10.6092/issn.2038-3460/17175
In this paper we recapitulate the history of the conceptual entwinement of biomedicine and translation and argue that a translational imperative (still peripheral to the practices that order the fields unified under the term biomedicine) has come to dominate public and institutional perceptions of biomedical research. We show this by first delineating a brief history of the conceptual developments in the sociology of science and technology, in particular in relation to translation and the complex multiagent social interactions contributing to the structure of this field. We then report the findings from our studies of translational spaces and how the actors in them conceive of the imperatives. At least in the field of cell therapy research, the push toward translational research from funding and science policy institutions seems not to have altered greatly the established practices of validation and merit that organise the disciplinary complexes that form cell therapy biomedical research today.
application/pdf
2038-3460
17175
1
en
Christine Hauskeller
https://creativecommons.org/licenses/by-nc-sa/2.5/
Tecnoscienza – Italian Journal of Science & Technology Studies
cell therapy
Translational Research: An Imperative Shaping the Spaces in Biomedicine
Text.Serial.Journal
https://tecnoscienza.unibo.it/
5
Scenarios
2014-07-14
2023-06-13
2014-07-14
2023-07-24
191-201
TS
Christine Hauskeller
2014/07/14
10.6092/issn.2038-3460/17175
191
University of Exeter
2038-3460
1
cell therapy
en
201
Translational Research: An Imperative Shaping the Spaces in Biomedicine
https://tecnoscienza.unibo.it/article/download/17175/16077
5
                                                                                Scenario

Translational Research: An Imperative
Shaping the Spaces in Biomedicine
!
         Jean Harrington                             Christine Hauskeller
           King’s College London                         University of Exeter

!

     Abstract In this paper we recapitulate the history of the conceptual en-
     twinement of biomedicine and translation and argue that a translational im-
     perative (still peripheral to the practices that order the fields unified under
     the term biomedicine) has come to dominate public and institutional per-
     ceptions of biomedical research. We show this by first delineating a brief
     history of the conceptual developments in the sociology of science and
     technology, in particular in relation to translation and the complex multi-
     agent social interactions contributing to the structure of this field. We then
     report the findings from our studies of translational spaces and how the ac-
     tors in them conceive of the imperatives. At least in the field of cell therapy
     research, the push toward translational research from funding and science
     policy institutions seems not to have altered greatly the established practic-
     es of validation and merit that organise the disciplinary complexes that
     form cell therapy biomedical research today.

     Keywords: translational research; biomedicine; translational space; transla-
     tional imperative; cell therapy.

     Corresponding author: Dr. Jean Harrington, Division of Health & Social
     Care Research, School of Medicine, King’s College London, Capital House,
     42 Weston Street, London, SE1 3QD, UK – Email: jean.harrington@kcl.
     ac.uk




1. Introduction

    We were invited to contribute a discussion of the concept of transla-
tional research and its emergence in biomedicine on the basis of our work
on this topic. The history of the intersection of biomedicine and transla-
tional research is complicated, and therefore we discuss in this article the
changing relationship between both, how they influence and grow to-
gether in what is a current translational imperative in which biological
!
TECNOSCIENZA
Italian Journal of Science & Technology Studies
5 (1) pp. 191-201 - ISSN 2038-3460
www.tecnoscienza.net                              2014
192                                                          Tecnoscienza - 5 (1)

and medical research give direction and set restrictions for one another.
We use examples from cell therapy research, an area we conducted ex-
tensive empirical research on, assuming that whilst the configuration of
biomedicine through translation may play out differently in detail in dif-
ferent fields of biomedicine, the degree and influence of the translational
imperative has similar structural effects.


