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about Stem cell science as a future therapy for diabetes.
Stem Cell Science As A Future Therapy For Diabetes
An orientation towards the future is implied when studying stem cell science and as a future to
therapy of diabetes too. There are two major discourses discernible; the institutions which create certain
influence and the stem cell and its effect on therapies, genetic modification and animal studies. Stem cells
have a common thing that is self renewal and cell differentiation .The differentiated cells always have to
remain as they are during movement from the body into the cell culture dish in the laboratory or to a newer
environment and function too as before.
However, this is not usually the case since the working has to be in accordance or chime with the
way it did in the body so as to prove the relevance or the ability to go all the way to an islet cell
maintaining it too as is the case when dealing with diabetic patients. (Atala & Lanza, 2013, pg 2) Stem
cells are viewed as plastic, meaning they are able to change into other cells.
The probability of them being triggered and changing into other cell types is usually high. The
genes are the ones mostly affected and one should therefore be able to identify whether the genes are
functioning or not and if so, not only functioning but like beta cells when applied. (Atala & Lanza, 2013,
pg 3)
Bench to bed side workings such as translational research therefore is seen as a solution to certain
problems and a difficulty when dealing with research problems.
STEM CELL SCIENCE AS A FUTURE THERAPY FOR DIABETES 2
An important fact of the stem cells is their ability to change into many cells .Such an example is the
tumor cells and therefore, proving wrong their possibility to function when dealing with a diabetic patient
at large as well as poor understanding of the stem cells by many scientists and therefore not being able to
come up with probable solutions to the many problems that come with it.
Reference
Atala, A., & Lanza, R. P. (2013). Handbook of stem cells. London: Academic/Elsevier
Stem cell science as a key barrier to therapies
In the second half of this paper, we investigate the
theme of biomedical science itself as a major
problem of imagined future stem cell therapies in
the field of diabetes. The scientists we interviewed
all saw one of the central barriers to future stem cell
therapies as a scientific one, as the next three short
quotations illustrate:
SW: What are the main clinical problems of using
stem cell therapy for diabetes?
Other than the obvious, in that we can’t make
beta cells! Scientist 3
A viable prospect for the future? I really
think that we are very much at the bench level.
Scientist 4
The principal problem is actually generating the
cell! Scientist 6
Our scientists identified a number of scientific
hurdles. Here we discuss three of the key difficulties
highlighted by them, but lack of space precludes a
more extensive discussion. We also recognise that in
the scientific literature, the list of potential problems
with stem cell science is much longer than this (see
Dawson et al., 2003).
Problems expanding and differentiating ES cells to
beta cells
All the scientists in the lab had a very guarded,
and somewhat pessimistic view on the prospects for
stem cell therapy for diabetes. Part of this gloomy
perspective for stem cell transplants stemmed from
the difficulties in eliminating the possibility of ES
cells becoming tumour cells (Dawson et al., 2003):
I am a bit sceptical about that whole thing to be
honest. The other problem is that you need to
expand the cells to get sufficient material for the
transplantation and once you start expanding
then you are selecting the cells which proliferate
which could be very dangerous so you need some
way of actually controlling that, to be sure that
what you’re selecting are not cancer forming
cells. Scientist 5
Another key problem with the stem cell to
specialised cell field was the extremely limited
understanding of stem cells by scientists (Gearhart,
2005):
I don’t want to be a Cassandra and say that it’s
never going to happen yI think we know very
little, and that’s why we are having trouble
directing them. Scientist 1.
I think people are trying to get ahead of
themselves at the moment in the field and there
is a lot of hype about using stem cells in the
clinic. The reality is that it’s going to be a very,
very long time before we are able to do that. I am
not sure in my own mind whether it’s even
possible, so I think we shouldn’t get too excited
about the prospects of using stem cells. In theory
it is an exciting idea, that you can take these
completely undifferentiated cells and make new
tissue. But there are so many problems, there are
technical problems, and ethical problems, and
there is a lack of understanding of the whole
process of how you do that. There are so many
hurdles to get over I think, before we can actually
do this. Scientist 6
One of the hurdles is the problem of encouraging
differentiated cells to remaining fully functioning
cells once they are removed from their natural
environment in the body and placed in the artificial
environment of a cell culture dish:
There is actually a major problem in tissue
actually maintaining a differentiated statey We
have no idea what factors are necessary even just
to maintain them in that state, which I think is a
real problem for stem cells. If you can’t even
maintain cells that are already differentiated in a
state that you are interested in, how on earth are
you going to get from something which is
nowhere near a beta cell to go all the way to an
islet cell and keep it in that state? It’s a huge ask.
