Animal experimentation in New Zealand—the three "buts"

Dr Michael Morris
Karori, Wellington
 
 

Abstract

When the subject of animal experimentation in New Zealand is raised, the most common reactions are either denial or an insistence that the experimentation is necessary. Intrusive animal experimentation involving "severe" or "very severe" suffering is more common in this country than generally believed. Furthermore, most experimentation is not necessary, if "necessary" is defined as the common perception of what constitutes acceptable experimentation. Many experiments are performed simply to increase agricultural production. I present evidence demonstrating that the use of animals as predictive tools either for other species or for humans is invalid, which calls into question much medical research. Other medical research aims for a more general understanding of biological processes, and this is scientifically valid. However, a consistent application of a utilitarian cost-benefit analysis should take into account the benefits of investing the resources currently going into animal experiments into alternative programmes of research or preventative medical treatment. I argue that if animal ethics committees used sound science and more rigorous cost-benefit analysis in their decision-making, then very few animal experiments would still be allowed. By using adequate operative and post-operative pain relief, the degree of suffering in these remaining experiments could be reduced to "moderate".
 

Introduction

The three "buts" in the title (chosen to correspond to the Three "Rs") refer to reactions by many members of the public when the subject of intrusive animal experimentation (vivisection) in this country is brought up. These can generally be summarised as:

"..but it doesn't go on here."
"..but it must be necessary."
"..but it is well regulated."

 Flaws in the New Zealand regulatory system have been adequately addressed in other studies (McCaw 1997: Bourke & Eden 2003; Cowperthwaite 2003; Kedgley 2003; Morris 2003). I will therefore confine this discussion to the first two "buts".

 The first "but" can be refuted quite simply by referring to the government's own figures. Each year the National Animal Ethics Advisory Committee (NAEAC) publishes a table of animal use according to severity scale. During 2002, 12,939 animals were subjected to "very severe suffering" according to scale devised by the Ministry of Agriculture and Forestry (MAF). Manipulations in the "very severe suffering" category include the following:
 

"conducting major surgery without the use of anaesthesia…; testing the efficacy of analgesics in animals with induced pain; toxicity testing using the traditional LD50 test; evaluation of vaccines where death is the measure of failure to protect; studies of the pathogenesis of fatal diseases caused by infectious or toxic agents; studies of recovery from third degree burns or serious traumatic injuries; induction of psychotic-like behaviour or of agonistic [fighting] interactions which lead to severe injury or death" (MAF 2001).

1. Short- or long-term applications to animal health, welfare or productivity;
2. Short- or long-term applications to medical research;
3. Control of vertebrate pests;
4. Education.

 I will discuss the first three applications below. Animal use in education has been covered previously (Morris 2004). I will be defining "necessary" research as that which leads to improvements in human or animal health and welfare, or protection of the environment. In this I am following the utilitarian argument of Peter Singer (1990, 1993) who evaluates experimentation on animals (and humans) on a case-by-case basis by balancing good and harm. The public in the Western world tend to follow this ethical principle in deciding what animal experiments are acceptable (Morris 2000), and our legislation is also based on this approach. Section 80(b) of the Animal Welfare Act 1999 is based on balancing harm to the animal and the general good that allegedly results from the experiment.

 I have therefore defined any experiment as "unnecessary" when the following conditions apply:

1. The experiments have no obvious short-term application.
2. The application is solely to achieve increased production or economic gain.
3. The same outcomes could have been achieved with little or no intrusive experimentation.
4. There is unnecessary duplication in experiments or number of animals used.
 

Agricultural experiments

Agricultural experiments constitute the majority of animal experiments in New Zealand (Bayvel 2000), and therefore make a major contribution to animal suffering.
 A survey of the New Zealand literature between 1996 and 2000 revealed 14 intrusive and unnecessary experiments on sheep internal and external parasites (Morris 2003) and 36 on other aspects of agriculture (Morris & Weaver 2003a). Among others, these include brain operations on sheep to discover what we already know, and inducing clinical parasitism into sheep after a major surgical operation .
 Rather than repeat the findings of my previous surveys, I have briefly described below some more recent intrusive experiments that have been published in the New Zealand Veterinary Journal or Australian Veterinary Journal. All the experiments below were performed in New Zealand, and thus would have had to pass muster by institutional Animal Ethics Committees (AEC) under the new Animal Welfare Act 1999, which came into force in January 2000.

