On ethics and Luke Dittrich’s “Patient H.M.”

On ethics and Luke Dittrich’s “Patient H.M.”

The scientific method is the best way to investigate the world.

Do you want to know how something works?  Start by making a guess, consider the implications of your guess, and then take action.  Muck something up and see if it responds the way you expect it to.  If not, make a new guess and repeat the whole process.

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Image by Derek K. Miller on Flickr.

This is slow and arduous, however.  If your goal is not to understand the world, but rather to convince other people that you do, the scientific method is a bad bet.  Instead you should muck something up, see how it responds, and then make your guess.  When you know the outcome in advance, you can appear to be much more clever.

A large proportion of biomedical science publications are inaccurate because researchers follow the second strategy.  Given our incentives, this is reasonable.  Yes, it’s nice to be right.  It’d be cool to understand all the nuances of how cells work, for instance.  But it’s more urgent to build a career.

Both labs I worked in at Stanford cheerfully published bad science.  Unfortunately, it would be nearly impossible for an outsider to notice the flaws because primary data aren’t published.

A colleague of mine obtained data by varying several parameters simultaneously, but then graphed his findings against only one of these.  As it happens, his observations were caused by the variable he left out of his charts.  Whoops!

(Nobel laureate Arieh Warshel quickly responded that my colleague’s conclusions probably weren’t correct.  Unfortunately, Warshel’s argument was based on unrealistic simulations – in his model, a key molecule spins in unnatural ways.  This next sentence is pretty wonky, so feel free to skip it, but … to show the error in my colleague’s paper, Warshel should have modeled multiple molecules entering the enzyme active site, not molecules entering backward.  Whoops!)

Another colleague of mine published his findings about unusual behavior from a human protein.  But then his collaborator realized that they’d accidentally purified and studied a similarly-sized bacterial protein, and were attempting to map its location in cells with an antibody that didn’t work.  Whoops!

No apologies or corrections were ever given.  They rarely are, especially not from researchers at our nation’s fanciest universities.  When somebody with impressive credentials claims a thing is true, people often feel ready to believe.

antibodies.JPGIndeed, for my own thesis work, we wanted to test whether two proteins are in the same place inside cells.  You can do this by staining with light-up antibodies for each.  If one antibody is green and the other is red, you’ll know how often the proteins are in the same place based on how much yellow light you see.

Before conducting the experiment, I wrote a computer program that would assess the data.  My program could identify various cellular structures and check the fraction that were each color.

As it happened, I didn’t get the results we wanted.  My data suggested that our guess was wrong.

But we couldn’t publish that.  And so my advisor told me to count again, by hand, claiming that I should be counting things of a different size.  And then she continued to revise her instructions until we could plausibly claim that we’d seen what we expected.  We made a graph and published the paper.

This is crummy.  It’s falsehood with the veneer of truth.  But it’s also tragically routine.

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41B1pZkOwmL._SX329_BO1,204,203,200_Luke Dittrich intertwines two horror stories about scientific ethics in Patient H.M.: A Story of Memory, Madness, and Family Secrets.

One of these nightmares is driven by the perverse incentives facing early neurosurgeons.  Perhaps you noticed, above, that an essential step of the scientific method involves mucking things up.  You can’t tell whether your guesses are correct until you perform an experiment.  Dittrich provides a lovely summary of this idea:

The broken illuminate the unbroken.

An underdeveloped dwarf with misfiring adrenal glands might shine a light on the functional purpose of these glands.  An impulsive man with rod-obliterated frontal lobes [Phineas Gage] might provide clues to what intact frontal lobes do.

This history of modern brain science has been particularly reliant on broken brains, and almost every significant step forward in our understanding of cerebral localization – that is, discovering what functions rely on which parts of the brain – has relied on breakthroughs provided by the study of individuals who lacked some portion of their gray matter.

. . .

