Medical classification and the experience of genetic haemochromatosis

DNA-based biomedical technologies create the possibility for new topographies of physiology and pathology. Based on biomedical science at the molecular level, these technologies are increasingly mapping disease in clinics and laboratories through genetically informed talk and work (Atkinson et al. 2001; Bharadwaj 2002). Genetic medicine is increasingly developing new biological and clinical categories, contributing to what Keating and Cambrosio (2003) refer to as ‘biomedical platforms’ that comprise new configurations of knowledge derived from the intersections of laboratory science and clinical practice. New genetic technologies create the possibility of new biomedical knowledge and the transformation of clinical entities. They also give rise to new definitions of health and illness. The identification of genetic risks or genetic susceptibility to one or more of a range of genetically-transmitted diseases can create new ambiguous categories of person who are neither perfectly healthy nor clinically sick, but ‘at risk’. The opportunity to screen populations for a growing number of conditions will create ever greater numbers of individuals who find themselves in such a position. While risk is not confined to genetic constitutions, and there are many risks defined by lifestyle and other circumstances, the estimation of genetic risk is a new technology of medical classification. It gives rise to the possibility of what we have called elsewhere the ‘genetic iceberg’ of susceptibility and potential anxiety (Bharadwaj et al. 2006; Bharadwaj 2002). There is, therefore, an intimate relationship between the changing boundaries and classifications of genetic disease and the shifting categories of patienthood and personal identity. Genetic haemochromatosis (GH) is one disease that has acquired new

clinical and scientific significance since the discovery of the HFE gene in 1996 (Beutler et al. 2002). Haemochromatosis is a genetic disorder causing the body to absorb an excessive amount of iron from the diet (Bothwell and MacPhail 1998). The excess iron is subsequently deposited in multiple organs, especially the liver, pancreas, heart, endocrine glands and joints. Excessive quantities of iron trigger progressive liver disease and may also

cause serious damage in other organs and body parts (Niederau et al. 1996; Bothwell and MacPhail 1998). The susceptibility to absorb excessive amounts of iron is usually associated with homozygosity for a particular mutation of the HFE gene. Since its discovery in 1996, this mutation (the C282Y mutation of the HFE gene) has been identified as the underlying cause of haemochromatosis in over 80 per cent of the patients (Beutler et al. 2002). It is estimated that in Europe, Australia and the USA 60-100 per cent of patients with genetic haemochromatosis are homozygous for this mutation (Worwood 1999). In Britain 1 in 200 people are susceptible homozygotes (i.e. they carry two copies of the mutation); the proportion who develop clinical haemochromatosis is small but not clearly defined. Therefore, while it is possible to screen individuals with the view to predicting their personal susceptibility to developing the condition, such risk prognostications are often tentative. A positive test result demonstrating this double dose of the mutant gene identifies an otherwise healthy individual only as susceptible to the development of the disorder. A recent study in South Wales, the region of our own study, showed that only one per cent of adult GH homozygotes had a clinical diagnosis of iron overload (McCune et al. 2002). There is as yet no firm clinical basis for the prediction of when and how

a healthy susceptible individual develops frank disease or overt iron overload, although it is becoming clear that variation at other genetic loci as well as environmental factors including diet are all relevant. Measurement of body iron stores serves as a proxy indicator – a very imperfect predictor – of future disease onset. This leaves clinicians and scientists still grappling with the multifactorial complexities underlying the condition. Conversely, the clinical diagnosis of haemochromatosis is by no means straightforward. Symptoms of iron overload are often diffuse, including lassitude and signs of impaired liver function. Primary health practitioners may readily attribute them to a variety of underlying causes other than haemochromatosis. If identified, the condition can normally be managed through regular bleeding, which depletes the body’s excess iron, and the condition is eminently treatable (Niederau et al. 1996). If it remains undiagnosed, then serious organ damage can result. (See McDonnell et al. 1999 for a survey of 2,851 patients’ experiences and symptoms.) In the current state of genetic knowledge and clinical practice, therefore, it is possible to identify individuals who have an inherited susceptibility to GH, but with only restricted prediction of disease onset, and it is equally possible to identify GH patients whose condition has been misdiagnosed or diagnosed late, and whose genetic status is only confirmed retrospectively. While it is not the main focus of this chapter, it should be noted, therefore, that the uncertainties surrounding clinical diagnosis make it very difficult to assess the penetrance of the gene with any degree of precision. Here we document how haemochromatosis and its clinical management

are experienced and understood by a series of individuals who have been

identified as affected by the condition. We examine the lay phenomenology of haemochromatosis: how affected patients make sense of the condition. We argue that individuals with GH may attempt actively to contribute to the production and narration of the condition by critically engaging with the clinical nosography. This creates what Waldby (2000: 466) has called ‘multiple ontologies of bodies, disease and medically constituted subjectivities’ amongst patients. Haemochromatosis patients are, in other words, engaged in making sense of the disease and seek actively to challenge and extend the boundaries of expert classifications and boundaries. Patients explore the interpretative space that is created by the relatively uncertain nature of the clinical diagnosis of haemochromatosis. Many of the affected individuals with frank symptoms of the condition report that they experienced difficulty in having their illness acknowledged and validated by medical practitioners. As a consequence, the disciplinary practices of the clinic – medicalisation, normalisation and objectification – are sought by patients in pursuit of clinical validation of their symptomatic manifestations of GH. Recent accounts of the construction of genetic disease include analyses

