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 money, nursing home care, and Covid-19.

In April, I wrote several essays and articles about our collective response to Covid-19.

I was worried – and am still worried, honestly – that we weren’t making the best choices.

It’s hard not to feel cynical about the reasons why we’ve failed. For instance, our president seems more concerned about minimizing the visibility of disaster than addressing the disaster itself. We didn’t respond until this virus had spread for months, and even now our response has become politicized.

Also, the best plans now would include a stratified response based on risk factor. Much more than seasonal influenza, the risk of serious complications from Covid-19 increases with age. Because we didn’t act until the virus was widespread, eighty-year-olds should be receiving very different recommendations from forty- and fifty-year-olds.

Our national response is being led by an eighty-year-old physician, though, and he might be biased against imposing exceptional burdens on members of his own generation (even when their lives are at stake) and may be less sensitive to the harms that his recommendations have caused younger people.

I’m aware that this sounds prejudiced against older folks. That’s not my intent.

I care about saving lives.

Indeed, throughout April, I was arguing that our limited Covid-19 PCR testing capacity shouldn’t be used at hospitals. These tests were providing useful epidemiological data, but in most cases the results weren’t relevant for treatment. The best therapies for Covid-19 are supportive care – anti-inflammatories, inhalers, rest – delivered as early as possible, before a patient has begun to struggle for breath and further damage their lungs. Medical doctors provided this same care whether a Covid-19 test came back positive or negative.

(Or, they should have. Many patients were simply sent home and told to come back if they felt short of breath. Because they didn’t receive treatment early enough, some of these patients then died.)

Instead, our limited testing capacity should have been used at nursing homes. We should have been testing everyone before they went through the doors of a nursing home, because people in nursing homes are the most vulnerable to this virus.

I realize that it’s an imposition to make people get tested before going in, either for care or to work – even with real-time reverse-transcription PCR, you have to wait about two hours to see the results. But the inconvenience seems worthwhile, because it would save lives.

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From March 25 until May 10 – at the same time that I was arguing that our limited Covid-19 tests be used at nursing homes instead of hospitals – the state of New York had a policy stating that nursing homes were prohibited from testing people for Covid-19.

I really dislike the phrase “asymptomatic transmission” – it’s both confusing and inaccurate, because viral shedding is itself a symptom – but we knew early on that Covid-19 could be spread by people who felt fine. That’s why we should have been using PCR tests before letting people into nursing homes.

But in New York, nursing homes were “prohibited from requiring a hospitalized resident who is determined medically stable to be tested for COVID-19 prior to admission or readmission.

This policy caused huge numbers of deaths.

Not only do nursing homes have the highest concentration of vulnerable people, they also have far fewer resources than hospitals with which to keep people safe. Nursing home budgets are smaller. Hallways are narrower. Air circulation is worse. The workers lack protective gear and training in sterile procedure. Nursing home workers are horrendously underpaid.

The low wages of nursing home workers aren’t just unethical, they’re dangerous. A recent study found that higher pay for nursing home workers led to significantly better health outcomes for residents.

This study’s result as described in the New York Times – “if every county increased its minimum wage by 10 percent, there could be 15,000 fewer deaths in nursing homes each year” – is obviously false. But even though the math doesn’t work out, raising the minimum wage is the right thing to do.

If we raised the minimum wage, we probably would have a few years in which fewer people died in nursing homes. But then we’d see just as many deaths.

Humans can’t live forever. With our current quality of care, maybe nursing home residents die at an average age of 85. If we raise the minimum wage, we’ll get better care, and then nursing home residents might die at an average age of 87. After two years, we’d reach a new equilibrium and the death rate would be unchanged from before.

But the raw number here – how many people die each year – isn’t our biggest concern. We want people to be happy, and an increase in the minimum wage would improve lives: both nursing home residents and workers. Which I’m sure that study’s lead author, economist Kristina Ruffini, also believes. The only problem is that things like “happiness” or “quality of life” are hard to quantify.

Especially when you’re dealing with an opposition party that argues that collective action can never improve the world, you have to focus on quantifiable data. Happiness is squishy. A death is unassailable.

Indeed, that’s partly why we’ve gotten our response to Covid-19 wrong. Some things are harder to measure than others. It’s easy to track the number of deaths caused by Covid-19. (Or at least, it should be – our president is still understating the numbers.)

It’s much harder to track the lives lost to fear, to domestic violence, and to despair (no link for this one – suddenly Fox News cares about “deaths of despair,” only because they dislike the shutdown even more than they dislike poor people).  It’s hard to put a number on the value of 60 million young people’s education.

But we can’t discount the parts of our lives that are hard to measure – often, they’re the most important.

On writing.

On writing.

At high doses, psilocybin mushrooms trigger transcendent, mystical experiences.  Many researchers are incorporating these into treatments for PTSD, depression, and other maladies that stem from a crisis of meaning or identity.

There are challenges inherent in using medicines that disrupt the workings of a person’s consciousness.  William Richards, who conducts psychedelic therapy at Johns Hopkins, writes in Sacred Knowledge that participants in his studies have felt their sense of self temporarily dissolve after a dose of psilocybin.

Most commonly, the term “death” is employed as the ego (everyday self) feels that it quite literally is dying. 

Though one may have read that others have reported subsequent immersion in the eternal and experiences of being reborn and returning to everyday existence afterward, in the moment imminence of death may feel acutely – and for some terrifyingly – real.

Because this sensation is so frightening, most researchers recommend a trip-sitter – in Richards’s words, “having someone present who one honestly can choose to trust without reservation.  The attitude ‘I can manage on my own and don’t really need anyone else’ clearly can be very counterproductive in some high-dose sessions when the ‘I’ needs to totally relinquish control.

At times, an arrogant attitude of self-reliance is unhelpful.  It is also, unsurprisingly, the attitude with which I approached nearly all aspects of my life.  I’m an athlete, an academic, usually in full command of my own mind and body.  I mostly work alone (although I’m very grateful that my spouse helps me run this website). 

Why wouldn’t I do my own psychotherapy?

I tried psilocybin mushrooms during graduate school.  Shortly after we met, the person who is now my spouse asked if we could visit her sibling in Portland for her birthday.  We left Stanford at 7 p.m. on a Friday, then drove north through the night.  We arrived at about dawn on Saturday morning, collapsed, and slept until noon. 

We were visiting a punk house, it seemed, where the bulk of the rent was paid by one person’s trust fund, with others occasionally chipping in money from various odd jobs (there was a nearby sporting event during the second day of our visit, and one of the housemates put on an official-looking reflective vest and charged people to illegally park in an abandoned lot down the street).  A dozen misshapen mattresses were strewn about the skunky-smelling attic; I picked the second-least stained to sleep on.

On Saturday night, for the birthday celebration, our hosts threw a party.  Several bands played – it was the sort of event where the scrawny white weed dealer’s terrible hip-hop group (bass, drums, and the dealer on the mic) was allowed to play a set.  The others were mostly metal bands.

One of the housemates (the faux-parking attendant, as it happens) brewed a large mason jar of psilocybin tea.  As he was gamboling about the house, we crossed paths and he proffered the nearly empty jar: “Hey, man, you want these dregs?”

I shrugged and drank it.

“Whoa,” he said.

“What?”

“Just, that was a lot of dregs.”

Which, honestly, was not the best moment to be warned. I’d already drank it. I obviously couldn’t do anything about it then.

Richards and other medical professionals involved in psychedelics research would find it unsurprising that the tenor of the evening turned intensely spiritual for me.  Ken Kesey and other psychonauts would find it unsurprising that the goings on seemed exceedingly trippy, as well.  I sat on a couch in front of the bands’ performance area and watched as a singer seemed to smear her face across the microphone; soon I saw her with three mouths, the two in her neck relegated to singing harmony.

I felt intense paranoia; as I waited in line for a bathroom, people nearby seemed to be snickering at me.  Of course, snickers often follow in my wake at parties – my behavior can be outlandish – and I might’ve been making goofy facial expressions.

I understood only snippets of conversation.  A squinty-eyed Thor-looking blonde man named Hyacinth was saying, “I always wanted to get with a Gemini, and then, bam, last winter, I met this older lady with these, like, enormous eyes, and I was like, whoa, and wouldn’t you know it, bam, she’s a Gemini!” 

(I later learned that he worked as an, ahem, “intimate massage therapist,” or “hired companion,” that sort of thing.  He also cornered me and spent thirty minutes explaining his take on quantum mechanics.  His version involved a lot of positive energy radiating from crystals.  The abundance of positive energy in his own life is part of what brought him together with that Gemini, it seems. The waning disorientation from psilocybin left me totally unable to extricate myself from the conversation.)

And, as per Richards’s expectations, I felt myself losing a fundamental component of my identity.  I temporarily forgot how to speak. Then felt as though I was losing all ability to translate my thoughts into external action. 

