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BOOK REVIEW |
Professor of Community Health and Associate Dean of Medicine for Public Health Brown University Providence, RI 02913
The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal, edited by Stephen G. Post and Robert H. Binstock. Oxford University Press, New York, 2004, 463 pp., $59.95 (cloth).
The Fight Over the Future: A Collection of SAGE Crossroads Debates that Examine the Implications of Aging-Related Research, edited by Sage Crossroads, iUniversity, Inc., New York, 2004, 91 pp., no price listed.
An age-old debate has recently been rekindled. Increasingly polarized arguments are being made regarding the appropriate goals and likely future of aging research. On the one hand, arguments center on several aspects of the question of just what is the optimal focus of aging research; some discussants assert that the only appropriate biomedical research is that aimed at conquering the diseases associated with old age, thereby improving function and quality of life of older persons. This group asserts that it is inappropriate and perhaps unethical to expend energy and resources in efforts to unlock the secrets of the aging process. Others argue that the study of the biology of aging has been improperly neglected, citing what they view as an imbalance of research funding by the National Institute on Aging (NIA) and other federal agencies, with too little attention being paid to understanding the basic biological processes of aging. Supplementing these anchoring positions are those who claim that much is already known and that this knowledge should be immediately applied to slowing the aging process in humans and alleviating its consequences. Still others argue that many of the claims made for interventions to reverse or slow the aging process are overly optimistic at best and, at worst, have the smell of "snake-oil" remedies about them. To make these arguments all the more complex, another layer of philosophical analysis is added, examining the questions of whether indeed scientists ought to strive to expand the human life span and what the potential consequences of such an expansion in longevity might be.
In the April issue of The Gerontologist, Tom Johnson (2004) reviewed books by Lenny Guarente (2002), Ageless Quest: One Scientist's Search for Genes that Prolong Youth, and Stephen Hall (2003), Merchants of Immortality: Chasing the Dream, of Human Life Extension, that provided recent historical perspectives on the search for genetic and other strategies to understand and increase the human life span. The Spring 2004 edition of the Public Policy and Aging Report focused on prolongevity and anti-aging medicine. The current books upon which this essay review is based take a broader perspective, seeking to put aging science into a social and cultural context.
The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal, edited by Stephen G. Post and Robert H. Binstock, provides a collection of essays from ethicists, philosophers, sociologists, political scientists, and biologists examining what is possible and what is likely, as well as what ought to be pursued in research to extend human longevity. These thoughtful, well-documented, and scholarly essays provide a solid base for understanding the increasingly heated debates around longevity research. The Fight Over the Future: A Collection of SAGE Crossroads Debates that Examine the Implications of Aging-Related Research offers transcripts of discussions sponsored by "SAGE Crossroads," a collaborative project between Science Magazine and the nonprofit Alliance for Aging Research. As intended, these transcripts provide lively, entertaining, and off-the-cuff perspectives from leaders in the field, structured as debates, enhanced by questions from the audience of experts in attendance and via the web.
The debate as presented in these books can be organized into three overarching questions. What is the appropriate focus of biomedical research on aging? What are the possibilities and promise of life extension interventions? What are the likely social, economical, and political consequences of the success of such research? Each is discussed briefly below.
What Is the Appropriate Focus of Biomedical Research on Aging?
Gerontologists concentrate their research on a variety of areas of science. Some focus on specific diseases of later life, examining the incidence, prevalence, and risk factors of such diseases. They study the etiology of these age-related diseases, seeking preventive strategies, early detection, treatments, and cures. Although their primary focus is not on life extension per se, their successes do have the outcome of improving quality of life for older persons and, in fact, adding to increases in life expectancy, if only modestly. There are also biogerontologists who focus on the basic processes of aging, seeking to separate out these phenomena from factors associated with diseases and conditions common among older persons. Their focus is on the genetic and metabolic events that determine the rate of aging within the organism. Of course, the dividing line between these two groups of researchers and their goals is not always clear and distinct.
