Animal Aid

The 'animal model' in medical research

'While animal experimentation is commonly credited by its own industry as responsible for nearly every discovery, time and again animal studies have merely mimicked what was originally observed in humans (6).'

Using animals as 'models' for the study of human disease is bad science. Any veterinary surgeon knows that there is a wide variation between drug responses in dogs and parrots, because of species differences. It is, therefore, not difficult to understand why the results of animal tests cannot be extrapolated to human beings with any degree of confidence. Medical scientists now admit that it is no longer safe to prescribe 'adult label' drugs to children. Equally, one twin may react to a drug in a different way from the other (7). If it is dangerous to give adult-only medicines to children, and twins exhibit different reactions, how can we justify extrapolating the results from animals to human beings?

Drug failures

According to a report in the British Medical Journal (8), a staggering five per cent of all hospital admissions are due to adverse drug reactions (ADRs). Two per cent of patients admitted with ADRs actually die. This translates into an overall mortality rate of about 18,000 people a year, more than treble the number killed in road traffic accidents and the fourth leading cause of preventable death in the UK. In financial terms, the cost of ADRs to the NHS is estimated at nearly £500 million annually. Since animal experiments constitute such an integral part of the pre-marketing 'safety screening' of all medical drugs, it is clear that they are not providing the right answers.

'Most adverse reactions which occur in man cannot be demonstrated, anticipated or avoided by the routine sub-acute and chronic toxicity experiment [in animals] (9).'

'The best guess for the correlation of adverse reactions in man and animal toxicity data is somewhere between five and 25 per cent (10).'

The case against animal experiments has been made all the stronger by evidence presented by the Department of Health (DoH) to the House of Lords Select Committee inquiry into Animals in Scientific Procedures, whose findings were published in July 2002. As part of its evidence-gathering, the Committee asked the DoH to provide published scientific papers that support the validity of toxicity tests on animals. One of the papers (11) actually lists several reasons why data obtained from animals is usually not predictive of human effects. Among the cited difficulties is that 'the lifespan of humans is from 4.4 to 66 times that of common test species. Thus, there is generally a much longer time available for toxic effects to be expressed or developed in people than in test animals.' Another of the DoH-endorsed papers reported that, in an assessment of 114 cases of adverse drug reactions seen in humans, only six could be demonstrated in laboratory animals - and then, only in retrospect (12). Yet another DoH-submitted report acknowledged that common side effects such as headaches, visual disturbance, dizziness and nausea are all difficult to detect in animals (13).

Even the 'best' animal model, the monkey, fails to predict human response time after time. Isoprenaline doses (for asthma) were worked out on animals, but proved too high for humans. Thousands of people died as a result (14). Carbenoxalone (for gastric ulcer) caused people to retain water to the point of heart failure. Scientists retrospectively tested both these failed drugs on monkeys to see if they could reproduce the adverse effects that had shown up in humans, but could not (15). The chimpanzee, our closest living relative, is essentially immune to AIDS, hepatitis B and common malaria - diseases which kill millions of people throughout the world every year. Unsurprisingly, therefore, the first five-year trial of an HIV vaccine, 'Aidsvax', based on successful tests in chimpanzees, was pronounced a failure (16) when it was found that 8000 high-risk volunteers in the human trial were not protected from HIV infection by the vaccine.

Heart disease and stroke

The most common cause of heart disease in people is atherosclerosis (fat deposition on artery walls), which may lead to clogging of the blood vessels and heart attacks. Dogs are often the model of choice for research into heart disease although 'it is virtually impossible to produce atherosclerosis in a dog (17).' Naturally-occurring strokes are extremely rare in animals. In humans, most strokes occur as a result of atherosclerosis in the blood vessels supplying the brain. Since there is no good animal model in which to reproduce this condition, researchers induce artificial strokes in rats, cats and monkeys by tying off or blocking arteries in their brains (18).

Cancer

There are more than 200 different types of cancer in humans, many of which have been 'replicated' in animals by exposing them to carcinogenic chemicals, radiation, cancer-causing viruses, by injecting them directly with tumour cells, or by inserting genetic material associated with the growth of cancers. Thomas E. Wagner, senior scientist at Ohio University's Edison Biotechnology Institute, remarked: 'We've cured mice of all sorts of tumors. But that isn't medical research (19).' And according to Dr Albert Sabin, developer of the polio vaccine, 'Giving cancer to laboratory animals has not and will not help us to understand the disease or to treat those persons suffering from it ... laboratory cancers have nothing in common with natural human cancers (20).'

In fact, the use of animals in the search for cancer drugs has been a costly failure. In the USA, the National Cancer Institute (NCI) has screened some 500,000 chemicals in animals, with a reported success rate of 0.0001 per cent (21). In 1998, Dr Richard Klausner, Director of the NCI, admitted:

'The NCI believes we have lost cures for cancer because they were ineffective in mice (22).'