Perhaps I should’ve noticed that I was still passively influencing my surroundings – nobody else could stand where I was standing, and Hyacinth wouldn’t have stood there simply lecturing the air – but the flickering of my short term memory caused these examples to slip away from me.  I felt like a ghost, and the sensation terrified me.

But I was lucky.  Even at parties (to be perfectly honest, especially at loud parties), I carry a pencil and paper.  That way, I can draw horrible cartoons. Sometimes I try to use these to communicate.

It should come as no surprise that I make few friends at parties.

I found a secluded corner of the party and began to write.  And then, minutes later, when I felt another wave of loss of self pass over me, I was able look at the sheet of paper in my hand and see. I wrote that.  I did change the world.  I am changing it. 

I was able to regain a sense of object permanence, despite the ego-erasing effects of psilocybin. If I were a ghost, my marks would wisp from the page like so much abluvion. But here they are.

Because I can still communicate with the outside world, I still am.

In all, the experience was probably good for me.  Someday I could write about why.  But for now, I’d simply like to stress that, in that moment, writing saved me.  Writing kept me anchored and tamped down the terror sufficiently that I could accept whatever was happening inside my brain.  (Indeed, one of the things I wrote that night was, “Without this paper, I’d wander the streets, wake tomorrow in a gutter with a rat gnawing on my eyeball.”)

And I’ve seen the way that writing has saved other people, too.  When people fear that they’re turning into ghosts – cut off from the outside world, unable to reach their friends and families – even severely dyslexic men will start sending letters.

Being held in jail can dissolve a person’s sense of self just as surely as psilocybin mushrooms.

Each week, I bring in another dozen pencils.  I occasionally wondered what was happening to the pencils, whether they accumulated like Lincoln Logs in the block.  But I kept bringing more because we need a way to write during our class. And I’d let the guys keep them. So much has been taken from these men that I couldn’t bear to ask for the pencils back.

Eventually, somebody told me.  “Oh, yeah, my bunkie, he writes a lot at night, he always sharpens like a dozen pencils before lockdown.”

The men in jail aren’t allowed to have pens.  They can’t have mechanical pencils.  And they don’t have sharpeners in their cells.

At night … or if there’s a disciplinary infraction … or if the jail is understaffed … the men are locked into their little cells.  Unless they sharpen pencils beforehand, they cannot write.  Each broken tip brings an inmate that much closer to enforced silence, unable to communicate with the outside world.

Recently, people have been forming a big line at the pencil sharpener whenever I teach class.  I slowly pass out the poems that we’ll read that week, then pass out pencils, then pass out paper, then sit and wait. The waiting takes a while.  Guys come with twenty or thirty pencils bristling from the shirt pocket of their orange scrubs, then stand and sharpen all of them.  A dozen men, sharpening perhaps twenty pencils each.

At the table, they mention trades they’ve made.  Losses, due to theft: “At the beginning of the week I had fifteen pencils; now I’m down to three.”  They exhort me to bring more.  I say I’ll do my best.

“There’s only one pencil sharpener in the block, and it’s been broken for three months.  It’s like that one, a wall mount.  The gears are all screwed up.  The handle was broken off, but you could sort of still use it then.  But now, anybody who doesn’t get to come to your class can’t sharpen any.”

“I’m sharpening some for my bunkie,” yells the guy currently cranking the handle.  A few of the others nod; they’ll also sharpen some for charity.

Image by emdot on Flickr.

Twenty … thirty … maybe forty sharpened graphite tips.  While those last, the guys will be able to write.  Time will pass, but they’ll be able to prove to themselves, and to the outside world, that they really do exist.

With luck, those sharpened pencils will last all week.

On attentiveness and names.

On attentiveness and names.

When a scientist first discovers a function for a gene, that scientist gets to name it.  Sometimes these names seem reasonable enough: I worked with a hematologist who did a study to identify proteins involved in apoptosis, which means roughly “programmed cell death” or “cellular suicide,” and so each gene wound up named “Requiem 3”, “Requiem 4,” etc.

Fruit fly geneticists tend to give their discoveries more creative names than other scientists.  There’s the gene “cheap date” – if a fruit fly is missing that gene, it will – ha ha – be unable to process ethanol and  so quickly passes out.  Another genetic mutation produced male flies that would court either males or females, and so this was known for over a decade as “fruity,” until another scientist decided that universal courtship could be less offensively described by the term “fruitless,” because clearly any mating-like activity that does not lead to progeny is a waste of time.

Yup, some gene names were bad.  One person’s idea of a joke might seem to somebody else like a mean-spirited reference to the wider world’s power dynamics.

Other gene names were bad not out of malice, but because humor at the expense of a fruit fly doesn’t make as many people laugh when a human child is dying. 

A gene that produces a somewhat spiky-shaped protein was named after Sonic Hedgehog.  It seemed funny at the time!  See?  The protein is spiky, the video game character has spiky hair, and … get it?  You get it, right?

 Okay, so this Sonic Hedgehog protein doesn’t look all that much like Sonic the Hedgehog.  But spend enough time staring at something like protein crystal structures and you’ll experience pareidolia, like seeing animal shapes in irregularly dappled plaster ceilings, or anthropomorphic gods amongst the twinklings of the stars.

Well, the Sonic Hedgehog protein establishes a concentration gradient that allows cells to recognize their spatial position in a developing body.  If a human fetus comes to term despite having a mutation in the Sonic Hedgehog gene (genetic abnormalities will often result in a miscarriage, but not always), the resulting child will have severe brain defects.

And then a doctor has to explain, “Your baby is suffering because of a Sonic Hedgehog mutation.”

And so, in 2006, geneticists capitulated to medical doctors. No more fanciful names for genes that might lie at the root of human health problems … which, because humans and fruit flies are actually pretty similar, means most genes.  Patients would now be told about a mutation in the SHH gene instead of Sonic Hedgehog, or a mutation in the LFNG gene instead of Lunatic Fringe.

Words have power, after all.


Some people are more attentive to their environments than others.  During evolutionary time, this trait was obviously good for humanity.  If your tribe is traveling through a hostile environment, it helps to have somebody around who is paying attention to the world.  A friend who’s primed to notice encroaching threats like a hungry lion about to leap out and attack.  Maybe we should take a different path.  Which, yeah, that sounds like a good idea.

Other people are particularly inattentive to their surroundings, so it’s easy for them to ignore the world and focus instead on one single problem.  During evolutionary time, this trait was surely good for humanity, too.  It’s helpful to have somebody on the lookout for threats that might eat you, obviously.  But it’s also helpful to have somebody who might discover a way of using dried grass to weave baskets.  A way of cooking mud into pottery that could carry or store water.

Image by Herb Roe on Wikimedia Commons.

Neurodiversity is a virtue in and of itself.  Over the millennia, the world has offered our species many challenges.  Populations that were sufficiently diverse that some members were good at each of a variety of tasks were most likely to flourish.  A cooperative species like termites or Homo sapiens benefits from specialization among its members.

Left to our their own devices, people would naturally fall asleep and wake up at different times.  Some brains are primed to work best in the early morning; others work best late at night.  And that’s good.  It reduces the amount of time that a tribe would be susceptible to attack, everyone asleep.

But in the modern world, we occasionally forget to feel grateful for the diversity that allowed our species to thrive.  The high school students whose brains are primed for late-night thinking drag themselves through morning classes like zombies.  They’ll be midway through first period before the sun rises.  Their teachers glance derisively at their slumped and scruffy forms and call them lazy.


Eventually, humans invented language.  Much later, we invented writing.  Much, much later, we invented the printing press, and then written words became so widely accessible that most humans could benefit from learning how to read.

Of course, reading is easier for people who are inattentive to their environment.

If I had been born earlier in human evolution, I totally would have been lion bait.  When I’m reading a book, or am deep in thought, the rest of the world melts away.  When I’m typing at home, K or the kids sometimes shout my name several times before I even realize that I’m being spoken to. 

People like me, or this kid at a library, totally would’ve been lion bait.

Luckily for me, I wasn’t born way back then.  Instead I was born into a world where inattentive people – the people best able to block out the world and instead focus on their own thoughts – are the most likely to find academic success.  People like me become medical doctors.  Then we get to name the world’s various conditions and maladies.

And so, when it came time to categorize the sort of person who is especially attentive to the world, people like me (who obviously thought that our way of being is the best way to be) referred to those others as having an attention deficit disorder.

Identifying those people’s awareness of their environs might sound like a virtue; instead, we castigated those people’s difficulty at ignoring the world.

I’ve never read the Percy Jackson books, but I’m glad that they exist, if only for passages like this (from The Lightning Thief):

“And the ADHD – you’re impulsive, can’t sit still in the classroom.  That’s your battlefield reflexes.  In a real fight, they’d keep you alive.  As for the attention problems, that’s because you see too much, Percy, not too little.”


Childhood trauma can cause symptoms that medical doctors term “attention deficit disorder.”  Which makes sense – if you’ve gone through an experience where your environs were threatening, you should learn to be more aware of your environment.  It should become more difficult to ignore a world that has proven itself to be dangerous.

