10.6092/issn.2038-3460/17440
We investigate translation in biomedicine by exploring how researchers supported by the British Pharmacological Society’s Integrative Pharmacology Fund (IPF) have responded to increasing translational aspirations within pre-clinical animal research. The IPF sought to enhance institutional capacities, collaborative practices, and personal skills within in vivo research in the quintessentially translational fields of pharmacology, physiology and toxicology. We identify three manifestations of the influence of translational aspirations: 1) shifting from the standardisation of animal models to the alignment of research on animals with human therapeutic pathways; 2) expanding relationalities of care in animal research from a focus on the animal body to institutional arrangements around clinical care; and 3) changing training around research ethics, integrity and good statistical practice. Concluding, we discuss the value of working interactively with those involved in the changing practices of animal research and translation as a means to foster reflexivity about what matters when “training to translate”.
application/pdf
2038-3460
17440
2
en
Gail Davies
https://creativecommons.org/licenses/by-nc-sa/2.5/
Tecnoscienza – Italian Journal of Science & Technology Studies
ethics
Training to Translate: Understanding and Informing Translational Animal Research in Pre-Clinical Pharmacology
Text.Serial.Journal
https://tecnoscienza.unibo.it/
10
Essays
2020-01-30
2023-06-26
2020-01-30
2023-10-09
5-30
TS
Gail Davies
2019
10.6092/issn.2038-3460/17440
5
University of Exeter
2038-3460
2
ethics
en
30
Training to Translate: Understanding and Informing Translational Animal Research in Pre-Clinical Pharmacology
https://tecnoscienza.unibo.it/article/download/17440/16290
10
                                                                                            Essay
                                                                                                     5




Training to Translate: Understanding
and Informing Translational Animal
Research in Pre-Clinical Pharmacology
 James W. E. Lowe                             Sabina Leonelli               Gail Davies
   University of Edinburgh, UK                 University of Exeter, UK   University of Exeter, UK



     Abstract: We investigate translation in biomedicine by exploring how re-
     searchers supported by the British Pharmacological Society’s Integrative
     Pharmacology Fund (IPF) have responded to increasing translational aspira-
     tions within pre-clinical animal research. The IPF sought to enhance institu-
     tional capacities, collaborative practices, and personal skills within in vivo
     research in the quintessentially translational fields of pharmacology, physi-
     ology and toxicology. We identify three manifestations of the influence of
     translational aspirations: 1) shifting from the standardisation of animal mod-
     els to the alignment of research on animals with human therapeutic path-
     ways; 2) expanding relationalities of care in animal research from a focus on
     the animal body to institutional arrangements around clinical care; and 3)
     changing training around research ethics, integrity and good statistical prac-
     tice. Concluding, we discuss the value of working interactively with those
     involved in the changing practices of animal research and translation as a
     means to foster reflexivity about what matters when ‘training to translate’.

     Keywords: translation; animal research; pharmacology; in vivo skills;
     standards; ethics.

     Submitted: July 19, 2018 – Accepted: November 08, 2019

     Corresponding author: James W. E. Lowe, Science, Technology and
     Innovation Studies, Old Surgeons’ Hall, High School Yards, Edinburgh, EH1
     1LZ. United Kingdom. Email: james.lowe@ed.ac.uk




1. Introduction

   This paper reflects on the changing research practices of in vivo
pharmacology through the lens of co-produced research carried out with
the laboratory animal community. In 2016, the British Pharmacological
Society (BPS) funded us to conduct an evaluation of the impact and

TECNOSCIENZA
Italian Journal of Science and Technology Studies
10 (2) pp. 5-30 - ISSN 2038-3460
www.tecnoscienza.net                                      2019
6                                                            Tecnoscienza – 10 (2)

achievements of the Integrative Pharmacology Fund (IPF), a programme
that aimed to support animal research and training in pharmacology,
physiology, and toxicology in the UK. This involved carrying out inter-
views with laboratory animal researchers, but also collaborating with BPS
members towards developing a framework for understanding the role of
in vivo skills and relevant training in the future of pharmacology and re-
lated research areas. In what follows, we report our experiences in this
project, with the aim of using them as an empirical ground to identify
ways in which translational discourse may affect pre-clinical practices of
animal research. At the same time, we reflect on how the changing under-
standing of animal research and translation in Science and Technology
Studies (STS) can contribute to the development of laboratory practices
within in vivo pharmacology.
    Intellectually, this study is located at the intersection of three evolving
literatures in STS. The first is work on the practices of laboratory animal
research, which since Lynch’s classic 1988 study has examined the mate-
rial transformations and ethical implications of turning animal bodies into
scientific data (Lynch 1988). The second is literature on the changing dy-
namics of translational research. Since the early 2000s, this has challenged
linear models of translation, and instead charted the complexities in-
volved in the movement of biomedical research into clinical practice
(Sunder Rajan and Leonelli 2013). The third is the growing literature on
engagement in STS, which is increasingly exploring when and whether
STS should intervene (Martin 2016) and the role of STS in ethics and ed-
ucation (Joyce et al. 2018). What these literatures have in common is an
interest in how ‘good’ science is understood and practiced. Animal re-
search always involves scientific and moral uncertainties, as researchers
and regulators work out “the proper relations between the suffering of
the research animal and the health of the human” (Dam and Svendsen
2018, 349). The growth of translational imperatives in biomedical re-
search (Harrington and Hauskeller 2014) is reshaping how these relations
are understood, adding moral dimensions to the wider collaborations
around animal research. These collaborations increasingly include social
science scholars (Davies et al. 2016), who are working with the laboratory
animal community to understand the practices of laboratory animal sci-
ence and further both animal welfare and human health. The mutual en-
twining of scientific and ethical practices in the generation of what
Thompson (2013) calls “good science” increasingly features reflexive so-
cial science as well.
    In this paper, we exemplify these shifts – and the role played by trans-
lational imperatives within them – by drawing on our experience in work-
ing with laboratory researchers and BPS officers towards the develop-
ment of discussions around good practice within in vivo research. We
start by exploring the existing STS literatures on animal research and
translation, drawing out the implications of a growing translational im-
perative in animal research for the organisational arrangements of animal
Lowe, Leonelli & Davies                                                      7
research, the roles and relations that are valued, and the changing priori-
ties around reproducibility and validity. We then introduce our collabora-
tive work and reflect on the potential for developing an STS-informed in-
tervention in the practices of translational animal research in pre-clinical
pharmacology, detailing the methods used to evaluate and analyse the
outcomes of the IPF. On the basis of our sustained interactions with bi-
omedical researchers, we then identify three ways in which the growing
translational aspirations have changed pre-clinical animal research prac-
tices. Each of these shifts provides a space for productive engagement by
STS researchers. They are: 1) shifting from standardising animal models
to aligning research on animals with human therapeutic pathways; 2) ex-
panding relationalities of care in animal research from a focus on the an-
imal body to institutional arrangements around clinical care; and 3) the
changing focus of training around research ethics and integrity, including
different interpretations of statistical good practice. Concluding, we dis-
cuss the value of working interactively with those involved in the chang-
ing practices of animal research and translation as a means to foster re-
flexivity about the relations and practices that matter when ‘training to
translate’.


2. Re-evaluating Animal Research in Translational
Pharmacology

     Since Lynch’s (1988) seminal work on how animals in the laboratory
are transformed from naturalistic beings into scientific data, there has
been considerable interest in STS concerning the complex practices of
laboratory animal research. Ethnographic research inspired by and draw-
ing on Lynch’s study has tended to focus on three different dimensions to
the work of transforming animals into data, which contribute to what re-
search participants consider ‘good’ animal research. These can be charac-
terised as: standardisation, care, and training. These dimensions are worth
recalling here, for they still describe critically important aspects of the re-
lations between animals, roles, and results that are choreographed in the
production of meaningful data from animal research; and they also help
to pinpoint how these imperatives have changes over the last thirty years.
The organisational arrangements, allocated roles, and nature of affective
relations with animals in the laboratory have all shifted slightly with the
growth of translational practices in biomedical research. Under UK law,
all animal research must be licensed by the Home Office (Animals (Scien-
tific Procedures) Act 1986). Only projects with a positive harm-benefit
analysis are authorised and all research must seek ways to replace animals
in their research, reduce the number of animals used, and refine methods
to reduce suffering and pain – that is, to apply the 3Rs approach of re-
placement, reduction and refinement (Russell and Burch 1959). The
growth of translational research imperatives is now increasing the atten-
8                                                           Tecnoscienza – 10 (2)

