by Sam Kean
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Notes and Miscellanea
Chapter One: The Dueling Neurosurgeons
1. whether this satisfied her: Welcome to the endnotes! Whenever you see an asterisk (*) in the text, you can flip back here to find bonus material about the topic at hand, or explanations to clarify a point. If you want to flip back immediately for each note, go for it; or if you prefer, you can read all the notes at once after each chapter, like an afterword or epilogue. But do flip back: I promise plenty of exotic facts and salacious gossip. To wit:
However creepy it sounds for a duke to caress the leg of a naked fourteen-year-old princess, it sure beats the wedding night of the girl’s mother, Queen Catherine. After arriving in Paris at the same age, Catherine had to consummate her marriage to Henri under the watchful eye of her new father-in-law, King François, who took a seat in the corner. François reported to advisors the next day that Henri and Catherine “both showed valor in the joust.”
Realism taken a little too far. a windowpane reflected in the unbroken amniotic sac around a fetus.
a fly prepares to snack on a dissected corpse.
2. marriages of art and science: After Vesalius, it became fashionable to make the drawings in anatomy textbooks as realistic as possible, to the point of absurdity. To show how faithfully they were copying every detail before their eyes, some artists included the flies snacking on the cadaver’s entrails, and one man sketched the windowpane that he saw reflected on the amniotic sac surrounding a fetus (see illustrations on previous page). A few gentlemen even bound copies of Fabrica and other anatomy books in human skin.
3. antipodal to the blow: We don’t quite know, even today, why Henri’s brain suffered only a contrecoup injury. Modern studies show that the sudden acceleration of the brain—usually the result of a moving object striking the head—more often causes damage on the same side as the blow. (These are known as coup injuries.) In contrast, deceleration of the brain—the result of a moving head striking something immobile—usually causes contrecoup injuries, damage on the opposite side. But these are not hard-and-fast rules: a brain can suffer either coup or contrecoup injuries in either case—or even both, as it bounces back and forth inside the skull. Regardless, the physics of Henri’s case was complicated by the fact that his head was already in motion when a moving object (the lance butt) struck it.
4. macho modern athletes: Junior Seau and many other professional athletes suffered concussion after concussion during their careers, and it seems obvious to link their subsequent troubles and even suicides to this violence. We have to be careful about pinning all their problems on brain damage, since many retired athletes find themselves adrift for other reasons. After being told what to do every day for years, they suddenly lose structure in their lives. After being feted and pampered, they might suddenly be alone. After becoming millionaires at age twenty, they’re suddenly broke. No wonder they can get depressed.
That said, there’s clearly something more going on. The brains of forty-year-olds shouldn’t look (as autopsies reveal) more or less identical to the brains of ninety-year-olds with neurodegenerative disease. The damage also resembles the trauma produced by IEDs in modern warfare. Military doctors have already declared chronic, widespread brain damage the “signature injury” of the recent wars in Iraq and Afghanistan. Football fans usually agonize over torn ACLs and turf toe, but brain damage may be a signature football injury, too.
The National Football League’s $765 million settlement with players over concussions and brain damage is a sign that the league is finally taking this issue seriously. But the cynic in me fears that little will change, and that the money will simply soothe the collective conscience of us fans. And in some ways, focusing on NFL players misses the point. The brains of high school and college football players are still forming and are much more susceptible to damage—and they receive no financial reward for their pain. I sometimes wonder whether mothers will let their children play tackle football in ten years’ time. We already have MADD. Will Mothers Against Tackle Football be next?
Chapter Two: The Assassin’s Soup
5. the black reaction: Another version of this legend holds that Golgi’s cleaning lady deserves at least a little credit for la reazione nera. According to this account, one night the woman dumped both the owl brain and the silver solution into the trash, where they mingled. Golgi fished them out the next morning and decided to take a look.
6. vertical organization: Neurons in the cortex generally organize themselves into six layers, and in addition to all his other discoveries, Cajal was the first person to describe this arrangement. This book doesn’t delve too deeply into the workings of individual cortex layers, but if you want a quick overview, here goes.
The layers are numbered I through VI, with I nearest the scalp and VI deepest inside the brain. Data usually enter the cortex through IV, the most complicated layer. (In fact, it’s often divided into sublayers—IVa, IVb, etc.) Layer IV neurons can send the information either up or down. If they send it up, layers II and III, especially, start processing it. This processing might require reaching out horizontally to other, nearby columns, but things often stay in-house. Layer IV neurons can also send information down to layers V and VI. V and VI send information to other parts of the brain, which makes sense, since they lie nearest the white matter cables that shunt information around. In general, V neurons reach out to distant parts of the brain or to the spinal cord, while VI neurons ping the all-important thalamus. (About which, more later…)
Interestingly, some scientists argue that we can tell what the brain is up to simply by noting which layers are active at any one time. If just the top layers are buzzing, that means the brain is thinking, anticipating, planning. If all six layers are active, action is likely imminent, since only the bottom layers reach into the thalamus hub and the spinal cord.
