# Genetics' exceptionality – A short perspective from clinical care

Catherine Bourgain

<figure><img src="image_1.png" /></figure>

## To cite this version:

Catherine Bourgain. Genetics' exceptionality – A short perspective from clinical care. Ethics, Medicine and Public Health, 2025, 33, pp.101104. 10.1016/j.jemep.2025.101104. hal-05052662

HAL Id: hal-05052662

https://hal.science/hal-05052662v1

Submitted on 30 Apr 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>
Humanities in health

# Genetics' exceptionality – A short perspective from clinical care

C. Bourgain *

Geneticist and sociologist of science, INSERM Research Director. Université Paris Cité, CERMES3, CNRS, EHESS, 7, rue Guy Moquet, F-94800 Villejuif, France

ARTICLE INFO

Keywords:

Bridging work

Genetic imaginary

Oncogenetics

Professional regulation

Uncertainty

ABSTRACT

Genetics exceptionality relies on the strong imaginaries associated with this particular type of biological information – its capacity to disclose the invisible intimate- and on the concerns for controlling its possibly negative social impacts – the genetic information is always both highly specific and shared within families and populations. The paper claims that together with specific legal frameworks, this exceptionality is also embodied by the amount of effort performed in the clinic to control the strong uncertainties associated with the usage of this scientific knowledge in care contexts.

Genetics is an information with an exceptional position among other kinds of similar biological data. This peculiar status relies both on the strong imaginary it conveys [1] and on the legal status that has been enforced to control its usages.

This situation is largely associated to its widely claimed capacity to reveal - literally to disclose – information of great importance to the individuals but held to be invisible to the eye, that relates to health - past, present or future -, origins, physical or intellectual capacities. A clear instantiation of this exceptionality is the informed consent to be signed prior to any genetic examination in many national laws in which alternative biological tests, sometimes with equivalent direct impact, are not subject to consent. This is the case in the field of thrombosis prevention. Coagulation abnormalities, considered as risk factors for a first episode or a recurrence of thrombosis, can be alternatively characterized by biochemical or genetic tests. Yet, only the latter are subject to a formal consent under the French law and this consent has turned to be the main material embodiment of this peculiar genetic nature, for patients and professionals alike [2]. The requirement to inform family relatives after a significant health related information has been disclosed is another illustration of this exceptionality. The genetic nature of this information is sufficient to justify a form of bypassing medical confidentiality.

Genetics claimed capacity to reveal the invisible, the intimate or the private, also makes this matter ethically, socially and politically sensitive. In addition to the specific legal framework mentioned, professional intermediaries have been historically involved in the regulation of its usages [3]. In France, only judges can order legally enforceable genetic fingerprint characterization or paternity testing and prescription of

diagnostic, predictive or theranostic tests are limited to clinicians trained in genetics. These experts are indeed entitled to use additional non-genetic contextual information, whether judicial or clinical, to clarify the potential utility and evaluate the relevance of the tests in the specific situation at hand. In a number of medical circumstances, the capacity to make sense of the genetic test results is conditioned on their scientific, medical and technical knowledge and expertise.

The tensions between the attraction and even fascination for the unveiling power of genetics, on the one hand, and the concern for controlling the negative impacts associated with possible excesses in the biologisation of identities [4], the biomedicalisation of lives [5], the control or discrimination of particular individuals or groups [6], on the other, are vivid.

These tensions are played out in a context of major technological developments. Over the last twenty years, genetic tests have been introduced in an increasing diversity of contexts. Largely driven by market dynamics, these developments have also been strongly supported by States. Genetics has been turned in an obligatory crossing point for policies supporting health innovations or public health, as the Covid-19 pandemic has demonstrated.

These tensions should, however, not be reduced to strictly moral or political choices regarding the relevance of individual use with respect to collective risks. Deciding to prescribe a test or making sense of its results, is often fraught with uncertainty about its ability to effectively provide relevant information, in the particular situation at hand. In a survey on newborn genetic screening in the US, Timmermans and Buchbinder [7] described how, in the everyday life of these tests, "diseases do not behave as expected based on previous scientific knowledge".

<footnote>* Corresponding author.</footnote>

<footnote>E-mail address: catherine.bourgain@inserm.fr</footnote>
Anomalous findings are constantly being identified, making clinical
decisions uncertain and problematic. To describe all the tasks performed
by professionals to adapt to these unexpected results, the two sociolo-
gists have introduced the concept of "bridging work". Very costly,
particularly in terms of human expertise, this bridging work remains
largely invisible outside the professional communities concerned. In
fact, their ability to act efficiently in situations of uncertainty tend to
mask the actual complexity of the tests' usage. On the contrary, it feeds
the imaginary of the tests' intrinsic revealing power, which genomic
innovation policy and market players are actively relaying.

The field of oncogenetic constitutes a stimulating illustration of the
complex issues involved in the use of genetic tests in the clinic, and of
their evolution over time, as genetics has been turn into genomics and
tests have expanded to larger scales -both in the number of people tested
and in the precision of the genetic information produced.

In the mid-1990s, following intense international collaborations,
mutations in two genes, BRCA1 and BRCA2, were identified in families
with a particular high proportion of women with breast or ovarian
cancer. In these families, the presence of a mutation was shown to in-
crease the risk of developing breast or ovarian cancer at the age of 70, by
up to ten times. In 1998, the first professional guidelines were published
by the French oncogenetic network [8]. They suggest, in particular, that
the tests should not be offered to all women indiscriminately. Rather,
only those with a particular family history of disease should be tested,
since they were the only women for whom the probability of actually
detecting a mutation could be considered sufficiently high to provide an
acceptable predictive value for the test. These professional guidelines
thus included ways of organizing the judgement on the opportunity to
prescribe these tests. But they were also a pragmatic choice aimed at
addressing the many uncertainties encountered. The guidelines stressed
the fact that "uncertainty is the hallmark of cancer genetics". It is present at
the family and individual level, concerns the risk of developing the
disease, its severity and the effectiveness of existing preventive
measures.

