Tuesday, January 01, 2002

Ponce de León Lives

The Dream of Eternal Life: Biomedicine, Aging, and Immortality

By: Walter Donway

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We are the first generation on earth that can ask, as a matter of science, not religious doctrine, whether man must die. Just a decade or two ago the question would have been posed only in the most general terms (“Will we ever discover genes for immortality?”) and viewed as the stuff of science fiction. Today, we might frame the question (in very abbreviated form) as follows: Since scientists have already identified a “death gene” in the threadworm C. elegans, and, by knocking it out, have doubled the worm’s life span, and since Harvard University researchers have identified a DNA segment coding for a gene strongly correlated with early death in humans, when might there be successful gene therapy for the disorder called death?

In protest, there are those who will remind us of the miles of rugged, unknown scientific terrain lying between today’s knowledge and any direct assault by serious scientists on death’s citadel. They will be right, yet the discussion itself will focus on specific problems and on the pace of molecular biology in our era. In reflecting on that pace, consider that the 1998 German edition of The Dream of Eternal Life by Mark Benecke, a scientist at the University of Cologne, had to be extensively revised for the 2002 English translation because the Human Genome Project had been completed —to the surprise of everyone except the entrepreneurs who snatched the task away from government and forced its completion.

The Dream of Eternal Life does several things well, without making them its goal. For example, Benecke’s discussion of research on the genetics of aging and death handles the technicalities of DNA research in some of the most readable, engaging terms I have encountered. He is also lively and imaginative about clinical approaches to extending life through transplantation; what diet, nutrition, exercise, reducing stress, or megavitamins and melatonin may contribute to longevity; and cultural expressions of the ancient human hope to avoid death.

The human brain and personality are at the core of Benecke’s discussion because, of the two types of immortality—the survival of our genes and the survival of our person—it is the latter that rivets our attention.

The book’s achievement, however, is that it hooks us on the question of immortality and then, firmly in command of our motivation, drives us down the gauntlet of scientific and technological advances, possible futures, and ethical dilemmas that make up biomedical science today. The Dream of Eternal Life is about choices already being made (albeit usually for us, not by us) as headlong research in biology is translated into medical practice. Unsurprisingly, the human brain and personality are at the core of Benecke’s discussion because, of the two types of immortality—the survival of our genes and the survival of our person—it is the latter that rivets our attention. As Benecke takes us through the options, we see that the key question is: What do we mean by the survival of the self?  That reduces, in turn, to questions about the brain, brain death, consciousness, and our ethical convictions about the value of the individual in balance with the species. Your own convictions on the latter will determine your level of satisfaction with The Dream of Eternal Life.

DEATH GENES AND THE DNA OPTION

As Benecke describes it, our best prospect for postponing death, perhaps indefinitely, would seem to lie in understanding the human genome. After all, aging and death must be coded into our DNA. “Survival” and “death” genes have been found in two animals, C. elegans and the fruitfly. The death genes appear to perform several functions. One is programmed cell death, or apoptosis: the instructions to our cells to commit suicide as when, for example, the human fetus sheds its finger webs or billions of extra brain cells die when an infant no longer requires them as scaffolding for its developing brain. Indeed, the only cells in our bodies that are not programmed to die eventually, that are immortal, are cancerous cells. Most of our other cells replace themselves throughout our lives, some more rapidly than others. The cells in lip skin die and are replaced every two weeks; cells in our lungs have an 81-day life span. In this way, our bodies renew themselves several times during our lives. Why not just keep going?

The answer is that cells are programmed to replace themselves a certain number of times, much more slowly as we age, and then to stop. This is what aging and dying are about. Since it is certain that these limits on cell divisions are coded into our genes, it is equally certain that scientists will find the genes that control it. When such a gene was found in C. elegans, and knocked out by a well-known process, the two-week life of the little worm was extended enormously to four weeks. We know how to implant new DNA into our cells, freighting it in aboard bacteria such as e. coli—so what about reengineering things someday to prolong cell division, perhaps indefinitely?

