|"Many of the most significant findings about
Alzheimer's disease have been learnt from humane research techniques
and not from animal experiments"
|"The cost of animal experiments is both human
|"The capacity of primates to experience pain,
suffering and distress is similar to our own"
|"The capacity of primates to experience pain,
suffering and distress is similar to our own"
|"Primates are intelligent with highly developed
brains, complicated patterns of behaviour and intricate social relationships"
|"Anything revealed by these 'models' is of dubious
relevance to humans, and can even be seriously misleading or delay
|"You can tinker with a mouse and insert human
genes, but basically it is still a mouse"
|Macaque. Credit: Iain Green
|"An increasing range of safe and non-invasive
methods of studying patients and volunteers are available"
|"Scientists can now safely probe the intact human
brain to produce 3D images and to watch the brain in action"
DR HADWEN TRUST
A Report on the use of (Non-human) Primates in Brain Research
This document has been prepared by the Dr Hadwen Trust, a registered
medical research charity with 30 years' experience of developing alternatives
to replace animal experiments.
The Trust is opposed to animal experiments on both scientific and ethical
grounds, however this document intends to focus on the scientific arguments
against using (non-human) primates in brain research.
Within the Animal Kingdom primates are biologically our closest relatives
and thus share many attributes with us. They are intelligent with highly
developed brains, complicated patterns of behaviour and intricate social
There are compelling ethical arguments against using primates in any
type of experiment. Their special and complex needs makes it virtually
impossible to house and maintain them adequately in laboratories. Most
importantly, the capacity of primates to experience pain, suffering and
distress is similar to our own. It is their very similarity to humans
that both makes them the subjects of research, whilst at the same time
strengthens the ethical argument against confining them in laboratories
and exploiting them in experiments.
Primates used in laboratories in the United Kingdom are mainly species
of monkeys, such as marmosets, macaques, and baboons. Experiments on great
apes (ie. chimpanzees, gorillas, and orang-utans) are not permitted in
the UK, for ethical reasons. The same is true in New Zealand and the Netherlands.
The latest Home Office statistics record 3,690 experiments on primates
in the UK during 2000 (1).
Building a new neuroscience research centre at Cambridge will almost
certainly increase the use of primates in the UK. The Dr Hadwen Trust
believes there are humane alternative methods of research that can allow
brain research to continue, without the use of primates, or other animal
This report is divided into four sections. The first section explains
the general scientific arguments against the use of primates in brain
research. Following this are three sections that deal in more detail with
the specific research fields of Alzheimer's disease, Parkinson's disease,
and fundamental brain research.
Limitations of animal research
The wrong species
In medical research the species of interest is the human species. Thus
the 'gold standard' medical research technique is clinical studies of
volunteers and patients. Any 'model' of the human situation is one step
removed from the ideal.
Despite the fact that we share 98% of our genes with chimpanzees and
92% with macaque monkeys, at the molecular level there are many small
differences between us. The molecular level is the very basis of how things
work in the body. Any minor variations there can be amplified, in a cascade
effect, at the cellular, organ and whole animal levels, creating troublesome
- For example, a mutation of a single gene has been identified in humans
that causes subtle changes to the chemistry of cell surfaces throughout
the body, and has implications ranging from susceptibility to disease-causing
organisms to brain development. This form of the gene does not occur
even in the closely related great apes (2).
- Differences in the quantity and activity of liver enzymes produced
by humans and monkeys, mean that they metabolise drugs differently,
and can respond differently to them (3).
Because of species differences, results from animal experiments are unreliable
at predicting human responses. Findings from animals may, or may not,
apply to humans, and the only way of finding out is to study the human
situation. This is a major limitation of all animal research - it produces
results of unknowable relevance to humans.
- Monkeys are susceptible to poliovirus through the nose, but humans
become infected via the mouth and intestine. This species difference
led scientists astray in the early part of the 20th century, when experiments
on monkeys eclipsed research with patients, and led to the development
of useless nasal sprays to prevent infection (4).
- HIV can infect both humans and other great apes, but only humans develop
AIDS. Monkeys are not susceptible to HIV infection and do not develop
the illness, and no one knows why. Primate research to find a therapeutic
AIDS vaccine has essentially been a failure according to a scientific
review published in 2000 (5).
In medical research animals are often used to 'model' a human illness.
The symptoms of the human illness are artificially induced in animals
in an attempt to mimic the disease, even though the species used may not
naturally succumb to that illness. Anything revealed by these 'models'
is of dubious relevance to humans, and can even be seriously misleading
or delay progress.