Even for somebody with my type of brain, it’s going to be easier to sit outside and read a book when there’s a squirrel nearby than if there’s a prowling grizzly fifteen meters away.

Some children have to learn early on that daddy’s sometimes a grizzly.  And if it can happen to him, why not other grown-ups, too?  Best to stay on high alert around the teacher.  She’s trying to get you absorbed in these number tables … but what if that’s a trap?


Certain drugs can narrow a person’s perception of the world.  They act like blinders, chemicals like nicotine, ritalin, and amphetamines, both un-methylated (sold under the trade name Adderall) and methylated (a CH3 group attached to the amine moiety of Adderall will slow its degradation by CYP2D6 enzymes in the liver, increasing the duration of its effects).

Note to non-chemists: the methylated analogue of Adderall goes by several names, including “ice,” “shard,” and “crystal meth.”  Perhaps you’ve heard of it — this compound played a key role in the television show Breaking Bad.  And it’s very similar to the stuff prescribed to eight year olds.  Feel free to glance at the chemical structures, below.

In poetry class last week, a man who has cycled in and out of jail several times during the few years I’ve taught there – who I’d said “hello” to on the outside just a few weeks earlier when he rode his bicycle past the high school runners and me – plonked himself down in the squeaky plastic hair next to mine.

I groaned.

“I know, I know,” he said.  “But I might be out on Monday.”

“What happened?”

“Failed a urine screen.  But I was doing good.  Out for six months, and they were screening me like all the time, I only failed three of them.”

“With … ?”

“Meth,” he said, nodding.  “But I wasn’t hitting it bad, this time.  I know I look like I lost some weight, dropped from 230 down to 205, but that’s just cause it was hard getting enough to eat.  Wasn’t like last time.  I don’t know if you remember, like, just how gaunt my whole face looked when they brought me in.  But, man, it’s just … as soon as I step outside this place, my anxiety shoots through the roof … “

This is apparently a common phenomenon.  When we incarcerate people, we carve away so much of their experience of the world.  Inside the jail, there is a set routine.  Somebody is often barking orders, telling people exactly what to do.  There aren’t even many colors to be distracted by, just the white-painted concrete walls, the faded orange of inmate scrubs, the dull tan CO shirts and dark brown pants.

The world in there is bleak, which means there are very few choices to make.  Will you sit and try to listen to the TV?  (The screen is visible from three or four of the twelve cells, but not from the others.)  Try, against all odds, to read a book?  Or add your shouting voice to the din, trying to have a conversation (there’s no weather, so instead the fall-back topic is speculating what’s going to be served for dinner)?

After spending time locked up, a person’s ability to navigate the wider world atrophies, the same as your leg would if you spent months with it bundled up in a cast.

And these are people whom we should be helping to learn how to navigate the world better.

“ … so I vape a lot, outside.  I step out of this place, that’s the first thing I do, suck down a cigarette.  And, every now and then … “

He feels physically pained, being so attentive to his surroundings.  And so he doses himself with chemicals that let him ignore the world as well as I can.

And, yes.  He grew up with an abusive stepfather.  This led to his acting squirrelly in school.  And so, at ten years old, medical doctors began dosing him with powerful stimulants.

Meanwhile, our man dutifully internalized the thought that he had a personal failing.  The doctors referred to his hyper-vigilance as an attention deficit disorder.


Words have power.

We can’t know now, after all the hurt we’ve piled on him, but think: where might our man be if he’d learned to think of his attentiveness as a virtue?

On nature.

On nature.

The modern world is a stressful place – some medical doctors advocate “therapeutic” nature walks.  Surround yourself with trees, wildlife, a babbling stream or waterfall, and your body will remember what it means to be alive.

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Image by Steven Depolo on Flickr.

For millions of years, our ancestors needed specific environments in order to survive.  Almost every animal species experiences instinctual urges toward healthful habitats – it would be surprising if our own minds didn’t have a residual response toward landscapes that provide what our forebears needed.  Running water, trees for shelter, grassy meadows to hunt, fecund animal life suggesting a thriving ecosystem.

But people who need to heal are cut off from these environs.

When somebody doesn’t fit in our world, they wind up in jail.  Maybe this person has trouble holding down a job and so forged checks, or counterfeited money, or robbed a store.  Maybe somebody is plagued by nightmares and takes methamphetamine to forgo sleep.  Or shoots opiates to stave off the pain of withdrawal.  Maybe somebody has so much tension and anger that he threw a television at his girlfriend.

These are people who’d probably benefit from a de-stressing stroll through the woods.

Instead, they’re surrounded by concrete, in a clanging, reverberating room with 25-foot-high ceilings, locked doors stacked atop each other, steel tables, boaters crowding the floor (with two tiers of 8 double-occupancy cells, the jail could hold 32 per block … but most have wobbled between 35 and 40 people all year, with the excess sleeping on plastic “boats” on the common area floor.  Things were worst in July, when they were so many inmates that the jail ran out of boats – then people slept on a blanket spread directly over the concrete), toilets overflowing with the excreta of many men shitting their way through withdrawal.

grow posterIn the classroom where I teach poetry, there’s a picture of a redwood forest.  It’s shot from the ground, the trunks soaring up to the canopy overhead, and at the bottom of the poster there’s the word “GROW” above a corny quote from Ronald Reagan.

Stephen “Greazy” Sapp wrote the following poem at the end of class one day; he’d spent almost the whole hour staring at the picture of those trees:

 

GROW

Greazy

 

I want to live to see things grow –

From the fury of a great storm, started from

A single drop –

To the ten foot tree from one tiny seed, one sheet

Of paper as from any other tree

Knocked down by a great storm –

The child who grew from a seed in the spouse

Of the man who held paper from the tree –

Maybe the seed buried in his mind could become

Greater in life than the tree that withstood

The storm, now given opportunity to transform

Into stories – of future, generations who dwell

In the single rain drop in

The forest of days to come –

 

Greazy told me that he loves plants.

(My inclination is to use people’s first names as a sign of respect, but he told me not to – “nobody calls me ‘Stephen’ unless they’re mad about something.  You know, like, my grandma, if she was pissed, I might hear her yell, like, Stephen!  Even the cops.  They pulled up one day, they were like, ‘Greazy, come here, we want to talk to you,’ I knew everything was fine.  They were like, ‘look, man, we know you’re selling pot … but stay up near 17th street or something.  We don’t want you downtown, selling it to college kids.’  But then, another day, they came down, spotted me, said ‘Stephen, get over here!’ I was like, ‘man, I know they’re gonna haul me in.’ ”)

Greazy was in the jail all through autumn, waiting on his trial, and he told me that one day he was sitting in his cell on the fourth floor, watching a leaf blowing around on the sidewalk down below, and he found himself thinking, “Man, I’d sign whatever, I’d take whatever plea they wanted, if they’d just let me out there, get to look up close at that little leaf.”

Another man told me that he felt so starved for the world that he started gardening inside the jail.  He didn’t want for me to include his name but graciously allowed me to share his story.  Here’s a poem I wrote:

 

OUR MAN GROWS AN ORANGE TREE

 

by sprouting seeds in a paper towel,

planting one in dust & dirt

he collected scraping his fingers along

each corner of the concrete walls,

& using an Irish Spring soap box as a shelf

to lift his sapling to the light.

 

Our man only wanted to

oxygenate his air

but soon the whole block shuffles by

checking on the tree each day.

They’re surprised that it survived,

but proud to see it grow

until the warden declares it contraband.

 

Young_orange_tree

On Sci-Hub, the Napster of science.

On Sci-Hub, the Napster of science.

Here’s a story you’ve probably heard: the music industry was great until Napster came along and complete strangers could “share” their collections online and profits tanked.  Metallica went berserk suing their fans.  It was too late.  The industry has never been the same.napster

Sci-Hub has been called a Napster equivalent for scientific research papers, and the major publishing companies are suing to shut it down.  The neuroscience grad student who created it faces financial ruin.  The original website was quickly shuttered by a legal injunction, but the internet is a slippery place.  Now the same service is hosted outside U.S. jurisdiction.

[Note: between writing and posting this essay, Sci-Hub has lost another lawsuit requesting all such sites to be blocked by internet service providers.]

The outcomes of these lawsuits are a big deal.  Not just for the idealistic Kazakhstani grad student charged with millions in damages.  Academic publishers will do all they can to accentuate the parallels between Sci-Hub and Napster – and, look, nearly a quarter of my living relatives are professional musicians, so I realize how much damage was wrought by Napster’s culture of theft – but comparing research papers to pop songs is a rotten analogy.  Even if you’ve never wanted to read original research yet … even if you think – reasonably – that content producers should be paid, you should care about the open access movement.  Of which Sci-Hub is the most dramatic foray.

My own perspective changed after I did some ghostwriting for a pop medicine book.  Maybe you know the type: “Do you have SCARY DISEASE X?  It’ll get better if you take these nutritional supplements and do this type of yoga and buy these experimental home-use medical devices!”  Total hokum.  And yet, people buy these books.  So there I was, unhelpfully – quite possibly unethically – collaborating with a friend who’d been hired to ghostwrite a new one.

