Don't Disappoint (Ch. 14)
by Martin van Cooper
Welcome back to a special Summer Edition of PILCROW. For the next five weeks, we’ll be serializing Martin van Cooper’s unpublished novel Don’t Disappoint (runner-up in our last contest, back by popular demand). Stay tuned for submission deadlines for our next quarterly contest (in which each of two runners-up receive $500, and the ultimate winner - voted on by you, dear subscribers - receives $1,000).
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In Don’t Disappoint, amidst a flailing career, a displaced midwesterner in Los Angeles goes home to confront the complications of a mother with advancing dementia, only for a marital sucker punch to leave him questioning what’s left of his family to salvage.
Martin Van Cooper writes the Substack Don’t Read the Dust Jacket
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On Monday the president sent an email canceling all classes for the rest of the quarter, moving instruction online and banning in person gatherings of 100 people or more. His last committee meeting before proposing a defense date was scheduled for Tuesday and no one bothered to check whether it was still scheduled.
John Billiard grew up on a corn and bean farm in Iowa, which miraculously his father had the foresight to sell most of, maintaining 100 acres for his parents’ retirement and for his brother to bring his growing family, having pursued corporate Ag and then moved to finance. An oops baby, there were 10 years between him and the oldest Mark. John’s high school was unremarkable despite, or perhaps because, him being highly intelligent but somehow shiftless. He had an autodidactic ability to work on anything with a motor, mostly cars and less frequently these days the farm equipment. There were fights in bars during his late teens and 20’s when he worked as a foreman at a grain distributor in town. His father would pick him up at the station, never one to lecture and pathologically taciturn, John would broil again in the passenger seat in his father’s ancient Dodge pickup on the way back to the farm, which had now been converted, the part his parents still owned, into an apple orchard and a bike track for the grandkids and a tiny vegetable garden for his mom’s tomatoes and peppers and a new, smaller cottage of sorts that his folks lived in, the old house basically repurposed for guests, who were varied and frequent, both his parents coming from large families and his mother being quite gregarious. But they still called it the farm. A new driveway had been poured a few years back. John found that unspoken expectations were far more painful, more invasive, than anything ever said and indeed it was some kind of catharsis when his father asked him simply, during what turned out to be the last of these rides home from city hall: are you finding yourself? His undergraduate degree was in biology—the puzzles of this field called to him, like a motor built by the most sophisticated engineer, waiting to be disassembled and put back together—there was the thought at the time of following his brother Mark into business but John’s mind could not focus on spreadsheets and his stomach couldn’t handle the dismal science. There was always the possibility of joining a drug or biotech company, but this required a PhD and he wasn’t wired for more school at 22. At 28, however, John decided maybe it was time to give it another go, and that finding himself—as his father finally admonished him to do—might happen in graduate school. The first year of classes was a revelation, he soaked up the material, read 10-15 original research articles a week in addition to his coursework, which was unexpectedly undemanding and which, to his amazement, he excelled at with relative ease, his 21–22-year-old classmates distracted by their phones and residual post-pubescent hormonal imbalances. For a year he advanced confidently. He chose an advisor, a surgeon in his mid-40’s (young by academic professor standards) studying the gut microbiome and its effects on cognition. There was this idea that the trauma of surgery, especially abdominal, liberated intestinal flora into the blood stream, which then took up residence elsewhere in the body and produced toxic metabolites that crossed the blood brain barrier and interfered with calcium homeostasis in specialized glial cells called astrocytes and maybe this was an unrecognized contributor to age related dementia. The decision to do something different everyday rather than the same thing. Well. He decided our modern society had decided, contravening 100,000 years of human evolution, to prize independence over community, creativity over competence, novelty over certainty, that this was the path to self-worth, that this is what his father, who did the same thing every day for 40 years of work and then retired to read in his wife’s vegetable garden, must have meant, although he didn’t say as much, of course, when he told his son to find himself. This was not how our lizard brains were wired. The campus was deserted except for a few scattered students and, oddly, what looked like a tour group of high schoolers. A Zamboni-like thing drove around cleaning up the muddy sidewalks from the previous day’s rain.
But then a year at the bench turned into five and no paper was imminent, his advisor, who himself had never worked in a research lab and spent all his time in the OR and who pursued research as some kind of show-offy perfunctory distraction necessary to one day be Chair, his mentor said to him that maybe John ought to wrap things up. And move on. This after 5 years in grad school and no publications and living in the megalopolis wasteland that was Los Angeles and basically having formed no meaningful relationships since relocating to the west coast and having no real job prospects, because of no publications and no patents, even if he did defend his thesis and get his degree, and none of these things alone were unbearable or really that bad. But together, along with not being able to form a long term relationship with a woman, and watching countless graduate students from other countries spend 14 hours a day 7 days a week in the lab and remain sanguine about the whole thing, and this making him reevaluate everything he was sure he knew about hard work and self-determination and self-reliance including his view of himself as someone uniquely able to work very hard without encouragement for long periods of time. And maybe this also needed reappraisal, and how his high school girlfriend would admonish him to grow up and accept that he was privileged because he was born in the empire and his parents were together and he was fed and not abused and to just get on with it and make use of it, this admonishment coming when he said he wanted to go out into the world with nothing and show that he could survive and claw it all back on his own and she kept saying it would never work, you would always know you had a net under you, and so you had to accept it and although she didn’t say it then, when he looked back he thought for sure she meant he had to accept a responsibility to deliver something. And so now he was having to reevaluate everything he knew about his own agency and frankly whether he had ever been in control of his life.
Not to mention that astrocytes, the cells he studied, are stunningly complex, anatomically speaking, and impossible to immortalize and grow in culture, the very act of isolating them already Heisenbergenly deranging their morphology and probably function before he could even get the bastards under the microscope, which necessitated killing hundreds of mice over the course of his project. Moreover the endogenous anatomy, with labyrinthine projections and highly compartmentalized internal organization, was lost soon after isolation, meaning that the experiments were affairs involving treating the mouse, euthanatizing it, dissecting the brain, digesting the cerebellum with collagenase to break down the extracellular matrix, fractionation and sorting by FACS based on a GFP tag transgenically encoded by an astrocyte specific promoter (which someone in another lab at a different university demonstrated, during the third year of his project, was also expressed in subpopulations of non-astrocyte glia, partially confounding the interpretation of John’s work) and then isolating and patch clamping individual cells, a technically demanding process that often failed to produce a valid patch, which thus required dozens of cells before a cell was suitably patched1, after which point the experiment could begin. So, he arrived at the small conference room for his committee meeting 20 minutes early and set up his laptop with his PowerPoint presentation queued and set his backpack on a chair in the corner of the room. Then he waited for his advisor and the other three committee members to arrive.
“Patching” a cell is the process by which a glass micropipette is employed to perforate the cell membrane and establish a contiguous connection with the cell’s internal soup of biology, enabling experimental manipulation of voltage, calcium and other cellular ions, as well as facilitating introduction of mRNAs (for transient transfection) or even proteins themselves. Once a patch is established, one can then “record” the cell’s internal dialog.