Determined, page 70
(The Sokal affair was seized upon by the likes of Rush Limbaugh as an exposé of the Left’s intellectual fraudulence, with Sokal embraced as some sort of right-wing scourge. This infuriated me, as Sokal had walked the walk as a leftist—for example, in the 1980s, he left his cushy academic post to teach math in Nicaragua during the Sandinista revolution. Furthermore, anything the Right had to say about truth ended with “alternative facts” in Trump’s first week in office. As an aside, in college, Sokal lived down the hall, two years ahead of me and thus too intimidating of a big kid to talk to; his brilliance, wonderful eccentricity, and willingness to call BS were already legendary.)
*Nitpicky aside: Why say “too little leptin signaling” rather than just “too little leptin”? Signaling is a broader term, reflecting that a problem can be at the level of the amount of a messenger (e.g., a hormone or neurotransmitter) or with the sensitivity of cells to the messenger (e.g., abnormal levels/function of receptors for the messenger). Sometimes the radio station is screwed up, sometimes it’s the radio in your kitchen. (Do people still have radios?)
*An extraordinary, famed example is the Dutch Hunger Winter, when the occupying Nazis cut off the food supply in the Netherlands in the winter of 1944–45, and twenty to forty thousand Dutch starved to death. If you were a fetus then, with you and your mother severely deprived of nutrients and calories, epigenetic changes produced a lifelong thrifty metabolism, a body voraciously adept at storing calories. Be one of those fetuses, and sixty years later, you had a dramatically increased risk of obesity, metabolic syndrome, diabetes, and, as we’ve seen, schizophrenia.
*And the world of processed foods involves scientists trying to achieve that state with whatever food their boss sells.
*Really, for the same BMI? Of course. More self-loathing, more secretion of stress hormones resulting in more preferential storage of fat in the gut (among other downsides), more of an increase in metabolic and cardiovascular disease risk.
*Then there’s the ghastly quora.com/Is-it-my-fault-my-husband-hits-me.
*James doesn’t see the same among higher-SES African Americans or among Whites at all.
*The words for “Mayn Rue-Plats” were in Yiddish, at a time when it was the language of socialist firebrands on the Lower East Side of New York rather than ultraorthodox ayatollahs. Rosenfeld wrote it in response to the Triangle Shirtwaist Factory fire in March 1911, in which 146 sweatshop workers—almost all immigrants, almost all women, some as young as fourteen—died because the owners had locked an exit, believing that otherwise, workers would sneak out the back way with stolen clothes. A jury found the owners liable for wrongful death, forcing them to pay all of seventy-five dollars compensation to each family of the dead, while the owners themselves received more than sixty thousand dollars for the loss of their factory. Seventeen months later, one of them was found to have once again locked the exits in his new factory and was levied the minimum fine of twenty dollars. One hundred two years later, the Rana Plaza building in Dhaka, Bangladesh, collapsed, killing 1,134 sweatshop workers inside. Cracks had been discovered in the building the day before, resulting in its evacuation; the owners informed workers that anyone not back on the job the next day would be docked a month’s pay.
*Translation by Daniel Kahn.
*I have been made aware that this bears some resemblance to the Buddhist concept of “unselfing.” I have absolutely nothing useful to say about Buddhism beyond that.
*As of 2022, eighty-five years in Japan, fifty-five in the Central African Republic.
*Which, among other things, is why the nervous system is so vulnerable to injury. Someone has a cardiac arrest. Their heart stops for a few minutes before it is shocked into beating again, and during those few minutes, the entire body is deprived of blood, oxygen, and glucose. And at the end of those few minutes of “hypoxia-ischemia,” every cell in the body is miserable and queasy. Yet it is preferentially brain cells (and a consistent subset of them) that are now destined to die over the next few days.
*For chemists: in other words, so that the distribution of charged ions inside and out balance each other.
*Jargon: that little bit of “depolarization.”
*Ironic footnote: Cajal was the chief exponent of the neuron doctrine. And the leading voice in favor of synctitiums? Golgi; the technique he invented showed that he was wrong. He apparently moped the entire way to Stockholm to receive his Nobel Prize in 1906—shared with Cajal. The two loathed each other, didn’t even speak. In his Nobel address, Cajal managed to muster the good manners to praise Golgi. Golgi, in his, attacked Cajal and the neuron doctrine; dickhead.
*More with the keys in locks—the reuptake pumps have a shape that is complementary to the shape of the neurotransmitter, so that the latter is the only thing taken back up into the axon terminal.
*What that also implies is that if a neuron is receiving axonal projections to five thousand of its spines from a neurotransmitter A–releasing neuron and five thousand from a neurotransmitter B–releasing one, it expresses different receptors on those two populations of its spines.
*Whoa, does that mean that you can regulate the amounts of neurotransmitters with your diet? People got very excited about this possibility in my student days. For the most part, though, this has been a bust—for example, if you were so deprived of proteins that contain tyrosine that you can’t make enough dopamine, you’d already be dead for lots of reasons.
*So, if SSRIs boost serotonin signaling and lessen symptoms of depression, the cause of depression must be too little serotonin. Well, maybe not. (A) A paucity of serotonin may be the cause of only some subtypes of depression—SSRIs most certainly don’t help everyone and to varying extents; (B) for other subtypes, serotonin shortage may be one of the contributing causes, or even completely irrelevant; (C) just because more serotonin signaling equals less depression, that doesn’t necessarily mean that the initial problem was too little serotonin—after all, just because duct tape can cure a leaking pipe doesn’t mean that the leak was initially caused by a shortage of duct tape; (D) despite the “selective” part of the SSRI acronym, the drugs are actually not perfectly selective and effect other neurotransmitters as well, meaning that these others may be relevant rather than serotonin; (E) despite what SSRIs do to serotonin signaling, it is possible that the problem is too much serotonin—this can arise through a scenario that is so multilayered that it leaves my students gasping for air; (F) even more stuff. As such, a controversy is now raging as to whether the “serotonin hypothesis” (i.e., that depression is caused by too little serotonin) has been oversold. Which seems likely.
*And this makes sense only after introducing an additional fact. Thanks to random, probabilistic hiccups with the ion channels now and then neurons will occasionally have a random, spontaneous action potential from out of nowhere (which is looked at in depth in chapter 10 when considering what quantum indeterminacy has to do with brain function [psst—not much]). So neuron A intentionally fires off ten action potentials, followed soon after by two random ones. That might make it hard to tell if neuron A meant to yell ten, eleven, or twelve times. By calibrating the circuit so that the inhibitory feedback signal shows up right after the tenth action potential, the two random ones afterward are prevented, and it is easier to tell what neuron A meant. The signal has been sharpened by damping the noise.
*Thanks to the wisdom of Dale, we know that the same neurotransmitter(s) is coming out of every axon terminal of neuron C. In other words, the same neurotransmitter can be excitatory at some synapses and inhibitory at others. This is determined by what type of ion channel the receptor is coupled to in the dendritic spine.
*Similar circuitry is also seen in the olfactory system, which has always puzzled me. What’s just lateral to the smell of an orange? The smell of a tangerine?
Robert M. Sapolsky, Determined