2. Concepts of Biomedicine and Translational Research

     That medicine relates to biology is a trivial notion. That increasingly
medical diagnosis has come to rely on biological/tissue tests, and that
therapies intervene into biochemically well-defined physiological or met-
abolic processes, is a product of the 20th century. In this context the
emergence of the concept of biomedicine has occurred. Biomedicine has
changed medicine and constitutes a whole set of new practices and locali-
ties of research, including multidisciplinary laboratories, new journals and
the grammar of research ethics and clinical trials. Viviane Quirke and
Jean-Paul Gaudillière date the rise of biomedicine to after the Second
Word War and characterize it as a: “step change in the scale of invest-
ment in research, a new role for the state as scientific entrepreneur, an in-
creasingly fundamental level of investigation in biology and medicine, and
a closer relationship between the laboratory and the clinic”, accompanied
by the idea of “the therapeutic miracle” and the “search for magic bullets
against tuberculosis, cancer, and cardiovascular disease” (Quirke and
Gaudillière 2008, 442-443). Cell therapy research developed in this peri-
od as studies into the effects of nuclear radiation on the body and how
destroyed cell systems could be repaired. The stem cell in the bone mar-
row and its regenerative function for the blood system, and with it the
leukaemia patient, were determined as biomedical cell therapy research
(Kraft 2009).


2.1. The Translational Imperative

    Translation between the laboratory and the clinic may seem to be at
the core of the activity we call biomedicine. In its Funding guide the UK’s
largest medical research funder, the Wellcome Trust, explains that:
“Translational research helps turn early-stage innovations into new health
products, advancing the innovation to the point where it becomes attractive
for further development by the medical industry or healthcare agencies”1.
This present-day definition suggests a one-directional flow of infor-
mation, from the laboratory into general medical care, identifying the en-
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
1
    http://www.wellcome.ac.uk/funding/Innovations/wtd027704.htm.
Harrington and Hauskeller                                                           193
visioned gaps between the different stages of such innovation. The imper-
ative, therefore, of what funding bodies and science policy managers have
introduced as translational research lies on the concept of ‘pulling
through’; the problem is how to effectively turn new biological
knowledge into widely used medical treatments. The 2014 overview for
the UK NIHR Biomedical Research Centres (BRC) stresses that all pro-
jects and project leaders must have a track record “in translating advances
in basic biomedical research into clinical research, and pulling through basic
biomedical research findings into benefits for patients, the public and the
NHS”2.


2.2. Biomedicine and Translation in Sociology

    The one-directional model stressed in the above notions of translation
is simplistic compared to the ways in which the sociology of science and
technology has been using this same concept since the 1960s. The
scientists’ use of the metaphor translation for flows of knowledge and
information across disciplines and their peculiar languages and practices
was followed by the emergence of the sociology of translation. A name
commonly attributed to Bruno Latour (1979), Michel Callon (1986) and
others who worked in this field in the 1980s. Translation is a key concept
in actor-network theory. Applied to the field of biomedicine it presents
its main actors as attempting to create a central network of interactions
that each actor has an interest in building and defending.

               The first is that of the reduction of the big world (the macro-
          cosm) to the small world (the microcosm) of the laboratory. The
          second stage is that of the formation and setting to work of a re-
          stricted research group that, relying on a strong concentration of
          instruments and abilities, devises and explores simplified objects.
          The third stage is that of the always perilous return to the big
          world [...].
                                                         (Callon et al. 2009, 48)

    This description points out that the flow of information and what is
needed to achieve biomedical innovation is not from the bench to the
bedside but a more complex interweaving of stages in which complexity
is reduced and then reintroduced again. The emphasis is on interactive
practices that produce translation as a reconfiguration of the macrocosm
(Callon et al. 2009, 68).

     !
!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
2
 http://www.nihr.ac.uk/files/pdfs/Briefing%20documents/4.2%20Biomedical%
20Research%20Centres.pdf.
194                                                            Tecnoscienza - 5 (1)

