[M]y family and I live in the yet. As the developmental pediatrician had said to us before the whole exome testing, “He’s got something; we’re just not smart enough to figure out what it is yet.” Taylor Harris, Catapult magazine, January 18, 2018.
Genetic medicine has always traded on promissory futures. For seventy years, the dream has been one of powerful new cures, and (more recently) tailored treatments. Today, genetic research creates exquisitely precise ways of defining very subtle differences between people, and increasingly rapid sequencing machines are creating a deluge of data on genomic variation. But even when genetic data can be sifted to reveal a link between a small change in a genetic sequence and a set of puzzling medical symptoms, that abstract discovery is not enough. It takes years of diligent work and alliances between experts and activists to make a variation matter—to general practitioners, physiotherapists, behavioural psychologists, teachers, concerned parents, and to those people presented with a diagnosis. As author Daniel Navon recently put it, “what it means to have a genetic mutation is as much a sociological phenomenon as it is a biomedical one.” 11 This essay draws on and summarizes recent sociological and historical work by Daniel Navon, author of Mobilizing Mutations: Human Genetics in the Age of Patient Advocacy (University of Chicago Press, 2019). It also draws from: Soraya de Chadarevian Heredity Under the Microscope: Chromosomes and the Study of the Human Genome (University of Chicago Press, 2020), Jenny Reardon The Postgenomic Condition: Ethics, Justice, Knowledge After the Genome (2017); Andrew J. Hogan, Life Histories of Genetic Disease: Patterns and Prevention in Postwar Medical Genetics (Johns Hopkins University Press, 2016); Keith Wailoo, Alondra Nelson, and Catherine Lee, eds., Genetics and the Unsettled Past The Collision of DNA, Race, and History, Rutgers Studies on Race and Ethnicity (Rutgers University Press, 2012); Grace Redhead, “‘A British Problem Affecting British People’: Sickle Cell Anaemia, Medical Activism and Race in the National Health Service, 1975–1993,” Twentieth Century British History 32 (2021): 189–211.
2 https://catapult.co/taylorharris
The social work needed to make genetics matter has been ongoing since the beginning of genetic research. In the 1950s, researchers in the young field of human genetics began providing radically new ways of defining differences between people. These were not visible characteristics that people could see for themselves, but molecular differences inside human cells revealed only by experts using specialist techniques. For the first time, scientists and doctors could use microscopes to look directly at chromosomes2 and assess their shape and number. Blood tests also revealed a remarkable range of inherited differences: such as a person’s blood group, molecular differences in enzyme levels, or the shape of the oxygen-carrying molecules in the blood (the haemoglobin). What did these differences mean? Much postwar research into genetics was driven by this question, and it was largely funded by atomic energy agencies anxious to know whether the fallout from nuclear weapons or energy could damage human chromosomes. This interest in radiation tapped into the longer-standing question: were there clinical ramifications to genetic differences between people?
The answer seemed to be yes. For example, in 1949 scientists found that molecular changes in a person’s haemoglobin was directly related to a dangerous and painful condition called sickle-cell anaemia. Although the disease had been known about for a long time, its link to a simple genetic variation generated excited claims about the “first molecular disease.” Soon, scientists and doctors had also started drawing links between patterns of symptoms and presence of an extra chromosome. Complex conditions such as Down Syndrome, Edwards Syndrome and Patau Syndrome could now be diagnosed prenatally and in newborns by looking at carefully prepared blood samples down a microscope. The young field of genetic medicine began trading on the promise that scientific understanding of these conditions would lead to the development and application of powerful new treatments.
But for all of the excitement about testing, interventions for many or most conditions remained thin on the ground. Sickle-cell anaemia was a case in point. For three decades after the discovery of the sickle cell variation, people affected by the condition saw no breakthrough cures or treatments. Sickle-cell anaemia primarily (but not only) affected people with recent African descent, and treatment of the condition in the US and UK was hampered by systemic racism within healthcare services, where most medical professionals had no knowledge or experience of the disease. In the US, many patients with sickle-cell anaemia continued to struggle to access basic medical care, and in the UK patients often struggled even to obtain effective pain relief. This was far from the dreams envisaged for genetic medicine.
As sickle-cell anaemia became intertwined with struggles for racial justice and civil rights, substantial change to the experience of the condition came about only in the 1980s when committed, activist medical professionals created new services devoted to sickle-cell anaemia and other haemoglobin conditions. Nurses, health visitors, social workers and physicians based at these new medical, community-based services acted as intermediaries between patients and physicians, made urgent referrals, created the conditions for screening, and offered counselling and support. On their own, the molecular differences that underlay sickle-cell anaemia were highly abstract, just as they had been thirty years before in the pages of the journal Science. What finally made the sickle-cell variation matter was the work by activists, nurses, doctors and patients to build support networks, to mediate between medical specialists, to educate healthcare workers and to deliver advice and counselling.
