The language and symbolism of death and old age in bio-gerontology by John A. Vincent

1. BSG Annual Conference 2006The Ageing Jigsaw: Interdisciplinary approaches to understanding old age 7th-9th September 2006, University of Bangor, Wales. The language and symbolism of death and old age in bio-gerontology by John A. Vincent

2. Introduction • Recent scientific interventions have achieved dramatic increases in longevity amongst nematode worms, fruit-flies and mice. It is suggested that these experiments open the possibility of greatly extended human longevity. • “We are now in the era of emerging ability to control our actuarial destiny in response to the desire in humans throughout history to live comfortably and to delay death (Holliday 2001; Preston et al 1978).” (Carey 2003:220) • This paper examines the impact of the culture of science on the meaning of old age. In particular it examines developments in understanding ‘cell death’ and their potential impact on the meaning of old age.

3. The sociological relevance of the issue • Social constructionism has played a key role in dismantling old age and exploring the possibilities that there are alternative ways to live a good old age. Old age not simply a matter of biological determinism. • But what are the limits to social constructionism? Surely death and the frailties of the fourth age are not social constructions? • We can see that different cultures approach death in very different ways; there are many myths and rituals that re-enact denials of death. But every one dies. Similarly experience tells us that everyone ages. • However, it is a false distinction to see social constructions as merely the products of a cultural imagination as opposed to scientific facts which represent the truth about nature. Two ways around this: • Psychological: W. I. Thomas “if people believe that something is real it is real in its consequences” • Phenomenological: We cannot observe the world without cultural framework to name and categorise it.

4. Accessing meanings of old age • Cultural concepts are necessary with which to understand and make sense of the world. But those cultural concepts are produced in historical and continuous process in which the social and the natural environment are critical components. • Cultural categories are established through boundaries - contrasts which mark semantic space. • To understand old age it is necessary to know its boundaries, how to recognise it, and thus the markers which indicate the boundaries between what is old age and what is not. • Meanings cannot be established in isolation, categories are part of historical and cultural meaning systems which interlock.

5. Life and death • Death contrasts with life. What is alive and what is dead and how do we know? This boundary is highly contested and fraught with moral dilemmas as to what is human and what is not. The medical definition of death has shifted in recent history – contemporary medical protocols for establishing death tend to use a concept of brain death. Death has ceased to be a ‘natural’ event. • Old age is the stage of life next to death. It takes it place in developmental cycles of organisms from conception and birth to decay and extinction. Ageing is then a concept parallel to maturation defined by contrasting life cycle stages. It is worth noting that many species don’t die. Mortality comes with sexual reproduction. But death is a necessary boundary marker for the cessation of old age and which is an important component in its meaning. • At the level of the cell, cells were thought to be capable of immortality until the discovery of the Hayflick limit. Thus cell senescence came to mean reproductive senescence; the inability of the cell to divide and replicate itself. There was the belief that old age was programmed at the cell level. If we could modify that programme perhaps we would not need to age. However, it turns out to be much more complicated than that.

6. Cell death • ”In the course of these relocations of life, disease, and death processes, the relationship between life and death has not remained constant. Through analysis of the morphology, genetics, and temporality of the body’s continuous cellular dying, the oppositional relationship between life and death that existed for Bichat and those who came after him was displaced by the vision of a multiplicity of death that maintains tissue homeostasis, shapes development, regulates the formation of the immune system, and serves as a protective mechanism against oncogenesis. Thus, with the localization and spatialization of death in the cell, death has become for biomedicine not necessarily that which life is opposed but is many cases, that on which life is dependent, or at least that with which life and disease are inextricably bound… p.55 • H. Landecker “On beginning and ending with Apoptosis” in Sarah Franklin and Margaret Lock 2003 Remaking Life and Death pp.23-60 James Currey: Oxford.

