Tag Archives: animal research

Objections to the Marginal Case Argument

Scientists are often challenged with the so-called marginal case argument.

We are asked to spell out the criteria that make our experiments justifiable in animals but not in humans with comparable abilities and therefore comparable interests. These criteria, we are told, must be evaluated for each individual separately (so-called moral individualism). The resulting argument against animal research consists in pointing out that no matter what criteria are selected, it is always possible to find some humans (e.g., the senile, the cognitively impaired or the comatose patient) who should also be candidates for invasive research. According to this line of reasoning, logically consistency demands that we conduct experiments with these human patients along or instead of using animals.  If we are unwilling to do so, then we must be guilty of speciesism.

Same moral status?

Let me bring up a few objections to this argument.

First, it seems clear (to me at least) that the intrinsic properties of an individual cannot possibly be all that matters in assessing moral status of living beings.  If such properties were all that mattered, then we should feel comfortable granting a rock, a dead cat, and human remains the same moral consideration since they can all be classified as inanimate objects with no interests of their own.  And yet, while nobody will object to a child playfully kicking a rock, most will not feel comfortable with him kicking a dead cat for his or her amusement or using human remains in an art project for school.  The suffering such acts will inflict on others must count as well.  Thus, we must reject moral individualism. Once that premise is gone, the entire marginal case scenario falls apart.

Second, even if for the sake of argument one accepts moral individualism, the resulting moral theory is impractical. Are we prepared to evaluate every single individual we encounter in life to decide on his or her moral status?  Should we assess the cognitive abilities of the child now crossing the street? The dog walking with her? The squirrel that just rushed in front of our moving car?  On one hand, consistency demands that we do so, but applicability demands that we come up with a more practical approach. Indeed, our ability to function in daily life is aided by organizing the world into different categories (or kinds) of living beings and making broad assessments of their interests and moral status. Our brain’s ability to quickly recognize species membership facilitates this. It enables us to determine that the squirrel running in front of our car is a living creature and to swerve to avoid running it over—unless doing so would endanger the child crossing the street. In most situations, we can assess the interests of living beings based on the normal life of the members of that species. We have no need to assess the specific interests and moral status of this particular squirrel and this particular child.

Third, the marginal case scenario is nearly always posed by using an impaired human and a non-human animal, rather than a normal human and a non-human animal with super-natural abilities. Why? Because there is a clear difference between these two situations.  On one hand, should an ape appear in front of us, such as in Kafka’s “Report to the Academy”, speaking in fluent English, asking to be treated as a peer, it seems difficult to think we could refuse on any grounds, even if it represents an extraordinary case.  On the other hand, when human patients are impaired from their normal state, in most cases, we have no absolute certainty the condition is permanent.  A cure for Alzheimer’s or autism may possibly be developed in the future and their mental capacities restored.  Moreover establishing the lack of cognitive function with confidence may be more difficult than we have anticipated, with new studies showing that patients in vegetative state may retain some cognitive function. And, as I mentioned earlier, even in cases were science tell us there is no hope for recovery on the horizon, harming these patients would cause suffering in others that must also be taken into consideration.

Finally, there is also a scientific objection: Even if one were to accept on principle the suggestion by animal philosophers and activists that if we experiment on animals we ought to be experimenting on impaired human patients, that population would not be best suited for scientific studies. Patients with pre-existing conditions have a wide range of abnormalities and individual differences that would make it extremely difficult to conduct properly controlled scientific studies.  Thus, in addition to moral considerations, there are valid scientific reasons to reject the proposal of using impaired humans rather than animal subjects in most studies.

Good, bad, useful? Reflections on animal models for Parkinson’s disease research

Parkinson’s disease is a relentless, ruthless neurodegenerative disorder that often strikes in the early “golden years”, around 60 years of age, but sometimes much earlier.  It progressively robs its victims of every capability that makes life enjoyable, from their ability to move, talk, eat by mouth, and in the worst cases, decreasing their cognitive abilities.

