End Times (The Telos of Telomeres)

For Aristotle, both ethics and politics flowed from the telos, the end or purpose of all things. In what may be record time for translating Nobel Prize benchwork to biotech snake oil, telomeres are the latest rage in high-tech diagnostics. Several startups are now pitching them as a way to tell your “biological age,” a new health metric that is as baffling as it is troubling.[1]

The 2009 Physiology or Medicine prize went “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.” Telomeres, as I wrote in 1991, are like aglets—the plastic tips on the ends of your shoelaces—for your chromosomes. They’re long stretches of repetitive DNA that essentially keep chromosome ends from unraveling. The thing is, unlike shoelaces, chromosomes duplicate themselves. They have to—otherwise half your cells would have no genes. And every time they do, because of one of those ubiquitous little design flaws that show there’s Nobody Home Upstairs, your telomeres get a tiny bit shorter. The telomere is therefore a sort of clock, ticking down the mitoses until a cell reaches the Hayflick Limit, at which point basically chromosomal Fukushima occurs. Telomerase counteracts that shortening in certain cell types, making those cells effectively immortal.

There have always been a few people who find it irresistible to think that cellular aging determines organismal aging. Seems logical, right? I mean, we all know an organism is made of cells. When you get old, doesn’t it have to be because your cells are getting old?

Well, sort of, sometimes, in some cases, but not in any simple way. Senescence is an incredibly complex process—and nowhere more so than in humans, naturally—and it mostly happens independently of your telomere length. It’s certain that your telomeres will be shorter when you’re old than they were when you were young, but old people can have long telomeres, and young people can have short ones. For that matter, short people can have old telomeres.

Further, cellular immortality is a mixed blessing, to say the least. On the one hand, slowing cellular senescence could in principle forestall certain degrading diseases of disintegration. On the other, there’s already a name for immortalized cells: cancer.

Anyway, cellular and organismal aging operate on different time scales, and the latter involves a lot of processes that have nothing to do with the former. To equate them is to confuse variation at two different levels—the same sort of error found in claims that racial differences in IQ result from genetics rather than systematic discrimination.[2]

That neat little fallacy is the foundation of the business plan at several new biotech companies, in Spain, Houston, and of course, in Menlo Park, CA. They claim to be able to take a few of your cells, open them like sacrificial goats, spread out their entrails, and tell you how old you “really” are. These new longevity companies claim to only be raising a warning flag, pointing you toward medical treatments you might want to consider.

A century ago, the Life Extension Institute had a similar model. The New York-based company offered medical exams, denying that they were offering any medical treatment. They pitched their product directly to individuals, but their biggest customers were employers and the many life insurance companies springing up in the Progressive Era. They eventually shut down in the wake of numerous lawsuits and accusations of fraud and misrepresentation. And LEI’s cofounder, Irving Fisher, went on to found the American Eugenics Society.[3]

For a few hundred bucks, these new companies will give you one-stop diagnostic shopping. With one measurement, they claim, they can tell you all sorts of things about your overall health and well-being. You even get to pick your metaphor: you either get a “wake-up call” about how fast you are really aging, or you can have your “check engine light” checked, according to spokesmen for the companies quoted in the Times article. The check-engine light in my car goes on for free, but after that I guess that in both cases it means a lot of expensive, computer-based diagnostics, and a lot of fervent hopes that all you did was pop a circuit-breaker.

Some of the scientists involved show a refreshing degree of candor. Jerry Shay, of UT Southwestern and on the board of the company Life Length (didn’t I get email from Nigeria about a similar product the other day?), acknowledged that although they won’t tell anyone how long they will live, insurance companies might want this information “to set rates or deny coverage.” In other words, they’re perfectly happy to sell the actuarial illusion that they can tell anyone how long they will live.

