The Worried Well

How much medical knowledge is too much?

PAINTING: “Moonrise,” by Alanna Siegfried Graboyes (asgraboyesart.com)

NOTE: I’m posting excerpts from my in-progress book manuscript, Fifty-Million-Dollar Baby: Economics, Ethics, and Health. The goal is to edit the manuscript in plain view, based on readers’ comments, corrections, suggestions, and criticisms.

In Prometheus Bound, by Aeschylus, the titan endows mankind with creativity— giving them fire, stolen from the gods, and also by giving them a fine balance of knowledge and ignorance about their mortality. Prometheus gives people the awareness that they will die, but denies them the knowledge of when they will die—and it is this terrifying balance that inspires them to create. This myth is profoundly relevant to an era when genetic testing and other means of long-term prognosis are proliferating.

Unaware of mortality, the Prometheus of Aeschylus tells us, humans are little different from ants—surviving, but not flourishing:

Confounded; knowing neither timber-work
Nor brick-built dwellings basking in the light,
But dug for themselves holes, wherein like ants,
That hardly may contend against a breath,
They dwelt in burrows of their unsunned caves.

But knowing the exact dates of their deaths would terrify them and rob them of incentive as the fateful day approached:

PROMETHEUS: I took from man expectancy of death.
CHORUS: What medicine found'st thou for this malady?
PROMETHEUS: I planted blind hope in the heart of him.

This knowledge-cum-uncertainty stoked the fire (or perhaps was the fire) that powered all of mankind’s subsequent creations. Prometheus recognized that knowledge is a mixed blessing.

In our Columbia University apartment building, in the mid-1980s, genius was ever-present, but did not always flash its ID card. Perhaps the outstanding example (but not the only one) was a dear, older lady, whom we regularly encountered in the elevator. Chien-Shiung Wu, whom we knew only as Madame Wu, always gave a big smile and insisted on knowing everything about our infant son’s progress in the world. We knew she was a physics professor but were unaware until years later that she had worked on the Manhattan Project, that she had shattered the fundamental idea of a symmetric universe, and that she was called the “Madame Curie of physics.” To us, she was simply the sweet professor who adored our infant son.

Another familiar figure in the elevator was a pleasant woman who always gave a quiet smile and a soft “hello,” but our conversations rarely went further. We were aware that she had some involvement in biological science but knew little more than that. After we had moved away, we saw her in a magazine photograph and learned that she was Nancy Wexler, who had conducted pathbreaking research into Huntington's chorea. (Her sister, historian Alice Wexler, has documented the illness in multiple books.)  Their mother, grandfather, and three uncles had the disease, and Nancy Wexler went with a team of researchers to remote villages near Lake Maracaibo, Venezuela, where it was prevalent. Over a period of years, Wexler gained the trust of tens of thousands of reluctant villagers and persuaded them to donate blood samples that could be used in genetic research. Wexler’s work enabled geneticists to identify the culpable gene and to devise a conclusive test. But then, both sisters faced the decision of whether or not to have themselves tested. In an NPR interview, Nancy Wexler described the pros and cons and, to me at least, her observations called to mind the logic expounded by the Prometheus of Aeschylus—knowledge is good, but too much knowledge can be harmful.

Huntington’s chorea is a genetic disease causing progressive degeneration of motor control, cognition, emotion, and involuntary movements; eventually, the disease kills the victim. The disease is caused by a specific genetic anomaly. This particular gene normally includes a trinucleotide (CAG) that, over a strand of the gene, repeats itself over and over again. According to Wexler, Huntington’s “is one of the most fully genetically determinant diseases known. If you carry an expanded allele of a certain size, you will get sick and die.” If this particular genetic component repeats 35 or fewer times, the person does not suffer from Huntington’s; if it repeats 40 times or more, he will definitely suffer the illness; if it repeats 36 to 39 times, he may or may not. In general, more repetitions of the sequence means earlier onset of the disease. Huntington’s is an autosomal dominant disease; it is only necessary to inherit the problem from one parent. If one of your parents has Huntington’s there is, in general, a 50% chance that you, too will fall prey to the illness. You can have yourself tested and know a great deal about when you will die. Or you can wait and see.

Singer/songwriter Woody Guthrie is perhaps history’s best-known Huntington’s sufferer. In his first three to four decades of life, Guthrie’s son, singer Arlo Guthrie, did not know whether he had won or lost the coin toss. (No genetic test existed at that time.) Since he faced a 50% chance of inheriting Huntington’s, any children he had would face a 25% chance (50% x 50%) of inheriting the condition as well. He chose to have children anyway. He said he thought of it not as a 25% chance that they would have the illness, but rather, as a 75% chance that they wouldn’t. His take was, “No matter how you cut it, that’s pretty good odds.” Arlo Guthrie never developed the illness, and his age means he almost certainly won’t, so his children and their descendants appear to have been absolved. Though I can’t find this quote, I recall hearing him interviewed on this topic when he was still unsure of his fate; in deciding whether or not to have children, he said that regardless of whether he developed the illness, he was glad to have been born—and hoped that his children would feel the same way. No doubt, Prometheus smiled.    

With something approaching certainty, a Huntington’s test tells a person either, “You will suffer from the illness,” or “You will not,” but BRCA screenings are different. A positive test tells a woman, “The other women in the street have a certain probability of developing breast cancer. You have a higher probability than women who have a negative test. If you have a family history plus a positive test, you have an even higher probability.” This is enough to persuade some women to have prophylactic mastectomies. (Actress Angelina Jolie is a notable example.) But there is still a fairly high likelihood that those who undergo such procedures would never have suffered from the disease.  