Scientist 5
The plasticity of ES cells, their ability to trans-
form into other types of cells, was also seen as
something that could undermine expectations of
ever producing a safe ES-cell-based therapy:
It’s the unpredictability of the stem cells them-
selves that I think is the major problem. Their
plasticity, the fact that it’s their job to differ-
entiate! There is always that danger that there is
something there that is going to affect them and
is going to switch on genes that shouldn’t be
switched on y Even if you get to a stage where
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you’ve got cells that you think are beta cells you
need to be sure of that, you need to be sure that
they are absolutely functioning like a beta cell,
having lost this plastic cell type. You can’t put a
molten cell into a person. Scientist 6
Problems with genetic modification of cells
A second set of problems clusters around the
genetic modification of cells, both to create beta
cells and to avoid the immune rejection of
transplanted bioengineered cells. One view is that
there is an equivalence between the UK public’s
aversion to genetically modified food and their
perceived opposition to the genetic modification of
cells for prospective cell therapies:
My guess would be in a society that won’t even
eat genetic engineered tomatoes that they are not
going to let us put genetically engineered cells
back into patients we can keep alive perfectly
normallyy When we started this all with
[clinician y] our approach was not to put genes
back in. In fact we didn’t do that for over two
years, because we foolishly thought two or three
years ago that we might have material that might
be useful, and the argument that we had in the
group was if we tamper with them genetically it
will never be clinically useful. Scientist 3
The lab had, however, recently shifted position on
this issue as many of the major papers that claim to
have produced beta cells from ES cells have used
genetic manipulation of these cells, for example, by
bioengineering ES cells with the insulin promoter
gene PDX1 (Bonner-Weir & Weir, 2005). The lab’s
view of the research literature on making beta cells
from ES cells (often achieved by adding various
growth factors) is that these scientists are largely
observing a process rather than directing development
through their interventions. Scientist 7 captures this
view:
With embryonic stem cells differentiating into
insulin creating cells, most of them I think are
spontaneous differentiations y [So to try and
direct ES cells to beta cells] I put PDX1 in, but
the efficiency is not very high and I can’t get
insulin secretion. Scientist 7.
We see here that adding insulin promoting genes
to cells is technically difficult. Moreover, even when
the PDX1 gene is added in order to direct ES cells to
beta cells, the resulting cells are not functioning beta
cells as they do not produce insulin. Our lab’s
current position is that if there were significant
medical breakthroughs in cell transplant therapy
that were the product of the genetic engineering of
ES cells to, say, beta cells, then pressure within
society would result in a change in public policy on
ES cell therapies (Salter & Jones, 2002). This now
makes genetic modification a worthwhile experi-
mental strategy for them to invest in.
One other barrier that is currently damping
scientists’ expectations of the move from bench to
bedside is the problem of the immune rejection of
any transplanted cells (Gaglia et al., 2005). As
Scientist 3 outlines below, there are two aspects to
this in patients with Type-1 diabetes:
I still would put ten years on it, I can’t see it
going quicker. There are lots of other things you
have to get round, you have to get round the
auto-immune rejection, you make a beta cell
from a human embryonic stem cell, it’s going to
look like a beta cell. If you put this into a Type 1
diabetic there is a reason why that Type 1
diabetic’s beta cells have been destroyed. It’s
because he has auto-immune antibodies against
beta cells, so the same thing is going to happen to
the stem cell you put in, so you’ve got to engineer
that stem cell to not look like a beta cell. You’ve
also got to make stem cells that aren’t going to be
rejected by the host. So if you take stem cells
from an embryo and put them into you, your
immune system will recognise those as foreign
and destroy them, so we have to be at a stage
where we can take skin cells from you and take
out the nucleus of an embryo, put your skin cell
in, and make cloned cells. Scientist 2
However, the scientific expectations of such
cloning of stem cell lines have recently been
seriously undermined with the retraction of Hwang
et al’s (2004) landmark paper from Science on the
twin grounds of the use of unethical sources of
embryos and fraudulent data (Check & Cyranoski,
2005).
