Animal Aid

BRED TO SUFFER - Full report

Photo by Iain Green

The full version of the Bred to Suffer report is available in its entirety below.

We humans suffer from a multitude of diseases and disabilities; some inherited, some induced by our lifestyle or environment, some acquired through infection and others just appearing spontaneously or through accident or injury.

The major causes of premature death in the western world are often called 'diseases of civilisation'; meaning that they are attributable to our modern lifestyle of poor diet, lack of exercise and environmental pollution. The 'big three' are heart disease, cancer and stroke.

The major causes of death in the 'developing world' are still infectious diseases and malnutrition; both being a consequence of poverty and inadequate living conditions, including lack of food and clean water.

In the west we no longer suffer (in such numbers) from diseases of poverty, such as TB, cholera, typhoid, diphtheria and dysentery, thanks entirely to improvements in our housing, sewerage, water supply and diet. (1,2) Instead, we are now suffering an epidemic of heart disease and cancer, whose massive growth can be clearly correlated with the rise in intensive farming and meat consumption following the Second World War. We could halve these deaths through dietary changes alone; in fact 80-90% of cancers are preventable. (3) Pesticides and other chemical pollutants contribute to the burden of cancers and other health problems. The Department of Health has estimated that up to 24,000 people in the UK every year may die prematurely because of air pollution. (4) Clearly our national health could be transformed through a range of disease prevention measures.

Sadly, though, we seem to prefer to become ill and then look to high-tech medicine for a cure. There is no shortage of patients to study and learn from, but in a catastrophic neglect of reason, we turn to animals for answers instead. Forgetting the biochemical and physiological differences between animals and ourselves, which have led to so many drug disasters, (5) we look to deliberately damaged animals to help solve human ills from which they do not even suffer in any equivalent way. The idea is to recreate symptoms of human disease in animals in order to use them as 'models' of our diseases and then find ways to cure them.

Which diseases?

Animals are used to mimic aspects of heart disease, cancer, arthritis, diabetes, cystic fibrosis, Alzheimer's and Parkinson's disease, epilepsy, AIDS, depression - in fact there is a 'model' for almost every conceivable human ailment.

Do animals naturally suffer from any of these diseases?

Not in any comparable way to humans. They are susceptible to various cancers but their tumours are different from ours in many important respects. According to Nobel laureate Renato Dulbecco, 'If we wish to understand human cancer, the [research] effort should be made in humans because the genetic control seems to be different in different species.' (6)

So how is disease induced in animals?

Animals are either physically or chemically damaged to produce some of the symptoms of the disease or, increasingly, they are specifically bred with a genetic defect which causes them to display one or more characteristics of the disease. Usually this involves 'knocking out' a gene, or inserting one from a human or another animal: the resulting animal is thus 'transgenic'. We will begin by looking at physically-induced models and then go on to consider transgenic models and the particular problems they face.

Physical/chemical manipulation

Heart disease

The most common cause of heart disease in people is atherosclerosis (cholesterol deposition on artery walls). This leads to bottlenecks in blood flow, thereby restricting oxygen supply, raising blood pressure and, ultimately, culminating in a heart attack.

Dogs are often the model of choice for research into heart disease although 'it is virtually impossible, for example, to produce atherosclerosis in a dog' even when vast amounts of cholesterol and saturated fat are added to their diet. (7) To imitate this condition artificially, the coronary arteries are tied around with wire (8) or blocked by plastic plugs. The most obvious cure for the condition in humans is to lower cholesterol levels but this would clearly have no effect in such a model, which is therefore of no real relevance.

Congestive heart failure is a gradually worsening disorder in humans. It is rapidly and artificially induced in dogs by giving them a series of heart attacks (by electrical over-stimulation) until their heart muscle is significantly weakened. Then they are given another heart attack to see if they respond differently from healthy dogs, who are also made to suffer an induced heart attack. (9) The results cannot be meaningfully applied to humans because the cause, as well as the nature, of the damage is completely different. Conscious baby rabbits are also given heart attacks to see if various drugs given beforehand may protect them. (10)

Dogs are also used to investigate changes in blood pressure, for example in experiments at Leeds University in 1998 where the blood of nine dogs was circulated out of their opened chests, so that the pressure could be rapidly altered. (11) The earth-shattering conclusion drawn was that bending down and then suddenly standing up could cause a person to feel dizzy or faint. These experiments were funded by the British Heart Foundation.

The British Heart Foundation is also trialing drugs to prolong the survival of bypasses, which often succumb to a build-up of scar tissue, causing their eventual failure. These experiments are conducted on human veins in culture, yielding results that will be directly applicable to patients. Perversely, the same researchers are also performing major bypass surgery on pigs to test the drugs' effectiveness, but the biochemical mechanisms involved have been shown to be quite different in pigs. (12)

Of course, a great deal of heart disease is avoidable and the money spent on such expensive treatments as bypass surgery would be far more profitably invested in strategies such as health and nutrition education. According to the National Heart Forum, if current knowledge were put into effective policy action, death and disability from avoidable coronary heart disease among people under 65 could be virtually eliminated. 'Inaction now creates a public health time bomb for future generations.' (13)

Stroke

Naturally occurring strokes are extremely rare in animals. In humans, strokes are 'brain attacks', much like heart attacks, where blood vessels in the brain become blocked by a clot or an atherosclerotic plaque (cholesterol build-up). The cause is usually high blood pressure (also high cholesterol, diabetes and smoking) and it takes years or decades to develop.

