aging and regenerative medicine

Aging and Regenerative Medicine

scientists begin to understand the age-imposed decline in the regenerative capacity of stem cells (Conboy, Yousef, and Conboy 2011). These advances in regenerative medicine raise a host of ethical, legal, and social questions that health-care providers, scientists, and policymakers will need to consider. These questions and concerns include definitions, source materials, appropriate applications, potential risks, and accessibility, as well as the impact on the environment and social structures (Glenn and Boyce 2012). AGING AND LONGEVITY

Regenerative medicine, by definition of the National Institute of Biomedical Imaging and Bioengineering, is “a rapidly growing multidisciplinary field involving the life, physical and engineering sciences that seeks to develop functional cell, tissue, and organ substitutes to repair, replace or enhance biological function that has been lost due to congenital abnormalities, injury, disease, or aging” (US Department of Health and Human Services 2005, 3). While the search for the “fountain of youth” has long been considered merely a fantasy, advances in regenerative medicine and biogerontology in the twenty-first century suggest that “the aspiration to modify the biological processes of ageing in humans—and thus delay the onset of all age-related disadvantages, as well as compress morbidity and mortality—may actually be achievable” (Farrelly 2010, 385). Although it has been demonstrated that human cells’ ability to divide is limited to approximately fifty times, after which they simply stop dividing (known as the Hayflick limit theory of aging), research on the restoration of telomeres to the end of their chromosomes has shown that the changes associated with aging can be slowed down or even reversed (Jin 2010). The debilitating lack of organ maintenance in the old could be ameliorated and, perhaps, even reversed, as

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While humanity has always been preoccupied with discovering the “fountain of youth,” advances in the field of biogerontology and regenerative medicine hold the promise of enabling scientists to regenerate damaged tissues and organs in vitro or in vivo, developing therapies for previously untreatable diseases and conditions, combating rising health-care costs, solving the shortage of transplantable organs, and offering improved quality of life for an aging population (Glenn and Boyce 2012). Where some see only benefit in the ability to slow, stop, or even reverse the aging process, others have argued that aging is inevitable and have warned that extending longevity could lead to undesirable consequences, such as social upheaval and a straining of limited resources (Hayflick 2000). AGING AS A DISEASE

The question of intervening in the aging process depends on whether or not aging is seen as a disease. The medical profession has not yet come to a consensus about treating aging as a disease, but opinions are in a state of flux.

ETHICS, SCIENCE, TECHNOLOGY, AND ENGINEERING, 2ND EDITION

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AGING AND REGENERATIVE MEDICINE

In the Stone Age and throughout much of the history of humanity, human life expectancy, without the intervention of modern medicine, is estimated to have been around 20 to 34 years (Bostrom and Roache 2007). As of 2012, in the United States, people who survive to age 65 can expect to live an average of 19.2 more years, nearly 5 years longer than people age 65 in 1960. In 2009 the life expectancy of people who survive to age 85 was 7 years for women and 5.9 years for men (Federal Interagency Forum 2012). These statistics reflect that there has been almost a tripling of life expectancy for humans in the last few thousand years. This gain is primarily the result of social and technological developments, such as sanitation, medicine, education, and nutrition (Bostrom and Roach 2007). The trend in extending longevity will continue; insurance companies have started banking on the notion that the first person to live to 150 years of age is now alive (Prudential 2013).


According to the Merriam-Webster online medical dictionary (2013), a disease is

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an impairment of the normal state of the living animal or plant body or one of its parts that interrupts or modifies the performance of the vital functions, is typically manifested by distinguishing signs and symptoms, and is a response to environmental factors (as malnutrition, industrial hazards, or climate), to specific infective agents (as worms, bacteria, or viruses), to inherent defects of the organism (as genetic anomalies), or to combinations of these factors.