Central_core_disease_NADH_stainI read huge numbers of research papers and wrote chapters about treating this particular SCARY DISEASE with different foods, nutritional supplements, and off-label pharmaceuticals.  My sentences were riddled with un-truths.  The foods and drugs I described are exceedingly unlikely to benefit patients in any way.

Still, I found research papers purporting to have found benefits.  I dutifully described the results.  I focused on the sort of semi-farcical study that concludes, for instance, that cancer patients who drink sufficient quantities of green tea have reduced tumor growth, at which point newspapers announce that green tea is a “superfood” that cures cancer, at which point spurious claims get slathered all over the packaging.

Maybe nobody has written a paper (yet!) claiming that green tea ameliorates your particular SCARY DISEASE.  But there’s also turmeric, kale, fish oil, bittermelon, cranberries… I’m not sure any ingredient is so mundane that it won’t eventually be declared a superfood.  Toxoplasma gondii has been linked to schizophrenia, but low-level schizophrenia has been linked to creativity: will it be long before cat excrement is marketed as a superfood for budding artists?

cat-shit-2-flat-1.jpgAs it happens, enough people suffer from our book’s SCARY DISEASE that many low-quality studies exist.  I was able to write those chapters.  And then felt grim.  The things I’d written about food weren’t so bad, because although turmeric, coconut oil, and carpaccio won’t cure anybody, they won’t cause much harm either.  But the drugs?  They won’t help, and most have nasty side effects.

My words might mislead people into wasting money on unnecessary dietary supplements or, worse, causing serious damage with self-prescribed pharmaceuticals.  Patients might follow the book’s rotten advice instead of consulting with a trained medical professional.  I’d like to think that nobody would be foolish enough to trust that book – the ostensible author is probably even less qualified to have written that book than I am, because at least I have a Ph.D. in biochemistry from Stanford – but, based on the money being thrown around, somebody thinks it’ll sell.

And I helped.

Whoops.  Mea culpa, and all of that.

But I didn’t perpetrate my sins alone.  And I’m not just blaming the book’s publishers here.  After all, the spurious results I described came from real research papers, often written by professors at major universities, often published in legitimate scientific journals.

It’s crummy to concentrate all that slop in a slim pop medicine book, I agree, but isn’t it also crummy for all those spurious research papers to exist at all?

Maybe you’ve heard that various scientific fields suffer from a “replication crisis.”  There’s been coverage on John Oliver’s Last Week Tonight and in the New York Times about major failures in psychology and medicine.  Scientists write a paper claiming something happens, but that thing doesn’t happen in anyone else’s hands.  That’s if anyone even bothers to check.  Most of the time, nobody does.  Verifying someone else’s results won’t help researchers win grants, so it’s generally seen as a waste of time and money.

Still, the news coverage I’ve seen hasn’t stated the problem sufficiently bluntly.  Modern academic science is designed to be false.

This is tragic.  It’s part of why I chose not to stop working in the field.  I became a writer.  Of course, this led to my stint of ghostwriting, which… well, whoops.

Here’s how modern science works: most research is publishable only if it is “statistically significant.”  This means comparing any result to a “null hypothesis” – if you’re investigating the effect of green tea on cancer, the null hypothesis is simply “green tea does nothing” – then throwing out your results if you had more than a one in twenty chance to see what you did if the null hypothesis were true.

If you have a hundred patients, some of their tumors will shrink no matter what you do.  If you give everybody buckets of green tea and see the usual number of people improve, you shouldn’t claim that green tea saved them.

Here’s a graphic from Wikipedia to help:

pvalue1pvalue2

Logical enough.  But bad.  Why?  Because cancer is a SCARY DISEASE.  Far more than twenty people are studying it.  If twenty scientists each decide to test whether green tea reduces tumors, the “one in twenty” statistical test means that somebody from that set of scientists will probably see an above-average number of patients improve.  When you’re dealing with random chance, there are always flukes.  If twenty researchers all decided to flip four coins in a row, somebody would probably see all four come up heads – doesn’t mean that researcher did anything special.

Or, did you hear the news that high folate might be correlated with autism?  This study probably sounds legitimate – the lead scientist is a professor at Johns Hopkins, after all – but the result is quite unlikely to be real.  That scientist hasn’t written about folate previously, so my best guess (this new study is currently unpublished) is that pregnant women were tested for many different biomarkers, things like folate, iron, testosterone, and more, and then tracked to see whose children would develop autism.  If the researchers tested the concentrations of twenty different nutrients and hormones, of course they’d see one that appeared to correlate with autism.

[Edit: these findings were recently published.  Indeed, the data appear rather unconvincing, and the measurements for folate were made after the fact, using blood samples – it’s quite possible that other data was gathered but excluded from the published version of the study.]

This is not science.  But if you neglect to mention how many biomarkers you studied, and you retroactively concoct a conspiracy theory-esque narrative explaining why you were concerned about folate, it can do a fine job of masquerading as science.  At least long enough to win the next grant.

Which means that, even though the results of many of these studies are false, they get published.  When somebody checks twenty nutrients, one might appear to cause autism.  When twenty scientists study green tea and cancer, somebody might get results suggesting green tea does work.  Even if it doesn’t do a thing.

In our current system, though, only the mistaken researcher’s results get published.  Nobody knows that there were twenty tests.  The nineteen other biomarkers that were measured get left out of the final paper.  The nineteen researchers who found that green tea does nothing don’t publish anything.  Showing that a food doesn’t cure cancer?  How mundane.  Nobody wants to read that; publishers don’t want it in their journals.  But the single spurious result showing that green tea is a tumor-busting superfood?  That is exciting.  That study lands in a fancy journal and gets described in even briefer, more flattering language in the popular press.  Soon big-name computer CEOs are guzzling green tea instead of risking surgery or chemo.

I generally assume that the conclusions of research studies using this type of statistical testing are false.  And there’s more.  Data are often presented misleadingly.  Plenty of scientists are willing to test a pet theory many ways and report only the approach that “works,” not necessarily because they want to lie to people, but because it’s so easy to rationalize why the test you tried first (and second, and third…) was not quite right.  I worked in many laboratories over a decade and there were often results that everybody in the lab knew weren’t true.  Both professors I worked under at Stanford published studies that I know weren’t done correctly.  Sadly, they know it too.

This subterfuge can be hard for outsiders to notice.  But sometimes the flaws are things that anybody could be taught to identify.  With just a little bit of guidance, anybody foolish enough to purchase the pop medicine book I worked on would be able to look up the original research papers and read them and realize that they’re garbage.

There’s a catch: most of those papers cost between twenty and thirty dollars a pop.  The chapters I wrote cite nearly a hundred articles.  I’d describe a few studies about the off-label use of this drug, a few about that one, on and on, “so that our readers feel empowered to make their own decisions instead of being held at the paternalistic mercy of their healthcare professionals.”  A noble goal.  But I’m not sure that recommending patients dabble with ineffectual, oft-risky alternative medicines is the best way to pursue it.  Especially when the book publisher was discussing revenue sharing agreements with sellers of some of the weird stuff we shilled.

So, those hundred citations?  You could spend three thousand dollars figuring out that the chapters I wrote are crap.  The situation is slowly getting better – the National Institute of Health has mandated that taxpayer-funded studies be made available after a year, but this doesn’t apply to anything published before 2008, and I’m not sure how keen sick patients will be to twiddle their thumbs for a year before learning the latest information about their diseases.  Plus, there are many granting organizations out there.  Researchers who get their money elsewhere aren’t bound by this requirement.  If somebody asks you, “Would you like to donate money to fight childhood cancer?” and you chip in a buck, you’re actually contributing to the problem.

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Photo by diylibrarian on Flickr.

I was only able to write my chapters of that book because I live next to a big university.  I could stroll to the library and use their permissions to access the papers I’d need.  Sometimes, though, that wasn’t enough.  Each obscure journal, of which there are legion, can cost a university several thousand dollars a year for a subscription.  A few studies I cited were published in specialty journals too narrowly focused for Indiana University to subscribe, so I’d send an email to a buddy still working at Stanford and ask him to send me a copy.

If you get sick and worry yourself into looking for the truth, you’ll probably be out of luck.  Even doing your research at a big state university library might not be enough.

That’s if you keep your research legal.

Or you could search for the papers you need on Sci-Hub.  Then you’d just type the title, complete a CAPTCHA on a page with instructions in Cyrillic (on what was until recently http://www.sci-hub.cc, at least), and, bam!  You have it!  You can spend your thirty dollars on something else.  Food, maybe, or rent.

Of course, this means you are a thief.  The publisher didn’t get the thirty dollars they charge for access to a paper.  And those academic publishers would like for you to feel the same ethical qualms that we’re retraining people to feel when they pirate music or movies.  If you steal, content producers won’t be paid, they’ll starve, and we’ll staunch the flow of beautiful art to which we’ve become accustomed.