Artificial strokes are induced in cats by blocking arteries in their brains, (14) which clearly gives no useful insight into the cause of a stroke. Neither does it give useful information about the effects, because the cerebral blood supply of cats (and most animals) is quite different from that of humans; there being a large reservoir that humans do not possess.

At London's Guy's, King's College and St. Thomas' Hospitals School of Medicine, five squirrel monkeys and eight cats were subjected to open-skull experiments for over five hours, under very low-level anaesthesia, to investigate a phenomenon that has been observed in animal models of strokes but that probably does not even occur in humans. The researchers found such confusing variation, they concluded that it is unsurprising that clinical trials of stroke medications based on animal models 'should have proved unsuccessful to date'. (15)

The damage caused by a stroke can be reduced if treatment is received quickly enough, and MRI scanners are proving invaluable in locating the damage so that it can be treated. All the currently accepted treatments, such as anti-clotting medications, have been identified in people, while animal experiments have an abysmal record in predicting useful treatments. For example, barbiturates protect monkeys, dogs, rabbits and gerbils against the effects of a stroke but have no protective effect in humans. (16) Conversely, the calcium-channel blocking drug nimodipine has no beneficial effect in cats or baboons but can be beneficial in people. (17) Researchers at the Mayo clinic concluded that 'over-reliance upon such animal models may impede rather than advance scientific progress in the treatment of this disease'. (18)

Again, prevention is far more valuable than cure, and most strokes could be avoided by improvements in diet and exercise. In fact, it has been calculated that the incidence of strokes could be cut by 39% by a daily reduction of 3 grams of salt in an individual's diet. (19)

Cancer

There are over 200 different cancers in humans, many of which have been 'replicated' in animals by exposing them to carcinogenic chemicals, radiation, onco-viruses or by injecting them directly with tumour cells or inserting some of the genes involved.

But, even in supposedly equivalent cancers, there are major differences between species that invalidate the models. For example, colon cancer affects the large intestine in humans but the small intestine in rats. These tumours do not spread in rats but kill them by obstructing the colon. In humans they kill by metastasizing (spreading) to other places in the body. These are dramatic differences, which negate the worth of any treatments or cures found to be effective in animals.

In fact it is true to say that the lack of success in finding treatments for cancer in humans is because the research effort has been concentrated in animals. Thomas E. Wagner, senior scientist at Ohio University's Edison Biotechnology Institute, remarked: 'God knows we've cured mice of all sorts of tumours. But that isn't medical research.' (20) 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.' (21)

Over a quarter of a million animals were used for cancer research in Britain in 2000. Ninety six per cent were mice; the others were rats, guinea pigs, hamsters, rabbits, dogs, pigs and sheep. The Cancer Research Campaign, the Imperial Cancer Research Fund (now merged as Cancer Research UK) together with the Medical Research Council fund much of the research. Even the UK Co-ordinating Committee on Cancer Research (the umbrella organisation distributing funds to the research charities) admits that 'animals with local or disseminated tumours are likely to suffer pain and/or distress'. (22)

For example, researchers are currently subjecting hairless mice to restraint under a sun-lamp three times a week for several months at a time so they can measure the development of skin tumours with or without olive oil application to their sore skin, to see if olive oil can protect them against skin cancer. (23) Not only do the mice suffer the pain of rapidly developing malignant melanoma, but they also have to endure repeated heat distress, which continues even after their cancer has become aggressive and life-threatening.

When it comes to curing these experimental tumours, the animal models turn out to be of little value. For every 30-40 drugs effective in treating mice with cancer, only one is effective in people. (24) This problem is inherent in all research using animals because 'for the great majority of disease entities, the animal models either do not exist or are really very poor'. (25)

Cancer research is especially sensitive to differences in physiology between humans and other animals. Many animals, particularly rats and mice, synthesize within their bodies approximately 100 times the recommended daily allowance for humans of Vitamin C, which is believed to help the body ward off cancer. (26)

Indeed, animal responses to human carcinogens are so different from ours that it took 50 years to induce lung cancer in laboratory animals forced to breathe tobacco smoke, (27) thus delaying the health warning to humans and resulting in millions more unnecessary deaths. The following words from Dr Irwin Bross, former Director of the largest cancer research institute in the world - the Sloan-Kettering, say it all:

'While conflicting animal results have often delayed and hampered advances in the war on cancer, they have never produced a single substantial advance either in the prevention or treatment of human cancer.' (28)

We know that 80-90% of cancers are preventable and yet, instead of investing seriously in preventive measures, we continue to fund research into animal cancers which will never have any relevance for the human animal and its unique diseases.

AIDS

Tens of thousands of primates and other animals, notably cats, have been consumed in AIDS research over the past 20 years. This is despite the fact that infecting animals, even chimpanzees, with HIV does not produce an equivalent disease to human AIDS.

The immune systems of different primate species are so diverse that data from one species does not even translate to another species, much less to humans. 'SIV (simian immunodeficiency virus) in monkeys is not the same as HIV in humans.' (29) This has long been recognised by many in the research community and by AIDS activists, who have campaigned hard against futile vaccine research in monkeys. Leading AIDS researcher Dr Mark Feinberg puts it thus, 'What good does it do you to test something [a vaccine] in a monkey? You find five or six years from now that it works in the monkey, and then you test it in humans and you realise that humans behave totally differently from monkeys, so you've wasted five years.' (30)

Everything we know about HIV and AIDS has been learned from studying people with the disease, through epidemiology and in vitro research on human blood cells, which is where the virus operates and, therefore, where it needs to be studied. 'It is now clear... that a strategy for an effective HIV vaccine can be devised only with a thorough understanding of the biology of HIV and the immunopathogenesis of AIDS.' (31)

According to Dr Ray Greek, President of Americans For Medical Advancement, 'Far too frequently animal models have been used to develop vaccines that are effective in laboratory animals but are ineffective, or worse, harmful in humans. AIDS is a terrible illness, and research money and personnel need to be directed toward methodologies that are viable. Using an archaic methodology like animal models to combat a 21st century disease is more than foolish, it is immoral.' (32)

Arthritis

In arthritis research, animals are injected in their joints (with collagen or various other substances) to produce the painful swellings and destruction of cartilage and bone that is characteristic of the disease. The usual subjects are rats, mice and rabbits, but sheep and dogs are used too. The extent of swelling (e.g. of a paw or knee) and its temperature are monitored. The degree of pain is also measured by various assays, including the speed of response to noxious pressure, a needle or hot-plate applied to a paw.