tion given to realising research benefits as both a scientific and ethical is-
sue (Davies 2018) and altering the ways by which the 3Rs are applied.
This is starting to change the way that standardisation, care, and training
are understood and practiced.
     The first dimension that has characterised the study of laboratory an-
imal research in STS are the practices of standardisation in the produc-
tion of ‘good’ laboratory animals. Historical studies on the development
of animal research throughout the twentieth century and contemporary
ethnographies of practices in animal research often stress standardisation
as the route to reliable animal research1. Lynch noted that researchers
designated particular laboratory animals as ‘good’ or ‘bad’, observing that
“[t]he ‘goodness’ of the animal referred to the readability, clarity, con-
gruence with anticipations of what the data should look like, and the ease
with which it could be treated as a standardized member of a cohort”
(Lynch 1988, 271). Standardisation remains an important consideration
in animal research, but the scientific literature is increasingly concerned
with questions around the standardisation fallacy (Würbel 2000) or how
certain forms of standardisation intensify issues around validity (Richter
et al. 2010). STS accounts increasingly talk about how translation is
achieved through “balancing standardisation and individual treatments”
(Dam and Svendsen 2018, 349). The unstable experimental humanised
mouse model generates value as it becomes a “collaborative thing”
around which new translational conversations can accrue (Davies 2012).
     The second dimension, evident in Lynch’s work and advanced subse-
quently, has been the STS attention to how animal research is co-
dependent on the provision of ‘good’ animal care (Lynch 1988,
Holmberg 2011, Bischur 2011, Viteritti 2013). Care is understood as a
bodily and affective skill that underpins the validity of the data by reduc-
ing animal stress and ensuring that animals perform in the requisite and
desired way. However, for much of the last thirty years, discussion of the
role of animal care has been premised on a division of labour between
care practices and research practices. Responsibility for care has normally
been practiced by animal technicians who work in the animal research fa-
cility, and who provide specialised care for laboratory animals and sup-
port for the work of principal investigators. There were inevitable ten-
sions between these roles, but as Birke and colleagues (2007, 117) sug-
gest, “animal technicians and high-ranking scientists […] are bonded by
shared understandings of what counts as ‘good’ animal care”. Animal
care remains critically important, but its scope is expanding in the con-
text of translational research and changing regulation. Researchers, as
well as animal technicians, are having to attend more carefully to animal
experience to facilitate translation (Friese 2013). There is a growing atten-
tion by regulators of animal research to the “culture of care” of an organi-
sation, which is concerned with how communication between roles hap-
pens within institutions, as well as the extent to which wider societal expec-
tations of humane animal care are reflected in practice (Davies et al. 2018).
Lowe, Leonelli & Davies                                                      9
     The third aspect of work on animal research in STS has been a focus
on what it means to train people to work well with laboratory animals.
Despret’s (2004) work has been inspirational in drawing attention to how
training generates the expectations and affects that authorises a good ex-
perimental performance and what it means to become an experimentalist
(Holmberg 2008). Despret recounts the work of Rosenthal (1966), who
used students enrolled in a laboratory course in experimental psychology
to explore how their expectations of what kind of rat they were working
with shaped the rat’s performance in the maze. Despret explores how
“the expectations of a good experimenter have authorized the rat to be-
come competent” (2004, 120), whilst also noting how the rat authorises
the student to become competent. Despret’s work has informed subse-
quent studies of how becoming a good experimenter involves learning to
“become with” animals. Yet, this too is changing as the expectations of
‘good’ experimental outcomes shift from the performance of the animal
in the apparatus to clinical outcomes. Learning with animals remains a vi-
tal component of translational research practices. Friese has observed
how training for translational research involved developing the “right
‘touch’ for surgery” (Friese 2013, 133), so that the researcher could now
move between the parts and the whole of the mouse appropriately. The
movements required for translation are now more complex: animals may
have to be made, unmade, and remade as complex circuits of translation
seek to match the performance of the animal to the human experience or
mechanism it seeks to model (Svendsen and Koch 2013; Nelson 2018).
This happens within experimental practices, but also through increasing
contestations over the design of experiments and their statistical infer-
ences (Würbel 2017).
     As suggested above, these questions around standards, care and train-
ing are not only dominant strands in the STS literature on animal re-
search, but are also growing discussions in the scientific literature. These
discussions are particularly evident in the literatures around translational
research and in pharmacology in particular. Pharmacology is quintessen-
tially translational in its objectives and practices, as it explicitly seeks to
bridge the gap between biological knowledge and drug development for
humans and non-human animals. Yet this purported translational
achievement is increasingly questioned. Discussions of the pharmaceuti-
cal ‘pipeline’ are frequently couched in terms of a crisis (Sunder Rajan
2017; Murphy 2017), referring to the failure of potentially promising new
drugs to progress through the different stages of drug discovery and de-
velopment from pre-clinical laboratory research (whether in vivo, in vitro
or in silico), through safety and efficacy testing in animals and humans, to
clinical trials in human patients. To date, this process of attrition has been
most visible when drugs have failed to show efficacy in human clinical tri-
als, for this is where ‘failures’ are most public and costly (Freedman,
Cockburn and Simcoe 2015).
10                                                          Tecnoscienza – 10 (2)

    At the same time, there is a growing sense that these problems may al-
so be identified and addressed through re-evaluating the practices of pre-
clinical animal research. While in vivo research has long been positioned
as vital to translational research, detailed discussion of the specific value
and limitations of animal models in furthering clinical advances is more
recent (for example, Collins 2011). Managing failures sooner in the drug
discovery process may be less expensive and have ethical gains in terms of
more effective human clinical trials and less animal wastage (Ioannidis et
al. 2014). Growing debate over the reproducibility of many studies using
animals in research (Academy of Medical Sciences 2015) and the failure
of drugs tested on animals that subsequently enter human trials is further
seen by some as a fundamental challenge to the ethical justification of bi-
omedical research in animals (Pound and Bracken 2014). Researchers and
learned societies are thus increasingly reviewing the different phases of in
vivo research to look closely and critically at the practices for translating
knowledge of disease mechanisms and treatment between species, includ-
ing around validity of animal models, experimental design, reporting
conventions and forms of animal husbandry and care (Begley and Ellis
2012; Concordat on Openness on Animal Research in the UK; Davies et
al. 2017; Nuffield Council on Bioethics 2005; Osherovitch 2011). This
raises questions about the operation of animal models, and also about the
organisation and implementation of institutional models of translational
research.
    The opening up of discussions around animals used as models within
the research community offers an opportunity to integrate STS studies of
animal research with STS work on translation. Earlier models of transla-
tion, which viewed the process of producing tangible outcomes from sci-
entific research in terms of a path – bench to bedside – strewn with ob-
stacles to be overcome (e.g. Pober, Neuhauser and Pober 2001), have
now largely been superseded. Many scientists and funders acknowledge
the complex trajectories involved in translation and the challenges of fos-
tering collaborative relations required to sustain interactive research (Col-
lins 2011; Collins and Tabak 2014; Moher et al. 2016; Zerhouni 2003).
Within STS, translation has increasingly been tracked and reinterpreted
through attending to how knowledge moves: developing laboratory re-
search with therapeutic outcomes relevant to humans requires organising
and managing translational processes so that “biomedical claims, objects
and practices” can “move across boundaries” between institutions, disci-
plines, and species (Sunder Rajan and Leonelli 2013, 466). This promotes
certain forms of collaboration, standardisation and regulation. Further-
more, these movements are not only one-way. The movement between re-
search, safety and efficacy testing and clinical trials is increasingly under-
stood as non-linear and recursive, constituting what Lewis and colleagues
(2014) characterise as “circuits of translation”, which involve both mate-
rial flows and conceptual transformations at each iteration (see also
Crabu 2016 and 2018).
Lowe, Leonelli & Davies                                                 11
    There is a significant body of work within STS focusing on patterns of
translational research in genomics (Maienschein et al. 2008), meta-
genomics (Levin 2014), stem cell research (Maienschein et al. 2008; Mar-
tin, Brown and Kraft 2008; Fagan 2013), neuroscience (Brosnan and Mi-
chael 2014) and plant science (Leonelli 2013). The complexity of transla-
tion they indicate can help in developing new ways of thinking about the
role that animals play in translational research and the training required
for researchers to facilitate these practices. Standardisation is no longer
the overriding imperative in animal research. Translational animal models
need to be stable enough to move, but also sufficiently adaptable to be
able to encompass the changing understandings of disease that happen
through circuits of translation (Davies 2012; Dam and Svendsen 2018;
Nelson 2018). Care for the animal is increasingly seen as not only a shared
ethical value, but also an essential component of research, when transla-
tion is dependent on stress-linked immunological and other responses
(Friese 2013; see also Seok et al. 2013). Training has to be opened up to
multiply the “the body we care for” (Despret 2004), to include attuning
to and transforming humans as well as animals. In translational research
“scientists calibrate animals against the medical phenomena which they
are intended to represent. In turn, human medical conditions and the pa-
tients who manifest them have to be calibrated against the rodent mod-
els” (Lewis et al. 2013, 776).
    The question for this study is how far the changing understanding of
animal research and translation in STS can contribute to shaping these
practices in productive ways. In the next section, we discuss the methods
and context for research that we carried out in collaboration with the
British Pharmacological Society (BPS) as part of their processes for eval-
uating past funding and developing future training for pre-clinical animal
research.


