The Art of Aging

by Sherwin B Nuland

  And then, to what would seem the obvious objection that such moral codes assume our current life span and not one lasting thousands of years:

  It’s an incremental thing. It’s not a question of how long life should be, but whether the end of life should be hastened by action or inaction.

  And there it is—the ultimate leap of ingenious argumentation that would do a sophist proud: By our inaction in not pursuing the possible opportunity of extending life for thousands of years, we are hastening death. A sin of omission thus becomes a sin of commission.

  No word of the foregoing quotes has been edited or changed in any way. De Grey speaks in formed paragraphs and pages. Those accustomed to being interviewed are all too familiar with how garbled they often sound when quoted literally or heard on a tape, requiring adjustments of phrases and sometimes entire sentences in order to make themselves understood if publication is contemplated. Not so for de Grey, who speaks with the same precision as he writes. Admittedly, some may consider his responses to have the sound of a carefully prepared sermon or sales pitch because he has answered similar questions many times before, but all thought of such considerations disappears when one has spent a bit of time with him and realizes that he pours forth every statement in much the same way, whether it involves some problem he has faced a dozen times before or something as commonplace as ordinary conversation while showing me the genetics lab where he works. His every thought comes out perfectly shaped, to amaze a bemused observer.

  De Grey does not fool himself about the vastness of the effort that will be required to attain his objective. Nor does he seem fazed by my reminder that his optimism might simply be based on the fact that, having never worked as a bench researcher in biology, he may not appreciate or even understand the nature of complex biological systems. Or his optimism may be based on his not fully taking into account the possible consequences of his tinkering with what he sees as individual components. Unlike the engineering approach that he considers his main conceptual contribution to solving the problems of aging, physiological events cannot be approached as distinct entities to be worked on as though none of them has any effect on the others. Each of de Grey’s interventions will very likely result in unpredictable and incalculable responses in the biochemistry and physics of the cells he is treating, not to mention their extracellular milieu and the tissues and organs of which they are a part. In biology, everything is interdependent, and all things are affected by everything else. Though we study phenomena in isolation to avoid complicating factors, those factors come into play with a vengeance when in vitro becomes in vivo. The fearsome concerns are many: a little lengthening of the telomere here, a bit of genetic material from a soil bacterium there, a fistful of stem cells—the next thing you know, it all explodes in your face.

  His reply to all this is similar to his reply to so much else, whether it be the threat of overpopulation, the changed relationships within families and whole societies when everyone is essentially the same age, or the need to find employment for vibrantly healthy people who are a thousand years old. We will deal with these problems as they come up, he says, and make the necessary adjustments, whether they are in the realm of potential cellular havoc or the tortuosities of socioeconomic necessity. He believes that each of them can be retouched and remedied as they become recognized.

  And de Grey does have some interesting notions of human nature. On the one hand, he insists that it is basic to humankind to want to live forever regardless of consequences, while on the other it is not basic to want to have children. When I protested that the two most formative driving forces of all living things are to survive and to pass on their DNA, he quickly made good use of the one and denied the existence of the other. Bolstering his argument by the observation that many people choose—like Adelaide and himself—not to have children, he replied, not without a hint of petulance and some small bit of excited waving of his hands:

  Your precept is that we all have the fundamental impulse to reproduce. The incidence of voluntary childlessness is exploding. Therefore the imperative to reproduce is not actually so deep-seated as psychologists would have us believe. It may simply be that it was the thing to do—the more traditional thing. My point of view is that a large part of it may simply be indoctrination…. I’m not in favor of giving young girls dolls to play with, because it may perpetuate the urge to motherhood.

  De Grey has commented in several forums on his conviction that, given the choice, the great majority of people would choose life extension over having children and the usual norms of family life. This being so, far fewer children would be born. He did not hesitate to say the same to me:

  We will realize there is an overpopulation problem, and if we have the sense we’ll decide to fix it [by not reproducing] sooner rather than later, because the sooner we fix it the more choice we’ll have about how we live and where we live and how much space we will have and all that. Therefore, the question is, what will we do? Will we decide to live a long time and have fewer children, or will we decide to reject these rejuvenation therapies in order that we can have children? It seems pretty damn clear to me that we’ll take the former option, but the point is that I don’t know and I don’t need to know.

  Of course, de Grey’s reason for not needing to know is that same familiar imperative he keeps returning to, the imperative that everyone is entitled to choice regardless of the possible consequences. What we need to know, he argues, can be found out after the fact, to be dealt with when it appears; without choice, we deprive humankind of its most basic liberty. It should not be surprising that a man as insistently individualistic—and as uncommon a sort—as he is would emphasize freedom of personal choice far more than he addresses the potentially toxic harvest that might result from cultivating that dangerous seed in isolation. As with every other of his formulations, this one—the concept of untrammeled freedom of choice for the individual—is taken out of the context of its biological and societal surroundings. Like everything else, it is treated in vitro rather than in vivo. All of the de Grey formulations are based on the great assumption that biology and culture work this way.