I once read of an 18th-Century German doctor whose medical notes spoke of a patient who had a bunion (which she worried a great deal about) and breast cancer (which she did not particularly worry about). Why this paradoxical difference? The bunion interfered with her life and work and her comfort, and it was a treatable condition. The breast cancer would eventually kill her, but what could one do? Better to focus the attention and emotion on the bunion. (I haven’t been able to locate this story, so I’d be happy to receive any information about its provenance.)

Some years ago, I developed some frightening digestive-tract symptoms which, fortunately, turned out to be a minor and transitory acid reflux problem. Before the diagnosis was made, my doctor’s advice was, “Whatever you do, do not go onto WebMD and search for what these symptoms can mean.” I told him I had no intention of doing so. Que será, será.

Thirty years earlier, I had a routine chest x-ray at the University of Virginia. Looking it over, the doctor said, “It looks fine,” and I went home. Shortly thereafter, the telephone rang. A voice at the other end said, “Dr. C― would like you to come back immediately.” … “Why?” I asked. … He just wants to check something. He says it’s probably nothing.” … I returned to the hospital and walked in to see the doctor. … “What can I do for you, doctor?” … “Oh, (nervous chuckle), I just want to check something. Probably nothing.” … I went down the hall to the radiologist who said he needed to take another X-ray. … “Why? I asked.” … “Oh, (nervous chuckle), we just want to check something. Probably nothing.” … The process repeated through several more individuals, and my tension rose markedly.

Finally, I cornered a young radiology resident and said, “I’m really tired of this. Would you please tell me what’s going on?” … “Do you really want to know?” he asked. … “Yes.” … He hung my X-ray on a light board and pointed with his finger. … “Portions of these two vertebrae in your neck are a different shade than the rest of the vertebrae. This could be because the film had a blotch on it—that sometimes happens near the edge of the film. If not, it means that those portions of your vertebrae are of a different density than the rest of your vertebrae.”

I looked at the X-ray a moment and said, “I’m guessing that if that’s true, then this would be cancer, and probably a bad one—correct?” … “Yes.” … “Fine,” I said. “I feel much better. I can worry about one thing rather than worrying about every possibility.” To this day, I have no idea whether my reaction made any sense, but I was suddenly calm. It turned out that the film had a blotch. There was no variation of bone density.

In 2011, I passed my one-half millionth hour on earth. In all of history, perhaps 100 people are known to have passed one million hours. Biomedical gerontologist Aubrey de Grey predicted some years ago that the first person to live to 150 is already alive today.

Nara Leão was a Brazilian singer and actress, whose inspiring effect on mid-century Brazilian musicians earned her the sobriquet, “the Muse of Bossa Nova.” In the early 1970s, amid Brazil’s ongoing political turmoil, she relocated to Paris and largely gave up music to focus on raising children. In 1979, she was diagnosed with an inoperable brain tumor and an uncertain span of time before it killed her. With this knowledge, she became furiously productive—racing against limited time to bolster her already considerable legacy. After a decade of enormous productivity, she finally succumbed to the illness in 1989.    

When I am not doing economics or journalism, I am a musician and amateur composer. I composed my first song in 1962, at the age of eight, and entered a national competition for young composers. My piece earned honorable mention, and in recent years, I’ve re-arranged the melody as a jazz number. Over the next half-century, I wrote additional pieces. Most went into my file cabinet and some disappeared. With the advent of the web, I recorded maybe two dozen pieces and posted them haphazardly online. When COVID-19 first arrived in early 2020, the general atmosphere, as we all know, was one of abject terror. One of my morbid thoughts was, “This virus could well kill me soon, and if that happens, no one will ever know that I composed some rather nice pieces. Thinking of Nara Leão’s mortality-driven productivity, I opened a YouTube channel and began composing and posting pieces at a rapid clip. (I should have 150-200 original compositions by the end of this year.) I don’t have Nara Leão’s fame, but I’m glad to have posted the music and gained a modest-sized audience that enjoys my work. Without the menace of COVID, I doubt that I would have produced this body of work. Here’s one of my pieces from 2022:

A 1960 broadcast of The Twilight Zone titled “A Nice Place to Visit” features a small-time hoodlum who finds himself in a very pleasant place which he ultimately determines is the afterlife. He is surrounded by beautiful women. He wins every gamble he makes at the casino tables. A police officer shrinks helplessly before him. Everything is perfect and utterly predictable. After a month, he is bored out of his mind and demands to know why a hoodlum like himself was sent to Heaven. He asks to be sent, instead, to Hell which, he assumes, will better suit his tastes. He is informed that he is, in fact, already in Hell.  

Thousand of genetic tests are now available, and many people are taking batteries of them through programs like “executive screenings.” A relevant question is whether the value of such tests is exceeded by the resulting hypochondria and unnecessary medical procedures they can spur.  

In his masterful, The Fragile Species, Lewis Thomas, dean of medicine at Yale and New York University and later president of Memorial Sloan-Kettering Institute wrote:

The dilemma of modern medicine, and the underlying central flaw in medical education and, most of all, in the training of interns, is the irresistible drive to do something, anything. It is expected by patients and too often agreed to by their doctors, in the face of ignorance.

In Woody Allen’s Annie Hall (1977), a Brooklyn doctor counsels a Woody-Allen-like 9-year-old, Alvy Singer, and his mother:

Doctor: Why are you depressed, Alvy?
…
Alvy: The universe is expanding.
Doctor: The universe is expanding?
Alvy: Well, the universe is everything, and if it's expanding, someday it will break apart and that would be the end of everything.
Alvy's Mother: What is that your business?  … He stopped doing his homework!
Alvy: What's the point?
Alvy's Mother: What has the universe got to do with it? You're here in Brooklyn. Brooklyn is not expanding.