3. Evaluating the Integrative Pharmacology Fund

    This research emerged from a commission, by the BPS, for the au-
thors to evaluate the outcomes of the Integrative Pharmacology Fund
(IPF). The BPS are a membership charity, whose mission is to promote
and advance pharmacology. They have played a role in the development
of in vivo skills in the UK by driving long-term collaborative partnerships
and providing funding. The BPS launched the IPF in 2004 as part of its
efforts to address a perceived in vivo skills gap (ABPI 2005). It was run
between 2004 and 2014 by a consortium involving the BPS and three ma-
jor pharmaceutical companies: AstraZeneca, GlaxoSmithKline, and Pfizer
(see Collis 2006, 2009; Lowe et al. 2016). The IPF was led by a steering
group comprising representatives of the funders. It worked with national
funding bodies (the Biotechnology and Biological Sciences Research
12                                                        Tecnoscienza – 10 (2)

Council, BBSRC; the Medical Research Council, MRC; and the Higher
Education Funding Council for England, HEFCE) to support in vivo ed-
ucation and training. The initial £4 million investment in the IPF was
used to leverage total support of £22 million for in vivo research, educa-
tion, and training. The IPF thus constituted a significant focus for the
BPS for over 15 years; was a substantial investment of both public and
commercial funding; and has played an important role in shaping the
practices, skills and training that have defined pharmacology in the UK
over the last 15 years.
    The authors were approached to provide an evaluation of the IPF be-
cause of past experience in working collaboratively with the laboratory
animal community (Davies et al. 2016). The overall scope and organisa-
tion of the evaluation project was co-produced between Davies, Lowe,
and Leonelli as independent researchers, Anna Zecharia and David Lewis
as representatives of the BPS, and BPS member Michael Collis as an in-
dependent consultant (following former leadership of the IPF). The pro-
ject was given ethical approval through the University of Exeter. Research
started with a review of the current literature on in vivo skills training
through academic and grey literature. Two questionnaires were delivered
to those who received IPF support as a Master’s or PhD student (25 were
returned) and those who were appointed to fellowships or staff positions
as a result of IPF support (17 were returned). These were used to gather
basic information and recruit participants for semi-structured interviews.
Lowe conducted 19 interviews with 20 participants. All participants had
been, and many still were, engaged in work using in vivo research. They
were asked about how the BPS had supported their work and invited to
reflect on the changes they made to the design and conduct of experi-
ments through this training, including around ethical practice, public
outreach and research translation. The transcripts of these interviews
were coded using the qualitative data analysis software NVivo. The evalu-
ation was completed through two stakeholder meetings organised by the
BPS, which provided feedback on the initial findings and enabled the
whole evaluation team to develop recommendations in conversation with
key stakeholders.
    The distinct roles of the University of Exeter researchers and BPS
representatives were negotiated at the start of the project to establish
boundaries that protected the independence of key aspects of the re-
search and the identity of research participants. A firewall was construct-
ed between the University of Exeter and the rest of the team, ensuring
only the University researchers had access to the full results of the ques-
tionnaires, including the identity of the respondents. Participants for the
qualitative research interviews were recruited from the lists provided by
the BPS and sampled by the authors to encompass a diversity of thematic
research areas, institutional positions, and personal experiences with the
IPF. Of the interviewees, for example: one was the head of an Integrative
Mammalian Biology centre (an IMB, discussed in section 4), eight were
Lowe, Leonelli & Davies                                                  13
researchers working as fellows or permanent research staff members at
IMBs, four encountered the IPF as postgraduate students, three worked
in senior technical positions at IMBs, two were recipients of ‘pump prim-
ing awards’, and a further two were well-established figures in animal re-
search who were not based at IMBs. To enhance the integrity of the data
collected, participants were promised full anonymity and only anony-
mised quotes from interview transcripts were shared with the BPS. It was
agreed at the outset that the data generated in the project would be
owned by the BPS but could be used by the authors in subsequent publi-
cations independent of the BPS.
    The final evaluation report was jointly agreed. The main body of it de-
tailed the empirical material generated, analysed and drafted by the Uni-
versity researchers. The introductory material and final recommendations
in the report were guided by the requirements of the BPS, drawing on the
interviews and workshops, and agreed in consultation with the BPS
council. For the authors, this project constitutes a constructive engage-
ment and intervention into science policy in an area for which the BPS as-
sumes professional responsibility. It is notable that this ‘serviceable STS’
was for an organisation with little executive power itself (Webster, 2007),
but with an established role in guiding norms and standards for its field.
The outcomes of the study thus focus on how the organisation and prac-
tices of translational pharmacology can be enhanced through education,
training, and reflexive conduct by practitioners. The intervention is
shaped by the aims and activity of the BPS itself, but also the restricted
and specific scope of the power and influence of that organisation within
a wider context of education, skills, research and industrial policy and ac-
tivity. The report was launched in December 2016. One of the initial out-
comes from this work has been the development of an undergraduate
core curriculum for pharmacology courses in the UK, which was
launched in 2018 and now has over thirty organisations signed up2.
    This paper has been developed subsequently and separately from the
commissioned work. The interview transcripts used for the evaluation
were further analysed to explore how researchers manage the different
accountabilities and changing aspirations in translational pharmacology,
drawing on coded responses to questions around ‘best practice’, ‘transla-
tion’ and ‘the 3Rs’. In the next section, we draw on this material to ex-
plore how translational aspirations are changing the practices of standard-
isation, care, and training indicated by earlier studies in STS. We show
how the work of transforming animals into data sources is being recali-
brated at an institutional level, changing what is valued as ‘good’ science
from standardising animals to aligning experiments, expanding institu-
tional interactivity, and in deliberations around balancing research design
with the 3Rs.
14                                                          Tecnoscienza – 10 (2)

4. Training to Translate: The Recalibration of Animal
Research in UK Pharmacology

    A key element of the IPF initiative was the establishment of four Inte-
grative Mammalian Biology centres (IMBs) across six UK universities.
These brought together the different disciplines involved in pharmacolog-
ical research, and were involved in employing staff, awarding PhDs and
establishing Master’s degree courses to build future capacity for in vivo
skills in pharmacology. The IMBs were intended to form centres of excel-
lence, with responsibilities for promulgating high standards of animal
welfare and developing innovative forms of research. An important aspect
of this was advancing the translational potential of research. This involved
a series of changes to practice that we identify below.

4.1 From Standardising Animals to Aligning Pre-Clinical and
Clinical Experiments

    Different forms of pre-clinical animal research use animal models in
different ways. While standardised strains are still used for regulatory tox-
icity and safety testing, research into specific human diseases or injuries
involves the use of ‘bespoke’ animal models created to model particular
aspects of a disease3. This dual use of animal models leads to a diversity of
proposed solutions to the problem of enhancing translation through in
vivo research. Some commentators demand greater standardisation in re-
search, for example through standardised reporting of animal research
(Kilkenny et al. 2010), the reduction of bias in publications through ex-
perimental randomisation and blinding, the publishing of negative results
(van der Worp et al. 2010), and the development of standards for recog-
nising the importance of genetic background effects in animal models
(Crusio et al. 2009). Others stress enhancing sensitivity to local experi-
mental situations and individual disease trajectories, including incorporat-
ing animal care and environmental enrichment into translational research
(Richter, Garner and Würbel 2009; Friese 2013), developing more per-
sonalised disease models (Davies 2012), or using biomarkers and so-
called reverse translation methods to move in non-linear ways between
animal models and individual disease trajectories (Garner 2014). These
are not mutually-exclusive, since standardised reporting and greater ex-
perimental variability can work together, but these debates do indicate
the tensions researchers face in striving for translation in their work.
    In our interviews, researchers talked about how they had increasingly
moved away from established ‘gold standard’ models in animal research,
instead seeking to match experimental and clinical treatment regimes.
This happens, for instance, when seeking to align in vivo research with
clinical trial protocols, and model patient experiences alongside disease
characteristics. In other words, there has been a sustained attempt to shift
Lowe, Leonelli & Davies                                                            15
research focus beyond the animal body and related forms of standardisa-
tion and control, and towards the circumstances and requirements of
clinical care and related institutional arrangements.
    Many researchers report making changes to experimental design, es-
pecially strategies around dosing techniques and levels, to enable them to
scale up to human clinical studies. Some have suggested that there has
been a recent shift away from using dose levels in animal research that
would generate a statistically meaningful – and thus publishable – effect,
towards asking whether the doses and methods of drug application could
translate meaningfully to humans, as exemplified by the following quote:

    Are they using the animal model that they are working with in the cor-
    rect way? Are they dosing at a dose that you could think of translating to
    a human equivalent that would be actually realistic? Are they thinking
    about what route of administration would you be giving it in humans in
    order to actually think about bio-distribution and those sort of things
    quite early on? (Senior researcher at a small university, 2016)

    As pointed out by the same interviewee, sometimes addressing these
questions means changing experimental protocols in animal research ‘up-
stream’, to match the likely downstream mode and dose of clinical appli-
cation:

    I’ve become increasingly convinced that if you are going to do a drug IV
    [intravenously] then it’s got to be IV in the mouse. […] And within the
    literature I work in, the [mouse model that the interviewee works on] is
    just littered with examples of mice being fed, or whatever, huge quanti-
    ties of a drug of some sort which is completely unfeasible in man, com-
    pletely unfeasible. That’s very disappointing because what we’ve seen
    historically is clinical trials being developed on the basis of the mouse
    work, but a disconnect where the human receives a fraction of the scaled
    dose that the mouse got and it’s not surprising that it’s not a very suc-
    cessful trial. (Senior researcher at small university, 2016)

    Further interviewees discussed how the design, validation, and use of
animal models are themselves modified to produce results of greater
translational potential. One researcher described a change in use of mice
models to simulate the human experience of neurodegenerative disease,
where drug treatment follows diagnosis rather than preceding the onset
of symptoms:

    We wanted to use an animal model and a time course that was going to
    be translational. What a lot of previous work does is set up an animal
    model, of Alzheimer’s or Parkinson’s for example, but they’d pre-treat it
    with the drug before the model was initiated. So translating that to peo-
    ple is effectively like treating anyone over 50 with a drug in the hope that
    a few of them get Alzheimer’s disease. They won’t get Alzheimer’s dis-
    ease because you’ve given them the drug. So that was one of the prob-
16                                                                 Tecnoscienza – 10 (2)

     lems in what we were doing. So we sort of worked quite hard to design a
     study so that you set-up the model, wait a certain period of time to make
     the animals how a person would be when they get to clinic with Parkin-
     son’s or Alzheimer’s, for example, and then that’s when you start the
     drug treatment. (Postdoctoral researcher at large research university,
     2016)

    Another researcher talked about moving from using adult rats to us-
ing elderly rats, and small focal lesions to larger ones, to better model im-
portant characteristics of people affected by stroke. As well as changing
the experimental temporalities through matching older animals to older
patients, they also changed the treatment period to match median hospi-
tal admissions and facilitate the organisation of later clinical trials:

     In one of our experiments we were infusing the protein into the muscles
     of the animals for a month after stroke, starting 24 hours after stroke. He
     [the clinician] challenged me on it. And he said, that’s really interesting,
     but why would you choose a month, because in practical terms it’s really
     hard to run a clinical trial like that, as the majority of our patients dis-
     charged, the median stay is 13 days. […] So he said, you’ve got to find a
     way to compress this down into a timeframe that’s compatible with our
     patients. (Mid-career researcher at a large research university with a
     neighbouring hospital, 2016)

    This search for a more ‘translatable’ animal model is recognised to
have trade-offs. The time involved in allowing disease aetiologies to de-
velop may be expensive, and there may be welfare implications if animals
with disease symptoms are used in procedures for longer periods (as, for
instance, in the case of diet-induced obesity in mice). In addition, out-
comes are still uncertain even using the ‘best’ available models. Some re-
searchers explained how they were including aspects of patient experi-
ence in their pre-clinical studies. Examples involved modelling co-
morbidities in experimental stroke research by using hypertensive rats;
and using analgesics on animal models, which better represents patient
experiences while also promoting animal welfare.
    The increasing interactivity fostered by aspirations for translational re-
search is promoting the alignment of drugs, doses, models, and temporal-
ities between pre-clinical research with clinical trials and clinical applica-
tion. The interviews indicate growing acceptance that the evaluation of
animal models requires revision to include their potential translational
value (as argued by van der Worp et al. 2010 and Garner 2014, among
others). The specifics of this vary by disease area, and researchers stress
how improving translational in vivo research is complex and iterative, ra-
ther than a one-way linear process. Several interviewees described collab-
orations as vital for changing both the experimental design and pharma-
ceutical agent, so that a viable compound can be taken from the laborato-
ry into a clinical trial or clinical setting:
Lowe, Leonelli & Davies                                                            17
      A lot of the drugs I was using in my PhD were quite unstable. So I
      couldn’t give them in drinking water or in their food, for example. I had
      to make up the drug fresh each day and give the animal an injection. In
      some of the work we’re doing here, with the help of [the pharmaceutical
      company funding the laboratory] we’ve been able to mix the drug for
      example into the mouse food so that they can eat it without having an in-
      jection twice a week. (Postdoctoral researcher at a large research univer-
      sity, 2016)

    Indeed, this trend towards context-specific alignments and equiva-
lences increases the complexity of pre-clinical research data and may
work against those who view standardisation as a solution to the transla-
tion gap (Lewis, Hughes and Atkinson 2014). This increasing complexity
demands renewed attention to how care is practiced in translational re-
search, both for animals and for people.

4.2      Caring for Animals; Caring for People

    Pre-clinical pharmacologists sit at a critical juncture between basic and
clinical research. In addition to the experimental realignments presented
above, this also involves working in new organisational configurations and
incorporating new relations of care for research subjects, whether they be
humans or non-humans. Interviewees talked about needing to be more re-
sponsive to the multiple responsibilities involved in developing interdisci-
plinary research collaborations, thus reflecting on the new forms of ac-
countability brought about by bringing laboratory and clinical practices
closer together. As Crabu suggests, in translational research “the laboratory
itself can be re-framed and adjusted to render laboratory facts and scientific
phenomena congruent with the processes of care and the clinical manage-
ment of patients” (Crabu 2016, 3). This changes where problems are de-
fined, how they are framed, and how they might be addressed.
    Throughout the interviews, participants highlighted their efforts to
develop new relations between basic, pre-clinical and clinical researchers,
so as to create the interactive and recursive mobilities between disciplines
that facilitate translation. One interviewee used the terminology of ‘back-
translation’ to identify this shift. This highlights the reversion of the ste-
reotypically linear, bench-to-bedside direction of translational research,
and acknowledges how researchers are now seeking to answer questions
coming from clinical care in pre-clinical research. In their words:

      In the past, mainly my research was based on research which was done
      on animal models and problems that people identified in more molecu-
      lar problems. Now it’s also directed by problems in the clinic. So […]
      I’m more thinking about how problems identified in the clinic can be
      back-translated and how animal models can help answer the question.
      (Early career researcher at a medical school, 2016)
18                                                                  Tecnoscienza – 10 (2)

    Beyond answering questions generated across basic, pre-clinical, and
clinical research contexts, the translational mobilities of in vivo research
also require understanding how answers are given value and statistical
significance within different experimental systems. Statistical measures of
biological significance have tended to be domain-specific and to some ex-
tent incommensurable with each other. Given this context, informal dia-
logue between pre-clinical and clinical researchers aids further under-
standing of the criteria by which answers will be deemed to be biological-
ly significant across other domains. Being involved in translational re-
search means adopting statistical standards that will protect patients in
clinical trials, which are not necessarily the same as those meeting the
thresholds for publishing in basic research, as highlighted by the follow-
ing interview quote:

     I am more aware of the clinical research and the types of designs for
     clinical trials, which maybe I wasn’t aware of before. So it’s widened my
     knowledge and my circle of reading and I am aware of the very stringent
     criteria there are for clinical trials which there isn’t in basic science […]
     There’s this fallacy that exists where people tend to think that an n of 6
     is enough for a significant experiment in the animal world, whereas
     that’s a ridiculous way of thinking now. The group on stroke, they are
     far further down this line than I am, so they have the pre-clinical stroke
     models and they work very closely with the clinicians, so they have much
     more dialogue. And so being involved with their lab meetings and in just
     general tearoom discussions, I’ve become more and more aware of how
     stringent we need to be when, first of all, designing experiments and
     then doing power calculations but also in interpreting our data as well
     and determining what is or what isn’t biologically significant. (Senior
     lecturer at a large research university, 2016)

