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Parkinson is a neurodegenerative, slowly progressive neurological disease which develops when certain nerve cells of the brain, in a region called the substantia nigra, die or become impaired. It affects muscle control, and balance, associated with the loss of dopamine-producing brain cells which are referred to as parkinsonisms.
To date, there has been little agreement on what is the best treatment for Parkinson disease. Levodopa (L-DOPA) has been widely used as the main drug to treat Parkinson. However, prolonged usage of this drug may lose the effectiveness of treatment, where the increment of dose is required.
Patients who were not showing positive responds to drugs were given alternative treatment such as the ablation of the subthalamic nucleus (STN) or globus pallidus internus (GPi), but stimulation of these areas were also found effective. However, deep brain stimulation (DBS) is preferable to ablation as it is adjustable and reversible (Krack et al., 2010). The controversy about scientific evidence for deep brain stimulation treatment for Parkinson disease has been debated over the years. One of the most significant current discussions in legal and moral philosophy in the ethical aspect is the safety and side effects of DBS. One question that needs to be asked, however, is where do we draw the line on manipulating the human brain function?
To begin with, DBS treatment was first tested using animal models. In the aspect of Bioethics, using animal models in brain surgery may cause harm to animals. However, these researches benefit to human, as the results are significant and can be applied to human beings. Therefore, it is ethically acceptable to sacrifice a few animals to conduct research at a higher level, for the future of our medical field.
These researches are aimed to understand the concept of brain functions and neural architecture, so that it is possible to conduct a DBS treatment on human patients. Researchers have shown an increased interest in implanting Deep Brain Stimulation leads in monkey models of Parkinson disease. STN-DBS in monkey experiments may protect dopaminergic neurons of the substantia niagra from cell death (Wallace et al., 2007).
Developments in finding the treatment for Parkinson disease have heightened the need for discovering the best techniques and surgical procedures to reduce the Parkinsonâ€™s patientsâ€™ suffer. It has been proven that implantation of DBS lead in animal models is useful in finding treatments for neurological disorders (Elder et al., 2004). This is done by adapting the similar procedures used in human Parkinson disease patients. DBS in animals is one of the more practical surgical methods before applying the same procedures on human patients.
The research to date has tended to focus on DBS rather than other drug usage in Parkinson treatment. DBS lead implantation in monkeys will improve the understanding of DBS mechanisms and Parkinsonian motor signs effects. A variety of methods are used in DBS using animal models. Each has its advantages and downsides. An example of this is the study carried out by Elder (2005) which include microelectrode mapping of target structure, lead extension and DBS lead implantation, and analysing stimulation effects to verify lead placement.
High success rate and strong evidence were found when implanting DBS lead into subthalamic nucleus (STN) which displayed effectiveness of this technique; where specific cells in a specific part of the brain can be controlled. DBS characteristics in animal models are reproduced and observed to be compared to human patients behaviour.
Human DBS lead at a scaled down version were used in the study, where mini-sized leads were implanted into animal models. Figure 1 below shows the comparison in size of lead used in monkey and human; where the STN width to electrode width ratio is 3 to 1. Different animal models require different scales of leads (Elder et al., 2004).
Mapping and microstimulation appear to be the most critical roles in determining target structures and mapping their borders and three dimesional extents (dorsal/ventral, anterior/posterior and medial/lateral extents of the structure). Tremor is analysed by arm and leg muscular activity electromyographic recordings.
Figure 2(A) describes the modulation of stimulation parameters by programming the internal pulse generator. The pulse width and stimulation amplitude are adjustable and comparable to those applied in human patients. Behavioural effects of DBS were examined by observing the changes in animal behaviour. A constant monitoring activity is required . In figure 2(B), pulse generation is being described through stimulating lead in target nucleus (Elder et al., 2004) .
The results of this study prove that DBS leads implantations may be applied in animal models of neurological disorders. These techniques allow scientists to thoroughly reproduce DBS characteristics which are observed in human patients in animal models. These findings further support the idea of DBS effects, where comparisons of results can be made from different laboratories investigating DBS effects in nonhuman models.
There are two positions on animal experiments : some scientists support animal experiments, but some investigators are against animal experiments. Experimenting on animals is only morally acceptable if minimised sufferings are involved in the research and if it benefits to human which cannot be obtained using other methods.
However, some scientists believe that conducting animal experiments are unacceptable as there are other methods in providing the research results using non-animal models besides causing sufferings to animals. Gluck (1991) concludes : â€œThe use of animals in research should evolve out of a strong sense of ethical self-examination. Ethical self-examination involves a careful self-analysis of one's own personal and scientific motives. Moreover, it requires a recognition of animal suffering and a satisfactory working through of that suffering in terms of one's ethical values.â€Â
The mechanism of DBS is still not fully understood, and many researches are conducted to investigate the DBS effects to human. Some may debate that is unethical to perform this treatment on human patients. If that is the case, should we wait until the solution is fully justified before applying on humans? On the other hand, DBS procedure is ethically justified as it has shown and proves success on animal models which may reduce the risk to the human patients with high potential benefits.
However, there is an inconsistency with this argument. Is it ethically right to apply DBS on human patients when the research of DBS long term effects are still in progress? Do we want to undergo a new type of surgery that may invade the brain really either causing negative or positive responds? Will there be another alternative treatment which is less at risk to replace DBS treatment?
As we all know, Parkinson disease is a progressive neurological disease. Patients cannot afford to wait for years for the research to be completed, before receiving the DBS treatment (Clausen, 2010). So it is ethically right for patients to undergo the most optimum current treatment, which is DBS. However, if there is a better alternative treatment available in future, it would be ethically arguable to perform DBS in human. Although the long term effects of DBS are still not fully understood, it is morally right to carry on with this treatment on patients who are not responding to any other types of drugs, so there will be higher chances of the patients to live a better quality of life.
In conclusion, it is ethically right to implant DBS leads in monkey models of Parkinson disease before conducting the real surgery onto real human patients as a test model to human beings. It is also important to fully understand the fundamentals of neural and brain functions so that the DBS treatment for Parkinson disease is more effective on humans.