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The biopolitics of CFS/ME Nikos Karfakis Business School, Alexander College/University of the West of England, 2 Artas Street, Aradippou 7110, Larnaca, Cyprus

A R T I C LE I N FO

A B S T R A C T

Keywords: CFS/ME Biopolitics Objectivity Biomarkers Standardisation Psychiatry

This paper argues that Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) constitutes a biopolitical problem, a scientific object which needs to be studied, classified and regulated. Assemblages of authorities, knowledges and techniques make CFS/ME subjects and shape their everyday conduct in an attempt to increase their supposed autonomy, wellbeing and health. CFS and CFS/ME identities are however made not only through government, scientific, and medical interventions but also by the patients themselves, a biosocial community who collaborates with scientists, educates itself about the intricacies of biomedicine, and contests psychiatric truth claims. CFS/ME is an illness trapped between medicine and psychology, an illness that is open to debate and therefore difficult to manage and standardise. The paper delineates different interventions by medicine, science, the state and the patients themselves and concludes that CFS/ME remains elusive, only partially standardised, in an on-going battle between all the different actors that want to define it for their own situated interests.

1. Introduction This paper examines Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), a contested and controversial medical category. In CFS/ME there is still no epistemic closure in the controversy surrounding its aetiology, diagnosis, prognosis, treatment, and prevention. Drawing on Foucault's notion of biopolitics (Foucault, 1979, 2007; Lemke, 2011), the paper argues that CFS/ME can be viewed as a biopolitical problem. CFS/ME subjects are caught up in between the various discourses that constitute it in the process of knowing it, and in between social authorities that would like to regulate it. I argue that diagnosis becomes a field of contestation not only in the clinic (e.g. Åsbring & Närvänen, 2004; Horton-Salway, 2004; Cooper, 1997; Swoboda, 2008), but on a larger scale too because especially under the prevailing neoliberal conditions welfare and insurance1 systems are concerned with the ‘excessive’ claims being made by parts of the population. Medicine treats non-organic illnesses as psychogenic or ‘medically unexplained’ (Jutel, 2010; Lipowski, 1984; Sykes, 2010; cf.; Greco, 2012), or as ‘malingering’ (Kanaan & Wessely, 2010). Contrary to claims of ‘objectification’ of patients, it is well-known that patients often actively participate in shaping biomedicine (e.g. Callon & Rabeharisoa, 2008; Epstein, 1997; Hacking, 1995; Rabeharisoa, 2006; Rabinow, 1999; Zavestoski et al., 2004). As other health activists have

done, CFS/ME organisations collaborate with and employ scientists who are sympathetic to their cause, and try to make their illness more visible and persuade state institutions to increase research funds and welfare benefits by various tactics such as documentaries,2 campaigns, and petitions. I focus in this paper not on the experiential side of the patients diagnosed with CFS/ME (e.g. Aroll & Senior, 2008; Bülow, 2004; Edwards, Thompson, & Blair, 2007; Travers, 2004; Whitehead, 2006), but on showing that CFS/ME is made not only through government, scientific, and medical interventions but also by the patients themselves who collaborate with scientists, educates themselves about the intricacies of biomedicine, and contest psychiatric truth claims.3 To do so I utilize Rabinow (1996; see also Dumit, 2000; Gibbon & Novas, 2008; Rabinow, 2008) notion of ‘biosociality’ and Novas' work on what he calls the ‘political economy of hope’. The paper thus claims that the CFS/ME community can be viewed as a ‘biosocial community’, that is a new collective identity gathered through various means around central shared vulnerabilities, beliefs and aims. Finally, the paper adopts a science and technology approach (explained below) with regards to the notion of scientific ‘objectivity’ which allows us to avoid taking illnesses as ‘mere’ ideological constructs or as pre-given. Abundant meticulous studies of scientific objects in the science and technology studies (STS) literature have convincingly shown that scientific objectivity is neither transhistorical nor a matter of

E-mail address: [email protected]. See Coetzer, Lockyer, Schorn, and Boshoff (2001, p. 170). It should be also noted that in the UK, disabled and ill people over the last years have been facing cuts in their benefits and attacks as being ‘lazy’ or as making fraudulent claims. 2 A new documentary about CFS/ME recently came out called ‘Unrest’. See https://www.unrest.film/(accessed 19 December 2017). 3 The ideas presented in this paper are influenced by Dumit (2003; 2006) work on CFS/ME patients' struggle for recognition and legitimacy. 1

https://doi.org/10.1016/j.shpsc.2018.05.009 Received 22 April 2017; Received in revised form 1 October 2017; Accepted 29 May 2018 1369-8486/ © 2018 Elsevier Ltd. All rights reserved.

Please cite this article as: Karfakis, N., Studies in History and Philosophy of Biol & Biomed Sci (2018), https://doi.org/10.1016/j.shpsc.2018.05.009

