On immunity.

On immunity.

Our efforts to “flatten the curve” of the Covid-19 epidemic are onerous. 

Children aren’t allowed to go to school.  We’re forcing small retailers out of business.  People aren’t hugging when they greet.

Some people think these sacrifices are worthwhile, though, if they reduce the number of people who die from Covid-19.

Unfortunately, the effort to “flatten the curve” can cause more people to die of Covid-19 — including more of our elders — than if we’d carried on with life as usual.

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Antibodies are like the memory of your immune system.  After you’ve been infected with a particular virus, your body can destroy further copies of that virus.

This memory doesn’t last forever.  Your body will “forget” how to fight off the coronavirus that causes the common cold within a year.

If we carried on with life as usual, the coronavirus that causes Covid-19 would probably make its rounds through the population of the United States within a few months.  After that, there would be no new people to infect, and so the virus would disappear.

If, however, we practice social distancing and slow the rate of transmission – the same number of infections spaced over eighteen months instead of eighteen weeks – your immune system has a chance “forget” how to fight off the virus while this virus is still circulating in the population.  By slowing the rate of transmission, you give yourself the opportunity to contract the infection twice

If we slow the rate of transmission enough, this coronavirus will survive indefinitely.  Then people will continue to die of Covid-19 forever.

Even if you are currently at risk — elderly or immunocompromised — you should still fear this possibility. Will you be less at risk when this virus hits your hometown again in another year?

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When a virus infects a cell, it uses that cell’s replicative machinery to make more copies of itself.  A virus can’t reproduce on its own – it can only co-opt its host’s cells into making more copies for it.

Each time the host makes a new copy, it must replicate the entire genome of the virus.  Our cells are pretty good at copying genomes – every time the cells of our own bodies divide, they produce a new copy of our 3-billion-base-pair genome, and the copies usually have only a handful of mistakes.

Of course, a handful of mistakes compounded over time can be deadly.  That’s what cancer is – your cells didn’t copy your DNA perfectly, and so you wound up with slightly mutated DNA, and this mutated DNA instructs cells to form a tumor that kills you.

The same accumulation of errors can change a virus.  In the 1918 influenza epidemic, huge numbers of people died because the virus mutated to become more deadly.

The longer we allow the Covid-19 outbreak to go on – the more we strive to “flatten the curve” – the more mutations will accrue in its genome. 

Consider a city in which ten people live, one of whom has the virus.  If they throw a party, the other nine will be infected all at once – they will all come down with the Nth generation of the virus, whatever the current sick person is shedding.  If, however, they practice social distancing and get sick one at a time, each passing the infection to the next, the last person in the chain will be infected with viral generation N+9.  It could be very different, and more dangerous, than the initial virus.

Mutation doesn’t always make a virus more dangerous.  It’s entirely random.  It was bad luck that a mutation in 1918 made that strain of influenza more deadly.

But the risk is real.  It’s a risk we aggravate if we “flatten the curve.”  Right now, very few young healthy people will be hurt by Covid-19, but no one can know what monstrosity we’ll produce if we allow this virus to cycle through enough generations.

Inconveniently for us, Covid-19 is caused by an RNA virus.  Our cellular machinary is pretty good at making copies of DNA – every round of cell division makes a few mistakes, but not so many.  Our cellular machinary is worse at making accurate copies of RNA.  A virus with an RNA genome will mutate faster.

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People are worried that, without drastic efforts to slow the rate of transmission of Covid-19, the influx of new cases would overwhelm our hospitals.  We might run out of ventilators and be forced to triage, providing heroic medical interventions only to those people most likely to survive.  Some number of elderly patients with a low chance of survival would not receive care.

Is this bad?

Most medical doctors have signed “do not resuscitate” orders.  I have, too.  Most medical doctors, who have seen over and over again what it’s like when elderly patients with a low chance of survival receive heroic medical interventions, don’t want it for themselves.  They would rather die in peace.

The New York Times – which, alongside the New York Review of Books, is my favorite news outlet, even though it’s been full of fear-mongering about Covid-19 – printed a quote from Giacomo Grasselli, who coordinates intensive care units throughout Lombardy, Italy.  Grasselli is working at the front-lines of the Italian Covid-19 outbreak.

“My father is 84 and I love him very much,” but it would be irresponsible, he said, to make him go through the invasive procedures of an I.C.U.