of the ‘expansion’ of diagnostic categories and clinical entities. In particular, Kerr (2000, 2004) and Hedgecoe (2003, 2004), examining the ‘geneticisation’ of cystic fibrosis (CF), have discussed the process whereby genetic medicine may extend the boundaries of the disease to include new clinical phenomena within its ambit: in the case of CF the boundary may be expanded to capture one variety of male infertility. The identification of genetic bases for a widening number of conditions can shift the boundaries of diseases and syndromes previously identified primarily on clinical grounds. The analytic value of the notion of ‘geneticisation’ in this context has been contested. It is clear that, on the basis of detailed explorations of the practice of contemporary genetic medicine, there is not a simple, reductionist process whereby genetic conditions become ‘fixed’ as a consequence of diagnostic genetic investigations. While susceptibility to GH can be identified in terms of genetic categories, new genetic technologies do not determine the classification and phenomenology of the condition. We should, therefore, be cautious (at best) of endorsing general claims as to the geneticisation of contemporary medicine, or that new genetic technologies necessarily determine professional and lay conceptions of clinical entities. It is certainly premature to extrapolate from specific cases to make general claims about the geneticisation of health and medicine in toto. These remain empirical issues. We are thus sceptical about the sort of claims made by Finkler (2000), or Haraway (1990), who suggest – from very different perspectives – that contemporary genetic technologies necessarily transform the nature of medical knowledge and lead inexorably to a geneticisation of medicine or the geneticisation of identity. It would, therefore, be inaccurate to account for the consequences of

new genetic medicine in terms of a simple, unilinear process whereby genetic science progressively furnishes unequivocal grounds for determining

the boundaries and diagnostic criteria of clinical entities. It is not only clinical geneticists and clinical scientists who can find themselves expanding or contesting the boundaries of disease classifications and criteria, however. Patients who find themselves experiencing a genetic disorder may also be engaged in exploring and contesting such boundaries. In this chapter we describe how patients with genetic haemochromatosis (GH) may seek to expand the condition to incorporate their everyday symptoms for inclusion within the nosography of the disease. When professional classifications are uncertain and shifting, lay nosographies of genetic disorders are implicated in the process of diagnostic inference. It is not necessary to invoke the notion of lay expertise (cf. Arksey 1994; Busby, Williams and Rogers 1997; Epstein 1995; Sarangi 2001) to recognise that the mundane phenomenology of illness can have considerable significance for patients and professionals in mapping clinical illness. As Prior’s review highlights, claims concerning expertise on the part of patients, activists and other lay actors can readily mask significant differences in the forms of knowledge between lay persons and professional practitioners (Prior 2003). Lay actors may undoubtedly become knowledgeable about restricted and specific phenomena, often on the basis of personal experience. But that does not mean that we can unequivocally assign them expert knowledge without emptying the latter of any analytic force. In approaching patients’ accounts of their own conditions we do not

assume a priori a high degree of symmetry between the contents of patients’ and professionals’ knowledge. We do not assume that patients should necessarily be regarded as lay ‘experts’ on their own conditions, nor that one should equate their practical interests with the knowledge of professionals. There are qualitative differences between the two. Patients can undoubtedly become highly proficient in recognising illness, symptoms and changes in physical status in their own bodies and in those of family members and other intimates. When they have a specific illness they can also become adept at describing, tracing and monitoring its physical and emotional effects. They become, in other words, practical phenomenologists primarily in illnesses that are their own or that they socially share. The illness can become a central feature of their own lifeworld. The particularities of the patient’s own condition may well present themselves differently from the generic categories of the professional practitioner’s knowledge. The professional is expert not in the particularities of the case but in the general categories of medical knowledge. Her or his knowledge is not grounded in the practical phenomenology of the self and the body, but in the theoretical knowledge of ideal-typical disease categories (cf. Mishler 1984). There are, however, some key aspects in which the interests of the lay and professional observer coincide. Both are engaged in the attempt to identify the appropriate characteristics, criteria and boundaries of diagnostic and pathological classifications. The patient seeks to establish one or both of two issues: Are all my symptoms explained by the disease I

have been diagnosed with? Will the medical profession accept my own descriptions of my symptoms and grant them legitimacy within the clinical description of my condition? The medical practitioner is also concerned with establishing the patient’s condition (symptoms, signs, family history, laboratory results) as a ‘case’ of an ideal-typical illness category. Both, therefore, have interests in tracing the boundaries between the normal and the pathological, and in mapping the categories of ‘normal’ disease entities. As we shall discuss more fully below, the epistemological problem of the boundaries of the normal and the pathological are not confined to the realm of the philosopher (e.g. Canguilhem 1989): they are also practical issues for lay and professional actors alike. Moreover, both have interests in identifying what is to count as ‘normal’ pathology, as opposed to idiopathic variations or coincidental symptoms.