10.6092/issn.2038-3460/17172
How and why are new gene-array techniques, which have been successfully introduced in medical contexts such as “post-natal” genetics, marked by uncertainty and dispute when they change context and are used in prenatal medicine? The so-called “molecular turn” in prenatal diagnosis has created a controversy that still divides the genetic community worldwide. The availability of an increased variety of high resolution-genetic data, including uncertain findings, divides the genetic community regarding production, treatment, and articulation with the older technologies, cytogenetics. Drawing on the methodological and conceptual framework of the “biomedical platform” (Keating and Cambrosio 2003), this paper intends to analyse these new biomedical molecular entities in the space where biology and medicine, science and technology, innovation and routine are intertwined. Empirical data from an ethnographic thick description of the intense debate that took place between Italian geneticists is used to analyze the different ways in which the material and immaterial elements of these platforms are organized. The different positions that emerge from the debate are traced back to two positions regarding the overlapping of biomedical work, technology transfer and research. This case study does not only reconstruct the fast-paced advancements of genetics in prenatal medicine, but also sheds light on the important questions at stake in structuring the expansive movement of molecular biomedicine.
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Mauro Turrini
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The Controversial Molecular Turn in Prenatal Diagnosis. CGH-array Clinical Approaches and Biomedical Platforms
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Mauro Turrini
2014/07/14
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The Controversial Molecular Turn in Prenatal Diagnosis. CGH-array Clinical Approaches and Biomedical Platforms
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                                                                              Essay
The Controversial Molecular Turn in
Prenatal Diagnosis
CGH-array Clinical Approaches and Biomedical
Platforms
!
Mauro Turrini
Université Paris I – Panthéon Sorbonne
!
    Abstract: How and why are new gene-array techniques, which have been
    successfully introduced in medical contexts such as “post-natal” genetics,
    marked by uncertainty and dispute when they change context and are used
    in prenatal medicine? The so-called “molecular turn” in prenatal diagnosis
    has created a controversy that still divides the genetic community world-
    wide. The availability of an increased variety of high resolution-genetic data,
    including uncertain findings, divides the genetic community regarding produc-
    tion, treatment, and articulation with the older technologies, cytogenetics.
    Drawing on the methodological and conceptual framework of the “biomedi-
    cal platform” (Keating and Cambrosio 2003), this paper intends to analyse
    these new biomedical molecular entities in the space where biology and
    medicine, science and technology, innovation and routine are intertwined.
    Empirical data from an ethnographic thick description of the intense debate
    that took place between Italian geneticists is used to analyze the different
    ways in which the material and immaterial elements of these platforms are
    organized. The different positions that emerge from the debate are traced
    back to two positions regarding the overlapping of biomedical work, tech-
    nology transfer and research. This case study does not only reconstruct the
    fast-paced advancements of genetics in prenatal medicine, but also sheds light
    on the important questions at stake in structuring the expansive movement
    of molecular biomedicine.

    Keywords: genetics and society; prenatal diagnosis; molecular turn; biomed-
    ical platform; biomedicine and innovation.

    Corresponding author: Mauro Turrini, Bureau D303, Esc. C - 1er étage,
    UFR Philosophie, Universitè de Paris I, Panthéon Sorbonne, 17 Rue de la
    Sorbonne, 75005 Paris – Email: mauro.turrini@univ-paris1.fr




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Italian Journal of Science & Technology Studies
5(1) pp. 115-139 - ISSN 2038-3460                 2014
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116                                                            Tecnoscienza - 5 (1)

I. Introduction: The Establishment of a Biomedical
Platform

    The development of biomedicine seems to be reflected in an increased
interaction of biological research, technological innovation and medical
work (Gaudillière 2002; Clarke et al. 2010; Keating and Cambrosio
2012). The recent introduction of Comparative Genomic Hybridization
array (CGH-array henceforth) technology has intensified these exchanges
even in medical areas such as prenatal diagnosis, i.e. the detection of con-
genital molecular anomalies in the foetus. Prenatal diagnosis used to
adopt a different technique, cytogenetics, disconnected from the rapid
advancements that molecular genetics has seen the last three decades. Da-
ting back to the beginning of the 20th century, and developed without
substantial successive changes in the seventies, cytogenetic procedures are
based on the analysis of the most visible cellular elements that carry ge-
netic information, the chromosomes. This technique was the disciplinary
standard until recently, and is still used in many settings for prenatal di-
agnosis. Only recently has cytogenetics been partially or even totally re-
placed by new molecular procedures, which allow for a much more sensi-
tive investigation of Dna sequences. This shift is part of a larger trend,
due to the rapid advancement of molecular genetic techniques and
knowledge, usually defined as the “molecular turn”. Several research pro-
jects have tracked the effects of this shift in clinics, in terms of the expan-
sion of care-subjects (from individuals to families), and the shift from
symptomatic disease to a-symptomatic risk, and so forth (see e.g. Conrad
and Gabe 1999; Cunningham-Barley and Boulton 1999). Although these
observations parallel our case study, they tend to revolve around the “dif-
fusion model”, according to which technological transfer is a linear and
universal process articulated from a scientific discovery to its industrial
application and, eventually, to the impact on society, deemed as an empty
space endowed only with a variable capacity to resist or accept technolo-
gy (Latour 1987; Bijker 1995; Akrich and Callon 1988a; 1988b). Other
more recent approaches from Science and Technology Studies have re-
cently criticized the monolithic conception of the evolution of genetics.
Some authors have shown that genetic tests are not immutable and self-
confined tools, but are moving entities with no “pre-defined” content
(Palladino 2002; Parthasarathy 2005). In a similar manner, the socio-
historical narrative of the introduction of molecular techniques in the
medical domain is presented here not as part of the general evolution of
biomedicine, but rather as an overall reconfiguration of biomedicine
characterised by multiple and tiny imbrications between laboratories and
clinics produced at the intersection of innovation, work and research.
    The theoretical and methodological framework of “biomedical plat-
forms” (Keating and Cambrosio 2003) addresses the contemporary cross-
fertilization that has occurred between medicine and biology since the
Turrini                                                                     117
Second World War, by focusing on its epistemological and organizational
shifts. Drawing on the French original meaning of platte-fourme (literally
“flat-form”), a “biomedical platform” is defined as the material support
on which the new regime of production and regulation of biomedicine
can be arranged and connected. In so doing, these theorists provide a
pragmatic perspective on biomedicine as a new space where new biomed-
ical entities bridge the gap between the qualitative, synthetic clinical eval-
uation of the pathology, and the quantification of biological variables:

              biomedical platforms [are] material and discursive arrange-
          ments that act as a bench upon which conventions concerning the
          biological or normal are connected with conventions concerning
          the medical or pathological.
                                          (Keating and Cambrosio 2003, 4)