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In the United States, we spent over three trillion dollars on medical care in 2016.  A huge fraction of this spending is used for minuscule extensions of life.  A third of all Americans have surgery during their last month of life.  We often spend more on interventions that extend the life of wealthy patients by a month than we do on all the pre-natal, preventative, and acute care that other people receive, ever.

What’s been missing, in the United States, is a conversation about what constitutes a good life.  What needs to happen for people to be able to face death with the thought that their lives have been enough? 

Covid-19 has killed thousands of people who were privileged to live to extremely old age.  In the United States, the worst outbreak will be in New York City – a city that is so expensive to live in that it harbors huge concentrations of wealthy elderly people.

In the United States, the life expectancy is 78 years.  Of course, there are major inequalities.  If you are wealthy, you might live longer than that.  If you are poor, you’ll probably die younger.  My spouse’s parents both died in their 60s.

Covid-19 has a high mortality rate for people who have already exceeded this life expectancy.  For people under retirement age, Covid-19 is less dangerous than seasonal flu.

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In the United States, life expectancy has been falling.  This decline is primarily due to an epidemic of “deaths of despair”: Drug addiction.  Suicide. 

In the United States, around 40,000 to 50,000 people die of suicide each year.  Around 60,000 people die of drug overdose.  Around 70,000 people die from alcohol abuse.

Each year, the epidemic of “deaths of despair” kill somewhere between 100,000 and 200,000 people.

Our efforts to “flatten the curve” will probably increase the number of people who die from deaths of despair.

Small towns across the United states have been gutted by the internet.  People used to visit local retailers, which could employ local salespeople.  Then we switched to buying things on Amazon, giving Jeff Bezos our money instead.

Now, local retailers are being forced to close due to fears about Covid-19.  People have to buy things online.  But local retailers still have expenses.  They still have to pay rent.  The owners still have to eat.  Many small retailers will run out of money and never open again after the Covid-19 epidemic is over.

As if our small towns needed yet more punishment.

In general, people will experience more financial woes because of our response to Covid-19.  Businesses are closed.  Work has slowed.  The stock market has tanked. 

And financial instability increases the risk of deaths of despair.  That’s a major reason why there’s been such a dramatic rise in deaths of despair among young people.

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Thankfully, our efforts to “flatten the curve” aren’t guaranteed to make this coronavirus mutate.  Our efforts aren’t guaranteed to make this virus a permanent parasite on the human race. 

We might cause these calamities, but we don’t know for sure.

Indeed, we know very little about this illness.  We do know that tens of thousands of elderly people have died.  But we don’t know whether ten thousand died out of a hundred thousand who were infected, or a million, or tens of millions.

Our perception of the disease would be very different in each of those scenarios.  But we do not, and can not, know.  We have no retrospective testing, and we have never tested a random sample of the population to investigate viral prevalence.

The best we can do is estimate from small data sets, the way Stanford epidemiologist John Ioannidis has done.  Ioannidis is very clear about his methodology, so if you happen to disagree with any of his assumptions, you can re-work the math yourself.

He concludes that our response is a horrific over-reaction.

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The people recommending these policies – social distancing, school closure, stay-at-home orders, or total lockdown – aren’t doing so out of malice.  They’re making the decisions they feel to be best.  But no policy is neutral, obviously. 

These policies prioritize the short-term needs of wealthy people who have exceeded their expected lifespans, at the expense of everyone under retirement age.  In particular, these policies do not value the needs of children.

Many of our country’s policies prioritize the desires of wealthy older people over the needs of children, though  “Flatten the curve” is just another example.

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In many places, we are probably attempting to “flatten the curve” after the epidemic has already run its course.

More likely than not, I already had Covid-19.  In early January, a co-worker of my children’s best friends’ parent left China, stayed briefly with her daughter in Seattle, then returned to Bloomington. 

A few days later, she came down with a high fever and a bad cough.  She went in for a flu test, but tested negative.  The doctors sent her home.

A week later, my children’s best friends’ parent – the sick woman’s co-worker – came down with a high fever and a bad cough.  His children were sick enough that they stayed home from school for a day.  He was sick enough that he missed a week of work.

A week later, on February 10th, my children and I got sick.  We had a high fever and a bad cough.  The kids felt better the next day.  I felt wretched for an entire week.  I am an endurance runner with strong lungs – still, I needed puffs of my spouse’s Albuterol inhaler four times a day.  I took naproxen but still had a hallucinatory fever.  I wouldn’t wish that illness on anyone.  For the next two weeks, I was vigilant about washing my hands and tried to minimize my contact with other people.

