Friday, July 28, 2017

Where a bad gene may be a good thing

My neighbor Pagan Kennedy is a multifaceted writer. When I met her two decades ago, she was writing mainstream novels, one of which received the Orange prize, a major honor for women writers in the United Kingdom and other English-speaking nations. In one of her first nonfiction books, The First Man-Made Man: The Story of Two Sex Changes, One Love Affair, and a Twentieth Century Medical Revolution, Kennedy went where other writers hadn’t.
These days, Kennedy is filing articles about science, technology and innovation for the New York Times, and her latest article concerns dementia. In “An Ancient Cure for Alzheimer’s?” Kennedy suggests that indigenous populations in Bolivia could lead researchers to a new understanding of Alzheimer’s, and how it might eventually lead to a cure. Back in 2011, the anthropologist Ben Trumble spent extensive time in the Bolivian jungle, collecting vials of saliva from tribesmen to gauge their testosterone levels. In return, Kennedy noted, Trumble agreed to field-dress the kill. The aim was to see if without industrialization, there might be different outcomes concerning dementia.
Trumble himself was touched, indirectly, by Alzheimer’s. He learned that a favorite uncle had been diagnosed with Alzheimer’s, and was declining rapidly. The uncle died in 2015. As Trumble commented, “We know almost nothing about how dementia affected humans during the 50,000 years before developments like antibiotics and mechanized farming.”
Researchers understand that Americans who carry two copies of the APOE4 gene are ten times likelier to develop later-onset Alzheimer’s compared to the people of the Tsimani. And here’s the surprise: “The Tsimane people have the cleanest arteries that have been studied.” Even more counterintuitive, “Many of those with an extra copy [of the gene] seemed to do better on the cognitive tests.” As Kennedy speculated, “Perhaps the APOE4 gene provided a survival advantage in ancient environments.”
Back at his office in Arizona State University, Trumble discovered what appeared to be a large pimple on his nose. But when the growth continued to enlarge, he recognized for what it was: a flesh-eating parasite. As Kennedy noted, “Chemotherapy saved his nose, and perhaps his life.” Trumble went on to review the data from the Tsimane volunteers. “Sure enough, he found that the Tsimane with infections were more likely to maintain their mental fitness if they carried one or two APOE4 genes. For them, the ‘Alzheimer’s gene’ provided an advantage. For the minority who’d managed to elude parasitic infection, however, the opposite was true.”
Kennedy speculated that the APOE4 gene served as a means of survival in a prehistoric period. “Today only about a quarter of us have a single copy of the APOE4 gene, and only about two in a hundred carry a double dose. But DNA analysis of ancient environments shows that thousands of years ago, the APOE4 genotype was ubiquitous.”
Given my shallow understanding of genetics—I did poorly in high school biology—I suggest that those of you who are interested in the topic, google “Pagan Kennedy ancient care for Alzheimer’s.” The article is worth reading in its entirety.

Friday, July 21, 2017

Unreliable narrators

Those of you who were English majors likely recall the term “unreliable narrator.” If you’re not familiar with the term, here’s one durable definition, coined in 1961 by the literary critic Wayne C. Booth: a fictional narrator whose credibility has been compromised. I myself was frustrated recently while trudging through a 500-page novel by the prolific Victorian-era writer Anthony Trollope. I found the unnamed narrator irritating—and, more to the point, confusing. A more well-known example, written a century later, is Vladimir Nabokov’s Lolita: a novel about an unreliable narrator obsessed with a twelve-year-old girl. And unreliable narrators don’t need to be fictional. One of them is the president of the United States. More to the point, I myself have shown signs at times of being an unreliable narrator myself.
This week I revisited a post from November 2015, titled “A kitchen accident.” At that time, I was more confident in my cooking skills, and I was looking forward to do more of the cooking, as a means of taking the pressure off Paula. That afternoon I rode my bike fifteen miles, and the release of endorphins made me feel exceedingly calm. But that evening’s dinner, a pumpkin melange, didn’t turn out so well. I recall the difficulty of using a paring knife to remove the pumpkin’s rind, and at one point removing the rind, I drew blood under my right thumb’s fingernail, drawing stinging pain. Then things became murky. The Dutch oven I was cooking in had a large Pyrex top, and rather then removing the top from the stove, I set it directly on top of a back burner, which was in the process of becoming cherry-red hot. When I probed the lid with a dinner knife, the lid disintegrated. After that, time slowed down, as in a nightmare.
That was my version, anyways. Paula’s version was different, and, not surprisingly, her version was the accurate one. I had written in my blog that Paula was in the kitchen when the Pyrex top. But that made no sense. If Paula had been in the kitchen with me, she would have been the one dealing with the shattered Pyrex top.
The upside, if there was one, came a couple days later, when I met with my neuropsychiatrist: She assuaged my concerns that I had experienced a hallucination. That, of course, was welcome news.