7. Interview data • In the small number of interviews I have conducted with scientists, particularly bio-gerontologists I have systematically asked about three processes ‘maturation’, ‘senescence’, and ‘apoptosis’. The differences in the manner of response are illuminating. • With maturation there is a dismissive approach, respondents invent something plausible but without interest or connection, they do not see it as a relevant and important part of their lexicon – perhaps it might be more relevant to biologist concerned with whole organisms and developmental process – but for the cell scientists it was irrelevant. • Apoptosis on the other hand was responded to immediately and with standard textbook answers. This was planned cell death. Many respondents even quoted the standard textbook example of the apoptotic removal of webs between the fingers in embryos. • However, the response to ‘senescence’ was interesting because there was not a standard answer but the respondents thought there should be and perhaps they were being caught out. The responses were full of linguistic devises such as hesitation, circumlocution, restatements which indicated unease or uncertainty from the respondents. Clearly the term was less well institutionalized. Most produced the idea of cessation of cell division but were uncertain whether that was sufficient and complete. • It was also clear from conversations with the scientist that many particularly non English speakers were aware of the non-scientific origins and use of the term senescence (c.f. Katz).

8. Faragher RG. (2000) “Cell senescence and human aging: where's the link?” Biochemical Society Transactions. 2000 Feb;28(2):221-6

9. Ageing and disease • There is another critical contrast that between natural processes and disease. If old age is thought of as a natural process like puberty, childbirth, or the menopause, it stands in contrast to disease. • Thus a successful old age is to die of old age and not one of the pathological risk factors associated with old age. Hence many gerontologists talk about extending the health span • Indeed many social constructionist medical sociologists have shown how particular phenomena come have the disease label attached and come under the scrutiny and control of medical institutions (Katz and Marshall 2004). • Bio-gerontologists are undermining this distinction between old age and disease. These revisions come from two directions one from evolutionary theory, the other from cell science.

10. Evolutionary approaches • Evolutionary theories of ageing were developed by Medewar. His insight was that the pressure for selection came in the early years of the life span enabling species to successfully reach breeding age and produce offspring. The selective pressures in older age, particularly beyond reproductive age (but note grandmother hypothesis) were not so strong and hence it was possible that genes for survival in youth also carried traits for decline and senescence in old age. Modern genetics of old age indeed suggests that particular genes have a range of functions which have positive and negative impacts on risk factors and survival rates at different ages. • Tom Kirkwood using the sophistication of modern maths and computer modeling to simulate evolutionary processes has developed the disposable soma theory. This is the idea that there is a trade off between the energy an organism expends on sustaining itself and the energy it puts into reproducing the next generation. If it fails to develop an optimum balance it will either wear itself out before it has a chance to produce maximum progeny or it will live so long as to present a competitive threat to its own offspring’s survival. He suggests that ‘in the wild’ specific genetic mechanisms to die at a specific age are unlikely as rates of predation would render such a mechanism unnecessary. • The logical consequence of this position is that, if people can avoid predation and eliminate the risk factors of specific diseases, there is no natural limit to the human life span.

11. Cell science • From the perspective of cell science it turns out the ageing is pretty much indistinguishable to the standard metabolic processes that happen in cells. In addition to the enormously complex bio-chemical processes of the cell cycle and or metabolism, there is a also highly complex repair and maintenance processes which ‘clean up’, ’police’, protect the cell from routine and accidental bio-chemical products of living. • When these mechanisms fail we can get disease in the form of tumours, or when they are overactive we get diseases in the form of autoimmune diseases (arthritis). Organ specific failures to repair which form the risk factors in old age are related to declining efficiency is some of these processes perhaps due to accretion of metabolic residuals over the life span, which in turn of course might be related to life course and environment factors. • The logic of this position is that if we could find ways to sustain the efficiency of the processes which keep cells on the bio-chemical straight and narrow we would both cure the diseases of ageing (and most others) and prevent death. Indeed model programmes for researching such a regime for immortality have been produced and are being advocated by a minority with the biogerontological community. Thus this new biology within cell science holds out the prospect that upregulating the metabolic process, or repairing the damage it routinely does, will inhibit ageing and thus also avoid the diseases of old age.

12. Biology and the certainty of old and death. • Harry Moody and Leonard Hayflick ask “Has any one died of old age?”[i] Moody makes the significant point that if you answer ‘yes’ to this question it means ageing is a disease so a cure can be found for it and people potentially will live for ever, and if you answer ‘no’ it means people die of some other disease for which cures can be found and thus people potentially will live for ever. • Mykytyn (2006)[ii] does an excellent job of deconstructing the President’s Council on the Bio-ethics of ageing demonstrating the rhetorical uses of ‘natural’ life spans as necessary to the separation of ageing from disease and how ‘anti-ageing medicine’ challenges this distinction by treating ageing as the subject of therapy. • Thus we reach a position where the certainties of death, disease and ageing as they are popularly understood (in both the general public and in social gerontology) disappear under close examination.