Over the next month, many other people in town came down with a cough and fever.  It would typically last a week, then they’d feel better.

But it was pretty scary for some people. I’d felt wrecked. Another friend of mine — 55 years old, cigarette smoker, & former methamphetamine addict — felt like he could barely breathe. The doctor said that if his oxygen flow had been any lower, she would’ve kept him at the hospital.

He wasn’t tested for Covid-19. There were still no tests available. And after a horrible week, he felt better.

And then, on March 12thafter the epidemic had probably run its course in our town – our schools closed.  The university students left for spring break, and the remaining populace of our small town began to practice social distancing.

And yet, in mid-March, the first case of Covid-19 was diagnosed here.  This patient could not trace the social connections that would have led back to a known Covid-19 outbreak.  As should be expected by that late stage of an epidemic.

All around the country, reported Covid-19 cases are exponentially rising.  But that doesn’t mean that Covid-19 infections are exponentially rising.  It only means that access to Covid-19 testing has risen.

When the epidemic likely spread through my town, it went undetected – no Covid-19 tests were available in the United States, and there’s no way to test whether someone was infected in the past.  The reported numbers of Covid-19 cases are guaranteed to be lower than the true number of people infected, because you can only be counted as a Covid-19 if you feel sick enough to visit a doctor, and then somehow manage to get access to the test.

The test will only register positive during the acute phase of the illness.  There is no possible way to test whether someone who isn’t currently shedding virus has been infected.

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A useful way to consider this epidemic is to imagine what would happen if the Covid-19 PCR test wasn’t invented. 

People would still get Covid-19.  We would take no extraordinary protective measures, because we wouldn’t realize what they were sick with.

This is like what happened at the beginning of the HIV crisis in the United States.  Medical doctors called the disease GRD, or “gay-related disease,” and it was terrifying.  Healthy young people suddenly wasted away.

If we lacked a PCR test to accurately diagnose Covid-19, though, we wouldn’t call it “age-related disease.”  We would call it “seasonal flu.”  This year, about 30,000 people will die of seasonal flu, including many healthy young people.  This year, my nephew almost died of the flu.  He couldn’t breathe.  He needed invasive ventilation to survive.

If we did nothing to staunch the Covid-19 outbreak, somewhere between 15,000 and 30,000 people probably would die from it.  Combined with the 30,000 deaths actually caused by influenza, we would think that between 45,000 and 60,000 people had died from seasonal flu.  No more than a dozen or so of the additional deaths would have been healthy young people.

That’s many more deaths!  But nothing exceptional.  In 2017, 60,000 people died of seasonal flu.

In 2017, we still let children go to school.  I’m not sure I read any news articles about seasonal flu in 2017.  And in the following years – after huge numbers of people died! –  about half our population didn’t bother to get a flu vaccine.

Influenza is a more dangerous illness, and it’s preventable.  But our country’s vaccination rate is too low to confer herd immunity.  Even if you are young and healthy, a bad case of the flu can kill you.  Even if you are young and healthy, your vaccination protects others.

Social distancing would protect people from the flu, also.  Every flu season, we could stay six feet away from each other for a few weeks, and then we’d vanquish the flu.  But social distancing comes at a tremendous cost, as we’re now learning.

Or we could get the vaccine.  But we, as a people, don’t.

On violence and gratitude.

On violence and gratitude.

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

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

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

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

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

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

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

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

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

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

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

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Human gametes by Karl-Ludwig Poggemann on Flickr.

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

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

From Suzana Herculano-Houzel’s The Human Advantage:

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

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

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

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

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

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

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

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

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

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

On correspondence.

On correspondence.

1280px-Plasmid_(english).svgDNA plasmids are small loops of genetic information that can change the behavior of bacteria.  With the right (wrong?) plasmids, you could take innocuous E. coli and make it very dangerous.

As best I could tell from a few minutes spent skimming the USPS documents describing “hazardous, restricted, and perishable mail,” it’s not actually illegal to ship plasmids.  Many biomedical researchers have long assumed that it was illegal, though.  Not that we didn’t do it.  But we always took steps to sneakily circumvent the laws we assumed existed.

Plasmids are dangerous, after all.  Why wouldn’t there be a law?