Naturally, the obstacles to such a procedure appear today to be insurmountable, or at the least daunting. But that, of course, is the point: It is remarkable enough that we can begin to enumerate the obstacles (for example, that cells accumulate waste and are thrown out with it, a baby-and-the-bathwater problem) and talk about what it would take to overcome them. That is a new conversation about immortality. Benecke, who is judicious and appropriately skeptical, as befits a scientist, will not commit himself on the possibility of immortality by the route of inserted DNA. Although the eventual technical feasibility of gene therapy for death is unknown, he appears to have firm ethical objections to it.

He points out that evolution had good reasons for writing death into the instructions for life. Without death there soon would be no room for new generations, which are indispensable for adaptation by a species to new environmental conditions. By begetting constant, multiple variations in our characteristics and genome, the human species is better prepared to survive future catastrophic changes in the environment. Such cataclysms have occurred at least three times in earth’s history, wiping out some 65 percent of existing species. In each case, a remnant of individuals, slightly better adapted to the new conditions, was able to survive and repopulate the earth.

Benecke argues that immortality would put an end to this process for humans, and that “it would hardly be imaginable that such a development could bring any adaptational advantage. Immortality would mean the final death of the species.”

If, forsaking biological evolution for immortality, we do not succumb to some unexpected environmental cataclysm, then surely we will succumb to overpopulation. 

AN ENVIRONMENTALIST’S WARNING

Readers will readily recognize this line of argument: A certain new technology (in this case molecular biology), projected onto a world scale, threatens our survival. Ultimately, Benecke’s stand on the question of immortality is an environmentalist one. If, forsaking biological evolution for immortality, we do not succumb to some unexpected environmental cataclysm, then surely we will succumb to overpopulation. The penultimate chapter of The Dream of Eternal Life is about Gaia, our mother earth, with the standard warnings about the threats of species extinction, global warming, overfishing, and overpopulation. One begins to wonder whether the author’s agenda here is to warn mankind not to further outrage Gaia by the hubris of the ultimate biotechnology.

But I wonder: If anxiety for earth’s fate has not persuaded us to reduce our consumption of oil, or even our use of so-called greenhouse gases in our refrigerators, is it likely to restrain us from exploiting biotechnology to achieve immortality? If the means become available to prolong life indefinitely, how many people who can afford to buy immortality will defer to the argument that their choice, if universalized, would result in overpopulation? I suppose about as many as now limit their family size exclusively on demographic considerations— or perhaps far fewer, since we are speaking here of volunteering to die. The procedure could be made illegal, of course, but that summons visions of high-priced black-market clinics in Switzerland or South Africa or Mexico. In 1994, a German pediatrician and an American plastic surgeon were reported to have set up shop in a side wing of a Russian clinic to provide thousands of indigent women with abortions. They froze and processed the fetuses and, for five-digit fees, injected the live cells into patients from all over the world as a supposed preventive for disease. (Benecke does not tell us whether the Russian government officially tolerated this.)

The lesson may be that when we frame ethical questions about who shall live, how long, and how, we would do well to be sure of our footing. Benecke builds his case on the basic premise that the good of the species should trump the interests of the individual. Sometimes he presents this as a biological principle, but in other contexts as an assumption of ethics. In framing such premises, it is important to ask, I think, if they will lead to conclusions that people are willing to live with. Or will ethics, including biomedical ethics, become but a platform from which to lament that mankind is not guided by ethical considerations? 

The problem with most attempts at achieving immortality is our brain, according to Benecke. 

TRANSPLANTS AND CYBORGS

Bracketing the ethical questions for now, what is our best shot at living beyond the current human life span—exceeding, say, even the record set by Jeanne Louise Calmet, who died in August 1997 at age 122? The problem with most attempts at achieving immortality is our brain, according to Benecke. Nature has worked out how to make an immortal organism. The multiarmed hydra, found in pond water, can generate new and identical organisms from pieces of its body; another simple organism also found in ponds, the volox, produces genetically identical daughters. These are, quite simply, clones; the offspring are as similar to the parent as identical twins are to each other. With the birth and survival of Dolly, a. k. a. sheep 6LL3, in 1997, the first large mammal had been completely cloned, meaning that information from an adult body cell supplied the entire blueprint for an offspring. Although some geneticists doubt that Dolly is a true clone, she was a major turning point; there is now little doubt that a human being could be cloned. Legislatures are enacting laws with criminal penalties against human cloning that, as scientists such as Gerald D. Fischbach, M.D., have testified, risk sweeping off the lab bench, along with cloning, techniques indispensable to progress against diseases.