Diabetes

Type I diabetes mellitus is a condition typically appearing in childhood. Rodent models of the disease are produced by injecting the animals with a chemical called streptozotocin, which damages the insulin-producing cells in their pancreas. But 'diabetic' rats and mice bear little relation to humans with diabetes, in that they do not always require insulin to survive.

Some of the animal models will not even have raised levels of glucose in their blood - a hallmark of the human disease. Also, hereditary factors are responsible for a significant number of insulin-dependent diabetics, and these cannot be reproduced in a laboratory animal. The best available rodent models for type 1 diabetes do not develop the long-term complications that constitute the major clinical problem in patients. Regardless, many researchers are studying numerous animal models, even while acknowledging that 'they differ markedly from the human disease (23).'

Unsurprisingly, drug catastrophes result from such animal-based studies. Rezulin, which was launched on to the market in 1997 after its success in treating 'diabetic' animals, was withdrawn three years later when it was found to cause liver failure and had killed several hundred people (24).

Disorders of the brain and the nervous system

Brain and nervous system conditions are varied and often extremely complex. They include such problems as migraine, dementia and epilepsy. Most of these disorders are unique to human beings. The most dramatic difference between humans and other species, including the great apes, is found in the central nervous system. Our brain is four times larger than that of a chimpanzee, which is four times larger than that of a macaque monkey. The human brain is enriched with specific cell types implicated in communication, language, comprehension and autonomic functions. Using much smaller, and less complex, monkey brains to study human neurological disease makes no sense. 'For cortical regions [in the brain], such as the language areas, we cannot use the macaque brain even as a rough guide as it probably lacks comparable regions (25).'

Neurological disease

Inevitably, the attempt to model human neurological conditions in primates is a sorry saga of bitter failure. Parkinson's disease becomes progressively worse in patients, while the chemically-induced marmoset version demonstrates gradual recovery (26). Brain-lesioned marmosets used in the study of Huntington's disease do not replicate the pathology or symptoms of the disease (27). Countless treatments for stroke have been developed in primates and other animals - yet all of them have failed and even harmed patients in clinical trials. 'Over-reliance upon such animal models [for stroke] may impede rather than advance scientific progress in the treatment of this disease (28).'

Mental illness

If researchers believe that animals are capable of experiencing the same kind of complex emotional stresses that give rise in people to conditions such as anxiety disorders, depression and schizophrenia, then they should not be experimenting on them in the first place. Yet animals continue to be brain-damaged and subjected to trauma, despite the fact that there are already many people suffering from these disorders who could reveal an abundance of relevant information if their cooperation was sought for non-invasive research.

Safety testing and public health

Regulatory authorities insist that new substances - ranging from pesticides and food additives to medical drugs - undergo 'safety testing' on rats, mice, dogs and other animals before being allowed onto the market. This is done by applying chemicals to animals' skin, by force-feeding directly into the stomach, or by making them inhale toxic fumes through a mask. Alternatively, the chemicals may be mixed with the feed, or injected by syringe into the body. If the test chemical happens to be highly toxic to the particular species of animal used, they may die slow, painful deaths. Often, the end-point of such testing is to see how many animals actually succumb to a given dose. At present, more than 30,000 chemicals have not undergone rigorous safety testing, according to the EU. In October 2003, the European Commission presented its new testing strategy - REACH (Registration, Evaluation and Authorisation of Chemicals). Implicit in the proposal is the use of millions of animals in lethal toxicity tests - tests that cause enormous suffering for the victims and provide no protection for human consumers. Modern biology has provided the tools necessary for species-specific toxicity testing at the cellular and molecular level. This is now being recognised, and indeed encouraged, by some government authorities, such as the US Food and Drug Administration (29).

Surgery

New calls from the medical profession to allow surgeons to practise on animals before being allowed to operate on human beings represent a backward step (30). The distinguished pioneer surgeon, Sir Lawson Tait (1845-99), a fellow of the Royal College of Surgeons, who developed several well-known surgical techniques still in use today, roundly condemned animal experiments, saying that they would serve only to mislead the surgeon. Just as any veterinary surgeon knows that dog bones and muscles handle very differently from those of a cat, so it follows that everything a trainee medical surgeon 'learns' on animals will have to be unlearned when facing human patients.

So how do trainee surgeons learn, for example, to remove an appendix?

'The aspiring surgeon should enter a training programme with competent senior surgeons who will see to it that the trainee is given gradual (very gradual) surgical assignments under their close tutoring and scrutiny (31).'

Animal experimentation and veterinary research

Those still in favour of animal research often claim that, if it were to end, animals themselves would suffer, as no cures or treatments would be found for their diseases.

Using dogs to study dog diseases makes scientific sense. Using dogs (or other animals) to study human diseases does not. However, even with the intention of finding treatments for dogs, we should not experiment on healthy animals and deliberately make them sick. We should, instead, study dogs who are already sick, and try to help them with therapies that have shown promise in the laboratory.

The fundamental principle should be to make as much use as possible of all the relevant research methods, to the point where, having exhausted every avenue, there is no other option but to try the experimental drug or therapy on a living animal who is already sick. This ethical groundrule should apply no less to humans as it does to animals.

