MEMORANDUM FOR HOME AFFAIRS COMMITTEE
Background
In spring of 2000, Uncaged Campaigns received an anonymous parcel
containing documents leaked from Imutran Ltd. These kinds of documents
had never emerged into the public domain before and are highly sensitive
and confidential. They describe pig-to-primate transplant research
conducted between 1994 and 2000, and comprised: research reports,
internal communications, meeting minutes, correspondence between
Imutran and their collaborators, particularly Huntingdon Life Sciences
(HLS) who were contracted to provide facilities for the experiments,
and communications with the Home Office.
It became immediately clear that the documents contained unique
and historic evidence that raised serious concerns regarding (1)
the Home Office's enforcement of the Animals (Scientific Procedures)
Act 1986 ('ASPA') and associated regulations, (2)
the indulgent relationship between the Home Office and licensees,
(3) compliance with regulations
on the part of the Imutran and HLS.
Over the next four months, a report was written based on the documents,
called Diaries of Despair. This was produced with the assistance
of a scientific advisor to the Government and in consultation with
lawyers. Mr Lyons' and Uncaged's view of the overwhelming public
interest in the disclosure of the confidential documents, due in
no small part to the weight of evidence of official wrongdoing,
was confirmed by their legal advice. The documents and report were
published on 21 September 2000, coinciding with a report in the
Express newspaper.
Immediately, Imutran applied to the High Court for an injunction
to prevent publication of all of their confidential documents, which
was granted until trial, when a full examination of the issues would
be possible. Legal aid was granted to Mr Lyons in June 2002, following
a decision by the Legal Services Commission which recognised the
highly "significant public interest" issues raised by
the case, including the adequacy of the enforcement of laws and
regulations. In October 2002, a second leak occurred, this time
from the Home Office, revealing further evidence of regulatory failure
and concerns about Imutran's conduct. The Home Office has not sought
to suppress this second leak, despite the documents being confidential.
With disclosure applications from the Defendants looming and a
trial appearing on the horizon, in April 2003 the High Court ratified
an out-of-court settlement that signified Imutran's abandonment
of their attempt to completely suppress the documentation. Imutran
and their parent company Novartis had argued that disclosure to
the regulatory bodies was sufficient. The Diaries of Despair report
and subsequent Defence pleadings consistently asserted that because
the documents revealed evidence of wrongdoing on the part of those
regulatory bodies, public disclosure was required. Despite the huge
financial disadvantage suffered by the Defendants, their case prevailed.
The new Order permits the publication of over 1,000 pages of documents
relating to the main public interest aspects of the Defence, particularly
Home Office bias and malpractice.
Main charges against the Home Office
The Diaries of Despair report mainly arranges and interprets the
Imutran documentation in relation to the regulatory structure. Key
aspects of that structure are the cost/benefit assessment, which
is the fundamental legal control on animal research in the UK (ASPA,
s 5(4)), and the absolute prohibition on "severe" suffering
(ASPA, para 3.2, Schedule 2A)
The Home Office's response to the Diaries of Despair report, particularly
the Chief Inspector's review, is also examined in this memorandum.
1. Cost-benefit assessment
These are some of the features of the crucial cost-benefit assessment,
as described by the head of the Home Office Inspectorate:
- "Judgement on the likely severity of the adverse effects
on animals"
- "Standards of care and accommodation"
- "Technical competence of the people and establishments
to be involved in the project"
- "Likelihood of 'success' "
- "Utility of the product or substance being tested"
Severity of adverse effects on animals
An assessment of overall severity is used to represent the likely
adverse effects on the animals in the cost-benefit assessment. The
vast majority of the Imutran xenotransplantation experiments were
assessed as of merely 'moderate' severity.
The Home Office's 'Guidance on the Operation of the Animals (Scientific
Procedures) Act 1986' described how the likely severity of procedures
is assessed. 'Moderate' procedures include "surgical procedures
provided that suffering can be controlled by reliable post-operative
analgesia and care", while on the other hand procedures regarded
as being of "substantial" severity include "Procedures…
[that] result in a major departure from the animal's usual state
of health or wellbeing… [including] some models of disease
and major surgery where significant post-operative suffering may
result. If it were expected that a single animal would suffer substantial
effects, the procedure would warrant a severity limit of 'substantial'."
Pig-to-primate kidney xenotransplantation experiments (classified
as 'moderate') involved the modelling of kidney rejection and thus
failure, causing nausea, vomiting, lethargy and death as a result
of blood poisoning. At the same time, various drug combinations
were tested in the primates to investigate how they affected the
rejection mechanisms. In actuality, these were just some of the
effects:
Two days after transplant, W560f was killed.