    Instead of assuming a paradigm-ordered or theory-driven analysis of
biomedicine, this pragmatic stance resorts to the constitution of laborato-
ry-clinic relations as enabled by the mediation of material and discursive
objects, such as protocols, reagents, instruments, procedures, representa-
tional spaces, clinical indications, etiologic accounts and scientific catego-
ries. These elements constitute the material and discursive infrastructures
where new biomedical entities are mobilized. The material organisation of
their various parts, which “do not need shared understanding in order to
operate, but just consistency” (Keating and Cambrosio 2003, 15), are thus
intertwined with the epistemological production of knowledge. At this
point a second significant aspect of biomedicine emerges: the continuous
monitoring of patients’ physiological variables in relation to environmen-
tal stresses on the human body. This trend towards the increased produc-
tion of health-data implies new connections with the industrial produc-
tion of instruments that “move the problem of automation out of the
sphere of pathology and human judgment into the sphere of biology and
quantification” (Keating and Cambrosio 2003, 60-61). In synthesis, this
perspective insists on dissecting the well-accepted oppositions not only
between biology and medicine, but also between science and technology,
innovation and routine.
    These are some of the reasons why investigating the development of
new genetics seems so pertinent. Studying the expansion of predictive ge-
netic diagnosis and testing for cancer after the discovery of the two sus-
ceptibility genes for breast and ovarian cancer, Brca1 and Brca2, Pascale
Bourret (2005) investigated the implications for clinical work. New forms
of collaborative, multidisciplinary activities cross professional skills and
specialties as well as laboratory and clinical data and tools, and they con-
stitute what she terms “bio-clinical collectives”. Recently, this concept
was expanded and more specifically applied to investigating how both
genetics and clinics work together to give clinical meaning to new syn-
dromes and pathologies. Accordingly, their interactions shape the very
118                                                            Tecnoscienza - 5 (1)

content of work, which consists in “simultaneously producing the clinical
relevance and the biological significance of mutations” (Rabeharisoa and
Bourret 2009). The endogenous elaboration of these new bio-clinical enti-
ties results from the production of evidence derived by their mobilization
in a clinical context. In some cases, the nosological explanation of a pa-
thology is derived from a genomic anomaly, and not from clinical symp-
toms. Daniel Navon (2011) has recently established the concept of “ge-
nomic designation” to indicate syndromes and diseases that did not exist
before molecular analysis. An even clearer example of this trend is the at-
tempt to isolate genetic entities that are considered “actionable”, i.e. that
can be articulated through current protocols, procedures, treatments and
clinical interventions (Nelson et al. 2013).
    In this sense, the molecular turn of prenatal diagnosis provides a valu-
able fieldwork, in that it offers the possibility to scrutinize the establish-
ment of a biomedical platform marked by uncertainty and controversy.
Even if the CGH-array technique has already been set as the gold stand-
ard of other clinical practices, such as in the post-natal diagnosis of psy-
chiatric impairment or other congenital syndromes, its application to pre-
natal diagnosis has raised issues that have not yet been settled. This dis-
pute, which divided the medico-scientific community over the world, as
well as, remarkably, the two most important medico-scientific societies on
the opposite shores of the Atlantic (Eca 2012; Acog 2013), is multifaceted
and shifts according to the perspective assumed.
    In the scientific literature, the quarrel is presented in a rather abstract
fashion. Not accidentally, the main issues that emerge concern the war of
numbers instead of the actual increased detection rate in molecular pro-
cedures as compared to cytogenetic ones. An exact evaluation is also
complicated by two factors. The first regards the uncertain clinical mean-
ing that characterizes the new biomedical entities mobilised by CGH-
arrays, i.e. the “sub-microscopic anomalies”. The sensitivity of CGH-
arrays is so high that not all of the detected genetic data is necessarily
clinically encoded. Technically they can be called “variants of uncertain
significance” (Vous). The second factor regards CGH-arrays limitations,
as compared with traditional cytogenetics. While producing more quanti-
tative genomic data, CGH-arrays are blind to so-called “structural or bal-
anced anomalies”, which are however very rare and usually not related to
a genetic disease or syndrome. Amazingly, if we turn our attention to the
exchanges within the geneticists’ community, we find totally different ar-
guments. The different positions refer not so much to scientific justifica-
tions, rather to matters that are strictly organizational and professional.
The Italian controversy provides a good framework with which to analyse
the process of organizing and fine-tuning this new biomedical platform,
because it provides a case study that is, both representative of many other
settings and specific. On one hand, the final statement of the Italian Soci-
ety of Human Genetics (Sigu, Società Italiana di Genetica Umana) re-
flects, as we will see later in detail, the position that was also assumed by
Turrini                                                                   119
the European Cytogeneticists Association (Eca). On the other, the Italian
debate assumed decidedly heated tones and drew widely on arguments of
extra-scientific nature, as each side implied that opposite party position
lied about economic and professional interests. This situation, thus, gave
a symmetrically opposite perspective than that provided by scientific lit-
erature.
    This paper intends to reject both positions as two different reduction-
ist versions, based respectively either on a purely epistemological evalua-
tion of a technique, or on economic or professional interests. Building on
the conceptual framework of biomedical platforms, the epistemological
status of the “sub-microscopic anomalies” produced by CGH-arrays is
strictly connected to organisational arrangements. In other words, the
production, circulation and interpretation of these new biomedical enti-
ties requires a multi-layered biomedical platform which involves intimate
and dynamic connections between equipment, tools, concepts, medico-
scientific guidelines, biotech companies, databases, health services, and so
forth.
    So far, interdisciplinary collaboration and bio-clinical collectives have
not particularly addressed prenatal diagnosis, even if it is one of the first,
and still remains one of the most important, applications of genetics in
the medical routine. In prenatal medicine, the cytogeneticist works in iso-
lation, without the possibility to triangulating genetic findings with “non-
genetic” information of the same level of reliability, and at best handles
the diagnosis communication (Turrini 2011). This clear division between
the laboratory and the clinic is partially comprehensible due to the nature
of the test-subject, the fetus. The subject is in a movement of rapid
change, not fully developed or organically autonomous (i.e. healthy in the
common sense). In addition the subject is located in the womb, where the
clinical observation is clearly difficult. The only obtainable phenotypic in-
formation is anatomical measurements obtained by ultrasound visualiza-
tion technology. Given that the clinical observation provides little and
uncertain data on the fetus, cytogenetic analysis has to and actually does
provide solid data, on which important clinical decisions are made. Aside
from the rare cases of surgery on a fetus (Casper 1998), the only available
practice after the diagnosis is the voluntary interruption of the pregnancy.
Genetic counseling is offered only in case of a positive result that indi-
cates the presence of a given pathology, and, since the most common
anomaly that this technique detects is the well-known Down syndrome,
even physicians without a specialty in genetics may communicate the di-
agnosis. Afterwards, the pregnant woman or couple is then often left to
their own resources regarding their decision.
    The advent of a molecular technique such as the CGH-array has dra-
matically changed the practices of prenatal diagnosis under many re-
spects. The doctor-patient relationship explodes into a complex constella-
tion of elements. Genetic counselling becomes mandatory before any ex-
amination due to possible uncertain outcomes. Likewise, any referral of
120                                                           Tecnoscienza - 5 (1)