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clinical entities. ME is, according to Twisk, a neuromuscular disease, while CFS's symptoms are measured by subjective measures. Moreover, as he puts it (Twisk, 2017, p. 2), ‘[p]atients can meet the diagnosis of ME, while not meeting the case criteria for CFS, while other patients can fulfill the diagnosis of CFS, without experiencing any of the distinctive ME symptoms’. It is therefore perhaps of little wonder that ME is often the preferred term of people diagnosed with CFS. On the other hand, doctors seem to prefer the term CFS because in most cases the main symptom is chronic fatigue.5 Moreover, the compound ‘CFS/ME’ or ‘ME/CFS’ is sometimes preferred instead of CFS as it is believed that it implies a more serious illness than CFS which focuses simply on fatigue. As with all illnesses, CFS/ME is permeated by socio-cultural beliefs and values and economic rationalities. The ‘nature’ of CFS/ME is passionately debated by psychiatrists and other medical scientists, researchers, patients' organisations, and social scientists. CFS/ME is discursively framed as an economic problem, an educational problem (van Hoof, De Becker, & De Meirleir, 2006, p. 46), possibly an infectious disease that needs to be securitised,6 and, finally, a moral problem as the persisting inactivity of these bodies is troubling. In the western, Anglo-American world, idleness and inactivity are considered a moral failure (Hay, 2010; see also; Rabinbach, 1992). CFS/ME bodies are unruly. They are bodies that have failed to be productive or to keep up with the frenetic work rhythms many of them previously had (e.g. Clarke & James, 2003; Ware, 1992). The majority of people diagnosed with CFS/ME are unable to work and function according to the dominant social norms while in line with the general tendency of the ‘responsibilitisation’ of individuals (Rose, 1999), people diagnosed with CFS/ME are discursively positioned as ‘autonomous’, ‘self-determined’ and ‘active’. Antony Pinching, Professor of Immunology and principal medical advisor for Action for ME (AfME), a UK CFS/ME advocacy group, believes that some of the reasons CFS/ME has not attracted much attention – despite the fact that epidemiology has increasingly showed CFS/ ME to have a relatively high prevalence in the US7 – include the lack of aetiology, the marginalisation of patients, its small market size, but also patients' ‘unproductive’ activism (Pinching, 2003). Shorter (1986) argues that the nature of ‘medically unexplained syndromes’ has changed, shifting from apparently neurological symptoms such as paralyses, tremors and fits, to more ill-defined and subjective symptoms such as fatigue and pain, while Showalter (1997) takes CFS/ME to be a contemporary form of hysteria like alien abduction.8 On the other hand, Richman, Jason, Taylor, and Jahn (2000) claim that, in contrast to multiple sclerosis which also disproportionately affects women, biomedicine's failure to provide a viral aetiology for CFS/ME led to largely psychosocial explanations that encompass a flight to a ‘sick role’ in order to escape burdensome social roles. In CFS/ME, it is said that women are twice as likely as men to have suffer from it (Yancey & Thomas, 2012, p. 741). Regarding ethnicity and socio-economic status, community-based studies in the US, for example, there appears to be a higher prevalence of CFS/ME in people of lower socio-economic groups, and in AfricanAmericans and Latino populations (see Luthra & Wessely, 2004). However, Luthra and Wessely (2004) note that these populations are not frequently referred for diagnosis and that these studies perpetuate the myth inherited from neurasthenia which takes CFS/ME to be an illness of the ‘developed’ countries. In the UK, as in other countries, CFS/ME seems to affect all social classes equally (while at least in the

representation but of intervention (e.g. Arabatzis, 2011; Daston, 1992; Fleck, 1979; Latour & Woolgar, 1979; Mol, 2002). From this perspective, objectivity is a matter of protocols, procedures, categories and definitions (Timmermans & Epstein, 2010), something achieved when some actors can ‘speak’ with greater volume and authority than others (Callon & Latour, 1981) and facts are just temporary results of long complex social processes. It is important to note, nevertheless, that much more than individual laboratories and professional journals are at stake in technoscientific controversies As Jasanoff (2011, p. 5) puts it, the production of facts and artifacts takes place through ‘law, money, political influence, enforcement capability, regulatory authority, [and] media access’. Thus, diseases should not be regarded as ‘natural kinds’ but as technoscientific arrangements enacted in particular, historically situated practices, performed in day-to-day socio-material practices (Mol, 2002). Lastly, relevant to my argument here is Cambrosio et al. (2006; see also Moreira, May, & Bond, 2009; cf. Latimer et al., 2006, p. 606) concept of ‘regulatory objectivity’. Regulatory objectivity refers to a new form of objectivity in the domain of biomedicine that is based on the systematic recourse to collective production of evidence. This form of objectivity and its evidence are produced by inter-laboratory studies, multi-centre clinical trials and research consortia that develop devices such as clinical and laboratory guidelines and protocols. The paper is structured as follows. After briefly describing the uncertainty that surrounds the illness, I look on the messy domain that is the nosology and diagnosis of CFS/ME. I describe how the CFS/ME community is in search of biomarkers that it believes will destigmitise and legitimise its illness but also improve its treatment. I then move on to look at the currently available treatments for the condition and, then, discuss the ‘discovery’ of a new virus which was originally believed to be the causative agent for CFS/ME. I conclude by looking at the current state of research in CFS/ME. Although I mostly focus on the construction and regulation of CFS/ME in the UK context where my research was carried out, I look also at the US context because there the prevalence of and research on CFS/ME is significant. 2. CFS/ME: A complex and performative scientific object CFS/ME is a complex and performative scientific object and condition. It is heterogeneously classified, diagnosed, treated, researched, and lived. CFS/ME has a long and complex trajectory (e.g. Ankeny & MacKenzie, 2016, p. 229–232; Ortega & Zorzanelli, 2010).4 The history of CFS/ME is characterised by periods where biological research on CFS/ME becomes strong and other periods where psychological explanations seem to dominate. Over the years, beginning in 1957 with the outbreak of a paralytic illness in UK which led to the ‘discovery’ of ‘Benign Myalgic Encephalomyelitis', many different terms have been such suggested for this condition; among them, post-viral fatigue syndrome (PVFS), chronic fatigue immune deficiency syndrome (CFIDS), and chronic fatigue & immune dysregulation syndrome (CFIDS), and more recently, in 2015, Systematic Exertion Intolerance Disease (SEID). In CFS/ME there are several case definitions (20 according to Brurberg, Fønhus, Flottorp, & Malterud, 2014) and diagnostic protocols, some complementary, some contradictory, exist defining it as a category of disease. Since 1994, the term ‘CFS’ has been accepted as the most common term for unexplained, severe chronic fatigue, and the Centre for Disease Control and Prevention (CDC) case definition has been the most widely used case definition internationally. Still, other, broader case definitions have been suggested, as the British or the Australian case definition that favours fewer symptoms. Not everyone agrees that Myalgic Encephalomyelitis (ME) and CFS are the same condition and many, especially in the UK, only view ME as a ‘scientific’ disease. As Twisk (2017) claims, CFS and ME are two distinct, partially overlapping

‘Chronic fatigue’ is sometimes referred to as a separate clinical entity. On 1st November 2010 people diagnosed with CFS/ME were banned from giving blood in the UK. 7 Estimates on CFS/ME's prevalence seem to vary (e.g. Johnston, Brenu, Staines, & Marshall-Gradisnik, 2013; Nacul et al., 2011). Holgate et al. (2011, p. 543), for instance, argue that in the UK it affects around 1% of the adult population. 8 Cf. Dumit (1997). 5 6

4 Scholars often treat the history of ‘CFS/ME’ as if this object has ontological stability. I make no such assumptions.

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US in the past it was considered the ‘yuppie flu’, the disease of the upper middle class). In terms of economics, in 2003, for example, the Action for M.E. estimated that the annual cost of CFS/ME in the UK was £3.5 billion, almost £15,000 for each person diagnosed with the syndrome (the figure was ‘based on the cost of medical treatment, loss of earnings, and the cost of state benefits’).9 Similarly, according to Ross et al. (2004, p. 1104; see also Jason et al.,2009 p. 237) alarmist discourse CFS/ME is more than a ‘medical mystery’, it is a serious economic problem.