The comparison between Napster and Sci-Hub is a false analogy.  Slate correspondent Justin Peters described the perverse economics of academic publishing, in particular the inelastic demand – nobody reads research journals for fun.

With music and movies, purchasing legitimate access funds creators.  Not so in academia.  My laboratory had to pay a journal to publish my thesis work; this is standard practice.  It costs the authors a lot of money to publish a research article, and “content producers” only do it, as opposed to slapping their work up on a personal website for everyone to read free, because they need publication credits on their CVs to keep winning grants.

With music and movies, stealing electronic copies makes content producers sad.  With research articles, it makes them happy.

In fact, almost everyone believes research articles should be free.  At the European Union’s recent Competitiveness Council, the member states agreed that all scientific papers should be freely available by 2020 – these  are the governments whose enforcement is necessary to maintain the current copyright system!  The only people making statements in favor of the status quo are employed by the academic publishers themselves.  Their ideological positions may be swayed somewhat by the $2 billion plus profit margins major publishers are able to extract from their current racket.

Academic publishers would argue that they serve an important role as curators of the myriad discoveries made daily.  This doesn’t persuade me.  The “referees” they rely on to assess whether each study is sound are all unpaid volunteers.  Plus, if the journals were curating well, wouldn’t it have been harder for me to fill that pop medicine book with so much legitimate-looking crap?

Most importantly, by availing yourself of Sci-Hub’s pirated material, you the thief no longer live in ignorance.  With our current healthcare model, ignorance is deadly.  The United States is moving toward an a la carte method of delivering treatment, where sick people are expected to be knowledgeable, price-sensitive consumers rather than patients who place their trust in a physician.  Most sick people no longer have a primary care physician who knows much about their personal lives – instead, doctors are forced for financial reasons to join large corporate conglomerates.  Doctors try their best moment by moment, but they might never see someone a second time.  It’s more important than ever for patients to stay well-informed.

Unless Sci-Hub wins its lawsuit, you probably can’t afford to.

On minotaurs (and whether or not mothers are the root of all maladies).

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While reading Eula Biss’s On Immunity, I was often reminded of Rebecca Kukla’s Mass Hysteria.  Both works analyze the permeability of bodies, especially mothers and children, while drawing from literature, philosophy, and medicine.  Their major divergence is in tone; Kukla’s work can veer academic (which I enjoy, being a pedantic fuddyduddy myself); Biss’s writing is much more accessible.  A great choice, in my opinion, since Biss seems to have a strong social justice motivation for her work.  The fact that her writing is so consistently chatty and approachable, and that the work as a whole is structured with snack-sized chapters perfect for reading while a napping baby was sprawled atop my chest, seems essential for reaching her intended audience.

I felt the works were most similar in sections discussing putative moral shortcomings in mothers and the way those ills could be passed along to children, either physically through the womb or breastmilk, or psychologically through maternal behavior.  Here’s Biss on the litany of ill-conceived castigations that have been applied to women, which I think of collectively as the “blame the mother” hypotheses:

In the twentieth century, psychologists blamed schizophrenia on overbearing mothers who smothered their children.  Homosexuality, categorized as a mental illness until 1973, was blamed on anxious mothers who coddled their children.  Autism, according to the prevailing theory of the 1950s, was blamed on cold, insensitive “refrigerator mothers.”  Even now, mothers provide “a convenient missing link in germ theory,” as the psychotherapist Janna Malamud Smith observes.  “If it is not viral or bacteria,” she quips, “it must be maternal.”

These are all relatively modern theories — we have to delve slightly deeper into medical history to reach my favorite “blame the mother” hypothesis: the maternal imagination theory that purportedly explained birth defects.

9780312427733I first learned about this theory from Jeffrey Eugenides’s wonderful novel Middlesex.  If you haven’t read it yet, you’re in for a treat!  As in, why waste your time reading this essay?  Go read his book!  Soon!  Now!

But if you’re still here (I should finish writing this essay, after all, in case you’re at work or something and stuck sitting at a computer), you’ll get only a small taste.

In this passage, Eugenides shows a doctor explaining the causes of birth defects to a nervous expectant mother; the doctor blusters forth with a charming (and in my opinion very true to life) lack of emotional intelligence.  He’s so pleased with his own erudition that he doesn’t even notice the burgeoning worries of his patient — the fearful mother is bearing her brother’s child.

Sourmelina let out an exasperated sigh and wiped her mouth with her napkin.  There was a strained silence.  Dr. Philobosian, pouring himself another glass of wine, rushed in.

“Birth is a fascinating subject.  Take deformities, for instance.  People used to think they were caused by maternal imagination.  During the conjugal act, whatever the mother happened to look at or think about would affect the child.  There’s a story in Damascene about a woman who had a picture of John the Baptist over her bed.  Wearing the traditional hair shirt.  In the throes of passion, the poor woman happened to glance up at this portrait.  Nine months later, her baby was born–furry as a bear!”  The doctor laughed, enjoying himself, sipping more wine.

“That can’t happen, can it?”  Desdemona, suddenly alarmed, wanted to know.

But Dr. Philobosian was on a roll.  “There’s another story about a woman who touched a toad while making love.  Her baby came out with pop eyes and covered with warts.”

“This is in a book you read?” Desdemona’s voice was tight.

“Pare’s On Monsters and Marvels has most of this.  The Church got into it, too.  In his Embryological Sacra, Cangiamilla recommended intra-uterine baptisms.  Suppose you were worried that you might be carrying a monstrous baby.  Well, there was a cure for that.  You simply filled a syringe with holy water and baptized the infant before it was born.”

“Don’t worry, Desdemona,” Lefty said, seeing how anxious she looked.  “Doctors don’t think that anymore.”

“Of course not,” said Dr. Philobosian.  “All this nonsense comes from the Dark Ages.  We know now that most birth deformities result from the consanguinity of the parents.”

“From the what?” asked Desdemona.

“From families intermarrying.”

Desdemona went white.

“Causes all kinds of problems.  Imbecility.  Hemophilia.  Look at the Romanovs.  Look at any royal family.  Mutants, all of them.”

3wombsTo me, that’s a great medical hypothesis.  Not the idea that consanguinity causes birth defects; that’s too commonly understood, and too true, to be a lot of fun.  But maternal imagination?  A fine piece of work.  Doctors, out of prudishness, refused to examine women’s bodies.  Then, in their ignorance, they claimed those bodies were malleable and consisted primarily of empty space that the women’s organs could migrate through (i.e. “hysteria,” from “hustera” meaning womb, a disease in which the uterus has wandered too far.  Like a parasitic worm, perhaps, if it reaches her brain the womb might cause a woman to say crazy things).  And so they logically assumed, hey, if women’s bodies are such porous, malleable things, and babies are growing inside them, then anything a mother does or even thinks might affect the baby!

Brilliant logic, right?

Here’s a snippet of Kulka’s perspicacious analysis about how the maternal imagination theory related to the culture of the times:

This cluster of anxieties is sometimes intertwined with other familiar social anxieties that circulate around reproduction.  In a fascinating twist, Sadler warns that the child of an adulteress may still look like her husband because she may have been thinking about him during coitus.  In this case, anxieties about how paternity can be secured intersect with anxieties about the maternal imagination, through the warning that fathers cannot even trust family resemblance as a marker of proper paternity.  This example doubles the call to carefully police women’s appetites: her wayward cravings may betray her husband and her child at once.  Sadler also cites a commonly mentioned report of a woman who “conceived and brought forth an Ethiopian” because she looked at a painting of a black man during conception, thereby adding anxieties surrounding racial purity to the mix of concerns.  Women’s cravings and imagination can thus deform and denature both the kinship order and the racial order, along with the order of their children’s bodies, in ways that normal, external controls over sexual activity cannot prevent.

Tight bind, eh?  If your baby looks “wrong,” it’s your fault: you, as a mother, must’ve somehow sinned.  You saw something you should not have seen.  You ate something you should not have eaten.  You made yourself impure.  And even if your baby looks “right,” there’s a chance that you’re bad anyway, that you somehow cheated and used virtuous thoughts while sinning in order to conceal your crimes.

Here is another passage from Kukla wherein she presents — from an ostensibly-scientific medical text! — a list of maternal-derived illnesses even broader and more morally-castigating than was delineated by Biss:

The seventeenth-century textbooks are particularly concerned about and often organized around the possibility of deformed births, with a special focus on the dangers of the impure, permeated womb.  Sadler’s book, for instance, is organized primarily as a list of ways in which the womb can fail to maintain its purity and its integrity–the womb here leaks and ‘weeps,’ and various ‘corrupt humours’ flow in and out of it, making nothing more ‘perilous’ to the body than the ‘ill-affected womb.’  Many of the works go into elaborate detail, describing and often visually representing famous cases of monstrous births.  Monstrous births could be the product of weak seed or impure blood, of conception during menstruation, of the woman fertilizing herself with her own seed (!), or, most importantly and consistently, of maternal ingestions of sights and substances that could pollute or deform the womb.  In justifying the need for careful knowledge and monitoring of the maternal body, in the preface of his book, Sadler warns us: “From the womb come convulsions, epilepsies, apoplexies, palseys, hecticke fevers, dropsies, malignant ulcers, and to bee short, there is no disease so ill but may proceed from the evil quality of it.”

