Not for me.
Rationale of replacing the upper part of the human skull with a biocompatible, re-chargeable, re-fillable and re-cleanable electrical/molecular device to safely and effectively treat and/or cure severe, currently intractable brain disorders
This article was written in response to the 8/6/2021 emailed request from the Academia Team of
Academia Letters
based in San Francisco. Considering the useful reviews of the first version, I extended the Letter to its present length and this version is considered final.The thesis of this Letter, fully described in the title, is based on my 35 years of basic and applied neuroscience research, recorded in 5 book chapters, 6 US patents, several online papers and 51 peer-reviewed journal articles registered in PubMed, including those listed in REFERENCES [1 - 6]. Why do I not just recommend the use of an “electrical/molecular device” for severe, currently intractable brain disorders but recommend the replacement of most of the upper part of the skull, the neurocranium, with such a device as well?There are 4 reasons for this recommendation.First, current medical technologies are inadequate for the safe and effective treatment of most severe neurological and psychiatric disorders. The 6 drugs available for American psychiatrists for the treatment of Alzheimer’s disease are all useless, and this is known. As for stroke, the CDC website, https://www.cdc.gov/stroke/facts.htm tells any visitor that “every 4 minutes someone dies of stroke”, including hospitalized patients. Malignant brain tumors are as deadly today as in the time of Senator Edward Kennedy, who died of glioblastoma12 years ago, within a year of his diagnosis despite the treatment he received at the best US
clinics. The devastating seizures of at least 20% of epileptic patients cannot be eliminated with drugs, neurosurgical intervention or electrical stimulators [3 - 4]. Therefore, those who wish to change this situation must expand their thinking beyond the therapeutic repertoire of current neurology and psychiatry.Second, just as the only way to stop the BP oil spill in the Gulf of Mexico in 2010 was to go 5,000 feet underwater and fix the problem onsite, or just as Space Shuttle missions were needed to fix all five problems with the Hubble telescope onsite from 1993 through 2009,– most problems of the brain also need site-specific treatment, inside the brain, where the problems occur. Why is this? This is because flooding the whole body with drugs, vectors, electroceuticals, nanoparticles or other treatments delivered via the bloodstream will always cause potentially severe side-effects in most organs which have nothing to do with the original brain disease. Furthermore, the Blood-Brain-Barrier (BBB) prevents most relatively large compounds – including proteins, nanoparticle encapsulated RNAs, gene vectors and electroceuticals, – to enter the brain even if they would do good if crossed this barrier.Therefore, those who wish to overcome these diffculties have no choice than treating the diseased brain tissue locally, onsite, with implants accessing the subarachnoid cerebrospinal fluid (CSF) compartment to bypass the BBB.Third, it is true that various electrical brain implants (RNS, DBS, etc.) have been introduced into the treatment of brain disorders. Yet they haven’t resulted in medical break throughs. Although made by the best scientific and engineering minds, all of these devices have the same, significant problem. Namely, they perform electrical stimulation only to correct the abnormal functions of diseased neural cells and networks. But the brain is a biological machinery fundamentally different from computers. Namely, the brain is not a digital electronic machinery, but a machinery in which digital electronic processes are controlled,adjusted and continuously refined with analog molecular processes. The brain is a hybrid computer where electrophysiological and neurochemical/molecular processes work together to let some brains initiate, create, and manage products like the “Philosophiae Naturalis -Principia Mathematica”, “Tristan and Isolde”, or the design of the Taj Mahal and the Lunar Module Eagle. I argued for the importance of this approach to therapeutic brain implants as early as 2000 [1]. Since then, several more elegant and more sophisticated articles have been published on the analog - digital nature of brain functions and its significance [7 - 9], – as pointed out by Reviewer Chand. Therefore, those who wish to treat errors of the electronic molecular machinery of the brain with the right implant have no choice than make this implantable to correct both electrophysiological and neurochemical/molecular abnormalities[10-13]of Alzheimer’s disease, stroke, malignant brain tumors, intractable epilepsy and other braindiseases.