For example, in humans a stroke occurs when the blood supply to the brain
is disrupted or blocked by a blood clot. Stroke is modelled in animals,
including primates, dogs, cats and rodents, by clamping or blocking a
blood vessel to the brain. This surgical onslaught mimics the gross effect
of a stroke, but does not duplicate the development of the full human
condition that is often accompanied by atherosclerosis or high blood pressure.
A scientific review of stroke drugs found that of 25 different compounds
of proven efficacy for treating stroke in animal models over 10 years,
none had been successful in stroke patients (6).
Parkinson's disease is a slow degenerative disease in humans of unknown
cause. Some of the symptoms of Parkinson's, tremors and abnormal movements,
are induced in monkeys by injecting a toxic chemical that damages the
brain. Despite its devastating effects, MPTP poisoning is not the same
as Parkinson's disease, and there are numerous differences. The animals
can gradually recover once the poisoning stops, but the human condition
The cost of animal experiments
The cost of animal experiments is both human and animal. Animals suffer
directly from being used in experiments. All too often the findings of
animal experiments confuse and delay our understanding of the real human
problem, and thus humans suffer as a result.
Despite strict legislation in the UK to regulate animal experiments,
animal suffering is inherent in much animal research, most especially
when it involves primates. Animal experiments covered by UK legislation
[The Animals (Scientific Procedures) Act 1986] are by definition procedures
carried out on living animals that are "liable to cause pain, suffering,
distress or lasting harm". Inflicting brain damage on animals or
inducing the symptoms of devastating disorders, such as Alzheimer's, Parkinson's
disease, stroke or depression, are certainly liable to cause substantial
suffering to the animals involved.
Animal experiments are only one method of scientific research, and they
are not the sole means of pursuing medical progress. Although animal experiments
represent just a small proportion of medical research, they still equate
to millions of animal lives. At the same time, the over weighted emphasis
put on them means that researchers can be misled about the nature of human
illnesses. Research that focuses on animal experiments is wasting time,
effort, money and lives.
Alternatives to animal experiments
At the dawn of the 21st century there are more advanced methods of conducting
medical research than archaic animal experiments. An increasing range
of safe and non-invasive methods of studying patients and volunteers are
available. There are improved techniques for keeping and studying human
tissue samples and cells alive and functioning in the laboratory. Computers
are being used to model the complexities of human body systems, such as
the immune system. Sophisticated analytical and 'test-tube' techniques
are enabling unparalleled advances in molecular and genetic analysis.
These cutting-edge tools are expanding the horizons of today's researchers
and paving the way for future medical progress.
The proposed Centre for Behavioural Neuroscience at Cambridge intends
to conduct research, including animal experiments, into how the brain
works and disorders of the brain. The next section of this document will
consider some of the more specific scientific limitations of using animals
in some areas of brain research, and will outline how humane approaches
could be used instead to expand our knowledge and further medical progress.
- Statistics of Scientific Procedures on Living Animals.
Great Britain 2000. Publ. HMSO.
- Molecular Phylogenetic Evolution (2001) 18:2-13
- Xenobiotica (1999) 29:467-82
- A History of Poliomyelitis by J R Paul, publ. Yale
University Press, 1971.
- Antiviral Chemistry & Chemotherapy (2000) 11:311-320
- Stroke (1990) 21:1-3
Alzheimer's disease (AD) causes confusion, memory loss and dementia in
millions of elderly people. The cause remains unknown and there is no
effective treatment. In the brains of AD patients an abnormal build-up
of proteins occurs, in the form of plaques and tangles. No one knows if
these protein deposits are a cause or a result of the disease. Eventually
the brain cells start to die, the brain shrinks and there is a loss of
mental abilities with increasing age.
No animals suffer from AD in the way humans do, yet many animals have
been used in an attempt to model AD. Much current research focuses on
the use of transgenic mouse models of AD. These are mice genetically modified
to possess human genes associated with AD Ñ genes identified from
studies of patients. Various mice have been created and each display some
of the characteristics of AD, but none of them accurately reflect the
full spectrum of symptoms seen in humans (1).
For example, various transgenic mice have been created that overproduce
the proteins that accumulate in the brain in human AD. However in these
mice the protein plaques are not distributed at the same levels or in
the same pattern as seen in human AD, the brain cells do not die, and
the mice do not suffer from the severe behavioural changes seen in humans
(2). So it seems you can tinker with
a mouse and insert human genes, but basically it's still a mouse.