Whatever the allure of cloning, it is not what most people mean by immortality. In some respects, immortality-via-cloning is more remote from eternal life than the “immortality” achieved by a great poet, playwright, or composer. None of my memories, ideas, or feelings is guaranteed to be carried forward by my cloned son. Even if my ideas and values (but, more predictably, my degree of intelligence and my temperament) were to become lodged in my biological replica, my satisfaction would be that of a teacher or an ordinary parent. Conceivably, I would face my death with more serenity; I would die with less sense that my private world was vanishing from the earth, but die I would. Unless there is a way to preserve the contents of my brain, my personality—my self—would perish.

Well, Benecke asks, how about brain transplantation? Science fiction? Certainly, but science, too. The brain is about the only major organ not yet successfully transplanted. The obstacles are awesome, to say the least. A decade ago, the simplest objection would have been that since the central nervous system cannot regenerate itself, there would be no way to hook the spinal cord of the body to the new brain. One of the biggest surprises of neuroscience in the 1990s, however, was the discovery that neurons do regenerate in parts of the brain, and even the severed spinal cord may one day be persuaded to reconnect.

If connecting up a transplanted brain (or just a neocortex) turned out to be possible, there would still be the problem of interfacing with a body that had spent a lifetime establishing signals with a different brain. A brain could find itself in a most uncomfortable new suit of clothes, when it leaves behind the arthritic body of a lifelong desk worker for the body of a 29-year-old rugby player who died of a gunshot wound.

The reader may begin to see how assessing the options for immortality becomes a veritable bioethics teach-in. Benecke’s skill is getting us to confront these ethical questions because we are intrigued, and even slightly persuaded, by the science that raises them. But are the medical scenarios that prompt the questions so outlandish, so far removed from reality, as to be only intellectual games?

Consider what Benecke has to say about a staple of science fiction, the cyborg, a robot in which a human brain resides. The premise is that the resident brain would command the robot’s movements. But the principle of operating a mechanical device solely by means of thoughts is now a reality. In developing prostheses for people unable to move, scientists have taught a person (and a monkey) to move a mechanical arm by thinking a command that is sent to a computer that initiates the motion. Or consider another cyborg encountered in science fiction, a brain floating in solution and able to transmit signals to a computer. Robert White of Case Western Reserve University kept a monkey brain alive apart from its body for three days. He was able to record brain currents similar to those of a rationally functioning brain.

ETHICS IN THE AGE OF BIOLOGY TRIUMPHANT

Although Benecke urges us to renounce certain possibilities of biotechnology in the name of our species, he does so with little conviction. He writes at one point: “Neither technology nor morality ever seriously limited the human struggle with death. Our will to do what is possible is greater than ever, and the ethical reservations of the scientific community regarding the application of gene technology to humans, animals, and plants have melted away at the turn of the millennium like snowflakes in spring.”

In the end, Bencke presents us with his recommendations (to wit, acknowledge our mortality, glory in it, and be content with the renewal of our species), but adds that human nature has shown no inclination to act on such recommendations: “if it is a matter of lengthening one’s own (valuable) life with new technology, who would want to turn down this possibility?”

Although obviously an intelligent, concerned scientist, and doubtless committed to his ideas, Benecke seems not to believe in the power of those ideas to motivate us when our vital interests are at stake.

Although obviously an intelligent, concerned scientist, and doubtless committed to his ideas, Benecke seems not to believe in the power of those ideas to motivate us when our vital interests are at stake. I sense in The Dream of Eternal Life more of resignation than of exhortation.

Morality is about ideals, but will we root those ideals in the realities of human nature—actual human capacities, needs, and requirements for life on this earth—or will we demand that human nature reshape itself to fit some other vision of the ideal? Through much of human history, moralists have chosen the latter, championing ideals created in the image of a higher being and higher realm, then condemning human nature for sinning against them. Is the ideal of sacrifice for the supposed long-term, greater good of our species any more consonant with human nature?