She had been lying on the cage floor and the grafted kidney had
failed to produce urine after the operation had finished. W548f
survived six days. For part of this time she had been reluctant
to use her swollen legs, and had produced green vomit on day two.
The morning of her sacrifice due to renal failure and a ureteric
obstruction (blockage of the ureter, which carries urine from
the kidney to the bladder), she was found "lying on the cage
floor" and subsequently "very weak and unsteady when
moving." (4)
On V337m's seventh and final day, he was observed:
am: Very quiet and subdued. Occasional trembling.
Appears unsteady.
pm: Huddled. Unwilling to move. Collapsed state. Sacrificed.
To study the actual effects of the 'moderate' procedures, please
refer to: www.xenodiaries.org/legal.htm#conduct
A 'moderate' severity classification is a gross underestimation
of the suffering caused by these procedures. It also skews the cost-benefit
assessment, facilitating the granting of licences for such research.
One confidential document provides a glimpse of the collusion between
Imutran and the Home Office to 'fix' the system in their favour:
"Sandoz [Imutran's parent company at the
time] have suggested kidney transplants, the Home Office will attempt
to get these classified as moderate procedures." (5)
'Benefits' of the research
Both publicly, and in submissions to the Home Office, Imutran repeatedly
claimed that they were on the verge of commencing clinical trials
of pig organ transplants, thereby giving the impression of a high
likelihood of substantial progress in their research towards a clinically-useful
therapy. In fact, Imutran made no significant progress in the course
of five years of severe experiments on some 500 primates, admitting
to the Home Office in early 2000 that there was no drug that could
reverse the form of rejection they had been investigating. The Department
of Health's xenotransplantation advisory committee, the UKXIRA,
having considered the Diaries of Despair documents together with
the obvious lack of progress, stated that the likelihood of clinically-viable
pig organ transplants was 'receding' (6)
- which was, as the New Scientist put it, a polite way of saying
that the technology was 'dead in the water.' (7)
The RSPCA's own report on the Imutran documentation, published
while the injunction was still in force, concluded: " ... we
do not consider that a significant and justifiable benefit was being
achieved." (8)
The core concern regarding the Home Office's operation of the cost-benefit
assessment is that it underestimated the level of suffering endured
by higher primates, while overestimating the probability of benefits
accruing from the research. The cost-benefit assessment is supposed
to be a continuous process. It is reasonable to believe that objective
scrutiny of Imutran's xenotransplantation research would have led
the Home Office to reject it on cost-benefit grounds. At the very
least, it should have become clear during the lengthy research programme
that the suffering endured by primates was not producing the benefits
claimed for it. Yet the Home Office failed to intervene. This failure
to conduct an honest and rigorous cost-benefit assessment - that
gives due weight to the interest of animals and thoroughly scrutinises
the claims of 'human benefit' put forward by researchers - is unlikely
to be a one-off.
2. "Severe" suffering
Another basic constraint on the harms caused by animal experimentation
is the prohibition on "severe" suffering. The secret Imutran
documents reveal several instances where there exists, at least,
a strong prima facie case for "severe" suffering to have
taken place. This section of the Diaries of Despair website - www.xenodiaries.org/legal.htm#illegal
- refers and links to the primates who appear to have suffered the
most severe adverse effects. It is worth reflecting on the terrible
condition of these animals to help appreciate the deep ethical significance
of this whole affair, and understand why the Home Office's failure
to regulate and subsequent failure to respond to evidence of wrongdoing
is a cause of very serious concern.
One problematic aspect of the enforcement of this limit is that
the Home Office does not appear to have developed any definition
at all for "severe" suffering. Furthermore, the suffering
caused by "substantial" procedures would, on a common
sense view, be reasonably regarded as "severe", especially
as such procedures normally cause "acute" symptoms and
are expected to lead to the death of the animal.
3. Inappropriate response from Home Office
The Home Office's response has been so inappropriate that it even
confounds the expectations of Imutran Ltd and the advisory committee,
the Animal Procedures Committee. Prior to Jack Straw's announcement
of an internal review, a witness statement submitted to the High
Court by Imutran, responding to Mr Lyons' reasonable contention
that the Home Office could not be trusted to conduct a thorough
inquiry, referred to a potential inquiry extending beyond the Chief
Inspector and stated: "Until the composition of the
proposed inquiry is known, it clearly cannot be said that it will
be lacking in independence. It can hardly be supposed that Ministers
will appoint persons whose conduct is criticised by the Defendants
to investigate their own conduct." Yet this is precisely
what has occurred.