A Spanish telomerista, Maria Blasco, said the telomere test might prove helpful to people “especially keen on knowing how healthy they are.” Never mind the deeply problematic notion of playing to the fears of bored upper middle-class hypochondriacs; outside of a couple of risk factors for very specific and rare diseases, no one has any idea what this tells you about how healthy you are. But hard data and actual products tend to be hell on stock prices anyway.

Everyone got that? They’re telling us this is a scam. Now look, I am not saying these folks are dishonest, or even cynical. I think they are a bunch of basically honest scientists swayed by the allure of high-tech translational biomedicine. It’s the scientific version of the American Dream. And it comes with the always-handy Biomedical Moral Pass. It’s a great example of overfunded, overhyped science that benefits corporations and stockholders but may well do patients more harm than good.

The thing I wonder about most, though, is this idea of “biological age.” Apparently, the age I think I am—which I have until now naively correlated to the number of birthdays I’ve had, and never mind—is now “non-biological.” It’s like an acoustic guitar. There was no such thing as an acoustic guitar until the electric guitar was invented. All guitars were acoustic. Are there now multiple kinds of time—chronlogical, biological, and who knows what else—where I can be getting older in one dimension and younger in another? Have these biologists have actually reinvented time?

Or have they figured out what time really is? Is my chronological age now merely a figment, a simulacrum—a fictive representation of some supra-biological horological process? If so, I don’t think I like where this is going. We’re not headed down the sunny, leafy lane of, “You’re only as old as you feel! Have another bran muffin and go enjoy the morning.” This is more like the gray, trash-strewn alley of, “You poor dumb bastard. You only think you want to go to that punk show downtown this weekend. Sit down, shut up, and drink your Mylanta.”

It sounds like the beginning of the end.

[1] Andrew Pollack, “A blood test offers clues to longevity,” 2011-05-18 (http://nyti.ms/iIO3gv).
[2] In other words, conflating within-group and between-group variation. Whatever IQ is, it is highly heritable. But heritability is a measure of variation within a group. The heritability of IQ is different for different groups under different conditions. It simply cannot be used as a measure of how “innate” a trait is.
[3] I write about Fisher in chapter 2 of my forthcoming book, “A Science of Human Perfection.”

Horace Judson: a eulogy

On May 6, at the age of 80, the writer Horace Freeland Judson died. He didn’t pass away; he would have insisted that he simply die. We worked together for five years, from 1997 to 2002, at The Center for History of Recent Science, George Washington University. Here is my appreciation.*

He was six feet in his stockings, which were certainly silk. He dressed impeccably. His leather shoes were glossy, his slacks pressed, even on writing days. His collar was crisp, his cufflinks shone. His houndstooth jacket might be a little worn at the seams, as if from catching too many brambles, but it was always clean. He wore a pocketwatch, and spoke with a vaguely “U” (upper-class, to the English) accent. He was raised in Chicago. A black, broad-brimmed hat, molded just so and rakishly tilted, cravat, and even a cape were not unknown on special occasions. I once saw him open a bottle of New Year’s champagne with a sword. Horace Judson was more than a little vain. But judgment should be tempered by the knowledge of two facts: his preening both reflected and masked enormous effort; and he had terrific taste. He seemed to put thought into every stitch of clothing on his body, every stick of furniture in his house, every book in his library, every word in his books.

His meticulous appearance was, like a peacock’s tail, a display of vigor, for he zipped his pants, buttoned his shirt, oiled his hair, and tied his shoelaces with only one good hand. The left. Childhood polio had withered the other, leaving it floppy and florid. The handicap slowed him down a little—he reconfigured that slowness into a magisterial pace—but prevented him from doing nothing. He shook hands cross-handed (I soon learned to shake left-to-left with him). He opened wine, canned tomatoes, and drove a stick-shift, flamboyantly flouting his disability. He never asked for help. His pride was his strength.