Fourth, such a brain implant must be sufficiently large not just to give space for all necessary engineered components but also to effciently treat large, multifocal, bilateral, pathologies. May I remind the reader that Alzheimer’s disease is the degeneration of the entire association cortex in both hemispheres; severe strokes often cause neuronal death and edemain such large areas in brain that hemicraniectomy is the only life-saving measure; malignant brain tumors often grow in multiple locations in both hemispheres; tens of thousands of American epileptics suffer from severe seizures because their multiple, bilateral seizure foci can not be treated with current epilepsy therapies. Furthermore, the brain implant I propose for the treatment of the mentioned diseases must also be positioned in the upper skull so that it can be easily and safely accessible: (a) to the implanted patient’s physician to re-charge the electronic section and re-fill/re-clean the molecular section daily in the post-operative phase, and then (b) to the patient himself/herself to do the same procedure weekly/biweekly at home.Thus, a single electrical/molecular structure replacing, bilaterally, most of the frontal, parietal and temporal neurocranium would be the only device sufficiently large to: (a) include all engineered therapeutic components, (b) make the treatment of extensive cortical pathologies possible, and (c) allow the physician and the patient to maintain it easily and comfortably.“How to build and test a device of this type?” – asked Reviewer Cruz with good reason. My colleagues and I did describe the basic structure [2 - 6]. The key component is a battery powered, microcontroller regulated, dual minipump connected to subarachnoid de-livery/drainage strips to not just deliver therapeutic small-molecule drugs, neurotrophic and other proteins and cell-permeable gene-editing agents into all diseased cerebral cortical tissues, but also to drain such neurotoxins out from the same tissues as excess glutamate, proin-flammatory cytokines, carcinogenic molecules, cellular debris and others. Please recognize that the drained solutions, available by the cleaning procedure, can be processed for routine clinical laboratory tests to keep the treatment optimized and run true precision medicine for the patient. The current system also records and transmits EEG feedback from the treated brain.To this system, an electrical stimulator can be added without diffculties [4]. This would both complement the molecular treatment and induce the beneficial neurochemical modifications that can follow electrical stimulus – as pointed out by Reviewer Dario – though not with the broad spectrum of receptor specific effects of drug delivery [4]. The only component that has yet to be constructed for this device is the safe and simple re-charging, re-filling, recleaning unit, of which blueprint I wouldn’t describe here to prevent its improper development and/or abuse.Are there data indicating that such a device could provide safe and effective treatment for patients suffering from currently intractable brain disorders? Reviewer Fellus was justifiably interested in this. Yes, there are such data. My team and I at SUNY Downstate Medical Center and the NYU Comprehensive Epilepsy Center proved that even the preliminary, muscimol-delivering and inflammatory cell/protein draining version of this device was able to prevent experimental neocortical seizures in non-human primates reliably, while the animals’ health and social behavior remained normal, as long as these tests lasted, often for a year [2 - 5]. This suggests that other, currently intractable, neurological and psychiatricdiseases could also be treated with such implants if each implant is modified to perform the right, disease specific, drug delivery and neurotoxin drainage. Especially, since these treatments should yield a new range of information on harmful molecular/cellular processes in the human brain, allowing the user community to continuously improve on the drug delivery –neurotoxin drainage methods. And it is this new range of information that (a) can also help the development of child specific cures Reviewer Ribeiro so passionately wants; (b) can also help to find the “biological solutions” Reviewer Bashir so correctly seeks; and (c) can also help to make the electrical/molecular device free of “depriving the brain of physiological defenses”,of which significance Reviewer Benna properly emphasized. What would it take to introduce this therapeutic device into medicine? It would take a lot, as it would need the global cooperation of not merely technically well-trained but also intellectually sophisticated neurosurgeons supported by broad-minded neurologists, psychiatrists and healthcare administrators genuinely agreeing with the vision of electrical/molecular therapeutic implants for brain disorders. Reviewer Larsen rightly pointed out the necessity of examining the Quality/Costs ratio of such devices. But this examination would require here a more compassionate capitalist thinking. First, this thinking should be at peace with the high manufacturing/implantation costs at the expense of profitability to deliver the best care for the patients selected for this therapy. Second, this thinking should also be at peace with the commercial limitation to those patients – still millions worldwide – whose condition is as severe and intractable that they themselves seek the implantation of this device. They may well open the way to the evolution of bionic humans, as deserved to be on Earth within a century or two as genetically modified humans and android robots.