In the sixties, pioneering work in animal models, primarily rats, led to the discovery of a “pill” that transformed the lives of many patients by restoring their ability to move and allowing them to perform daily tasks, often continuing to work, travel, and to enjoy sports and family time.  In research that earned him a Nobel prize many years later, Arvid Carlsson and colleagues reproduced in these rats the main chemical deficit that exists in patients, and found that administration of l-dopa (sinemet) could greatly improve the motor deficits of PD patients.

Subsequent work, always based on generating a “model” of the disease in animals by destroying the neuronal cells that also die in patients, have led to refinement of this treatment; additional advances have led to surgical methods (deep brain stimulation) that further improved quality of life for many patients.

Why should we continue to use animals to study this disorder?

First, as any patient will tell you, the available treatments do not work on all the symptoms they experience, such as depression, sleep disorders, and digestive problems that plague their lives often even more deeply than their motor disorders. Second, the current treatments do not cure the disease, and their benefits do not last forever. In time, the treatments progressively lead to side effects, for example uncontrolled movements or spasms that leave the patient to chose between not moving at all or moving too much. Today’s medications do not stop the progressive loss of nerve cells in the brain, which will ultimately lead to disability and death.

A real treatment for the disorder will have to address its root cause and stop its process, perhaps even reverse them. This is where a lot of confusion on the utility and value of the animal models arises. In the press and even the scientific literature there are statements expressing concern that there is “no good model” of Parkinson’s disease, and sometimes that existing models are useless because some drugs that work in animals fail in the clinic.  It is a complex issue that is a source of debate among scientists and lay people alike. However, one has to examine the roots of the problem.

Models are only as good as our understanding of a human disease at a given time. Science is an evolving process and so are our models of disease. There was a time when we did not understand why some people would die from blood transfusion and others did not, because blood types had not yet been discovered. In the case of Parkinson’s disease, we have known for about a century which cells die in the brain of patients but we still do not know why. The early models, those that led to the major breakthroughs in treating some of the symptoms of the disease, reproduce this loss of cells but do not address its mechanism. We now know more about this mechanism because of research on the causes of rare cases of the disease that have a genetic component and run in families. We also know that even though most cases of Parkinson’s disease do not have a clear genetic component, the mechanisms may be the same. New understanding has led to a new generation of models, in which defective genes are introduced in mice to reproduce the mechanisms thought to cause the disease in people.

GM mice help to uncover the processes of Parkinson's disease. Image courtesy of Understanding Animal Research.

Are those models perfect?

No model is perfect. No model can be expected to reproduce all the symptoms that occur in patients. Even if similar, the brain and nervous system of mice are not identical to those of a human, who walks on two legs, not four paws, and can live up to a hundred years rather than two. Yet, a lot of the general functions that are affected by the disorder in humans are present to some extent in the mouse model.

More importantly, only in an animal can one examine the very beginning of the disease process. Many studies in humans have now shown that diseases like Parkinson’s begin to affect a person’s body decades before they even know it. The disease causes subtle changes that are not even perceived as abnormal but have long-term consequences, just as a minute water leak can over years rot a wooden beam and lead to a roof collapse. As the disease progresses, it can manifest itself with minor troubles, so unremarkable that they are not recognized as related to Parkinson’s disease, for example problems with sleep and smell, that are very common and have many different causes.

Thus, in a human, we will never be able to understand the beginning of the disease, the water leak, because we do not know in which individuals they are occurring. This is where animal models are the most useful. By reproducing anomalies, such as the overexpression of the protein alpha-synuclein, that cause the disease in people, we can study the mechanisms from the beginning and find ways to stop the damage as early as possible.

Why then are people writing that animal models of Parkinson’s disease did not accurately predict whether a new treatment can be effective in patients? For one thing, those drawbacks were largely based on old models, which were – and still are – useful for some things (developing treatments for symptoms and evaluating new approaches to restoring lost function such as gene therapy) but were only minimally productive in developing treatments to halt the development of Parkinson’s disease because of our limited knowledge of mechanisms at the time.