    This exchange can also go the other way, with clinicians being trained
in animal use and care. One interviewee, who was appointed within an
IMB centre to help share expertise on animal research, talked about how
they were able to introduce clinical researchers to the required skills to
conduct animal research. Clinicians were guided through the process of
initiating a project, matched up with potential collaborators, and given
training to design and conduct experiments with them. In their words:

     In terms of marrying up clinicians to any in vivo research side, things
     have certainly progressed. Those individuals had never had any experi-
     ence of working in an animal model, but [want to] in order to progress
     their work […]; essentially, they’ll ask, ‘I want to do some animal work.
     Who do I talk to?’ Then they end up talking to me. (Research and tech-
     nical support at a large research university, 2016)

    Some collaboration focused around formal roles allocated via the IMB
centres, such as the research management role above. Other forms of in-
teractivity were brokered through jointly-supervised PhD studentships,
Lowe, Leonelli & Davies                                                               19
which were “always highly favoured where there were two supervisors for
different faculties […] which could bring together basic and translational
skills” (senior manager at a large research university, 2016). Other collab-
orations were more informal, facilitated by the co-location of IMB centres
near large teaching hospitals. As one researcher suggested, informal meet-
ings with a clinical researcher with everyday experience of patient care
had provided advice that would not have been available from the litera-
ture, but which had affected how they designed and conducted their ex-
periments:

      We probably meet once or twice a year on average, and he asks me what
      I’ve been doing, and I tell him what I’ve been doing, and he explains
      what the challenges are in translating this kind of thing. He’s given me a
      couple of really good bits of advice which made me think about how to
      do the work that I do. It’s these kinds of little gems of information that
      you can’t get from the literature and from chatting with your friends. It
      needs to be someone that works with stroke patients every day that can
      tell you the realities of it. (Mid-career researcher at a large research uni-
      versity with a neighbouring teaching hospital, 2016)

    These informal collaborations do not involve formal working relation-
ships and typically they do not result in the clinician being involved in co-
authoring publications. Nevertheless, our interactions with IPF research-
ers show that informal collaboration plays an important role in facilitating
access to clinical knowledge that comes from day-to-day interactions with
patients. Informal collaborations supplement the technical and experi-
mental knowhow developed through circuits of translation, by helping to
identify matters of care in both clinical settings and animal research.

4.3      Reporting, Reproducibility, and the 3Rs

    In this final empirical section, we explore how translational expecta-
tions in animal research are increasingly intertwined with policy and
training on research integrity, reproducibility, and applications of the
3Rs. Training to become a ‘good experimenter’ today means conforming
to multiple expectations, whilst navigating a shifting methodological
landscape in light of the so-called crisis in the reproducibility in biological
research (Academy of Medical Sciences 2015). Researchers in pre-clinical
academic settings are often working in environments where there are ca-
reer pressures to “win a place in a select few journals” (Horton 2015,
1380). However, top-ranking journals have been criticised for poor re-
porting of animal research, with few articles containing information on
randomisation, blinding, and sample size estimation (Macleod et al.
2015). Training students in pre-clinical pharmacology means teaching
them to negotiate the pressures and policies around research integrity, re-
search reproducibility, and the 3Rs. This sort of training rarely appears in
the literature on animal research in STS but is an increasingly significant
20                                                                 Tecnoscienza – 10 (2)

part of becoming a good experimenter (Leonelli 2017). Producing ‘good’
results may not involve working directly with animals but will require
making ‘good’ calculations to get sample sizes right, avoid bias, and be
transparent about the relationship between hypotheses and data.
    Debates over rigour and reproducibility are particularly acute in in vi-
vo research, where underpowered experiments and p-hacking result in
animals’ lives being wasted (Ioannidis et al. 2014)4. Several initiatives are
seeking to enhance the conduct of biomedical research through improv-
ing reporting in academic journals, ensuring rigorous grant review, and
supporting institutional leadership (Begley and Ioannidis 2015). The
ARRIVE guidelines refer to the reporting of animal research and are in-
creasingly incorporated into journal submission processes (Kilkenny et al.
2010). The PREPARE guidelines are intended to be used prior to re-
search taking place (Smith et al. 2018). The National Centre for the 3Rs
(NC3Rs) is developing resources to help in vivo researchers in the UK
meet legal requirements to replace, reduce, and refine the use of animals
in their research. These attempts to standardise and harmonise the con-
duct of experiments and programmes of research mirror international ef-
forts on care and welfare of laboratory animals (see Bayne et al. 2015).
They also change the attunement between expectations, animals, and af-
fects that go into training animal researchers (Despret 2004). These are
now mediated through written guidelines, checklists, and protocols. The-
se document what matters in communicating research quality and animal
care, but they do not resolve tensions for researchers who have to work
out how to articulate their research to meet these expectations.
    Our interactions with IPF staff revealed widespread support for the
3Rs, accompanied by a recognition that overall efforts to reduce animal use
in research should not be at the expense of the statistical power of each ex-
periment. Many had been involved in both teaching and outreach activities
that prompted them to think about relations between research translation
and the 3Rs. One researcher had contributed to the development of the
Experimental Design Assistant5, an online tool developed by the NC3Rs to
assist the design of experiments. Nevertheless, divergence in practice re-
mains. In interviews, we found that researchers talking about the require-
ments for reporting, reproducibility and the 3Rs held different views on the
most appropriate experimental design for translating in vivo research.
    One researcher, who otherwise sought reduction in the use of animals
in education, argued for increased sample size as a way to improve a
study’s statistical significance:

     If I decide that a study’s worth doing, I do my sample size calculations.
     But then in most cases, for a four-month study I’m talking about where
     you have a significant investment in time and energy, we do as many an-
     imals as we can in that timeframe. So, we don’t attempt to reduce the
     number of animals, because when we do our sample size calculations, we
     realise that for all the additional animals we put in we increase our abil-
Lowe, Leonelli & Davies                                                             21
    ity to detect a benefit of a drug and you reduce the chances of getting a
    false positive by accident. So I don’t actually try to minimise my animal
    use, I just decide which experiments are really worth doing well, and do-
    ing them properly. And the reason for that is I think a lot of the low-
    hanging fruit is gone now, there are no easy stroke therapies that are out
    there. They’re all going to be most likely small effect sizes, modest effect
    sizes, so you just need to power your studies as fully as possible. (Mid-
    career researcher at a large research university, 2016)

   Another researcher preferred instead to use smaller numbers of ani-
mals, thus shifting focus to the magnitude of experimental effects:

    So if you do an experiment in an animal model with a human condition
    and you get a small change for the better, that shouldn’t be used as a ra-
    tionale for going into man. You need to see a big change. A big change
    at a rational dose. I do quite a lot of consulting now in the neuromuscu-
    lar field and I’m seeing datasets where I tell the company on the basis of
    this, that drug is not going to be clinically effective because the change is
    too small, and yet I’ve seen these programmes go through to full clinical
    development. (Senior researcher at a small university, 2016)

     Both of the above researchers are concerned with the potential value
of their experiments for future drug development and with ensuring that
their results are reproducible and useful. Their experimental design is
guided by their understanding of how data deriving from the drug
achieves translational value in their field. If only marginal effects are
thought to be possible, then larger sample sizes are used. If larger exper-
imental effects can be anticipated, then using smaller sample sizes consti-
tutes better practice. Even for people working in similar fields, on similar
organisms, there are different understandings of what constitute good sta-
tistical practices for interpreting results in translational research. The ex-
tent to which experimental practices are sensitive to the concrete transla-
tional goals depends not only on the biology, but also on the prior history
of investigation and therapeutic development in the relevant area of re-
search, and the historical constitution of that research itself. The expecta-
tions between researcher and animals that Despret (2004) identifies as vi-
tal to producing “good experiments” are supplemented by researchers’
interpretations of the technical requirements of translation.
     While the two approaches discussed above come from established in-
vestigators, there are important lessons here for training early-career re-
searchers. Future efforts to improve experimental design and statistical
power would benefit from a better understanding of how researchers in-
terpret the overlapping imperatives around the 3Rs, reproducibility, and
translation in their everyday research practices. Again, our research sug-
gests that standardised prescriptions of good practice should be ap-
proached with caution. Checklists and standards need to be supplement-
ed with explicit discussions among pre-clinical researchers about the as-
22                                                          Tecnoscienza – 10 (2)

sumptions that they make in their experiments, as well as discussions be-
tween pre-clinical and clinical researchers to ensure the applicability of
findings across domains. Innovation around translational practices from
animal research will not be achieved through compliance with reporting
policies alone, but also requires discussion around the validity and mobil-
ity of the data that results. Minimum standards in check-boxes at the
point of submission of a journal article need to be augmented by oppor-
tunities to encourage dialogue and reflexivity around research practice.
This is exemplified by the very exchanges between STS and animal re-
searchers that characterised our collaboration with BPS, and the uptake
of the recommendations produced through these interactions, as dis-
cussed below.