At first blush, this definition would certainly cover most symptoms and impairments that result from the process of aging; pathological changes and morbid processes are generally the criteria used in determining age in autopsies or when obtaining a medical history is impracticable (Caplan 2005). The common risk factor for two major causes of death worldwide, cancer and cardiovascular disease, are age; postpone aging, and one postpones these diseases (Bourzac 2012). Yet there are those who argue that “ageing is not a disease because it is not a dysfunction” (Schramme 2013, 182). That is, to explain further, functions are relative to age, so processes that are functional earlier in life (e.g., reproductive ability) are not necessarily functional later in life. Others argue that because aging is “natural”—or “inevitable” and “universal”—there should not be intervention; but viral infections, gingivitis, acne, hypertension, and tooth decay are all of those things, but they warrant intervention. Considering the arbitrariness of these criteria, it is not intrinsically wrong to try to reverse or cure aging (Caplan 2005). At least one author argues that a new model of disease has emerged based on numerical deviations rather than symptoms and that it arose in concert with the development and use of safe, effective, marketable, and highly profitable prescription drugs (Greene 2007). This suggests that if treating aging as a disease is profitable, then aging will be treated as a disease because of market forces. RESEARCH AND ETHICAL CONSIDERATIONS

Source Materials. One of the primary ethical conundrums in using regenerative medicine is the source of the stem cells that are used. Adult stem cells, which have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis, do not pose an ethical challenge; but even though they are pluripotent, they are somewhat limited in their capacity to differentiate. Embryonic stem cells, by contrast, are totipotent—able to differentiate into any cell in the body. Embryonic stem cells are controversial

because of differing beliefs regarding the moral status of embryos. Those opposed to human embryonic stem cell (hESC) research believe that the fertilized egg has the moral rights of personhood and that the destruction of blastocysts devalues human life and dignity (Glenn and Boyce 2012). In the center of the spectrum of beliefs are people who do not object to the use of existing (or future) frozen blastocysts that are destined to be destroyed, rather than used for reproductive purposes, to derive new hESCs for research, but they do not want new blastocysts created specifically for experimentation. The current policy in both the United States and Canada is that the federal government will pay only for research conducted with stem cells harvested from leftover embryos developed via in vitro fertilization procedures, and only with the donors’ consent (Glenn and Boyce 2012). To avoid this ethical controversy, researchers have found ways of creating induced pluripotent cells (iPCs), which are adult or midrange stem cells (such as those found in umbilical cord blood or menstrual blood) that have been used to successfully reprogram skin cells to behave like hESCs (Chan and Harris 2008). The area of iPC research is attractive for several reasons, including the following: first, it does not require the gathering and use of human eggs; second, it is genuinely gender neutral because it does not impose a disproportionate burden on one gender over the other, in terms of the risks and burdens of egg collection/ donation (Glenn and Boyce 2012). Therapy versus Enhancement versus Altering Human Nature. One of the more controversial areas of research within the field of regenerative medicine involves brain implants—namely, the potential not only for brain repair or axon regeneration but also for the merger of artificial intelligence with human capabilities (Acey 2013). The ethical, legal, and societal concern is that merging humans with technology would change what it means to be “human” or a “person” and change basic human nature (Glenn 2003). Although technologies often start out for therapeutic use, use for enhancement often follows. Brain implants that create interfaces between human neural systems and computers would allow for (1) the improvement and augmentation of human capabilities; (2) the advent of “human” immortality through cloning and the implantation of bioelectronic chips with the uploaded emotions, memories, and knowledge of the source human; and (3) the possibility that humanity may be replaced by the next stage in guided evolution (Glenn and Boyce 2012). Access. With a widespread aging population, regenerative medicine will be in peak demand in the decades to come. As the American Medical Association notes, equal access to health care is also an ethical issue:


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Caplan, Arthur L. 2005. “Death as an Unnatural Process: Why Is It Wrong to Seek a Cure for Ageing?” EMBO Reports 6 (supp. 1): S72–S75.

Equality of opportunity is essential for each of us to fulfill the American promise of life, liberty, and the pursuit of happiness, and personal health is an essential ingredient to ensure opportunity. (Levine et al. 2007, 15)

Cibelli, Jose, Robert P. Lanza, Keith H. S. Campbell, and Michael D. West, eds. 2002. Principles of Cloning. Amsterdam: Academic Press.