13. Fragmentation of biogerontology • Thus what can be observed with the developments in contemporary bio-gerontology is an undermining of the key categories through which we understand ageing and old age. This is highly significant for the future given the importance of biology and medicine in setting the cultural meaning and the institutional framework within which ageing is lived in Western society. • But also what is going on is a fragmentation of biology. The biology of ageing has moved from a minor non-prestigious corner of biology, to become centre stage in the new biology which focuses on genetics, cell process and the bio-chemistry of complex proteins.

14. Genomics of ageing • The major recent advances in bio-gerontology have resulted from an increased knowledge about cell processes which stem in turn from the genomics revolution and from the complex bio-chemistry of cell processes. • But it is important to appreciate that the contemporary science is a considerable distance from popular understanding of genetics and even that commonly found in popular science. • Biological ageing is not all in the genes. There is no single gene for ageing, or even a combination of genes. There are a large number of genes with some association with longevity, or processes which appear to lengthen or shorten the life spans of particular species. But single gene, single trait models of the genome are obsolete. There are enormously complex pathways by which genes get turned on, express themselves, interact with one another, and initiate hugely complex chains of protein synthesis and transformation. • Sheer complexity creates a demand for new models and methods of analysis.

15. ‘Ageing’ moves centre stage • A leading biologist at the ICFGA said that “ageing turns out to be about living: basically it is metabolism…” • As a symbolic statement it tells us, the life and death are the same thing, while culturally they may be conceptually opposites, in biology the basic process of living is also dieing. The basic process of consuming energy to stay alive creates the conditions for ageing and death. • However, for biology it means that ‘ageing’ is no longer a distinctive process for which there is a distinct sub-branch of biology and reflecting that knowledge base, gerontology as a single medical specialism is having its exclusivity challenged. Understanding the genetics and bio-chemistry of cell processes is at the fundamental core of biology. • This fragmentation is evident in my attempts to map the attendees at the ICFGA in terms of their disciplines. It proved immensely complex and the following diagrammes illustrate:

16. Venn diagramme of mirco-biology disciplines at ICFGA

17. Venn diagramme of medical disciplines at ICFGA

18. The possibilities of life extension undermine the contemporary cultural value of old age and old people. • Bio-gerontology largely positions itself in categorizing old age as a failure. In defining it in terms of the body, it specifically foregrounds bodily failure as the essential nature of old age. • In looking for ways in which a cultural revaluation of old age might occur, my argument, developed elsewhere is that a healthy death is necessary for a good old age (meaning the final part of life before death), otherwise old age is always defined by its failure, i.e. dying. • In this work I have drawn on the social constructionist traditions out lined at the beginning of this paper. If dying cannot be a positive event then nor can old age. • The notion of a healthy death; one which escapes the apparatus, technical and institutional, of the medical professionals and disease control, it has been met with incredulity and incomprehension. The power of the medical model is such that it is difficult to think about old age outside its frame. • But here I have argued that the biology of ageing is fragmenting. There is no longer a single biological story of ageing. Does the biology offer possibility of more positive models of ageing and old age? Does the fragmentation leave space for other new perhaps liberating models of old age? Here we come to the interesting metaphor of ‘apoptosis’ which I will develop below.

19. H. Landecker “On beginning and ending with Apoptosis” in Sarah Franklin and Margaret Lock 2003 Remaking Life and Death pp.23-60 James Currey: Oxford. • “Although many commentators call the insistent presence of narratives of human death in cell death science anthropomorphism and comment on its “danger” to the practice of science (Clark 1996; Debru 1998; Friedman and Brunet 1995), I believe that these narratives and their tensions point to a more complicated and more interesting role for the cell in contemporary biomedical culture than that of an irrational being incorrectly endowed with human qualities. The cell is a site through which all kinds of changing material, semantic, economic, and conceptual relationships are played out: cell to body, cells to one another, scientists to doctors, patients to laboratories It is a site in which what it is to be cellular, in life, death, and disease, is constantly being produced.” p.57

20. Cell death Biology defines a limited number of ways a cell can age and die • Senescence • Apoptosis • Necrosis Like most things in contemporary biology, this including the terminology is challenged. Some others associated with cancer and disease function (oncosis etc.)