Another scientist reflected the general pessimism
and felt that perhaps only genetic manipulation of
ES cells was likely to produce scientific break-
throughs, but also argued that this would create
significant ethical and social disquiet which would
inevitably limit the move of such an approach from
the lab to the clinic:
I still do think that probably ultimately one day
there will be a cure that people are waiting for. I
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just think that maybe it requires genetic mod-
ification, mainly the cells need to be genetically
changed before you actually are going to be able
to get a cell that behaves enough like a beta cell.
That then requires a wholesale change of ethical
thought as to whether you can put some
genetically modified cell back into a human,
and that’s going to take years and years of
legislation. (Scientist 2)
Problems with animal studies
A third major set of problems centred on
transferring findings from rigorous experimental
studies in animals (usually rodents) to clinical
studies in humans (Rees & Acolado, 2005).
Nobody wants to cure diabetes in mice! So the
underlying assumption is that if it works it will go
into human ES cell work. Scientist 3
There is also a parallel here with the ‘Mickey
Mouse’ view of medical research from basic
biomedical scientists. In this case a similar boundary
between ‘good and bad’ science is being drawn
(Gieryn, 1999), only this time it is between ‘rigorous
animal modellers’ and the biomedical scientists who
work on humans (Paton, 1993):
I think there are two very clear groups of
researchers, those who have done a lot of animal
work, who very rarely do anything in humans,
and then there are a group who say, ‘working on
mice is a waste of time!’ Quite often what you
find is that there isn’t so much crossover,
unfortunately. It’s surprising really. It’s very
quick to identify susceptibility genes for an
animal model because you have got all the
breeding that can be set up very quickly, we
have done a few generations and got very good
answers. But then you think, ‘well, this is a
diabetic mouse, it should be the same in humans’,
but there are very few genes which are common
or you can show are relevant to the human
disease. Scientist 5
The assumption is that animal studies will lead to
similar studies with human cells, but as Scientist 5
illustrates, this is often not the case (Birke, 1999).
Another reason why non-human cell work was
seen as important centres on the expectations of
academic productivity in the life sciences. The
pressure of these expectations can be used as an
excuse for scientific fraud (as the Hwang case, and
the Nobel prize winning biologist Baltimore case
illustrate—see Kevles, 1998). Outputs, especially in
the form of publications in leading international
journals, have a huge impact on academic careers.
Ensuring that several sets of experiments are
running concurrently and which use ‘off-the-shelf’
biological materials such as animal cell lines, means
that scientists are far more likely to generate more
high-quality data and hence more papers:
If you are going to design a research programme
then you need something to do every day and if
your [human] pancreases only arrive once every
three weeks then you need some other way of
actually looking at the question. You can go up
to the animal house any day and obtain an
animal pancreas or you can maintain cell lines
and look at those, so I think it will always be
preferable to study basic biology with an islet in a
rodent pancreas or ideally a cell line. To plan a
proper research programme you need regular
access to the tissue and you are never going to get
that with donor material, particularly if the
primary objectives are research, because the
relatives just don’t see it as important to give
permission for all this to be used for research.