Macaque monkeys also develop protein deposits in the brain as they age,
but they do not suffer from the severe form of disease seen in humans.
Because monkeys live beyond 30 years, it is generally too expensive to
keep them in laboratories for so long before using them in an Alzheimer's
research programme. Consequently, mice are the species of choice in AD
research, for economic rather than scientific reasons.
Studies of the brains of ageing great apes have shown that like humans
they develop protein deposits in their brains. However, they do not suffer
the brain damage and brain cell death seen in humans. Genetic studies
have identified genes associated with AD in humans, but confusingly, chimpanzees
who also possess these genes do not develop the disease (3).
Overproduction of a brain chemical, galanin, may be associated with Alzheimer's
disease. Galanin is found within a distinct population of brain cells
in humans, but is much more widely distributed in the monkey forebrain
The distressing behavioural symptoms of human dementia, such as confusion,
memory loss, delusions, hallucinations, depression, decline in reasoning
and lack of speech, are simply not seen in animals or are not measurable.
Alternatives - the humane way forward
Many of the most significant findings about AD have been learnt from humane
research techniques and not from animal experiments. Alois Alzheimer first
described the main features of the illness in 1907 when studying post-mortem
brains of AD patients. Since then, research on post-mortem brain tissue
has provided much of what we now know about the pathology of the human
disease, and continues to reveal new insights, such as the potential involvement
of toxins and viruses (5).
There is a wealth of humane research techniques that could be used to
continue to study AD without resorting to animal experiments. Brain cell
cultures have been used to study cellular processes involved in the accumulation
of protein deposits, and identify potential treatments (6,7).
New molecular techniques are revealing important genetic components to
the disease, and providing new insights that may lead to better treatments
(8,9). Brain scanners, such as CAT,
MEG and MRI are being used to non-invasively "look inside" at
the functioning brains of living AD patients. PET scans can be used to
diagnose AD, and may even be able to detect changes in the brain several
years before the symptoms appear, enabling a vital chance for intervention
(10). Population studies have identified
risk factors associated with AD, and revealed that drugs such as aspirin
and ibuprofen may reduce the risk of developing AD (11).
- Nature (2000) Vol 408:915-916
- The Alzheimer's Forum. www.alzforum.org
(Interview with Karen Duff PhD, NYU School of Medicine, 1999)
- New Scientist 27 Jan 2001, p18
- Annals of the New York Academy of Science (1998) 863:291-304
- Alzheimer's Reports (1998) 1:173-178
- New Scientist 19 June 1999, p10
- Journal of Biological Chemistry (1999) 400:173-177
- Science (2000) Vol 290:2303-2304
- New Scientist 1 July 2000, p12
- New Scientist 8 September 2001 p4
- Nature Medicine (2000) 6(9): 973-4
Parkinson's disease is another common disease of the elderly, affecting
1% of the population over 65. Patients suffer from tremors, stiffness,
rigidity, slow shuffling movements, and hunched posture. These symptoms
are the result of irreversible brain decay. The condition is slowly debilitating
and there is no cure. Some treatments are available, but they are of limited
effectiveness and have serious side-effects.
Parkinson's disease (PD) is widely modelled in monkeys by injecting them
with a toxic chemical, called MPTP. The animals suffer brain damage and
succumb to symptoms superficially like those seen in PD patients. These
brain damaged monkeys are used in laboratories to study the disease and
investigate potential treatments. Rodents and cats are also susceptible
to MPTP poisoning.
There are however major differences between the induced condition in
animals and the human disease:
- In spontaneously occurring human PD the symptoms develop slowly, and
grow progressively worse over time. In experiments, healthy monkeys
are subjected to a toxic assault, the symptoms appear rapidly and then
gradually lessen. Unlike PD patients, the poisoned monkeys can actually
recover if the MPTP poisoning stops.
- The brain damage caused to monkeys by MPTP poisoning is very selective
affecting only specific parts of the brain, whilst in PD patients brain
damage is much more widespread.
- There are significant changes in the levels of brain chemicals in
PD patients, that are not seen in MPTP poisoned monkeys.
- A hallmark of human disease is the presence of Lewy Bodies, protein
bodies that accumulate in the brains of AD patients. Lewy bodies are
either not present in monkeys' brains, or they occur at reduced levels
in some monkey species.
Despite these significant differences monkeys continue to be widely used
in Parkinson's research. The monkeys injected with MPTP suffer substantially.
They display tremors, rigidity, abnormal posture, loss of balance, drooling,
incontinence, compulsive behaviour, constipation, and may be incapable
of feeding themselves. At the end of experiments, sometimes after many
months, the animals are killed and their brains examined.