CaptureGiven that my novel is primarily about violence against women, especially as has been affected in the name of science, I couldn’t resist incorporating the theory of maternal imagination.  For linguistic reasons (and because the traditional myth impugns women and their appetites still further), the problem children in my work are minotaurs.

Surprisingly, the old medical texts do not specifically address monsters from mythology, but it’s not much of a stretch to imagine one of those books containing explicit warnings about women and bestiality.  Or that barns be kept out of the sight line of bedroom windows.  Or that pregnant women stay away from farms in general.  In a time when medical texts posited the sponge-like permeability of women, risk must have seemed to be everywhere.

Of course, doctors could have checked.  Perhaps they would have noticed that human women in all variety of circumstances were giving birth to perfectly normal human babies.

But where’s the fun in that?  And, worse, if it did turn out that women’s thoughts were no more dangerous than men’s, how would you argue that they needed to be shielded from dangers like the pursuit of meaningful professions?

On autism and vaccines.

The_cow_pock
Another vaccine in the news.

Let’s get one thing out of the way first, shall we?  Vaccines don’t cause autism.  If you’ve got a kid with a standard operating immune system, you oughta get that sucker vaccinated.  If you yourself have a standard operating immune system, and you’re considering living in a place where certain diseases that you aren’t immune to are prevalent, you oughta get yourself vaccinated.

But, okay, now that we’ve stated that much, there is an essay about vaccines and autism that I’ve been meaning to write.  Prompted, at the moment, by my turn in the queue for Eula Biss’s On Vaccination finally arriving.  Biss writes, with a lack of emphasis that I assume is ironic, though I am of course only a quarter of the way through her book at the time of this writing and so cannot know for certain, “Even so, the evidence reviewed by the committee ‘favors rejection’ of the theory that the MMR vaccine causes autism.”

Sure.  Let’s reject that theory.  There’s no evidence that vaccines cause autism; a scientist might use the word “hypothesis” to describe the idea that one might, but never “theory,” not given the data we have (by way of contrast, evolution is a theory.  Gravity is a theory; the next thing you drop, unless you’re on the space station, is probably gonna fall).  The conjecture that vaccines cause autism is a hypothesis, one that’s been tested and rejected.  Unless we accumulate a lot of new data that’s very dissimilar from the data we have now, rejected is how that hypothesis will stay.

And yet.  I wanted to write an essay about my favorite contemporary model for the cause of autism, and the idea that vaccination (or “mock vaccination,” actually, in which a child undergoes the ritual of vaccination but nothing is injected) might trigger the onset of autism.  This would happen only in children who were more or less guaranteed to have autism, but I can envision a compelling narrative in which the parents of many such children would all be able to point to an incidence of vaccination as the triggering moment.

There are, you may have noticed, many theories about what causes autism.  There’s the hippocampal under-pruning hypothesis; people with autism might have too many neural connections, trigger too many memories when it’s time to make decisions!  And of course there is also the over-pruning hypothesis; yup, the exact opposite idea has been proposed as the cause of autism, too!  It’s been proposed that autism results in underactivation of the fusiform gyrus, which is a part of the brain associated with processing faces and emotions.  And, yes, it’s been proposed that autism results in overactivation of the fusiform gyrus in emotional contexts, as though it’s hard to make eye contact, process emotions, etc., because they are perceived too strongly, not too weakly.  It’s been proposed that the condition is akin to a defensive response to stress, or that it’s linked to a deficit of oxytocin (the “cuddle molecule,” which K is planning to get a tattoo of once she’s done nursing), or that there are insufficient GABA-mediated inhibitory signals.

In short, many proposals, and nobody knows what’s correct.

Honestly, we don’t even how many people have autism.  You could read the CDC report and say, ah, 1 in 68 children have an autism spectrum disorder, but there are clear peculiarities in their numbers.  For instance, the huge increase relative to prior reports.  For instance, massive regional disparities; should we believe that autism is 4-fold more common in New Jersey than Alabama, or is there a difference in diagnostic capabilities?  And, as a point of contention near and dear to my own heart, the possibility that autistic children learn to mask their own condition.  If you asked K, for instance, she’d tell you that I have a mild autism spectrum disorder, but I’ve never been diagnosed.

And there are many proposed cures for autism.  Exogenous oxytocin (would hugs work instead, to promote endogenous oxytocin?); suramin, which reduces stress response (this hasn’t been proposed as a cure for humans, because the compound is toxic, but it seems to ameliorate autism-like symptoms in a mouse model); behavioral therapies …

… and my nomination for the all-time absolute WORST proposed cure, daily injection of massive doses of LSD. (This was first tested in humans, orphaned children, primarily, and was sometimes coupled with electroshock therapy.  But I should point out that our definition of the word “autism” has evolved somewhat in the time since these experiments were performed; if we go by modern usage, I think a more accurate description of these children would be “surly” rather than “autistic.” Still, reason enough to give them daily LSD. For months.)

All of which I’m mentioning so that you know to take everything I say about a possible “link” between autism and the practice of vaccination with a hefty dose of salt.  Clearly, nobody knows what’s up.

So, with all our caveats carefully stipulated, let’s get to it!  My current favorite model for the cause of autism, and how that might also relate to vaccines!

(Do I need to mention, here, that my use of the word model, singular, is somewhat silly since it seems very likely that there are multiple causes, perhaps multiple brain states that all get referred to as “autism” but which have differing neurological mechanisms?  I’m not sure.  I’ll mention it coyly, like this, in a parenthetical aside… that’s a good halfway approach, right?)

The model: maybe certain babies get too stressed out during birth, and that triggers autism (there is a nice summary of this model on the Simons Foundation Autism Research Initiative website).

A fetus’s brain activity is supposed to be suppressed during delivery, a process mediated by K’s favorite molecule. But something might be awry in autism, causing the suppression of brain activity to fail.  Seems there are suspicious clues speckled throughout the literature, like the fact that diazepam (Valium) often excites people with autism instead of calming them.  Indeed, my sister and I took an overnight bus ride through the mountains when I visited her in Ecuador (she was there for a three-year stint in the Peace Corps before medical school), and one of her friends lent us some Valiums.  My sister slept soundly.  I spent twelve hours chittering and jabbing her in the side with my elbow.

And, yeah, birth seems like it’d be incredibly traumatic… definitely seems like a good thing for babies’ brains to be conked.  Why not imagine that someone would be constantly musing “The horror, the horror” if there was any trace of memory about that whole ordeal?  There’s an increased percentage chance of autism after birth complications, though it’s difficult for me to say what types of delivery a baby would consider most stressful (like, would a baby think that a Cesarean delivery was easier?  Dunno, but Cesarean delivery is correlated with higher autism incidence, not lower like you might predict if your only working model were this highly speculative one I’m expounding upon).

In rodent models where pretreatment (either genetic or chemical) of fetuses tends to produce animals with some of the social disorders considered to be hallmarks of autism, it seems you can reduce the chance of producing an autistic-like animal by giving the birthing mothers a drug that stills the mind of the fetus.  Conk the baby chemically, it won’t remember its own birth, it grows into a neurotypical adult.

Within this framework, it seems possible that any episodes involving extreme stress could trigger autism onset in highly-susceptible individuals.  Vaccination, typically involving a shot, is stressful for some children.  So, there you go.  If you want to believe that there is *any* correlation between vaccination and autism beyond a coincidence in timing (i.e. when it’s first possible to diagnose autism and the standard vaccination schedule) this speculative hypothesis is the best I can come up with.  And it suggests that even if you believe there’s a link between autism and vaccination, there’s a strategy you could employ other than refusing vaccination, which endangers your own child and others.  You can simply make vaccination not stressful.

It’s not that hard, actually.  Yes, your kid is getting jabbed with a needle.  And it hurts, a little bit.  Not that much.  About as much as a hard pinch, which is crummy, and makes most kids cry, but easily fixable.  I’d say N has cried on average for about three seconds with each of her vaccinations, then we cuddle her some, she nurses, she’s happy again.  Part of why this works so well is that K stays calm and placid and cheerful throughout (I wish I could say the same about myself, but I have that thing where my blood pressure drops and I feel faint around needles.  K doesn’t; she performed thousands of injections on frogs during her doctorate and that experience washed away her needlephobia for good).  And our pediatrician is great.  And we sing, before, during, and after shots.

In summary… vaccinate your kids, kids.

*****************

p.s. Was this all too chipper?  I do want people to be vaccinated against preventable diseases.  But, here, let me throw in a brief passage that I had to cut from an early draft of my novel to show that I understand why people are afraid of doctors; obviously bad things have been done.  Bad enough that any reasonable human would feel distrustful.  It’s just that, as regards contemporary pediatric vaccination, I don’t think the mistrust needs to be acted upon.  But, here you go, a little bit of horror to mitigate the preceding essay’s good cheer.