This marked an extremely rapid and unexplained u-turn, as less
than a month earlier Home Office Minister Mike O'Brien had told
Parliament that future investigations into allegations of regulatory
breaches would involve the Animal Procedures Committee (9)
(APC - though this would still not meet the requirement for a competent
and independent inquiry). The APC wrote three times to the Minister
expressing their surprise at the failure to establish any form of
special inquiry, given the seriousness of the concerns raised by
Diaries of Despair, and requested an explanation. No such explanation
has been forthcoming. (10)
4. Scope of Chief Inspector's review
The entire 150 page Diaries of Despair report was structured around
the question of the adequacy of the cost-benefit assessment, which
is the responsibility of the Inspectorate. Subsidiary issues included
the relationship between Imutran and the Inspectorate, questions
of "severe" suffering, the severity bandings, the technical
competence of the researchers, and Imutran and Huntingdon Life Sciences'
compliance with laws and regulations. The attitude of the Inspectorate
is a matter of grave concern. One document reveals that Imutran's
Inspector reassured the company on several occasions that a crucial
meeting of the APC to discuss one of Imutran's applications would
be a "rubber-stamping" exercise. (11)
In the event, the Home Secretary ordered an internal review into
just one aspect: Imutran's compliance. Even the APC has stated:
"Most members were concerned that the remit [of the
Chief Inspector's review] had not been wide enough."
(12) The fundamental issues
raised were not considered, and the review was conducted by the
body specifically criticised in Diaries of Despair.
5. Adequacy of Chief Inspector's review
Responding to a previous Inspectorate report, the APC remarked:
"Many members felt that the report sought to exonerate Harlan-Hillcrest."
(13) The review of Imutran's
compliance adopted the same approach.
The Chief Inspector's report, published in July 2001 while the
blanket injunction was in place, itself contains several significant
inaccuracies and omissions, downplays the suffering of animals,
and attempts to shield the Home Office, Imutran and HLS from legitimate
criticism.
Here are a few examples:
Unauthorised experiments hidden
Leaked Home Office papers show that Imutran performed experiments
on primates without the prior knowledge or consent of the Home Office,
(14) in direct contradiction
to claims made in the Chief Inspector's report. (15)
Distorted cost-benefit assessment
The Chief Inspector claimed that in conducting the cost-benefit
assessment, Imutran did not advance, and the Home Office did not
consider, clinical trials in the near future as a realistic benefit.
(16) Now the injunction has
been lifted, it can be revealed that such claims were in fact repeatedly
advanced by Imutran. (17)
Furthermore, a Home Office letter to Mr Lyons in 1998 refers to
clinical trials as the only benefit that could justify these experiments
(copy available from Uncaged Campaigns). The Chief Inspector appears
to have tried to 'move the goalposts' in terms of the benefits that
were said to justify such severe research, in order to give the
impression of a consistent and coherent cost-benefit assessment,
a crucial aspect of the regulatory system. The Chief Inspector instead
claimed that the Government licensed this research merely on the
basis of new scientific insights that could be gained. Not only
is this untrue, but merely gaining biological data would not in
itself justify to most reasonable people the infliction of severe
suffering on higher primates. Presumably this why such a weak justification
was not offered by either Imutran or the Home Office while the research
was taking place.
Horrific procedures ignored
The Chief Inspector's report did not deal with the horrific suffering
experienced by primates in procedures involving the transplantation
of pig hearts into their necks. (18)
These procedures, and others that caused severe suffering, were
classified as 'moderate', but, incredibly, no breaches were found
by the Inspector.
Dismissal of animal suffering
It is inaccurate for the Chief Inspector to claim that the twice
daily clinical observations of the animals reproduced in the Diaries
of Despair do not take account of treatments given to primates.
(19) Clearly, the recorded
observations give a prima facie impression
of the condition of the animals in the context of any treatments
given, and Diaries of Despair did not assert that no such treatments
were administered.
The treatments given to the animals cannot, in any case, contradict
the clinical observations, even if those observations do not give
the complete picture. The fact of the matter is that despite any
"clinical management", those harrowing observations were
made. Hundreds, if not thousands, of observations record that primates
endured "vomiting", "diarrhoea", "swellings",
"seeping wounds", "body tremors", that they
were "subdued" and "reluctant to move", "collapsed",
were "unsteady", suffered "breathing difficulties",
were "distressed" etc. That cannot be argued with. Clearly,
whatever treatments were administered only had a limited effect,
otherwise those observations simply would not have been made.
The deeper point, that the Chief Inspector has sidestepped, is
the intrinsic and unavoidable severe suffering caused by the entire
experiment: the surgery, immunosuppressive toxicity, organ failure,
infection, etc.
The fact that the Chief Inspector's report:
- fails to even acknowledge the concerns about the severity of
suffering, and simultaneously
- denies the validity of the clinical observations
is stark evidence of the agenda behind the Chief Inspector's report
and the frankly callous attitude of the Home Office Inspectorate.
Many of those animals must have suffered greatly, and the Chief
Inspector's refusal to deal with the issue openly is very disturbing.