the anomaly requires a consultation with international databases, and,
therefore promotes a tighter interface between pre-natal and post-natal
diagnosis by collecting and correlating genetic anomalies detected in in-
dividuals before and after birth. Further, the relationship with research as
well as with biotech companies grows more dynamic, as equipment is
constantly advancing to keep pace with the ever-increasing amount of
new diseases and the ever-higher sensibility needed to detect them. The
last point, indeed, emerges from our analysis as the crucial bone of con-
tention, in that it affects the way in which to locate and organize sub-
microscopic abnormalities.
    After an introductory section on materials and methods, and a brief
explication of the aforementioned process, we will expand the descrip-
tion of this emerging biomedical platform through a discussion of the sci-
entific controversy. First, we will indicate the general terms in which the
technology is presented in scientific literature, and, second, we will look
closer at the Italian debate. In the final section, we will analyse the con-
troversy in terms of two different ways to conceive and organise the bio-
medical platforms, by focusing in particular on the important relationship
with technological transfer and biomedical research.


2. Materials and Methods

    The methodology adopted combines the analysis of scientific litera-
ture with the more traditional methods of qualitative research, like in-
depth interviews and ethnographic observation of laboratory practices.
More precisely, we collected all of the relevant literature on PubMed that
had a title and abstract related to “array comparative genomic hybridiza-
tion” and “prenatal diagnosis”. After reading the abstracts of the 143 re-
sults, we have selected those that have been considered the most relevant
articles from a clinical point of view. They include, for example, two spe-
cial issues that two important journals, “Human Mutation” and “Prenatal
Diagnosis”, devoted to this topic in 2012, entitled respectively “Focus on
Cnv detection with diagnostic arrays” and “New Cytogenetic Technolo-
gies in Prenatal Diagnosis”.
    Beyond the scientific literature, we also gathered the position state-
ments and guidelines of the most important US, EU and Italian medical-
scientific societies: The American College of Obstetricians and Gynaecol-
ogists, Acog, and the already mentioned Eca and Sigu. We conducted ex-
tended, and in some cases multiple, interviews with 16 geneticists (either
biologists or physicians) from nine different clinics (all Italians apart from
one, in Austria). In order to reconstruct the development of this tech-
nique in Italy, we addressed both the “core group” involved in the Italian
debate, and those involved in the research aimed at the establishment and
validation of CGH-array technology. Regarding the Italian controversy, I
Turrini                                                                  121
was able to reconstruct parts of the Cytogenetic Working Group of Sigu
meeting in which the dispute broke out, as well as the criticism that fol-
lowed, through the testimony of individuals present at the event. We also
gathered the opinions of those who, after having worked for several dec-
ades in cytogenetics, saw their expertise (and therefore jobs) threatened
by the molecular turn. In this case, the intergenerational separation be-
tween older practitioners, and those who started their career in the mid-
2000s with CGH-array research, is clear. We selected three different
groups of professionals: first, young researchers who have worked at least
for several years of research in Italian health service as Ph.D. students,
post-docs or with other forms of research funding; second, directors and
managers of genetics departments, or big laboratories who handle the
process of clinical genetics; and third, older cytogeneticists. We supple-
mented this aspect with the direct observation of genetic laboratories in
order to unpack how CGH-array works.


3. The Molecularization of Clinical Genetics

   The introduction of molecular instruments in clinical genetics repre-
sented a radical alternative to traditional methods encompassed by the
family of cytogenetic practices. Up until a few years ago, these two kinds
of genetic methods were complementary. Whereas the older cytogenetic
techniques gave a broad overview of the entire set of chromosomes, the
molecular techniques, like Pcr, were used to detect specific targets with a
higher sensibility. In the 21st century, this distinction became obsolete
with the development of new molecular, high-throughput (hyper-fast)
techniques like CGH-arrays and Next generation sequencers, which can
produce an overview analysis of the whole genome at a high-resolution.
Cytogenetics was the only technique able to obtain an overview of the
whole chromosomal set and therefore the most used technique in clinical
genetics. However, it is a rudimentary and artisan discipline, essentially
based on manual manipulation and microscopic diagnosis. It is a residual
exception on the verge of extinction in an era when most clinical testing
has become more and more automated or ‘‘high tech”. It is not by chance
that its craft-like practices have recently captured the attention of several
social scientists (Rapp 1999, 193-222; Martin 2004; Turrini 2012). It is a
long and articulated procedure that consists in arresting the cell cycle dur-
ing the metaphase, just before the process of division, when the chromo-
somes are most visible, and then fixing them on a slide and banding them.
In addition to being more time-consuming, this procedure requires the
counting and analysis of the chromosomes under the microscope. The
width, brightness, and the arrangement of the stripes – bands according to
the laboratory vernacular – constitute the specific appearance by which
each chromosome can be recognized by peering into microscope.
122                                                             Tecnoscienza - 5 (1)




      Fig. 1 – CGH-array protocol (source: Emmanuel Barillot, Laurence Calzone,
Philippe Hupé, Jean-Philippe Vert, Andrei Zinovyev, Computational Systems Biolo-
gy of Cancer, Chapman & Hall/CRC Mathematical & Computational Biology,
2012).

