Distinguishing the Truth from the Lies

There has been much media coverage lately about exactly how the discovery of deep brain stimulation techniques came about. Most vivisectors don’t like to miss an opportunity at misleading the public as to just how vital they are to human health and just how important vivisection is in helping find cures for human disease. Unfortunately much of the media have bought into these lies without looking at the facts. A classic example of this is the recent media coverage given to Prof T A of Oxford University who has recently been given a very high media profile. Prof T A claims that the treatment of deep brain stimulation given to Parkinson sufferers owes everything to his research on monkey brains and could not have been made in any other way. As the following article illustrates, the key discovery regarding electrical stimulation of the subthalamic nucleus was actually made some years prior to Prof T A abusing monkeys and came about because of experiments conducted by a Professor Alim Louis Benabid while studying a human patient. Parkinson’s patients and their doctors owe nothing to experiments on monkeys: rather, they owe everything to the patients and doctors who preceded them, who made the crucial observations that led to deep-brain stimulation becoming available as a treatment for Parkinson’s disease. The Oxford University professor is essentially using the innovate work of others, that didn’t involve using animals, in order to defend his own abuse of animals in a redundant scientific practice.

The claim that monkeys are useful tools that enable us to understand human illness and devise treatments is ludicrous. The differences between humans and other primates are too many, too large, and too far-reaching. Human illnesses are rarely found in other animals – including other monkeys – and when they are, they have a different cause and nature, so comparing the two is impossible. Even if the illnesses were found in monkeys we still wouldn’t be able to test potential treatments. Monkeys react differently to treatments, so tests would still mean nothing.

A high profile area of debate about this point is brain illness. This is a crucial area of debate for the future of vivisection, because of the implications when the debate is resolved. Monkeys are the animals that have the most similar brains to humans. As we demonstrate that they are not similar enough, it reveals that the rest of vivisection is even further removed from reality, and even more obviously pointless. In other words, once we disprove monkey research, support for the remainder of vivisection will be stripped away all the more easily.

An example of such hotly-contested research is Parkinson’s Disease. PD is a human illness, and there is no animal model that will aid the study of it. The best attempt so far has been to use MPTP (a by-product of synthetic heroin), injecting it into primate brains to create an animal model. In reality, this only recreates some of the symptoms. It is sufficiently different from human PD that the animal experimenters, usually eager to over-state their work, can’t even call it PD, but rather call it ‘parkinsonism’.

Animal Models Are Unlike Humans

Jay Schneider, who experimented on macaques with the method, explained, “Some monkeys had cognitive deficits and no motor deficits. Other monkeys had full parkinsonism that was produced after short-term high dose MPTP exposure, and some monkeys had full parkinsonism after long-term low-dose MPTP exposure.”

Also, the damage is temporary. As a leading neuroscientist explained in 2000: “The best model of PD to date, is the…(MPTP)-lesioned marmoset….; unlike human PD, which is progressive, the neurotoxic damage produced by MPTP is reversible.” [1]

Furthermore, when using a monkey we need to remember that these illnesses affect each species differently. Another expert explains:

“Animal models are generally …subjects with behavioural repertoires and anatomical characteristics very different from humans…. striatial degeneration in humans is frequently associated with dyskenesia, whereas in rat or non-human primates, striatial excitotoxic lesions alone are not sufficient to induce dyskenisia or chorea...”[2]

Another says animal models: “do not reflect the complexities of the human basal ganglion.”[3]

In other words, the symptoms aren’t the same, the conditions caused by the technique are inconsistent, the activity in the brain is different, and the experimental animal gets better without any treatment. By contrast the human patient suffers from a condition with a specific, well-defined set of symptoms including smaller handwriting and ‘pill-rolling’ – a movement that looks like the patient is rolling an imaginary pill between his fingers. The brain activity is specific, and unlike the lab animals, when a human patient gets it, it will just continue to get worse.

Experiments on monkeys have served to divert time, money and other resources from genuine research. In fact, a textbook concerned with lab animal use notes the high cost of experiments on monkeys in PD experiments.[4] All the progress has come from human studies.

Real Scientists, Real Humans

Autopsies have proved invaluable. It was this method that revealed that a part of the brain called the substantia nigra had degenerated in PD patients, and was producing very little dopamine.[5] Dopamine is a neurotransmitter that regulates emotion and movement, and is the main carrier of nerve signals in that part of the brain. Test-tube experiments on brain tissue from autopsy confirmed this dopamine deficiency. It is worth noting that the cause of this problem, in the substantia nigra is in a part of the brain called the basal ganglia. As we’ve already read, animal models: “do not reflect the complexities of the human basal ganglion.”[6]

Through this work, scientists understood for the first time that what was happening was that nerves containing dopamine were dying, and the brain had insufficient dopamine to function properly. This led to the use of treatments that would boost the levels of dopamine in the patient. These treatments had beneficial results. [7]

However, this research didn’t just benefit PD patients. Epileptics, schizophrenics and other neurological patients were to see new research into their conditions. The autopsy team was led by Hornykiewicz of the University of Vienna, and their work was said to have “fundamentally changed how neuropharmacology is practiced”.[8] When the Nobel prize was awarded to others who followed the work pioneered by Hornykiewicz, over 250 neuroscientists wrote to the Nobel committee condemning the decision.[9]

Clearly their work was successful because it examined the patients in detail, attempting to understand what had changed to cause their illness, and trying to find a way it could be treated. This contrast’s sharply with the clumsy method of inducing vaguely similar conditions in another species and hoping something will be found that will affect the animals, and – coincidentally – human patients.