Academia Letters
based in San Francisco. Considering the useful reviews of the first version, I extended the Letter to its present length and this version is considered final.The thesis of this Letter, fully described in the title, is based on my 35 years of basic and applied neuroscience research, recorded in 5 book chapters, 6 US patents, several online papers and 51 peer-reviewed journal articles registered in PubMed, including those listed in REFERENCES [1 - 6]. Why do I not just recommend the use of an “electrical/molecular device” for severe, currently intractable brain disorders but recommend the replacement of most of the upper part of the skull, the neurocranium, with such a device as well?There are 4 reasons for this recommendation.First, current medical technologies are inadequate for the safe and effective treatment of most severe neurological and psychiatric disorders. The 6 drugs available for American psychiatrists for the treatment of Alzheimer’s disease are all useless, and this is known. As for stroke, the CDC website, https://www.cdc.gov/stroke/facts.htm tells any visitor that “every 4 minutes someone dies of stroke”, including hospitalized patients. Malignant brain tumors are as deadly today as in the time of Senator Edward Kennedy, who died of glioblastoma12 years ago, within a year of his diagnosis despite the treatment he received at the best US
clinics. The devastating seizures of at least 20% of epileptic patients cannot be eliminated with drugs, neurosurgical intervention or electrical stimulators [3 - 4]. Therefore, those who wish to change this situation must expand their thinking beyond the therapeutic repertoire of current neurology and psychiatry.Second, just as the only way to stop the BP oil spill in the Gulf of Mexico in 2010 was to go 5,000 feet underwater and fix the problem onsite, or just as Space Shuttle missions were needed to fix all five problems with the Hubble telescope onsite from 1993 through 2009,– most problems of the brain also need site-specific treatment, inside the brain, where the problems occur. Why is this? This is because flooding the whole body with drugs, vectors, electroceuticals, nanoparticles or other treatments delivered via the bloodstream will always cause potentially severe side-effects in most organs which have nothing to do with the original brain disease. Furthermore, the Blood-Brain-Barrier (BBB) prevents most relatively large compounds – including proteins, nanoparticle encapsulated RNAs, gene vectors and electroceuticals, – to enter the brain even if they would do good if crossed this barrier.Therefore, those who wish to overcome these diffculties have no choice than treating the diseased brain tissue locally, onsite, with implants accessing the subarachnoid cerebrospinal fluid (CSF) compartment to bypass the BBB.Third, it is true that various electrical brain implants (RNS, DBS, etc.) have been introduced into the treatment of brain disorders. Yet they haven’t resulted in medical break throughs. Although made by the best scientific and engineering minds, all of these devices have the same, significant problem. Namely, they perform electrical stimulation only to correct the abnormal functions of diseased neural cells and networks. But the brain is a biological machinery fundamentally different from computers. Namely, the brain is not a digital electronic machinery, but a machinery in which digital electronic processes are controlled,adjusted and continuously refined with analog molecular processes. The brain is a hybrid computer where electrophysiological and neurochemical/molecular processes work together to let some brains initiate, create, and manage products like the “Philosophiae Naturalis -Principia Mathematica”, “Tristan and Isolde”, or the design of the Taj Mahal and the Lunar Module Eagle. I argued for the importance of this approach to therapeutic brain implants as early as 2000 [1]. Since then, several more elegant and more sophisticated articles have been published on the analog - digital nature of brain functions and its significance [7 - 9], – as pointed out by Reviewer Chand. Therefore, those who wish to treat errors of the electronic molecular machinery of the brain with the right implant have no choice than make this implantable to correct both electrophysiological and neurochemical/molecular abnormalities[10-13]of Alzheimer’s disease, stroke, malignant brain tumors, intractable epilepsy and other braindiseases.