Because the idea is to find drugs to relieve the pain or swelling, the animals are force-fed these candidate substances. Alternatively, they are injected into their spine or swollen joint. After weeks of such misery, the animals are killed to assess the effectiveness of the treatment.

For example, scientists at the Kennedy Institute of Rheumatology in London operated on beagles to surgically induce symptoms of osteoarthritis, which was then allowed to develop for six months until the dogs were killed for analysis of their cartilage. (33) Even one of the scientists conducting the research acknowledged that animal cartilage differs from human cartilage in important ways and that studying human surgical specimens is preferable. (34) There is no shortage of these!

Rheumatoid arthritis is an autoimmune disease whereby the body's own immune system attacks cartilage and bone cells. Recent research has shown that the biochemical mechanisms involved are quite different in rats from those in people, meaning that the rat 'model' is not suitable. (35)

Diabetes

Type 1 diabetes is an autoimmune disease appearing in childhood, which necessitates insulin injections up to four times a day for life.

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 require insulin to survive. Some 'models' do not even have raised levels of glucose in their blood - a hallmark of the human disease. Regardless, many researchers are studying numerous animal models, even while acknowledging that 'they differ markedly from the human disease'. (36)

There are long-term complications in diabetes, including cataract formation, leading to blindness - itself the subject of further study in animals. The Royal National Institute for the Blind used to fund such research but now only conducts human-based research; an acknowledgement of the invalidity of the animal 'models'.

The more common Type 2 diabetes usually affects overweight people later in life. Dramatic improvements in their condition can be made through dietary control and exercise, which can also significantly reduce the chances of getting the disease in the first place. Its incidence is projected to double in the next ten years, so the need for preventive strategies is urgent. Sadly, research into these important factors has been neglected in favour of the search for treatments effective in animals. One such medication, Rezulin, was launched onto the market in 1997 after its success in treating 'diabetic' animals, only to be withdrawn three years later when it was found to cause liver failure and had killed 391 people. (37)

Brain disorders

Neurological conditions such as Alzheimer's and Parkinson's diseases are particularly amenable to study in conscious human patients using non-invasive scanning techniques such as MRI, PET and CAT scans. These remarkable techniques are able to show the healthy or diseased brain (or other organs) in action while performing a variety of cognitive tasks. Donated brain tissue from patients who have died, but wanted to help research into the condition they suffered, is also extremely useful to researchers. The Humane Research Trust funds work using human neural cell cultures at the Cambridge Brain Bank at Addenbrooke's Hospital.

Despite these technological advances, animal models of ageing and associated neurological disorders are a large and rapidly growing area of research worldwide. The following experiment is a recent example from Japan:

In order to test a theory that chewing may help prevent short-term memory loss in old age, researchers extracted the molar teeth from mice who had already been engineered to develop signs of human ageing, such as hair loss, cataracts and failing memory. (38) The mice were then made to swim in a water maze to see if they could remember the way to a hidden platform. They were then killed so that the extent of deterioration in their brains could be examined.

At Cambridge University, marmosets were repeatedly injected into the brain (ten times) with destructive, seizure-causing chemicals. Then they were injected with drugs that made them spin uncontrollably in their cages, up to 300 times in an hour. They were also timed while they bit sticky labels from their feet, or reached for objects with one arm plastered to their side. The researchers claim their intentions were to advance treatment of Huntington's Disease, even while admitting that the brain damage they inflicted 'did not replicate the pathology or the symptoms of Huntington's Disease'. (39)

Marmosets are also popular in 'Parkinson's research' even though their brains do not develop Lewy bodies, a generally recognised marker for the disease in humans. At Guy's, King's and St. Thomas' School of Biomedical Sciences in London, 18 marmosets were brain-damaged to 'mimic' Parkinson's Disease and then treated with a range of drugs, which elicited reactions opposite to those produced in rats. The researchers admitted 'the reason for this conflicting result is unclear'. (40) Yet it is very clear to anyone who understands that data cannot be extrapolated from one species to another. In order to avoid such conflicting results, research must be conducted in the species of interest.

One thing we can be sure about is that the causes, progression and manifestation of neurological ailments in humans are far too complex and multifarious to model in animals in such a crude and barbaric fashion.

Recent epidemiological studies suggest a link between Alzheimer's disease and consumption of dairy products. (41) Other research shows a link between garden pesticide usage and Parkinson's disease. (42) Surely these are the types of enquiry we should be pursuing, rather than generating spurious data in animals.

Mental illness

Mental illness is perhaps even more complex than age-related neurological degeneration; being extremely variable between individuals in both cause and presentation.

If researchers believe animals are capable of experiencing the same kind of complex emotional stresses as people, they should not be experimenting on them in the first place. Yet this is indeed the basic premise of such wilfully cruel experiments as separating young animals, including primates, (43) from their mothers at an early age. The deliberate intent is to cause them stress and induce symptoms of schizophrenia and other disorders for further study.