Table 1 Center for Disease Control and Prevention Diagnostic Criteria for Chronic Fatigue Syndrome (information in Fukuda et al., 1994; also in Yancey & Thomas, 2012). Severe fatigue lasting longer than six months, and at least four of the following symptoms: Headache of new type, pattern or severity Multijoint pain without swelling or erythema Muscle pain Postexertional malaise for longer than 24 h Significant impairment in short-term memory or concentration Sore throat Tender lymph nodes Unrefreshing sleep

• • • • • • • •

3. The nosology and diagnosis of CFS/ME In its International Classification of Disease (ICD-10, 1996)10, the World Health Organisation (WHO) categorises ‘CFS’ under the heading of ‘Symptoms, Signs and Abnormal Clinical and Laboratory Findings, Not Elsewhere Classified (R00-R99)’. The World Health Organisation categorises ‘fatigue syndrome’ under the general category of ‘Mental and Behavioural Disorders (F00-F99)’ and under the specific category of ‘Neurasthenia (F48)’. On the hand, it puts ‘Benign Myalgic Encephalomyelitis’ under the general category of ‘Disorders of the Nervous System (G00-99)’. Now the World Health Organisation is to revisit its system for the revised ICD-11 in 2018. The ICD-11 will reclassify ‘CFS’ as ‘R53.82 Chronic Fatigue, unspecified’, something that has worried CFS/ME patients and activists.11 ‘Any illness lacking a diagnostic test is in danger of being put into this non-specific category which helps no one’, the UK CFS/ME patients association Invest in ME (IiME) has claimed.12 As already mentioned, there is currently no specific diagnostic test for CSF/ME and routine medical investigations do not usually find significant abnormalities. In 1988, the Center of Disease Control and Prevention (CDC) in the US suggested a working case definition of CFS, later to be revised and replaced by the 1994 CDC case definition (Fukuda et al., 1994). CFS/ME is diagnosed when other conditions associated with chronic fatigue have been excluded (Fukuda et al., 1994), a quite complex procedure. In that case definition, CFS is defined as an unexplained, persistent or relapsing chronic fatigue of new or defined onset; it is not the result of ongoing exertion; it is not substantially alleviated by rest; and, it results in substantial reduction in occupational, social or personal activities. Additional requirements are the concurrent occurrence of four or more specified symptoms like impairment in short-term memory or concentration, sore throat, muscle pain, headaches, non-refreshing sleep, and postexertional malaise lasting more than 24 h (Table 1). After the initial physical examination, the patient may then have blood tests and scans to rule out other conditions like Adrenal insufficiency or ‘Malignancy’. Other laboratory studies that often take place and may indicate CFS/ME in the patient are thyroid test and the Erythrocyte Sedimentation Rate (ESR) and White Blood Cells (WBC) tests (see Shepherd, 2006, p. 666). The question of whether the diagnosis of CFS/ME should be applied in patients with co-morbid psychiatric disorders has also been an issue of debate (Evengård, Schacterle, & Komaroff, 1999, p. 457). One of the leading researchers in CFS/ME was Simon Wessely, professor of epidemiological and liaison psychiatry at the Institute of Psychiatry at King's College London. Wessely consistently denied there is any ‘objective’ pathological evidence in CFS/ME patients. CFS/ME

patients are often frustrated with the ‘all in the mind’ attitude of many doctors. Wessely had claimed that CFS/ME is essentially the same as neurasthenia (David & Wessely, 1993, pp. 1247–1248). Wessely believed that attribution by patients to a virus (a common narrative of CFS/ME patients) is ‘somatisation’ par excellence. According to Emeritus Professor of Medicinal Chemistry at the University of Sunderland, Malcom Hooper (Hooper, 2010; see also Hooper & Williams, 2008), whose views had gained much currency in the UK CFS/ME community, and his collaborative work with the ME Association UK (MEA), the socalled ‘Wessely School’ (i.e. the psychiatrists affiliated with Wessely) takes CFS/ME to be a condition of ‘medically unexplained’ fatigue that is perpetuated by ‘inappropriate illness beliefs’, ‘pervasive inactivity’, ‘current membership of a self-help group’, and ‘being in receipt of disability benefits’, and that it should be managed by behavioural interventions. Indeed, according to psychiatric discourse, people diagnosed with CFS/ME suffer from ‘depressive attributional style’ (Courajet, Schotte, Wijnants, Moorkens, & Gosyns, 2009, p. 14). The ‘Wessely School’, according to UK CFS/ME patients and activists (Hooper & Williams, 2008), marginalises them by a number of tactics and practices such as: they attempt to subvert the international classification of this disorder from neurological to behavioural; they propagate ‘untruths’ about the disorder; they build affiliations with corporate industry; they denigrate those diagnosed with CFS/ME (which could be described as ‘epistemic injustice’ (Blease, Carel, & Geraght, 2017; Fricker, 2007)); they suppress published findings; and they refuse to see or acknowledge the multiplicity of symptoms. In contrast to a psychogenic (or biopsychosocial) view of CFS/ME, Ulvestad (2008) has proposed the dissolution of the ontological separation of the body and the mind, suggesting that CFS/ME can be properly understood only by taking an integrated perspective in which evolutionary, developmental and ecological aspects are considered. Many people diagnosed with CFS/ME believe that new tests would be able to show the biological abnormalities in their bodies. That is what diagnosis does; it ‘provides structure to a narrative of dysfunction […] and imposes official order, sorting out the real from the imagined’ (Jutel, 2009, pp. 278–279). The CFS/ME community is in search of biomarkers13 that would legitimise and destigmatise its illness but also improve its treatment. The CFS/ME community's search for a diagnostic biomarker – the ‘holy grail’ of CFS as a patient recently put it14 – is a struggle against the ‘psychiatrisation’ of CFS/ME, although this struggle is characterised by tensions and ambiguities with regard to psychiatry's role in explaining and treating this condition. The brain has emerged as a possible ‘objective’ explanation of the illness – this being the result of the general trend to consider the brain as the locus of ourselves (e.g. Rose, 2003; Vidal, 2009). According to Ortega and Zorzanelli (2010), in CFS/ME the explanatory hypotheses reinvent the brain as the aetiological locus. Some of the involved neuroscientists and people diagnosed

