Curiosity Killed the Dog
This special report was prompted by Animal Aid's discovery of a long-running series of terminal experiments on dogs,carried out at a leading UK medical school and funded, in large part, by one of the country's biggest charities the British Heart Foundation.
Begun 16 years ago and aimed at measuring physiological responses to experimental heart-related procedures, the Leeds Medical School-based project seemed to Animal Aid to be both repugnant (it has involved opening the chests of anaesthetised dogs, cutting their spinal cords, draining and recirculating theirblood, and cutting nerves to the brain, gut and diaphragm) and without scientific merit.
We presented a dossier of the team's work to heart specialist and medical researcher, Dr. John J. Pippin,* and asked for his written assessment as to the merits of the work, in terms of human medicine.
Dr Pippin's response was scathing. In fact, he has called for those involved to have their Home Office licences revoked. It is a call that Animal Aid endorses.
In his critique to the Home Office, Dr Pippin declared: `This work provides an exceptional example of a common practice: the manipulation of animal models for convenience and usefulness, regardless of the effects upon the validity of results obtained. This is not uncommon among those researchers who propose and perform studies to satisfy their scientific curiosity and sustain their careers, without sufficient regard for potential applications to humans.
`Very evident in this collection of papers is the characteristic use of one study to justify the next. In many cases, unanswered (usually unforeseen) questions arising from one study produced the rationale for a later study. In several instances, the team invokes conflicting or erroneous results from previous studies (sometimes their own) to justify another study.'
The larger scandal disfiguring this long-running research project has been the willingness of the Home Office regulators to sanction an enterprise that, by any objective assessment, fails to demonstrate obvious benefits for human medicine. The same charge of lack of due diligence can be levelled at the British Heart Foundation, a major research charity that, for many years, has directed publicly donated money at the Leeds team.
The team's activities are categorised, under the official Home Office formulation, as `basic' or `fundamental' research. These are catch-all terms that may or may not promise tangible benefits for human or even animal medicine. The regulators are content for the research to be speculative. It need only carry the suggestion that at some future, unspecified date something concretely beneficial might emerge.
Blue skies research is all very well, many people would agree, where public money is not involved and where the research materials are inanimate. But the Leeds team have been working at a publicly funded institution, with additional funds coming from a charity Furthermore, the object of their attention has been beagle dogs.
While the Leeds Medical School project is a particularly shocking example of basic research using live animals, this report demonstrates that there is a good deal that is fundamentally problematic about this whole area of work.
* John J Pippin MD graduated from the University of Massachusetts Medical School in 1980 and subsequently specialised in nuclear cardiology. Among his academic appointments are faculty positions at Harvard Medical School and the Medical College of Virginia. In addition to his numerous scientific publications, he is the recipient of several prestigious awards for clinical and research excellence.In February 2005, he presented evidence at a US Food and Drug Administration hearing on the misleading results of animal tests with respect to the anti-inflammatory drug, Vioxx.
Basic Research (aka `Fundamental Research') involves experiments whose primary purpose is an increase in the fund of knowledge available in a particular field of scientific endeavour. Typically, questions are posed and answers sought by means of animal experiments. Such studies, according to a Home Office definition, may be aimed solely at an increase in knowledge, an application of existing knowledge beyond the scope of the investigator, or else, at providing a practical solution to an existing medical or veterinary problem.
In reality, claims of relevance to human medicine will always be made by those involved in basic research. This is to give weight to their application for funding and for a Home Office licence.
Basic research is normally subdivided into toxicological and non-toxicological procedures. The latter (non-toxicity tests) may include efficacy studies (where a procedure is designed with the aim of achieving a particular desired effect), metabolism (bodily function), nutritional evaluation (food studies), etc. In addition, basic studies may be categorised according to the body system in question, e.g. respiratory, cardiovascular, nervous, digestive, reproductive.
Legislation covering basic research
All animal experiments are `regulated' by the Home Office, under the 1986 Animals (Scientific Procedures) Act.
While current law makes it difficult to avoid animal testing during the safety evaluation phase of new pharmaceutical products, scientists conducting basic research have no legal requirement to use animals. It is left to the individual scientist to judge what is worth studying, and whether or not to use animals. In order to perform an animal experiment (referred to as a `procedure'), a researcher must obtain a personal, as well as a project, licence. The proposed research programme will be scrutinised by a professional body (the Home Office Inspectorate), `composed of medical and veterinary graduates with higher professional and academic qualifications and experience of clinical practice and quality research' (1).
The scope of basic research in the UK
According to official Home Office figures, there has been a steady increase in the number of animals used in basic research over the last 10 years, from 24% of the total number of procedures in 1993, to 30% in 2003 (the total number of procedures in 1993 and 2003 was the same i.e. 2.8 million).
Categories of basic research
Of the various fields of basic research, the largest single category in 2003 was the immune system (nearly half a million procedures), involving several different species of animal. The next largest category was the nervous system, followed by the cardiovascular, respiratory and digestive systems.
Examples of basic research - 1
Ten five-week-old kittens had the eyelids of one eye sewn together and kept closed for ten days. In five of the kittens, the sewn eye was then opened, while the healthy eye was surgically manipulated to make it squint. Fourteen days later, the kittens were anaesthetised and had part of their skulls removed in order to expose the brain area that is responsible for vision. Behavioural and optical imaging experiments were subsequently performed.
There is no mention in the article of whether the kittens were allowed to recover from the experiment or whether they were euthanased. The authors do not provide any clear conclusion. Instead, they explain why their study appears to contradict that of other researchers, and also why the results could differ when the experiment is performed in monkeys.