While the therapeutic value of the lobotomy remained murky, its scientific potential was clear: Human beings were no longer off-limits as test subjects in brain-lesioning experiments.  This was a fundamental shift.  Broken men like Phineas Gage and Monsieur Tan may have always illuminated the unbroken, but in the past they had always become broken by accident.  No longer.  By the middle of the twentieth century, the breaking of human brains was intentional, premeditated, clinical.

Dittrich was dismayed to learn that his own grandfather had participated in this sort of research, intentionally wrecking at least one human brain in order to study the effects of his meddling.

Lacking a specific target in a specific hemisphere of Henry’s medial temporal lobes, my grandfather had decided to destroy both.

This decision was the riskiest possible one for Henry.  Whatever the functions of the medial temporal lobe structures were – and, again, nobody at the time had any idea what they were – my grandfather would be eliminating them.  The risks to Henry were as inarguable as they were unimaginable.

The risks to my grandfather, on the other hand, were not.

At that moment, the riskiest possible option for his patient was the one with the most potential rewards for him.

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By destroying part of a brain, Dittrich’s grandfather could create a valuable research subject.  Yes, there was a chance of curing the patient – Henry agreed to surgery because he was suffering from epileptic seizures.  But Henry didn’t understand what the proposed “cure” would be.  This cure was very likely to be devastating.

At other times, devastation was the intent.  During an interview with one of his grandfather’s former colleagues, Dittrich is told that his grandmother was strapped to the operating table as well.

It was a different era,” he said.  “And he did what at the time he thought was okay: He lobotomized his wife.  And she became much more tractable.  And so he succeeded in getting what he wanted: a tractable wife.”

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Compared to slicing up a brain so that its bearer might better conform to our society’s misogynistic expectations of female behavior, a bit of scientific fraud probably doesn’t sound so bad.  Which is a shame.  I love science.  I’ve written previously about the manifold virtues of the scientific method.  And we need truth to save the world.

Which is precisely why those who purport to search for truth need to live clean.  In the cut-throat world of modern academia, they often don’t.

Dittrich investigated the rest of Henry’s life: after part of his brain was destroyed, Henry became a famous study subject.  He unwittingly enabled the career of a striving scientist, Suzanne Corkin.

Dittrich writes that

Unlike Teuber’s patients, most of the research subjects Corkin had worked with were not “accidents of nature” [a bullet to the brain, for instance] but instead the willful products of surgery, and one of them, Patient H.M., was already clearly among the most important lesion patients in history.  There was a word that scientists had begun using to describe him.  They called him pure.  The purity in question didn’t have anything to do with morals or hygiene.  It was entirely anatomical.  My grandfather’s resection had produced a living, breathing test subject whose lesioned brain provided an opportunity to probe the neurological underpinnings of memory in unprecedented ways.  The unlikelihood that a patient like Henry could ever have come to be without an act of surgery was important.

. . .

By hiring Corkin, Teuber was acquiring not only a first-rate scientist practiced in his beloved lesion method but also by extension the world’s premier lesion patient.

. . .

According to [Howard] Eichenbaum, [a colleague at MIT,] Corkin’s fierceness as a gatekeeper was understandable.  After all, he said, “her career is based on having that exclusive access.”

Because Corkin had (coercively) gained exclusive access to this patient, most of her claims about the workings of memory would be difficult to contradict.  No one could conduct the experiments needed to rebut her.

Which makes me very skeptical of her claims.

Like most scientists, Corkin stumbled across occasional data that seemed to contradict the models she’d built her career around.  And so she reacted in the same was as the professors I’ve worked with: she hid the data.

Dittrich: Right.  And what’s going to happen to the files themselves?

She paused for several seconds.

Corkin: Shredded

Dittrich: Shredded?  Why would they be shredded?

Corkin: Nobody’s gonna look at them.

Dittrich: Really?  I can’t imagine shredding the files of the most important research subject in history.  Why would you do that?

. . .

Corkin: Well, the things that aren’t published are, you know, experiments that just didn’t … [another long pause] go right.

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On Colson Whitehead’s ‘The Underground Railroad.’

