| Abstract|| |
Biobanks are set to become the norm. The explosion of new and powerful technologies like genomics and other multiomics has catapulted research from individual laboratories to multi-institutional and international partners. Today, with increasing life span, and the rising incidence of brain diseases, Brain Banks have become an invaluable source for unravelling the pathogenesis of several brain disorders, and develop effective therapies. The article briefly reviews the evolution of brain banking, rise of global networks, with a brief overview of steps involved from donor recruitment, protocols of processing, storage, annotation, and tissue distribution. The ethics of biobanking is one of the most controversial issues in bioethics, the key issues being consent, confidentiality, and commercialisation. Regulatory authorities in different countries and in India, the Indian Council of Medical Research has taken a lead to formulate new ethical guidelines for research involving human participants protecting rights, and well-being of research participants. Although brain banks have been established in the 1960s, in India, the first Brain Bank was established in 1995 at the National Institute of Mental Health and Neurosciences, Bengaluru. Now a network with two more Brain banks is being established in the country. The challenges and benefits of establishing the first Brain Bank as a National Research Facility in India is shared. For optimising available resources and promote brain banking, it is essential for medical professionals, and the public to perceive the crucial advantage in conversion of biological waste into invaluable resources for neuroscience. This will be the greatest “gift of hope” that we can offer for the future generations to overcome hitherto untreatable disorders such as dementias.
Keywords: Brain banking, human brain tissue repository, India, neurosciences, research
|How to cite this article:|
Shankar S K, Mahadevan A. Brain banking in India: Relevance in current day practice. Indian J Pathol Microbiol 2022;65, Suppl S1:218-25
| Introduction|| |
The brain has long been an organ of fascination for man; and the subject of much research aimed at seeking answers to many of the mysteries that surround it, its manifold functions and disorders. Although the 'neuron', the basic unit of the nervous system, is the same throughout the animal kingdom, evolution into Homo sapiens, followed extensive specialization of the neuron. In this context, the practice of extrapolating results of research into neurological disorders unique to man, from animal models, appears counter intuitive, particularly due to species barrier, differences in anatomy, physiology, biochemical pathways, and genetics. Transgenic animal models developed for several neurodegenerative and psychiatric disorders have limitations, providing at best, the pathological features, but the clinical manifestations and progression as seen in human disease is not seen. This growing realization that animal models cannot substitute for human nervous tissue created an acute need for availability of diseased human brain tissues to support research. The explosion of advanced technologies such as molecular, proteomic and genomic profiling applicable to brain tissue and fluids like cerebrospinal fluid (CSF), serum, saliva has greatly helped in studying alterations at molecular, biochemical, and cellular level to dissect out the pathobiology of various human disorders including neurodegenerative disorders, neuro-oncology and neuroinfections, and opened up avenues for novel and effective therapy. Neuroscience research has reached its zenith ever since, for which the human brain banks has been an invaluable research resource. This article briefly reviews utility of brain banks and, focus on the first brain bank in India, and review the challenges faced by brain banking and its future perspectives.
| Brain Banking: A Brief History|| |
It was with the objective of subserving neuroscience research, medical centres attempted to collect, and store human brain and associated nervous tissues in what came to be called as 'Brain Banks'. This is different from collection of formalin fixed brain specimens used for teaching medical students that primarily served the purpose of learning human anatomy and pathology of diseases. Detailed examination of cadaveric brains undertaken centuries ago by Alois Alzheimer in 1906, discovered the argyrophilic senile plaques and neurofibrillary tangles of Alzheimer's disease.
The concept of brain collection to promote brain research has been in existence since the end of nineteenth century.[reviewed in ,] Collecting, preserving, and providing adequately cryopreserved nervous tissue in a systematic fashion was initiated by Wallace W Tourtellot in Michigan. Surprisingly, contrary to long held belief, human brain collected at autopsy with postmortem delay of even up to 24 hours was found to be useful for molecular and biochemical studies. Ehringer and Hornykiewicz discovered dopamine depletion in striatum in Parkinson's disease that translated into treatment. Similarly, detection of fall in choline acyltransferase and depletion of cholinergic neurons in Alzheimer's disease was the basis for instituting cholinergic and anticholine esterase regimens, whereas dopaminergic overactivity in nigrostriatal pathway in Huntington's disease, was the basis for use of dopamine receptor antagonists in treatment. Similarly, virus as cause of SSPE and JC virus in progressive multifocal leukoencephalopathy was discovered., Several other neurological disorders have since been studied using human postmortem brain tissues. This was possible only because of dedicated pathologists and neuroscientists, who facilitated the collection of well-characterized human brains for study. This provided the necessary impetus to neuroscientists to seek and use the human brain for research.