The supervision of these tests has not followed a uniform trajectory
in all countries [9]. In the United States, the initial granting of patents to
Myriad Genetics by the USPTO enabled the company to enforce a mo-
nopoly on the tests, throughout the country until the 2013 revocation by
the Supreme Court. The importance of market players in the regulation
of tests led to a significant expansion of their prescription. In 2018, the
Food and Drug Administration (FDA) even allowed a
Direct-To-Consumer company to include testing for three mutations in
the BRCA genes in the panel sold to consumers. This decision endorsed
the possibility of performing the tests without the intervention of a
prescribing clinician. It opened the way for a test usage independent of
clinical, epidemiological or family criteria. In this context, genetic tests
became autonomous examinations, whose reliability seemed to be
reducible to the sole quality of a molecular characterization process,
guaranteed by technical industrial standards.

Yet, this expansion of testing raised new questions about the value of
genetic data. In March 2016, the New York Times reported the story of
Angie Watts, who was prescribed a BRCA test after being diagnosed with
a breast tumor [10]. Based on the test results, her oncologist encouraged
her to undergo a bilateral mastectomy rather than radiotherapy. How-
ever, the patient received a different recommendation from a clinical
geneticist, who argued that there was no evidence that the identified
genetic variant predicted a significant recurrence risk. A consensus
could not be reached between doctors, and the final choice was left to
her. The journalist noted that "what appears to be a simple test can produce
worrying information for patients without a treatment choice being made".
The Angie Watt variant is part of a new category of genetic variants: VUS
for Variants of Unknown Significance. This category now accounts for
almost 50% of the mutations described in the BRCA1 gene. In 2017, a

study of 2,500 American women with breast cancer found that 30% had
been tested [11]. VUS were detected in 9% of them, and mutations
considered to be causal in only 7% of them.

The rise of VUS is challenging the capacity to produce reliable pre-
dictions based on molecular analysis only. Released from the strict
control exercised by the intense work of professionals, the tests publicly
reveal their limited ability to provide an undisputable basis for decisions
as heavy as a bilateral mastectomy. In fact, professionals, supported by
research institutions and private stakeholders in the sector, have
invested in the setting up of large international databases [12] whose
ambition is to reduce the uncertainties of these VUS, by sharing indi-
vidual genetic data, combined with other data, particularly clinical data.

In doing so, they require a new form of work around molecular data to share, protect, make comparable and interpret it. This work involves the standardization of clinical data collected in the context of care, a particularly complex task given the high degree of heterogeneity in national clinical practices. Increasingly, diverse actors are involved. Clinicians and biologists must now collaborate with bioinformaticians, database curators, lawyers or even logisticians. The bridging work, to reconcile the promises of technologies with the reality of their clinical implementation, is thus becoming particularly costly and complex to organize.

In a sense, the tremendous investments and work load entailed by the routinization and massification of genomics in the clinic, can be analyzed as a new enactment of its exceptionality.

Funding

This work was supported by grants from the French National Insti-
tute for Cancer (Inca) and the French National Research Agency (ANR).

Declaration of competing interest

The authors declare that they have no known competing financial or
personal relationships that could be viewed as influencing the work
reported in this paper.

References

[1] Jasanoff S, Kim SH. Dreamscapes of modernity – Sociotechnical imaginaries and the fabrication of power. Chicago: The University of Chicago Press; 2015.

[2] Turrini M, Bourgain C. Genomic susceptibility in practice: the regulatory trajectory of non-rare thrombophilia (NRT) genetic tests in the clinical management of venous thrombo-embolism (VTE). Soc Sci Med 2020;112903.

[3] Cassier M, Gaudillière JP. Recherche, médecine et marché: la génétique du cancer du sein. Sciences Sociales et Santé 2001;18:29-51.

[4] Rose N. Genomic susceptibility as an emergent form of life? Genetic testing, identity, and the remit of medicine. In: Burri RV, Dumit H, editors. Biomedicine as culture: Instrumental practices, technoscientific knowledge, and new modes of life. New York-London: Routledge; 2007.

[5] Clarke AE, shim JK, Fosket JR, Fishman JR. Biomedicalization: technoscientific transformations of health, illness, and US biomedicine. Am Sociol Rev 2003;68: 161-94.

[6] Duster T. A post-genomis surprise: the molecular reinscription of race in science, law and medicine. Br J Sociol 2005;66:1-27.

[7] Timmermans S, Buchbinder M. Expanded newborn screening: articulating the ontology of diseases with bridging work in the clinic. Sociol Health Illness 2012;34: 208-20.

[8] Eisinger F, Alby N, Bremond A, Dauplat J, Espié M, Janiaud P, et al. Recommendations for medical management of hereditary breast and ovarian cancer: the French National Ad Hoc Committee. Ann Oncol 1998;9:939-50.

[9] Löwy I, Gaudillière JP. Localizing the global: testing for hereditary risks of breast cancer. Sci Tech Hum Val 2008;33:299-325.

[10] Kolata G. When gene tests for breast cancer reveal grim data but no guidance. New York Times; 2016, March 11.

[11] Kurian AW, Li Y, Hamilton AS, Ward KC, Hawley ST, Morrow M, et al. Gaps in incorporating germline genetic testing into treatment decision-making for early-stage breast cancer. J Clin Oncol 2017;35:2232-9.

[12] The Global Alliance for Genomics and Health. A federated ecosystem for sharing genomic, clinical data. Science 2016;352:1278-80.