The full cause of PD is not known, but the discovery showed it was possible to decrease acetylcholine – the chemical that is in excess due to the decrease in dopamine. By chance it was discovered in humans that the nightshade plant does this – and relieves some symptoms.[10]

Similarly, it was discovered by studying patients that the recreational drug ecstasy does the same by altering serotonin levels. Human studies by Dr Brotchie showed that PD patients have differences in their serotonin receptors, and so the possibility of using similar – but safer - drugs to ecstasy has been raised.

Levodopa has been discovered to cross the blood-brain barrier in the brain and boost dopamine production. This was discovered through human studies, and treatment with levodopa relieves symptoms by converting itself into dopamine.[11]

Studying humans has also made other advances.

Autopsies showed that the loss of levodopa is due to the dopamine receptor degenerating.[12]

Dopamine can be metabolised more slowly if the patient has been given a particular compound, such as that found in a depression treatment, Selegiline. [13]

Epidemiology (population studies) has led to concerns that pesticide use may cause PD.[14]

A genetic cause is suspected, and a discrepancy on the 4q chromosome has been linked to adult-onset PD[15] [16] [17] [18]. The discovery of the protein involved has been described as “the first major breakthrough in the understanding of the disease in thirty years.”[19]

Similar clinical (human) methods of research identified the 6q chromosome as the one responsible for juvenile-onset PD.[20]

Genetic profiling also identified the role chromosome 2p13 may be playing in an intermittent version of the condition.[21]

These advances were all made scientifically, by studying the human patient in a careful, methodical manner, and being aware of developments elsewhere which helped make discoveries by accident. However, the most important discovery remains. That is, understanding why, in human PD patients, the substantia nigra dies. Although this hasn’t been discovered yet, hopes may be raised by the technology available to today’s clinical researcher.

Relief at the Flick of a Switch

One of the most attention-grabbing treatments is the recent introduction of deep-brain stimulation to PD patients. It enables patients to use a remote control box to stimulate electronically the brain and give instant relief from tremors.

Before this technique was available, doctors used thalamotomies: a chance discovery in the 1950s revealed that destroying a small part of the brain would relieve PD symptoms.[22] To help them find the right part of the brain, surgeons would use electrical currents to excite the neurons and identify them. In 1987, Dr Benabid found by chance that a different frequency current would calm the neurons, and when he applied this current to certain brain areas, he could stop the symptoms entirely. All this was discovered at work with human patients.[23] He soon came across a patient for whom the traditional thalamotomy was too risky, so he tried permanently implanting the electrodes to enable the neurons to be repeatedly calmed. In America the method was approved for treating tremor in 1997, and Parkinson's disease in 2002. Europe and Australia approved the treatment in 1998.

There are side effects and this is not an ideal method, but it has produced startling results which have transformed people’s lives. Dr Bernabid, described as “the technique's developer” in New Scientist,[24] has videos of patients waltzing after receiving the treatment. His work leading to this, at Grenoble University Hospital in France, was through studying human patients. Given the specific nature of the illness and the precision required for treatment with the method, it’s hard to believe the technique could even be used in monkeys with any relevance, let alone developed in them and applied to people.

The Future of Research

Thanks to the PET scanner, TMS and fMRI, the dopamine activity in a living human patient can now be monitored. The whole of the dopamine process can now be imaged with the technology.

As with many areas of science, we need to study the nature of Parkinson’s Disease on a very exact and specific level. This means that the vague similarities animals may have, or may appear to have, are just not good enough. Patients deserve better, and continuing animal use in researching PD will only serve to divert resources away from the clinical methods, which have enabled advances so far.

Conclusions

Animal models have similar symptoms – not the same cause as human patients.

The ‘best’ animal model recovers; human PD patients just get worse.

Autopsy revealed how the illness works.

Treatments and further understanding are due to clinical study, population study, genetics and technology.

1 Kau & Creese in Emerich, Dean and Sanberg (Eds) Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic, Humana Press 2000
2 Nuc Med Biol 1998; 25:721-8
3 Current Opinion in Neurology 1996;9:303-7
4 Kau & Creese in Emerich, Dean and Sanberg (Eds) Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic, Humana Press 2000
5 Science 2001;291:567-9
6 Current Opinion in Neurology 1996;9:303-7
7 Science 2001;291:567-9
8 Science 2001;291:567-9
9 Science 2001;291:567-9. Parkinsonism and Related Disorders, March 2000
10 Gerlach, M & Riederer, P Journal of Neural Transmission 1996;103:987-1041
11 Journal of the Neurological Sciences 1973;20:415-55
12 Reuters Health, October 18th 2000
13 Reuters Health, November 17th 1999
14 Parkinson’s Disease Council (UK) Annual report, 1983-4
15 Science Vol 276, June 27, 1997
16 Science Vol 277, July 18, 1997, p387
17 Nature Genetics 1998;18:106-108
18 Nature 1997; 388:839-40
19 Science Vol 276, 27 Jun 1997, p378 & Vol 277, 18 Jul 1997, p387. Nature 1997; 388:839-40. Nature 393 p702. Nature Genetics 1998;18:106-108
20Nature Vol 329, April 9, 1998, p605.
21 Nature Genetics 1998;18:262-265.
22 New Scientist vol 183 issue 2457 - 24 July 2004, page 40
23 New Scientist vol 183 issue 2457 - 24 July 2004, page 40
24 New Scientist vol 183 issue 2457 - 24 July 2004, page 40

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