Friday, July 14, 2017

A temporary constellation

As I mentioned in my previous post, the writer I most admire of my generation of novelists is Jonathan Franzen, whose sprawling novels evoke the ambition of nineteen-century writers such as George Eliot. Only recently did I learn that Franzen’s father had died from Alzheimer’s.
Writing in 2001, the same year he published his first major novel, The Corrections, he commented in a New Yorker essay that Alzheimer’s is “a disease of insidious onset.” But, he continued, “The problem was especially vexed in the case of my father, who was not only depressive and reserved and slightly deaf but also taking strong medicines for other ailments. For a long time it was possible to chalk up his non sequiturs to his hearing impairment, his forgetfulness, his depression, his hallucinations, to his medicines; and chalk them up we did.”
A meticulous observer, Franzen duly noted that his father’s brain weighed 1,225 grams. This suggests that Alzheimer’s had done its work thoroughly. A typical healthy brain is in the range of 1300 to 1400 grams. According to the research at the time, “The brain is not a photo album in which memories are stored discretely, like unchanging photographs.” Instead, a memory is “a temporary constellation of activity”—a necessary approximate excitation of neural circuits that bind a set of sensory images and semantic data into the momentary sensation of a remembered whole.” Franzen went on to comment, “The human brain is a web of a hundred billion neurons, with trillions of axons, and dendrites exchanging quadrillions of messages by at least 50 different chemical transmitters….The organ with we observe and make sense of the universe is, by a comfortable margin, the most complex object we know in the universe. And yet it’s also a lump of meat.”
And, in the central thrust of the article, Franzen stated, “I’ve come to tell, then, as I try to forgive myself for my long blindness to his condition that [his father] was bent on concealing that condition and, for a remarkably long time, retained the strength of character to pull it off.” Referring to Alzheimer’s as a classically “insidious” onset disease, Franzen commented, “Since even healthy people become more forgetful as they age, there’s no way to pinpoint the first memory to fall victim to it.” I’m not sure that’s correct. Thanks to a journal I keep, I’m certain that my short-term memory decline was in progress as early as the spring of 2012.
But back to Franzen’s father. As long as the elder Franzen was still working, the rest of the family “enjoyed autonomy in the respective fiefdoms of home and workplace.” But after the father retired in 1981, the marriage became strained. A letter from Franzen’s mother in 1990 suggests cognitive decline: “Last week one day he had to skip breakfast time medication in order to take some motor skills at Washington University where he is in the Memory & Aging study. That night I awakened to the sound of his electric razor, looked at the clock & he was in the bathroom shaving at 2:30 A.M.”
 Within a matter of months, Franzen’s dad was making so many mistakes and omissions that his wife was led, correctly, that something was deeply wrong. One example: Two times in one week, he had to summon AAA because of dead car batteries. Before long, his wife noted, “I really don’t like  the idea of leaving him in the house for more than a short while.” And, over the years ahead of him, his fate slowly playing out, and without any hope of a medical miracle, Franzen’s remarkable writing skills were no help in this gloomy venue, the elder Franzen left with only impotent words.

Friday, July 7, 2017

Summer reading

Three summers ago, The New Yorker published an essay, “A Place Beyond Words: The Literature of Alzheimer’s.” At that time, just the headline would have made me uncomfortable. Late in 2013 I was informed that I was at an elevated risk for dementia. Dementia? In my early fifties? At that time, the last thing I wanted to read about was dementia.
Now, of course, I am immersed in the topic. And recently I came across a useful survey of fiction about Alzheimer’s. The article, written by Stefan Merril Block, states that “Because the full experience of Alzheimer’s is an account that fiction alone can deliver, it’s no surprise that the go-to book for caregivers and early-stage sufferers is a novel…. Nearly every novel I’ve read that attempts to depict the internal experience of Alzheimer’s also attempts to fit the disease’s retrogenic symptoms to one sort of sentimental trope: a reckoning with a repressed or unacknowledged truth that must come before acceptance is possible. (Retrogenesis, loosely speaking, is the theory that in Alzheimer’s and similar diseases, symptoms appear in the reverse order of the normal aging process, putting some people in  jeopardy of developing Alzheimer’s or similar diseases.)
One novel about Alzheimer’s that Merril Block commented on was Debra Dean’s prize-winning The Madonnas of Leningrad. The book involves a survivor of the siege of Leningrad, which lasted for more than two horrific years. A novel that I read a few months ago—Not Me, by Michael Lavigne—provides some superficial parallels, with a key character who survived one of the Nazi death camps. But Lavigne is essentially a satirist, writing in an era—Not Me was published in 2005—when novelists are free to write about history’s most hideous atrocities in a comic vein.
Among other novels Merril Block cited are Barbara Kingsolver’s 1990 Animal Dreams and Samantha Harvey’s In the Wilderness. In Kingsolver’s novel, Alzheimer’s forces to the surface the memories of a lost grandchild. Samantha Harvey’s In The Wilderness is described as reminiscent of the writing of Virginia Woolf. And I was pleased to see that Merril Block included in his survey Jonathan Franzen, the best living writer of my generation, in my opinion.
Franzen’s break-out novel, in 2001, The Corrections, featured an elderly father who attempted to commit suicide by plunging off the deck of a cruise ship. It’s a striking moment, one that has stayed with me. In the novel, the father is described as being deeply depressed, and the disease in question is Parkinson’s. But Franzen’s father actually succumbed to Alzheimer’s. Franzen put some distance between his father and his fictional creation.
Next week I’ll discuss Franzen’s nonfiction account of his father’s decline and death.