This is yet another minor variation on a category of research called `monocular deprivation', often used to study the human condition known as amblyopia (`lazy eye'). Cats were used in this experiment even though their eyes lack a macula and fovea two areas of critical importance in the human eye. A Harvard trained pediatric opthalmologist commented on this type of research in 1990 in an affadavit (next column) presented in an Israeli court of law. This document, together with several other sworn statements made by eye specialists, all concurred on the lack of applicability of these experiments to the human condition.
`I do not believe that straining to find out new ways of depriving cats of visual input has added, or will add, to our knowledge about the connections of the eye to the visual cortex in cats... even if it adds a little to our knowledge of visual connections in cats, the applicability of this knowledge to human amblyopia is essentially nil.Clinical research, done with children who
are actually suffering from amblyopia, would seem to be the only way to find out more about how to treat this important condition which affects about two per cent of the population.'
Affidavit by Robert Petersen MD, The Children's Hospital, Boston USA
Source: Correlated binocular activity guides recovery from monocular deprivation.
Nature 2002; Vol. 416: 430-433. Kind P Mitchell D, Ahmed B, Blakemore C, Bonhoeffer T, Sengplel F.
University laboratory of physiology, Parks Road, Oxford.
Funding: Wellcome Trust, Medical Research Council (UK), Max-Planck-Gesellschaft, Canadian Institutes of Health Research, Oxford McDonnell Centre for Cognitive Neuroscience.
Examples of basic research - 2
Sixty-two ferrets, of whom 39 were albino, were used in this study. Their age ranged from ten weeks to 24 months. Eight of the ferrets were anaesthetised and had a radioactive compound injected directly into their left eye. In conjunction with general anaesthesia, a neuromuscular blocking agent was used the use of such drugs giving cause for special concern, because the paralysis they produce may mask signs of pain.
Other animals were anaesthetised and surgical slits made in the skull through which to insert several electrodes into the brain. In another six albino and six non-albino ferrets, a fluorescent compound was injected directly into the brain. Again, these procedures were made under a combination of anaesthesia and paralysis. The skull wounds were covered and the ferrets allowed to recover from the anaesthetic. Seven more albino animals were anaesthetised and received deep brain injections. These animals were allowed to recover and then euthanased 2-7 days later.
The authors conclude that `the results presented here on anaesthetised, paralysed pigmented ferrets are similar to previous studies'.
The experiment was directed at the discovery of scientific data for its own sake a crumb amongst the millions of other crumbs of basic research that are discoverable, but totally inapplicable to human or animal health.
Source: Relay of visual information to the lateral geniculate nucleus and the visual cortex in albino ferrets
The Journal of Comparative Neurology 2003, vol 461: 217-235. Akerman J, Tolhurst D, Morgan J, Baker G, Thompson I. University Laboratory of Physiology Oxford.
Funding: Medical Research Council (UK), Wellcome Trust, McDonnell-Pew Foundation.
The peer review process of approving animal research
Peer review, with respect to basic research, is a twin process it occurs prior to an animal experiment taking place and, once again, subsequent to the data being obtained from the animal research.
The initial peer review is undertaken by Home Office officials and by a local ethical review committee the latter, at the institution where the research takes place. The task of these two bodies is to examine the research proposal and decide whether to approve it. Assuming the proposal is approved, a subsequent review process will be undertaken by an editorial board, after the study has been carried out. At this point, the results of the completed research are assessed with respect to publication in a scientific journal.
Based on the above, one might be tempted to conclude that all animal research is conducted and monitored to very high welfare standards. Alas, this is not the case. Leaked documents and undercover video footage have revealed horrific animal suffering and researcher incompetence, which Home Office inspectors failed to detect (2).
Critique of the peer review process
It follows that the peer review process that takes place within the research institution, as well as the subsequent Home Office `cost-benefit analysis' aimed at quantifying animal suffering, should both be open to public scrutiny. In practice, however, this is rarely, if ever, the case. Institutional ethical committees do not contain public representatives, and certainly would not host a scientist with an opposing view.
Leading medical journalists, including the editor of the British Medical Journal, have gone on record as saying that `Peer review is a very flawed practice... and prone to abuse and bias. Much of the time it doesn't pick up errors' (3). It can also be observed that the peer review community is an elite group who, researchers will acknowledge in private, are not above looking favourably upon a colleague, on the one hand and being unhelpful to a researcher with whom they have had a scientific or personal dispute.
There are certainly more objective ways of assessing animal research than the current peer review system.
One such method is `citation analysis' the process whereby the impact or `quality' of a piece of science is assessed by counting the number of times other scientists mention it in their work (4). This is particularly suited to animal experimentation in basic research, since the justification for such animal studies invariably points to human benefit.
A recently published study on applications of biomedical research involving animal models makes a compelling case for using citation analysis in the peer review process. The authors of this study investigated the frequency of citations of the animal research in clinical (human) publications. The outcome was unambiguous.
Less than 10 per cent of all citations in the clinical publications contained references to the animal research. More significantly, only in two publications could a direct correlation between the results from animal experiments and observations in humans be noted. However, even in these two cases, the hypotheses that had been verified successfully in the animal experiment failed to yield any clinical advance (5).
The acquisition of knowledge for its own sake does not justify inflicting pain and suffering on sentient creatures.
The animal research described above and in the case history is, in our view, not about science or helping human beings through rational research. It is about the search for grants, academic prestige and career development.
The Home Office (Animals Scientific Procedures Division) must clearly take a large share of the blame for reinforcing deficient systems of vetting and oversight, and thereby allowing repetitive research of unproven scientific merit to gain its seal of approval. Indeed, the Home Office has gone on record as saying that peer review and support of animal research by a reputable funding body `cannot be taken to guarantee the relevance, importance, or scientific validity of any individual experiment or publication' (6).
Finally the charitable organisations that fund animal research urgently need to review their grant-awarding criteria.