"NEW DOCUMENTS"
A second
leak of documents concerning Imutran's primate vivisection occurred
in October 2002, and emanated from the Home Office. This briefing
explains the disturbing aspects of the Home Office and Imutran's
conduct that are revealed by these documents.
1. Primates as proposed sources of xenografts
Documents ND1
& ND2
reveal that Imutran successfully applied for permission to conduct
primate-to-primate heart xenotransplantation experiments in order
to develop "the use of concordant
[i.e. non-human primate to human] xenografting
for infants with otherwise untreatable congenital heart disease.
This could be a possibility within a relatively short period of
time." (See document ND1.7.)
At least four such experiments were performed (see document ND2.1),
though permission was granted for the use of 50 juvenile baboons
per year as recipients of cynomolgus monkey hearts (see document
ND1.15)
implanted into the necks of the baboons ("cervical heterotopic
heart xenotransplantation", see document ND1.23).
This is the most controversial type of experiment imaginable, and
to the best of the Uncaged Campaigns' knowledge, information about
the occurrence of such experiments is not in the public domain.
The Kennedy Committee report on the ethics of xenotransplantation,
which has laid the framework, on paper rather in practice, for the
Government's policy on xenotransplantation, concluded that "it
would be ethically unacceptable to use primates as source animals
for xenotransplantation, not least because they would be exposed
to too much suffering."
Regarding the proposed use of infants as recipients of primate
organs, the Kennedy report states "We recommend
that children should not be included in trials..."
To the best of the Uncaged Campaigns' knowledge, both Imutran and
the Home Office have failed to refer to or explain the justification
for these horrendous and extreme experiments at any time. The Chief
Inspector's limited review of Imutran's research omitted to deal
with the concerns raised in Diaries of Despair regarding these experiments,
thereby giving the false impression that the only proposed source
animal in Imutran's research was pigs.
These experiments, as revealed by these documents, raise serious
concerns about the adequacy of the Home Office's ethical scrutiny
of Imutran's research proposals. The apparent lack of openness regarding
this research on the part of both Imutran and the Home Office reinforces
these concerns.
^
2. Imutran's exaggeration of potential benefits
It is Uncaged Campaigns' assertion that Imutran has exaggerated
the likelihood of 'benefit' (i.e. which in their terms would consist
of a move to successful clinical trials) accruing from their research,
both in public statements and in their submissions to the Home Office,
by glossing over the immunological obstacles to successful xenotransplantation,
for example. Imutran's research has not realised the likely benefits
claimed by the company in its submissions to the Home Office, further
information about which is revealed in these documents.
In response to concerns about Imutran's claims about the likelihood
of clinical trials as a potential benefit and the assessment of
such claims by the Home Office in its conduct of the cost/benefit
assessment of Imutran's applications, the Chief Inspector claimed
in his report: "In considering whether
and on what terms to grant the project licence applications the
Home Office judgment of 'potential benefit' was based upon new scientific
insights that might be gained. Imutran did not advance, and the
Home Office did not consider, claims of imminent clinical trials
as a realistic short-term benefit."
This claim is brought into question by Imutran's documents originally
received by the Defendants in spring 2000 (see our response to the
Chief Inspector's report paragraph
2.4). We also refer in regard to this matter to a letter from
Steve Wilkes at the Home Office to Mr Lyons of Uncaged Campaigns
dated 3 March 1998: "... Ministers and
the APC are fully aware that the main and ultimate benefits of this
research can only accrue if xenotransplantation can be used in clinical
practice."
These statements by Imutran contained in the new documents shed
further light on this aspect of the operation of the regulatory
system and totally undermine the validity of the Home Office's public
response to Diaries of Despair:
-
Page ND1.7:
"It is our objective that the transplantation of organs
from animals to humans will provide a solution to the current
shortage of donor organs."