Although the MPTP monkey model of Parkinson's was devised in the 1980s,
the animal research has done little to improve the treatment of PD patients.
The standard treatment for PD remains L-DOPA, which has been in use since
the 1960s. Treatment with L-DOPA alleviates symptoms, but its effectiveness
wanes after several years, and side-effects develop that are similar to
One advance in the treatment of PD in the last 30 years has been "deep
brain stimulation". This involves surgery to implant electrodes into
the brain to stimulate a part of the brain called the subthalamic nucleus,
which can help to control tremors in some PD patients. This therapy was
not discovered by animal experiments, but resulted from the observations
of French scientists in the 1980s, who noticed that in patients undergoing
brain surgery, stimulation of certain parts of brain appeared to stop
tremors (1). Although animals have
subsequently been used to investigate the technique, trials in PD patients
have shown it to be an effective in some cases and have helped to refine
the technique (2).
Studies of families have revealed genetic elements to some forms of PD.
This knowledge has immediately been used by some scientists to create
genetically engineered mice with genetic defects, although they have so
far failed to produce a mouse model displaying all the characteristic
symptoms of human PD.
Much recent research has focused on the idea of treating PD by transplanting
embryonic cells into the brain, in attempts to replace damaged brain tissue
with new healthy brain cells. After partial successes in animal experiments,
brain cell implants were attempted in humans in the 1980s, but initial
results were disappointing. Researchers have continued to pursue this
form of therapy, and subsequent improvements in the technique yielded
some promising results in a few limited human trials (3).
However, such hopes were recently dealt a severe blow when the first full
trial of the technique showed no improvement in PD patients over 60, and
tragically left some patients with irreversible side effects (4).
Five patients in the trial suffered devastating effects, with uncontrollable
movements worse than the disease, although in animal models of PD brain
cell implants had the very opposite effect (5).
There are also ethical concerns over using human embryonic tissue as a
source for implants, yet some researchers continue to hope that this approach
might one day provide a cure for PD, and other brain disorders, such as
Huntington's and Alzheimer's disease.
Alternatives - the humane way forward
Studies of human populations (epidemiology) have suggested interesting
connections between an increased risk of PD and exposure to environmental
toxins, such as pesticides, herbicides, or metals (6,7).
There are also indications that diet and smoking may play role in susceptibility
to PD (8,9). Further investigation
into confirming these links could help to prevent future cases of PD.
Non-invasive brain scanners such as PET and MRI are already being used
to study PD patients and will continue to increase our understanding of
the effects of PD on the living human brain. Future improvements in these
methodologies are likely to shed more light on the illness; help with
diagnosis and monitoring of PD; provide a means of assessing new therapies
and improve current ones, such as deep brain stimulation.
Post-mortem research on the human body after death is invaluable to medical
science, particularly in following-up the progression of a disease, and
the effects of treatments and interventions. A few brain banks already
exist, to which people can donate their brains after death, although more
could be done to encourage the public to donate their organs to research
via a properly regulated system. Studies of human tissues and cells are
providing insights into the cellular mechanisms that bring about the death
of brain cells in PD, and indications of possible treatments and interventions.
Follow-up post-mortem studies of the brains of PD patients who have received
brain lesioning treatment, could provide vital information to optimise
the lesion procedure that would be of direct benefit to future patients.
Such studies would be a direct alternative to current experiments in which
monkeys have their brains purposely damaged to induce Parkinson's symptoms
and to mimic the lesion treatment.
Computer simulations of the interactions between brain cells are being
used to shed light on what causes the symptoms of PD, and how therapies
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- Neurology (2000) 55:S40-S44
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Fundamental brain research
Some of the most distressing brain research on primates is "fundamental
research" which aims to find out which parts of the brain do what.
Monkeys are trained to carry out tasks and then have their brains damaged
to investigate the functions and locations of different regions of the
This type of research often involves implanting brain electrodes for
recording or electrically stimulating different parts of the brain. These
are fitted to the animal by drilling into the skull under anaesthesia.
Animals prepared like this will be used when conscious in experiments,
recordings being made from their brains, whilst they carry out tasks that
they have been previously trained to do, usually for rewards of food,
or water. Later their brain may be damaged to see how this affects the
way they carry out their tasks. These experiments can involve the animals
being strapped into restraining chairs, sometimes for several hours at
a time. Their heads may be fixed still by means of a peg cemented into
their skull. Experiments may continue for many months.