For example, rat pups were removed (temporarily) from their mothers at the age of nine days and then subjected to sudden loud noises for the next three months to assess their 'startle response' with or without anti-psychotic drugs. (44) These animals are intended to serve as 'models' of schizophrenia, but the very idea of studying such conditions in animals is patently absurd. Schizophrenia manifests as speech disturbances, delusions and hallucinations. How can these problems be diagnosed in animals?

Anxiety disorders have been 'modelled' in rats at Nottingham University by rearing them in isolation and then monitoring how readily and aggressively they fight when brought together. (45) Lifelong pairs of gerbils have been separated at Leeds University 'in order to model depression in divorcees'! (46)

Many animals, particularly monkeys, have been deliberately brain-damaged over the years to monitor the effects on their behaviour and mental state. Many psychology researchers themselves have asked questions such as 'is the infliction of so much pain and terror warrantable?' (47) Such callous 'research' can clearly have little relevance for humans, plenty of whom are suffering these various disorders and who could reveal an abundance of information for study if they were only asked.

For example, MIND has been conducting a fascinating 'food and mood' project, (48) which is revealing much about how diet can affect our mental wellbeing - even showing there can be a link between wheat and dairy consumption and some cases of autism. It has long been known that different foods can affect our mood, but that has not stopped researchers from removing the adrenal glands of rats, severing their sympathetic nerves and starving them for four days before killing them to analyse their tissues. (49) All this to show that mood can be affected by diet - something that was already known through direct observation of people.

Brain injury

There is, unfortunately, no shortage of human accident victims whose brains could be studied - with their consent - during recovery or after death. Yet healthy animals are still subjected to deliberate brain damage, despite important differences between species that render extrapolation to humans invalid.

Monkeys and baboons are traditionally the subjects of brain injury research. Until they were exposed by animal rights campaigners, researchers at the University of Pennsylvania were strapping baboons into crash-simulation devices designed to inflict brain damage by forces of up to 3,000gs. They did not administer any anaesthetic, and they were filmed wilfully tormenting the animals before removing their brains for analysis. (50)

More recent research includes deliberately brain-damaging newborn and juvenile piglets, in order to show that the extent of injury can be dependent on age. (51)

Monkeys at Oxford University were brain-damaged to assess the effect on their emotion and motivation. This was measured by depriving them of food and then placing food in front of them, but out of reach. The animals resorted to biting their own limbs. (52)

Others had parts of their brains' visual cortex removed and were then tested at various times for their visual abilities over the next nine years, until they had all died. (53)

The Dr Hadwen Trust for Humane Research is funding other research at Oxford University using an innovative technique called transcranial magnetic stimulation (TMS). This temporarily disrupts the functioning of the brain in human volunteers, allowing scientifically valid study of the human brain itself.

Spinal injury

If the spinal cord is severed in an accident, the result is usually permanent paralysis of that part of the body below the point of injury. Scientists have always believed that nerve cells are unable to regenerate, but tests to challenge this assumption have been carried out in animals, which involve deliberately cutting or crushing their spinal cords.

For example, researchers trained monkeys to switch off electric shocks to their legs when they became too painful. Then they cut their spinal cords and continued to give them electric shocks for months to see if they recovered any feeling in their legs or reflex ability to avoid pain. (54)

New research suggests the possibility that spinal damage could be repaired by injecting neural stem cells into the spinal cord or cerebro-spinal fluid. Many hundreds of sport- or road-accident victims are willing to be 'test beds' for this new technique. However, the experiments are, instead, being carried out on animals. As a consequence, when the time comes for the first human patient to be treated, we will still have no idea whether the procedure will be safe and effective in people, even if it was in animals.

Rats and mice have their spinal cords cut right through, causing their back legs to be paralysed, and are then injected with stem cells into the spine. (55) Over the ensuing weeks or months they are tested for their ability to stand, walk or swim when placed out of their depth in water. The 'control' animals, who have their spinal cords cut but do not receive any treatment, must also paddle furiously with their front paws to avoid drowning, until they are rescued when it is clear that their back legs are still completely useless.

Pain

Pain in humans is a subjective experience whose assessment and treatment can be complex but, in general, most people can tell a doctor where and how much something hurts. This is clearly not possible for animals, in whom the measurement of pain must rely on other indicators, such as attempted movement away from a painful stimulus. In fact, the quantification of pain in laboratory animals is the subject of a huge literature, which recognises the highly subjective nature of the whole pain assessment process. Some people simply do not recognise the symptoms of distress and, of course, there is no way of telling if an animal feels nauseous or dizzy or has a headache or double vision.

There is a range of pain assessment tests employed in laboratories that would not be out of place in a medieval torture chamber. These include the 'mouse writhing test', induced by injecting acetic acid into the stomach, the 'tail-clip assay', the 'paw-licking response' to wounds induced by injections of formalin, the 'rat tail-flick response' to intense heat or the 'hot-plate response' and, of course, electric-shock avoidance responses. Scientists in Japan are investigating pain transmission in cats by administering electric shocks to their canine tooth pulp and recording the impulses generated in the spinal column. (56)

Scientists have discovered that subjecting rats to persistent pain when they are pups makes them more sensitive to pain in later life; (57) knowledge they clearly believe will be helpful for people with children. Most parents, however, do not need scientists to tell them that protecting their children from harm is a good idea.