On Colson Whitehead’s ‘The Underground Railroad.’

Whenever one of her students finished, my graduate school advisor took everyone out to dinner and paid for the meal.  These were expensive meals, too – between San Francisco’s culinary culture and Silicon Valley’s sudden money, many restaurants near Stanford turned very pricey.

I wouldn’t eat.  I’d order a glass of water, no more.  If it were lunchtime, I’d say that I planned to go running early in the afternoon.  If it were dinner, I’d murmur that K & I had eaten already.  My advisor would frown, but after the first few times this happened, she stopped arguing.  She probably thought I was anorexic, or deranged.

Nope.  But I’d read Lewis Hyde’s The Gift.  In his words:

gift_us_newGift exchange must … be refused when there is a real threat in the connections that it offers.  In ancient tales the hero who must pass through hell is warned that charity is dangerous in the underworld; if he wishes to return to the land of the living, he should lend a hand to no one, nor accept the food offered by the dead.

Gifts from evil people must also be refused lest we be bound to evil.  In folk tales the hero is well advised to refuse the food and drink offered him by a witch.

We often refuse relationship, either from the simple desire to remain unentangled, or because we sense that the proffered connection is tainted, dangerous, or frankly evil.  And when we refuse relationship, we must refuse gift exchange as well.

If I’d nibbled an eight dollar plate of french fries, I probably wouldn’t have been trapped in California.  But it wasn’t worth the risk.  That was a world with which I hoped to maintain no ties.

urThe stakes for Cora, the hero of Colson Whitehead’s The Underground Railroad, are higher.  I was miserable during graduate school, but Whitehead writes of a world in which innocent people are routinely tortured and murdered in all variety of grotesque, horrifying manner.

When Cora stumbles to the road after trekking for days through a secret subterranean tunnel, she sees several wagons trundling westward.  The first two wagons are driven by white men – she ignores the first, and, when pressed by the second, turns down his offer to help.

The third wagon was commanded by an older negro man.

You hungry?” the man asked.  He was from the south, from his voice.

I’m very hungry,” Cora said.

Despite her hunger, Cora could not accept aid from the whites.  Although her escape was facilitated by several white people (most of whom were then tortured and murdered for having aided her), she cannot trust strangers with pallid skin.

Indeed, a minor character, another survivor of the final massacre that Cora fled, gives a pithy summary of this distrust in her old age:

She lived on Long Island then, after roaming all over the country, in a small house with a Shinnecock sailor who doted on her to excess. She’d spent time in Louisiana and Virginia, where her father opened colored institutes of learning, and California.  A spell in Oklahoma … The conflict in Europe was terrible and violent, she told her sailor, but she took exception to the name.  The Great War had always been between the white and the black.  It always would be.

Several pages earlier, Whitehead proffers a speech from a character highly regarded for his intellectualism; this speech delineates the sides in this war:

Our ancestors came from all over the African continent.  It’s quite large. … They had different ways of subsistence, different customs, spoke a hundred different languages.  And that great mixture was brought to America in the holds of slave ships. … We are craftsmen and midwives and preachers and peddlers. … The word we.  We are not one people but many different people.  How can one person speak for this great, beautiful race – which is not one race but many, with a million desires and hopes and wishes for ourselves and our children?

For we are Africans in America.  Something new in the history of the world, without models for what we will become.

Color must suffice.  It has brought us to this night, this discussion, and it will take us into the future.  All I truly know is that we rise and fall as one, one colored family living next door to one white family.  We may not know the way through the forest, but we can pick each other up when we fall, and we will arrive together.”

The world in Whitehead’s novel is stark and brutal.  What’s worse, the most horrific elements of the story are real.

colson_whitehead_2014The Underground Railroad is a blend of historical fiction and Man-in-the-High-Castle-esque sci-fi.  The novel is set in a world that resembles the 1800s United States, but it is not our world.  Underground tunnels crisscross the country, secretly built by a coterie of technologically-advanced, presumably African-American citizens (when asked of the provenance of the tunnels, a character gnomically replies “Who builds anything in this country?”).  And a century’s worth of racial injustice has been condensed into the several years that Cora spends fleeing the torturers who claimed to own her.