For example, in vision research monkeys may be taught to recognise the
size or position of a shape on a computer screen. To do this, they are
held captive in restraint chairs in darkened rooms for several hours a
day for up to nine months whilst they learn the visual task. Recording
from implanted electrodes may continue for up to six months at a time.
Some animals will have parts of their brains damaged under anaesthesia,
and subsequently undergo recordings whilst conscious, to see the effects
of the brain damage. At the end of experiments animals are usually killed.
Animals fitted with electrode chambers may be kept alone in separate
cages, to prevent cage mates from tampering with or damaging the equipment,
even though single housing of primates is not recommended in official
guidelines as it is known to be stressful and cause psychological suffering.
A limitation of the animal experiments is that they record the activity
of single brain cells. Single cell recordings from the human brain are
not possible, so there is simply no way to compare findings to see if
they are relevant to humans. Recording the activity of just a few brain
cells, out of several billion in a monkey's brain, might be of academic
interest, but such precise recording is not of practical or medical relevance.
Despite some broad similarities between animal brains, there are also
clear differences in the brain anatomy of even closely related species,
such as humans and monkeys. Science currently knows a great deal about
monkey brains, but relatively little about the human brain. However, as
new technology allows the investigation of the human brain there are increasing
differences being found between the human and monkey brain.
- The primary visual area of the human brain is twice the size of, and
in a different location to, that of macaque monkeys.
- Research with volunteers has demonstrated that the region of the brain
associated with eye movements is in a different part of the brain in
humans compared to monkeys (1).
- A visual area known as 4A has a unique arrangement in humans, different
even to that in chimpanzees (2).
- There are differences between humans and great apes in both the organisation
and relative size of an area of the brain known to be involved in taking
initiatives and planning future actions (3).
- Differences have been found between chimps, monkeys and humans in
the organisation and arrangement of cells in the cerebral cortex, an
important part of the brain whose functions include control of movement,
co-ordination and posture (4).
- Brain tissue from humans, marmosets, vervet monkeys, guinea pigs,
rats and mice have shown significant species differences in the levels
and distribution of 'receptors' in the brain that detect chemicals thought
to control behaviour and mood (5).
- A study of blood from chimps and humans found significant differences
in thyroid hormone metabolism, which is known to play a major role in
the development and metabolism of many organs, including the brain (6).
- An area identified in the monkey brain as important in aspects of
working memory, is located in a different position in humans (7).
Alternatives - the humane way forward
Non-invasive imaging techniques, such a fMRI, PET, MEG have revolutionised
brain research. Scientists can now safely probe the intact human brain
to produce 3D images and to watch the brain in action. These technological
advances have made studying animals brains less appropriate, as human
brains are now accessible. Brain imaging techniques are still relatively
novel, and continued improvements in accuracy and sophistication are likely
to expand their potential even further in the future.
At present brain imaging techniques may not provide exactly the same
precise data as single cell recordings from implanted electrodes, but
studying humans has innumerable advantages over experiments on monkeys,
- Studying the species of interest and producing results that are directly
relevant to medical progress.
- Lack of species differences.
- Humans are quicker to train than monkeys.
- Humans are far easier to communicate with and can provide direct feedback.
- Restrained monkeys are likely to be highly stressed, which can confuse
- Patients suffering from spontaneously-occurring illness or brain damage
can be studied, rather than artificially induced brain damage in monkeys.
- Imaging techniques can provide an overview of the human brain, revealing
the interaction of different parts of the brain and the timing of events,
aspects which cannot be studied with single brain cell recordings.
A highly innovative technique called transcranial magnetic stimulation
(TMS) uses a magnetic pulse to temporarily and reversibly disrupt areas
of the brain in human volunteers. This method allows researchers to safely
and momentarily mimic the effect of brain damage in human volunteers,
instead of inflicting permanent brain damage of monkeys (8).
TMS is being utilised for both fundamental research, and in studies of
brain disorders such as migraine.
Analysis of human post-mortem brain tissue can contribute greatly to
our understanding of the structure and function of the brain. Analysis
of patients' brains after death can help validate some of the new imaging
technologies, and fresh post-mortem human brain tissue can be used to
track connections between individual brain cells and different parts of
the brain (9).
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- Proceedings of the National Academy of Science (1999)
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- American Journal of Anthropology (2001) 115:99-109
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- Trends in Cognitive Sciences (1998) 2(3):103-110
- ATLA (2000) 28:315-331
Arguments for a Centre of Excellence >>
Prepared by The Dr Hadwen Trust for Humane Research,