-
Page ND4.1:
"These data suggest that organs taken from our transgenic
pigs would provide a useful source of organs for transplantation
into man. It is our intention to demonstrate the long-term viability
of these xenografts by transplanting them into cynomolgus recipients
which would then be immunosuppressed with clinically acceptable
drug protocols." [Note, the clinical relevance of the protocols
used by Imutran has been questioned by other scientists, e.g.
Prof Herb Sewell of UKXIRA.]
-
Page ND5.7:
"Preclinical trials: Studies extending over the last ten
year period have now led us to this application for the final
trial before human utilisation of the techniques."
-
Page ND5.22:
"Biopsies [of pig hearts in baboons] would be taken at
day 10 after the operation and then at three weekly intervals
for three months. Until the first anniversary biopsies will
be done two monthly and thereafter annually!!!"
-
Page ND9.2/9.3:
"This information is an important step forward in progressing
the xenograft procedure to the clinical setting. However there
is still a requirement to work out the optimal immunosuppressive
drug protocol before pig xenografts can be used clinically in
man... [I]t is hoped that the APC will agree to consider requests
at a later date in such a way as to facilitate a continuous
research programme to define the best immunosuppressive regime
to allow xenografts to be tested clinically in man."
-
Page ND10.3:
"In order, therefore, that we can continue our programme
of work from both the animal welfare and move to the clinic
viewpoints, we wish to apply for a change of procedure to be
applied to the 36 remaining baboons... We are confident that
this will help us to achieve our objective..."
-
Page ND12.2:
"Potential Benefits: It is our objective that the transplantation
of organs [in this case livers, see below] from transgenic animals
to humans will provide a solution to the current shortage of
donor organs."
-
Pages ND16.1/16.2/16.3:
"The purpose of these studies in baboons [in late 1996/early
1997] to which you refer in your letter was to develop a safe,
clinically applicable immunosuppressive regime to provide prolonged
survival of a transgenic pig heart in a non human primate...
From the studies, we believe that we have achieved our primary
objective - that is a clinically acceptable immunosuppressive
regime... I hope that.. we would be allowed to submit formal
research plans to allow us to progress a research programme
of enormous potential scientific and clinical benefit."
-
Page ND21.8:
"This work [pig-to-primate heart xenografts] is required
in order to present to the Xenotransplantation Interim Regulatory
Authority, before gaining approval from the Government to conduct
clinical trials."
- Page ND24.3:
"Our objective... is to develop an immunosuppressive regime
that is effective in dealing with rejection crises whilst maintaining
the health and welfare of the animals...". This passage goes
on to refer to the establishment of an advisory board to recommend
what primate research is required to move to clinical trials -
the protocols applied for are based on these recommendations.
The "potential benefits" claimed by Imutran focus solely
on the clinical use of pig kidneys.
This submission of "False Information" potentially constitutes
a criminal offence.
^
3. Liver xenotransplantation
Document ND12
reveals Imutran's involvement in a project licence application involving
pig-to-primate liver xenotransplantation. According to the RSPCA
report, the APC recommended an initial small-scale study should
be permitted, but in the end the application was not pursued. This
application is a matter of concern for the following reasons:
-
The potential benefits of pig livers in human transplantation
have been in greater doubt even than the heart and kidneys due
to the complex, species-specific function of the liver (see
para 2.44 of Kennedy report). But the significance of these
physiological and biochemical obstacles does not appear to be
discussed in the project licence application in section 17,
"Background, Objectives and Potential Benefits".
-
Imutran appear to have denied involvement in this project,
judging from the text of the RSPCA report (see page 23).
It is a matter of serious concern that Imutran, the Home Office
and the APC contemplated severe experiments with such a remote chance
of achieving the stated benefits.
^
4. Imutran's "cavalier" attitude
Many of the documents cast further light on the relationship between
Imutran, the Home Office and the APC, the attitude of Imutran to
the regulatory system, and the difficulty experienced by the Home
Office in controlling Imutran's research.
