Determined, page 28
Suppose there’s a problem with this system. Some protein is out of whack, so that the refractory period doesn’t occur. Consequence? There are abnormal bursts of high-intensity clusters of action potentials, one on top of the other. Or suppose some inhibitory neurons stop working. The result is a different route to neurons having abnormal clusters of excitation. What we have just described are the two broad underlying causes of epileptic seizures—too much excitation or too little inhibition. Scores of textbooks and tens of thousands of research papers have explored the causes of such synchronized overexcitation—faulty genes, concussive head injury, birth complications, high fevers, some environmental toxins. Amid all this complexity, this disease, which afflicts forty million people worldwide and kills more than a hundred thousand a year, is about too much excitation and/or too little inhibition in the nervous system.
Predictably, all this was discovered only recently. But epilepsy is an ancient disease. The subtype of seizures that most people are familiar with is a grand mal seizure, where the sufferer convulses and writhes with automatic movements, frothing at the mouth, and the eyes roll up. All sorts of opposing muscle groups are stimulated at once. The person falls to the ground, explaining the name given to epilepsy by many of the ancients—the falling sickness.
Clinically accurate descriptions of seizures go back to at least the Assyrians, almost four thousand years ago. Some of the insights generated were remarkably prescient. Ancient Greek physician Hippocrates, for example, noted that chronic seizures often arise with a delay after a traumatic brain injury, something we’re still trying to sort out on a molecular level. Mind you, though, there were plenty of scientific missteps. There was epilepsy supposedly being caused by phases of the moon and their influence on brain fluids (with 1,600 years going by before someone was able to statistically disprove a link between epilepsy and lunar phases). Pliny the Elder thought someone got epilepsy from eating an epileptic goat (sidestepping the issue of “Okay, but where did that goat get its epilepsy from?”—carnivorous epileptic goats all the way down). The second-century physician Galen worked with the prevailing wisdom that the body is built on the four humors—black bile, yellow bile, phlegm, and blood. Galen’s theory centered on the ventricles of the brain.[*] According to him, phlegm could occasionally thicken into a plug in the ventricles, and a seizure was the brain’s attempt to shake it loose. Note that in this framework, the clotted phlegm is the disease, and a seizure is a protective response that just happens to cause more problems than it solves.[1]
These first hints of scientific explanation also produced stabs at treatment—in Greece in the fourth century BC, one involved the person with epilepsy drinking a concoction made of the genitals of seals and hippos, the blood of a tortoise, and the feces of a crocodile. Other supposed cures included drinking the blood of a gladiator or of someone who had been decapitated. There was rubbing the sufferer’s feet with menstrual blood. Or consuming burned human bones. (Just to put our current single-payer health insurance debates in perspective, Athenaeus of Naucratis, another second-century sage, reported on one physician who claimed to be able to cure epilepsy, details unclear, but who would do so only if the patient agreed to become his slave afterward.)[*]
These primitive attempts at understanding the disease produced plenty of horrors. There was the erroneous belief that epilepsy was an infectious disease, leading to people with epilepsy being marginalized and stigmatized—unable to share food with others, unwelcome in sacred places. Even worse was the mostly erroneous belief that epilepsy was heritable (only a tiny percentage of cases are due to heritable mutations). This led to prohibitions on people with epilepsy marrying. In various European locales, men with epilepsy would be castrated, a practice lasting into the nineteenth century. Among the sixteenth-century Scots, if a woman with epilepsy became pregnant, she would be buried alive. And by the twentieth century, the same medical ignorance led to the compulsory sterilization of thousands with epilepsy. In the U.S., the landmark case was Buck v. Bell (1927), where the Supreme Court upheld the legality of the state of Virginia forcibly sterilizing “the feeble-minded and epileptic” in a law that was not repealed until 1974. The practice was legal in most states during the twentieth century and was particularly common in the South, where it was sardonically known as a “Mississippi appendectomy.” The same was the case throughout Europe, with the practice peaking, naturally, in Nazi Germany. In 1936, the Third Reich arranged for an honorary doctorate for Harry Laughlin, the American eugenicist who was the architect of the Virginia law, and at the Nuremberg trials, Nazi doctors explicitly cited Buck v. Bell in their defense.
