Read Animal Aid's scientific Briefing on the Bristol experiments

More documents

Recommendations

Info

Paws poked with wires, heated up and injected with corrosives After enduring nerve damage surgery, mice had their hypersensitive back paws poked repeatedly with fine wires, they were heated with thermal beams or they were injected with formalin (a highly irritant corrosive). This infliction of pain was performed on repeated occasions, from shortly after surgery until the end of the experiments two weeks later. In other procedures, mice with nerve damage had their paws dipped in food colouring, and were then made to walk on white paper, to establish how crippled they were. Others had their skin injected with substances that caused violent itching, or had the active ingredient in chilli pepper injected into their cheeks. Distressing and lethal ‘side effects’ of genetic modification Many animal victims of genetic manipulation suffer unforeseen and unpredictable ‘side effects’, in addition to the intended suffering from their designer diseases. The Bristol researchers report how they generated knockout mice with the gene for galanin production disabled, through gene targeting in embryonic stem cells 3 . The team reported that ‘mutant females fail to lactate and pups die of starvation/dehydration unless fostered onto wild-type mothers. This apparent failure of lactation was absolute during the first two pregnancies.’ Clearly, many pups were callously allowed to die, as ‘in subsequent pregnancies, 80 per cent of pups died but on some occasions one or two survived to the weaning period’. Mass destruction of living creatures The researchers created and bred their own lines of genetically engineered mice for subsequent experimentation. These procedures are notable for the waste of lives and sheer scale of animal killing required. The initial creation stages, for example, entail the deaths of hundreds of animals to produce only one ‘founder’. Mice who are judged to be ‘excess’ or ‘failures’ are generally gassed or have their necks broken. Contradictory findings even between animal studies On several occasions, the researchers reported findings that contradicted previous animal experiments in different species, findings in other GM mice and other mouse pain ‘models’, as well as the ‘existing pharmacological data’. They stated in one case that ‘the most obvious explanations for the apparent discordance in nociceptive (pain) behaviours between these two different GalR2-MUT (mutant) lines are that each study has used a different model of neuropathic pain, and the animals have been generated on differing genetic backgrounds’. In other words, the results of the experiments are not even verifiable between different kinds of mice. The absurdity of their extrapolation to humans, therefore, is glaringly obvious. The researchers, however, proposed further pain experiments on more knockout mice to clarify the problem. ‘An eye fixed firmly on the marketplace’ <strong>Briefing</strong> sheet www.animalaid.org.uk • tel: 01732 364546 The Bristol papers do not specify how many ‘surplus’ mice were killed prior to the creation of a stable GM line. Minutes of a Bristol University Ethical Review Meeting from 2010, however, refer to an experimental series entitled: ‘The adaptive response of the nervous system to injury’. This title is identical to that found on the Bristol University website of the lead researcher, and to a Home Office public summary that describes the experimental protocols. It is highly unlikely that the Ethical Review does not refer to the experiments detailed in this <strong>Briefing</strong>. The minutes, released under the Freedom of Information Act, show that ‘very high numbers of animals are needed for the maintenance of genetic lines due to several factors including the size of the research group and the fact that the use of multiple crosses means only 1 in 64 animals may be usable. However, there was concern that the use of 18,000 animals in the renewal application was not justified in the text. It was noted that large numbers of animals were also quoted in the original application.’ Despite these concerns, the Ethical Review Body approved the renewal of the project licence. As in many cases of university research, there are clear links between the researcher’s publicly funded experiments and their potential for private profit. A continuous flow of public and charity money (including a £4.3 million grant in 2010 from the Wellcome Trust) has sponsored the programme for the last 15 years. In 2007, its lead researcher was paid out of public funds (from the Medical Research Council) to spend six months at GlaxoSmithKline learning about drug development – having founded his own ‘spinout’ drug company from Bristol University some years earlier. In fact, the lead researcher is clearly keen to tap the ‘billion dollar market’ for drugs for neuropathic pain. The Bristol University Annual Report from 2004 describes his drug company ‘bounding forward with its eye fixed firmly on the marketplace’, with its founder extolling the commercial potential of Bristol’s many research programmes. For patients in pain, the wait continues An article in Nature Medicine (2010) highlights the ‘abysmal track record’ of animal pain experiments - they ‘have produced an explosion of information