Will the new models be better at predicting drug efficacy in the clinic? It is too early to tell because none of the new compounds developed and currently being tested in these models has yet been tested in patients. Should these animal models be replaced by computer modeling of the disease?  Probably, but this is years in the future. The science of modeling all the molecular interactions that take place within a cell, and of all the connections this cell establishes with other cells in a complex organism in a way that could illuminate a disease process and make sound predictions leading to effective treatments is in its infancy. In the meantime, patients are diagnosed, grow worse, and die every day.

We cannot wait. Just as previous models, although imperfect, led to transforming discoveries that bought years of functioning to patients who otherwise would have been locked in a chair and condemned to an early death, the new models continue to lead every day to discoveries that bring us closer to an effective treatment. Nothing can replace them at the moment.

Marie-Francoise Chesselet, M.D., Ph.D.
Charles H. Markham Professor of Neurology
University of California, Los Angeles

The new face of transplant surgery, thanks to animal research

Yesterday the University of Maryland Medical Center (UMM) announced most extensive full face transplant completed to date, including both jaws, teeth, and tongue. In a marathon 36-hour operation the surgical team led by Professor Eduardo Rodriguez were able to transplant a face of an anonymous donor onto their patient Richard Lee Norris, who had been injured in a gun accident 15 years ago.  The operation was the culmination of years of clinical and animal research undertaken at UMM under the leadership of Professor Stephen Bartlett, and funded by the Department of Defense and  Office of Naval Research due to its potential to help war veterans who have received serious facial injuries.

This successful operation, termed a vascularized composite allograft, was made possible not only by the selflessness of the family of the anonymous donor, but also by the years of animal research undertaken by Professors Rodriguez and Bartlett and colleagues. For example, a key factor in the success of this operation was that they transplanted high amounts of vascularized bone marrow (VBM), which came inside the transplanted jaw, a technique that was developed by the team after observing that tissue rejection following composite tissue allotransplantation in a cynomolgus monkeys was greatly reduced when VBM was included in the transplant. This discovery will also help to reduce the amount of immunosuppression that Mr. Norris and future patients require following facial transplants.

Of course this is far from the first contribution that animal research has made to transplant surgery, from the development of the techniques of kidney transplant through research in dogs by Joseph Murray and colleagues, to the careful experiments in dogs conducted by Norman Schumway and Richard Lower that led to the first successful heart transplants, to the studies in mice and rats that identified the immunosuppressive properties of the drug cyclosporin that transformed the transplantation field in the 1980′s, animal research has made a crucial contribution to this field. Indeed, in his 1990 Nobel Lecture Edward Donnall Thomas stressed the importance of animal research to his Nobel prize winning discoveries concerning bone marrow transplantation.

Finally, it should be noted that marrow grafting could not have reached clinical application without animal research, first in inbred rodents and then in outbred species, particularly the dog.”

Animal research continues to make key contributions to transplant science, and we have had several opportunities to discuss its role in the development of lab-engineered tissues for transplant, such as the artificial trachea and bladder, on this blog.

Yesterday’s news from the University of Maryland is another reminder that animal research is still crucial to advances in transplant surgery. It is also worth remembering that when animal rights groups attack animal research conducted by the Department of Defense, it is work such as that which led to yesterday’s breakthrough that they are attacking.

Paul Browne

Hypothermia in stroke: EuroHYP moves from rats to man

Earlier today the BBC reported that European Stroke Research Network for Hypothermia (EuroHYP) has announced the launch of a major clinical trial – involving 1,500 patients in 15 centers across Europe – to evaluate whether cooling the body by 2 degrees can reduce the risk of death and disability in ischaemic stroke.

CT image of an ischemic stroke. The dark area in top left quadrant of brain shows the damaged brain area. Welcome Images.

The trial, known as EuroHPY-1, is being lead by Professor Malcolm McLeod of the University of Edinburgh, and its design is supported by very strong evidence from studies in animals – mostly rats -that we discussed on this blog just over a year ago, with the trial synopsis stating that:

Systematic review of animal studies modelling ischaemic stroke suggests that cooling is the most promising intervention identified to date. In these animal studies, cooling to 35˚C reduced infarct size by about one third, and cooling to 34°C by around 45%.”