Fourth, such a brain implant must be sufficiently large not just to give space for all necessary engineered components but also to effciently treat large, multifocal, bilateral, pathologies. May I remind the reader that Alzheimer’s disease is the degeneration of the entire association cortex in both hemispheres; severe strokes often cause neuronal death and edemain such large areas in brain that hemicraniectomy is the only life-saving measure; malignant brain tumors often grow in multiple locations in both hemispheres; tens of thousands of American epileptics suffer from severe seizures because their multiple, bilateral seizure foci can not be treated with current epilepsy therapies. Furthermore, the brain implant I propose for the treatment of the mentioned diseases must also be positioned in the upper skull so that it can be easily and safely accessible: (a) to the implanted patient’s physician to re-charge the electronic section and re-fill/re-clean the molecular section daily in the post-operative phase, and then (b) to the patient himself/herself to do the same procedure weekly/biweekly at home.Thus, a single electrical/molecular structure replacing, bilaterally, most of the frontal, parietal and temporal neurocranium would be the only device sufficiently large to: (a) include all engineered therapeutic components, (b) make the treatment of extensive cortical pathologies possible, and (c) allow the physician and the patient to maintain it easily and comfortably.“How to build and test a device of this type?” – asked Reviewer Cruz with good reason. My colleagues and I did describe the basic structure [2 - 6]. The key component is a battery powered, microcontroller regulated, dual minipump connected to subarachnoid de-livery/drainage strips to not just deliver therapeutic small-molecule drugs, neurotrophic and other proteins and cell-permeable gene-editing agents into all diseased cerebral cortical tissues, but also to drain such neurotoxins out from the same tissues as excess glutamate, proin-flammatory cytokines, carcinogenic molecules, cellular debris and others. Please recognize that the drained solutions, available by the cleaning procedure, can be processed for routine clinical laboratory tests to keep the treatment optimized and run true precision medicine for the patient. The current system also records and transmits EEG feedback from the treated brain.To this system, an electrical stimulator can be added without diffculties [4]. This would both complement the molecular treatment and induce the beneficial neurochemical modifications that can follow electrical stimulus – as pointed out by Reviewer Dario – though not with the broad spectrum of receptor specific effects of drug delivery [4]. The only component that has yet to be constructed for this device is the safe and simple re-charging, re-filling, recleaning unit, of which blueprint I wouldn’t describe here to prevent its improper development and/or abuse.Are there data indicating that such a device could provide safe and effective treatment for patients suffering from currently intractable brain disorders? Reviewer Fellus was justifiably interested in this. Yes, there are such data. My team and I at SUNY Downstate Medical Center and the NYU Comprehensive Epilepsy Center proved that even the preliminary, muscimol-delivering and inflammatory cell/protein draining version of this device was able to prevent experimental neocortical seizures in non-human primates reliably, while the animals’ health and social behavior remained normal, as long as these tests lasted, often for a year [2 - 5]. This suggests that other, currently intractable, neurological and psychiatricdiseases could also be treated with such implants if each implant is modified to perform the right, disease specific, drug delivery and neurotoxin drainage. Especially, since these treatments should yield a new range of information on harmful molecular/cellular processes in the human brain, allowing the user community to continuously improve on the drug delivery –neurotoxin drainage methods. And it is this new range of information that (a) can also help the development of child specific cures Reviewer Ribeiro so passionately wants; (b) can also help to find the “biological solutions” Reviewer Bashir so correctly seeks; and (c) can also help to make the electrical/molecular device free of “depriving the brain of physiological defenses”,of which significance Reviewer Benna properly emphasized. What would it take to introduce this therapeutic device into medicine? It would take a lot, as it would need the global cooperation of not merely technically well-trained but also intellectually sophisticated neurosurgeons supported by broad-minded neurologists, psychiatrists and healthcare administrators genuinely agreeing with the vision of electrical/molecular therapeutic implants for brain disorders. Reviewer Larsen rightly pointed out the necessity of examining the Quality/Costs ratio of such devices. But this examination would require here a more compassionate capitalist thinking. First, this thinking should be at peace with the high manufacturing/implantation costs at the expense of profitability to deliver the best care for the patients selected for this therapy. Second, this thinking should also be at peace with the commercial limitation to those patients – still millions worldwide – whose condition is as severe and intractable that they themselves seek the implantation of this device. They may well open the way to the evolution of bionic humans, as deserved to be on Earth within a century or two as genetically modified humans and android robots.
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