    Comparative genomic hybridization is a technique that was developed
at the beginning of the 1990s in the field of clinical research on cancer. Its
principle action is to compare small fragments of a genome sample to the
same fragments of a “reference sample” deemed “normal” and, thus, see
if there are extra or missing pieces of genetic material. At the end of the
1990s this technique was conducted by Dna microarrays. The arrays al-
lowed for a visualization beyond the “metaphase plate”, in the “digital
space” of a matrix, in which each square corresponds to a specific chro-
mosomal region, according to the library of cloned Dna fragments with
known locations throughout the human genome that was produced by
the Human Genome Project. In practical terms, in CGH-arrays, Dna is
chopped into thousands of shorts sequences (called “probes”) that are
then labelled, coloured, arranged on a slide with a precise grid (it is called
a “biochip” for that reason), and finally compared with probes of a dif-
ferent colour from a reference sample. The resulting gains and losses of
chromosomal material are read by a scanner, which provides an analysis
as broad as cytogenetics but with a definitely higher resolution that is au-
tomated and fast.
    While cytogenetics produces chromosomes analysed by the human
eye under the microscope (fluorescent or not), the CGH-array produces
signals that are automatically read by an electronic scanner. In describing
this innovation some geneticists use a telling geographical analogy. If the
images of chromosomes produced and analysed by cytogenetics are com-
Turrini                                                                           123
pared to a traditional map of any given country level, then the maps pro-
duced by the biochips are a sort of Google Earth that permit us to zoom-
in down to street level. To make things still clearer, the image in figure 2
compares a conventional chromosome as it appears through microscope
and a digital chromosome image from an array.




          Fig 2 – Digital and conventional chromosomes (Fiorentino et al. 2011)


    The molecularization and digitization of genetic analysis has several
advantages over traditional karyotyping, in that it allows for the detection
of thousands of genetic variations, up to one hundred times smaller than
those that can be detected by peering into the microscope, in an automa-
tized procedure. Thanks to the detection of these sub-microscopic altera-
tions (technically called micro-deletions, micro-duplications, and so
forth), new syndromes have been coded, or genetically re-coded.
    This is one of the primary reasons why genome-wide arrays have
quickly become the primary tool of chromosomal evaluation in certain
medical areas, such as oncology. They have also significantly improved
“post-natal” diagnostics with respect to conventional karyotyping for
children with developmental delays, intellectual disabilities, multiple con-
genital anomalies, and autism. This led to an international consensus
statement according to which gene arrays technologies should be used in
124                                                          Tecnoscienza - 5 (1)

the diagnostic workup of such patients (Miller et al. 2010), and, as a re-
sult, more laboratories are now introducing biochips as the first-tier test-
ing technique. Although this has had a deep impact in the classification of
syndromes (Navon 2011), it has raised no controversy within the genetic
community.
    Due to the reasons we briefly summarised in the introductory para-
graph, things are more slippery in prenatal settings, where questions re-
garding certain aspects of clinical implementation still remain unan-
swered.


4. A Special Challenge. The Scientific Debate On CGH-
   array

    Biochips were first applied to a clinical practice in the US in 2006
(Shuster 2007). In the same period, genetic laboratories all over the world
were experimenting with this technique in clinical practice. Yet, after al-
most ten years of practice and experiments, the usage of biochips in pre-
natal diagnosis still raises many issues. In 2011, when array technologies
had already replaced conventional karyotypes as the standard for genetic
diagnosis after birth, the International Congress of Prenatal Medicine of
Amsterdam at “a very well-attended debate” discussed whether CGH-
array could be considered as a replacement for this routine testing in the
near future (Bui et al. 2011, 235). This article intends to look at the rea-
sons for which the use of arrays in prenatal diagnosis is still considered “a
special challenge” (Vetro et al. 2012), to paraphrase the title of an article
written for the Genetic Services Quality Committee of the European So-
ciety of Human Genetics by a large group of geneticists working in six
different clinics.
    In the scientific literature this controversy revolves around the war of
numbers over the effective rise of detection rates brought about by the
passage from cytogenetics to the CGH-array. Findings vary, but in gen-
eral there is agreement regarding the advantages of biochips over tradi-
tional cytogenetic techniques (see. e.g., Wapner et al. 2012). What make
the assessment of the actual gain provided by the CGH-array so difficult
to assess, is, first and foremost, the issues that the increased quantity of
results produced by CGH-arrays pose in terms of clinical interpretation.
Even if cytogenetic procedures also produce some uncertain results, mo-
lecular instruments drive this uncertainty to an extreme, in that some of
these results are beyond the current comprehension of genomes. The dif-
ferent methods for organizing the introduction of CGH-arrays for prena-
tal diagnosis depend on the different approaches to the so-called “vari-
ants of uncertain significance” (Vous). The assessment of the actual limi-
tation of CGH-arrays, as compared with traditional cytogenetics clinical
definition of the anomaly, also contributes to rendering the assessment of
Turrini                                                                     125
effective gain provided by the CGH-array even more difficult. While
producing more quantitative genomic data, CGH-arrays are blind to
some kinds of anomalies. These anomalies may be defined as out of place
Dna fragments, derived from the movement of a filament piece from a
chromosomal region to another. Since arrays read genomes resulting from
a cut and copy process, they cannot detect those anomalies, but only
those due to either a gain or a loss of Dna. Similar problems can be found
regarding another kind of genetic abnormalities, mosaicism, i.e. the pres-
ence of two or more populations of cells with different genotypes in one
individual.
    Some papers on the debate tend to polarise these different positions
into two practical options regarding the introduction of CGH-array in
prenatal diagnosis. For some, the use of molecular instruments should be
restricted to pregnancies that are considered “high risk” based on ob-
served ultrasound abnormalities, or as a second-tier test to confirm and
characterise those chromosomal anomalies that resulted from conven-
tional cytogenetic analysis. For others, this type of test should be provid-
ed indiscriminately to all pregnant women who seek invasive prenatal
testing, as the universal, primary tool of genomic evaluation of the foetus.
Besides the war of numbers, ethical and regulatory issues are mentioned
in these debates. They refer first and foremost to the elaboration of new
strategies to inform pregnant women or couples about such a test that
produces a vast and sometimes incomprehensible amount of information.
In any case, beyond this debate, what is really at stake in practical terms is
two different ways of arranging the biomedical platform of one of the
most important clinical genetic practices in quantitative terms.
    In this regard it is important to recall the socio-economic dimension
of this phenomenon. The first medical practice to bring genetics to the
public, prenatal diagnosis is still nowadays one of the genetic practices
with the most experience in the clinics1, used on over one hundred thou-
sand pregnant women a year in Italy alone. These different approaches,
which can be summarized as either indiscriminate use or the use as a se-
cond-tier test, have a deep economic implication and are dividing the ge-
netic communities all over the globe. The strong discrepancy between the
last guidelines of the American College of Obstetricians Committee on
Genetics (Acog 2013), which changed its position from the previous ones
(Acog 2009), and the Europeans Cytogenetic Association (2012) lies just
in that choice. The former is in favour of a total replacement of cytogenet-
ics with gene array technologies, which would then be used as a first-tier
test, while the latter is in favour of partial use only, just for at-risk cases.
The Italian controversy tellingly counters this perspective on the debate
by providing a diametrically different one.
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
1
 Nowadays, genetics techniques as applied to the study and treatment of cancer
are rapidly expanding, and are undoubtedly the most promising sector of ge-
nomics both from a clinical and economic point of view.
126                                                           Tecnoscienza - 5 (1)




