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.

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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

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Questions for the Home Office

  1. 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?

  2. 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?

  3. 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?

  4. 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)?

  5. 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?

  6. 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?

  7. 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?

  8. 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?

  9. 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

  1. www.xenodiaries.org/overview.htm
  2. Report of the Animal Procedures Committee for 1997: 50-59.
  3. Guidance on the Operation of the Animals (Scientific Procedures) Act 1986, paras 4.9-4.10: 10. (published 1990, updated 2000)
  4. See page 412 of Study Reports and document CY16.2
  5. See document CY14.1
  6. UKXIRA Third Annual Report, September 1999 - November 2000. Department of Health, published February 2001, paras 6.8-6.15.
  7. New Scientist, "Waiting for a miracle - time is running out for organ transplants from animals", 12.1.02, p.3.
  8. RSPCA Report: Non-Human Primates in Xenotransplantation Research in the UK: 39.
  9. Written Answer, O'Brien to Gordon, 1 November 2000.
  10. Para 4.6, Meeting minutes for Oct 2001 (www.apc.gov.uk/reference/oct01.htm)
  11. See document CY24.2
  12. Para 4.7, October 2001 Meeting minutes (www.apc.gov.uk/reference/oct01.htm)
  13. Para 5.6, April 2000 meeting minutes (www.apc.gov.uk/reference/apr00.htm)
  14. See document ND13.1
  15. Paragraph 1.3 of the Chief Inspector's report.
  16. ibid., para 3.2.
  17. See www.xenodiaries.org/newdocs.htm#imutran
  18. www.xenodiaries.org/evidence.htm#itn6
  19. Paragraph 5.13.1
  20. "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

 

Baboon operation
Credit: Organ Farm

"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."

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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