ONE
Genomic Designation: How Genetics Creates New Medical Conditions
But this order of the solid, visible body is only one wayâin all likelihood neither the first, nor the most fundamentalâin which one spatializes disease. There have been, and will be, other distributions of illness.
Michel Foucault, The Birth of the Clinic
From the clinical standpoint, [22q13 deletion] syndrome may be underdiagnosed because of the lack of a recognizable phenotype that would lead the clinician to request studies to rule out this specific chromosome 22 deletion.
Phelan et al., â22q13 Deletion Syndromeâ
For sixty years now, we have been delineating medical conditions that are united not by observations of patientsâ bodies, evaluations of their psyches, or predictions of their fate, but by specific genetic mutations. Finding a mutation can lead experts to report a completely new category of human disease and difference. In other cases, it can result in the lumping together, splitting up, or recalibration of existing disease categories. This chapter introduces and defines this practice, which I call the genomic designation of medical conditions.
Genomic designation is the delineation and diagnosis of medical conditions strictly according to observations of abnormal genomes, be it whole chromosome duplications, tiny point mutations, or anything in between.1 When a newly discovered mutation does not line up with an existing condition and instead comes to designate a new disorder, we have a case of genomic designation. Most genomically designated conditions lack the phenotypic coherence or distinctiveness to be clinically diagnosable at all. Instead, the genome itself is the locus of classification.
Ever since 1959, genomic designation has been endemic to genetics research. As we explore in chapter 2, the ability to see, count, and distinguish between chromosomes under a microscope led almost immediately to the first cases of genomic designation. In the decades that followed, innovations in genetic testing quickly led to the discovery of new genomically designated conditions. Meanwhile, long-standing mutations have been rendered visible and more or less stable across different genetic testing platformsâfrom karyotype analysis to whole genome sequencing. Hundreds of conditions have now been discovered or reshaped through genomic designation. So far, however, only a much smaller number have become the sorts of categories that can truly transform peopleâs lives. Beginning in this chapter, we are going to explore the varied history of carving up human difference through genomic designation.
For people with a genomically designated condition, having a genetic mutation means something that is at once crystal clear and deeply uncertain. Take one of our main case studies in this chapter: the microdeletion of genetic material at site 13.3 on the long arm of the twenty-second chromosome. Having this 22q13.3 chromosomal deletion means someone has 22q13 Deletion Syndrome (22q13DSânot to be confused with 22q11.2DS). Yet had the 22q13 deletion never been discovered, 22q13DS would be unthinkable. Even the researchers most responsible for establishing 22q13DS in the medical literature noted the âlack of a recognizable phenotypeâ that could even indicate genetic testing (Phelan et al. 2001:98).
This makes 22q13DS quite unlike most well-known genetic disordersâHuntingtonâs disease, cystic fibrosis, Down syndrome, and so onâor genomic risk factors like the BRCA variants. In all of those cases, established medical conditions were found to have a significant relationship with genetic mutations. By contrast, 22q13DS reverses this sequence of genotype-phenotype association. This syndrome is actually one of the most consistently severe conditions discussed in this book. Even so, it could never have been conceived of until after the identification of the 22q13 (pronounced twenty-two-q-one-three) chromosomal deletion. Hence, the 22q13 deletion became a subject of scientific investigation around 1988, some thirteen years before the syndrome named after it was proclaimed and the 22q13 Deletion Syndrome Foundation was formed. The patient population and its clinical profile depend entirely on the people found to carry a 22q13 deletion and what they are like. Today, knowledge about 22q13DSânow known as Phelan-McDermid syndrome (PMS)âand the work of the renamed Phelan-McDermid Syndrome Foundation have a powerful impact on the lives of patients and their families. This very clear process of discovery, delineation, and mobilization captures the essence of genomic designation.
A New Front in the Social Studies of Genetics and Medicine
While genomic designation establishes an unusual level of certainty at the level of etiology, it often does so at the expense of clinical specificity. In most cases it is unlikely that diagnosis could, even in principle, take place on the basis of what someone is actually like (i.e., their phenotype). Conditions like 22q13DS therefore go beyond the matter of social action undertaken on the basis of reductionism or risk, which in one form or another has been the focus of most of the social scientific literature on genetics and medicine (e.g., Callon and Rabeharisoa 2003; Hacking 2006a; Hedgecoe 2001; Lippman 1991b; Rabinow 1996; Rose 2007b). In this way, genomic designation builds upon but also powerfully subverts the âclinical gazeâ (Foucault 1973; Rose 1998b)âthe nosological relationship between the observed and the unobserved that privileges localized anatomo-clinical observationâwhich has dominated medical classification since the nineteenth century. In conditions like 22q13DS, genetic mutations take on great meaning, not as a proxy in the form of a predisposition or an essentializing explanation, but as the core referent of a new category of human difference. The sociological interest in genomic designation therefore goes beyond the study of a bunch of new disease entities, or what Hacking called âhuman kinds.â Instead, it extends to the emergence of a new kind of human kind that can reconfigure the way we understand and act on difference, illness, and disability.
