliveable for future generations. And we haven’t taken action to stop it.

None of these failings are children’s fault. We, older people, have failed. We fucked up. And now we’re asking children to make sacrifices to dampen the impact of our mistake (although, again, it won’t work – it’ll just delay the eventual repercussions).

I think today’s children deserve a fair shot at a good life, and I think that school is an essential part of that.

But don’t let anybody try to convince you that it’s safe to re-open schools because hydroxychloroquine will stop Covid-19.

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.