We are very pleased to learn that this trial – which has the potential to radically alter and improve the way in which ishaemic stroke is treated – has now received sufficient funding to go ahead.

In another interesting report on the BBC today, scientists at the University of Colorado have reported that they have used studies of genetically modified mice to identify the mechanism through which the brain-derived neurotrophic factor (BDNF) interacts with other regulatory proteins to control appetite and body fat levels.  In some people with the genetic disorder WAGR syndrome it was observed that having only one copy of the gene encoding BDNF was associated with excessive appetite and obesity, but until now the mechanisms through which BDNF regulates appetite was not clear.

This research fills in another important gap in our understanding of how genetic differences between individuals influence the risk of becoming obese, and we know already that genetics makes a very large contribution to that risk. While the complex nature of the influence of genes on obesity means that it is rarely possible for a single medication to have a dramatic impact – though there are a few examples such as the treatment of leptin deficiency with recombinant leptin (following studies in the leptin-deficient Ob/Ob mouse) – increasing understanding of the influence of the impact of an individuals genetic makeup on their risks of becoming obese will aid the development of both new medicines to help combat obesity, and the development of more targeted lifestyle interventions that are more likely to be successful for that individual.

Taken together these two items reported in the BBC highlight the importance of animal research to medical progress, both as a way to uncover the processes involved in health and disease in basic research, and as a way to evaluate potential therapies in order to obtain sufficient information to proceed to trials in human patients.

Addendum:

More good clinical trial news that I missed earlier!

On Friday the Cystic Fibrosis Trust announced that thanks to major grants from the Medical Research Council (MRC) and National Institute for Health Research (NIHR) they will soon launch their clinical trial of non-viral gene therapy for Cystic fibrosis.

We briefly discussed the important role played by animal research in the development of this therapy in a blog post last August, and it is great to see that the UK Cystic Fibrosis Gene Therapy Consortium (UK CFGTC) has now raised sufficient funds to proceed with this exciting trial.

The UK CFGTC has also announced that it received a further £1.2 million fund research to develop a lentiviral vector for improved delivery of gene therapy in cystic fibrosis, much of which will like earlier work on this vector require the use of animal models.

Paul Browne

The 21st Century Scientist

Earlier today we discussed some of the characteristics of the animal rights crank, so it’s perhaps appropriate that an award announced earlier this week has highlighted the best qualities of the scientists who are really shaping 21st century medicine.

The Grete Lundbeck European Brain Research Foundation has awarded its 2nd €1-million Brain Prize to Professor Karen Steel of Cambridge University, founder of the Mouse Genetics Programme at the Wellcome Trust Sanger Institute, and Professor Christine Petit of the College de France, head of the Genetics and Physiology of Hearing laboratory at the Institut Pasteur in Paris, for:

their unique, world-leading contributions to our understanding of the genetic regulation of the development and functioning of the ear, and for elucidating the causes of many of the hundreds of inherited forms of deafness”

Continue reading

The Animal Rights Crank

We live in a world where science is increasingly being denied, an age where some appear to value ignorance more then knowledge, where everyone is an expert, where celebrities give medical advice, where every idea is equally valid and worthy of being called a theory, where evidence and fact attain the same stature as delusions and fabrications, where information is diluted in noise, and where bullying is activism.

We see this play out every day, when apparently thoughtful people reject scientific facts to conjure their own, making it nearly impossible to have a reasoned and civil debate on any number of important topics in our society, from climate change, to vaccines, stem-cells, evolution and the use of animals in research.