The implementation of the Patient Protection and Affordable Care Act of 2010 shows some promise of significant gains in coverage and access to basic care for populations in need, but the promise is tempered with concerns about enrollment coverage and sustainability. Only time will tell if regenerative medicine will become standard or a luxury of only a privileged few. Biotech Ethics; Medical Ethics; Posthumanism; President’s Council on Bioethics.

SEE ALSO

BIBLIOGRAPHY

Acey, Madeleine. 2013. “Brain Implants: Restoring Memory with a Microchip.” CNN, May 8. http://www.cnn.com/2013/05/ 07/tech/brain-memory-implants-humans Binstock, Robert H. 2003. “The War on ‘Anti-aging Medicine.’” Gerontologist 43 (1): 4–14. A scholarly analysis of how mainstream biogerontologists are countering the practitioners of antiaging medicine who biogerontologists believe are exploiting the public’s ignorance of the science for financial gain.

Bostrom, Nick, and Rebecca Roache. 2007. “Human Enhancement: Ethical Issues in Human Enhancement.” In New Waves in Applied Ethics, edited by Jesper Ryberg, Thomas Petersen, and Clark Wolf, 120–152. New York: Palgrave Macmillan.

Chan, Sarah, and John Harris. 2008. “Adam’s Fibroblast? The (Pluri)potential of iPCs.” Journal of Medical Ethics 34 (2): 64–66.

Conboy, Irina M., Hanadie Yousef, and Michael J. Conboy. 2011. “Embryonic Anti-aging Niche.” Aging (Albany, NY) 3 (5): 555–563. Farrelly, Colin. 2010. “Equality and the Duty to Retard Human Ageing.” Bioethics 24 (8): 384–394. Federal Interagency Forum on Aging-Related Statistics. 2012. “Health Status.” http://www.agingstats.gov/Main_Site/Data/ 2012_Documents/Health_Status.aspx Glenn, Linda MacDonald. 2003. “Biotechnology at the Margins of Personhood: An Evolving Legal Paradigm.” Journal of Evolution and Technology 13: 35–37. Glenn, Linda MacDonald, and Jeanann S. Boyce. 2012. “Regenerative Nanomedicine: Ethical, Legal, and Social Issues.” In Nanotechnology in Regenerative Medicine, edited by Melba Navarro and Josep A. Planell, 303–316. New York: Humana Press/Springer. Greene, Jeremy A. 2007. Prescribing by Numbers: Drugs and the Definition of Disease. Baltimore: Johns Hopkins University Press. Gruman, Gerald J. 2003. A History of Ideas about the Prolongation of Life. New York: Springer. First published 1966 by the American Philosophical Society. Probably the best history ever written on the evolution of human thought about longevity from the first written records until 1800.

Hall, Stephen S. 2003. Merchants of Immortality: Chasing the Dream of Human Life Extension. Boston: Houghton Mifflin. Developments in the fields of research on aging, stem cells, regenerative medicine, and cloning are considered in this well-written and carefully researched history of these fields. Biological advances, political positions, and ethical debates are covered in detail.

Hayflick, Leonard. 1994. How and Why We Age. New York: Ballantine Books. An overview of the aging process written for the lay reader with a chapter on the probability and desirability of intervention.

Hayflick, Leonard. 2000. “The Future of Ageing.” Nature 408 (6809): 267–269. Hayflick, Leonard. 2001. “A Brief History of Cell Substrates Used for the Preparation of Human Biologicals.” In Developments in Biologicals, vol. 106, Evolving Scientific and Regulatory Perspectives on Cell Substrates for Vaccine Development, edited by Fred Brown, Andrew M. Lewis Jr., Keith Peden, and Philip Krause, 5–23. Basel, Switzerland: Karger. Hayflick, Leonard. 2004. “Aging: The Reality; ‘Anti-aging’ Is an Oxymoron.” Journal of Gerontology A 59 (6): B573–B578.