Incidentally, it’s long been popular to think about the neurons in these layers as little logic gates doing computations. That’s not a bad metaphor—our brains compute a lot of things—but it misses something essential about neurons. Logic gates in electric circuits are static in one sense: they do the same thing every time. Neurons aren’t static. They’re dynamic, and they change behavior over time, even over hours and minutes. As some scientists
and philosophers have pointed out (stretching back to Plato!), a more accurate metaphor would be to think about the brain as a city and about neurons as little people. People within a city are alike in many ways—we all eat, breathe, sleep, work, complain, and so on. But we all do different activities each day, and as we mature, we change our behavior. The same goes for neurons.
7. a blur of boots and rifle butts: Accounts differ about what exactly happened after Czolgosz fired the second shot—especially where people stood in line, and who knocked Czolgosz down first. I’ve reconstructed things as best I could. Part of the problem is that McKinley’s guards changed their stories before Czolgosz’s trial, perhaps embarrassed that a private citizen—and a black man—had jumped into the fray first.
Regardless, big Jim Parker became a local star. People bought scraps of clothing off his body, and he got offers on the shoes that had kicked that bastard Czolgosz as well. Things turned somewhat sour for him later, when the guards began altering their testimony. One newspaper article—headlined “Did Jim Parker Do It?”—even floated the idea that Parker himself had pulled the trigger, not Czolgosz.
8. time of death, 7:15 a.m.: On the morning of October 29, a film company run by Thomas Edison showed up outside Auburn prison to record Czolgosz’s execution. Upon being turned down, they decided to restage the execution with actors a few days later. (You can see the film at http://www.youtube.com/watch?v=bZl-Z8LKSo0.) Edison did all this for the rather despicable reason that he owned patents for direct current (DC) technology and wanted to smear his business rivals, whose alternating current (AC) technology powered the electric chair.
9. troubled brain was no more: After Czolgosz’s death, Spitzka fils kept on studying how the brain changes in response to being electrocuted. In lower-profile capital cases, he often got to keep the brain, even. Unfortunately, his habit of whisking away people’s brains came to the notice of organized-crime types, who resented his poaching. He started getting anonymous phone calls saying things like, Lay off Fat Tony’s brain. Otherwise, you’ll regret it. After a score of such threats, Spitzka got pretty paranoid. There are stories of him walking into a hall to give a lecture with two pistols clanging on his belt. He proceeded to check behind every door, with the guns cocked and his fingers on the triggers. He finally laid them down—and delivered a brilliant lecture on, ahem, nervous ailments. Sadly, years of continuous paranoia—coupled with a demonic work ethic—led Spitzka to start hitting the sauce pretty hard, and he became a brooding drunk. He “retired” at thirty-eight, and died at forty-six of a cerebral hemorrhage, the same ailment that killed his father.
10. he had to flee: Loewi was actually arrested before fleeing. But rather than focus on, I don’t know, freeing himself, his top priority was making sure his latest research results got published. He badgered his guard for a pen and paper, and then spent what could have been his last days on earth writing up a scientific article from memory. Luckily, the Nazis eventually released Loewi, albeit after he’d lost one hundred pounds in jail.
Loewi emigrated to England, then accepted a job at New York University. The only hitch was that he needed a visa first, and the U.S. embassy demanded proof that he’d actually worked as a teacher in Austria. All Loewi had was his dismissal letter from the Nazis, which wasn’t exactly a glowing reference. Loewi finally found a copy of Who’s Who and looked up his bio. The entry praised Loewi in the highest terms, and the functionary handling his case was impressed. After Loewi obtained the necessary signatures, he asked the man if he knew who’d written the entry. The man didn’t. Loewi admitted he’d written it himself, then skedaddled.
Loewi’s close calls didn’t end there. At Ellis Island he handed over his sealed medical records to a doctor, and when the doctor opened them, Loewi read, upside down, the words “senility, not able to earn a living.” In an instant Loewi saw himself being shipped back to Austria and thrown in jail to die. But the doctor had some sense, and admitted Loewi anyway.
11. over one hundred different neurotransmitters: A long note, but a goodie!
The discovery of most of the hundred or so known neurotransmitters followed a similar pattern: scientists came across some new chemical in the brain, isolated it, then proved that it somehow altered the activity of neurons. The major exception to this pattern was the brain’s natural painkillers, called endorphins. In this case scientists started off studying drugs like morphine and opium, which dull sensation by locking onto receptors in the brain. As the neurotransmitter doctrine emerged, scientists realized that the brain must already employ chemicals with a similar structure, or else neurons wouldn’t have a receptor for morphine and opium to dock with.