An age of biology can do better. We have the means, as never before, to understand human nature, man’s place in it, and the capacities that are his glory: reason and the creative power to shape nature to his values. We are more likely to define an ethos that affects the individual’s critical choices if we begin, not with the premise of species loyalty or deference to Gaia, but the reality of a species that survives by adapting nature to its needs, has no inherent limits to its knowledge, and experiences individual happiness as a self-justifying good.

The virtue of The Dream of Eternal Life is that it forces us to ask these questions.

EXCERPT

From The Dream of Eternal Life: Biomedicine, Aging, and Immortality by Mark Benecke. ©2002 by Mark Benecke. Reprinted with permission of Columbia University Press.

Cloning humans for the purpose of creating completely identical people fails because our biology does not entirely define our personality. Our personality is not mapped out in our cells but develops as we grow and experience the world. It seems logical to conserve our brains in their entirety, our whole consciousness—instead of mere strands of DNA—for the time when our bodies age, fall ill, and we plan for that second chance, that second life. 

Nowadays, some people even decide during their lifetimes that either their head or their entire body be frozen and preserved. If one day a cure is found for the disease that might have killed them, their bodies could be retrieved from their icy slumbers and they might be able to continue their lives. In cases in which only the brain could be retrieved, a new body would be needed. The optimal solution would be to “re-create” the very same body, that is, to clone it from its own cells. As just described, we cannot grow a new identical body from a single cell the way we can with plants. The hurdle is the complex structure of the human organism. Such a hurdle, however, might be circumvented, even if it could not be conquered entirely. If some smaller unit of a cell, a single strand of its DNA, for example, could be extracted (and stored early enough), containing the complete instruction set for the entire body, a complete human being could theoretically be reproduced in its original form.

Whether and how this would be possible was the subject of Michael Crichton’s novel Jurassic Park and Steven Spielberg’s film version of that novel. The subject of the sensational best-selling book and movie was not human beings but rather ancient creatures that lived hundreds of millions of years ago. In the imagined Jurassic Park, a modern “theme” park, dinosaurs were reconstructed. Insects fossilized in amber provided scientists with dinosaurs’ DNA. The idea behind it: the insects might well have feasted on the blood of living dinosaurs, and the preserved contents of their digestive tracts could contain the DNA necessary to clone actual dinosaurs. The question remains, of course, whether the preserved insects carried dinosaur blood or some other animal’s blood. In reality, the experiment would probably fail in its earliest stages. In the book and film, however, the scientists were faced with the problem that the extracted dinosaur DNA was broken in thousands of pieces. Naturally, the fictitious scientists manage to solve this problem. But could this ever really happen?

Up until a few years ago, it was absolutely impossible to entertain even the most remote possibility of the reproduction of dinosaur genes from the existence of old, broken apart DNA. Today, things are different. But first we must answer this question: why does DNA fall apart during the course of time, even when it is preserved in amber, protected from bacterial and other microbial attacks? The answer: DNA, itself an acid, is especially sensitive to acidic environmental influences. Acidic influences are found everywhere, including some soils of the earth, and in the decomposing remains of living things: plants and animals. DNA also breaks apart when exposed to sunlight. Sun, or more precisely, its ultraviolet radiation, does not take an immediate effect, but if a piece of tissue is exposed to light particles for hours, not to mention millennia, the DNA contained within it inevitably falls apart.

Previously, the DNA information strand could be read only when complete, like a book that must contain all its pages in sequence. The genetic blueprints could no longer be read by a single cell from individual fragments of DNA, especially if they were found in severely altered form, as they would surely be in the case of the remnant dinosaur DNA of Jurassic Park. Currently, it would take longer than the lifetimes of one hundred scientists to bring the fragments of DNA into sensible order.



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Scientific Advisory Board
Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Robert Malenka, M.D., Ph.D., Stanford University School of Medicine
Bruce S. McEwen, Ph.D., The Rockefeller University
Donald Price, M.D., The Johns Hopkins University School of Medicine

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