  A major factor in de Grey’s success in attracting a following is one that is less about his science than himself. As I discovered during our two sessions of Abbot-quaffing at the Eagle, it is impossible not to like him. Despite his unhesitant verbal trashing of those who disagree with him, there is a certain untouched sweetness in the man that, combined with that uncaring appearance and the sincerity of his commitment to the goals that animate his life, is so disarming that the entire picture is of the disingenuousness of genius, rather than of a remote and self-promoting false messiah. His likability was pointed out even by the detractors to whom I later spoke. It is a quality not to be expected in such an obviously odd and internally driven man.

  In campaigns that occur across the length of several continents, de Grey’s purpose is only secondarily to overcome resistance to his theories. His primary aim is to publicize himself and his formulations as widely as possible, not for the sake of personal glory but as a potential means of raising the considerable funding that will be necessary to carry out the research that needs to be done if his plans are to stand any chance of so much as partial success. He has laid out a schedule projecting the timeline on which he would like to see certain milestone events reached.

  The first of these milestones is to control the aging of experimental mice sufficiently to triple their life expectancy. He believes adequate funding will make this doable “ten years from now; almost certainly not as soon as seven years, but very likely to be less than twenty years.” Such an accomplishment, de Grey believes, will “kick-start a ‘War on Aging’” and will be “the trigger for enormous social upheaval.” In an article for the Annals of the New York Academy of Sciences in 2002 listing seven coauthors after his own name, de Grey wrote, “We contend that the impact on public opinion and (inevitably) public policy of unambiguous aging-reversal in mice would be so great
that whatever work remained necessary at that time to achieve adequate somatic gene therapy would be hugely accelerated.” Not only that, he asserts, but the public enthusiasm following upon such a feat will cause many people to begin making life choices based on the probability that they too can reach an equivalent number of years. Such life choices include several that even a skeptic like me would look on with pleasure: For example, when people know that they may live as long as four to five hundred years (with ongoing research during that time sure to add multiples of such a figure), they will take fewer chances of involving themselves in anything that might kill them, like wars, crime, bad driving habits, and other hazardous activities. Not only that, but when death of a disease such as influenza is considered premature at the age of two hundred, the urgency to solve the problems of infectious disease will massively increase government and drug company funding in that area.

  In addition to accelerating demand for the appropriate research on human applications, the survival of a nine-year-old mouse born to live a third that long is projected to bring in new sources of funding. Because governments and drug companies tend to favor research that promises useful results in a relatively short time, de Grey is not counting on them as a source. He is relying on an infusion of private money to supply the approximately one hundred million dollars per year that he estimates it will take to successfully fight his “war.” It is his contention that once mouse-success has been achieved, billionaires will come forward, intent on living as long as possible and having the personal means to support the studies that might make it happen.

  Of course, such an optimistic visionary would hardly call attention to the likelihood that quite the opposite effect might result from the appearance of a photograph of his long-lived mouse on the front page of every newspaper in the world. Is it conceivable that such an event would be greeted with the unalloyed enthusiasm of a unanimous public universally eager to open an unlabeled can of worms and begin eating its contents with such voracious appetite as he predicts? I doubt it. More likely, one man’s acclaim would be at least one other man’s horror. Ethicists, economists, sociologists, members of the clergy, and many worried scientists can be counted on to join huge numbers of thoughtful citizens in a reaction the likes of which would make the present uproar over human cloning seem like a genteel tea party. But, of course, if we are to accept the line of reasoning that follows so logically from de Grey’s first principle, that the desire to live forever trumps every other factor in human decision-making, then self-interest—or what some, including me, might call narcissism—will win out in the end. I have more confidence in human nature than to believe that.

  De Grey projects that fifteen years beyond the mouse may be enough time in which to reach the goal of tripling human life expectancy, though he concedes that it may take as long as a century. What he does not concede, of course, is that it is more likely not to happen at all. He cannot seem to imagine—considering all the realistic pitfalls along the way—that the odds are heavily against him. And he also cannot seem to imagine that not only the odds but society itself may not come out in his favor. So convinced is he that the inborn urge to conquer death is sufficiently strong that it supersedes any other consideration—including the possibility of destroying our civilization, just the thing that is meant to be enhanced—that he will provide any listener or reader with a string of reasons (more like rationalizations) to explain away why it is that most mainstream gerontologists remain so conspicuously absent from the ranks of those cheering him on. Despite his publicized face and the increasingly loud fanfare that attends some of his pronouncements, he has safeguarded himself against the informed criticism that one might reasonably expect should give him cause to rethink some of his proposals. He has accomplished this self-protection by constructing a personal worldview in which he is made inviolate. He stubbornly refuses to budge a millimeter; he will not give ground to the possibility that any of the barriers to his success may prove to be insuperable.

