According to Jain (2009: 5), the adoption of PGx into mainstream medicine represents an ‘evolution and not a revolution’ as personalisation has always been central to medical practice. As such, the clinical practices arising from PGx represent the next phase of the personalised medicine story rather than a completely novel ideology or approach.
Perhaps the earliest known example of personalised medicine principles is Pythagoras’ observation in 510BC that some individuals developed a fatal reaction to ingesting fava beans. More recently, nineteenth century Korean Sasang Constitutional Medicine (SCM) divided the human population into four discreet categories based on individuals’ physiological, psychological and physical characteristics which are thought to result in herbal medicine response variation (Kim et al., 2009; Shim et al., 2008). Drawing upon these characteristics, practitioners in this sphere of medicine are able to diagnose the constitution of each patient and offer them a personalised therapy regime. In this vein, SCM can be understood as a form of Pickstone’s (2000) ‘natural history’ medical practice where patients’ constitution is explained and managed in natural, rather than supernatural terms. More recently, this personalised natural history approach has been somewhat legitimised by ‘technoscience’ discourses of genetics where the four categories of patients identified in SCM have been shown to have a genetic basis (Kim et al., 2009).
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medicine. He argues that personalised care and therapy can be seen throughout the history of western medical practice where a conflict between ‘universalism and specificity’ can be seen throughout recent medical history. This is not to say that ‘personalised medicine’ per se has always existed in medical practice but rather that different historical forms of personalisation have been enacted throughout nineteenth and twentieth century medicine (Tutton, 2012). He traces the trajectory of personalised western medical practice since the mid-19th century at which time new emerging field of scientific research, most relevantly therapeutics, shifted the focus of medical practice away from what Jewson (1976) calls ‘bedside medicine’ to ‘laboratory medicine’. Within this way of seeing and practising, bodies, diseases and therapeutics became less individualised and more focused on quantifiable universality.
This approach, however, was contested from within the medical profession throughout the nineteenth and twentieth centuries where the conflict between the ‘universalism’ of laboratory medicine and the ‘specificity’ of medical practice routines developed. Tutton (2012) argues that whilst nineteenth century British doctors discursively positioned the practice of personalised medicine as a set of skills- or ‘art’- which no-one else could claim to possess, twentieth century researchers drew attention to the individual psychological and socio-economic factors affecting patients’ health. More recently, laboratory science itself has begun investigating personalisation and individuality through the field of pharmacogenetics.
The foundations for what one might call the scientific discipline of PGx were discursively laid down by the English physician Sir Archibald Garrod in 1931 when he observed that inherent individual differences were medically significant and should be taken into account during treatment decisions (Kalow, 2006). Following this, the discreet field of PGx emerged during the 1950s as an experimental science focusing on inherited differences in human reactions to drugs (Council for International Organisations of Medical Sciences, 2005). The majority of the empirical groundwork in the field was done in the early 1950s using succinylcholine (a short-term muscle relaxant), isoniazid (an anti-TB medication) and primaquine (an anti-malarial medication) (Weber, 2008).The results from these, and other,
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experiments were drawn together in arguably the most seminal and influential paper in the discipline, Arno Motulsky’s (1957) Drug Reactions, Enzymes and
Biochemical Genetics. In this paper, Motulsky (1957: 170) argued that the
differential reactions found in these studies demonstrated that ‘hereditary gene- controlled enzymatic factors determine why, with identical exposure, certain individuals become ‘sick’, whereas others are not affected’. Two years after the publication of this seminal work, the term ‘pharmacogenetics’ was coined by Friedrich Vogel to describe this burgeoning field of research and in the following decade the importance of genetics in drug metabolism variation was demonstrated through numerous twin studies (Vesell and Page, 1968a; Vesell and Page, 1968b).
Although the interest in PGx gained and sustained a great deal of interest in the decades following the foundation of the discipline in the 1950s, the field expanded at a relatively slow pace with drug-gene relationships being extrapolated as researchers came across them rather than there being an active search for such relationships (Hedgecoe, 2004). In the 1980s, however, the ‘molecular turn’ in biological science meant that molecular testing was becoming more widespread in laboratories and scientists working within PGx were able to identify polymorphic nucleotides within the genes which encode enzymes which were known to be responsible for drug response variance (Weber, 2008). The molecular turn in PGx more specifically can be traced to 1988 when Frank Gonzalez and colleagues at the National Cancer Institute in the USA successfully cloned the complementary DNA (cDNA) of the CYP2D6 gene, which forms part of the P450 cytochrome system of enzymes. This was a significant breakthrough in the field of PGx as the enzymes of cytochrome P450 are responsible for clearing over half of all clinically used drugs, with the genes CYP2D6 and CYP2C19 being responsible for the metabolism of most of these (Gonzalez et al., 1988; Meyer, 2004). Hence, changes on these genes have subsequently been shown to affect drug reactions and metabolic ability.
Findings from Gonzalez’s study and the development of a number of new technologies, such as recombinant DNA and polymerase chain reaction (PCR) opened up the field of PGx to ‘the new genetics’ which was sparked by the 1953 discovery of the double helix structure of DNA and concerned with providing genetic explanations for various traits, diseases, behaviours and idiosyncrasies
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(Conrad and Gabe, 1999). Latterly, in the 1990s, the HGP provided a tool with which scientists could deepen their understanding of genetically-influenced human diversity and located PGx within the biomedical field of genomics (Clarke et al., 2003).
Following the successful completion of the first draft of the HGP’s findings, PGx was seen as ‘the next great challenge’ (Liggett, 2001: 285) for the application of the technologies and information generated from the Project. Building on the somewhat diverse, although ultimately successful, partnership between public and private approaches to the HGP, the SNP Consortium was founded as a collaborative effort between eleven private companies7 and the medical charity the Wellcome Trust to locate, detail and make publicly available, 3,000,000 SNPs in the human genome over a two year period (Holden, 2002; Thorisson and Stein, 2003). When the project reached its conclusion in 2001, it had far exceeded this expectation and successfully located and published details of 1.4 million SNPs, which helped to mobilise industrial interest in PGx research (see Hedgecoe, 2004). Following this in 2002, the International HapMap Project was launched as a means of detailing the most common haplotypes (a set of related SNPs which are important in drug response variability) in the global human population. More recently, in 2011 the UK Technology Strategy Board announced stratified medicine as a key five year priority area and launched the Stratified Medicine Innovation Platform with the objective to invest £200 million in stratified medicine projects by 2016.
The principles of personalisation, then, can be traced from an early ‘natural history’ way of knowing to their centralisation within contemporary technoscientific biomedicine approaches to the body, disease and wellbeing. The disjuncture between personalisation discourses in traditional medicine and more contemporary biomedicine is, arguably, a reflection of the multiplicity of interests which are currently served in the latter. In other words, personalised approaches in traditional medical practice existed primarily for the benefit of patient vis-a-vis maximising efficacy and reducing ADRs. Contemporary approaches to personalisation, however,
7 The companies involved in the SNP are: Amersham Biosciences, AstraZeneca, Aventis, Bayer AG,
Bristol-Meyers Squibb Company, F. Hoffmann-LeRoche, GlaxoSmithKline, IBM, Motorola, Novartis, Pfizer and Searle (Hedgecoe, 2004: 11).
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co-construct the interests of a number of groups of actors- public healthcare institutions, private drug development companies and patients. This chapter now turns to an examination of the ‘promises’ (Hedgecoe and Martin, 2003) which PGx holds for these different groups of actors.