5. The Italian Controversy: Socio-economic Interests and
   Technology Transfer

    While scientific literature has focused on the technicalities of gene ar-
ray technologies in terms of diagnostic sensitivity, in the Italian scientific
community this dispute has taken a decidedly animated tone, which is
more focused on socio-economic aspects. There are undoubtedly struc-
tural reasons behind this controversy. It suffices to mention here that ge-
netic laboratories are fragmented, often of small or even tiny dimensions.
A recent survey counted over 160 laboratories (Dallapiccola et al. 2006).
This number includes private laboratories, many of which operate on a
larger scale (including Toma in Busto Arsizio (Va), Genome in Rome),
and also respond to the demand of public structures, mostly of small di-
mensions.
    In any case, the controversy arose almost by accident, after a meeting
of the Sigu (the Italian Society of Human Genetics) Working Group on
Cytogenetics, in which they attempted to re-elaborate the guidelines for
the use of the CGH-array. During the meeting that took place on April 7
2011, a clear majority position emerged which desired to limit these tech-
niques to subsequent diagnostic investigation, and consequently, to dis-
courage the hasty replacement of traditional procedures. Dissenting voic-
es were raised. In particular a private laboratory that was betting on
CGH-arrays, involved in research aimed at evaluating its benefits among
other things, railed against this measure. The aim was to produce empiri-
cal results regarding the usefulness and reliability of the CGH-array-
technique in prenatal diagnosis. In practical terms, this would mean
switching to an analysis procedure that examined biological samples “in
parallel”, making use of both the traditional cytogenetic techniques and
those of molecular genetics, so as to be able to compare the results of the
two. The research had by then reached a conclusive stage and the results,
which would be submitted one month later to an international scientific
journal (Fiorentino et al. 2011), seemed encouraging. The representatives
of this facility rejected this prudent attitude, and proposed a chromoso-
mal array approach as first-tier approach for all pregnancies. During an
animated correspondence that took place immediately after this meeting
in the mailing list of Sigu Working Group between these two positions,
an advocate of the immediate and indiscriminate application proposed to
initiate a large-scale multi-centred study involving the most important
Italian centres, and thus creating prestige for Sigu.
    The position that was agreed upon, however, was decidedly more cau-
tious. The introduction of gene array technologies for prenatal diagnosis
thus became the central issue of a bitter dispute that seemed to divide
critics and advocates of this innovation. On one hand, Sigu reiterated its
Turrini                                                                       127
cautious attitude first in a public document in Italian, distributed
amongst its members, and then in a position statement, that is the public
stance of a scientific society, published in an international scientific jour-
nal. As from this last document: “we recommend the use of Cma [chro-
mosomal microarray analysis] in prenatal testing: 1) never as a substitute
for conventional karyotyping; 2) for specific diagnostic purposes in se-
lected pregnancies and not for general screening in all pregnancies” (No-
velli et al. 2012, 386). This approach echoes the European Association of
Cytogenetics guidelines, which were published in those same months
(Eca 2012).
     On the other hand, the private Italian laboratory’s adverse position
did not subside, if anything, it intensified. In addition, in virtue of the
positive results obtained by the previously mentioned research, the com-
pany definitively abandoned cytogenetics in favour of chromosomal array
analysis, which was then used as the only first-tier test for all women un-
dergoing invasive prenatal tests. Their dissent was then expressed in an
official manner through a “correspondence” (e.g. letters sent to a scien-
tific journal to distance oneself from one of its articles) in which the Sigu
position statement is described as anachronistic and ignorant of the most
recent results that have emerged from research. A group of geneticists
from the National Taiwan University Hospital intervened in support of
this critical position, signing a second “correspondence” in the columns
of the same magazine. In these letters, we find a discussion that rests on
arguments that are quite similar to those mentioned in the previous sec-
tion on scientific literature. The subject of discussion is the manner
through which to objectively evaluate the actual detection-rate increase of
the array techniques in light of the loss of certain types of data and, above
all, the uncertainty of some of the results. However, as we have men-
tioned, what is at stake in practical terms is the way in which to arrange
the biomedical platform of one of the most important arenas in quantita-
tive terms.
     If we turn our attention to the exchanges between the more promi-
nent members of this controversy, we find not only decidedly heated
tones, but also reasoning of entirely different nature. The different posi-
tions refer not so much a scientific justification, as to matters that are
strictly organizational and professional. It created a situation in which a
constructivist agenda, committed to exposing those contingencies that are
usually deleted or forgotten in scientific literature, was adopted outside of
social science research. The Italian debate on the molecular turn in prena-
tal diagnosis activated “a sociology of knowledge machine” (Lynch, 1996)
which promoted a passage from scientific arguments to others grounded
on social interests that lay behind the adversaries’ position2. The following
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
2
 Deconstructivist efforts conducted within scientific controversies to discard ad-
versaries’ arguments have been widely analysed within STS. See, for example,
Collins and Pinch (1979) and Lynch (1996).
128                                                               Tecnoscienza - 5 (1)

opinion stated by a protagonist of the controversy has been reiterated by
others interviewed, especially by experienced geneticists:

           The reasons why the scientific community takes a certain path
       can be understood through many different factors. Science was
       not what was mainly used in this circumstance.