Epilepsy

Scientists have devised around 50 methods to induce epileptic fits in mice, rats, baboons and other animals. These include the use of electric shocks, chemical treatments and exposure to flashing strobe lights. At Porton Down, guinea-pigs had holes drilled in their heads and electrodes and probes implanted into their brains, in order to monitor cerebrospinal fluid and electrical activity during the course of chemically-induced seizures. (58) Yet, even according to epilepsy researchers themselves, 'none of the models is fully trustworthy as an imitation of clinical epilepsy'. (59)

Meanwhile, other researchers are using a non-invasive brain scanner called MEG (magneto-encephalography) to study patients with light-sensitive epilepsy, one of the commonest forms of epilepsy affecting children.

Anti-epileptic drugs are now being developed rationally, through molecular biological techniques that allow molecules to be designed to bind to specific targets in the human brain. Potentially effective new products developed by these techniques are, however, likely to be derailed by the requirement for animal testing. This is because 'unfortunately, many anti-epileptic drugs show marked pharmacological differences between animals and man'. (60)

The director of a leading epilepsy research facility in Europe said, 'As a scientist, I am of the opinion that animal experiments bring no progress in the diagnosis and therapy of epilepsies. I have a well-founded suspicion that similar facts apply in other areas of medicine.' (61)

Epilepsy is twice as prevalent in the 'developing' as in the 'developed' world, where it is often caused by tapeworm larvae infecting the central nervous system. Incidence of epilepsy here could be halved by improvements in basic healthcare, but that is not a research priority. (62)

Blindness and deafness

Blindness and deafness are inextricably related to the development and functioning of the brain, the mechanisms and intricacies of which, in humans, are unique to humans. New brain-scanning techniques are increasingly valuable in pinpointing damage and the related brain areas involved. However, animals, particularly cats, have been deliberately blinded and deafened in pointless attempts to model the human afflictions:

Researchers deafened 3-6 month old kittens with chemicals before implanting electrodes in their inner ears and electrically stimulating their auditory system for several weeks. The animals were then killed to examine their brain-stem for any signs of response to the electrical stimulation. (63)

Cats and monkeys have had their eyelids stitched shut, their optic nerves or optic lobes of the brain removed, polystyrene beads injected into their eyes, and have been reared in total darkness. Concerning a series of such experiments using two species of macaque monkey, in whom the results were quite different, the British Institute of Medical Ethics concluded that 'neither can serve as an animal model for human myopia, because there is no way to decide which, if either, mechanism is similar to the human'. (64) Similarly, a group of American researchers showed that 'the feline visual system is a poor analogue to the human one'. (65)

All of the 'disease models' described above are created in a crude and artificial manner that renders them invalid for comparison with the naturally occurring disorder in humans. Indeed, the Medical Research Modernisation Committee analysed ten animal models of human illness and found 'little, if any, contribution towards the treatment of patients'. (66) It seems so obvious that complex human disorders require sophisticated models based on human anatomy, physiology and biochemistry. It is surely equally obvious that the maimed and broken animals described in this report do not fulfil that requirement.

Transgenic animal disease models

Animals have been genetically manipulated to model all of the diseases mentioned above and many more. In fact many scientists think that animals can now be engineered to represent practically any human complaint simply by adding or disabling bits of DNA.

Numbers rocketing

Many species of animals are used in this research. But mice are the favourite (at present) and their usage is rocketing - up by 960% over the past 10 years, with this rate of increase predicted to continue for the foreseeable future. (67) There are already over 650 different transgenic mouse models sold commercially through catalogues, as though they were just another piece of laboratory equipment. (68) The RSPCA has expressed concern that 'GM animals may be produced simply because it is possible, and not because it is necessary.' (69)

Transgenic mice are popular for reasons of cost and convenience. But many scientists view them as an intermediate step on the path to creating transgenic primates and other 'higher' mammals, which would supposedly make better 'models' of human diseases. The first GM monkey, ANDi, has already been produced in America (70) amid preposterous claims of valuable future models of all kinds of human diseases. ANDi was the only survivor of 224 eggs and 40 implanted embryos who had incorporated the experimental gene (a fluorescence gene from a jellyfish), but even he has failed to express the gene as expected. The idea that multiple genes for complex diseases can be inserted into monkeys and controlled to turn on or off at the right times, in the right places and to the right extent is clearly pie in the sky, or 'monkeyshine', as the Editor of New Scientist called it. (71)

Sheep, cattle, pigs and chickens have all been genetically modified to increase their production of milk and meat, which is already beyond the limits their bodies can bear without damage. They have also been engineered to secrete therapeutic protein products (which could be obtained more safely and cheaply from transgenic micro-organisms or plants) for human medicine; a process called 'gene pharming'. These abuses are outside of the scope of this report, but see 'The Gene and the Stable Door' - a Compassion in World Farming Trust report (2002), available at www.ciwf.co.uk.

Suffering at every step: creation of transgenic animals

In order to create a new strain of transgenic mice, young females are injected with powerful hormones to make them superovulate. 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 before or after giving birth. Many of the resulting baby mice are malformed and die before or shortly after birth. The surviving babies have to be tested to see if they have the new gene: this can be done by saliva or faecal sampling but is more often conducted by cutting off the tips of their tails or a notch from their ears.

Massive failure rate: millions of animals killed as 'rubbish'

Only 1-10% of the baby mice will have successfully incorporated the new gene. The other 90-99% will be destroyed as 'failures'. This translates into so much killing that many of the animal technicians responsible for killing all the 'waste' animals find it traumatic and are left feeling 'physically and emotionally exhausted'. (72) While hundreds of animals are sacrificed to produce a new transgenic 'model', life for the survivors can be even worse than for the failures.