DNA is very stable.  Its stability is probably the whole reason it exists.  Most scientists assume that life began as self-replicating strands of a molecule called RNA, which is very similar to DNA except more prone to falling apart.  Each of our cells is like a tiny factory – proteins are the machines, RNA are blueprints, and DNA is a file cabinet.

(K says this analogy is no good because a file cabinet is an “archaic technology.”  I have several early drafts of my novel – plus the entire three-year run of Evil Dave vs. Regular Dave – in a file cabinet next to our bed.  I wonder, am I an archaic technology?)

DNA is so stable that it can be dried out and shipped across the country without coming to any harm.

To send plasmids through the mail, we would draw a circle on a piece of filter paper, dab a liquid solution of it onto the paper, then slip the sheet into the center of a catalog.  The catalog would look harmless, like junk mail.  Whomever received it would flip through, find the filter paper, cut out the circle, and immerse it in water.  Voila!  The plasmid is ready to change bacteria into something new!

The good people at the post office never notice.  The only snags are undergrads – a sophomore who was working with us happened to open the mail.  Our advisor asked later, “Where is that plasmid?  It was being sent by the ______ lab.”

“We got a package from them … but it was just an old catalog.  I recycled it.”

Oops.

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Pink_Elephants_on_Parade_Blotter_LSD_DumboAs it happens, numerous psychoactive chemicals can wig out a human brain at concentrations low enough to dissolve on paper.  Somebody sends a saturated sheet through the mail – you cut it out and, instead of using it to transform bacteria, you get high.

Apparently this works well with suboxone – which can be used either as a treatment for or a substitute for heroin – and the THC analogs marketed as K2, spice, or synthetic marijuana.  LSD has long been sold dissolved on blotter paper with goofy cartoons.

And so the Indiana Department of Corrections recently decided to ban all correspondence to inmates that isn’t handwritten on blue-lined white paper.  No greeting cards, no photocopies, no drawings.

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Photo from Pat and Steve Cole / St. Basil Greek Orthodox Church in Chicago, IL.  I first saw it in the Indy Star.

A Chicago-based church sends greeting cards to many prisoners over the holidays.  This May, the entire batch of Easter cards they’d sent to Indiana prisoners were returned with a brief note explaining the new mail policy.  Even now, it’s unclear what the policy actually is.  The only regulations for offender correspondence available from the Indiana Department of Corrections are dated September, 2015.  Even these guidelines are vague, mentioning that all decisions are made on a case-by-case basis.

For the correspondence writing workshop I run, I often send printed materials.  Because these are being mailed on behalf of a non-profit corporation, they are supposed to go through – only private mail is supposed to be axed by the new policy.

Or so we’ve been told.

When our corporation sends letters or packages sometimes they go through, sometimes they do not.  The fate of each letter depends on which guard happens to be working in the mail room when it arrives, obviously.  The policy is sufficiently vague that each enforcer will interpret it differently.

A letter’s fate also seems to depend on the identity of the recipient.  If you receive a package while in prison, I’ve been told, the guards are supposed to open it in front of you, show it to you, and then have to either give it to you or explain why you can’t have it.  But with so many and such vague rules, the guards should always be able to think of a reason to bin it.  I’ve noticed that many of our packages that get returned for flimsy reasons were sent to people with long lists of disciplinary infractions.

The rich get richer.  And those who seem to need love most … get nothing.  If you’re disliked, they can sever you from the world.

On scrutiny.

On scrutiny.

We can be attentive to only a small sliver of the world.

We’re constantly surrounded by so much noise, so many smells, so many different colors, textures, tastes.  The amount of sensory information that we’re bombarded with every moment would be overwhelming if we weren’t so good at ignoring our environment.

Consider smells.  Chemicals waft through the air, bind to olfactory receptors in our nose, and cause a signal to ping our brain: there’s the floral scent of an ethyl acetate here …  But, if we stay near the source of that chemical, our brain will keep receiving that signal.  Thankfully, this information is discarded by our subconscious minds.  As long as the types of smells in a space aren’t changing, we soon notice nothing.

If our clothes feel the same against our skin from one moment to the next, all the tactile information being sent from the surface of our body is similarly ignored.  But the information is still there.  If we focus your attention on your shirt, you can feel it.

The-Pearl-294878In The Pearl, John Steinbeck reveals how this glut of information can cause us to be hoodwinked.  A poor diver becomes suddenly wealthy when he finds a giant pearl.  The diver’s infant child was stung by a scorpion and has begun to recover … but a greedy doctor would rather the child receive an expensive cure.  The doctor knows that he can fool the diver by drawing his attention to details that never seemed important before.