This was also the lesson drawn when genetic differences were found to underpin a range of other genetic conditions, including Huntington’s Disease, cystic fibrosis, and Tay-Sachs disease (to name just a few). The increasing availability of genetic testing presented some people with the option to terminate pregnancies (although for many this raised complex ethical quandaries and for some raised the spectre of eugenic selection). But testing and the increased visibility of these conditions also helped to create and consolidate support groups for those affected. Such groups—initially knitted together by telephone networks and newsletters—offered forums for sharing emotional responses, comparing therapeutic experiences, offering advice about what to ask general practitioners, and providing information for educators. By foregrounding the lived experiences of patients and families, advocacy groups and umbrella networks created new social worlds and alternative narratives about these ‘genetic’ conditions, which went beyond laboratory science and its expertise.
At the turn of the twenty-first century, with most of the human genome pinned down, inherited conditions could be mapped more quickly and precisely than ever before. And as sequencing techniques became increasingly rapid, scientists’ interest shifted to the comparison of multiple genomes, bringing to light not just variations with clear links to disease, but much rarer and more subtle differences, which might be associated with health in combinatorial ways. Although this kind of genomic variation has been very hard to sift and study, the collection of such data has in some cases led to the precise identification of subtle variations associated with known clinical conditions, or the clustering of symptoms previously not known to be associated with one another. Sometimes this, in turn, has enabled health professionals to make new links between medical specialities, or scientists and doctors to redefine disease categories. As genetic advocacy groups have grown and multiplied, today even the most subtle genetic differences can lead to the creation of social and kinship groups—often through social media sites like Facebook or Instagram, sometimes more formally.
No person is defined by their genetic sequence, and genetic conditions are almost always highly variable in their expression. But today, formal genetic diagnoses are powerful devices within healthcare systems. And as genetic variations become an increasingly authoritative way of classifying people, they are leading to the creation of new social identities, with profound effects on people’s lives, socially as well as medically, creating access to extensive networks of care, support, advocacy and research.
Abstract genetic data is not enough to have a meaningful impact on people’s lives. Scientific discovery and social work go hand in hand to define what is known—and what is left unknown. Families can be left painfully adrift when genetic information does remain abstract: when support is inadequate or misleading, or when a genetic variation is without clear meaning and without the social mobilization needed to make it matter. The epigraph to this essay comes from one of a series of moving articles published in Catapult magazine written by Taylor Harris under the heading “What Genes Can’t Tell Us”.33 Taylor Harris, “Living in the ‘Yet’" When Genetic Tests Don’t Reveal the Answers You Seek,” Catapult [Online], January 8, 2018, https://catapult.co/stories/what-genes-cant-tell-us-when-genetic-tests-dont-reveal-answers Harris is the mother of Tophs, a little boy with some unexplained medical features that (at the time of writing) had not yet coalesced into a pattern that medical doctors could pin to a named condition. Harris’s series of essays poignantly depict the experience of navigating an arduous diagnostic odyssey through the clinics of developmental paediatricians, gastroenterologists, endocrinologists, and, ultimately, geneticists—with the hope that genetic testing would help point to the source of the differences in her son’s body. But when the genetic counsellor announced the results of highly advanced sequencing tests, Harris recalled her saying: “‘We found some changes in the genes…but none that really explain what we’re seeing in him.”44 “More Mother, Less Detective: Where I’ve Found Grace Without a Diagnosis for My Son | Taylor Harris,” Catapult, June 25, 2018. https://catapult.co/stories/column-what-genes-cant-tell-us-more-mother-less-detective-finding-grace-without-a-diagnosis
Tophs’ doctors had highly detailed sequence data available to them, but Tophs was the only person known to them with this particular set of characteristics—the little boy and his family could not yet put a name to his condition, mobilize resources from a defined roster of medical professionals, reach for support from kindred families. They did not know what the future would hold for their child. Harris wrote: “You can find us here in the in-between, somewhere between Knowing Nothing and Understanding Cause. We stand in a space defined by what it is not, formed by what we don’t know.”55 The Human Cell Atlas project differs from genetics in their separate aims. The Human Cell Atlas endeavours to understand when and where genes are expressed and function in cells, while genetics seeks to identify which genes and genetic variations mediate changes of phenotype (the set of observable characteristics or traits of an organism). These two distinct projects intersect when brought together within medical research, in projects such as the international Common Disease Alliance (iCDA), which draws upon data from both projects within their research on common complex diseases. She was articulating a state of limbo created by genetic medicine, and that might, yet, be resolved by genetic medicine. These were genetic differences that had promise, but were so far without experience and without meaning.