Multiple misery

A gene is not a unit, but part of an integrated system. When introduced into a foreign environment it may take effect in the wrong tissue, switch on at the wrong time, or be uncontrolled in its effects and inflict damage on non-target organs or tissues. As a consequence there is always a likelihood that the animals will suffer unpredicted side effects in addition to the intended suffering resulting from their designer disease. For example, 'giant' mice were given a human growth hormone gene to make them bigger than normal. But they also suffered unplanned-for liver and kidney damage, grossly deformed hearts, spleens and genitalia, together with high infant mortality and a shortened life-span. (73)

Often, scientists create a 'model' by removing or disabling a gene. The resulting animals are called 'knockouts'. The effects cannot be predicted in advance. Researchers can guess, for example, that knocking out a receptor gene for thrombin (a blood-clotting enzyme) in mice will affect their control of blood coagulation. But only by creating the animals can they discover that such a deletion causes half of the altered embryos to bleed from multiple sites so that they die in the womb. (74) Other mice have been accidentally produced with no legs or with only one eye. (75)

Models of dubious value

Just as physically damaging animals results in poor 'models' of human disease, human conditions cannot be replicated in mice simply by giving them a human gene or two.

For example, none of the current 'cystic fibrosis' mouse strains accurately models the human condition, in which the major symptoms are excess mucus in the lungs, leading to lung infections. The mice, in contrast, suffer principally from bowel disorders and are clearly not a very helpful model of the disease. (76)

In another ludicrous study, researchers (including Professor Colin Blakemore) at Oxford University have observed that mice with the 'Huntington gene' stay healthier for longer if they have interesting things to explore in their cages. This leads them to claim that a busy lifestyle may help to delay the onset of Huntington's disease. (77) But such experiments can have little relevance for people because, as the leading researcher says himself, 'an enriched mouse is more like a normal human'. No humans, with the possible exception of prisoners in solitary confinement, live a comparable lifestyle to a laboratory animal. The experiment is a nonsense, from which the only conclusion that can be drawn is that mice in normal, barren laboratory cages suffer so much that they are more susceptible to illness. More evidence, in fact, if any were needed, that environmental factors are more important in triggering disease than genetic factors.

Arthritis researchers have found that deleting a certain gene in mice causes them to suffer painful bony spurs in their joints, which they hope will help in producing a cure for the disease. (78) Many other researchers, however, point out that the 'numerous roads that lead to human joint degradation make a single cure-all unlikely'.

As already discussed, many human cancers have been 'replicated' in animals by inserting some of the genes involved. 'One might expect that these animals would mimic human symptoms, not just the genetic mutations. In fact, that is usually the exception, not the rule.' (79) (emphasis added)

Even the industry's own Lab Animal magazine stated, 'Mice are actually poor models of the majority of human cancers.' (80) Yet the media constantly announces 'breakthrough' cancer treatments (developed in mice), raising false hopes in patients and their families. Dr Richard Klausner, director of America's National Cancer Institute commented, 'The history of cancer research has been a history of curing cancer in the mouse. We have cured mice of cancer for decades, and it simply didn't work in humans.' (81) Worse than that, '... some findings in colon cancer mice actually led to clinical trials in humans which resulted in an increase in cancer.' (82) And in another example, Bayer had to withdraw a drug that was causing patients' cancer to progress faster than the placebo in clinical trials. Bayer's director of Cancer Research said, 'The finding was very surprising to us and very contrary to preclinical [animal] data which confirmed the drug inhibited tumours in rodents.' (83)

In reality, each kind of cancer seems to demand its own treatment. For example, chronic myeloid leukaemia can often be successfully treated by selectively blocking an enzyme responsible for causing the defect. Researchers isolated this enzyme and a drug to inhibit it (Gleevec) was engineered, using in vitro and computer-modelling technologies in a process called 'structure-activity analysis'. Gleevec has been tested, approved and found to be effective without causing the side effects usually associated with chemotherapy. 'This is what cancer research has been waiting for', enthused Dr Brian J. Druker of Oregon Health Sciences University. 'It is the beginning of a whole new era in cancer therapeutics. If we understand the critical abnormalities that drive a cancer, we can target the cancer with an effective and non-toxic therapy.' (84) The president-elect of the American Society of Clinical Oncology said of Gleevec, 'Read my lips, this is real, not mice.' (85)

Fundamental flaw

The whole concept of modelling diseases on the basis of their genetic component alone is fundamentally flawed. There is indeed a genetic element to our susceptibility to many diseases, but our genes are not an automatic ticket to illness or health. In all the fanfare about the sequencing of the human genome, their contribution has been massively exaggerated. Other factors such as diet, lifestyle and environmental pollution are far more important in determining whether or not we will succumb to a particular disease at a particular time. Most of us are carrying the genes for a variety of serious diseases but are not suffering from them. This is because these 'disease genes' are not switched on unless triggered through, for instance, exposure to cigarette smoke, a high-fat diet or some other environmental risk factor. Even if one identical twin suffers from a particular disease, the other twin usually does not, (86) showing that genes alone are not enough to cause disease. (Except, of course, inherited disorders like cystic fibrosis.)