Of course, he typed the quarter million or so words of The Eighth Day of Creation, and everything else he wrote, with one hand. The deliberation this required contributed to the precision and elegance of his prose. Though a journalist by training, he wrote not like a reporter but like an essayist or a novelist. His style was always formal, never slangy (though he was not averse to the occasional earthy vulgarity), and occasionally pompous. He used every rhetorical trick in Aristotle, and had a flair for the dramatic. But his prose was always muscular, and he regularly knocked off passages of such clarity, insight, and grace as to leave the attentive reader breathless.

Consider his definition of X-ray crystallography, an arcane science if ever there was one, from chapter 2 of The Eighth Day. He begins with an analogy simultaneously quantitative and yet immediately apprehensible: “The X-rays used in crystallography are shorter than visible light by some four thousand times.” That does what good writing must, especially when it is on a technical subject: it connects the unknown to the known. Any educated person has a rough idea about visible light, and a sense of how big four thousand times is. Judson then explains the one thing everyone wants to know about X-rays. “Their wavelength is 1.5 Angstroms, which is the same order of size as the spacing between atoms in many solids, and that is why X-rays go through substances that are opaque to the eye.” Did you know that? “Penetrated by a thin beam”—thin beam is nice, both as explanation and in sonority—“the orderly array of atoms in a crystal, layer upon layer, scatters the X-rays in an orderly way, causing a repeating series of overlapping circles of waves.” Note the repetition of orderlyorderly, prefiguring the repeating series of the following clause. Powerful rhetoric illustrates the underlying concept. “At intersection with the flat sheet of film”—note the alliteration, intercalated by the contrasting long vowel sound—“the troughs and peaks of these waves reinforce each other at some points and cancel each other out elsewhere.” The image recalls every child’s game of dropping two stones into a pond and watching the ripples crash. Here is the crucial insight: “The interference pattern that results is characteristic of the structure that produced it,” he writes, and he abruptly ends the lesson by waving a hand at the Nobel-winning mathematics behind it, which would confuse and bore his audience: “…though to figure back to the structure takes mathematics and experience.” That’s all you need to know, really, and not a word more than it takes to describe it.

He never matched that book. How many of us get even one book of that magnitude? Judson is by far the non-PhD most quoted by historians and philosophers of twentieth-century biology, and scholars hate the fact. “Molecular biology is a discipline, a level of analysis, a kit of tools,” he wrote at the beginning of chapter 4. “Which is to say, it is unified by style as much as by content.” There’s a dissertation in that casual observation. He had hundreds like it. At the same time, the book is notoriously difficult to teach, and so few do. (I like to assign chapter 3. Students love it, but find it challenging.) Teachable books show their scaffolding and leave their beams exposed, so that students can skim for argument and get on to their orgo problem sets. Not so Judson. He draws you in, makes you read slowly. The paragraphs are meticulously constructed, but the themes are buried a sentence or two deep, and the arguments build incrementally. You end up highlighting every line.

That quality, combined with his pomp and occasional arrogance, alienated many historians of science. He could be difficult. Yet three things saved him for me. First, his intelligence and his skill as a writer and editor. Many times he annoyed me by ignoring my requests to comment on my green prose, only to read through it once and mark it up on the fly, effortlessly extracting the voice and meaning that I had buried in murk and flab and cliché. He still sits on my shoulder as I write, insisting that I justify the sequence of items in a list, put a twist on every cliché, and, unless I have a specific reason to do otherwise, narrate my story in strict chronological order. Second, his generosity. He often went far out of his way for people, with no expectation of recognition. Behind the formality was a genuinely warm person who loved sentiment but hated sentimentality. And third, his tragedy. He wanted to be accepted as a historian, and never quite was. I think he idealized the university as only someone can who doesn’t have the professorial press pass. Which is too bad, because he was better—gave more insight and more pleasure—than many credentialed scholars. His obituary in the Times listed him as a historian of science, which would have pleased him but which underestimated him. He was a writer.

*Thomas Soderqvist has also posted a piece on Judson. Highly recommended.