5. Discussion and Conclusion

    Our research with representatives from the four IMB centres funded
by the BPS suggests widespread identification with current translational
research imperatives. It also indicates that translational research practices
are multi-dimensional and, at times, contested. In this paper, we identi-
fied and discussed three kinds of ways in which researchers who use ani-
mals in pre-clinical research are responding to imperatives to make their
work more translatable. These include moving from the standardisation
of animals to the alignment of experiments, connecting practices of ani-
mal care and patient care, and reflexivity in the calculation of statistical
power and the 3Rs. Collectively, these constitute different dimensions
through which the researchers with whom we interacted conceived of
striving towards translatable science. These supplement the ways in which
STS scholars talk about animal research and translation. They can also be
used to inform the future training of animal researchers. In closing, we
briefly discuss the practical implications of these findings for the im-
provement of in vivo research, and reflect on how, through sustained dia-
logue and reciprocal learning across STS and animal researchers, co-
produced qualitative research can contribute to a productive reframing of
how scientific practice is enacted, understood and evaluated.
    Applying insights from STS scholarship within the initial evaluation of
the IPF helped us to contribute concrete recommendations for the BPS.
Many of these recommendations relate to the increasing complexities
found in “circuits of translation” charted above, and sought to avoid be-
ing prescriptive, focusing instead on ways of enhancing reflexivity and
learning across organisations and for individuals. The final evaluation re-
port included key recommendations for supporting and assessing in vivo
education, strengthening networks for sharing good practice, recognising
the diversity of activities and careers involved in translational biomedical
research, and enhancing collaboration between them (Lowe et al. 2016).
It also details practical examples, including the emergence of new roles
Lowe, Leonelli & Davies                                                   23
for managing and facilitating the increasingly complex modes of dialogue
and collaboration required for translational research.
    The evaluation report also identified some specific challenges and op-
portunities for change. Some of the challenges relate to how translational
research is changing career structures for scientists. There are potential
barriers in the credit structures in science which value publication within
discipline-specific journals. The researchers interviewed here do not ex-
hibit strong disciplinary affiliations; they conduct problem-focused re-
search, and some were members of more than one learned society. Work
tracing the pathways taken by translational research indicate that these
results are rarely in the highest impact factor journals (Cambrosio et al.
2006). However, regimes of scientific credit are evolving to accommodate
new forms of publication and patent applications (see Rasmussen 2014),
which are more aligned with translational researchers’ interests. Some of
the opportunities relate to how translational research is relocating animal
research within a wider context of organisational practices and research
skills. The new BPS core curriculum concerning the use of research ani-
mals includes training that puts knowledge, skills and attitudes about an-
imal research into context. However, it no longer requires undergraduate
students to undertake hands-on research with animal in education set-
tings6. This decision was part of the harm-benefit analysis around the use
of animals in education that the report facilitated, suggesting that learning
outcomes at this stage could be achieved through observation, using sim-
ulations or videos, or through working with an animal facility where re-
search is ongoing.
    Our study adds further dimensions to the accounts of what constitutes
‘good’ animal research in STS with which we started. Striving for good
translation can be understood through the notion of “good science” de-
veloped by Charis Thompson, in which scientific and ethical practices are
understood to be “mutually entwined” (Thompson 2013). Thompson’s
articulation of good science centres on stem cell research, where she ar-
gues that “ethical concern lies at the heart of innovation” (Thompson
2013, 221). In the case of pre-clinical animal research, striving towards
translation involves raising questions about model reproducibility and va-
lidity, rather than standardisation; connecting care for animals with care
for patients; and balancing the reduction in harms to animals with the po-
tential benefits in clinical practice. These questions about the planning,
conduct, and outcomes of scientific research are important in driving in-
novative practices but cannot be resolved by adhering to (external) ethi-
cal guidelines and norms. Training for ‘good’ animal research requires at-
tuning experiments to complex contexts, learning what matters to differ-
ent bodies, and interpreting statistics and ethics in situ. Many researchers
valued taking part in this research as an opportunity to reflect on their
experiences of being trained, developing research careers, and informing
the next generation of pre-clinical pharmacologists. Their accounts of
what makes good pre-clinical animal research links science and ethics,
24                                                             Tecnoscienza – 10 (2)

encompasses policy and politics, and draws on individual beliefs and
conduct. Good translation is enhanced by this reflexivity. The recom-
mendations to the BPS aim to generate researchers able to construct their
research practice and collaborations in ways that support the multi-
directional forms of attention that support translational research. Work-
ing collaboratively with social scientists has helped to identify and en-
hance these opportunities in future training for translation.


References
ABPI (2005) Sustaining the Skills Pipeline in the Pharmaceutical and Biopharma-
  ceutical Industries, London, ABPI.
Animals (Scientific Procedures) Act 1986. Available online at:
   https://web.archive.org/web/20191016095329/https://www.legislation.gov.u
   k/ukpga/1986/14/contents (retrieved 16th October 2019).
Academy of Medical Sciences (2015) Reproducibility and Reliability of Biomedi-
   cal Research: Improving Research Practice, London, Academy of Medical Sci-
   ences.                  Available                online                 at:
   https://web.archive.org/web/20191016095407/https://acmedsci.ac.uk/file-
   download/38189-56531416e2949.pdf (retrieved 16th October 2019).
Ankeny, R. and Leonelli, S. (2018) Organisms in Experimental Research, in M.
   Dietrich, M. Borrello and O. Harman (eds.) Handbook of the Historiography
   of Biology, Berlin, Springer, doi:10.1007/978-3-319-74456-8_15-1
Bayne, K., Ramachandra, G.S., Rivera E.A. and Wang, J. (2015) The Evolution of
   Animal Welfare and the 3Rs in Brazil, China, and India, in “Journal of the
   American Association for Laboratory Animal Science”, 54 (2), pp. 181-191.
Begley, C.G. and Ellis, L.M. (2012) Drug Development: Raise Standards for Pre-
   clinical Cancer Research, in “Nature”, 483 (7391), pp. 531-533.
Begley, C.G. and Ioannidis J.P.A. (2015) Reproducibility in Science: Improving
   the Standard for Basic and Preclinical Research, in “Circulation Research”,
   116 (1), pp. 116-126.
Birke, L., Arluke, A. and Michael, M. (2007) The Sacrifice: How Scientific Exper-
    iments Transform Animals and People, West Lafayette, IN, Purdue Universi-
    ty Press.
Bischur, D. (2011) Animated Bodies in Immunological Practices: Craftsmanship,
    Embodied Knowledge, Emotions and Attitudes Toward Animals, in “Human
    Studies”, 34 (4), pp. 407-429.
Brosnan, C. and Michael, M. (2014) Enacting the ‘Neuro’ in Practice: Transla-
   tional Research, Adhesion and the Promise of Porosity, in “Social Studies of
   Science”, 44 (5), pp. 680-700.
Cambrosio, A., Keating, P., Mercier, S., Lewison G. and Mogoutov, A. (2006)
   Mapping the Emergence and Development of Translational Cancer Research,
   in “European Journal of Cancer”, 42, pp. 3140-3148.
Lowe, Leonelli & Davies                                                        25
Collins, F.S. (2011) Reengineering Translational Science: The Time Is Right, in
   “Science Translational Medicine”, 3 (90), pp. 90cm17.
Collins, F.S. and Tabak, L.A. (2014) NIH Plans to Enhance Reproducibility, in
   “Nature”, 505 (7485), p. 612.
Collis, M.G. (2006) Integrative Pharmacology and Drug Discovery — Is the Tide
   Finally Turning?, in “Nature Reviews Drug Discovery”, 5 (5), pp. 377-380.
Collis, M. (2009) The British Pharmacological Society (BPS) Integrative Pharma-
   cology Fund, in “Proceedings of the British Pharmacological Society”, 7 (3).
Concordat on Openness on Animal Research in the UK, 2014. London, Under-
   standing        Animal         Research.     Available   online      at:
   http://concordatopenness.org.uk/wp-content/uploads/2017/04/Concordat-
   Final-Digital.pdf (retrieved 4th November 2019).
Crabu, S. (2016) Translational Biomedicine in Action: Constructing Biomarkers
   Across Laboratory and Benchside, in “Social Theory & Health”, 14 (3), pp.
   312-331.
Crabu, S. (2018) Rethinking Biomedicine in the Age of Translational Research:
   Organisational, Professional, and Epistemic Encounters, in “Sociology Com-
   pass”, 12, e12623.
Crusio, W.E., Goldowitz, D., Holmes A. and Wolfer, D. (2009) Standards for the
   Publication of Mouse Mutant Studies, in “Genes, Brain and Behavior”, 8 (1),
   pp. 1-4.
Dam, M.S. and Svendsen, M.N. (2018) Treating Pigs: Balancing Standardisation
  and Individual Treatments in Translational Neonatology Research, in “BioSo-
  cieties”, 13 (2), pp. 349-367.
Davies, G. (2012) What Is a Humanized Mouse? Remaking the Species and Spac-
   es of Translational Medicine, in “Body & Society”, 18 (3-4), pp. 126-155.
Davies, G. (2018) Harm-Benefit Analysis: Opportunities for Enhancing Ethical
   Review in Animal Research, in “Lab Animal”, 47, pp. 57-58.
Davies, G., Greenhough, B., Hobson-West, P., Kirk, R.G.W., Applebee, K., Bel-
   lingan, L.C., Berdoy, M., Buller, H., Cassaday, H.J., Davies, K., Diefenbacher,
   D., Druglitrø, T., Escobar, M.P., Friese, C., Herrmann, K., Hinterberger, A.,
   Jarrett, W.J., Jayne, K., Johnson, A.M., Johnson, E.R., Konold, T., Leach,
   M.C., Leonelli, S., Lewis, D.I., Lilley E.J., Longridge, E.R., McLeod, C.M.,
   Miele, M., Nelson, N.C., Ormandy, E.H., Pallett, H., Poort, L., Pound, P.,
   Ramsden, E., Roe, E., Scalway, H., Schrader, A., Scotton, C.J., Scudamore
   C.L., Smith, J.A., Whitfield L. and Wolfensohn, S. (2016) Developing a Col-
   laborative Agenda for Humanities and Social Scientific Research on Labora-
   tory Animal Science and Welfare, in “PLoS ONE”, 11 (7), e015879.
Davies, G., Golledge, H., Hawkins, P., Rowland, A., Smith, J. and Wolfensohn, S.
   (2017) Review of Harm-Benefit Analysis in the Use of Animals in Research,
   London, Animals in Science Committee.
Davies, G., Greenhough, B., Hobson-West, P. and Kirk, R.G.W. (2018) Science,
   Culture, and Care in Laboratory Animal Research: Interdisciplinary Perspec-
26                                                            Tecnoscienza – 10 (2)