It is as I thought,” [the doctor] said.  “The poison has gone inward and it will strike soon.  Come look!”  He held the eyelid down.  “See – it is blue.”  And Kino, [the diver], looking anxiously, saw that indeed it was a little blue.  And he didn’t know whether or not it was always a little blue.  But the trap was set.  He couldn’t take the chance.

If we scrutinize the world, we can always find something that looks strange.

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When I was in high school, I had to get a medical physical each year.  Those cost $5 – a school nurse would measure my blood pressure, listen to my heart, and look at the curvature of my spine.  I felt healthy enough when I signed up for these physicals, and the nurses invariably agreed.  Even repeatedly-concussed football and soccer players were given a clean bill of health.

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This $5 exam was insufficient to find anything wrong with us.  But if we’d been subjected to a $25,000 battery of diagnostic scrutiny instead, I’m sure we’d have seemed flawed.

Indeed, in a recently-published study designed to shill the new $25,000 physical from a company called “Health Nucleus” in California – which includes DNA sequencing, metabolite analysis, full-body MRI, two weeks of heart monitoring, and more – 40% of their seemingly-healthy study participants were diagnosed with “something seriously wrong.”  In several study participants, doctors found clusters of aberrant cells: pre-cancer.

In sexually-reproducing multicellular organisms, most cells carry DNA instructions to sacrifice themselves for the sake of the whole.  Some of these instructions code for contact inhibition, which means that cells stop growing when their edges bump into neighbors.  Other DNA sequences code for apoptosis, which means that cells commit suicide once they’re no longer needed.

But the mechanism for transmitting these instructions is imperfect.  DNA is copied again and again by jiggling protein machines called polymerases, and these make about 60 mistakes each time they copy our genomes.  Worse, DNA is copied from copies, so the mistakes pile up over time.  Like classroom handouts that have been photocopied from photocopies so many times that the words blur into static, DNA sequences that instruct our cells to cooperate can become unreadable.  At which point a cell is cancerous.

4.0.4Cancer cells continue growing without regard for the neighbors they’re crowding.  They carry on dividing – spewing forth copies of themselves – long after a team-player would’ve snuffed itself.

Most human adults harbor cancer cells.  All the time, they lurk in us.  And our immune systems destroy them.  Chemotherapy drugs do not kill cancerous cells – they slow the growth of all cells, giving a patient’s own immune system time to fight the menace.

So it’s unsurprising that doctors found pre-cancer in some of the study participants who underwent this $25,000 physical.  Study participants were as old as 98.  Their average age was 55.  After so much time alive, of course some of their cells had gone bad.

Early detection of cancer does boost a patient’s chance of survival, but sometimes in a trivial way.  Healthy patients whose immune systems would have destroyed a population of aberrant cells without any intervention … who might never have realized that anything was ever wrong … are counted as “cancer survivors.”  Extremely sensitive diagnosis can identify cancers early enough to be cured, but has the drawback of mis-labeling healthy people as diseased.

Every diagnosis of disease leads to harm – from worry, from the risks inherent in all medical treatment – and so has to be balanced against the expected outcome from doing nothing.  With some conditions, doing nothing would be deadly.  But by scrutinizing healthy people, you can always find something that looks strange.  Of course you’ll find “evidence of age-related chronic disease or risk factors” when you subject older people to a $25,000 battery of medical tests.  If you aggressively treat all of these, you’ll cause more harm than good.

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Because overdiagnosis can cause so much harm, the search for pre-cancer reminds me of the search for pre-criminals.  We can always find something wrong when we look hard enough.

I assume the researchers investigating children to find “pre-criminals” mean well.  I can imagine a world in which at-risk children are given more resources.  If it’s true, for instance, that a brief assessment of 3-year-olds or surveys filed by the teachers of 6-year-olds can predict future criminal behavior, we should cut spending on prisons and law enforcement to fund childhood nutrition, education, and enrichment instead.

Instead, we respond to intimations of future disobedience by watching people more closely.

Adorable Preschooler Playing with Colorful Dough

Our predictions of criminality become self-fulfilling: lifelong mistrust makes people criminals.  The racial injustice of mass incarceration is caused in part by unequal enforcement.  As far as we know, U.S. citizens of all ethnicities break laws equivalently often, but police scrutinize minority neighborhoods more closely, so that’s where they find crimes.