 C. Morris et al. (2002) continued experiments on a line of sheep selected for susceptibility to facial eczema. This disease is preventable though at some cost (Radostis et al. 1994). Any experimentation with the aim of finding a cure therefore is strictly concerned with economics and not animal health. Another issue with the experiment is the choice of end point (Morton 1998). Thirty-four experimental sheep had a liver injury score of above 3 (over 60% of the liver damaged) and 4 had a liver injury score of 4. MAF (2001) lists experiments on facial eczema in its "severe suffering category".

 Girling et al. (2002) administered hormones to quail by means of a surgical operation, in an attempt to stimulate feeding. The birds were then killed by stunning followed by decapitation. The purpose of the experiment was simply to improve production in poultry. In addition, the researchers used the problematic approach of using quail as a predictive "model" for a different species (see discussion on medical experiments below)

 Gibson et al. (2002) tested an implant method for its efficacy in curing lameness (tendinitis) in horses, in spite of the fact that clinical data had already been published and cited by the authors. Horses were given an operation to induce lameness, and killed after 48 weeks. The authors noted that tendinitis can be cured by long periods of convalescence and rest, but that re-injury is common during training for race horses. The purpose of the experiment was to enable race horses to be more productive, and not to improve their health.

 MacIntye & Weston (2003) investigated the safety of calcium formate as a treatment for calcium deficiency in horses, although it is already known that this preparation can cause inflammation of the abomasum (Scott & Van Wijk 2003). Calcium deficiency can be treated with calcium chloride with no side effects, so again the purpose of the test was entirely commercial.

[Error deleted from here].

 Sutherland et al. (2002) used scoop dehorning on cows, although it is already known that this method is more painful than cauterisation (Petrie et al. 1996). Animals were also dehorned without anaesthetic to measure cortisol responses, though the authors themselves noted that the pain-relieving effect of a local anaesthetic is already known.
 

Medical experiments

Greek & Greek (2002) list five ways in which intrusive animal experiments are used in medical research . Animals can be used as:

1. "models" for human disease;
2. test subjects for drugs, toxins or surgical methods;
3. spare parts (e.g., heart valves);
4. factories (e.g., monoclonal antibodies, "pharming" operations);
5. for pure research.
 

Animals as predictive tools

For the first two applications, the usefulness of the results depends on the predictive value of the animal "model". It is assumed that a disease, disorder or traumatic effect in an animal is equivalent to the corresponding effect in a human, and furthermore that the animal and human will react in the same way to the same drugs, toxins or trauma.
 Since the anti-vivisection movement gained momentum over 100 years ago, physicians and scientists have claimed that the predictive model is false, that the differences between animals and humans are so great that any extrapolation from one to the other is useless. Such people have cited historical examples such as the thalidomide disaster to back up their claims. However, the animal experimentation industry have made equally strong claims for the usefulness of animal experimentation in curing illness.
 It is not possible to come to the conclusion that animal experimentation is useless on purely historical grounds unless one can know about the historical development of all fields of medicine where animals are used (an impossible task). For many years I was therefore forced to conclude that although there is much experimentation that is "wasteful and misleading" (Barnard & Kaufman 1997), there must also be some that is "vital to medicine" (Botting & Morrison 1997).

 Nevertheless, the fallacies inherent in the predictive model can be proved more conclusively on general scientific principles. LaFollette & Shanks (1994) point out that our assumptions about the validity of the animal model are based on the 19th Century scientific paradigm of Claude Bernard. These include a belief that equal causes produce equal effects, and a distrust of the statistical and largely anecdotal nature of clinical medicine. These beliefs, the authors propose, are now outdated. First, advances in statistical techniques have put clinical medicine on a more scientific footing, so that there is less necessity for animal experimentation. More importantly, complexity theory predicts that in complex systems such as living beings, a small difference in structure can result in vastly different effects (LaFollette & Shanks 1994; Kauffman 1995).