| Global Scenario|| |
Rapid advances in lab investigations and neuroimaging, cell culture techniques and development of transgenic animal models have significantly contributed to the understanding and diagnosis of CNS diseases. But the complexity of brain function in health and disease and need to develop sensitive diagnostic and effective therapeutic strategies, necessitate study of diseased human brain tissues. The initial interest in brain banking to study neurodegenerative diseases has widened to include study of brain tumors, infectious diseases on surgically resected fresh, and fixed specimens. With advances in methodological procedures, now applicable to brain tissue and tissue fluids like CSF, serum, saliva for proteomic and genomic profiling has brought the international community together to establish 'biobanks' much beyond limited brain banks and it has become an emerging speciality. Time magazine (May 12, 2009) hailed biobanking as one of the “Ten ideas changing the world right now”. The biobanks have different characteristics based on the national needs and the investigator demand. Population-based biobanks are useful for the analysis of community health, and contribution of genetics and environment in disease causation. These banks assist in collecting, analysing, and policy planning for disease control. The 'clinic based biobanks' are disease oriented, facilitating research toward diagnosis and therapeutic strategies. The 'project driven' banks are small, controlled by the investigator and evolved to answer specific question the investigator is pursuing.
The availability of human tissues has drastically declined globally due to alarming decline in autopsy rate, thanks to availability of new imaging modalities, biochemical and molecular imaging that provided the clinicans with information on the cause of death, rendering the utility of autopsy for determining cause of death as obsolete. The phobia of the clinicians and pathologists to handle high risk autopsies has made the medical fraternity reluctant to request for autopsies. The same wrong notion has been conveyed to the general public and relatives of the deceased, making consent for postmortem examination has become increasingly difficult to obtain. The emerging new trend is of 'needle autopsy' – the practice of collecting needle biopsies from various accessible organs for pathological evaluation and extrapolating to the systemic disease. However, several of the neurological diseases are neuroanatomical site specific and may not be accessible by needle biopsy for study (except by stereotaxic biopsy in operation theatre) and require whole brain collected for study. Inadequate availability of human tissues makes research into rare disorders difficult.
To meet the global demand for well characterized, 'Networks of Brain Banks' emerged. These serve the research community by providing well annotated tissues. The key feature is a harmonized protocol for tissue collection and a centralized, harmonized data base, that can be accessed (http://www.brainnet.europe.org, consortium of European Brain Banks; Australian Brain Bank Network http:/www.unf.com.au/platforms/uuntrel) [Figure 1]. The International Society for Biological and Environmental Repositories (ISBER), trains, monitors, and assigns accreditation certification. All the centres and consortia are not accredited but listed. The biobanks in the consortia share the biospecimens as a policy. The ISBER brings out Recommendations for repositories as ISBER Best Practices for collection, long-term storage, retrieval, and distribution of specimens.
Sources of brain tissues for banking
There are two main sources of brain tissues for banking for research – whole brain obtained from postmortem and brain tissues obtained following surgical resection.
The formulation of effective donor recruitment is the key to establishing brain banks. Specifically, recruitment and consent for brain donations can occur either during life or after death. The latter form of recruitment is applicable to in hospital deaths. These could also be medicolegal autopsies from victims of road traffic accidents. These are a critical source of relatively normal control cases for comparative studies; however, there are limitations in terms of lack of availability of clinical data.,,
Recruitment of donors to sign up during life is most effective for studying chronic neurodegenerative disorders that have long-term follow-up allowing for detailed imaging, neuropsychological assessment and other relevant investigations. The availability of premortem clinical information, and other information imperative is crucial for structure function correlation. A well-coordinated donor recruitment program is crucial for a bank., However, in many cultures, including India, existing religious beliefs, cultural traditions and familial or societal views can limit the availability of before-death brain tissues. It is imperative to establish empathetic methods to advocate the importance of brain donations to advance neurological research in India. Donations, even if willed by the donor during life need to be authorised by informed consent from next of kin as per prevailing laws of our country. Donors as well as next of kin have the right to withdraw at any point, even after signing up. The autopsy is performed in the hospital mortuary by the brain bank personnel, where a neuropathologist is involved, prior to which informed consent is obtained from the next-of-kin. In addition to the brain collected at autopsy, blood and CSF, spinal cord, eye, pituitary, trigeminal ganglia, nerve, muscle biopsies, and other visceral organs can be collected.