In the Animal Procedures Committee's Annual Report for 1996, they
state in relation to Imutran's research as described in the documents:
"... The speed of development of this work and
its sensitivity makes it essential that the Sub-Committee and, indeed,
the full Committee keeps fully appraised of the progress of this
work and its direction. It is also essential that the work is carefully
and closely controlled."
The documents listed here confirm that these experiments were not
'carefully and closely controlled'.
The information revealed by these documents also demonstrates that
comments made by the Home Office Chief Inspector in his partial
review of Imutran's research were economical with the truth:
-
Page ND13.1:
"The Inspectorate has expressed concern with the timeliness
of the reports and the pattern of animal use... It is therefore
of great concern to the Home Office to find from your monthly
reports that you appear to have used an additional 16 baboons
(i.e. 25 in total) under one particular immunosuppressive regime....
, without the Home Office's prior knowledge or consent."
(The Chief Inspector's review claims: "A number of the
Imutran project licences were subject to a condition of issue
requiring the periodic submission of summary progress reports.
These were generally timely and informative." (para 5.19.1)
and "All protected animals used by Imutran were... used
with the knowledge and consent of the Home Office." (para
1.3))
-
Pages ND15.1/15.2:
"The Committee (APC) shared our concerns about the direction
of this work and unanimously felt that your report did not adequately
address the specific questions raised in my letter [i.e. document
ND13]...
The Committee was particularly incensed by your assertion that
authority for the change in direction of this work was given
by the Committee in February 1997... No-one present had any
recollection of such authority being sought or given. The Home
Office and the Committee have recognised the importance of your
work [based presumably on the far-fetched predictions of likely
clinical trials put forward by Imutran] and we have given you
some latitude within the authorities granted in your project
licence to make small modifications to your studies to take
account of the results of your research and rapid developments
in the science. In doing so, we extended to you a degree of
trust that you would continue to work within both the spirit
and the letter of the controls of the 1986 Act. Subject to further
explanation, both the Home Office and the APC feel that you
have violated this trust."
-
Pages ND17.1/17.2:
"2. Two animals X220 and X198 are listed as having been
used on 6 May, after we notified you that we had accepted the
Committee's advice that no further work should be authorised
at this time... [see para 1.3 of the Chief Inspector's report,
quoted above at point 1] The APC discussed these matters again
at its meeting on 5 June. Members strongly expressed the view
that your response was still not satisfactory and that the failings
listed above indicate a cavalier attitude to the controls of
the Act. They are also extremely concerned that this attitude
may extend to the care and welfare of animals."
^
5. Animal suffering underestimated
This is generally included in section 19b(vi) of the project licence
applications (ND1,
ND12,
ND21
& ND24).
References (or the absence of them in relevant places) to the welfare
impact of Imutran's experiments also appear in other documents.
These are still being analysed. Here we focus on Imutran's statements
in their project licence applications.
Generally speaking, Imutran's estimates of suffering downplay the
likelihood and severity of pain, suffering and distress caused by
their experiments (see particularly pages ND1.39,
ND1.42,
ND1.45,
ND1.49,
ND21.20,
ND21.27/28.
In document ND24
Imutran at least refer to some of the potential adverse effects
but still tend to downplay the likely incidence and the level of
suffering caused. A comparison with the evidence
of suffering contained in the original Diaries of Despair documents
and discussed in the report (see chapters
4 and 6)
illuminates the difference between Imutran's claims to the Home
Office and the horrific reality of their research.
Drug toxicity resulting from the administration of immunosuppressive
substances is one particularly lethal and painful adverse effect
that is absent, particularly in earlier project licence applications
(see documents ND1.25-26,
ND1.30-31,
ND1.35-36,
ND1.39,
ND1.42,
ND1.45,
ND1.49,
ND1.56,
ND1.62,
ND21.20
and ND21.27).
The likelihood of surgical failures also appears to have been wildly
underestimated, particularly at ND1.31
(d), ND1.36
(d), ND1.56
(c).
This submission of "False Information" potentially constitutes
a criminal offence. |