    The extra-scientific interests referenced here are of a purely socio-
economic nature. On one hand, the National Health Service (Servizio
Sanitario Nazionale – Ssn) is essentially accused of adopting a conserva-
tive position. The reasons for this reside in an inability to keep up with
innovations due to the slowness of bureaucracy and, above all, the desire
to defend a particularly important national scientific tradition as ad-
vanced as cytogenetics. By scientific tradition we intend to refer here to a
series of “scientific styles” developed over the years (Turrini 2012). These
“styles” involve both skills and job positions that are framed in the con-
text of clinical laboratories and universities. In the event of a radical
technological substitution, these components would be put at serious
risk. Using once again the words of a protagonist in this controversy:

           There is a shift from cytogenetics to molecular genetics. What
       does that entail? Where will this situation bring us? When we no
       longer perform cytogenetic karyotyping, the cytogeneticists will no
       longer have power or a role, meaning they will no longer have
       work. (Francesco Fiorentino, Director of Laboratory Genoma of
       Rome)

    In this regard, it is important to clarify the importance of prenatal di-
agnosis in terms of employment. Just to give an idea, in 2004, out of
283601 cytogenetic tests done in Italy, 51.7% were prenatal (Dallapiccola
et al. 2006). The prevalence of prenatal diagnosis touches not only the
number of workers employed in various capacities (technical, biologists
or doctors) in this area, but also an economic volume that is extremely
relevant in the context of genetics.
    On the other hand, CGH-array enthusiasm is mainly attributed to the
purely commercial private laboratories:

           Everything that is introduced into clinical practice, and there-
       fore in its routines, has to be assessed and developed by disease
       control centres, a system that provides a record of safety and effec-
       tiveness. [...] What I pose as a problem is that it shouldn’t be the
       market to decide, it should be a relaxed scientific community that
       does not have other interests in the decision regarding what you
       can and can’t do. (Antonio Novelli, Chair of Cytogenetics Labora-
       tory of Istituto Mendel of Rome and Chair of the Working Group
       “cytogenetics” of Sigu)
Turrini                                                                  129
    The interests at stake are many. Antonio Novelli balances the reduc-
tion of personnel costs related to procedures with a level of automation
with a prudent attitude towards innovations that are quickly commercial-
ized by biotech and pharmaceutical companies. According to this per-
spective, the presentation of any given procedure as the most effective
and rapid, which reduces waiting times from an average of two weeks to a
handful of days, seems to respond more to economic interests than a sub-
stantial improvement in the service of care. Not surprisingly, the private
Roman genetic laboratory’s report, along with the previously mentioned
Taiwanese’s study, appear in a brochure in which a British biotech com-
pany introduces biochips for clinical diagnosis to the market – CytoChip
Focus produced by BlueGnome3.
    The controversy “heats up” when these two divergent attitudes lock
horns, caution versus enthusiasm, towards the innovative proposals that
biomedical companies put on the market. However, describing the two
factions as simply private and public would be inaccurate. The cautious
attitude seems to depend on the desire to both better protect the patient
from illusions generated by the medical industrial complex, and ensure
greater sustainability of medical services. This position is criticized as
medical paternalism. Supporters of the introduction of CGH-array tech-
niques also add that a conservative and “directive” strategy is a rhetorical
means used to justify an economic and technological inability to keep up
with the pace of current technological transfer.
    While this article adopts the analytical-perspective of biomedical plat-
forms, it also attempts to examine the political aspects that the analysed
dispute presents in the first place. As it has already been pointed out, the
opposition between advocates and critics is deliberately simplistic. The
controversy does not divide those in favour of the use of this technique
from those who oppose it. Instead, the variety of stances and positions
developed inside the different choices reflects the relationships of the in-
vested parties to the issue. In this regard, this debate provides insight on-
to complexity involved in gene array technologies, new procedures, other
existing procedures, medical and scientific associations, biotech compa-
nies, work groups, publications, and so forth. It also points out the rela-
tionship between the “biomedical collectives” (Rabeharisoa and Bourret
2009) and the biomedical industry. However, we do not intend to explain
the differences of these position with a causal model based on economic
and professional interests. Even if they undoubtedly play a crucial role,
we would like to grasp the epistemological and organisational difference
of the “biomedical platform”, articulated around the molecular genetic
diagnosis of the foetus, in greater detail.

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
3
 BlueGnome, Delivering decisions from DNA, “CytoChip”, (http://www. cam-
bridgebluegnome.com/products/cytochip-isca/product-information/cytochip -
oligo-spike-in-controls/, last visited on the 3rd of May 2014).
130                                                            Tecnoscienza - 5 (1)


6. A “Lab-on-a-Chip”
                                  “It's the platform that makes the difference.”
                                                        A geneticist interviewed

    The notion of biomedical platform is used in this article with a seman-
tic ambiguity much like the synecdoche rhetorical figure. Biomedical plat-
form does not refer only to a specific conceptual framework. In the field-
work the term “platform”, without the adjective “biomedical”, was used
quite frequently to mean the slide, the matrix on which the analysis is
physically carried out. This meaning is more limited and specific, basically
indicating the glass slide on whose grid the thousands of short sequences
of Dna are arranged.
    The two meanings, despite their apparent differences, are actually
contiguous under different aspects. The first meaning comes from a re-
flection on a tendency towards biologization and automation in contem-
porary medicine, and the second comes straight from the biomedical field
in which this transformation has already reached a very advanced stage.
These objects share not only a historical and technological proximity, but
also some functional/operational elements. The biochip incorporates a
wide range of tasks that were previously conducted by hand. Thanks to
the chip, even the reading of the results themselves is performed by a
computer scanner. In other words, biochips are the result of scaling sev-
eral laboratory procedures down to a chip-format. This is the reason for
which they are generally referred to as “lab-on-a-chip” (Loc), which, cu-
riously, is another synecdoche widely used for this kind of miniaturization
processes. All of these considerations indicate the extraordinary closeness
of the two semantic levels of platforms. Through sociological reflection
“biomedical platforms” are defined as criteria for the arrangement of the
various discursive elements and materials. In molecular genetics, “plat-
forms” are defined as extremely flexible and encompassing variables in
much the same way, on which however, the entire material and epistemo-
logical data production cycle depends on. This correspondence is not an
accident, but is rather understood through ethnomethodological reflec-
tion on “perspicuous phenomena”, i.e. overlapping areas where concerns
of particular groups resonate with social science categories or issues
(Lynch 1993). Indeed, the arrangement of the slide where the analysis is
carried out reflects on the broader regime of production and regulation of
the new biomedical entities analysed by CGH-arrays. If one were to play
with the multiple meanings of this category, one could argue that the
physical type of platform chosen for the lab predominantly influences the
articulation of the overall biomedical platform. Returning to the debate in
the light of this perspective, the type of array that will be used emerges as
one of the primary obstacles upon which the controversy was built. As
the researcher seen at the beginning of this section states, “it’s the plat-
form that makes the difference!”
Turrini                                                                             131
    One of the most meaningful differences among the number of array
platforms that have been commercially offered by a wide range of com-
panies in recent years regards the optimal resolution of these arrays. In-
creasing the resolution has the advantage of detecting a larger number of
anomalies; however, the number of benign or uncertain significance in-
creases exponentially. Although there are publications that indicate a
specific level of sensitivity, each laboratory practically chooses its own in-
house detection-rate resolution (Vermeesch et al. 2012). At the same
time, the two most common families of technologies used for biochips,
namely “targeted array” and “whole-genome array”, represent the general
difference between low and high resolution. Targeted arrays, also known
by the technical name of Bac arrays or Bobs, have a lower sensitivity,
while whole-genome arrays, or oligonucleotide arrays, have higher sensi-
tivity.
    Those who are in favour of immediately replacing the conventional cy-
togenetics with gene array technologies adopt targeted array biochips. As
the name says, these chips target “hot spots”, the gene-dense regions
where the most common genetic anomalies are located, yet have low reso-
lution for the rest of genome. This mixed resolution responds to the need
to facilitate data interpretation by keeping uncertain and unsolicited re-
sults to a minimum. The rationale underlying this technology is a strategy
that seeks to balance technological innovation with the needs of pregnant
women who want the maximum amount of information currently obtain-
able by prenatal diagnosis. For this reason, the supporters of this platform
consider it the only option that is genuinely respectful of the patient, as it
allows for “a more accurate test”, and the right to have the most accurate
analysis of the foetus. Depriving patients of the most advanced medical
techniques is therefore considered the effect of a paternalistic medical
culture, and a resistance to change, typical of some clinical facilities:

              And what does it involve [the decision of using conventional
          karyotype, even when the molecular one is available]? It really
          means medical malpractice, going against everything that should
          be a goal of a doctor, a biologist, to give the patient at least an op-
          tion other than the test that has been used for more than forty
          years, the cytogenetic karyotype. (Francesco Fiorentino, Director
          of Laboratory Genoma of Rome)

     Others, however, do not take kindly to these products. In their eyes
the immediate availability of these techniques, especially in an area as sen-
sitive as prenatal diagnosis, would primarily respond to economic inter-
ests instead of clinical ones. Of course, the targeted platforms are specifi-
cally designed for an indiscriminate and exclusive use at prenatal diagno-
sis, while whole-genome arrays, although used as a second-tier analysis in
prenatal medicine, are also used for the diagnosis of rare diseases and in-
tellectual impairment. Instead of being considered the gold standard, tar-
132                                                               Tecnoscienza - 5 (1)

geted platforms are seen as backward compared to oligonucleotide or ge-
nome-wide platforms, which detect even smaller anomalies throughout
the whole genome. Here, for example, is the opinion of a researcher spe-
cialized in CGH-arrays:

           Making a new technology available is also right, making it
       available to the patient, and therefore the pregnant woman [...].
       Using low-resolution platforms, however it shouldn’t mean closing
       your eyes and saying, “yes, I used a low-resolution platform, I'm at
       ease because I have no doubts about the interpretation.” I don’t
       think that’s how it is, because even a low-resolution platform
       leaves you with interpretative doubts, plus it also leaves you with
       something you haven’t seen. I am very puzzled about this plat-
       form, although I realize that from the commercial point of view it
       makes a lot of sense.

    Another researcher, states more concisely: “I’m not crazy about tar-
geted platforms because they limit the openness of the array”. As emerges
from these testimonies, the type of platform one uses is a choice, that is
not only related to the commercial volume of extremely sophisticated
platforms, but also to epistemological choices that once again involve a
reorganization of the medical work. In this regard, the whole-genome
platform option provokes closer interaction between prenatal diagnosis
and post-natal diagnosis, which is confirmed by the role played by bi-
obanks.


7. Biobanks, the Molecular Body and the Prenatal Medicine
   to Come

    In order to understand how the molecular breakthrough is transform-
ing and complicating clinical genetics, it is worth mentioning the episte-
mological change produced by it. This advance is not only due to the in-
creased number of coded diseases created by increasingly precise infor-
mation. It is also a logical step. Up until a few years ago, clinical genetics
mainly utilized Mendelian “one gene-one trait” or the “gene for x-
disease” logic. This model tied each genetic abnormality to a given condi-
tion. The molecular turn promotes the establishment of multiple and flex-
ible relationships. In the diagnosis of intellectual disability, autism, and
multiple congenital diseases in the prenatal and postnatal field, the new
approach is seen primarily in the evaluation of “penetrance”, and interac-
tions between genes (see e.g. Lock, 2005).
    The categories and practice of clinical genetics are subverted and re-
written by submicroscopic reality, beginning with assumptions regarding
heredity. The first assumption that is subverted is the idea that a genetic
variance not present in the parents (technically a de novo anomaly) should
Turrini                                                                        133
always be considered pathological. This principle is still considered valid
for anomalies detected with cytogenetics techniques. However, not all
microanomalies necessarily have negative health consequences. There-
fore, one cannot consider them pathological based on the mere fact that
they were not present in either parent.
    In a manner symmetrical to the first example, the second principle of
clinical genetics to be challenged by molecular techniques is considering
an abnormality inherited from the parents benign in the case they do not
manifest a genetic condition. This reality does not necessarily protect
from the development of a disease, because some microanomalies are ac-
tivated under particular conditions. It is easy to understand, therefore,
that the quantitative difference brings with it a basic qualitative difference
regarding interpretation, so much so that the clinical use of these tech-
nologies necessitates many years of data interpretation experience.
    If, therefore, gene array technologies have automated the long cytoge-
netics laboratory procedures, they have instead made the clinical interpre-
tation of the data extremely complex and indeterminate. In the words of
one researcher:

             Technically, it has become much easier than it was to prepare a
          chromosome. Technically it has really become much easier to pro-
          duce the data. What has become difficult is to interpret the data.

