The scientific case against primate research
In May 2000, the University of Cambridge announced plans to build a large-scale primate facility for research into neurological diseases.
In January 2004, the University declared that it did not intend going ahead after all, citing financial reasons. In reality, it faced mounting opposition both from within and outside the University.
More than 130 MPs and numerous scientists and academics had gone on record opposing such research. And, a majority of the public had expressed their opposition in opinion polls (NOP, 2003). Perhaps more crucially, a government-appointed Planning Inspector, presiding over a public inquiry into the affair, had recently ruled that the University had failed to make a scientific case for the proposed centre. In the Inspector's view, building what would be Europe's largest monkey research centre would not be in the national interest, despite claims to the contrary by the University.
At a time when human neurological disease, such as stroke, Alzheimer's and Parkinson's disease seem indeed to be more prevalent than ever before, how should we invest our precious research resources?
Human neurological conditions are varied and often extremely complex. They include such problems as migraine, anxiety disorders, dementia, depression, epilepsy and schizophrenia, in addition to those mentioned above. Whereas a few of these disorders are shared by certain animal species (e.g. epilepsy), most are unique to human beings. Even between human being and our closest genetic kin, the biological gulf can be considerable. Researchers at the Medical College of Georgia have found, for instance, that there are important differences between the circuitry of brain cells in humans and non-human primates. Their findings suggest that, when this circuitry in the human brain goes wrong, it could trigger conditions such as schizophrenia, autism and epilepsy (1). These unique attributes of the human brain have no counterpart in the animal kingdom.
As with any human medical condition, a treatment plan should ideally be tailored to suit the particular symptoms of the individual receiving the treatment. Neurological diseases are no exception to this rule. It is important to stress this fact because it clearly demonstrates the scientific futility of trying to apply the results of non-human primate brain experiments to people. It is hard to imagine how any animal research could be applied to a treatment plan for people suffering from such diseases. For example, patients suffering from Parkinson's Disease are at risk from long term complications of their treatment (2). Animal tests are typically short term. In addition, the treatment of young patients is quite different to that of adults, again something which animal experiments cannot predict.
The failure of the animal model in studying human neurological disorders
"Experimenting on monkeys in the hope of unlocking the secrets of the human brain is an exercise in futility. The most dramatic differences between humans and other primates are in the brain. Our brain is four times larger than that of a chimpanzee, which is four times larger than that of a macaque. Biochemical pathways in the brain are unique. Gene expression in our brain is dramatically different from that of the chimpanzee" (3).
Trying to replicate a human disease condition in an animal is scientifically highly questionable. The animal is usually healthy at the start of the experiment, and so must be made ill by artificial means, in an attempt to reproduce the human symptoms. Monkeys are subjected to deliberate and severe brain damage, through surgery or by the use of toxic chemicals injected into the brain. As soon as the monkeys recover from these procedures, they are usually forced to perform repetitive tasks in the laboratory. In addition, food and water deprivation may be used to motivate the monkeys.
Inevitably, any attempt to induce in monkeys these specifically-human neurological diseases is going to result in confusion. For example, Parkinson's disease becomes progressively worse in human patients, while the chemically-induced marmoset version demonstrates gradual recovery (4). Plaques and tangles in the brain are the hallmark of Alzheimer's disease in humans but not in monkeys (5). Brain-lesioned marmosets used in the study of Huntington's disease do not replicate the pathology or symptoms of Huntington's disease (6). Countless treatments for stroke have been developed in primates and other animals - yet all of them have failed or even harmed patients in clinical trials (7). Thus, whatever is discovered through the animal experiment must necessarily be "re-discovered" in the patient, because of species differences.
When it comes to drug development, non-human primates have repeatedly failed to predict dangerous side effects subsequently suffered by human patients.
Isoprenaline doses (for asthma) were worked out on animals, but proved too high for humans. Thousands of people died as a result (8). Carbenoxalone (for the treatment of gastric ulcer) caused people to retain water to the point of heart failure. Scientists tested it retrospectively on monkeys, but could not reproduce this effect (9), clearly demonstrating the fact that research on non human primates would not have predicted the fatal outcome.
Similarly, monkeys don't help humans in infectious disease research. The "best" animal model, the chimpanzee, is essentially immune to AIDS, hepatitis B and common malaria, diseases which kill millions of people throughout the world every year. This would help to explain why the experimental "Aidsvax" HIV vaccine, deemed a success in animals, was recently pronounced a failure (10). The 8 000 high-risk volunteers in this clinical trial were not protected from HIV infection by the vaccine.