Quite rightly I think, they don’t feel it’s going to
somebody else’s benefit and research is going to
be a lower priority. Scientist 5
The tension between the relevance of ‘human
studies’ and the rigour of ‘animal experiments’
colours expectations for future cell transplant
therapies. Our scientists see the target of ES-driven
cell therapies as something that may be unachie-
vable, except in very specific and limited areas. In
contrast, they see the prospects for significant
scientific breakthroughs from stem cells in under-
standing basic cell and developmental biology as
achievable. Perhaps there is a shift here, with some
scientists now specifying expectations around stem
cells as scientific tools rather than medical therapies:
I can see huge complications. I think it will tell us
a huge amount about introducing new ways at
looking at therapies, particularly on the human
side, which you can’t study in vitro. I think it’s
going to tell us a huge amount about experi-
mental biology. I am yet to be convinced that it’s
going to have any clinical applications, except
maybe on the cardiac side, and the neurological
side. Scientist 5
To summarise the performative aspect of the
discourses illustrated in this sections, we have seen
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that there are a number of ways in which stem cells
are technically difficult materials: they sponta-
neously differentiate and de-differentiate; they can
develop into teratomas; they are prone to rejection
(Dawson et al., 2003). This is allied to other
problems: stem cells are morally difficult materials,
and to genetically modify hES cells is ethically
highly sensitive (Maienschien, 2003; Wainwright
et al., in press). Moreover, animal stem cell studies
seem difficult to extrapolate to humans (Birke,
1999). What we have is a discursive landscape of
barriers and pitfalls. It would seem that everywhere
we turn we find material and moral recalcitrances.
However, such dampening of expectations is func-
tional (Brown & Michael, 2003). It marks to
clinicians especially, but also to regulators and
funders, that this research programme is highly
vulnerable. Indeed, to dampen expectations is to
absent oneself from a particular present—that of the
current drive from bench to bedside. However, it is
also to leave oneself in a position to return to a
future present in which the bench contribution
might be altogether more hopeful. Such talk is a
matter of ‘kairos’ (see Brown, 2000), that is a matter
of timing, or of choosing the ‘right time’—in this
case, of raising expectations. The notion of kairos
denotes in rhetoric the choosing of the right time to
speak—of responding appropriately to circum-
stances. By contrast, we can also use this notion
to connote the making of the right time. As such, the
dampening of expectations is also about making
future kairos, in which scientists can better inter-
vene in the development of clinically viable stem cell
treatments for diabetes.
Conclusions
In this paper, we have identified two main
discourses on the prospects for the translation of
research from bench to bedside in the area of
diabetes: firstly, institutional influences on interac-
tions between scientists and clinicians; and secondly,
stem cell science itself as a major barrier to potential
future therapies. Throughout the paper, we have
emphasised the performative nature of the dis-
courses of expectations highlighted within our case
study. For instance, we argued that scientists
framed their work in the context of the expectations
of others, such as research funding bodies. More-
over, we claimed that the performative dimension of
such discourses distances scientists from ‘over
expectations’. This chimes with other sociological
research on science where ‘distance (from labora-
tory experiments) lends enchantment’ (Collins,
2004). In other words, distance raises expectations
as bench science is viewed through a (relative) ‘veil
of ignorance’ (Brown & Michael, 2003; MacKenzie,
1990). We also described collaboration between the
lab and the clinic performatively, as a form of
institutional boot-strapping, whereby the more an
institution can successfully be portrayed as a
domain of collaboration, the more it will attract
researches and clinicians who want to collaborate,
who in turn enable the institution to be depicted as
an exemplar of collaboration (Keating & Cambro-
sio, 2003).
Scientists weave a complex tapestry of expecta-
tions (Brown et al., 2000; Kitzinger & Williams,
2005, 2006). In particular, we draw 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. Moreover, we highlight ways
in which scientists are torn between identifying and
promoting collaboration on the one hand, and not
over-selling the prospects of translational research
on the other hand. In this process, there is a weaving
together of institutional and material (scientific)
expectations. Thus, enactments of material expecta-
tions (about research outcomes) are partially
structured by expectations about institutional (e.g.,
funders) expectations around the prospects of stem
cell therapy. Conversely, institutional expectations
about the possibility of collaboration are enabled by
expectations about the successful manipulation of
stem cells. The institutional and the material are
thereby intimately entwined. The complex cloth of
translational research is a difficult thing to keep
from unravelling, as our scientists seem only too
aware. What helps hold this cloth together is a
tempering of material and institutional expectations
that recognises the limitations of current clinical
collaborations and stem cell research, and also
keeps open the possibility of future collaborations
when the success of stem cell therapy might be more
likely. In other words, scientists’ talk about
expectations performs expectations-about-expecta-
tions, which sets the ground for the collaboration
necessary for translational research.
It is often argued that translational biomedicine
has the potential to transform basic biomedical
science, clinical practice and the nature of modern
society (Ioannidis, 2004). However, in this paper we