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
. 2.  Imutran's exaggeration of potential benefits
  3.  Liver xenotransplantation
  4.  Imutran's "cavalier" attitude
  5.  Animal suffering underestimated

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:

  1. 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."

  2. 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.]

  3. 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."

  4. 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!!!"

  5. 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."

  6. 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..."

  7. 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."

  8. 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."

  9. 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."

  10. 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:

  1. 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".

  2. 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:

  1. 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))

  2. 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."

  3. 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.


Pig organs
Credit: Organ Farm


"... the Home Office will attempt to get the kidney transplants classified as moderate procedures."

Imutran report
























Monkey in cage
Credit: Organ Farm


Day 1 "Quiet, sitting on floor in corner of cage, eyes closed, appears reluctant to move."

Day 2 "Quiet but alert. Reluctant to move, appears weak when moving."

Day 3 "Subdued, sitting on perch, reluctant to move when stimulated."

Day 7 "Very quiet, laying on cage floor... colic... diarrhoeic... Haemorrhages in skin."

Day 8 "Laying on cage floor, reluctant to move. Generalised bruising all over body."

Day 9 "Found in a collapsed state. Petechiae all over body, bloody froth at nose. Sacrificed..."


























Baboon operation
Credit: Organ Farm


"Questions remain as to whether the suffering of these animals was accurately predicted and assessed by the project licensee [i.e. Imutran] and how the predicted suffering was weighted.

"This requires access to the relevant section in the licence applications, which we do not have for the purposes of preparing this report." (This is now in the public domain thanks to the Uncaged Campaigns' legal victory - see linked docs listed below.)

"We believe it is essential to further investigate these questions, particularly with respect to the comparison of predicted against the actual suffering, in order to inform future decisions."

RSPCA report, section 5.3, p.35


































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