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Postulates for brain transplantation
164
Surg Neural 1991;35:164
Editorial
Postulates for Brain Transplantation A recent publication [l] of a single case report dealing with neurological improvement in a patient with parkinsonism following fetal brain transplantation, which received front-page coverage in The New York Times and other major newspapers throughout the world, raises a number of serious public and scientific issues. This latest example of clinical experimentation in the area of brain grafting for degenerative diseases of the nervous system was undertaken by an extremely experienced Swedish group of investigators who had previously pioneered cerebral transplantation in both animals and humans. In this most recent article, the authors have, at long last, provided what appears to be confirmatory evidence that the grafted fetal brain tissue had survived and was chemically active by utilizing PETT scanning technology and demonstrating an increase in dopamine activity in the intracerebral region where the grafted tissue had been stereotaxically placed. This is in marked distinction to the neuropathological examinations that have been conducted on patients who have died following adrenal gland transplantation, in which, to date, there has been no morphological evidence that these tissue grafts have survived. In spite of the Swedish success, there are many unsolved problems facing investigators in the area of human brain transplantation. For example, we know very little of the immunological properties of the human brain, particularly as they relate to exposure to cellular implants; thus, the neuroimmunological and structural reaction of this complex organ to even grafted fetal cells is not known at this time. Additionally, these grafts require surgical placement, either by needle or open surgery, into regions where the tissue has already undergone degeneration and will be further injured by the mechanical distortion necessary to prepare the graft bed and insert the fetal tissue. Finally, almost all of the experimental data in this field have been derived from rat model studies, requiring a quantum jump in terms of size and complexity from the rodent to the human brain. Can one really feel confident that what occurs in rodent brain transplantation should happen in human brain grafting? While the above list only provides a description of a few of the problems in this area, we have also obviously
forgotten that, for several decades in this century, it was fashionable to obtain significant neurological symptomatic relief for parkinsonian patients by open destructive surgery in the basal ganglion and thalamus. The popularity of brain transplantation with the public and the medical profession requires, in my opinion, a set of scientific requirements to be in place before these invasive techniques are carried out in additional groups of patients. Something akin to the 1881 Koch Postulates, which were established for providing the causal relationship between an organism and infectious disease, should be developed to truly substantiate the relationship between the fetal brain graft and the results seen in the neurological condition of the patient. The following “Postulates for Brain Transplantation” are suggested: Prolonged survival of the graft in a cellular volume with appropriate cytoarchitectonic structure that justifies the documented neurological improvement. Neuroanatomic demonstration of dendritic, axonal, and synaptic integration with host brain to a degree and extent to provide significant functional activity. Measurements of the biochemical and neurophysiological performance of the graft sufficient to offer specific enhancement or suppression of cerebral activity to significantly modify the disease process. With inactivation or destruction of the transplant, clinical improvement ceases and/or regresses. Before brain transplantation becomes an international industry, we need something equivalent to the postulates set forth above to provide a scientific base for interpreting and substantiating the results of these invasive intracerebral procedures. ROBERT Cleveland,
J. WHITE, Ohio
M.D.,
Ph.D.
Reference 1. Lindvall 0,
Brundin P, Widner H, Rehncrona S, Guscavii B, Frackowiak R, Leenders K, Sawlc G, Rothwell .J, Marsden C, Bjorklund A. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 1990;247:574-7.
Surg Neural 1991;35:164
Editorial
Postulates for Brain Transplantation A recent publication [l] of a single case report dealing with neurological improvement in a patient with parkinsonism following fetal brain transplantation, which received front-page coverage in The New York Times and other major newspapers throughout the world, raises a number of serious public and scientific issues. This latest example of clinical experimentation in the area of brain grafting for degenerative diseases of the nervous system was undertaken by an extremely experienced Swedish group of investigators who had previously pioneered cerebral transplantation in both animals and humans. In this most recent article, the authors have, at long last, provided what appears to be confirmatory evidence that the grafted fetal brain tissue had survived and was chemically active by utilizing PETT scanning technology and demonstrating an increase in dopamine activity in the intracerebral region where the grafted tissue had been stereotaxically placed. This is in marked distinction to the neuropathological examinations that have been conducted on patients who have died following adrenal gland transplantation, in which, to date, there has been no morphological evidence that these tissue grafts have survived. In spite of the Swedish success, there are many unsolved problems facing investigators in the area of human brain transplantation. For example, we know very little of the immunological properties of the human brain, particularly as they relate to exposure to cellular implants; thus, the neuroimmunological and structural reaction of this complex organ to even grafted fetal cells is not known at this time. Additionally, these grafts require surgical placement, either by needle or open surgery, into regions where the tissue has already undergone degeneration and will be further injured by the mechanical distortion necessary to prepare the graft bed and insert the fetal tissue. Finally, almost all of the experimental data in this field have been derived from rat model studies, requiring a quantum jump in terms of size and complexity from the rodent to the human brain. Can one really feel confident that what occurs in rodent brain transplantation should happen in human brain grafting? While the above list only provides a description of a few of the problems in this area, we have also obviously
forgotten that, for several decades in this century, it was fashionable to obtain significant neurological symptomatic relief for parkinsonian patients by open destructive surgery in the basal ganglion and thalamus. The popularity of brain transplantation with the public and the medical profession requires, in my opinion, a set of scientific requirements to be in place before these invasive techniques are carried out in additional groups of patients. Something akin to the 1881 Koch Postulates, which were established for providing the causal relationship between an organism and infectious disease, should be developed to truly substantiate the relationship between the fetal brain graft and the results seen in the neurological condition of the patient. The following “Postulates for Brain Transplantation” are suggested: Prolonged survival of the graft in a cellular volume with appropriate cytoarchitectonic structure that justifies the documented neurological improvement. Neuroanatomic demonstration of dendritic, axonal, and synaptic integration with host brain to a degree and extent to provide significant functional activity. Measurements of the biochemical and neurophysiological performance of the graft sufficient to offer specific enhancement or suppression of cerebral activity to significantly modify the disease process. With inactivation or destruction of the transplant, clinical improvement ceases and/or regresses. Before brain transplantation becomes an international industry, we need something equivalent to the postulates set forth above to provide a scientific base for interpreting and substantiating the results of these invasive intracerebral procedures. ROBERT Cleveland,
J. WHITE, Ohio
M.D.,
Ph.D.
Reference 1. Lindvall 0,
Brundin P, Widner H, Rehncrona S, Guscavii B, Frackowiak R, Leenders K, Sawlc G, Rothwell .J, Marsden C, Bjorklund A. Grafts of fetal dopamine neurons survive and improve motor function in Parkinson’s disease. Science 1990;247:574-7.