 Similarities in the genome between humans and chimpanzees, for example, may thus result in a similar structure in terms of gross morphology, but at the more complex cellular and biochemical level even the 1% difference between the genomes of the two species will manifest itself in vastly different biochemistry. Greek & Greek (2002) point out that diseases and drugs act at the cellular level, and provide empirical evidence to back up their assertions that the differences between even closely related species make any extrapolations between species meaningless. In fact in a complex system like the human body even extrapolations from adults to children or men to women have to be treated with caution, as shown by recent evidence that the opioid receptors in men and women react differently to pain killers (Gear et al. 1996).

 In addition, through studies of convergent evolution and natural selection we already know that organisms may evolve processes with the same function, but the causal mechanism by which this function is achieved may be vastly different. It is this causal/functional disanalogy that makes direct extrapolation of results between the species so unreliable (LaFollette & Shanks 1996).

 For an illustration of how the predictive model has been used in New Zealand, two examples will suffice.
 Papers obtained under the Official Information Act have revealed that The University of Auckland scientists are conducting "very severe suffering" tests on mice in an effort to test the efficacy and toxicity of anti-cancer substances. The scientific principle that animal "models" cannot be extrapolated to humans is backed up by empirical studies on cancer in rodents and humans. Drugs that were effective against human cancers did not work in mice 63% of the time (Greek & Greek 2002). Differences between the way tumours develop in rodents and humans have led pro-vivisectionist Anton Berns (2001) to conclude that genetically modified mice are "poor models of sporadic cancer". Professor Bruce Baguley at The University of Auckland has compared characteristics of cancer cell lines grown on mice with tumour cells, and has come to the conclusion that the results cannot be reliably extrapolated to humans (Baguley 2003). In his oral presentation, Baguley informs us that "new technology overrides the use of mice".
 The second example concerns work in progress by Dr Susan Schenk at Victoria University of Wellington. The AEC application forms obtained under the Official Information Act revealed that the AEC approved two experiments involving "moderate" to "severe" suffering on rats.

 In the first experiment, rats were made into alcoholics by forcing them to drink alcohol, and then their relapse behaviour after "cold turkey" treatment was studied under a variety of conditions. The second experiment involves administering the drug Ecstasy to rats and testing the effects on their short-, medium- and long-term memory. The experimental procedure included surgical operations, food deprivation and electric shocks.

 Given the complexity of relapse behaviour in human alcoholics and its multifactorial nature it is unclear why researchers believe any useful information can be gained by studying the disorder in an animal that does not naturally succumb to alcohol addiction. Similarly, the means of inducing addiction in the rats has no bearing on the complex psychological factors that lead to addiction in humans. In addition, the brain in rats is less complex than the human brain, and so any studies on memory loss are unlikely to have any relevance for human drug users. Rats only live for about 3 years, so long-term memory loss would be impossible to determine.

 Alcohol has been the most popular recreational drug of choice since the dawn of history, and there is no shortage of human studies on alcoholism. One suggestion for a less intrusive alternative use of research funding may be for researchers to firstly conduct a literature review. Gaps in knowledge could then be filled by designing experimental protocols around human volunteers or by an epidemiological study of both alcohol and Ecstasy abuse.

 Animal experimentation advocates are keen to cite studies that have shown similarities in the response of animal and humans (e.g., Harding 2003). However, the point about using animals as models is that it is not possible to know in advance which models will show similarities or what those similarities may be. Animal models have no predictive value and thus are misleading when used for medical purposes.

 Scientists are not keen to publish negative results, nor are journals keen to accept them. In addition, animal experimentation advocates are bound to concentrate on the few successes of the animal model, and ignore the many expensive and painful failures. The presence of counter-examples therefore does not refute the basic premise that direct extrapolation from animals to humans has no scientific validity, any more than the occasional accurate forecast in the newspaper horoscope column refutes the questionable nature of astrology as a scientific discipline.