     tives on the History and Future of the 3Rs, in “Science, Technology, & Hu-
     man Values”, 43 (4), pp. 603-621.
Despret, V. (2004) The Body We Care For: Figures of Anthropo-Zoo-Genesis, in
   “Body & Society”, 10 (2-3), pp. 111-134.
Fagan, M.B. (2013) Philosophy of Stem Cell Biology: Knowledge in Flesh and
   Blood, London, Palgrave-Macmillan.
Freedman, L.P., Cockburn I.M. and Simcoe, T.S. (2015) The Economics of Re-
   producibility in Preclinical Research, in “PLoS Biology”, 13 (6), e1002165.
Friese, C. (2013) Realizing Potential in Translational Medicine: The Uncanny
    Emergence of Care as Science, in “Current Anthropology”, 54 (S7), pp. S129-
    S138.
Garner, J.P. (2014) The Significance of Meaning: Why Do Over 90% of Behav-
   ioral Neuroscience Results Fail to Translate to Humans, and What Can We
   Do to Fix It?, in “ILAR Journal”, 55 (3), pp. 438-456.
Harrington, J. and Hauskeller, C. (2014) Translational Research: An Imperative
   Shaping the Spaces in Biomedicine, in “Tecnoscienza: Italian Journal of Sci-
   ence & Technology Studies”, 5 (1) pp. 191-201.
Holmberg, T. (2008) A Feeling for the Animal: On Becoming an Experimentalist,
   in “Society and Animals”, 16 (4), pp. 316-335.
Holmberg, T. (2011) Mortal Love: Care Practices In Animal Experimentation, in
   “Feminist Theory”, 12 (2), pp. 147-163.
Horton, R. (2015) Offline: What Is Medicine’s 5 Sigma, in “The Lancet”, 385
   (9976), p. 1380.
Ioannidis, J.P., Greenland, S., Hlatky, M.A., Khoury, M.J., Macleod, M.R.,
   Moher, D., Schulz K.F. and Tibshirani, R. (2014) Increasing Value and Re-
   ducing Waste in Research Design, Conduct, and Analysis, in “The Lancet”,
   383 (9912), pp. 166-175.
Joyce, K.A., Darfler, K., George, D., Ludwig J. and Unsworth, K. (2018) Engag-
    ing STEM Ethics Education, in “Engaging Science, Technology, and Society”,
    4, pp. 1-7.
Julien, J.-P. and Kriz, J. (2006) Transgenic Mouse Models of Amyotrophic Lateral
    Sclerosis, in “Biochimica et Biophysica Acta (BBA) – Molecular Basis of Dis-
    ease”, 1762 (11-12), pp. 1013-1024.
Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson M. and Altman, D.G. (2010)
    Improving Bioscience Research Reporting: The ARRIVE Guidelines for Re-
    porting Animal Research, in “PLoS Biology”, 8 (6), p. e1000412.
King, A.J.F. (2012) The Use of Animal Models in Diabetes Research, in “British
   Journal of Pharmacology”, 166 (3), pp. 877-894.
Kirk, R.G.W. (2008) ‘Wanted—Standard Guinea Pigs’: Standardisation and the
   Experimental Animal Market in Britain ca. 1919–1947, in “Studies in History
   and Philosophy of Biological and Biomedical Sciences”, 39 (3), pp. 280-291.
Lowe, Leonelli & Davies                                                         27
Leonelli, S. (2013) Integrating Data to Acquire New Knowledge: Three Modes of
   Integration in Plant Science, in “Studies in History and Philosophy of the Bio-
   logical and Biomedical Sciences”, 4 (4), pp. 503-514.
Leonelli, S. (2017) Biomedical Knowledge Production in the Age of Big Data.
   Report for the Swiss Science and Innovation Council. URL:
   https://web.archive.org/web/20191016094620/http://www.swir.ch/images/st
   ories/pdf/en/Exploratory_study_2_2017_Big_Data_SSIC_E-N.pdf (retrieved
   16th October 2019).
Levin, N. (2014) What’s Being Translated in Translational Research? Making and
   Making Sense of Data between the Laboratory and the Clinic, in “Tecnosci-
   enza: Italian Journal of Science & Technology Studies”, 5 (1), pp. 91-113.
Lewis, J., Atkinson, P., Harrington J. and Featherstone, K. (2013) When is an An-
   imal Model Good-Enough? Representation and Embodiment in the Labora-
   tory, in “Sociology”, 47 (4), pp. 776-792.
Lewis, J., Hughes J. and Atkinson, P. (2014) Relocation, Realignment and Stand-
   ardisation: Circuits of Translation in Huntington’s Disease, in “Social Theory
   & Health”, 12 (4), pp. 396-415.
Lowe, J.W.E., Collis, M., Davies, G., Leonelli, S., Lewis D.I. and Zecharia, A.Y.
   (2016) An Evaluation of the Integrative Pharmacology Fund: Lessons for the
   Future of in Vivo Education and Training, London, British Pharmacological
   Society.
Lutz, T.A. and Woods, S.C. (2012) Overview of Animal Models of Obesity, in
   “Current Protocols in Pharmacology”, Unit 5.61.
Lynch, M.E. (1988) Sacrifice and the Transformation of the Animal Body into a
   Scientific Object: Laboratory Culture and Ritual Practice in the Neuroscienc-
   es, in “Social Studies of Science”, 18, pp. 265-289.
Macleod, M.R., Lawson McLean, A., Kyriakopoulou, A., Serghiou, S., de Wilde,
   A., Sherratt, N., Hirst, T., Hemblade, R., Bahor, Z., Nunes-Fonseca, C., Pot-
   luru, A., Thomson, A., Baginskitae, J., Egan, K., Vesterinen, H., Currie, G. L.,
   Churilov, L., Howells D.W. and Senaet, E.S. (2015) Risk of Bias in Reports of
   In vivo Research: A Focus for Improvement, in “PLoS Biology”, 13 (10),
   e1002273.
Maienschein, J., Sunderland, M., Ankeny R.A. and Robert, J.S. (2008) The Ethos
   and Ethics of Translational Research, in “The American Journal of Bioethics”,
   8 (3), pp. 43-51.
Martin, B. (2016) STS Interventions: Preparing, Defending, Learning, in “Engag-
   ing Science, Technology, and Society”, 2, pp. 83-87.
Martin, P., Brown N. and Kraft, A. (2008) From Bedside to Bench? Communities
   of Promise, Translational Research and the Making of Blood Stem Cells, in
   “Science as Culture”, 17 (1), pp. 29-41.
Moher, D., Glasziou, P., Chalmers, I., Nasser, M., Bossuyt, P.M., Korevaar, D.A.,
  Graham, I.D., Ravaud P. and Boutron, I. (2016) Increasing Value and Reduc-
  ing Waste in Biomedical Research: Who’s Listening?, in “The Lancet”, 387
28                                                               Tecnoscienza – 10 (2)