In early vaccine trials, orphaned children drank the pureed spinal chords of smallpox-infected monkeys.  Doctors put it in their milk.  The initial vaccination attempts failed: the virus was “insufficiently inactivated.”  Some of the children got sick.  Some were crippled for life.

Of course, they were living in an orphanage.  Not the most sanitary of conditions: some number of them were going to get sick anyway.  And for that study, the intent was therapeutic.  The drink might have been a vaccine.  Much more respectful toward what might’ve been the children’s wishes than, say, the hepatitis studies, in which orphans were deliberately infected so that attending doctors could track progression of the disease.  In that study, they were fed a slurry of pooled feces from other already-sick children.  Also in their milk, although for that study the noxious agent was blended into chocolate milk.  Probably seemed like a special treat.

On the PubPeer lawsuit, scientific fraud, and anonymity.

CaptureThere are some problems with academic bioscience.

That much seems to be well agreed on.  There are a lot of contributing factors — the pyramid-scheme-like training & employment setup, the recent propagation of soft money positions (universities hiring without setting aside money for salaries, expecting salary money to come out of research grants instead), a reduction in real money available for research at the same time as more people are applying for funding, and then the myriad issues arising from journal policies.  Things like an emphasis on unexpected results, disinterest in publishing reproductions, allowing material to be published with scanty experimental details and, worse, heavily-processed data in the form of graphs and charts as opposed to raw data itself.

Which, if you’re interested in that sort of thing, probably the best place to start would be last year’s paper from Alberts et al., “Rescuing US biomedical research from its systemic flaws.”  The authors provide a thorough, accessible introduction to many of these problems.

Today, I’m just going to focus on one issue: the difficulty of identifying scientific misconduct.  As in, principal investigators publishing work that they know should not be published, at least not in the way they’re presenting it.

Which, sure, you could use the word “fraud” for this, but that’s a very harsh word that I don’t think is entirely appropriate to encompass the range of issues we ought to consider.  Like work that’s presented misleadingly to make it seem more exciting than it really is.  Or work that’s found out to be inaccurate (or partially inaccurate) after it’s sent for publication, but is never retracted.  Classifying those types of cases with the same word used to describe fabricated data seems overly harsh, even though none of that is okay.

For starters: yes, this issue has been in the news a lot more lately than it used to be.  Part of the problem is directly related to issues addressed in the Alberts article.  Biomedical research seems more competitive now than it used to be, and the people involved are objectively more replaceable; the number of available persons with the necessary training per professorship has increased, largely because each professor needs a team of people to conduct experiments, and the way those teams are currently assembled is primarily from the ranks of trainees.

The other main driver for an increase in apparent fraud is that it can pass by undetected more easily now.  Modern experiments are hard — the techniques require a lot of training to even understand the underlying physical principles, let alone to be able to correctly interpret data.  Even researchers who’ve come to very different conclusions than myself about what ought to be done acknowledge that experimental difficulty is a huge issue for the reproducibility of modern work; you could read Mina Bissell’s article “The risks of the replication drive,” for instance, where she writes:

“So why am I concerned?  Isn’t reproducibility the bedrock of the scientific process?  Yes, up to a point.  But it is sometimes much easier not to replicate than to replicate studies, because the techniques and reagents are sophisticated, time-consuming and difficult to master.  In the past ten years, every paper published on which I have been senior author has taken between four and six years to complete, and at times much longer.  People in my lab often need months–if not a year–to replicate some of the experiments we have done on the roles of the microenvironment and extracellular matrix in cancer, and that includes consulting with other lab members, as well as the original authors.”

So, let’s start with that.  Experiments are sufficiently involved that they might be difficult to reproduce even if the results were correct.  And let’s set aside the issue of whether or not results are robust; in her article, Bissell points out that tiny variations in cell line can have dramatic impacts on their response to assays.  So it might be fair to wonder in those cases whether observed results matter, but not whether they’re correct.

But there’s a confounding factor, because some results presumably are not correct.  Both John Ioannidis’s article “Why Most Published Research Findings Are False” and Chabris et al.’s article “Most Reported Genetic Associations with General Intelligence Are Probably False Positives” consider the math behind p-testing, the typical ways that researchers collect and process data, and journal publishing policies to show that our current system is likely to yield many inaccurate results. Indeed, there seem to be enough incorrect results published that many drug companies no longer trust academic results, as described in Begley and Ellis’s article “Raise standards for preclinical cancer research”  (although it’s worth noting here that Begley and Ellis are basing their conclusions on numerous instances in which famous results could not be reproduced.  Bissell’s objections, as mentioned above, could still apply).

Okay.  That’s probably a lot to take in, especially since this is all just preamble to the point I wanted to make today.  Let me give a quick summary: experiments are hard.  That makes testing reproducibility hard.  But some of what’s out there is in fact not true (almost assuredly, based on the numbers, although this can only be proven on a case by case basis).

So, how do we separate the cases of things being not true because, yes, science is hard, and it’s easy to reach incorrect conclusions, and it’s a journey, a journey in which no one expects to unravel all of nature’s mysteries right away… cases where a published result is innocently not true for those reasons, and cases of fraud?

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A nice shot from PhD comics.

Because there is fraud in our current system.  Papers knowingly not retracted.  Inaccurate data published.  Data work-ups that obscure questionable aspects of a group’s results.  And it’s very difficult to draw attention to: when people do find out about it, they tend to be powerless underlings.  An ethical stance against fraud can easily result in a destroyed career: consider Peter Whoriskey’s article about a Johns Hopkins researcher who drew attention to some problems with research he was working on and was summarily fired, then harassed.  Or you could consider Yudhijit Bhattacharjee’s article about Diederik Stapel, a sociology professor who simply made up all his experimental results for decades.  Because of his past successes, his students were extremely reticent to confront him about suspected fraud, allowing the scam to persist far longer than you might imagine it should’ve.  And, and this is an excellent point that Bhattacharjee made, “Fraud like Stapel’s — brazen and careless in hindsight — might represent a lesser threat to the integrity of science than the massaging of data and selective reporting of experiments.”

And, right, the reason why I’m writing about this today?  There is an anonymous platform for commenting on scientific papers called “PubPeer.”  And, look, I know that anonymous bullying is a problem, that there are lots of horrible issues with systems like Yik Yak allowing people to write vituperative comments online with no accountability.  But PubPeer seemed like an important service simply because it can be so difficult for outsiders to know when there are flaws in scientific research, and because the insiders who do know, and who might have an incentive to report the truth, could suffer grave consequences for doing so.

And yet… PubPeer was ruled against recently.  A judge said that PubPeer should be forced to turn over identifying information for an online commenter who supposedly cost Fazlul Sarkar a job at the University of Mississippi.  To me, this is bad, because any suspicion of fraud not validated by a university investigative committee could be considered defamation — but university investigative committees are often slow to act and do not necessarily protect the careers of informants.  It seems bad to take away an anonymous venue for potentially spreading scientific truth, especially since this is an arena where the anonymity really is important for the accuser, and should not be important for the accused: the accused has objective science to defend themselves with if they are in the right.  If Sarkar had separate pieces of data for all his published experiments, he could have shown that data to whomever at the University of Mississippi to quell their concerns.  Whereas a commenting graduate student or post-doc or whomever has no guarantee that levying an accusation won’t render him or her permanently unemployed in the field.

On immortality.

Ravana_Statue

In my last essay, I mentioned Ravana’s boon.  Immunity to harm from gods.  But that wasn’t what he wanted.  Here’s another quotation from the Uttara-kanda, this time from the Robert Biggs translation (it’s less literal than the Dutt translation, which means fewer bizarre sentences.  Less poetic, though.  But I definitely appreciate that he did all that work and then posted it online, free of charge):

“[Ravana]* fasted for ten thousand years, and at the end of each thousand years he offered one of his heads into a sacrificial fire.  In this way he passed nine thousand years and offered nine of his heads into the sacrificial fire.  At the end of ten thousand years when he was about to cut off his tenth head, Lord Brahma appeared before him.  Very satisfied by [Ravana]’s austerities, Lord Brahma stood there accompanied by other demigods.  Then he said: ‘O [Ravana], I am so pleased with you.  Quickly choose the boon you desire, O knower of what is right.  What desire should I now fulfill.  Your effort should not go in vain.’  Then, with an overjoyed heart [Ravana] bowed his head and replied in a faltering voice: ‘O lord, the greatest fear for living beings is death.  I choose immortality.’  When requested in that way, Lord Brahma replied: ‘You cannot have complete immortality, therefore ask me for some other boon.’