2.3. Science as Social Practice

    This focus on the performance of science also dates back to the 1960s
when the knowledge practices of science became a study object for
sociologists and they began to perform science on science, a turn of
attention aimed at rational policy decisions on science and technology
innovation in the future. Proponents of the Sociology of Scientific
Knowledge (SSK) studied science as a social practice and consequently
scientific knowledge as a social product (Barnes 1974; 1977; Bloor 1976,
Collins 1985; Shapin 1982). In policy contexts this was taken up as a new
imperative to understand the developments in the sciences in their
relationship to technology and economic growth and, above all, how “to
get returns on the money we spend on science” (Edge 1995, 6).
    SSK and its precursors, especially Ludwik Fleck ([1935] 1979) and
Thomas Kuhn ([1962] 1970), began to understand science as the product
of social processes and negotiations, which mediate scientists’ accounts of
the natural world, raising fundamental questions about taken-for-granted
divisions between “social versus cognitive, or natural, factors” (Shapin
1995, 289). The ‘truth’ or ‘falsity’ of scientific claims derives from the
interpretations, actions and practices of scientists rather than residing in
nature as a separate world of facts that exists objectively for the scientists,
independent of the methods and practices they employ to study it.
Understanding science as a social practice includes not only studying its
methods but also its social structures and the vested interests and social
objectives that operate on and within the activity of making scientific
knowledge.
    This perspective presents translation as a process in which the
knowledge practices of different fields in the macro-and-microcosms in
biomedicine cooperate with social practices that influence the epistemic
and internal stratification processes in complex webs of interactions.
Scientists and clinicians balance many and often conflicting expectations
of what counts as achievement as set out by funding organisations, the
scientific community, publics, patients, industries and policy makers. The
art of translation is to balance these expectations across disciplines and
turn them into individual and institutional successes and desirable
medical innovations. Biomedicine and translation thus is multi-layered, an
interweaving of interests and activities. From 2000s onward, the concept
was further expanded in sociological studies on cell therapy research to
different concepts of intersecting social spheres.


3. Cell Therapy Research: New Understandings of
Translation

      From its beginnings in bone marrow repair, research on cell therapies
Harrington and Hauskeller                                              195
has taken several forms over the past decades, diversifying into many ex-
pert areas. Thus the term cell therapy research now ties together a range
of types of specialist expertise in both biology and medicine, strongly in-
fluenced by cultural and political factors (Hauskeller 2004). Paul Martin,
Nik Brown and Alison Kraft (2008) chart the development of haemato-
poietic stem cell research over a fifty-year period and describe the rela-
tionship between basic science and clinical research communities as a
two-way flow of knowledge in which clinical innovation has played a key
role. They emphasize the communities of promise that form around
emerging cell therapies and that national governments incentivize the ex-
ploitation of basic research and the creation of new policies and institu-
tions to ensure that scientific findings can be applied in the clinic.
    The large body of social science work on the external societal
influences on cell therapy research from the past 15 years is accompanied
by a number of studies on the translational processes within scientific
communities. For example, Steven Wainwright, Clare Williams, Mike
Michael, Bobbie Farsides and Alan Cribb describe a distinction between
the “warp of discourses which enact the improbability of collaborations
between ‘bench’ and ‘bedside’, and the weft of other discursive strategies
which enact the possibility of collaboration between the lab and the
clinic” (2006, 2062). Steven Wainwright and Clare Williams (2008) draw
on Livingstone’s metaphor of geographies of science, which he described
as “sites of speech and locations of locution” (2003, 23) to explore the
spatial shaping of science and the scientific shaping of conceptual, social
and political spaces.


3.1. Platforms and Trading Zones

    The metaphor of the platform is moved from being applied to
biomedicine to being used to characterize processes of translation. Peter
Keating and Alberto Cambrosio describe biomedicine as a ‘hybrid-
practice’ and their notion of the biomedical platform draws together
panoply of diverse actors (technicians, physicians, researchers, policy
makers, regulators) with material objects (Keating and Cambrosio 2003).
They argue that in the 1990s biomedicine itself had become an
independent actor in cancer research, alongside basic and clinical
research (Cambrosio et al. 2006). Joelle M. Abi-Rached, Nikolas Rose and
Andrei Mogoutov re-configure the translational platform as an array of
heterogeneous actors including technologies, practices and techniques
and enabling multiple transactions between the clinic, the laboratory and
society. They stress that the products of translational research, be they
specific applications (drugs, neurodevices, etc.) or practical guidelines
(systematic reviews, meta-analyses etc.) allow a change in both clinical
practice and population behaviour, as identified by Steven Woolf (2008).
In the context of their study on the new brain sciences, Abi-Rached et al.
196                                                             Tecnoscienza - 5 (1)