about pain, but this knowledge has failed to yield new painkillers for humans’. A 2010 meta-analysis of 174 randomised controlled trials (RCTs) of neuropathic pain treatments found that the majority of patients saw no benefit, with a high number of early drop-outs because of adverse drug reactions. A London researcher commented at that time: ‘The animal models of neuropathic pain just don’t seem to be that efficient.’ poor mimic of human disease. The damage induced in young, genetically identical and usually male animals is fundamentally different from the pain experienced by patients with chronic diseases, who are often elderly. The kind of neuropathic pain experienced by patients with diabetes, post-viral syndromes and cancer, for example, is not due to injury of their peripheral nerves such as that inflicted on the Bristol mice. The Bristol experiments are no exception. Despite inflicting considerable suffering on animals, they have so far produced no concrete benefits for patients. Galanin was discovered in 1978. It belongs to a group of substances known as neuropeptides, because of their role in biological communications between nerve cells. Galanin is found widely in mammalian central and peripheral nervous systems, and also in hormone producing organs. The chemical is involved in several biological processes, including pain perception, eating and sleep regulation and mood. However, despite decades of basic research (mainly but not exclusively using rodents), the roles of galanin in the human body remain far from clear. Molecules that both block and stimulate galanin receptors have been tested in ‘animal models’ of pain, epilepsy, Alzheimer’s disease, morphine addiction, alcoholism, eating disorders, depression and anxiety. Many of these experiments involve manifestly cruel physical and psychological torments. The disconnect between the preclinical animal studies and the subsequent human trials is enormous. A 2008 article, authored by animal pain researchers, points out that ‘of the 123 interventions assessed in the 105 RCTs included in a recent clinical meta-analysis, 53% were conducted in patients with peripheral polyneuropathies and 21% were in post-herpetic neuralgia patients. In contrast, only 9% of the RCTs studied patients with peripheral nerve injury.’ Another reason for the systematic failure to help human patients is the measurement of largely irrelevant data. These experiments are measuring evoked hypersensitivity of a mouse paw after a peripheral nerve injury, via withdrawal from a painful stimulus. However, the predominant symptom suffered by patients with neuropathic pain (and therefore the primary measure of a treatment’s efficacy) is spontaneous pain. Limb withdrawal in an injured animal is expected to somehow represent patients’ pain intensity and character, psychological status, sleep disturbance, physical function and overall quality of life. ‘A measurable failure of replacement and reduction’ <strong>Briefing</strong> sheet www.animalaid.org.uk • tel: 01732 364546 Mouse in nerve damage experiment However, this continued infliction of suffering has not resulted, to date, in even one galanin-based drug being approved for use in any human disease. In fact, the <strong>scientific</strong> literature is littered with speculative declarations of therapeutic breakthroughs that date back at least 25 years. The Home Office summary of the Bristol experiments makes clear that the primary purpose of the experiments is not patient care, but the acquistion of ‘new knowledge’, and that ‘the aim is to publish the findings in academic journals’. Human health is only a ‘secondary potential benefit…in so far as the results may at some later stage be of value in the development of new pharmaceutical products’. Pain research on mice does not translate to humans The Bristol experiments are basic research, involving the laboratory destruction of animal physiology and anatomy in the hope of finding out something clinically relevant. It has been estimated that this kind of work has only a 0.004 per cent chance of leading to a new class of drug. The pain model used in these experiments is a very ‘Researchers conducting prolonged pain research on mice are paying little, if any, heed to 3Rs principles in the planning and execution of their research.’ This was one of the damning conclusions of a literature review published in January 2013. The study details how the total amount of prolonged pain research (defined as that which subjects mice to a source of pain for at least 14 days), and the number of mice used, has increased dramatically in the past decade. The use of transgenic mice has also risen significantly. The authors discovered that neither the 3Rs concept, nor any of the 3Rs components - replace, reduce, or refine - were mentioned in any of 55 randomly selected recent studies. This ‘suggests that prolonged mouse pain researchers may be unaware of or indifferent to the 3Rs framework’, and that ‘adherence to guidelines and/or animal use committee requirements is not translating into significant progress from a reduction or replacement perspective’. This is hardly surprising, given the highly permissive and non-critical attitude of most Ethical Reviews. Science Corrupted Despite these failings, Bristol University currently remains committed to animal-based research, much of which involves GM mice. <strong>Animal</strong> Aid has produced a fully referenced <strong>scientific</strong> report, Science Corrupted, which reveals how, every year, millions of these sensitive and vulnerable animals suffer a chain of misery. It begins with the invasive procedures needed to create new genetic lines, and then continues with the harmful effects of genetic alteration, colony
Page 1: Genetically modified mouse experime

Read Animal Aid's scientific Briefing on the Bristol experiments

Create successful ePaper yourself

Delete template?

Save as template?