GM animals and medical research

Trends indicate a growing use of GM (genetically modified) animals in research. Between 1990 and 2003, the number of experimental procedures involving such animals increased from 50,000 to more than 750,000. (32).

Animals have been genetically manipulated in an attempt to mimic many different human diseases (e.g. diabetes, atherosclerosis, asthma, cystic fibrosis). There are major animal welfare problems associated with the production of GM animals. In order to create a new strain of mice, (the most frequently used species), young females are injected with powerful hormones to make them ovulate in excess. After mating, they are killed to extract the embryos, which are microinjected with the foreign DNA. These altered embryos are then surgically implanted into many surrogate mothers who have also been hormone-injected to assist implantation and who will later be killed just before or after giving birth. For every 'successfully' produced GM animal, hundreds either die in the womb or soon after birth, or are killed as unwanted surplus. Even when the desired result is obtained, the GM animal will suffer from a host of unintended ailments, ranging from arthritis and heart defects, to premature ageing.

The most common types of genetic manipulations are transgenic (animals with added genes) and knockout (animals with genes deleted). Inbred strains are also specially developed to exhibit particular genetic effects. From a scientific perspective, using GM animals produces results that are no more reliable than those obtained from ordinary animal experiments. Although the research is focused on the activity of one or more genes, these do not exist in a vacuum. Inside the cell, the gene will interact with other genes, proteins and various cell factors. Because these interactions are unique for every species of animal - humans included - it is not possible to extrapolate results from one species to any other.

Another complicating factor is the existence of structural as distinct from regulator genes. While the former are responsible for the production of new cell products, the latter turn structural genes 'on' or 'off', thereby regulating the amount of cell product manufactured. Once again, these activities are very species-specific. This would explain why, for example, none of the current 'cystic fibrosis' mouse strains accurately replicate the human condition, in which the major symptoms are excess mucus in the lungs, leading to lung infections.

The GM mice, in contrast, suffer principally from bowel disorders and are clearly not a very helpful model of the disease (33). Mice lack mucus secreting cells. Therefore, lung disease is mild and infrequent (but up to 90 per cent fatal in humans). Other conditions studied in GM mice include various forms of cancer, muscle development, neurological disorders, asthma, obesity, diabetes and cardiovascular disease (34).

Weapons testing on animals - the battle goes on

The number of animals used in weapons research in British laboratories tripled between 1997 and 2002, from 4,500 to more than 15,000.

They were poisoned by chemical warfare agents, subjected to blast injuries, dosed with sensory irritants, killed by bacterial toxins and deliberately wounded. Most of this research took place at the Ministry of Defence establishment at Porton Down in Wiltshire. Guinea pigs, rabbits, mice, dogs, rats, sheep, pigs, goats and monkeys were amongst the species used.

Pig experiments

Pigs are a particularly popular choice for weapons research. In one experiment at Porton Down, ten female Large White pigs were used to test the effects of Phosgene, a highly toxic gas. The animals were anaesthetised and exposed to the gas for varying lengths of time. Most died from severe lung damage. Those who survived were euthanased at the end of the experiment (35).

Pigs have also been used to study physiological shock and peritonitis (severe and life-threatening inflammation of the abdominal cavity, often associated with gunshot wounds). In one experiment, 17 animals were anaesthetised and then subjected to massive blood loss by the withdrawal of 40% of their blood volume. Peritonitis was induced by the deliberate placement of sepsis-causing bacteria within the abdomen. The animals were subsequently resuscitated with intravenous fluids and various drugs. The anaesthetised pigs were monitored for 24 hours. Those still alive after this period were subsequently killed (36).

Private sector killing

In addition to the labs at Porton Down, a facility at Alverstoke, Hants, has used goats in simulated dives, employing a dry pressure chamber. These tests are defended on the grounds that they provide advice for submariners on escape procedures from crippled underwater vessels. Between 1993 and 1998, more than 700 goats were subjected to extremely painful and often lethal decompression experiments. Animals who survived were used in further tests.

Gulf war syndrome

Many experiments have taken place at Porton Down, following a range of debilitating and life-threatening diseases reported by veterans of the first and second Gulf Wars. These have included tumours, brain and respiratory disorders, and birth defects in their children. Marmoset and rhesus macaque monkeys are among the species widely used in an attempt to test whether the combination of vaccine jabs and anti-nerve damage tablets given to troops resulted in Gulf War illness.

A senior UK government scientist indicated that the monkey tests did not suggest any problem for the troops (37). In sharp contrast, US scientists found a clear link between exposure to toxic chemicals and Gulf War syndrome (38). This difference highlights the 'alibi' role of animal tests. They can prove or disprove virtually anything to suit the aim of the experimenters.

Despite repeated official statements that weapons research on animals is essential to protect frontline troops, the government has effectively disowned their own men and women in uniform - refusing to recognise that their ill-health could be Gulf-linked.

Click here for part 3 of Bad Ethics, Bad Science, in which we look why animal experiments persist, outline the alternatives and draw our conclusions.