9 See http://news.bbc.co.uk/2/hi/health/3014341.stm (accessed 23 July 23, 2012). On the economics of CFS/ME, see Reynolds, Vernon, Bouchery, and Reeves (2008) and Jason, Benton, Valentine, Johnson, and Torres-Harding (2008). 10 Here I follow Moss's (n.d.) study of CFS/ME. On ICD more generally, see Bowker and Star (2000). 11 Although I can't develop this further due to lack of space, it should be noted that (as is the case in other studies of health activism) between the UK CFS/ME activist associations that I studied significant differences exist as some could be regarded as more ‘grassroots’ and others as more ‘aligned to the State’. 12 See http://www.investinme.org/Article-420%20APA%20DSM-V%20Submission. htm (accessed 23 July 2012).

13

On biomarkers, see Metzler (2010) and Singh and Rose (2009). See https://cfsremission.com/2017/03/21/the-cfs-holy-grail-the-biomarker/(accessed 19 December 2017). 14

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Fig. 1. Regional differences between CFS/ME patients and controls. Areas with significantly reduced gray-matter densities in the CFS/ME patients were located at bilateral prefrontal areas, which were surface rendered onto the highresolution MRI (Magnetic Resonance Image). Reproduced from Okada, Masaaki, Kuratsune, Yasuyoshi, and Sadato (2004).

4. Treatments

with CFS/ME think that brain can provide a conclusive aetiological account for CFS/ME (an example of this is illustrated in Fig. 1).15 A similar development perhaps took place in the explanation of Post-Traumatic Stress Disorder (PTSD) for example. It was suggested that PTSD exhibits a distinct pattern of brain activity that can be found with great accuracy by a new brain scanning technique called magnetoencephalography (MEG) (Drummond, 2010). What was once called a ‘soft disorder’ without an objective diagnosis that had to be distinguished from mental illnesses, seemed to have an accurate assessment. Moreover, at least in the US, there are practical reasons for the popular endorsement of equating mental diseases with those of the brain, since a disease considered to be real is better remunerated than diseases which are psychogenic or with no medical explanation (Ortega & Zorzanelli, 2010, n. p.). One of the most prominent neuroscientists on CFS/ME is John DeLuca (2005), director of Neuroscience Research at the Kessler Medical Rehabilitation Research and Education Corporation in the US. Johnson and DeLuca (2005, p. 148) argue that ‘[n]otions that CFS is nothing more than depression or some other psychiatric condition is too simplistic’. Johnson and DeLuca (2005; cf. Ortega-Hernandez & Shoenfeld, 2009, p. 600) instead suggest that CFS is a heterogeneous, multidimensional illness that may be related to brain dysfunction. Abnormalities or differences in the cerebral ventricular volumes can be observed by various brain imaging techniques such as Magnetic Resonance Imaging (MRI) or Near-Infrared Spectroscopy (NIRS). There have been indeed numerous studies that try to find some pathology for CFS located in the brain (e.g. Cook & Natelson, 2001; Schmaling, Lewis, Fidelak, Mahurin, & Ruchwald, 2003). Ortega and Zorzanelli (2010) find such attempts problematic because a given part of the brain can implement multiple processes and, therefore, the results should be considered only as another source of convergence of the evidence. Importantly, nevertheless, as they explain, the visual expressivity of neuroimages is rhetorically used to construct what is intended to be shown in the first place. For his part, DeLuca (2005) believes that CFS/ ME patients exaggerate and are aggressive at psychiatry. DeLuca believes modern psychiatric research has made great progress and that is why he does not appreciate the notions of ‘medically unexplained syndromes’ and ‘somatisation’ problematic and is against what might be called the ‘psychologisation’ of fatigue, which are all connected with depression and anxiety that he takes to be an effect of the spread of psychology in the popular culture.

The management of CFS/ME subjects' symptoms, again, varies. Through a variety of clinics, methods and treatments, CFS/ME subjects try to find the best possible way for the optimisation or stabilisation of their energy levels and the management of their symptoms.16 This of course does not mean that all CFS/ME subjects accept the contemporary dominant bodily norms, nor that they struggle to improve their health according to those precise norms. In fact, sometimes some of them give up hope altogether of ‘restoring’ their prior ‘energy levels’ or their ‘original’ selves and create new and sometimes ‘better’ selves (e.g. Clarke & James, 2003; Travers, 2004). Individuals diagnosed with CFS/ ME might try to increase their ‘energy levels’ by experimenting with and combining different sorts of treatments and medications (official or unofficial). Some of the people diagnosed with CFS/ME could be regarded as ‘neurochemical subjects’ (Rose, 2003; see also Ortega, 2009), as regions or processes of their brains have become an integral part of their identities. People diagnosed with CFS/ME try to understand what is happening in/to their bodies. Of course this is not pure intellectual curiosity but stems from their quest for objectivity, legitimacy, and ‘energy’. They want a ‘cure’17 or at least the knowledge to reduce their symptoms and make their selves more ‘controllable’. While there is a range of mainly non-pharmacological ‘treatments’ or ‘rehabilitation strategies’, only two have demonstrated reproducible evidence for their efficacy in non-severely affected CFS/ME patients: cognitive behaviour therapy (CBT) and graded exercise therapy (GET). Based on evidence from multiple randomised clinical trials (RCTs),18 a Cochrane systematic review (Chambers, Bagnall, Hempel, & Forbes, 2006; see also, Twisk, 2017, p. 3; Yancey & Thomas, 2012, p. 741–742) claimed that cognitive behaviour therapy and graded exercise therapy interventions showed promising results, appearing to reduce symptoms and improve function.19 According to the cognitive-behavioural model of illness, the patient's interpretation of symptoms plays an important role in perpetuating the illness (e.g. Sharpe, 1991; Wessely, 1989).