It should be noted that the major gains in average life expectancy during the past 100 years have not been attributable to interventions that directly impact basic processes of aging but, rather, to public health and medical strategies that prevent disease, provide more individuals the opportunity to grow old, and deliver healthier humans into old age. Whether such interventions have had or will have noticeable impact on maximum human life span remains a matter of disagreement among demographers. Nonetheless, the near doubling of average life expectancy that took place during the past century in the United States is occurring at an accelerated pace in many developing countries around the world and is primarily attributable to advances in better living conditions and disease prevention and treatment. Although there are a few commentators who have argued that research on prevention or treatment of diseases of old age is at times inappropriate (Callahan, 2002), most would agree that disease-specific research should be supported, even for diseases of the very old. Moreover, much of the science that has extended life expectancy to date has had its primary focus on disease at younger ages, with the identified prevention and intervention strategies then applied to individuals of all ages.
Those who argue that there is an imbalance in federal funding of research with an overemphasis on the study of diseases of the old often note that a large proportion of the NIA's budget is directed toward Alzheimer's disease and other dementing illnesses associated with aging (Adelman, 1995). In the early 1990s the NIA was designated by Congress as the lead federal agency for Alzheimer's research, and in subsequent years, substantial increases in the NIA appropriation were targeted toward Alzheimer's-related research. Prior to that time, relatively little funding from any federal source supported Alzheimer's disease research, despite the heavy toll taken by the disease. Advocates for Alzheimer's research, including Dr. Robert Butler, the founding director of the NIA, helped to redefine cognitive loss and dementing illnesses in the elderly. They challenged the commonly held belief that this was a normal part of aging and advocated the position that dementia in aging is an abnormal process meriting research into the etiology of the underlying diseases, strategies for symptom relief, curative treatments, and prevention. Increased attention and improved funding mobilized the scientific community, improving the status of research not only on Alzheimer's disease but also for other areas of aging research as well. During this same period, funding for basic research on the biological processes of aging also increased, though, admittedly, not at the same rate as that for Alzheimer's research. It should also be noted that, due to the nature of the National Institutes of Health research expenditure reporting systems, much of what is "counted" as Alzheimer's research has direct relevance to our understanding of the basic processes of aging, particularly in the central nervous system. Accordingly, the question of relative expenditures across categories at the NIA is complex, but to staunch advocates of basic aging research, the absolute amount expended remains too low.
Among the three major research goals in the NIA strategic plan (National Institute on Aging, 2001), the second is to "unlock the secrets of aging, health, and longevity" with a sub-goal of identifying "factors that pace the aging process and slow the clock." Understanding the basic processes of aging remains among the key goals of the NIA. There are, however, those who would argue that any research into the basic processes of aging aimed at increasing longevity (prolongevity) is an inappropriate expenditure of federal monies, for several reasons. Binstock and Post summarize these arguments in their opening chapters of The Fountain of Youth, with more detailed arguments provided by Leon Kass and Eric Juengst in later chapters. The arguments range from the philosophical—that a sense of finitude is important to the individual and to societies, conferring interest and engagement, seriousness and aspiration, beauty and love, and virtue and moral excellence (Kass)—to the societal—issues of justice, scarce resources, and appropriate familial roles (Audrey Chapman). Some in this group argue for a moratorium on such research until the social, political, economic, and familial issues can be worked through, while others advocate for an absolute ban on such research because of the implications for our very sense of self and place in time and society. Yet others note that whether or not there is a federal moratorium on such research, there is strong public interest in the interventions that such research might provide, and therefore private funding is and will continue to be available in large amounts. Many in this group would argue that having federal funding and therefore a public eye on the research conducted is imperative in tracking progress, applying appropriate safeguards, controlling quality, countering unsupportable claims, and influencing the appropriate application of such research for human beings.
What Is the Possibility and Promise of Life Extension?
The second key question addressed by these volumes relates to the probability or even possibility that prolongevity research will have a major impact on human life span. Again, there is a strong mix of opinion among biogerontologists. This disagreement can be attributed, in part, to the anticipated time frame of potential advances, but also is embedded in perspectives regarding the mechanisms at work in biological human aging. Section II of The Fountain of Youth: Cultural, Scientific, and Ethical Perspectives on a Biomedical Goal, provides overviews of the major avenues of prolongevity research, with opinions regarding the likely success of these avenues.