The discovery of endorphins in the early 1970s was one of the messier projects in science history. A brusque young cockney lad working in Scotland, John Hughes, decided to seek endorphins—which he called “Substance X”—inside pig brains. This required Hughes to bike down to the slaughterhouse each morning before dawn with a hacksaw, hatchet, and knife in his bicycle’s basket. He picked up dry ice along the way. To get his hands on the brains, Hughes had to rely on the largesse of the slaughterhouse workers who chainsawed the pigs’ heads off. At first Hughes secured their cooperation by expounding on the nobility of medical research. He soon realized that scotch earned their cooperation much more quickly, and started adding a bottle to his basket. The workers brought Hughes twenty or so pig skulls each day, and while he fought off the rats, Hughes hacked out the grapefruit-sized brains in about ten minutes each, then packed them into dry ice. After returning to the lab he would pound the brains into a gray mash, then dissolve them in acetone. (Colleagues remember the lab smelling like airplane glue and rancid fat.) Finally, he’d centrifuge and evaporate off various layers, to test whether they were Substance X.
Now came the strange part. Hughes’s mentor, Hans Kosterlitz, was the world’s unchallenged expert on two extremely specific pieces of anatomy—the Cavia ileum, and the murine vas deferens, better known as the guinea pig intestines and the mouse sperm tube. Somewhere along the line Kosterlitz had determined that each of these bits—they looked like tiny, coiled worms—was superlatively sensitive to morphinelike chemicals. That is, if you suspend a Cavia ileum or murine vas deferens in liquid and spark a certain nerve leading into it, it will contract over and over, much like Loewi’s frog hearts. But even trace amounts of morphine halt the contractions immediately. So Kosterlitz and Hughes spent months sparking the sperm tubes and intestines—producing disembodied bowel movements and orgasms in a beaker—and injecting chemical after chemical from the pig brains, to see if anything interrupted this. They finally found a substance—a yellow wax smelling of old butter—that interfered with the contractions just as morphine did. It became known as an endorphin, a portmanteau of “endogenous morphine.”
By the by, drugs (illicit and otherwise) are a great way to study all the various steps involved in neurotransmission. Ecstasy, for instance, artificially floods the synapses between neurons with serotonin, allowing you to study neurotransmitter release. Cocaine prevents the vacuuming up of dopamine and other chemicals after their release. PCP, among other effects, interferes with dendrite receptors, preventing certain neurotransmitters from locking on and passing messages along. LSD lowers the ability of a neuron to inhibit its neighbors, and thereby allows sensory input to bleed from one brain region to another. Basically, for any step in the neurotransmission process, there’s a drug out there that will get you high by fiddling with it.
The story about Hughes comes from Anatomy of Scientific Discovery, by Jeff Goldberg. You can find out more about the general history of soups and sparks in the wonderfully informative The War of the Soups and the Sparks, by Elliot Valenstein.
12. Lee Harvey Oswald: Assassins have cut down two other U.S. presidents, Abraham Lincoln and John. F. Kennedy. Medically, both cases were straightforward—each man was as good as dead from the start. But one interesting neurological detail did arise with Kennedy in Dallas. In the Zapruder film
, Kennedy famously jerks his arms up at one point, as if choking. Conspiracy-mongerers have interpreted this as evidence of his being shot from the front. But a few doctors have declared that Kennedy was actually exhibiting a primitive neurological reflex—an involuntary yanking upward of the arms in response to trauma.
By the by, Lincoln did have one interesting connection to neuroscience. As a prosecutor in the 1850s, he argued one of the first cases in U.S. history on temporary insanity. (He lost.) In the interest of space I won’t go into it here, but you can read Lincoln’s story online at http://samkean.com/dueling-notes. I’ve posted many other neurological oddities there as well, everything from why consciousness is like an old-school Nintendo to why Phineas Gage is like an android. Check it out.
Chapter Three: Wiring and Rewiring
13. 250,000 miles: I can think of one other set of garments in history that possibly traveled farther than Holman’s weeds: whatever unmentionables the Apollo astronauts wore beneath their spacesuits. And while people change clothes more nowadays, some modern folks of course have traveled vastly more than Holman ever could have. Hillary Clinton, as U.S. secretary of state, traveled an estimated 956,733 miles in four years, equal to two round-trips to the moon.
14. segments of his optic nerves: As explained in A Sense of the World—a fantastic biography of Holman, by Jason Roberts—a condition called uveitis almost certainly destroyed Holman’s optic nerves. But that diagnosis actually tells us a humblingly small amount, since no one knows what causes most cases of uveitis.
Holman did retain hallucinatory flashes of vision throughout his life. For instance, while chitchatting with a lady friend, a vision of what he imagined her to look like might rise before him. This proves, per the discussion at the end of the chapter, that his brain could still “see,” even if his eyes couldn’t. These visions delighted him for a moment but ultimately left him depressed, since they reminded him of what he’d lost.