Animals as spare parts or factories

One of the more common uses of animals (usually mice) in New Zealand is for the production of monoclonal antibodies. Mice are injected with an antigen together with an adjuvant, a molecule that stimulates an immune response. Cells producing the antibody are collected and fused with tumour cells to form a hybridoma. Another mouse is then used to grow a tumour producing the antibody, and this antibody is harvested by removing the peritoneal fluid.

 The procedure is far from painless. First, the injection of the adjuvant can cause abscesses and inflammation. Growing the tumour in mice is also stressful, as it results in a rapid filling of the body cavity (ascites). Continuous removal of the peritoneal fluid can also be painful (McArdle 2000). The US National Academy of Sciences (1992) recommends euthanasia for animals suffering from "abnormal tumour growth or ascites".

 Monoclonal antibodies can be produced without requiring live animals for tumour culture. At a series of workshops, the Alternatives Research and Development Foundation concluded that:
 

"There are a wide variety of in vitro methods available today that can produce more than 90% of needed monoclonal antibodies with quality, quantity and cost comparable to ascites" (McArdle & Lund 1999).

 A recent internet search revealed a number of commercial companies marketing monoclonal antibodies produced without the use of ascites. If New Zealand researchers are truly committed to the Three Rs, then a switch to in vitro antibody production should become a priority.

Animals in pure research

Scientists involved in pure research on the nature of living systems are using animals not as predictive models, but simply as a means of understanding basic biological principles. And it cannot be denied that a study of living animals has contributed to the knowledge of human systems, though generally only in the long term. Such experiments, unlike those which attempt predictions based on animal models, therefore have scientific validity.

 It is because we can never know in advance when a research project will yield something of value that some philosophers (e.g., Leahy 1991) advocate unlimited animal experimentation. However, such thinking assumes first that animals are of no moral consequence whatsoever, an opinion which is at odds both with public sensibilities and with the Animal Welfare Act 1999.

 Moreover, intrusive animal experimentation is not the only means of improving our understanding of living systems. Non-intrusive observations of animals, mathematical modeling and other analogues have also played a major part in scientific advancement. In the field of chronobiology, for example, early insights into biological rhythms were gained from non-intrusive observation of animal activity rhythms, mathematical modeling and studies of oscillations in chemical reactions. The knowledge gained from this research has proved valuable in the understanding of heart arrhythmia (Winfree 2001). If we do not know in advance the fruits of a research programme involving expensive and intrusive animal experimentation, then equally we do not know whether an alternative research programme involving non-intrusive work will prove equally or more valuable.
 All other things being equal, the ethical alternative should therefore be preferable. When considering allocating funds to research programmes to understand more about a human disorder, it would also be appropriate to seriously consider the cheaper option of investigating preventative strategies.

 For a recent New Zealand example to illustrate the above points I will discuss the work of Simon Malpas and his co-workers at The University of Auckland (Leonard et al. 2000; Malpas & Burgess 2000; Ramchandra et al. 2002). These researchers conducted "severe suffering" experiments on rabbits with the aim of understanding the role of the renal nerve in feedback control of blood pressure. The experiments involved intricate surgical operations to implant electrodes and cannulae.

 The authors discovered some interesting findings regarding blood pressure control, but they themselves admitted that the control in the rabbit was different from the dog. They did not explain why they thought the rabbit could provide a good predictive model for the human, but instead made some rather tenuous links stating that the findings "may eventually" produce a diagnostic tool.

 If a utilitarian approach is taken to animal suffering, then it makes sense to consistently apply the utilitarian principle and make a cost-benefit analysis for all possible uses of research funding. In this regard, the authors provided no justification or comparative figures on the number of lives that could be saved through their long-term project, compared with other ways the funding could have been used to improve human health. It should be remembered that high blood pressure is largely a treatable disease, and funding may have been better utilised in making better use of the treatment programmes already available.