And a mouse with a gene for a human disease is still a mouse, whose 30,000 or so other genes will affect the expression and behaviour of the gene in question. The gene will perform in a completely different way in the mouse from the way it is expressed in its natural human environment. As Philip Abelson, editor of the prestigious journal Science commented, 'Are humans to be regarded as behaving biochemically like huge, obese, inbred, cancer-prone rodents?' (87)

Even when scientists think they have a 'good model' it is difficult to determine how much its attributes are due to its genes or to environmental factors. Wildly differing results have been found to occur in different laboratories using the same strains of animal in the same procedures. (88) Part of the explanation is that the stress of handling, confinement and isolation alter an animal's physiology in various ways - increasing susceptibility to certain diseases and tumours and altering levels of hormones and antibodies. (89) But new research has also shown that the brains of animals housed in standard barren laboratory cages are severely abnormal. (90) The sheer boredom of cage life literally drives them insane, causing brain damage, which must surely render much accepted research invalid. (91)

Pseudoscience

Some of the most despicable abuses of GM animals are 'behavioural experiments', where they are subjected to psychological torture with the excuse that this will usefully inform us about human psychological conditions. While all human disease research employing animal 'models' is pseudoscience, the following examples surely could not be publicly justified by even the staunchest supporter of animal research.

Scientists have bred strains of rats who are good or bad at swimming when forced to do so. They have found that amphetamines make the good swimmers better but have little effect on the poor swimmers. When they are killed and analysed, it appears that there is a difference in their dopamine metabolism. The scientists conclude, as a result, that the poor-swimming rats will be a useful model for depressed people. (92) It is hard to imagine that supposedly intelligent scientists could believe that these crude and simplistic measurements can possibly have relevance for such a complex and environmentally-influenced condition as depression.

An American research team claims they have engineered mice to be more intelligent and have better memories. The 'evidence' for this claim is that the mice in question are better at learning to avoid electric shocks and also lick deliberately-inflicted wounds for longer. (93) Other scientists dispute this interpretation, saying instead that the mice behave differently because they are more sensitive to pain. (94) Such confusion is inevitable when trying to explain the behaviour of intelligent animals whose experience of inflicted trauma we cannot possibly comprehend.

One research team found that mice with a gene for Alzheimer's Disease 'exhibit severe hypoglycaemia and death following food restriction or restraint stress' (95) - clearly a useful indicator that we should not starve or tie up patients with Alzheimer's disease. Such experiments are utterly inexcusable. Everything we know about Alzheimer's Disease has been learned from studies of humans, 'rendering animal-modelled recreations a complete mockery.' (96) Many experts agree; 'there is no successful animal model of Alzheimer's Disease'. (97)

Transgenic animals also used to test poisons and carcinogens

Transgenic rats and mice are used in toxicity tests, for example to measure the carcinogenic (cancer-causing) potential of various chemicals. The animals are designed to be genetically susceptible to cancer and it is claimed that this is beneficial to animal welfare because the tests should be less prolonged and use fewer animals than the traditional 'chronic rodent bioassay', which consumes 400-500 animals per compound. However, human hazard would be better predicted by using human cells. 'Toxicogenomics' (or pharmacogenetics) is a new technique using DNA arrays: tiny glass plates or 'chips' covered with a matrix of DNA fragments are washed over with fluorescent 'probes' that can detect which fragments have been affected by the substance in question. Thousands of chips can be processed in a matter of hours. The results are more accurate and sensitive than animal tests and (when human DNA is used) are directly relevant to humans. (98)

Legal protection inadequate

Having read this far, it will be apparent that no laboratory animals are properly protected under the 1986 Animals (Scientific Procedures) Act. But there are certain problems unique to GM animals, which require changes in the law to afford them due consideration. This is, not least, because their use, certainly on its current scale, was not foreseen when that legislation was introduced. Even the Home Office recognised this inadequacy and, in 1999, published guidance notes for project licence applicants intending to create or use GM animals. These notes stipulate, for example, that mice should be at least five weeks old before they can be superovulated by repeat hormone injections - a week after which they will be killed for egg/embryo harvesting. The notes also specify a maximum of 0.5cm tail-tip removal, or a maximum 15% of total blood volume removal by tail-bleeding for DNA-typing. However, DNA can be typed by faecal or saliva-sampling: clearly these more humane methods should be mandatory. The massive wastage of animals as 'failures' should be prohibited. There are methods (including breeding from homozygous lines and ensuring more accurately targeted transgene insertion) that achieve much greater levels of success and these should be mandatory. Equally significant is that the Home Office notes still classify the production and maintenance of GM animals as 'mild' severity procedures. Yet, as we have seen, the consequences of transgenesis cannot be predicted and often seriously compromise the welfare of the resulting animals.

Ethical, moral and religious concerns

Altering the genetic material of animals raises a whole host of ethical, moral and religious questions. As the controversy over GM crops has shown, many people are deeply disturbed by the notion of humans 'playing God' with the fundamentals of life itself.

Conclusion

A fatal mistake

Using animals as model humans is absolutely unscientific. It contravenes the fundamental principles of evolutionary biology, which posit that species adapt to diverse niches in varied and unrelated ways, thus precluding the extrapolation of data from one to another. This is fully explained by Drs. Ray and Jean Greek in their books Specious Science (Continuum 2002) and Sacred Cows and Golden Geese (Continuum 2000) - both highly recommended reading. The consequence of our continued use of animals in this manner is to put all of our lives at risk. In the words of Dr Irwin Bross, former Director of the largest cancer research institute in the world, 'the moral is that animal model systems not only kill animals, they also kill humans.' (100)

In fact, adverse reactions to animal-modelled medicines are now the fourth largest cause of death in America, accounting for two million people being hospitalised every year - 100,000 of whom die. (101) The figure for the UK has been estimated as 70,000 deaths and cases of serious disability per year. (102) French scientific association Pro Anima estimate one million EU citizens die prematurely every year because of toxins in their food or environment - all of which have been passed as safe by animal tests. (103) According to Dr Greek, our unscrupulous dependence on animal data means these deaths 'are not accidents; they are inevitabilities'. (104)