     (10027), pp. 1573-1586.
Murphy, S.J. (2017) Essays in Pharmaceutical Economics. Unpublished PhD the-
  sis, Massachusetts Institute of Technology.
Nelson, N.C. (2018) Model Behavior: Animal Experiments, Complexity, and the
   Genetics of Psychiatric Disorders, Chicago, Chicago University Press.
Nuffield Council on Bioethics (2005) The Ethics of Research Involving Animals,
   London, Nuffield Council on Bioethics.
Osherovitch, L. (2011) Hedging Against Academic Risk, in “SciBX”, 4 (15).
Pober, J.S., Neuhauser C.S. and Pober, J.M. (2001) Obstacles Facing Translation-
   al Research in Academic Medical Centers, in “The FASEB Journal”, 15, pp.
   2303-2313.
Pound, P. and Bracken, M.B. (2014) Is Animal Research Sufficiently Evidence
   Based to Be a Cornerstone of Biomedical Research, in “BMJ”, 348 (3387),
   g3387.
Rader, K.A. (2004) Making Mice: Standardizing Animals for American Biomedi-
   cal Research, 1900-1955, Princeton, Princeton University Press.
Rasmussen, N. (2014) Gene Jockeys: Life Science and the Rise of Biotech Enter-
   prise, Baltimore, Johns Hopkins University Press.
Richter, S.H., Garner J.P. and Würbel, H. (2009) Environmental Standardization:
   Cure or Cause of Poor Reproducibility in Animal Experiments?, in “Nature
   Methods”, 6 (4), pp. 257-261.
Richter, S.H., Garner, J.P., Auer, C., Kunert J. and Würbel, H. (2010) Systematic
   Variation Improves Reproducibility of Animal Experiments, in “Nature
   Methods”, 7 (3), p. 167.
Rosenthal, R. (1966) Experimenter Effects in Behavioral Research, New York,
   Appelton.
Russell, W.M.S. and Burch, R.L. (1959) The Principles of Humane Experimental
   Technique, London, Methuen.
Schneider, J.S. and Markham, C.H. (1986) Neurotoxic Effects of N-Methyl-4-
   Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in the Cat. Tyrosine Hydroxylase
   Immunohistochemistry, in “Brain Research”, 373 (1-2), pp. 258-267.
Schneider, J.S., Yuwiler A. and Markham, C.H. (1986) Production of a Parkin-
   son-Like Syndrome in the Cat with N-Methyl-4-Phenyl-1,2,3,6-
   Tetrahydropyridine (MPTP): Behavior, Histology, And Biochemistry, in “Ex-
   perimental Neurology”, 91 (2), pp. 293-307.
Seok, J., Warren, H.S., Cuenca, A.G., Mindrinos, M.N., Baker, H.V., Xu, W.,
   Richards, D.R., McDonald-Smith, G.P., Gao, H., Hennessy, L., Finnerty,
   C.C., López, C.M., Honari, S., Moore, E.E., Minei, J.P., Cuschieri, J., Bankey,
   P.E., Johnson, J.L., Sperry, J., Nathens, A.B., Billiar, T.R., West, M.A., Jesch-
   ke, M.G., Klein, M.B., Gamelli, R.L., Gibran, N.S., Brownstein, B.H., Miller-
   Graziano, C., Calvano, S.E., Mason, P.H., Cobb, J.P., Rahme, L.G., Lowry,
Lowe, Leonelli & Davies                                                      29
    S.F., Maier, R.V., Moldawer, L.L., Herndon, D.N., Davis, R.W., Xiao, W.,
    Tompkins R.G. and Inflammation and Host Response to Injury, Large Scale
    Collaborative Research Program. (2013) Genomic Responses in Mouse Mod-
    els Poorly Mimic Human Inflammatory Diseases, in “Proceedings of the Na-
    tional Academy of Sciences of the United States of America”, 110 (9), pp.
    3507-3512.
Smith, A.J., Clutton, R.E., Lilley, E., Hansen K.E.A. and Brattelid, T. (2018)
   PREPARE: Guidelines for Planning Animal Research and Testing, in “Labor-
   atory Animals”, 52 (2), pp. 135-141.
Sunder Rajan, K. (2017) Pharmocracy: Value, Politics, and Knowledge in Global
   Biomedicine, Durham, Duke University Press.
Sunder Rajan, K. and Leonelli, S. (2013) Introduction: Biomedical Trans-actions,
   Post-Genomics and Knowledge/Value, in “Public Culture”, 25 (371), pp.
   463-475.
Svendsen, M.N. and Koch, L. (2013) Potentializing the Research Piglet in Exper-
   imental Neonatal Research, in “Current Anthropology”, 54 (S7), pp. S118-
   S128.
Thompson, C. (2013) Good Science: The Ethical Choreography of Stem Cell Re-
   search, Cambridge, MA, MIT Press.
van der Worp, H.B., Howells, D.W., Sena, E.S., Porritt, M.J., Rewell, S.,
   O’Collins V. and Macleod, M.R. (2010) Can Animal Models of Disease Relia-
   bly Inform Human Studies?, in “PLoS Medicine”, 7 (3), e1000245.
Viteritti, A. (2013) It’s the Body (That Does It)! The Production of Knowledge
    Through Body in Scientific Learning Practice, in: “Scandinavian Journal of
    Management”, 29, pp. 367-376.
Webster, A. (2007) Crossing Boundaries: Social Science in the Policy Room, in
  “Science, Technology, & Human Values”, 32 (4), pp. 458-478.
Würbel, H. (2000) Behaviour and the Standardization Fallacy, in “Nature Genet-
  ics”, 26 (3), p. 263.
Würbel, H. (2017) More Than 3Rs: The Importance of Scientific Validity for
  Harm-Benefit Analysis of Animal Research, in “Lab animal”, 46 (4), p. 164.
Zerhouni, E. (2003) The NIH Roadmap, in “Science”, 302 (5642), pp. 63-72.


    1
      See for example Rader (2004) and Kirk (2008). For a detailed overview of
the historiography of animal research, see Ankeny and Leonelli (2018).
    2
      https://web.archive.org/web/20191016093215/https://www.bps.ac.uk/-
educati-on-engagement/research-animals/curriculum-for-the-use-of-research-
animals/ab-out-the-curriculum-for-the-use-of-research-anima, retrieved 16th
October 2019.
    3
      These kinds of animal models can be produced by surgical intervention (for
example, removal of most of the pancreas, a pancreatectomy, to induce
hyperglycaemia and symptoms of type 1 diabetes in pigs, dogs and non-human
primates; King 2012); chemically-induced (the injection of the neurotoxin MPTP
30                                                                 Tecnoscienza – 10 (2)


into cats to simulate Parkinson’s disease, Schneider and Markham 1986;
Schneider, Yuwiler and Markham 1986); naturally-occurring (e.g. homozygous
mutations resulting in obesity in mice, as a model of obesity; Lutz and Woods
2012); environmentally-induced (e.g. raising mice in obesogenic environments to
make them obese; Lutz and Woods 2012); and produced by genetic modification
by knockout of genes or transgenesis, the introduction of DNA into the genome
(e.g. the transgenic mouse with mutant SOD1, a model of amyotrophic lateral
sclerosis; Julien and Kriz 2006).
     4
        P-hacking involves generating a large amount of data then conducting
statistical analyses to find statistically significant relationships between variables
without an a priori hypothesis.
     5
       https://web.archive.org/web/20191016095130/https://www.nc3rs.org.uk-
/expe-rimental-design-assistant-eda, retrieved 16th October 2019.
     6
       https://web.archive.org/web/20191016094917/https://www.bps.ac.uk-
/educati-on-engagement/research-animals/curriculum-for-the-use-of-research-
animals/ab-out-the-curriculum-for-the-use-of-research-anima, retrieved 16th
October 2019.