Now these were all the horrors generated by wrong science. But science, wrong or otherwise, was an obscure sideshow when it came to epilepsy. Because starting millennia ago, for most people, ranging from peasants to sages, the explanation for seizures was obvious—demonic possession.
The Mesopotamians called epilepsy “the hand of sin,” considering it to be a “sacred” disease, and were impressively attuned to the heterogeneity of seizures. People with what was probably petit mal epilepsy with auras were viewed as having a good kind of sacred possession, often associated with prophecy. But what were most likely grand mal seizures were the doings of demons. Most Greek and Roman physicians believed the same, with the most cutting-edge integrating demonic interpretations with materialistic, medical notions—demons made the soul and body become unbalanced, producing the falling disease. Among Galen’s followers, demons caused phlegm to thicken.
Christianity got on the bandwagon, thanks to a New Testament precedent. In Mark 9:14–29, a man brings his son to Jesus, saying there is something wrong with him—since he was a child, a spirit comes and seizes him, making him mute. And then the spirit throws him to the ground, where he foams at the mouth, grinds his teeth, and becomes rigid. Can you cure him? Of course, says Jesus.[*] The man presents his son, who is promptly seized by that spirit and falls to the ground, convulsing and foaming. Jesus perceives that the boy is infested with an unclean spirit[*] and commands it to come out and be gone. The seizing ceases. And thus the epilepsy/demonic possession link was established in Christianity for centuries to come.
Now, harboring a demon inside you can cut a couple of different ways. One is where an innocent bystander is cursed into possession by some witch or warlock. I saw this attribution in the parts of rural East Africa where I worked, usually leading to efforts to identify and punish the perpetrator. But the other is where epilepsy is a sign of the person themselves having welcomed in Satan; this view predominately held sway throughout Christendom.
Naturally, a late-medieval-period Christian did not have Jesus’s power to purge epileptics of their demon. Instead, a different sort of solution emerged, made most consequential by a pair of German scholars.
In 1487, the two Dominican friars, Heinrich Kramer and Jakob Sprenger, published Malleus maleficarum (Latin for Hammer of the Witches). It was in part a religiopolitical polemic, a vigorous refutation of any bleeding hearts of that time who suggested that there was actually no such thing as witches. And once that liberal tomfoolery was out of the way, the book was an instruction manual, the definitive guide for both religious and secular authorities to recognize witches for who they were, get them to confess, and then dole out justice. One reliable indicator that someone was a witch? Seizures, of course.
Hundreds of thousands of people, almost all female, were persecuted, tortured, killed, during this period of witch-hunting. Malleus maleficarum arrived just in time to take advantage of the recently invented printing press, went through thirty editions over the subsequent century, and was read throughout Europe.[*] While the focus of the book was not remotely epilepsy, its message was clear: epilepsy was brought on by someone’s own freely chosen evil, and such demonic possession represented a danger to society and needed to be dealt with. And masses of people with some haywire potassium channels in their neurons were burned at the stake.
With the enlightenment of the Enlightenment, witch hunts began to be more metaphorical. But epilepsy was no less burdened with a perception of its sufferers being at fault in some manner. It was a disease of moral turpitude. It joined going blind and growing hair on your hands as the supposed wages of sinful masturbation—excessive and synchronized action potentials in neurons all because someone was pleasuring themselves too often. For women, it could be caused by an unseemly interest in sex (and occasionally cured in the nineteenth century by genital mutilation); sex outside of holy matrimony was a risk factor as well. In 1800, the British physician Thomas Beddoes came up with one of the most low-energy versions of blaming the victim I have ever heard of, positing that seizures were caused by people being excessively sentimental and reading too many novels, instead of living the vigorous outdoor life of gardening. In other words, over the course of a few centuries, we’ve gone from epilepsy being caused by grasping Beelzebub to your bosom to its being caused by reading too many Harlequin romances.