Similarly, when an elementary teacher decides that a student is trouble, that student gets scrutinized.  Equivalent misbehavior reaps unequal discipline.  In the U.S., children in preschool are targeted for school suspension based on the color of their skin.  A suspension disrupts education, pushing students further behind.  When a teacher decides that a student won’t learn, that student is prevented from learning.

And researchers have developed an automated image analysis that predicts the likelihood that someone is a criminal just from a photograph of his clean-shaven face.  Which isn’t as evil as it sounds.  Or, rather, it is evil, but not because a computer is doing it – the computer algorithm is simply revealing and quantifying the evil way we humans judge people by their appearances.

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Genetics differences are real, and they do make a substantial contribution to people’s proclivities.  But human brains are so plastic that the way we’re treated matters more: if you’re curious, you might want to check out this inadvertent identical twin study.

With a glance, we form strong opinions about people’s characters.  Some children we brand “pre-criminals.”  Is it shocking that, after decades of mistreatment and scrutiny, these children become the lawbreakers we always expected them to be?

On how human different humans happen to be (hint: equivalently human).

CaptureI finally read some of the initial papers (circa 1981) describing an outbreak of opportunistic infections among previously-healthy homosexual men in the United States.  The case studies are harrowing — a dispassionate litany of suffering, ending with death.

And, yes, these are papers from before I was born.  I should’ve read them already, or at least know enough about them that they’d have no impact.  To someone like my father, for instance, who has worked with HIV patients for most of my life, the old case studies would not seem shocking — I recently read Henry Marsh’s Do No Harm, which carries a beautiful epigraph from Rene Leriche (I’m not sure who translated this from the French — if somebody knows, please tell me!): “Every surgeon carries within himself a small cemetery, where from time to time he goes to pray — a place of bitterness and regret, where he must look for an explanation for his failures.” — my father, like most medical doctors, can surely close his eyes to summon up memories more bleak than the case studies I’ve been reading.

But to me, a medical naif, the papers remind me of the horrifying violence against women section of Roberto Bolaño’s 2666.  Personal tragedy and heart-wrenching suffering condensed into clinical prose.  Not fun.

But I had a reason for subjecting myself to this!  A recent NPR news investigation alerted me to Susan Smith’s article “Mustard Gas and American Race-based Human Experimentation in World War II.”

To put these experiments in perspective, I think it’s worth considering how mustard gas works.  Luckily, I took a medicinal chemistry class with Rick Silverman where we discussed the mechanism of both mustard gas and the early mustard-gas-esque chemotherapy drugs known as nitrogen mustards.  It was a cool topic, so I still remember it: I’ve drawn out the mechanism (with some helpful notes!) below.

mechanism001

And, looking back on this, there are a few things worth noting.  One is, yeah, it’s perhaps obvious why I was emotionally leveled by reading those AIDS case studies — most of what I know is massively abstracted.  It’s very different to hear the words “mustard gas” and envision a lines-and-letters mechanism  versus seeing a image of Rollins Edwards juxtaposed with another depicting a jarful of his own skin (which appears halfway down the page for the NPR story).

Capture
See the NPR article here.

I’d like to think that the scientists who originally designed these experiments were picturing everything on that same level of abstraction.  Not that this excuses what they did, but it’s slightly less awful to imagine that they were simply oblivious to the human harm they were causing.

The second is, well, look!  Mustard gas crosslinks DNA!  How different from black or Puerto Rican or Japanese soldiers did those white scientists imagine themselves to be to think that mustard gas would show differential efficacy?

And that’s why I was looking up the AIDS papers.  Because I attended a symposium in 2002 where Lane Fenrich read excerpts from those original papers.  His message was that the authors of those original papers implied that homosexuals are distinct on a cellular level.

I no longer remember which passages he chose to read, but here are two quotes that convey his point.  The first is from the paper by Gottlieb et al.:

Depression of T-cell numbers and of proliferative responses to the degree observed in our patients has not been reported to occur in ctyomegalovirus-induced syndromes in normal persons.

Should I be doing something cheeky with font to add emphasis to the words “normal persons” at the end of that sentence?  Naw, I think you probably get the point.

The second quote I thought I’d include is from a 1982 Center for Disease Control report:

Infectious agents not yet identified may cause the acquired cellular immunodeficiency that appears to underlie [Kaposi’s sacroma] and/or [Pneumocystis cainii pneumonia] among homosexual males.