Grappling with genomic designation forces us to rethink the relationship between genetics, medical classification, and human difference. Existing research has shown how discovering explanatory mutations may or may not reshape diagnostic protocols for conditions like Huntingtonâs and Cystic Fibrosis, how finding a mutation in a seemingly normal patient can create a âpatient in waiting,â and how it takes a network of experts to simultaneously understand the clinical and biological significance of mutations.2 Looking at genomic designation, however, shows us how knowledge about genetic mutations can be used to carve out novel medical conditions and communities, not just refine, destabilize, or help us understand old ones.
Genomic designation therefore both challenges and extends three seminal concepts in social studies of genetics: biosociality, geneticization, and the molecular gaze. Abby Lippmanâs work on geneticization helped spark an explosion of interest in the âongoing process by which differences between individuals are reduced to their DNA codes, with most disorders, behaviors and psychological variations defined, at least in part, as genetic in originâ (1991a:19). Scholars have paid particular attention to the way this process of geneticization essentializes differences between persons, sometimes in ways that contribute to stigmatization (see Phelan 2005; see also Hedgecoe 2001 on âenlightened geneticizationâ).
So, genomic designation could be understood as a radical form of geneticization: it is, if nothing else, built on the premise that we should parse human difference according to genetic abnormality. Many of the concerns Lippman raised when she introduced geneticization to the social sciencesâthe power of genetics to define abnormality and disability, the social implications of prenatal testing, and the resurgent specter of eugenicsâmay even be more likely to emerge through genomic designation than the gene-for model. And yet, genomic designation does not simply reduce existing categories to genetic mutations: it produces new categories of disease and difference.
Paul Rabinowâs (1996) discussion of biosociality was a similarly formative moment in the social sciencesâ engagement with genomics (Hacking 2006a). Rabinow foresaw biosociality playing out on two dimensions. First, there was the potential for altering human DNA in pursuit of socially derived endsâhardly a novel topic. Second, and far more innovative, was the idea that social action and network formation might occur on the basis of a perceived genetic predisposition or risk for developing a clinical disorder. As Rabinow ([1992] 1996:102) presciently argued, âIt is not hard to imagine groups formed around the chromosome 17, locus 16,256, site 654,376 allele variant with a guanine substitution.â He even predicted these groups âwill have medical specialists, laboratories, narratives, traditions, and a heavy panoply of pastoral keepers to help them experience, share, intervene, and âunderstandâ their fate.â In this way, he explained, âOlder cultural classifications will be joined by a vast array of new ones, which will cross-cut, partially supersede, and eventually redefine the older categoriesâ (103). However, Rabinowâs discussion of this new biosociality was clear that the social power of genomic difference would remain limited to questions of risk for something else. Observations of the genome, he averred, âcarry with [them] no depth; . . . it has no meaningâ (102).
Cases like 22q13.3 deletion allow us to extend the incredibly productive concept of biosociality. Mutations can acquire meaning when networks of knowledge production and social mobilization are assembled around them. Knowledge about genetic mutations can give rise to entirely new categories of human difference and therefore forms of identity that go far beyond mere risk factors. Furthermore, I show how these networks powerfully shape the course of biomedical research and the very knowledge produced about genetic mutations. Knowledge about the genome can set new forms of biosociality in motion, as Rabinow presciently recognized, but biosociality can also transform the way we understand the mutations themselves.
Genomic designation also represents a clear realization of what Nikolas Rose has called the âmolecular gazeâ (2007b, 2007a). Rose outlined the transformation of contemporary biomedicineâs âstyle of thoughtâ (Ludwik Fleck, cited in Rose 2007a:12) via an array of techniques aimed at understanding the body at the molecular level. By turning to molecular processes, Rose argues, contemporary biomedicine has begun to supplement the âclinical gazeâ famously documented by Foucault (1973), with its focus on localized bodily observation as the basis for medical classification (Rose 2007b:11â15). To take just a couple of examples, previously indistinguishable forms of breast cancer have been differentiated on genetic grounds, and disjunct diseases have been found to share a genetic etiology, leading researchers to draw distinctions and see underlying unities that would not have been possible on a clinical basis (see Loscalzo, Kohane, and Barabasi 2007). In sum, the hegemony of anatomo-clinical classification is facing a serious assault from researchers armed with new molecular technologies.
Still, it is genomic designation that represents a molecular gaze in the true Foucauldian sense. Rather than localized anatomo-clinical observation (Foucault 1973:3â4), disease is increasingly classified ac...