*The name used for Ravana throughout that passage is Dashagriva, which means “Ten-necked one.”  I substituted it throughout.  And, right, maybe it’s worth quoting just the final lines of the Dutt translation of that passage, cause it’s rather more abrupt in its denial: “Thus accosted, Brahma spoke to the Ten-necked one, ‘You can not be immortal.  Do you therefore ask of me some other boon.’ ”

So, the dude did all that meditating; once he was getting offered gifts, he wanted eternal life.  And Brahma, like most gods, was not thrilled at the request.  Jehovah was equally ticked at the prospect of his newly-enlightened playthings gaining immortality: here’s a passage from the King James Bible:

“And the Lord God said, Behold, the man is become as one of us, to know good and evil: and now, lest he put forth his hand, and take also of the tree of life, and eat, and live for ever:

Therefore the Lord God sent him forth from the garden of Eden, to till the ground from whence he was taken.

So he drove out the man; and he placed at the east of the garden of Eden Cherubims, and a flaming sword which turned every way, to keep the way of the tree of life.”

So, people want to live forever, and gods aren’t going to help them do it.  That sounds like a job for science!  Indeed, many laboratories are researching ways to extend lifespan.  I don’t think any bioscientists imagine their efforts will ever result in immortality — that’s more a computer science aim than a bioscience one at the moment; here’s a reasonable introductory review into the study of human connectomes — but it seems pretty clear that they’re hoping their work can aid human longevity.  Which I get, obviously, despite my penchant for Malthusian pessimism (“Assuming then my postulata as granted, I say, that the power of population is indefinitely greater than the power in the earth to produce subsistence for man.  Population, when unchecked, increases in a geometrical ratio.  Subsistence increases only in an arithmetical ratio.  A slight acquaintance with numbers will shew the immensity of the first power in comparison with the second.”Thomas Malthus, a legendary curmudgeon).

CaptureLike there’s my graduate school baymate (the way our labs were set up was pairs of desks tucked into long alcoves of bench space, so there always wound up being one person who you talked to and collaborated with most), who planned to study lobsters after getting his doctorate: lobsters have limited senescence.  That is, they show fewer signs of aging than humans do; if we were more like lobsters, perhaps nursing homes would be rowdier places.  Of course, they’d needed to widen the hallways, reinforce the floors, etc., but I’m sure that’d seem like a fair trade for a little bit more vivacity.  Currently my buddy isn’t actually working on lobsters – he’s pursuing research more likely to help people in the near term – but someday maybe he’ll get back to it.

But the research into lobsters is focused on figuring out why they live a long time.  And there are similar studies focused on the secrets of other long-lived creatures; the most recent one I caught was a paper on whales.  The authors analyzed the bowhead whale genome and found that there might be extra copies of some DNA repair enzymes, and less of certain metabolic proteins (like a premature stop codon in a protein named UCP1 that generates heat).  About what you might expect: if you want to live a long time, DNA repair is good, metabolism is bad.  And it’s interesting, sure, but, again, unlikely to extend lifespan in the near future.  Good-lookin’ droids, but not the droids Ravana was looking for… anything that comes from that work will help other people a long time from now.  And that’s no good.  Honestly, interrogate any Malthusian and eventually they’ll tell you: the problem with longevity is that everyone else might attain it too.  If there were an a magic plant to provide immortality to just me, right here and now, then that’d be fine.  Unless a serpent happened by and stole it.  Then I’d probably be sad and start to weep.

But in the meantime, we’ve got some strategies for life extension to discuss!  Things that you could try today.  Like perfusion with hydrogen sulfide.  That’s right – inhale a horrible toxin in order to live!

(Don’t actually try this, by the way.  Hydrogen sulfide isn’t good for you.)

The first study using hydrogen sulfide to lower metabolic rate was done in Mark Roth’s lab: they were gorking mice with it, the idea being that a low metabolic rate, low oxygen consumption, etc., might make you more likely to survive massive blood loss or nasty surgery without physiological damage ... if you’re not in a suspended animation-like state and you experience hypoxia, bad things happen to your brain.

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Figure 2A, Miller and Roth (2007).

Or course, that’s all for acute episodes dosed with hydrogen sulfide.  The Roth lab also did a study where they raised worms with or without 50 parts per million hydrogen sulfide in the atmosphere, and the worms with hydrogen sulfide lived longer (see Figure 2A for a nifty graph).

The next strategy is to supplement your diet with glucosamine.  This is an inhibitor of glycolysis: roughly speaking, the process by which your cells turn food into energy.  Work done in Michael Ristow’s lab showed that when mice were fed glucosamine every day for the bulk of their lives, they lived a little longer (see Figure 3C for the nifty graph).   And they presented significance testing for whether or not lifespan was increased… but didn’t mention a percentage for how much longer the mice lived.  Glancing at it, I’d say not much.  But some!  A little bit more time!

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Figure 3C, Weimer et al. (2014).

Or there’s caloric restriction.  Caloric restriction is something that’d be more reasonable for you to try at home than the whole huffing hydrogen sulfide thing, although I still wouldn’t recommend it.  Even though there’ve been very promising results in a variety of species… even in humans, so if you happened to decide today that this is something you’d want to do, the evidence is on your side.  Massively reduce the amount you eat and you might live longer.  Or not.  Caloric restriction also sounds a lot like anorexia, which causes horrible health problems.  Good job, photoshop!  And it’s apparently tricky to balance caloric restriction to be exactly right to promote lifespan without succumbing to all those anorexia-related health problems.

But in summary, it seems to be metabolism that kills you.  Oxygen eventually destroys cells.  And mitosis, which has to occur to replace your cells, involves doubling your DNA, which can never be 100% error-free.  So once you live enough, you’ll die.

The current strategies used to extend life – hydrogen sulfide, glucosamine, caloric restriction – seem primarily to slow metabolism.  So I don’t really think you’d be getting much more life.  You would persist in the world for more time, but would you be having more fun?  Would the integral of your fun vs. time graph over your entire lifespan even match that of someone living faster and less healthily?

I mean, I know my answer.  Not that I’m particularly unhealthy, but I volunteer as an assistant coach for the high school long distance runners, which means I go out and run with them a couple times a week, which means my metabolism works pretty hard.  I’m using up my heartbeats young; I won’t live forever.  But I still like doing it; I like running and I like running with them, talking with kids on the team, trying to make their time in high school a little less horrible than mine was.

img466psAnd as a last salvo for this essay, it might be worth quoting at one more curmudgeonly writer who’s pointed out some of the flaws in the whole “help everyone live longer” scheme: good old Jack Vance, whose debut novel “To Live Forever” is the best allegory for pursuing a tenure-track academic career I’ve ever read.  Seriously, if that’s your gig, you should check it out.  Yes, Jack Vance wrote pulp, but he was still a great stylist (it’s taking a great deal of restraint on my part not to quote a passage from his “Eyes of the Overworld” here… maybe I’ll try to find a way to work it in to a later, shorter essay) and the world he describes in “To Live Forever” feels eerily familiar to me, despite Vance having never taken part in it.  Here, I’ll quote a few passages from the beginning of that book: as you read, perhaps you’ll want to imagine modern terms like “impact factor” or “citation tracker” where he wrote “slope.”

At this time the word “slope” was charged with special meaning.  Slope was a measure of a man’s rise through the phyle; it traced the shape of his past, foretold the time of his passing.  By the strictest definition, slope was the angle of a man’s life line, the derivative of his achievements with respect to his age.

The Fair-Play Act carefully defined the conditions of advance.  A child was born without phyle identification.  At any time after the age of sixteen he might register in the Brood, thus submitting to the provisions of the Fair-Play Act.

If he chose not to register, he suffered no penalty and lived a natural life without benefit of the Grand-Union treatments, to an average age of 82.  These persons were the “glarks,” and commanded only small social status.

The Fair-Play Act established the life span of the Brood equal to the average life span of a non-participator–roughly 82 years.  Attaining Wedge, a man underwent the Grand-Union process halting bodily degeneration, and was allowed an added ten years of life.  Reaching Third, he won sixteen more years; Verge, another twenty years.  Breaking through into Amaranth brought the ultimate reward.

To apply this formula to the record of each individual, an enormous calculating machine called the Actuarian was constructed.  Besides calculating and recording, the Actuarian printed individual life charts on demand, revealing to the applicant the slope of his lifeline, its proximity either to the horizontal boundary of the next phyle, or the vertical terminator.

If the lifeline crossed the terminator, the Emigration Officer and his assassins carried out the grim duties required of them by the Act.  It was ruthless, but it was orderly–and starkly necessary.

The system was not without its shortcomings.  Creative thinkers tended to work in proved fields, to shun areas which might prove barren of career-points.  The arts became dominated by academic standards; nonconformity, fantasy and nonsense were produced only by the glarks–also much that was macabre and morose.

So, as soon as humans learned how to live forever — Jack Vance postulates an uploading methodology similar to the connectome-based schemes I linked to earlier — there had to be a way of determining which humans would live.  And it’s at that point that many of the most promising candidates would resort to conservative behavior; better to inch toward success than swing with all your might and maybe miss.  Better to propose a project that you know will yield something than to throw all your effort into a grand scheme and maybe come up with nothing. No publication, no grants, no tenure.