Again, the message being sent is that there are cellular differences.  An infectious agent targets basic human biology among homosexual males.  Which is a crazy message to send.  Sure, they only had a small data set — they didn’t have any evidence yet that the same infectious agent might cause immunodeficiency in heterosexuals, or in women.  But, wouldn’t that be a reasonable assumption to make?  You have to presume pretty extreme levels of otherness to think that would not be the case.

ZPp_fotx0TiwtLE3nEBnVw_sharegeneswmeReading these papers made me pretty happy that a friend sent us a copy of 23andMe’s board book You Share Genes with Me shortly after N was born.  With corny rhymes the book celebrates how similar we are to organisms ranging from grasses, flies, fish, up to chimpanzees and our (presumed) human friends.  With numbers, too — if N could speak, perhaps she could let you know that chimpanzees share ca. 96% of her DNA sequence, and another human baby ca. 99.5%.

Which is a nice message to send.  Human brains are so good at presuming otherness; it’s charming to have a book for her that makes clear how similar we all are, people, animals, and even plants.

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p.s. Maybe you’ve read reports about pharmaceuticals with race-based differential efficacy.  And, yes, despite over 99% DNA sequence identity between any two human beings, there are some differences that correlate with ethnicity.

Appearance, for one — many people assume they can assess ethnicity well from photographs.  Lactase persistence is another, and that seems to have developed recently (as far as evolutionary timescales go).  It’s not so unreasonable to imagine differences in drug metabolism between humans of differing genetic ancestries, and that can have a big impact on efficacy: two people taking the same dose of a medication might experience significantly different concentrations of the active ingredient.

I’ll include more about these issues when I finally get around to posting that essay on the evolution of skin color, but on the whole these seem to be pretty minor differences, and nothing that would affect sensitivity to mustard gas, which takes a baseball bat to your DNA long before you’d have a chance to metabolize it.  And the only big news story about race & pharmaceuticals that I know about is for that heart medication, BiDil.  In that case, it seems most likely that their rationale for claiming race-based efficacy was to help them file a new patent.  If you’re curious, you could read Dorothy Roberts’s article chastising the race-based claims; here I’d like to highlight just these three lines:

In the past, the FDA has had no problem generalizing clinical trials involving white people to approve drugs for everyone.  That is because it believes that white bodies function like human bodies.  However with BiDil, a clinical trial involving all African Americans could only serve as proof of how the drug works in blacks.

On Y chromosomes, surnames, and reproduction.

On Y chromosomes, surnames, and reproduction.

Invisible-History-Human-Race_Author-ImageFor me, the most interesting section of Christine Kenneally’s “The Invisible History of the Human Race” was the section on Y chromosomes.  Because, sure, if I’d spent a moment thinking about it I would have realized that sons of sons of sons carry the same Y chromosomes as their forebears… but it isn’t something I’d bothered thinking about.

But the connection that was most interesting for me – and, yeah, also retrospectively obvious – was that in a patriarchally-named society, surnames will make the same journey as Y chromosomes.

They are coupled throughout time, in ways that researchers have investigated for, say, Scottish clans: a sort of scientific validation for the lineage claims that even in modern times are accompanied by property rights.  From Kenneally’s book:

“It wasn’t until 1957 that the ancient chiefly Arms were finally officially recorded.  Donald’s father assembled a significant amount of evidence to prove that he was in fact descended from the last known MacLaren chief, and he presented it to the Court of the Lord Lyon in Edinburgh, the Scottish heraldic authority that rules on title and is famously rigorous in its judgement.  The court decreed that Donald’s father had indeed descended from the last-known chief of Clan MacLaren.  When he was made chief, he acquired the legal title to some of the clan lands at Balquhidder that had been lost a few centuries earlier, including the famous Creag an Tuirc, the Clan’s rallying point from earliest times.  When he died in 1966, his three golden feathers were passed on to his eleven-year-old son, now the twenty-fifth chief since Labhran.”

Obviously the evidence presented at the time, as described in the above paragraph, did not include DNA testing – but apparently the MacLarens have been quite involved in DNA testing recently, and current results correlate with the prior historical claims.

The interesting thing to me is that names, and land, and Y chromosomes, all traveled together.  There has long been the sense that sons are special – even in western cultures, where to me it has not seemed like sons provide for their aging parents any better late in life than daughters do – with the idea that some special spark is passed from fathers to their sons.  And the journey of names reflects that.