21. One model of the relationship:Soti C, Sreedhar AS, Csermely P.(2003) “Apoptosis, necrosis and cellular senescence: chaperone occupancy as a potential switch” Aging Cell. 2003 Feb;2(1):39-45.,

22. Senescence • Senescence is the cell in old age. That is how it is thought of as metaphor even if the belief that there is a specific direct link to organism ageing is contentious. Variously in biology its meaning has shifted from senescence as specific form of decline, loss of efficient function in all aspects, including the accumulation of ‘junk’. But increasingly it is specifically used in the sense of replicative senescence - the cessation of mitosis (cell division). This links to telomere theories. But recent research evidence suggests that revival from senescence can occur.

23. A new test developed by LBL researchers uses blue stain to detect the presence of senescent cells. The assay top left shows young tissue with no presence of blue; top right is young sunburned tissue, also negative. Older tissue cells, pictured in the bottom four assays, contain blue areas revealing evidence of the existence of senescent cells. Senescence imaged

24. Necrosis • Necrosis is accidental death. The cell is injured ruptured and spills it contents to the detriment of other cells in its vicinity and causing inflammation. The damage can be mechanical but it might also be poisoning or other fatality. ‘Act of God’ in the insurance world. The purveyors of immortality always point out that mortality can never be reduced to zero, there will always be fatal accidents. Some biologists have suggested the boundary with other forms of cell death may not be as clear cut as this definition suggests.

25. apoptosis • But what about apoptosis? The biology text books and popular science media have it off pat as suicide. Sometimes called murder when it occurs as a result of extra cellular stimuli, but I found only one use of the term euthanasia. However, Apoptosis is clearly good death. It is a vital part of life and the continued health of the organism. Here is a model of good death. It is the individual (cell) playing its part in the overall life of the body. Its death at the right time and the right place is a necessary and desirable outcome for the health of the multi-cellular soma (peoples bodies). • The metaphor is clear, death is an essential part of life. Conversely universal immortality or systematic attempts to increase the life span will transform life and essential human qualities. This may or may not be desirable but a radical departure from humanity, as it is currently understood and experienced, is inevitable with the elimination of old age and death. It will not be more of the same experience of age but frozen in time, but rather an essentially different semi-natural entity of uncertain meaning.

26. The final stage of apoptosis; cleaning up after the death

27. Death defines the category ‘old age’ • ‘Age’ is both a verb and a noun: it stands for both a process and also a set of categories. Some parts of the trajectory of social and biological change over time are identified as ‘ageing’. It is understood as a sequence of stages and statuses to which specific age based normative expectations are attached. The specific content of those processes and categories are contested; their meanings are not fixed. The future life course may have different life stages; new divisions in the 20C have included teenager, and ‘third ager’. There may also, in addition or instead be a breakdown in the structure of the life course with less definite stages or sequences. • As old age becomes increasingly ‘biologised’ it is in fact, in parallel to biology, becoming fragmented and loosing coherence as a concept. There are many biological stories of ageing, and more are being produced, - there is not a single story of the biology of human ageing.

28. Positive images of ageing from the new biology • Negative cultural constructions of old age spill into biology but are transformed; biological concepts become transformed when used in popular discourse to legitimate ageist practice. • This has been illustrated by the way the concept of senescence entered and has been transformed in biogerontology along with the way debates over different kinds of cell death – apoptosis, and necrosis – form a repertoire through which ageing and death can be imagined. • With the fragmentation of biology and the concomitant lack of single authoritative biological voice telling us what ageing is, there become room for alternative visions for the nature of old age and the future possibilities for ageing. There are at least two possible contenders. • Firstly, the good old age as a positive final stage in life concluded by a healthy death. And we now have a model of healthy death from biology, namely apoptosis. • Secondly there is the good old age as an enhanced/super human being/ cyborg with death defying capabilities.

29. A copy of the paper and the power point presentation is available on my personal website. • http://www.people.exeter.ac.uk/JVincent/Bangor/