16 A number of individuals diagnosed with CFS might use complementary and alternative medicine (CAM) like Reiki or Yoga. 17 Importantly, Wasserman and Hinote (2011, p. 42) note that the epidemiological shift moves away from infectious diseases towards chronic, sometimes manageable but rarely curable, illnesses like diabetes. 18 On randomised clinical trials, see Wahlberg and McGoey (2007) and Petryna (2007, p. 26). Here I am also influenced by Richards (1988). 19 The aforementioned reports were based on the premises of evidence-based medicine (EBM), and its correlative, the health care trend of evidence-based treatment (EBT) according to which specific treatments for symptom-based diagnoses are recommended. On evidence-based medicine, see Mykhalovskiy and Weir (2004) and Timmermans and Mauck (2005).

15 On brain scanning and the uncertainty that exists in its scientific application, see Alac (2008), Beaulieu (2002), Dumit (2003), Johnson (2008), and Prasad (2005).

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Cognitive behaviour therapy aims to help the patient change the ‘negative beliefs’ that s/he has with the goal being either to reduce the symptoms and help the patient cope with the illness or to fully recover. On the other hand, graded exercise therapy is a physical activity that starts very slowly and gradually increases over time. Despite some limitations with the evidence and the generalisability of the findings, two reviews cautiously concluded that some patients may benefit from graded exercise therapy (Chambers et al., 2006; Edmonds, McGuire, & Price, 2004). Lastly, pacing is probably the most accepted form of treatment after cognitive behaviour therapy and graded exercise therapy. Pacing therapies encourages behavioural change, but unlike cognitive behaviour therapy, they acknowledge the typical patient fluctuations in symptom severity and delayed exercise recovery. Pacing's goal is to increase over time the level of ‘routine functioning’ of the individual. A randomised clinical trial concluded that pacing with graded exercise therapy had statistically better results than relaxation therapy (Deale, Husain, Chalder, & Wessely, 2001; Wallman, Morton, Goodman, Grove, & Guilfoye, 2004), and a 2008 patient survey by the Action for ME in fact found pacing to be the most helpful treatment.20 CFS/ME organisations have often lobbied in favour of particular types of research or, alternatively, protested against studies they considered unethical or harmless. The National Institute for Health and Clinical Excellence (NICE) issued their guidelines for CFS/ME in August 2010 amid protests from patients and medical researchers that they had not followed correct protocols in producing the guidelines.21 Patient groups feared that some patients could be pressured into accepting treatments which at best may be useless and at worst could cause real harm and campaigned against them. Professor Peter Littlejohn, NICE's public health director, welcomed the decision by saying ‘these are very good news for the thousands of people with ME, who can continue to benefit from evidence-based diagnosis, management and care for this disabling condition’.22 In its 2007 Clinical Guideline 53 on CFS/ME, the National Institute for Health and Clinical Excellence recommended that the Canadian case definition of CFS/ME, which excludes patients with symptoms of mental illness, should not be used in the UK. According to the Hooper (2010, p. 14):

Ankeny and Mackenzie (2016) work on CFS/ME policy-making forces us to recognise and stress out the importance of the specificity of the national context when discussing decision-making (e.g. over diagnostic categories or the provision of health-care) in controversial areas in medicine where uncertainties exist. As Ankeny and MacKenzie (2016) show, the UK and the Australian contexts seem to be less democratic in that they do not favour much input from the sufferers themselves. In contrast, the Canadian context is deemed, by Ankeny and MacKenzie, more dialogical and democratic, allowing much more input from the sufferers. Furthermore, there was criticism of the scientific integrity of the panel of the trial (which apparently consisted mostly of members of the ‘Wessely School’), the legitimacy and credibility of statisticians, and the aim of the trial in the first place. Between 2002 and 2003 many members of the ‘Wessely School’ were appointed to Medical Research Council boards including Michael Sharpe and Simon Wessely.23 The panel, it was claimed, had direct affiliations with insurance companies. The PACE trial was the only clinical trial that the Department for Welfare and Pensions (DWP) has ever funded and the only one that patients and their organisation tried to prevent, CFS/ME patients claimed. Wessely himself set up and directed The Mental Health & Neuroscience Clinical Trials Unit in 2002, which was the first unit in the UK to specialise in mental health and the neurosciences, and which, in its first six years of operation, provided advice and support to a large number of grant applications. Furthermore, when the Medical Research Council, that classified CFS/ME as a mental health problem, was challenged, Dr Robert Buckle, member of the Medical Research Council and of the PACE Trial Steering Committee, subsequently stated that CFS/ME was classified as a mental health problem for a ‘pragmatic’ reason ‘related to the Medical Research Council grants classification associated with the activities of one section of the office’ (Hooper, 2010, p. 47). After a proposal from the interdisciplinary Medical Research Council CFS/ME Research Advisory Group, that includes experts from a wide range of disciplines as well as input from the major UK-based CFS/ ME patient charities, the Medical Research Council has now a dedicated budget for research in areas such as autonomic dysfunction, immune dysregulation, and sleep disorders in patients diagnosed with CFS/ME.

ME/CFS is the only condition for which behavioural modification is the primary (indeed only) management approach in a NICE Guideline. The MRC [Medical Research Council] declines to fund biomedical studies, yet the cost of implementing the Wessely School regime in the UK is £3.75 million annually, in addition to non-recurrent costs of £26.45 million (Breakthrough, ME Research UK, Spring 2008).