That’s why today an increasing number of people spend their time decrying the denial of science:

Some animal right activists are veterans in this game. They have a long history of twisting facts,  cherry-picking data, and quoting others out of context to suit their interests. The intelligent crank has become an essential ingredient of the animal rights movement.  The crank regards everyone else as ignorant and stupid, except for himself, of course.  He will accuse scientists of dishonesty, and of having other ulterior motives for their work and opinions. If his ideas are ignored, the crank will declare victory and his arguments to be unanswerable. He will display public tantrums when his work is rejected from scientific journals or when he is refused to lecture in academia. His “theories” are typically based on complexity rather simplicity, ambiguity rather than clarity, and fabrications rather than facts.  He will publicize these ideas in volumes that advertise his vast erudition.

When the crank and his followers face a simple fact that contradict their views, such as the discovery of a novel therapy from breast cancer based on the antibody from a mouse, they will have to offer an explanation. Rather than accepting the rejection of their beliefs, they will make up a story, such as suggesting the discovery was the outcome of chance. In this regard, there is absolutely no difference between their behavior and that of the Seekers who, upon realizing the Aliens did not show up to rescue them as their prophet had assured them, had to rationalize an explanation to prevent their entire belief system from collapsing.

We appear to live in an age where a prophet and his cult have the same standing as a scientist and his method. But science, facts and knowledge will prevail, and together, we will get through the STORM:

A Brief History of Deep Brain Stimulation

An on-going campaign against the use non-human primates to study Parkinson’s disease (PD) at the University of British Columbia prompted me to summarize some basic facts about the work and the history of a successful therapy was developed.

Why is the work done?

In the U.S. alone there are between 500,000 and 1 million people living with PD, with about 50 to 60 thousand new diagnoses every year.  The National Institutes of Neurological Disorders and Stroke (NINDS) estimates the cost to our society is at least $5.6 billion, including both direct medical expenses and indirect costs from lost income, disability payments and so on.  Moreover, the emotional toll of Parkinson’s on patients and families is enormous.

One of the most successful therapies developed for PD  involves the electrical stimulation of deep structures within the human brain — so called deep brain stimulation (DBS).  The technique works remarkably well for some patients.

How was the method developed?

Back in 1983 Langston and colleagues reported on a clinical case study of four patients that developed Parkinsonism after illicit drug use.  Analyses of the drugs they had taken via mass spectroscopy revealed primarily MPTP, but there were also traces of MPPP. They suggested MPTP might be the most likely culprit and suggested that:

“Given the pathologically studied case, the relative purity of the clinical syndrome seen in our patients, and its remarkable clinical resemblance to Parkinson’s disease, the drug [MPTP] may be of value in producing an animal model of Parkinson’s disease.”

In other words, a group of clinicians studied a handful of human patient cases, identified a potential link between MPTP toxicity and the development of PD, and proposed to follow up with animals studies.

In 1983, Burns and colleagues follow up on this idea by trying to replicate the disease in monkeys.  Indeed, intravenous administration of MPTP caused the animals to develop rigidity, postural tremor, eyelid closure, and many other symptoms of Parkinsonism.  Moreover, their symptoms could be relieved by the administration of L-dopa, exactly as it was the case with the Langston et al patients. The animal model also allowed them to characterize the selective destruction of dopaminergic neurons in the subtantia nigra and a marked reduction in the dopamine content of the striatum.  They offered MPTP treated monkeys as a model to explore therapies for PD.  How many animals were used?  Twelve.

Although these anatomical studies shed light into the brain areas that might be involved in PD it was unclear what functionally was causing the observed symptoms.  Subsequent work by Mitchell et al (1989) using single unit recordings and lesion studies in monkeys pointed to increased activity in the subthalamic nucleus (STN) as generating motor abnormalities.  How many monkeys were used?  Eight.

A natural question arose from these studies.  Would suppressing the activity of these hyperactive neurons help in alleviating the symptoms of the disease?

Two studies showed that lesions of the STN could reverse the effect of Parkinson symptoms in the monkey MPTP model, with studies by Bergman et al (1990) and Aziz et al (1991).  These studies not only began to dissect the functional connectivity within the basal ganglia-thalamocortical circuit, but also offered evidence that inactivation of the STN could work as a potential therapy for Parkinson’s.   How many monkeys were used in these two studies?  Four.