This does not sound like good research. In fact, some of the strongest scientific arguments against the use of non-human primates in medical research have been voiced by scientists who themselves have performed experiments on various animal species. Some of their key concerns can be summarised as follows:
The use of such highly sentient creatures (non-human primates) is morally indefensible - the main reason for the desire to use them, their similarity to ourselves, is also a most compelling reason for not doing so (11).
The higher primates, by their very nature, cannot be institutionalised and remain healthy, which fundamentally comprises their well-being (11).
There is little evidence that primates provide effective models for human disease (11).
Trying to reproduce animal models of human disease is an outdated approach, especially since there are now many non-invasive ways of working with human patients (11).
The UK already conducts far more procedures on primates than any other EU member state (the total number of procedures on these animals used in the UK in 2002 was 3977).
Dr Charlotte Uhlenbroek, a leading primatologist and BBC science presenter has said: "I have yet to hear a sufficiently compelling scientific argument that justifies the suffering inflicted on primates in medical research".
"Over-reliance upon such animal models (such as for stroke) may impede rather than advance scientific progress in the treatment of this disease." (12).
There are other fundamental arguments against using monkeys as animal models of human brain disease. Human thought and speech patterns, which are impaired in patients with Alzheimer's disease, would be impossible to study in laboratory animals.
In addition, genes in the brains of humans and non-human primates, including chimpanzees and rhesus monkeys, differ in their levels of activity. In other words, the differences in brain activity between humans and monkeys can be traced right down to the molecular level. This supports the thesis that all animal species exhibit unique biological activities that arise from their particular genetic make-up. Interestingly, the human genes exhibit greater protection against activity-related damage, as compared with monkey brains. This could help to explain why humans live longer than non-human primates and also why humans are more susceptible to age-related neurodegenerative diseases, such as Alzheimer's and Parkinson's (13).
Prevention and diagnosis of neurological disease in humans
State of the art research: functional MRI scanners can monitor the brain activity of volunteers, undertaking tests of memory and other skills, to reveal brain areas that are active during particular activities. Further advances in our understanding and treatment of neurodegenerative diseases will come from where they always have - human based observation and clinical research, autopsies and human cell research. "Alzheimer's, Parkinson's and other neurodegenerative diseases occur in humans and it is in human tissue that we will find the answers to these diseases" - Dr John Xuereb, Director of the Cambridge Brain Bank Laboratory (14).
While the exact origins of neurodegenerative brain conditions in human patients may still be unclear, some disturbing clues are beginning to emerge. For example, the majority of modern pesticides are designed to target the nervous system of insects. It is quite possible that these same pesticides cause damage to our nervous systems as well, albeit in more subtle ways. Given human beings' average life expectancy, our bodies are being exposed to these pesticide chemicals for a period of several decades, in a cumulative fashion. According to a WWF survey, it would appear that every person in the UK is contaminated by a cocktail of known highly toxic chemicals, some of which were banned from use in the UK in the 1970's (15). There is no doubt that chemical pollution of the environment and the harmful chemical additives in the food we eat contribute to human ill health - lead and mercury being the best known for damage to our nervous systems.
Preventive measures for conditions such as stroke are in the same category as heart attacks, since they are both often the result of atherosclerosis (clogged arteries). Important disease prevention measures would include weight reduction, cessation of smoking, adoption of a low fat diet, and control of blood pressure.
There is total consensus between researchers and non-researchers alike, that funding and resources are limited. A choice must therefore be made: we can choose to invest time, money and effort into yet more animal experiments, or we can invest those same precious resources in human based research aimed at preventing, as well as treating, patients with neurodegenerative conditions.
Written by André Menache BSc(Hons) BVSc MRCVS FRSH
- Medical College of Georgia, news release, 4th September 2001
- Lundbeck Institute, CNS forum
- R Greek, Monkeying Around with Human Health, May 2003
- S Carson et al, Pharmacologist (1971) 18: 272
- PH St. George-Hyslop and DA Westaway, Nature (1999) 400: 116-117
- AL Kendall et al, Brain (2000) 123 (7): 1442-1458
- Stroke (1990) 21: 1-3
- S Carson et al, Pharmacologist (1971) 18: 272
- CT Eason et al, Regulatory Toxicology and Pharmacology (1990) 11:288-307
- New Scientist (2003) 177 (2385): 7
- M Balls, ATLA (2003) 31: 545-547
- Stroke (1990) 21: 1-3
- Emory University Health Sciences Center press release, 13 October 2003
- BBC Radio Cambridge, 7th February 2002
- WWF-UK National Biomonitoring Survey, 2003