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.”

DNA Day and Body Modification

The scientific study of human heredity has and has always had two types of practical application: relief of suffering and human improvement. Research programs with those ends in mind have existed at least since the beginning of the 20th century—maybe earlier, depending on how you define things. But by the Progressive Era (roughly 1890–1920), research in human heredity and genetics explicitly sought to reduce or eliminate human disease, raise the average level of our intelligence, beauty, and longevity, and improve our character.

For a long time, the only way to accomplish those goals was to regulate behavior. At the highest level—i.e., the least invasive of bodies but the most invasive of liberty—you regulate the relationship between people who might have children together. In the Progressive Era, many states passed laws prohibiting marriage between two people who were mentally retarded, or certifiably insane, or had tuberculosis (though its infectious nature was recognized, researchers also understood that there was an inherited predisposition). Immigration restriction laws, too, were a form of regulating behavior in the supposed interest of the national heredity (at least in part). They can’t breed if you don’t let them in in the first place.

Many people at the time saw surgical sterilization as much less invasive than marriage or immigration restriction. Advances in surgical technology and practice shifted the target of modification from the relationship to the individual. Modify the individual body and you can afford to be unconcerned with who that person marries or lives with or next to. From our perspective today, sterilization is an appalling invasion of autonomy, but in the 1930s, the heyday of eugenic sterilization—worldwide, by the way, not just in Germany—many people saw it, like abortion, as a way to loosen restrictions on the behavior of the sick, imperfect, and impure while still working toward improving society.

For a long time, then, “applied” human genetics was synonymous with what we think of as the worst excesses and sins of eugenics. Science historians and historically minded scientists have often written that human genetics got “tangled up” with eugenics because the researchers back then did not have sufficient knowledge. Now that we understand the science better, the argument runs, we can avoid the kinds of simplistic fallacies that drove the eugenics movement—fallacies such as the idea that there is a single gene for “feeblemindedness.” Or, ahem, the love of the sea.

But that argument gets it backward. Eugenicists resorted to marriage laws and sterilization for the same reason that there was so little reliable data on human genetics: genetics required sex. Because human geneticists couldn’t carry out breeding experiments, they couldn’t do backcrosses, self-fertilizations, and all the other kinds of matings that other geneticists could do. They could, though, control who mated with whom to some degree on a broad social scale.

The significance of DNA is that it made it possible to do genetics without sex. It wasn’t just DNA, of course—cell culture as well as lots of advances in biochemistry and microbial genetics also contributed—but by the 1960s DNA had emerged as the emblem of a “new genetics.” From the beginning, the DNA double helix had an iconic aspect. The first published image, in Watson and Crick’s first paper (the anniversary of which is the impetus for DNA Day), had a stripped-down, cartoonish quality, and was described in the figure legend as “purely diagrammatic.” Everyone understands DNA, then, to mean much more than “deoxyribonucleic acid.” It stands for the relationship between heredity and health.

The new, DNA-based, molecular genetics finally made it possible to do genetics without sex. Reducing or preventing disease no longer required controlling who married whom, or (more theoretically) even which babies got born. Technology made it possible to select which genomes made it into the next generation, and even, in principle, to alter and “correct” genes in the individual.

“DNA” thus solved the fundamental ethical problem of eugenics. State-level involuntary coercion of reproductive behavior simply makes no sense in a developed country with sophisticated biomedical facilities. It is pointless and paranoid to fear a “return to eugenics” if what you mean is that good ol’ time Progressive eugenics.

In the DNA era, human genetics is still about relief of suffering and human improvement. The NIH touts the disease side of things, but what counts as a disease is heavily freighted with subjectivity, cultural bias, gender, and racial prejudice. Further, at the molecular level, the difference between preventing disease and genetic enhancement dissolves. If you up-regulate transcription of the gene for Human Growth Factor, for example, it makes no difference technically whether you do it in a dwarf, a short person, or a person of normal stature. And the moral distinction between remediation and enhancement relies on soft, unsatisfying philosophical arguments that basically amount to “Ugh!”—in the same way that a conservative parent reacts when his child comes home with blue hair and a lip piercing.

In 1957, Julian Huxley—grandson of Darwin’s bulldog, a distinguished biologist in his own right, and an articulate, politically liberal eugenicist—coined the term “transhumanism.” He wrote, “The human species can, if it wishes, transcend itself —not just sporadically, an individual here in one way, an individual there in another way, but in its entirety, as humanity.” This is what he defined as transhumanism, and he intended us to accomplish it by a variety of means, but of course at the root of it would be the conscious, deliberate manipulation of the human germ line. Throughout the 1960s, geneticists fantasized about using the new knowledge of the genetic code to control human development and evolution, to tinker with the design of human beings. The overwhelming majority of this fantasizing was done with the noblest of intentions. Huxley, JBS Haldane, HJ Muller, Joshua Lederberg, Edward Tatum—these were not ignorant fools but rather some of the greatest, most sophisticated minds in biology. They wanted not to rule the world but to reduce suffering and improve happiness, compassion, and noble achievement.

Muller’s eugenic scheme was called “germinal choice.” We’ve all heard of the Nobel sperm bank that William Shockley (inventor of the transistor) wanted to establish—that was Muller’s germinal choice. Present-day transhumanists prefer Muller’s term to “eugenics,” which is irritating because it requires so much explanation about how their eugenics isn’t the same eugenics as the bad old eugenics. But it’s eugenics. The only reason to deny it is the bad publicity the term gives you.

Transhumanists such as Gregory Stock and ScienceBlog’s own Eveloce tend to argue that genetic enhancement is coming whether we drag our feet or not, and they may be right. The sociotechnical power of contemporary biomedicine is astonishing—and on the rise. I’m not yet sure how I feel about this. I am inherently suspicious of any structure with such a concentration of technological and economic power, and power leads to hubris. It is a truism that 21st century DNA science has the potential for enormous benefit as well as catastrophic harm.

The problem is that the largest benefits tend to be long-term, while the largest risks are in the short term. It is not paranoid to be worried about such a situation, nor is it inconsistent to enjoy and admire positive results as they come out while maintaining a healthy, grouchy skepticism about the larger project.

I’m actually encouraged by the fact that transhumanism has a significant overlap with the blue-dreads-and-lip-piercing set. I’m more comfortable with tweaking our genes to, say, be able to grow horns or have Mr. Spock ears than to make everyone tall, white, and smart. Sure, it can be trendy and pretentious, like other body modification subcultures such as the “modern primitives,” but at bottom these folks are interested in it as a form of expression, not social control. Anything that breaks down barriers rather than reinforcing them gets my vote.