Shortly after, Benazzouz et al (1993) showed that instead of lessoning the STN one could use high frequency stimulation of the STN to alleviate the symptoms in MPTP treated monkeys.  Supposedly, the high frequency stimulation suppresses the activity of these cells acting as a “virtual lesion”.  How many monkeys were used here?  Two.

Indeed, Limousin et al (1995) successfully applied this method in three patients and concluded:

“In this study, bilateral subthalamic nucleus stimulation improved akinesia and rigidity in three patients with Parkinson’s disease.  This is in agreement with the results obtained in monkeys with MPTP-induced parkinsonism by lesions or stimulation of the sub-thalamic nucleus.”

Number of humans used?  Three.

And to dispel any remaining doubts he writes in a recent review that:

“The knowledge of the functional changes of basal ganglia activity in the parkinsonian state as it emerged from extensive experimental studies on animal models has provided the theoretical basis for surgical therapy in PD. The 6-hydroxydopamine (6-ODHA) rat model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD provided powerful research tools for uncovering the pathophysiology of changes in functional basal ganglia activity in PD.” 

And finally one may ask, ho many human patients have benefited from this type of work?

The answer is 80,000 and counting.

What do these patients think of such studies?

Here is one — please listen to him carefully.

And if you truly want to learn more here are some extra resources:

SfN brain briefing on PD discoveries.
The Michael J. Fox Foundation
Information from National Institutes of Neurological Disorders and Stroke.
Information from Understanding Animal Research.

STOP lying about research at the University of British Columbia

In a post a couple of weeks ago entitled “End of primate research at the University of Toronto?” Allyson Bennet wrote about the truth behind the spin that primate research has ceased at the University of Toronto (UT), commenting that:

 If nothing else, those inclined to dodge should consider that they are deriving benefit from the work of their colleagues at the institutions still willing to assume the risk and responsibility.”

It hasn’t taken very long for other animal rights groups in Canada to pick up on UT’s perceived change of policy, with a Vancouver-based group named STOP UBC Animal Research (STOP) quick to demand that the University of British Columbia (UBC) follow UT’s example.

For more than a year now STOP have been engaged in a high-profile campaign against animal research at UBC, prompting UPC to respond by providing information about the animal research they undertake. One of their main targets has been Professor Doris Doudet, who employs advanced imaging modalities such as positron emission tomography (PET) for the evaluation of functional, neurochemical, and anatomical changes in the brains of animal models of Parkinson’s disease.

In a paper published online last November in the Journal of Cerebral Blood Flow and Metabolism Professor Doudet and her colleagues reported that they had used PET to confirm that abnormal metabolic patterns recently observed in the brains of Parkinson’s disease patients are also found in the brains of monkeys which have been treated with the drug MPTP to kill the dopamine producing neurons in the brain and induce Parkinsonism. This result both confirmed the close similarity between MPTP-induced Parkinsonism and Parkinson’s disease, and provides another useful way in which the effects of candidate therapies for the treatment of Parkinson’s disease can be evaluated in this much-used animal model of Parkinson’s disease.

Unfortunately in the course of the experiment four of the eleven monkeys treated with MPTP developed an unusually severe response, and rather than recovering after the experiment – as is usually the case with monkeys treated with MPTP – they had to be euthanized. The Journal of Cerebral Blood Flow and metabolism paper makes it clear that Prof. Doudet and her team responded quickly and correctly to the unexpected situation to minimize any suffering the animal’s experienced.

Not surprisingly STOP are seeking to make capital out of this event…but this is where animal rights propaganda parts company with the facts.

In a statement to the UBC student newspaper Ubyssey STOP claim that far from being accidental the four monkey deaths were planned:

a 2010 progress report on Doudet’s study indicated four monkeys were to be “sacrificed to neuropathology”—two at the six-month mark after showing mild symptoms of Parkinson’s, and the final two after twelve months.

“Animals should be able to recover from the Parkinsonism that researchers inflict on them,” Birthistle said. “She’s intending to kill them all along, and then they’re talking about it as being unforeseen circumstances.””