 In these proceedings, Malpas et al. (2003) describe how their work on developing methods of monitoring physiological signals in animals without wires have applications for use on humans where the removal of wires could be beneficial. I do not dispute this conclusion. However, it remains to be determined whether animal research was essential to this development. In order to justify animal use and make a more informed decision based on a cost-benefit comparison, AECs need to be provided with more discussion on the efficacy of using human volunteers in a clinical setting or some other non-intrusive alternative to generate the same outcome.

Vertebrate pest control

The most significant pest in the country is without doubt the brushtail possum. This pest causes massive environmental damage, is believed to directly predate on native birds and is the main reservoir for the spread of bovine tuberculosis (Tb) (Montague 2000).
 When making a decision to eradicate possums, their lives and welfare need to be balanced against those of cattle infected with Tb, native birds and the general health of the environment. The public also generally accepts that possums need to be eradicated, though there is also concern that such eradication must be humane (PCE 2000; Wilkinson & Fitzgerald 2001).

 Experiments involving possum eradication and control generally centre around finding vaccines for bovine Tb, testing traps and poisons, and ways of controlling possums through immunocontraception or other ways of disrupting their reproduction.
 Some bovine Tb experiments involve using a guinea pig as a "model" for the cow in order to test vaccines (Morris & Weaver 2003b). Such experiments, many of which involve "severe" suffering, display the same shortcomings discussed under the "medical experiment" section, namely the inability to extrapolate from one animal to another when using them for predictive tests.

 Other experiments involve testing new poisons for effectiveness and humaneness. Such experimentation would be excusable if it could genuinely lead to improvements in possum control or welfare. Too often, however, such experimentation is performed in laboratory conditions with poisons administered in ways that would not be possible in the wild (Morris & Weaver 2003b). The utility of such experimentation is unclear, and at the very least needs to be justified fully before an AEC gives permission to go ahead.
 One type of experiment that could be of use in improving the welfare of possums is research into an immunocontraceptive, or other means of disrupting the reproductive system of the possum. This is arguably the most humane means of possum control (Singer 1997), and, furthermore, the public is generally in favour of this type of control (PCE 2000). Before this can be achieved, however, a phenomenal amount of basic research is required, much of which will involve intrusive experimentation (Eckery 2003), though this could be minimised with judicious use of painkillers so that the suffering does not rise above "moderate" level as described in the MAF (2001) criteria.
 

Conclusion

In this conference, participants have been making emotive appeals about children dying of cancer or rare diseases, and the role of animal experimentation in preventing this (Palmer 2003; Smith 2003). Such appeals are purely speculative and do not make any mention of human lives that could have been saved if funds were used in more productive human-based research and not scientific blind alleys. In my own oral presentation I raised a question (admittedly also speculative) on how many babies could have been saved if we had made earlier use of research funding for epidemiological work on sudden infant death syndrome (SIDS or cot death), rather than squander it on animal experiments. It was epidemiologists, not animal experimenters, who unearthed the risk factors associated with cot death, thereby greatly reducing mortality from this syndrome (Davidson-Rada et al. 1995).

 Emotive arguments can be used to great effect by both sides in the debate, but the central argument on the necessity of animal experiments is one of ethics and science, not speculation. The case can be made that most animal experiments are unnecessary, not only according to the standards of idealist animal rights activists but by the standards of public sensibilities as reflected in legislation. Animal experimentation could be vastly reduced if the justification for using animals was based on sounder science and a more rigorous examination of alternative uses of funding.

 If this was done, some experimentation may still be justified, for example, experiments on possums or other vertebrate pests for control purposes, and some experiments on animal vaccines. These could be conducted with sufficient care to ensure that adequate anaesthesia and analgesia are provided and that the experiment is terminated before the level of suffering becomes too great (Morton 1998). If this is done, there should be no need for any suffering to be more than "moderate". I therefore look forward to a future in New Zealand where, at the very least, the "severe suffering" and "very severe suffering" categories become a thing of the past.
 

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