And, right – now might be a reasonable time to mention that when K and I married, neither of us changed our names.  And we gave N a surname distinct from either of ours.  I am not particularly keen on the idea of patriarchy, and didn’t want to make my own contribution to that system of beliefs by giving my daughter her father’s name.  And, sure, some people pass along a mother’s name instead, but I personally don’t feel like the solution to a patriarchy is to institute practices that we’d have in a matriarchy…although in the short term it does seem reasonable.

(Like, okay, affirmative action in hiring – I assume that most people think that in an ideal world, employers wouldn’t care about your ethnicity and so affirmative action would not be needed.  But given that you can find numerous studies on racist hiring decisions – every few years there are articles about the effect of stereotypically black names in America, and here is a similar study on the effect of African/Arabic names on hiring decisions in Sweden – it seems like affirmative action is definitely still a worthwhile policy in many countries.

And that’s in cases where there is an equivalence between CVs, etc., between people with different names.  You could make a much stronger argument by suggesting that employers should care most about a person’s ability to make the best of their circumstances, or overcome challenges, so if race were correlated with a difference in material advantages at birth, you’d not only want to preference minority applicants with equivalent CVs, but also those who might appear slightly worse based on numerically-documented facts on a job application.)

So, N has a new name.  She does have some amount of my genetic material, though.  Almost 50%.  So there’s that.

Although you could make an argument for using more of the trappings of matriarchy in cultural decisions.  Especially as reproductive science moves forward – it isn’t difficult to imagine a world that doesn’t need men.  Which isn’t just a joke, although I do recall their being a good joke-y treatment of this in a dialogue at the beginning of “Roger Dodger.”  Because you can produce mammalian offspring without the aid of men  – yeah, you need to deliver the genetic material in a laboratory instead of having it be carried by sperm, but is that such a big cost?  Already many couples in the U.S. employ the help of laboratory personnel for reproduction.

And, yes, recently it’s proven possible to engender children with the nuclear genetic material of two males, but this technique still requires a mother to carry the embryo, and a female to provide the egg (and the mitochondrial DNA, although presumably you could develop a technique to displace the mother’s mitochondria with those of one of the fathers).  So you could have a world without men, and humans would be able to propagate, but at the moment a world without women wouldn’t work.

(Bonus parenthetic insert!  Because I already have one exceedingly-long parenthetical inserts in this essay already – why not another one?

Many of those laboratory techniques to aid in reproduction were developed by men, and many of the doctors implementing them are men.  So is it unreasonable to think that this may have influenced the remunerations received by sperm donors, which are relatively high given the low risks and low time input after initial screening, versus those received by women, which are pretty crappy… crappy in a way reminiscent of the low prices flowing to organ donors.  Egg donors, like organ donors, tend to be impoverished and relatively un-educated.  And it seems that there has been collusion on the part of medical providers to keep compensation low.  From Kimberly Krawiec’s analysis of gamete markets:

“In February 1998, the Saint Barnabas Medical Center in New Jersey set off a firestorm of controversy when it placed advertisements in several New York-area publications offering potential egg donors $5000, twice the $2500 that the center had been paying.  The firestorm was provoked not because Saint Barnabas proposed to pay egg donors for their services, which it and other fertility clinics had been doing for years, but because the proposed payment increases were made in violation of an alleged understanding among New York-area fertility centers to pay no more than $2500 for eggs.  The ensuing debate (during which many fertility doctors openly discussed the need to control egg prices) quickly garnered newspaper and other media attention, and generated arguments in major medical journals.”)

And yet, despite the fact that reproduction from women alone is much more reasonable than reproduction from men alone, the production of offspring from men appears much more often in mythology.  There’s Zeus, creating Athena from his head.  A similar story associated with the Ramayana, in which Ravana created Sita with a sneeze.

Presumably men throughout time have felt bad about their limited role in propagation of the species and created stories to celebrate that men could have an important role… they just often don’t.

And there are others: Shiva created a mountain range by ejaculating onto the ground.  The sage Bharadwaja saw a beautiful woman bathing and ejaculated into a basket, creating his son Drona.

Which, right, scientifically seems ridiculous – children arising from spilt sperm?  Eggs, maybe… but sperm?  So naturally I had to include the phenomenon in my work.  As a twist on the very-real possibility of a world propagated by women alone, and a nod to the underlying mythology.