5. The ‘discovery’ of the XMRV virus: A new ‘political economy of hope’ Biomedicine's growing demand for standardisation is illustrated by the fact that while biomedical researchers need clear diagnostic tests to justify applications to funding agencies that increasingly demand comparable and reproducible results, pharmaceutical corporations require standardised diagnosis if they are to develop and sell their products (Knaapen & Weisz, 2008, p. 127). Biomedical companies are in an ever-increasing search for new market niches but not fertile ground has been found in the CFS/ME field. In the US context, various experimental anti-retroviral drugs have not managed to be granted approval. Currently, the US Food and Drug Administration (FDA) do not approve any drug for treating CFS/ME, although a number of CFS/ME trials that set out to test the efficacy of experimental drugs have had mixed findings. Furthermore, a considerable number of these studies were based on only a small number of patients and hence consistent results have been hard to replicate. Ampligen (Ritatolimond), for instance, an experimental immunomodulatory drug developed by US pharmaceutical Hemispherx, has been tested as a treatment for a wide array of illnesses including AIDS and, more recently, CFS/ME, with limited success. Being a controversial drug, its critics said that Hemispherx was desperate to make some money on a failed project. Hemispherx reported the completion of a Phase III clinical trial for CFS/ME in 2004

The aforementioned criticisms and interventions by CFS/ME activists illustrate the growing activism of biosocial communities or to use different terminology, ‘embodied health movements’ (Brown et al., 2004) and that medical knowledge and expertise is nowadays less unequally distributed between practitioners and patients. Moreover,

20 See http://www.actionforme.org.uk/Resources/Action%20for%20ME/Documents/ get-informed/ME%202008%20%20What%20progress.pdf (accessed 23 July 2012). 21 See http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/ PublicationsPolicyAndGuidance/DH4064840 (accessed 23 July 2012). 22 Another example of the UK CFS/ME community's activism is their involvement in the ‘PACE’ trial. The ‘PACE’ trial was a relatively large-scale government-funded CFS/ME trial conducted between 2006 and 2011 in the UK. Its purpose was to compare the efficacy and safety of four treatments: cognitive behaviour therapy, graded exercise therapy, Specialist Medical Therapy (SMT) (care delivered by experienced clinicians at treating CFS/ME) and Adaptive Pacing Therapy (APT). The results showed that CBT and GET were moderately effective compared to SMT alone. APT was not found to be effective when added to SMT. Patient groups criticised the PACE trial for over-simplified and exaggerated conclusions, for using a ‘flawed psychosocial illness model’ that ignores biological evidence, for testing a ‘non-representative’ version of pacing, and because the results seriously conflicted with their member surveys which showed that pacing is effective and that cognitive behaviour therapy and GET can cause deterioration in many patients who use the treatments; see http://www.pacetrial.org/(accessed 23 July 2012).

23 See http://www.cfstheresistance.com/the-wessely-school-and-the-medicalresearch-counci.php (accessed 23 July 2012).

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and filed a new drug application (NDA) with the FDA to market and sell Ampligen for the treatment of CFS/ME.24 Ampligen would have been the first FDA-approved treatment for CFS/ME. However, it was rejected in 2009 and again in 2011 because the FDA concluded that the randomised clinical trials did not provide credible evidence of efficacy due to their small numbers.25 Many involved patients and researchers believed that the ‘discovery’ of a new virus (the third known human retrovirus after HTLV (Human T-lymphotropic virus) and HIV), XMRV (Xenotropic murine leukemia virus-related virus), would prove to be the causative agent of CFS/ME, thus giving rise to a new ‘political economy of hope’ (Novas, 2006) in the CFS/ME world. A study by Lombardi et al. (2009) claimed to have found XMRV in the peripheral blood mononuclear cells of patients with confirmed CFS/ME, and a second study by Lo et al. (2010) reported that scientists from the FDA's Center for Biologics Evaluation and Research and the National Institute of Health (NIH) have found MLV (Murine Leukemia Viruses)-related gene sequences in patients diagnosed with CFS/ME and in some healthy blood donors. Those findings, which were published online on 23rd August 2010 in the Proceedings of the National Academy of Sciences, added to the evidence that a virus may play a role in some, if not all, cases of CFS/ME, and lend support to Lombardi et al.’s study. Lo et al.’s study showed that 86.5% of 37 people diagnosed with CFS/ME had evidence of that virus in their blood, as did 6.8% of healthy blood donors, backing up a report by researchers at the Nevada Centre for Biomedical Research in US (before 2016 named Whittemore Peterson Institute for Neuro-Immune Disease (WPI)), which showed similar results. ‘Other labs have not found this virus, so a dilemma at present is how to reconcile that some labs find the association and others do not’, said Harvey Alter, a hepatitis expert and chief of clinical studies and associate director for research in the department of transfusion medicine at the NIH Clinical Center.26 Nevertheless, later studies found no results whatsoever (Erlwein et al., 2010; Groom et al., 2010; van Kuppeveld et al., 2010). The Nevada Centre for Biomedical Research27 claimed it was ‘leveraging an international network of dedicated virologists, immunologists, geneticists and other highly skilled researchers’. The virologist and spokesperson of the CFS/ME cause, Dr Judy Mikovits, was one of them. The National Cancer Institute in the US has already started working on a vaccine and clinical trials are expected to begin at the Nevada Centre for Biomedical Research sometime next year, Mikovits said in 2009. The world's largest pharmaceutical companies, among them LabCorp and Quest, have been calling the institute asking if they can test their lines of a drug now used to treat patients with HIV to see if their anti-viral drugs can be adapted to treat CFS/ME patients, Mikovits said.28 The drug companies would pay for the Reno Institute's cell lines – an institute located in the university of Nevada with which the Nevada Centre for Biomedical Research was affiliated—, the established cultures that would grow the XMRV retrovirus, so they can test their antiviral drugs on them. According to the Nevada Centre for Biomedical Research, future research and biotechnology stemming from the initial study was expected to generate more research and intellectual property, and Mikovits and Dr Ruscetti filed for a patent for an antibody test for XMRV.29 Suspicion arose in the CFS/ME community internationally

