AGING AND REGENERATIVE MEDICINE

Advances made in research on the biology of aging and on the repair, replacement, and regeneration of tissues and organs (regenerative medicine) have drawn attention to old and new ethical issues. The principal concern among those who anticipate intervention in the aging process is whether or not attaining the power to do so is a desirable goal. The issues for those who are concerned about using human cells or tissues for research or therapeutic purposes are as follows: (1) whether the donor is, or is not, capable of giving informed consent; (2) if not, whether it is ethical for others to make that decision; and (3) whether the taking of one or a few potential lives for the benefit of many is ethically sound. When the source of the cells or tissues is a fetus or embryo, debate centers on the ethics of using tissue from induced or spontaneous abortion and when human life begins.

Where some see only benefit in the ability to slow, stop, or even reverse the aging process, others see an array of unintended consequences. There have been efforts made to intervene in the aging process throughout recorded history, and also warnings given that doing so could lead to undesirable consequences (Hayflick 2000).

The only way humans have succeeded in extending their longevity is by eliminating or delaying the appearance of disease or pathology. The greatest success occurred during the twentieth century when actuaries recorded the largest increase in human life expectancy at birth in developed countries.

The thirty-year increase from about forty-seven years in 1900 to about seventy-seven years in 2000 resulted from the implementation of public health measures for the control of acute infectious diseases, the discovery of antibiotics and vaccines, and the great advances made in other medical and health care disciplines. The result has been an enormous reduction in mortality rates in early life and a concentration of deaths in later years. In the early-twenty-first century, in developed countries, infectious diseases are no longer a leading cause of death. They have been replaced by cardiovascular disease, stroke, and cancer.

The maximum number of additional years attainable by the elimination of deaths caused by disease or pathology is between fifteen and twenty (Hayflick 2000). Once the leading causes of death are resolved, immortality will not occur, but we will have revealed the underlying, inexorable aging process that leads to causes of death attributable to the loss of function in some vital organ.

The Aging Process and the Ethics of Intervention

The process of aging is the inevitable loss of molecular fidelity that occurs randomly in the molecules of most animals after reproductive maturation. The status of biomolecules before they undergo age changes determines potential longevity or degree of resistance to age changes. No intervention that increases the stability of biomolecules before they undergo the aging process is known, nor is any method that can slow, stop, or reverse the aging process in humans.

The fundamental aging process increases vulnerability to what is written on the death certificates of older people. There seem to be no ethical issues that would oppose the goal of eliminating all causes of death attributable to pathology, violence, or accidents. But ethical issues do arise when considering interventions in either the aging process or the determinants of longevity. However, at this time, these can only be considered in the abstract.

Those who favor intervention in either the aging process or the determinants of longevity see a benefit in increasing the chronological time during which life satisfaction and good health are at their maximum levels. Critics see an array of ethical issues. These include the determination of when to intervene, because in order to determine when life satisfaction is at its greatest one must experience that time of life. If subsequent events reduce life satisfaction, choosing to return to a former happier state will depend on methods known to occur only in science fiction. It is also science fiction to expect that the environment that contributed to such better conditions will remain unchanged (Hayflick 2004).

Of the many bizarre scenarios that can be imagined, one would not be surprised to find families in which adult children, who chose not to slow or stop the aging process, are themselves biologically older than their parents, who did. Finally people who are highly satisfied with the quality of their lives are those most likely to contemplate arresting the aging process. It is not likely to be an attractive option for a substantial part of the world population, that is, the poor, oppressed, and sick.

Hundreds of thousands of septagenarians, and even older people, who are in relatively good health say that their current age is the happiest time of their lives. They contend that arresting the aging process at an earlier age would have either denied or delayed for them the contentment of retirement, travel, freedom from child-rearing responsibilities, and time to pursue personal interests that do not demand income generation. Human interactions depend to a substantial degree on perceptions of relative age. The destruction of those relationships could have enormous negative personal and societal consequences.

Presumably any method for intervening in the aging process would first become available to those able to afford expensive treatment and would be unavailable to those who could not. The intervention would also become available to antisocial and asocial persons, as well as those who do not harm or who benefit human civilization. The effect of manipulating the aging process could be disastrous for many human institutions.

Proposals to circumvent aging by replacing all old parts with younger parts are unlikely to be an option. For example, replacement of the brain could not only compromise one's sense of self-identity but the attendant loss of memory would erase the most essential part of what makes one human. Absent unrealistic scenarios in which a computer might be used to first upload the contents of an aging brain, cleanse it of old thoughts, and then download it to a new erased brain, it is unlikely that replacement of one's brain would ever be an attractive option. Also the eventual replacement of all old parts with younger or new parts in both animate and inanimate objects would result in both the physical and philosophical dilemma of having lost the original entity.

If it is true that mental processes continue to change for the better with age, one might equate the goal of arresting the aging process with that of arresting developmental processes. Arrested mental development in childhood is viewed universally as a serious pathology. If it is undesirable to retard the physical and mental development of a seven-year-old for ten years in order to gain an equivalent increase in longevity, arresting one's aging processes in later life should not be attractive for the same reasons.