If it is so harmful to us, why does animal experimentation continue? One reason is simply the momentum of convention - it has been happening for a long time, many careers have been built upon it and, with little scientific dispute until recently, it has become deeply ingrained. 'Sadly, young doctors must say nothing, at least in public, about the abuse of laboratory animals, for fear of jeopardising their career prospects.' (105)

But the main reason is money. The vested interests intent on maintaining the very profitable status quo are an immensely powerful lobby. The pharmaceutical industry in Europe alone will be worth over $100 billion by 2005. (106) Many in the industry are well aware that animal experiments are scientifically invalid but recognise that they are a convenient means of generating 'safety' and 'efficacy' data that will allow a new drug to jump the regulatory hoops and win licensing approval. Or, as one leading exponent acknowledged, '... the chief objective here is to keep us all employed.' (107) German surgeon Werner Hartinger asserts; 'There are, in fact, only two categories of doctors and scientists who are not opposed to vivisection: those who don't know enough about it, and those who make money from it.' (108)

Homo sapiens: a much better model

Proponents of animal experiments claim that medical progress would cease without them. In reality, precisely the opposite would be the case, with immeasurable benefits flowing from the development and application of superior non-animal techniques, a wealth of which we already have at our disposal. The truth is, enormous improvements have been made in the diagnosis and treatment of many diseases, thanks to advances in technology that have nothing to do with animal experimentation. The arsenal of medical tools and techniques available today includes ultrasound, arterial catheters, lasers, electron microscopes, pacemakers, electrocardiograms, electroencephalograms, laparoscopic surgery, bone and joint replacements, artificial organs and much more.

MRI, CAT and PET scanners, for example, allow detailed analysis of the brains and other organs of conscious patients without surgery or even discomfort. Scanning techniques are becoming ever more sophisticated, one impressive new advance being voxel-based morphometric analysis (VBM). 'This is the first opportunity to link brain development and function with the actions of a specific gene', said a leading neurologist. 'The technique will allow accurate measurement of neurological disease progression and the effects of drug therapy.' (109)

New tissue and organ culture techniques provide human material for analysing disease processes and testing new therapies. At a stroke, interspecies differences that have plagued biomedical research for decades are eliminated. After all, 'the only universal model for a human is other humans.' (110) British pharmaceutical company Pharmagene tests drugs exclusively on human tissue with the philosophy, 'If you have information on human genes, what's the point of going back to animals?' (111)

Computer modelling is a sophisticated way to analyse and design the molecular structure of drugs to target specific receptors. For example, the protease inhibitors given to patients with HIV were designed by computer and tested in human tissue cultures and mathematical and computer models, bypassing animal tests because of the urgent need. (112) In 1997, Hoffman La Roche had a new heart drug approved on the strength of data from a virtual heart because the animal data was inconclusive. Research teams around the world are working on a 'virtual human', (113) which is designed to predict drug metabolism and metabolite interaction with any given organ - information that animal models will never be able to provide.

Autopsy studies are immensely valuable: 'Virtually the whole of modern medical knowledge was created through the study of autopsies.' (114) There is still much more to be learned.

Clinical (patient) research and clinical trials of drugs and other therapies are very powerful tools, shaping treatment decisions for individual patients and advancing the standards of medical care. So long as they are conducted responsibly they can make enormous contributions to medical progress. Sadly, money taints this process too, prompting 13 of the world's leading medical journals to speak out against corruption of trials by the pharmaceutical industry (and government). (115) Richard Horton, Editor of the Lancet, said, 'We are all completely fed up with being manipulated by the industry... Research papers are now used more as a marketing exercise than as scientific reports'. (116) But it is imperative that new treatments and medications are tested carefully on patients and volunteers to establish efficacy and safety, after all the in vitro and other tests have been conducted to ensure minimum possible risk. Clinical trials would be safer for participants if the animal testing stage was removed. 'It is impossible to establish the reliability of animal data until humans have been exposed.' (117)

Technological improvements continue to be made, and provide potential for substantial medical advancement. At the technological cutting edge, claims are made that human stem cells may be able to repair and even replace damaged organs in the future. (118) It is also predicted that genetic screening could allow medicines to be better tailored to individual patients, thus potentially eliminating many harmful side-effects responsible for so many deaths as described above. (119) Advocates also say that such screening programmes will encourage people with particular disease risks to adopt preventive health strategies. Time will tell if these promises translate into genuine and lasting benefits. Recent years have also seen the public turn increasingly to non-allopathic therapies, based on a holistic model of health and disease, whereby the focus is on strengthening and nourishing the body's immune defences rather than making a 'self-destructive' high tech war on pathogens, tumours and the like.

Disease prevention offers the greatest hope for the 'big three' killers - heart disease, cancer and strokes. All the evidence for the major risk factors (smoking, high-fat diets, lack of exercise, etc.) has come from epidemiological (population) studies of people and their lifestyles. Prevention is always better than cure, and as far as illnesses such as AIDS are concerned, 'prevention is not just better than cure - it is the only cure.' (120) Epidemiology has taught us how the AIDS virus is transmitted and how we may combat it. Combined with genetic, clinical and in vitro research, epidemiology is a very powerful tool whose scope is unlimited. The animal model, by contrast, is 'an archaic paradigm whose scope peaked 100 years ago. It must be replaced if we expect to improve the quality of human life.' (121)

Thanks to advances in molecular biology and other technologies, and also to a greater appreciation of the holistic, integrated nature of humans and their diseases, we may be entering a new phase of medical advancement. But as long as animal research is involved in any way, it will continue to de-rail progress as it has done so often and with such devastating consequences in the past.

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