    We could describe this complexity in terms of the loss of the pheno-
type-genotype correlation that was established in the first period of clini-
cal genetics. Restoring such a connection is a far from easy undertaking,
and requires the development of genetic data databases from both
healthy subjects and those with intellectual disabilities, developmental
disorders, autism and multiple congenital diseases at both global and lo-
cal levels. The reconfiguration of what is normal and what is pathological
occurs through the mediation of these institutions, biobanks, which col-
lect, collate, and compare the vast amount of data produced by clinical
laboratories around the world. Biobanks have become a fundamental el-
ement of molecular genetic biomedical platforms, establishing a link be-
tween anomalies detected in prenatal and post-natal diagnosis, which did
not yet exist with cytogenetics. What is most significant is that the rela-
tionships between biobanks and laboratories are regulated by the type of
platform that is used. Oligonucleotides platforms (those with higher reso-
lution) require a continuous relationship with biobanks. Each result has
to be confronted with those stored in several genetic databases, and these
references are a mandatory section of the bio-clinical report. In case the
result has not been perfectly codified, research for the scientific state of
art regarding that anomaly should be conducted and interpreted, and
then explained to the pregnant woman or the couple accompanied by
other members of the medical team specialized in genetic counselling. In
practice, to quote a junior researcher who works with gene array technol-
134                                                            Tecnoscienza - 5 (1)

ogies, it means that:

           we must study the genes that are involved in the relevant re-
       gion, and see, for example, if there are animal models, or cases
       partly described in scientific literature on the subject.

     At the same time, each new case enriches the database, and helps es-
tablish a link between genetic information and disease. Since knowledge
in this field is rapidly expanding, new syndromes associated with micro-
anomalies are continuously being reported. As a result, a good example of
“translational medicine” emerges, where clinical results are used to build
a dynamic and ever-changing model of the “genetic molecular body”.
     The same genetic molecular body is instead incorporated in fixed
form by Bac platforms, where the analysis is roughly limited (never fully)
to known areas of the genome. In this case, the work of interpretation is
largely (but not completely) embedded in the technology itself. There is
still a relationship with genetic databases, but that is limited to the few
uncertain cases that emerge in the analysis, and to updates that such plat-
forms with targeted designs requires now and again. In essence, the con-
tinuous mutation of the molecular body is frozen by these technologies
into a series of still images, which serve to lighten the task of interpreta-
tion and, therefore, to implement a higher level of automation. Clearly,
once again, increased automation, while minimizing the number of uncer-
tain cases and lowering unit costs, potentially extends these tests to a
greater number of people and therefore plays into the hands of the com-
panies that manufacture these devices. At the same time, to a lesser ex-
tent, increased automation contributes to the codification of the “molecu-
lar body”.
     The platforms build a relationship with the future of prenatal medi-
cine in a second and equally important sector, in relation to other tests
that seem to redefine the practice of prenatal diagnosis. A particular
comparison can be made with non-invasive prenatal diagnosis (Nipd),
which is based on cell-free foetal Dna in maternal serum. Although this is
not yet widely available in Europe, it is already widely practiced in North-
America. It is possible that in the near future this technique will replace
all other current techniques of prenatal screening and diagnosis. Even if,
at the moment, it addresses only a handful of anomalies, such like triso-
mies 21 (Down’s Syndrome), 18 and 13, it may be extended to wide set of
genetic anomalies, including genes of susceptibility like Brca1 or Brca2.
As part of the molecular turn, they will pose again similar issues about
how to organise materially and clinically new biomedical entities, which
in this latter case are not only molecular/submicroscopic, but also non-
invasive.
Turrini                                                                   135
8. Conclusions

    Defined as the biomedical platform, the introduction of molecular ge-
netic techniques in the field of prenatal diagnosis is a far from concluded
process based on a stronger interaction between techno-scientific innova-
tion and research and clinical routines. In a recent public speech, Eric D.
Green (2013), the Director of the National Human Genome Research In-
stitute at the National Institute of Health, stated that prenatal diagnosis is
one of the “hot areas” of genomic research. With the advent of Nipd, ge-
netic analysis seems to have lost one of the main obstacles to its diffusion,
that is the inherent risk of miscarriage that the process of foetal biological
material extraction carries. The possibility to analyse foetal Dna present
in maternal blood opens even new possibilities. Dna sequencing may pro-
vide a genetic analysis still more accurate than CGH-arrays, and its clini-
cal application seems not so far. The Mit Technology Review mentioned it
as among the ten breakthrough technologies of 2013, namely, the possi-
bility for a pregnant woman to obtain the complete Dna sequence of her
foetus through a simple, non-invasive blood draw (Regalado 2013). Bio-
ethics approaches the phenomenon with a prescriptive approach regard-
ing the ethical norms that should be applied to the new techniques of
prenatal diagnosis and screening. This paper tries to deal with these trans-
formations from a different approach, focusing instead on the pragmatic
changes that such innovations bring, and the various methods with which
geneticists articulate these new technologies. In this sense, the concept of
biomedical platform proves useful as a perspicuous conceptual frame-
work that allows us to grasp the crucial role played by the ever increasing
intersection of activities between not only the laboratory and clinics, but
also among biomedical routines, innovation and research. The platform is
not only the complex network of heterogeneous actors involved in the
production and reproduction of new submicroscopic anomalies detecta-
ble by gene array technologies, but also indicates the central element on
which the other elements revolve, namely the biochip.
    Consequently, we have analysed the controversy over this embryonic
biomedical platform as a multi-layered debate. The selection of submicro-
scopic anomalies that will be detected depends on the kind of arrays cho-
sen for prenatal diagnosis. At the same time, the differences in the way
these biomedical entities are produced affects the arrangement of the
platform in which they are mobilised. In other words, this dispute shows
the multiple possibilities in which it is possible to mediate relations
among procedures, instruments, the representational space of Dna, clini-
cal indications, etiological classification and scientific categories. Through
the investigation of the correlations between routines, innovation and re-
search, the organisational and epistemological way in which these materi-
al and immaterial entities are collectively arranged appears to impact
connections between biotechnology companies, genetic database,
136                                                              Tecnoscienza - 5 (1)

healthcare institutions and practice, the human body, and the nor-
mal/pathological divide. The controversy, therefore, drew attention to the
important stakes involved in the material and discursive arrangement of
the biomedical platform. Geneticists manage the prenatal diagnosis of the
present, and prepare the future by playing with the organizational flexi-
bility of the platform. We can identify the political sense of the biomedi-
cal platform as the manner in which the material and discursive inter-
twinement of biology and medicine, the normal and the pathological, is
arranged. In synthesis, the framing and structuring of the extension
movement of the medicine to come.


Acknowledgements

    I would like to thank, first and foremost, the geneticists and researchers who
granted me access to the field and spent patiently their time to speak about their
work practices. I also am grateful to Alberto Cambrosio as well as to three anon-
ymous reviewers for invaluable comments on drafts of this paper. I would also
like to especially thank Federico Neresini and Assunta Viteritti for their encour-
agement and moral support. Finally, a special thank to Daniela Crocetti, for her
help with the English translation.



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