During the legal proceedings, Imutran also attempted to undermine
the relevance of the clinical signs by referring to the existence
of other information and observations. However, in apparent contradiction
to Civil Procedures Rules, they failed to disclose these documents
to the Court to substantiate their assertions. Furthermore, the
leaked Home Office papers, which included licence applications from
Imutran, contain statements from Imutran to the Home Office that
directly contradict their earlier submissions to the court in respect
of the clinical signs, describing how certain observations are indicative
of terminal renal failure, for example. (20)
The eventual publication of the clinical signs, and the endorsement
of their relevance by RSPCA experts, reinforces their historic relevance
and raises profound concerns about the failure of both Imutran and
the Home Office to acknowledge openly the intense pain and distress
experienced by the primates.
The review of the Chief Inspector's report, submitted to the Home
Office back in autumn 2001, is now published at: www.xenodiaries.org/responsetoaspi.htm
Discussion of the information revealed in the October 2002 leak
from the Home Office, much of which demonstrates inaccuracies in
the Chief Inspector's report, can be found at: www.xenodiaries.org/newdocs.htm
Questions for the Home Office
-
Why has the Home Office not initiated an independent investigation,
or responded in any way, to Uncaged Campaigns' allegations of
regulatory failure on the part of the Home Office Inspectorate?
-
What is the Home Office's response to concerns regarding the
banding of all heterotopic xenotransplantation experiments as
"moderate" and the question of breaches of the absolute
prohibition on "severe" suffering?
-
Does the Home Office accept that a conflict of interest arose
when Ministers blocked an inquiry into circumstances surrounding
research that was personally authorised by Ministers?
-
Why did the Home Office break its pledge to include the APC
in investigations of allegations of regulatory breaches (Written
Answer, Mike O'Brien to Eileen Gordon, 1 Nov 2000)?
-
Why did the Home Office exclude consideration of Huntingdon
Life Sciences' compliance with regulations from its review,
despite initial assurances by Mike O'Brien to the contrary and
evidence of several breaches and mistakes on the part of that
establishment which were acknowledged by the Minister?
-
Does the Home Office now accept that the likely benefits -
clinical trials - advanced by Imutran and accepted by the Home
Office as the only justification for the primate xenotransplantation
research, did not in fact accrue, and that an independent retrospective
review of the operation of the cost-benefit assessment is necessary
to ensure that animals are given the level of consideration
and protection promised by the Animals (Scientific Procedures)
Act 1986?
-
Will the Home Office publish advice received from the Department
of Health and UKXIRA regarding the likelihood of Imutran's research
leading to clinical use of pig organ xenografts?
-
Will the Home Office take disciplinary action against the Chief
Inspector in view of the inaccuracies in his report on Imutran's
compliance with regulations?
- Will Home Office Ministers issue an apology to the House in
respect of the inaccurate Written Answer given by Mike O'Brien
in relation to the failure to acknowledge regulatory breaches
in the design of transport crates in which 3 monkeys were found
dead while en route to the UK for the purpose of Imutran's research?
FOOTNOTES
- www.xenodiaries.org/overview.htm
- Report of the Animal Procedures Committee for
1997: 50-59.
- Guidance on the Operation of the Animals (Scientific
Procedures) Act 1986, paras 4.9-4.10: 10. (published 1990, updated
2000)
- See page 412
of Study Reports and document CY16.2
- See document CY14.1
- UKXIRA
Third Annual Report, September 1999 - November 2000. Department
of Health, published February 2001, paras 6.8-6.15.
- New Scientist, "Waiting
for a miracle - time is running out for organ transplants from
animals", 12.1.02, p.3.
- RSPCA Report: Non-Human Primates in Xenotransplantation
Research in the UK: 39.
- Written Answer, O'Brien to Gordon, 1 November
2000.
- Para 4.6, Meeting minutes for Oct 2001 (www.apc.gov.uk/reference/oct01.htm)
- See document CY24.2
- Para 4.7, October 2001 Meeting minutes (www.apc.gov.uk/reference/oct01.htm)
- Para 5.6, April 2000 meeting minutes (www.apc.gov.uk/reference/apr00.htm)
- See document ND13.1
- Paragraph 1.3 of the Chief Inspector's report.
- ibid., para 3.2.
- See www.xenodiaries.org/newdocs.htm#imutran
- www.xenodiaries.org/evidence.htm#itn6
- Paragraph 5.13.1
- "Clinical signs associated with progressive
and irreversible renal failure can typically be characterised
by a number of common features... Physically the animal becomes
progressively quieter (listless) and adopts a huddled/hunched
posture, reflecting the rising blood creatinine level." (See
document ND24.23)
Uncaged Campaigns, June 2003 |