Personally, I felt that this speculative re-imagining of America weakened the story.  By picking and choosing various injustices throughout history and shifting them into the past, Whitehead creates the illusion that these sins all pre-dated the Civil War.  After all, the passage about the “Great War” quoted above implies that Whitehead’s world experienced a similar abolition of slavery toward the turn of the century, else how could “colored institutes of learning” be opened in the south?

But the Tuskegee Syphilis Study, as with many of the abuses documented in Harriet Washington’s Medical Apartheid, is so chilling because it transpired long after the Civil War – the syphilis study did not officially end until the 1970s.

And Whitehead imagines a region that has outlawed the presence of any human with too much melanin in his or her skin (perhaps even European immigrants living here stayed indoors, or routinely smeared themselves with thick swaths of titanium dioxide, lest they be mobbed & murdered for a tan).  But, within the context of a sci-fi alternate history, readers might believe that the violent enforcement of a “whites only” district ended long before it did in this country.

bloodattherootThese abuses were ongoing a mere thirty years ago.  From Carol Anderson’s New York Times review of Patrick Phillips’ Blood at the Root:

A few years later, in 1987, the civil rights legend Hosea Williams … took marchers … into Forsyth County [outside Atlanta].  It wasn’t a fair fight.  Men, women, children and Klansmen, proudly waving the Confederate flag and a noose, overwhelmed law enforcement and hurled stones, debris, and epithets as they surged at the nonviolent protesters.  “Keep Forsyth white!” scraped through the air like fingernails on a chalkboard.  The only thing that finally broke Forsyth County open was the pressure of Atlanta’s sprawl and the onslaught of economic development.

Especially at this moment in history, when millions of young black men are ensnared in our nation’s incarceration crisis, when dozens have recently been murdered by the law enforcement officers sworn to protect them, it feels strange to condense horrors into a small sliver of long-ago time.  Slavery itself in many ways continued into the 1940s, as documented in Douglas Blackmon’s Slavery By Another Name.  If you read the Thirteenth Amendment, you’ll find that slavery is still constitutionally legal even today, as long as a mockery of justice is enacted first.  In The New Jim Crow, Michelle Alexander documents how egregiously unfair these mockeries of justice often are in the present-day United States.

Some of the violence in Whitehead’s The Underground Railroad is thankfully confined to the past.  The unpunished multi-day torture-cum-murder of re-captured fugitives, for instance.  And the Underground Railroad itself is an idea firmly rooted in the pre-Civil-War United States.

But I worry that, by linking these ideas to more recent examples of injustice, Whitehead’s novel won’t draw this violence into the present, but rather make contemporary injustice seem long past.  After all, we humans are adept at forgetting the suffering we cause.  After the slave catcher in Whitehead’s novel asks Cora whether she feels bad about having killed a boy during her escape, the slaver summarizes,

Of course not – it’s nothing.  Better weep for one of those burned cornfields, or this steer swimming in our soup.”

 

On comics.

On comics.

During graduate school, I was stuck sitting around a lot.  Even after I finished all my coursework, there were near-compulsory seminars to attend, and  lab-mates’ practice talks, and weekly group meetings wherein everyone would describe all the experiments that failed over the past few days.  Which could be a bit dull, sure, but I’m an indefatigable optimist.  When I was stuck in meetings, I would draw cartoons.

I’ve included a few episodes from my old webcomic, Evil Dave versus Regular Dave, in previous posts (here & here), but I thought that for today’s post I would slap up a few more.  The site where I’d originally posted these has apparently vanished, so unless I display them here they’ll be stuck doing the electronic equivalent of moldering in an out-of-the-way file folder.  That doesn’t help anyone!