So what is this “2010 progress report? Well, another statement by STOP quoted in a Vancouver newspaper explains that they are referring to a study named “L91”.

So what is L91 all about?

It’s not the first time that STOP have complained about study L91, back in January of last year they staged a protest against it. L91 is a project planned by Prof. Doudet to use PET to study the effect of injection of the proteasome-inhibitor Lactacystin on the brain function of four macaques, and a description of the proposed project can be found on page 25 of this TRIUMF publication. Lactacystin injection is a relatively new animal model of Parkinson’s disease, recreating the damage to the proteasomes of the dopamine secreting neurons of the substantia nigra region of the brain observed in Parkinson’s disease patients, and has the potential to become a valuable resource for evaluation new therapies.

So it’s abundantly clear that the proposed study L91 is NOT the same as the study published last November in the The Journal of Cerebral Blood Flow and Metabolism, as the former plans to use lactacystin to induce Parkinsonism while the latter used MPTP. It is equally clear that STOP are well aware that these are not the same study, as they have access to all the relevant documents.

Yet, not only to STOP repeatedly and dishonestly claim that these are the same study, but on the basis of this claim they go on to make false allegations of professional misconduct against Prof. Doudet and demand that UBC suspend her from her duties and carry out a full investigation.

And I’ll bet that they will express surprise and outrage when UBC refuses to comply with their demands!

Before leaving this subject it’s worth addressing the importance of the role of animal research in Parkinson’s disease research, something that we are well aware of thanks to Pro-Test’s own Prof. Tipu Aziz, whose research using the MPTP model of Parkinsonism made major contributions to making deep brain stimulation (DBS) for Parkinson’s disease the success it is today.  I’ll value the views of the neuroscience community as a whole – including great neuroscientists such as the physician-scientist Prof. Alim-Louis Benabid, pioneer of DBS for Parkinson’s disease – over those of the few fringe scientists that STOP can scrape together.  Prof. Benabid and other genuine experts on Parkinson’s disease recognize that while Parkinsonism models such as the MPTP monkey do not recreate every aspect of Parkinson’s disease they play a vital role alongside clinical research in uncovering the process that cause the disease and its symptoms, and in the development of new therapies for Parkinson’s disease.

As Prof. Benabid wrote in a review in 2004:

The knowledge of the functional changes of basal ganglia activity in the parkinsonian state as it emerged from extensive experimental studies on animal models has provided the theoretical basis for surgical therapy in PD. The 6-hydroxydopamine (6-ODHA) rat model and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD provided powerful research tools for uncovering the pathophysiology of changes in functional basal ganglia activity in PD. “

and in a review published this year

The specific effect of DBS at high frequency, discovered during a VIM thalamotomy, was extended to the older targets of ablative neurosurgery such as the pallidum, for tremor in Parkinson’s disease (PD), dyskinesias, essential tremor, as well as the internal capsule to treat psychiatric disorders (OCD). A second wave of targets came from basic research (in this instance animal research –PB), enabled by the low morbidity, reversibility, and adaptability of DBS. This was the case for the subthalamic nucleus (STN) which improves the triad of dopaminergic symptoms, and the pedunculopontine nucleus (PPN) for gait disorders in PD. “

As with so many areas on medicine it is the confluence of animal and clinical researhc that is driving advances in the treatment of Parkinson’s disease.

Rather ironically animal rights organizations like STOP and their supporters are very quick to claim that Prof. Benabid’s serendipitous discovery that electrical stimulation of the ventralis intermedius could reduce the tremor associated with Parkinson’s disease demonstrates that research using the MPTP model is unnecessary. They seek to co-opt his stature as a leading neuroscientist while simultaneously ignoring the fact that he not only recognizes the importance of animal models of Parkinson’s disease but himself undertakes studies with the MPTP Monkey model and other animal models of Parkinson’s disease.

So, the question is who you are going to believe, leading neuroscientists like Prof. Doudet and Prof. Benabid, or STOP? Somehow I doubt it will take you long to come to a decision!

Paul Browne