(2010) distinguish areas of research that act as vectors between the
laboratory, the clinic and society, arguing that each specialized
community is centred around its own journals, institutes and
organizations. These are connected in trading zones, a notion they
develop following Peter Galison (1997), to capture not merely zones of
passive exchange and flow of information but:

           Zones which facilitate the active transactions and
       transmutations of diverse devices, practices, techniques, and
       perhaps above all styles of thought. They are platforms which
       allow the emergence of new disciplines and discursive practices
       and along with them a reorganization of their objects of study.
                                             (Abi-Rached et al. 2010, 13)

    This notion of trading zones where translational activity is enacted is
helpful to identify agency. However, engagement in the translational trad-
ing zone is not always deliberate, but affected by targeted policy deci-
sions. Whether we prefer the image of interconnected platforms or of the
webs woven through multiple centers of agency, a social and political im-
perative to be translational acts upon biomedicine as shown across the
range of social science studies. To illustrate this we provide a brief sum-
mary of findings from empirical research concerning the scientists’ view
of, and practical engagement with, this imperative.


3.2. The Utility Imperative in the Translational Space of Cell
Therapy Research

    Between 2006 and 2011 the authors carried out ethnographic studies
on stem cell research for the heart in laboratories, clinical environments
and at networking events. Analysis drew on observation and semi-
structured interviews with laboratory scientists, clinicians and focused on
the regulatory, disciplinary and ethical tensions that shape the
“translational space” (Harrington 2011). In addition, we studied from its
inception in 2004 the British Cardiovascular Collaborative for Stem Cell
Repair of the Heart (Collaborative), a clinician-led multi-disciplinary
group of top UK biomedical researchers who aimed at developing stem
cell treatments together (instead of competitively) in order to achieve fast
clinical implementation. One of the aims of our research was to explore
the motivations and attitudes of the stakeholders working in this field.
The data on practices, networks of interactions and interdisciplinary
exchanges show that differently positioned participants in the field
employed different strategies to negotiate the translational imperative.
The quotes below exemplify opposite views on translational research and
what we call the translational imperative. First a molecular biologist
working in a laboratory funded for translational research:
Harrington and Hauskeller                                                        197

              So I have to play the game, I have to play the rules of the game
          because in the end what I want is to be funded and to be in a lab
          working and doing research. [...] There are many things you can
          do with the cells I work on. They are not necessarily going to
          translate into something useful, but you can do the research and
          that research will be useful anyway. It may not be translated, but
          the point is, in a paper when I send my project to the funders, it’s
          like, yeah, stem cells, a disease, a cure! So… it’s more about,
          [pause] giving the people what they want to read, even if inside
          you know it’s not necessarily achievable, or it’s not your first
          priority, but again you have to combine all these things, basic
          research with translational research and get the money.

   The scientist states that conforming to the translational imperative is
necessary in order to get funded. Translational research is performed as
an adjunct to the biological inquiry. The opposite perspective is
presented by a clinical–scientist who states that biological research should
be driven by medical needs and requirements, describing the purpose of
the Collaborative and the view of the multidisciplinary group that met
several times a year over a period of 7 years, as:

              All agreed that clinical researchers had first to define which
          problems they would attempt to treat with transplanted cells (e.g.
          heart failure, dilated cardiomyopathy, or myocardial infarction)
          and by what route (e.g. intravenous, percutaneous, or surgical).
          Then the groups working on animal models would adapt their
          models to that clinical need […] The group working on cells and
          gene transfer to cells would define the best cells to transplant, or
          the best way of stimulating endogenous cells to activity.

    The clinicians participated in the Collaborative in order to find new
methods to change the function of the ailing heart and expected the
scientists to provide them with the biological knowledge and cells to aid
that goal without necessarily fully understanding the mechanisms by
which the cells regenerate heart tissue. The clinical focus is on whether
procedures are safe3 and in the long term prove to be efficacious4.