Or not. Amid the continuity of blaming the victim, there was also the continuity of those with epilepsy being viewed as a threat, but on medicolegal rather than theological grounds. We live in a remarkable time, with an array of medications available that prevent most seizures in most people with epilepsy. But prior to the early twentieth century, a person with epilepsy might experience many hundreds of seizures in their lifetime; Temkin describes one survey in the early nineteenth century documenting that chronically hospitalized people with epilepsy averaged two seizures a week for years.[2]
One consequence of this is the eventual emergence of considerable amounts of brain damage. My lab spent decades studying how seizures can damage or kill neurons (and trying, mostly unsuccessfully, to develop gene-therapy strategies to try to protect such neurons); basically, the repeated bursts of firing deplete neurons of energy, leaving the cells without the energetic means to clean up damaging things like oxygen radicals in the aftermath. Decades of damaging seizures typically produced extensive cognitive decline, accounting for the numerous nineteenth-century hospitals and institutes devoted to the “epileptics and feebleminded.” In addition, seizure-induced damage often occurred in frontal cortical regions involved in impulse control and emotional regulation, accounting for another flavor of institution, that devoted to the “epileptic insane.”[3]
Independent of people with epilepsy undergoing a vastly larger number of seizures than is commonplace today, the prevalence of epilepsy was higher, thanks to higher rates of head injuries and of febrile epilepsy due to infectious diseases that we are now spared. The higher prevalence, coupled with someone with epilepsy typically experiencing far more seizures than we are accustomed to today, made people back then more aware of the extraordinarily rare cases of epilepsy being associated with violence. This can involve automatisms of aggressive behavior during a psychomotor seizure (which was given the Victorian label of furor epilepticus). More common is aggression immediately following a seizure, where the person, in a state of agitated confusion, violently resists being constrained. Rarer are bursts of violence coming hours later. The violence typically follows a cluster of seizures, shows no evidence of premeditation or motive, and comes in a rapid, fragmentary burst of stereotyped movement that lasts for less than thirty seconds. Afterward, the person is stricken with remorse and remembers nothing. A 2001 paper describes one such case, of a woman whose rare, intractable epilepsy produced seizures virtually daily that were associated with outbursts of agitated aggression. She had been arrested thirty-two times for such violent incidents; the severity of violence escalated, culminating in a murder. The seizure focus was near the amygdala, and after surgical removal of that part of her temporal lobe, both the seizures and the aggressive outbursts stopped.[4]
Cases like these are so immensely rare that a single example merits a paper being published; the millions of people with epilepsy have no higher rates of violence than anyone else, and the majority of any such violence is unrelated to the disorder. Nonetheless, by the nineteenth century, there was a widespread public association of epilepsy with violence and criminality.[*] Malleus maleficarum redux—people with this disease brought it on themselves with their moral failings and constitute a threat to society for which they must be held responsible.[5]
But there was a glimmer of hope. Nineteenth-century science was advancing in such a way that you could imagine the chain of insights that would link that time’s knowledge to the present’s. Autopsy studies had finally eliminated the notion of plugs of phlegm; statisticians had finally eliminated the moon from the picture. Neuropathologists were beginning to note extensive damage in the postmortem brains of people with a history of repeated seizures. This was the era of galvanism and animal electricity, the growing recognition of the electrical nature of the signals by which the brain made muscles move, that the brain itself was some manner of electrical organ. Which suggested that epilepsy might involve some manner of electrical problem. A giant among neurologists named Hughlings Jackson, an utter genius, introduced the idea of localization—where in the body convulsive twitching and movements at the start of a seizure could tell you where in the brain the problem was centered.