During the past decade, substantial progress has been made in understanding the genetics of aging in lower life forms, as well as the function of homologous genes in humans. Single gene mutations have been shown to more than double life span in nematode worm populations, and different mechanisms by which separate genes increase life span have been identified. Moreover, the pathways through which multiple genes express themselves, each in a different step of the process in the simplest of organisms illustrate the complexity of developing a deliberate genetic intervention to extend human life span. There are other aspects of genetic research with important implications for prolongevity, and these are associated with repair of DNA damage and other harm at the cellular level. These repair mechanisms are important for dealing with the stochastic damage that occurs with time.
Another important area of genetic research is the telomere story. In most types of cells, telomeres—structures found at the very end of chromosomes, a bit like the end of a zipper—shorten with each replication of the chromosome and cell division. Some have hypothesized that the telomere helps maintain the integrity of the chromosome as the cell divides and that preserving the length of telomeres would result in a greater number of healthy cell divisions and longer life for the tissue. Expression of the enzyme telomerase has been associated with maintenance of telomere length, but is also expressed in "immortal" cancer cells, complicating any intervention intending to use telomerase to extend longevity. My criticism of The Fountain of Youth is that research into the genetics of aging is not given the same level of attention as other aspects of research on aging and longevity.
Among the most successful interventions to extend life span in lower animals is caloric restriction, in which animals are placed on diets with adequate nutrients but are one fourth to one third lower in calories than the diets of control animals that feed ad libitum. Populations of calorically restricted animals experience life spans that are 30%–40% longer than control animals. Perhaps, more importantly, these calorically restricted animals remain healthier longer into their life spans, with good physical function and fewer tumors than the controls. Gemma Casadesus and her associates provide a rich discussion of this arena of research and its potential application to humans in The Fountain of Youth.
Other interventions are discussed with considerably more skepticism concerning current application to human populations. While it is recognized that treatment of declining levels of hormones, enzymes, proteins, and other biological factors may provide benefit in laboratory animals, the data from human studies, where available, tend to be more complex and raise serious concerns regarding harmful side effects and long-term consequences. Premature application of research findings or, even worse, interventions derived from untested hypotheses risks true harm to individuals who may have difficulty separating claims from reality, possibility from promise. An overview of these issues presented in brief in the Public Policy and Aging Report (2004) and in the June issue of The Gerontologist (Mehlman et al., 2004) is discussed in more detail in The Fountain of Youth.
Suffice it to say, those looking for a "silver bullet" to slow or reverse the aging process are bound to be disappointed in the short run and are unlikely to experience such an intervention in our lifetime. However, over the longer run, there may well be developed a "silver shot-gun" shell that targets multiple aspects of aging processes, making minor adjustments, which in the aggregate have substantial impact. This will result from painstaking research, not only into the short-term effects of each component, but also into the aggregate and long-term effects of the package of interventions. In any event, it will be difficult, if not impossible, to disentangle interventions aimed at increasing longevity from those interventions intended to improve health and function. So perhaps we are in search of the fountain of health, rather than the fountain of youth.
What Are the Likely Social Economic and Political Consequences of the Success of Prolongevity Research?
The discussion of the implications of success of such research is broad and far-reaching. From a social justice perspective, one consideration is just who would have access to life-extending interventions. It could be argued that, as with many new pharmaceuticals, life-extension medications are likely to be quite expensive when first available, and therefore, only the very wealthy would have access, leading to a widening in the gap between the haves and the have-nots. Another level of social justice analysis involves distribution of scarce resources across generations and intergenerational obligations. If substantial increases in longevity could be achieved for populations or subpopulations, a rethinking of major social institutions, such as Social Security and Medicare, as well as population norms for retirement age, family relationships, and work roles would be required. As Chapman notes in her chapter, "Human societies are built around expectations of a life cycle of limited duration. Increasing the life expectancy would challenge these arrangements and the web of social relationships based on them" (p.341).
I recommend The Fountain of Youth to those wishing to learn more about the debates surrounding life extension. The text is accessible, and the authors were chosen for distinct points of view. It would behoove each of us with an interest in gerontology and the future of aging populations to consider the possibility of life extension and its implications for individuals, families, and societies. If we do not anticipate and address the promise and potential challenges of life extension, we will be doomed to a reactive and much less effective response to current arguments regarding research goals, prolongevity interventions, and the context of aging and longevity.
References
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