that the Nevada Centre for Biomedical Research was supporting the financial interests of certain pharmaceutical companies. The Nevada Centre for Biomedical Research would deny such allegations, stating on their website that none of their staff has ‘any financial interests or holdings in the various pharmaceutical companies who produce drugs used to treat chronic diseases’.30 Let us now turn to what happened with the battle over the publication of findings around XMRV. In May 2011, the editors of Science (Alberts, 2011) asked the coauthors of the Lombardi et al. paper to voluntarily retract the paper following other studies that have failed to detect the retrovirus. Mikovits, one of the paper's key authors, strongly refused to retract, citing the fact that other studies have indeed found evidence of the retrovirus infection, that no study to date has replicated or disproved her original research, and that other major scientific investigations into gamma retrovirus infection are being conducted. In addition, there was a delay of a publication related to XMRV. This happened in the case of Alter and his team, who identified viruses similar to XMRV in 32 of 37 people diagnosed with CFS/ME and in 3 of 44 healthy people and were preparing to publish their results in the Proceedings of the National Academy of Sciences, but because scientists at the Centre for Disease Control and Prevention were about to publish a negative report, they had to delay their publications to assess discrepancies (Callaway, 2011). Moreover, some scientists (Kearney et al., 2012; Oakes et al., 2010) claimed that some studies have used samples contaminated with mice samples and therefore the credibility of those studies was seriously challenged. After XMRV was found in some CFS/ME patients' blood, the Invest in M.E., for example, published these findings in their 2010 conference, considering them a major ‘breakthrough’ in the understanding and treatment of CFS/ME. The Invest in M.E. claimed that for 2011 the way forward was to focus on translational biomedical research into CFS/ME with the initiation of clinical trials using ‘homogeneous patient cohorts’ and ‘correct clinical guidelines’. The International ME/CFS Conference 2011: The Way Forward for ME was oriented toward providing ‘knowledge of the latest research and the biomarkers which allow appropriate treatments to be prescribed’.31Apart from knowledge of the ongoing biomedical research, it was necessary for healthcare staff to be aware of the multiple symptoms exhibited by CFS/ME patients and the possible treatments available. Research data, experiences of treating CFS/ME, and findings from the latest biomedical research were presented. Similar attempts to expand biomedical research on CFS/ME have been made. One of them was the NIH's ‘State of Science’ meetings on CFS/ME in 2012 in the US, of which the planning committee included members of the CFSCC and other patient advocates.32The workshop concentrated on various areas including infectious diseases, immunology, neurology, diagnosis and biomarkers, treatments, gaps in existing knowledge and opportunities. Scientific director of CFIDS Association of America, Dr Suzanne Vernon, presented a comprehensive summary of the gaps and opportunities in CFS/ME research identified during the workshop.33 Some of the gaps in then current knowledge and research studies included: lack of enough money and researchers; lack of animal models; lack of doctors to treat CFS/ME patients; lack of standard operating procedures for studies; and that biomarkers are not

24 See http://www.cfs-info.com/joomla/index2.php?option=com_content&do_pdf=1 &id=1398 (accessed 23 July 2012). 25 See http://www.hemispherx.net/content/investor/default.asp?goto=738 (accessed 23 July 2012). 26 See http://online.wsj.com/articles/ SB10001424127887324731304578191951426646118 (accessed 15 November 2014). 27 See http://www.examiner.com/article/breakthrough-for-chronic-fatigue-syndrome (23 July 2012). 28 See http://www.patentmaps.com/inventor/Mikovits_Judy_A_1.html (accessed 23 July 2012) and http://www.ei-resource.org/functional-laboratory-tests/gastrointestinal/ neurotoxic-metabolite-test-%28nmt%29 (accessed 23 July 2012). 29 See http://www.plosone.org/annotation/listThread.action;jsessionid= CA8A144D535CB340555FCA9B7EEEA090?root=18075 (accessed 23 July 2012).

30 It should be noted that Mikovits was at the time director of research at the Genyous Biomed International Inc and Kenny DeMeirleir a member of Protea Pharma; see http:// www.vitalatherapeutics.com/about.htm (accessed 23 July 2012). It should also be noted that the Nevada Centre for Biomedical Research was linked to Cerus Corporation, a US biomedical company focused on commercialising internationally the INTERCEPT Blood System to enhance blood safety; see http://www.americasblood.org/download/File/ newsletter_sample.pdf (accessed 23 July 2012). 31 See http://www.investinme.org/IIME%20Conference%202011/IiME %202011%20International%20ME%20Conference.htm (accessed 23 July 2012). 32 See http://www.research1st.com/2011/06/28/meeting-summary-mecfs-state-ofthe-knowledge-workshop/(accessed 23 July 2012). 33 See http://www.cfids.org/profresources/grants-guidelines.asp (accessed 23 July 2012).

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both in the clinic and in the laboratory and to change the classifications of CFS/ME. While the standardisation of diagnostic categories, biomarkers, and evidence are an increasing demand for biomedicine, CFS/ ME is difficult to standardise. The attempts to standardise the treatment of CFS/ME have also been strong, even if none of the results of largescale randomised clinical trials showing a statistical benefit for one treatment or another have been conclusive. Although the XMRV virus was not proven to be the causative agent of CFS/ME, to the disappointment of people diagnosed with CFS/ME internationally, it gave rise to a new ‘political economy of hope’ (Novas, 2006) and was significant in augmenting biomedical research on CFS/ME. But as long as CFS/ME is broadly considered a psychogenic illness it remains illegitimate or with little legitimacy. None of the actors in the CFS/ME network has managed to ‘speak’ on behalf of all others, to force everyone else to accept its own language and logic. CFS/ME remains trapped between medicine and psychiatry, in an on-going battle between all the different actors that want to define it for their own interests.