But something arguably even more important was happening—the whispers of modernity, the first time that people were starting to say, “It’s not him. It’s his disease.” In 1808, a person who had killed while having a seizure was acquitted,[*] with more such cases to follow. By midcentury, psychiatry heavyweights like Benedict Morel and Louis Delasiauve were more generally arguing that people with epilepsy could not be held responsible for their actions. In a key publication in 1860, the psychiatrist Jules Falret wrote, “The epileptic who, in a state of post-ictal [i.e., postseizure] delirium, attempted or committed suicide, homicide, arson had not the slightest responsibility. . . . [They] strike mechanically, without motivation, without interest, without knowing what they do.” He’s teetering on the edge of the first half of this book. But he can’t quite follow through and concludes oxymoronically:
Still, when we do not limit our observations to those [with epilepsy] secluded in the mental asylum, when we also take into account all those who live in society, without anyone suspecting the existence of their illness, it becomes impossible not to attribute to some of them the privilege of moral responsibility, if not for the entirety of their lives, then at least for significant periods of their existence.[*],[6]
Thus, someone has not the slightest responsibility, while still having moral responsibility. You’re sure you still want to hitch your wagon to modern versions of this impossible compatibilism?
Which brings us to the present. Imagine the tragic scenario of some middle-aged man on his way to work who, in the middle of driving, suddenly has a grand mal seizure. He’s otherwise perfectly healthy, zero prior history of anything that could have predicted this. Utterly from out of nowhere.[*] In his convulsing, arms twisting the wheel every which way, foot repeatedly slamming on the gas, he loses control of the car. He strikes a child, who is killed.
Here are some of the things that are unlikely to happen:
—The man, slumped over the wheel, still convulsing and frothing, is pulled from the car and beaten to death by the witnesses.
—The man, when eventually brought to court for a hearing, has to be spirited in the back way, wearing a bulletproof vest, because of the vengeful mob on the courthouse steps threatening to string him up if he is not punished appropriately.
—The man is convicted of anything like murder, manslaughter, or vehicular homicide.
Instead, the loved ones of that child, with their lives ripped apart by pain, will lament forever the monumentally bad luck of what happened, akin to if the driver had had a fatal heart attack from out of the blue, if a comet had fallen from the sky, if an earthquake had come and split the earth open, swallowing their baby.
Oh, it isn’t that clean, of course. We desperately search for attribution. Wait, he had no medical history of anything? Was he taking some sort of medicine at the time that was the cause and no one warned him? Was he drinking and that somehow triggered a seizure? When did he have his last checkup? Why didn’t the doctor spot this brewing? He had to have been acting oddly that morning—no one at home stopped him from driving? Was there some blinking strobe light at the time that triggered the seizure, someone who should have known that that was unsafe? On and on. We seek attribution, we seek blame. And if we are lucky, the facts become emotionally acceptable as well and we reach a conclusion that would have been unthinkable to a sixteenth-century parent grieving over the febrile death of their child, convinced that some witch caused it: it is not the driver’s fault that this happened, that he lost control of the car; there is no one who had the freedom to have willed this not to have happened. Just the most sickening bad luck that any parent’s heart should have to bear.
And this is some approximation of what now happens, in that the driver would not be charged with anything. We’ve done it; we now think differently than people did in the past. Of course, there is still massive societal stigma about epilepsy, particularly among those who are less educated. Because of a still widespread belief that epilepsy is contagious and/or a form of mental illness, half of people with the disease report feeling stigmatized; when this happens to children, it predicts lower performance and more behavior problems in school. In the developing world, there is still a common belief that epilepsy has supernatural causes, and nearly half of the people queried would object to sharing a meal with someone with epilepsy. To quote the Indian neurologist Rajendra Kale, “The history of epilepsy can be summarised as 4000 years of ignorance, superstition and stigma, followed by 100 years of knowledge, superstition and stigma.”[7]