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
3
  The Clinical Trials observed in this research were Phase 1 that is designed to
‘assess safety’ although often the conversations between clinicians were centred
on ‘efficacy’. This dilemma raises questions concerning the ‘focus’ of a clinical
trial and the ethics surrounding this position.
4
  When discussing this divide between the scientist and the practicing clinician
reference was made to ‘Aspirin’ [acetylsalicylic acid (ASA)] and the fact that it’s
functioning mechanisms have only relatively recently been discovered although it
has been in use since 1500BC when an infusion of dried myrtle leaves (which
contain salicylic acid) was used to relieve back pain and since 1899 under the
trade name ‘Aspirin’.
198                                                            Tecnoscienza - 5 (1)

Innovation pathways for new cell therapies from the laboratory into the
clinic have been promoted and pre-planned by both funding
organisations such as the Wellcome Trust and regulatory institutions such
as the UK Human Tissue Authority5 and the scientific interest currently
focuses on new ways of creating cells with regenerative potential. Some of
the clinicians involved in the Collaborative have formed a significant
European Network that won funding in 2011 for a large clinical trial with
established stem cells, which they perceive as the ultimate test. The
Collaborative as a group however ceased meeting in 2012. This may be
interpreted as a case in which the tensions between biological and
medical research could not be resolved and the translational imperative
failed to pull through the new treatments originally envisaged.
    The heteronomy of success indicators in the different fields of
biomedicine seems still stronger than the commitment to translation,
which is not directly one of them. Scientists and clinicians need to publish
papers in top journals and the criteria which the translational imperative
aims to introduce and add to the success stories of a particular biological
or medical laboratory’s achievements, are not aligned with the internal
workings of the sciences that contribute to biomedicine. The platforms
are not aligned and thus the difference between publicly accountable
research and research excellence still overshadow compliance with this
imperative of social and commercial utility.
    This case of stem cell research for the heart offers a valuation of the
imperative for translational research that so far has not been very
successful. Research in other fields within biomedicine is likely to show
equal levels of complexity, in which the justifications, initiatives, rhetoric,
funding support, and other strategic mechanisms of facilitating
translation may more successfully create the normative basis for science
that translates into improved health.

   !
4. Conclusion

    Biomedicine and translational research as concepts have different
historical origins, yet, the necessity for multidirectional and multi-actor
engagement is inherent in both. Sociology has been analysing and
reflecting on the social practices which shape the developments of
translation and its penetration of more and more areas of biology and
medicine which draws in a growing number of social sectors and agents.
That research has to be oriented toward therapeutic application to
deserve public funding and be of societal value is an imperative that
contradicts and challenges to the point of denial the complexity of

!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
5
 http://www.hta.gov.uk/_db/_documents/Role_of_regulators_in_regenerative_
medicine.pdf
Harrington and Hauskeller                                                      199
successful interactions and transfers between multiple agencies.
Biomedicine is pregnant with translation. Implied in the use of the
metaphor of translation is that exchanges are transformations in which
the meaning, however well captured, shifts slightly between original text
– be it the clinical or the laboratory’s – and the new text. With narrow
reins regulators try to predetermine with simplistic notions of translation
and to-do-lists the outcome of the science yet to be conducted and how
its results ought to be implemented. They negate the potential that lies in
biomedicine as an evolving project for many kinds of therapeutic
innovations and understandings of biology.


Acknowledgements

    The authors gratefully acknowledge the Economic and Social Research
Council (ESRC) as funder of both the project Stem Cell Research in Context
(Project No. RES-349-25-0002) and the ESRC Centre for Genomics in Society in
Exeter, which was part of the ESRC Genomics Network.
    The Corresponding Author, Jean Harrington, also acknowledges the support
of the National Institute for Health Research (NIHR) Biomedical Research
Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s
College London. The views expressed are those of the author(s) and not
necessarily those of the NHS, the NIHR or the Department of Health.


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Harrington and Hauskeller                                                  201
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