Not that displaying these here will necessarily help, either.  Cartoons drawn in the midst of boring meetings tend more toward the absurd than uproariously funny.  Honestly, most episodes of Evil Dave versus Regular Dave aren’t humorous in the slightest.  For instance, the following: perhaps you can imagine the sort of lulling drone (“many of you in the audience today might have thought that we already understood yeast DNA replication well enough, but what I wanted to address was, what if we investigated these same processes with an eye to more rigorous mechanistic detail?”) could inspire this sort of cartoon.  Especially if the cartoonist was both an inept artist and someone who’d read too much Camus during high school.

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Or the following (“I tried purifying another batch of the enzyme, and I followed Garret’s protocol exactly, but, after elution from a Q column, it precipitated.  So I tried leaving out the ion-exchange chromatography, but that time, after elution from a size-exclusion column, it precipitated.  So then I tried…”):

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Even the few vaguely-humorous sentiments I included seemed to be primarily impulse control.  Rather than stand up and scream in the middle of a crowded auditorium full of emeritus professors nodding off while a colleague discusses his efforts to understand how bacteria assess optimal breeding strategies (this is called “quorum sensing,” and refers generally to the way gene expression changes as a function of population density in bacteria.  It’s also something that humans seem to be much worse at than bacteria.  Around the globe, it often seems like some of the highest rates of reproduction are found in places so crowded that infrastructure and the environment are already taxed to their limits), I’d draw something like this:

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Who cares whether either Dave would really do that …  I wanted to leap up and pour juice on my head and start babbling demonic incantations!  Unfortunately, it seemed likely that my thesis committee would frown upon that sort of eccentricity.  And I’d never pour juice on my head.  Juice is too sticky, and too expensive.  For the final year or two of graduate school there was a song I sang every time I drove home from the grocery store: “There’s a hole in my head where the money goes … it’s called depression … I drink my juice.”  Although there were times when not even a ritzy juice like pomegranate or black cherry could cheer me up.

On the whole, I am much happier these days.  My current work — especially teaching the writing classes, which has a chance both to improve the dudes’ lives and to increase the chance that someone reading their work will recognize their fundamental humanity and feel ashamed of how we’ve treated them — feels meaningful in a way that my laboratory research did not.  My little family has enough money to live on. Our house is within a twenty minute walk of numerous libraries. We even have friends in town.

The only downside is that happiness, and a busy schedule, and very few doldrumish meetings to sit through, have led to Evil Dave versus Regular Dave languishing into near oblivion.  For something like two or three years while we were living in California, I posted these comics once a week.  The few I included in this post were culled from August 13th, 2009 to September 14th of that same year. There are many, many equally un-funny others. Now, it’s been ages since I’ve even looked at them.

With luck, perhaps my daughter will enjoy drawing.  Perhaps someday the strip will return, if she and I could sit and work on them together.

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On the shifting sands of family, specifically: whose counts?

On the shifting sands of family, specifically: whose counts?

In her fourth year of graduate school, an acquaintance of mine realized that 1.) her project was going nowhere, 2.) she was uninterested in the particular field of developmental biology she’d been assigned, and 3.) she wanted to devote her life to anything but research.  She began dragging herself to work later and later each morning, checking out earlier and earlier in the afternoon.  In a department where most people worked from ten a.m. till eight p.m., she arrived near noon and left by four.

Her advisor — who at one of our departmental retreats gave a fifteen minute presentation describing the need for a slightly better animal model of the developmental process they were studying, then clicked forward to a slide showing a rare primate cuter than anything I even realized existed and announced his hope that his students would soon be dissecting them — was flush with grant money.  He was managing a huge team of students and post-docs.  It took months before he noticed her slothful behavior.

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Mouse lemur.  See, I told you: incredibly cute.

Eventually, though, he did.  At which point he called her into his office, closed the door, and told her sternly, “_____, I don’t even leave that early, and I have a family.”

I’d like to imagine that he meant to say he had school-aged kids.