  Many decades ago, in my naïveté and ignorance, I used to think that the ultimate destruction of our planet would be by the neutral power of celestial catastrophe: collision with a gigantic meteor, the burning out of the sun—that sort of thing. In time, I came to believe that the end of days would be by the malevolence of a mad dictator who would unleash an arsenal of explosive or biological weaponry: nuclear bombs, engineered microorganisms—that sort of thing. But my notion of the nature of “that sort of thing” has recently been changing. If we are to be destroyed, I have now become convinced, it will not be a neutral or malevolent force that will do us in, but one that is benevolent in the extreme, one whose only motivation is to improve us and better our civilization.

  If we are ever immolated or ever self-immolate, it will be by the efforts of well-meaning scientists who are convinced that they have our best interests at heart. We already know who they are. They are the DNA-tweakers who would enhance us by allowing each set of parents to choose the genetic makeup of their descendants unto every succeeding generation ad infinitum, heedless of the possibility that breeding out variety may alter factors necessary for the survival of our species and its relationship to every form of life on earth; they are the biogerontologists who study extreme caloric restriction in mice and promise us an expectancy extended by 20 percent of a peculiarly nourished existence; they are those other biogerontologists who emerge from their laboratories of molecular science every evening optimistic that they have come just a bit closer to their goal of having us live 250 years by engineering genes, adjusting telomerase, or some other such strategy, downplaying the unanticipated havoc at both the cellular and societal levels that might be wrought by their proposed manipulations.

  And now, finally, it is the unique and strangely alluring figure of Aubrey de Grey, who, orating, writing, and striding tirelessly through our midst and the midst of some less-thanfully convinced sympathizers, proclaims like the disheveled herald of a new-begotten future that our most inalienable right is to have the choice of living as long as we wish. With the passion of a single-minded zealot crusading against time, he has issued the ultimate challenge, I believe, to our entire concept of the meaning of humanness. And paradoxically, his clarion call to action is the message of neither a madman nor a bad man, but of a brilliant, beneficent man of good will, who wants only for civilization to fulfill the highest hopes he has for its future. It is a good thing that his grand design will almost certainly not succeed. Were it otherwise, he would surely destroy us in attempting to preserve us.

  DRINKING FROM THE FOUNTAIN OF YOUTH

  I sometimes find myself thinking about a long-dead Frenchman named Brown-Séquard, whose distinguished reputation as a medical scientist dissolved virtually overnight when he pridefully reported that he had discovered a treatment to stave off certain of the ravages of aging, especially those having to do with sexual performance.

  Charles-Édouard Brown-Séquard was born in 1817 on the island of Mauritius, to an American father and a French mother. A brilliant researcher, he made many notable contributions to the understanding of the nervous system and metabolism during his career, and was rewarded by being named professor of experimental physiology at the Collège de France in 1878, in recognition of these and other important advances. He and his predecessor in the college chair, Claude Bernard, are properly credited with introducing the notion that hormones, those protein substances secreted into the bloodstream by ductless glands, control much of the functioning of the internal organs. So impressed was Brown-Séquard by the role of hormones in energizing the animal body and supporting its stability that he began to experiment with them in an effort to rediscover youth.

  In 1889, when he was seventy-two years old, Brown-Séquard reported to the French Academy of Sciences that he had been conducting self-experiments in rejuvenation. His method was to crush the testicles of guinea pigs or dogs and innoculate himself with a solution of the fluid thus obtained. Within three days of starting the treatments, he boasted, “I ha
d recovered at least all of my former vigor…. My digestion and the working of my bowels have improved considerably too…. I also find mental work easier than I have for years.” And he added that he had regained his sexual prowess.

  Unfortunately, inoculating the same material into others helped no one but Brown-Séquard. The testicular juice may not have helped him very much either, because he died five years later without demonstrating so much as the most minimal objective evidence that he had accomplished anything in the interim except to age in the usual manner of septuagenarians.

  Brown-Séquard’s attempt to regain his youth became such a target of derision that it besmirched his scientific heritage. But that did not deter others from involving themselves in similar undertakings, whether with testicular or ovarian extracts or the implantation of the organs themselves. Some of the experimenters were established scientists, but others were hucksters in search of a fast buck. A Kansas charlatan named Charles R. Brinkley became wealthy by implanting goats’ gonads into many of those suckers who are born every minute, to treat not only aging and impotence but high blood pressure as well. No amount of debunking clamor by physicians or the press in those economically deprived yet in some ways high-flying years of the 1920s and ’30s could dim his star, which soared to a height so lofty in the firmament that he eventually ran for governor of his state, electioneering from his own radio station. There is not a shred of evidence that any animal’s testicles, ovaries, or similar implanted or injected tissue ever helped so much as a single man or woman to return to youth or sexual potency, nor did it result in other of the consummations devoutly to be wish’d. No one’s aging process was halted, and no one became younger.