reproducible, replicated and validated. However, these difficulties, Vernon added, can be addressed and progress made. While the hopes of establishing the XMRV virus and the polytropic MLVs viruses as the causative agents had been minimised, if not completely abandoned, then Chair of Trans-NIH ME/CFS Research Working Group at the NIH and in charge of the CFS/ME programme at the Office of Research For Women's Health in the US, Dennis Mangan remarked that ‘this does not alter the evidence of neurologic dysfunction in CFS, and it does not have a bearing on evidence linking CFS/ME with other neurotropic viruses – particularly human herpesvirus 6 and enteroviruses’ (Holgate, Komaroff, Mangan, & Wessely, 2011, p. 543). Besides demanding more biomedical research, people diagnosed with CFS/ME and associated organisations were fighting the then new DSM (Diagnostic Manual for Mental Illness)-5 proposals, which they believed would affect both research and clinical care. The Patient Alliance for Neuroendocrineimmune Disorders Organization for Research and Advocacy, Inc. (P.A.N.D.O.R.A) is one of these organisations in the US. The proposed changes of DSM-5 would combine several existing somatic categories into one larger category, the so-called ‘complex somatic symptom disorder’ (CSSD), the P.A.N.D.O.R.A. claimed. In trying to prevent this, the P.A.N.D.O.R.A. sent a letter of concern to the American Psychiatric Association (APA), saying they were deeply concerned by that potential reclassification which not only may include CFS/ME as a somatoform disorder but also other illnesses such as fibromyalgia.34 The P.A.N.D.O.R.A. claimed that researchers from the both the NIH and the Centre for Disease Control and Prevention have documented the pathophysiological underpinnings of the illness and that the Centre for Disease Control and Prevention has launched a campaign of a million dollars within the past few years to underscore that CFS/ME is a multisystem disorder. In a paper dedicated to CFS/ME's future, Mangan together with Wessely, concluded that the neurosciences is the field where new insights into the nature of CFS/ME are most likely to emerge, a field which has strong connections with other domains of CFS/ME like infection and inflammation, immune dysfunction, and sleep (Holgate et al., 2011, pp. 543–544). More recently, ME Research UK funded work which looks for an ‘immunosignature’ that can predict patients' responses to rituximab therapy (e.g. Lawrence, 2016; Twisk, 2017, p. 3). Vincent Lombardi now concentrates on exactly such research. As he and his collaborators put it in a recent paper:

Acknowledgements Thanks a lot to the two anonymous reviewers whose insightful readings revealed blind spots and helped to improve the arguments in the paper, and to the editor Rachel Ankeny for her help during the editing process. I would also like to thank Dimitris Papadopoulos for his perceptive comments on an early version of the article. Any remaining limiting limitations are, of course, my responsibility. References Alac, M. (2008). Working with brain scans: Digital images and gestural interaction in fMRI laboratory. Social Studies of Science, 38(4), 483–508. Alberts, B. (2011). Editorial express of concern. Science Express. Available at: www. sciencemag.org/content/early/2011/05/31/science.1208542.full.pdf, Accessed date: 23 July 2012. Ankeny, R., & MacKenzie, F. (2016). Three approaches to chronic fatigue syndrome in the United Kingdom, Australia, and Canada: Lessons for democratic policy. In S. Dodds, & R. Ankeny (Eds.). Big pictures bioethics: Developing democratic policy in contested domains (pp. 227–243). Switzerland: Springer. Arabatzis, T. (2011). On the historicity of scientific objects. Erkenn, 75(3), 377–390. Aroll, M., & Senior, V. (2008). Individuals' experience of chronic fatigue syndrome/ myalgic encephalomyelitis: An interpretive phenomenological analysis. Psychology and Health, 23(4), 443–458. Åsbring, P., & Närvänen, A. (2004). Patient power and control: A study of women with uncertain illness trajectories. Qualitative Health Research, 14(2), 226–240. Beaulieu, A. (2002). Images Are not the (only) truth: Brain mapping, visual knowledge, and iconoclasm. Science, Technology & Human Values, 27(1), 53–86. Blease, C., Carel, H., & Geraght, K. (2017). Epistemic injustice in healthcare encounters: Evidence from chronic fatigue syndrome. Journal of Medical Ethics, 43, 549–557. Bowker, G., & Star, S. (2000). Sorting things out: Classification and its consequences. London: The MIT Press. Brown, P., Zavestoski, S., McCormick, S., Mayer, B., Morello-Frosch, R., & Altman, R. (2004). ‘Embodied health movements: New approaches to social movements in health’. Sociology of Health & Illness, 26(1), 50–80. Brurberg, K., Fønhus, M., Flottorp, S., & Malterud, K. (2014). Case definitions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): A systematic review. British Medical Journal, 4(2). Bülow, P. (2004). Sharing experiences of contested illness by storytelling. Discourse & Society, 15(1), 33–53. Callaway, E. (2011). Chronic fatigue syndrome: Life after XMRV. Available at: http://www. nature.com/news/2011/110603/full/news.2011.347.html?s=news_rss, Accessed date: 23 July 2012. Callon, M., & Latour, B. (1981). Unscrewing the big leviathan: How actors macro-structure reality and how sociologists help them to do so. In K. Knorr-Cetina, & A. Cicourel (Eds.). Advances in social theory (pp. 277–303). London: Routledge & Kegan Paul. Callon, M., & Rabeharisoa, V. (2008). The growing engagement of emergent concerned groups in political and economic life: Lessons from the French association of neuromuscular disease patients. Science, Technology & Human Values, 33(2), 230–261. Cambrosio, A., Keating, P., Schlich, T., & Weisz, G. (2006). Regulatory objectivity and the generation and management of evidence in medicine. Social Science & Medicine, 63(1), 189–199. Chambers, C., Bagnall, A.-M., Hempel, S., & Forbes, C. (2006). Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: An updated systematic review. Journal of the Royal Society of Medicine, 99(10), 506–520. Clarke, J., & James, S. (2003). The radicalized self: The impact on the self of the contested

In contrast to identifying biomarkers that are directly involved in the pathological process, an immunosignature identifies antibodies raised to proteins expressed during, and potentially involved in, the pathological process (Singh et al., 2016: 1). Moreover, research now seems to concentrate on a different potential biomarker, activin (Lidbury et al., 2017), a protein complex. Various other biomarkers for both diagnostic and treatments purposes have been suggested and there is in Europe a large project dedicated to this called ‘The European ME/CFS Biomarker Landscape project’ (Scheibenogen et al., 2017).35 All these actions once more attest to the fact that CFS/ME organisations, this time on a pan-European level, are very active, aware of the current biomedical research on CFS/ME, and that they strive to biomedicalize CFS/ME. To conclude, people diagnosed with CFS/ME demand a biomedical explanation that will destigmatise their condition and potentially improve it. This paper has argued that there has been a remarkable effort by CFS/ME organisations and medical scientists to standardise CFS/ME

34 See http://www.pandoranet.info/documents/LetterAPA-DSMCONCERNS2010.pdf (accessed 23 July 2012). 35 According to Scheibenogen et al. (2017, p. 3), [i]nstead of searching single markers fitting for diagnosing all patients, multiplexed determinations of biomarkes analyzing pathways together with patient stratification, may be necessary to develop diagnostic assays with sufficient sensitivity and specificity’.

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