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The same report notes that to be successful, the contents and limits of health-care benefits must be established through an ethical process and the health-care system must be sustainable. To ensure fairness and equity in coverage decisions, the practical application of the following principles would be useful: transparency, participation (of stakeholders), equitableness and consistency, sensitivity to value, and compassion. While this would be ideal, many questions remain unresolved: Will regenerative medicine be available only to a privileged few who can afford it? Can health care be comprehensive and include regenerative medicine, while at the same time being equitable and sustainable? Is individual responsibility and accountability incompatible with sensitivity to value and compassion?

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Bourzac, Katherine. 2012. “Interventions: Live Long and Prosper.” Nature 492 (7427): S18–S20.

Most Americans understand this: 72 percent think our society should ensure universal access to health care, and 60 percent consider it to be a moral rather than a strictly political or economic issue. We hold that three core American values are at stake: equality of opportunity, justice, and compassion.

The failure to define common terms in the field of gerontology has contributed to the many conceptual misunderstandings that have hindered progress and contributed to serious communication failures.

Hayflick, Leonard, Stanley Plotkin, and Robert E. Stevenson. 1987. “History of the Acceptance of Human Diploid Cell Strains as Substrates for Human Virus Vaccine Manufacture.” Development of Specifications for Biotechnology Standards 68 (1987): 9–17.

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Details how the struggle to have normal human fetal cells used for the production of many of the world’s human virus vaccines was ultimately won. The early use of primary monkey kidney cells for this purpose revealed contamination with several dangerous viruses. Yet it took more than a decade to overcome the scientific, political, and economic resistance to have them replaced with the safe, normal, human fetal cell strain WI-38 discovered by Leonard Hayflick. Many safe and efficacious vaccines made in Hayflick’s human fetal cells have since been administered to almost one billion people.

Jin, Kunlin. 2010. “Modern Biological Theories of Aging.” Aging and Disease 1 (2): 72–74. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC2995895/ Levine, Mark A., Matthew K. Wynia, Paul M. Schyve, J. Russell Teagarden, David A. Fleming, Sharon King Donohue, Ron J. Anderson, James Sabin, and Ezekiel J. Emanuel, for the Ethical Force Program. 2007. “Improving Access to Health Care: A Consensus Ethical Framework to Guide Proposals for Reform.” Hastings Center Report 37 (5): 14–19. Merriam Webster. 2013. “Disease.” Accessed September 1. http:// www.merriam-webster.com/medical/disease Olshansky, S. Jay, Leonard Hayflick, and Bruce A. Carnes. 2002. “No Truth to the Fountain of Youth.” Scientific American 286 (6): 92–95.

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A declaration with much supporting evidence that, in the early twenty-first century, there is no way of intervening in the fundamental aging process in humans. Signed by fifty-one of the world’s leading researchers on aging.

Patient Protection and Affordable Care Act of 2010, Pub. L. No. 111-148, §2702, 124 Stat. 119 (2010). http://www .gpo.gov/fdsys/pkg/PLAW-111publ148/pdf/PLAW111publ148.pdf Prudential. 2013. “New Prudential Ad Debuts during Super Bowl: Ad’s Live Experiment Highlights the Financial Challenges of Living Longer.” News release, January 31. http://news. prudential.com/article_display.cfm?article_ id=6490 Schramme, Thomas. 2013. “‘I Hope That I Get Old before I Die’: Ageing and the Concept of Disease.” Theoretical Medicine and Bioethics 34 (3): 171–187. World Health Organization. 2012. “Defining Disease Types I, II, and III.” http://www.who.int/phi/3-background_cewg_agenda_ item5_disease_types_final.pdf U.S. Department of Health and Human Services (DHHS). 2005. 2020: A New Vision—A Future for Regenerative Medicine. Washington, DC: DHHS. http://www.scribd.com/doc/ 37338866/2020-A-New-Vision-a-Future-for-RegenerativeMedicine

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Linda MacDonald Glenn


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