Perhaps the least imperfect scenario would have each person live to be 100, while remaining in good physical and mental health, and then quickly and painlessly die at the stroke of midnight (as in "The Deacon's Masterpiece or The Wonderful One Hoss Shay" by Oliver Wendell Holmes [1857–1858]).

Humankind will probably not face these ethical issues in the near future because it is unlikely that biogerontologists will find ways to intervene in the fundamental aging and longevity determining processes for several reasons. First, most research done under the rubric of aging research in humans is done on age-associated diseases, the resolution of which cannot extend human longevity more than fifteen years. This accomplishment will not provide any insight into the fundamental aging process. The resources devoted to research on the underlying aging process are, by comparison, infinitesimal. Second, there are no generally acceptable criteria for measuring whether or not an intervention in humans is affecting either the aging process or the determinants of longevity. Finally, although the determinants of longevity might be altered, the aging process, because it is a fundamental property of all matter, is unlikely to be changed.

Regenerative Medicine Research and Ethical Considerations

The ethical issues that derive from research in regenerative medicine are more immediate than those that might result from intervening in the aging or longevity determining processes. In the early twenty-first century, several major advances are close to, or have become, reality (Cibelli, Lanza, Campbell, and West 2002).

The central ethical issue in regenerative medicine is whether the taking of human cells or tissues for research or therapeutic purposes is acceptable when a donor is incapable of giving informed consent. If no informed consent is possible, does consent by others, for the purpose of promoting research that will benefit society, outweigh the taking of what some believe to be a potential life?

When the potential source of cells or tissues is a fetus or embryo, ethical considerations usually center on the pros and cons of induced abortion. The arguments are frequently based on some arbitrary time in embryonic or fetal development when it is thought that human life begins. Many biologists argue that human life does not have a beginning (except on an evolutionary time-scale) because both sperm and egg cells must be alive from the start and fusion of the two is simply another of the many critical steps that, if successful, can lead to the development of a viable offspring. Others contend that the potential for human life only occurs at the moment of conception. This is another arbitrary point because equally critical events must occur both before and after fertilization to insure that the potential for human life is realized. This issue could become even more clouded if it is shown, as it has been in some animals, that a jolt of electricity or a needle prick can stimulate an unfertilized egg to develop—a process known as parthenogenesis.

However the vast majority of sperm and eggs produced never fuse to form a zygote and if they do, a substantial number of zygotes subsequently are lost naturally. Yet this enormous loss of potential human life that far exceeds the number of successful births is rarely deplored.

In order to circumvent some ethical objections, the use of somatic cell nuclear transfer (SCNT) has been shown to be a practical alternative. Here the nucleus from a body cell (other than a gamete or its precursors) is inserted into an egg whose nucleus has been removed. This is done in vitro with the resulting dividing cells used for research or for potential therapy in the nuclear donor where problems of immunological incompatibility are reduced. Like the fusion of a sperm and egg in vitro, it is not possible for this cluster of cells to become a viable embryo unless the zygote is implanted into a uterus. Despite the fact that the nucleus used in SCNT comes from a single donor, the cells that form the zygote, or later developmental stages, could be used therapeutically when compatibility problems are overcome.

What must be weighed in considering the taking of human fetal cells or tissue is if anyone has the right to make the decision and whether or not the benefit that might accrue to many potential recipients outweighs the loss of one or a few potential lives. One significant precedent for making this decision in the affirmative is the often overlooked fact that, in the last forty years, hundreds of millions of people throughout the world have benefited from the use of many common virus vaccines, all of which were produced (and are still produced) in cells obtained from one or two surgically aborted human fetuses on which research had been publicly supported (Hayflick 2001).

LEONARD HAYFLICK

BIBLIOGRAPHY

Binstock, Robert H. (2003). "The War on 'Anti-aging Medicine."' The Gerontologist 43(1): 4–14. A scholarly analysis of how mainstream biogerontologists are countering the practitioner's of anti-aging medicine who biogerontologists believe are exploiting the publics' ignorance of the science for financial gain.

Cibelli, Jose; Robert P. Lanza; Keith H. S. Campbell; and Michael West. (2002). Principles of Cloning. San Diego, CA: Academic Press.

Gruman, Gerald J. (1966). "A History of Ideas about the Prolongation of Life." Transactions of the American Philosophical Society 56, Part 9. Probably the best history ever written on the evolution of human thought about longevity from the first written records until 1800.

Hall, Stephan S. (2003). Merchants of Immortality. New York: 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 Aging." Nature 408: 37–39.

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, ed. Fred Brown, Keith Peden, Philip Krause and Andrew M Lewis. Basel, Switzerland: Karger.

Hayflick, Leonard. (2004). "'Anti-aging' Is an Oxymoron." Journal of Gerontology 59A(6): 573–578. 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." In Developments in Biological Standardization Vol. 68, eds. John C. Petricciani, and
W. Hennessen. Basle, Switzerland: Karger Publishing. Also published in Bookchin, Debbie, and Jim Schumacher. (2004). The Virus and the Vaccine. New York: St. Martin's Press. 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. Now many safe and efficacious vaccines made in Hayflick's human fetal cells have been administered to almost one billion people.

Olshansky, S. Jay; Leonard Hayflick; and Bruce A. Carnes. (2002). "No Truth to the Fountain of Youth." Scientific American June: 92–95. 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.