A few months later, our department hosted a special event for women in science.  Invitations were sent to a dozen female post-docs around the country, rising stars who were interviewing for faculty positions.  They were wined & dined.  There were, as ever, several seminars.  The women met privately with various professors to discuss grant writing, laboratory management, that sort of thing.

At a luncheon for these professors-to-be hosted by the two female professors from my department, one of the guests asked, “How many female professors at Stanford have families?”

It’s a pertinent question.

The tenured professor sitting at the head of the table leaned forward and said, chidingly, “________, we all have families.”

The woman who had asked felt too embarrassed to clarify that she’d meant children and so never (officially) received an answer.  Personally, I don’t remember the percentage for the university as a whole.  Not high.

Woman_teaching_geometryI do know that neither of the female professors in my department had children.  As it happens, this absence was something that the woman who’d leaned forward to answer the question had complained about frequently to her students.  And yet she also declined to hire a promising post-doctoral candidate when she learned that the woman had a child (and sternly lectured her students, who had chatted with the woman, that they should’ve reported this bit of espionage back to her sooner so that she wouldn’t have wasted so much time considering a mother), and demoted a hard-working post-doc to effectively “research assistant” status after the woman gave birth.  That post-doc, deeply aggrieved, soon switched laboratories and went on to considerable success.  Despite her “strange” priorities.

The concept of family can shift and squirm, becoming whatever those in power want it to be.

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Of course, it’s hard to see the blight from here.

I found myself thinking about this while reading a recent New York Times article titled (on paper) “Violence in St. Louis traced to cheap Mexican heroin.”  The article is bleak, as you might expect.  The current culture of the United States values instant gratification and devalues suffering, so it’s perhaps unsurprising that there’s been a boom in painkiller prescriptions.  But painkillers are addictive.  And painkillers are expensive.  After people acquire a taste for opiates, many switch to heroin — compared to vitamin V, it’s a bargain!

Heroin is cheaper for consumers than most pharmaceuticals, but it still yields hefty profits for the dudes at the top of the supply chain.  Hawkers on the street eke out sub-minimum wage, but they can see the big money at the top and dream the dream.  And those hefty profits have lured bad men with guns to the trade.  Feel free to read my recent post on Ioan Grillo’s Gangster Warlords here.

So, there’s a lot of money involved.  And the product is illegal, which means there are no state-sanctioned protections for that money.  Inevitably, this leads to violence.  That’s what the Times article was about.  Nothing you wouldn’t expect.

What struck me was this line:

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Mr. Slay in conversation with U.S. Sen. Clarie McCaskill (Flickr).

“These heroin addicts are daughters, sons, husbands, wives, or, in my case, a brother,” Mr. Slay [the mayor of St. Louis, whose brother was arrested for possession] told reporters last month.

It’s nice that Mr. Slay is able to distinguish these addicts from the addicts of the past, who were all robots, test-tube babies, science experiments gone wrong, and other socially-isolated monstrosities.  Or, wait.  No.  Those heroin addicts were minorities, as opposed to daughters, sons, husbands, wives, or brothers.  Which was why they deserved incarceration, as opposed to the treatment options that have been vociferously proposed recently.

And even that was never true.  The popular misconception was that most heroin users were black people.  But, even when our brutal imprisonment of drug addicts was at its peak, it’s unlikely that more than about 15% of heroin users were black.  All the statistics are vaguely suspect — it’s not easy to study criminal behavior — but most data suggest roughly equal rates of heroin abuse across ethnicities.

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Graph on the left by Timeshifter (Wikipedia).

Black users were over-represented in prisons, but that’s because our criminal justice system (from police officers to district attorneys to judges) views black people’s drug use as scarier than drug use by “these heroin addicts.”  The mothers and sons and brothers.

(It’s perhaps worth noting that, although heroin use does not seem to enrich for any particular ethnicity, it is inversely correlated with wealth.  People with money can afford prescription painkillers.)

I’m not upset that politicians are finally willing to acknowledge that drug users have families.  Or that drug users deserve our compassion and mercy.  It’s true.  They do.

They always have.