An alternative source is tissues removed at brain surgery for diagnostic purposes. Tissues from brain tumors, epilepsy surgeries, neuromuscular disorders, demyelinating diseases obtained by biopsy/resection, after completing diagnosis, can be stored for future research. Biobanking is essential for neurooncology research. The rapid explosion in molecular diagnosis, methylation studies, proteomics, and genomics has made it essential important to archive nucleic acids and proteins for comprehensive diagnosis and keep it available for research for developing effective treatment, improve life span, and reduce morbidity. In addition, advances in technology allows proteomics and molecular genetic studies to be performed on formalin fixed paraffin embedded tissues; hence, the traditional archives of pathology lab assumes enormous utility and importance.
This requires changing the traditional workflow of a pathology laboratory, developing economical and effective strategies for tissue fixation, to achieve optimum preservation of cell membrane and organellar integrity. Knowledge of the biochemical changes that take place in archived biological material is essential for determining its efficacy for use for various molecular, genomic, and proteomic studies.,
Sample processing for banking
Following tissue retrieval, the tissue is transported on ice to the bank. The brain is sliced into two sagittal halves, one of which is fixed in 10% neutral buffered formalin and the other is sliced along the coronal plane into 1 cm thick slices to be frozen at -80 deg C. As a general rule, if the disease has involved both hemispheres in a symmetric fashion, the dominant hemisphere is frozen, while the non-dominant hemisphere is fixed in formalin for histopathological evaluation. If there is asymmetric involvement of both hemispheres and sampling of bilateral hemispheres is required for diagnosis, then portions of brain can be frozen, retaining sufficient issue in formalin for histopathological diagnosis. If the lesions are unilateral, the involved areas should be reserved for histopathology and fixed in formalin. However, portions of the lesions should also be frozen and corresponding tissues available for formalin fixation for diagnosis. This calls for discretion of the neuropathologist. Photographic documentation of slices at the time of dissection is valuable information for annotation.
The formalin fixed tissues are processed routinely for paraffin embedding and standardised protocols followed for characterization of diagnosis. Accurate characterization is essential prior to distribution. Return of results by providing the donors/their families a copy of the final pathology report is important.
Annotation and confidentiality
All samples are anonymised to protect patient confidentiality and ensure privacy. Coded or reversibly anonymised is essential with link to patient records with strict access restriction for providing requisite clinical information to researchers which is deidentified of identifiers. Unique numbering system should be developed as per the laboratories' convenience for retrieval of tissues.
All samples, whether collected postmortem or at surgery should have basic demographic and clinical information obtained from medical records, or next of kin in medicolegal cases. The specific type of medical information to be collected is dependant on the diagnosis. For instance, in neurodegeneration, detailed cognitive function and neuroimaging findings are critical. Postmortem MRI is increasingly advocated in cases if antemortem MRI was not performed. An ideal bank will have electronic records including demographics, clinical information, investigations, diagnosis, treatment, and donor information feedback with appropriate backup.
The practices and procedures employed within BBs vary greatly across countries, dictated in part by differences in legislative and scientific practices. Efforts are on globally to evolve robust criteria and standardization of procedures for collection and preservation of human tissues for research.
This is governed by local and Institutional guidelines for ethical considerations and ensure equitable and transparent procedures for distribution. All requests for tissues from researchers should go through a Scientific review board which has representatives from the bank as well as independent clinical experts in the field to review the study proposed, the researchers expertise and track record, methodology, relevance of study, ethical compliance, tissue availability, etc. It is good practice, when distributing tissues to obtain a material transfer agreement signed by both parties, which clearly spells out rules governing secondary uses of tissues, non-commercialization, benefit sharing, authorship issues, etc. In event of sharing of tissues between countries, the of national and international transport regulations for human samples varies between countries, and should be adhered to. The Indian Council of Medical Research (ICMR) has strict guidelines regarding sharing of tissues for biomedical research overseas.
Personnel training and safety
Personnel training is essential to ensure adherence to banking protocols. Safety should be strictly enforced. All human tissues are potentially biohazardous. The personnel should undergo periodic training on precautions to be followed in handling biological samples. All staff should be vaccinated against the hepatitis B virus with periodic testing for titres and administered boosters if needed. All disposable equipment should be sterilized and wastes generated disposed according to a recommended protocols.
Accreditation of biobanks
All biobanks must enrol for accredidtation to ensure that they are periodically evaluated by independant expert group to scertain that minimum criteria for biobanking is stringently followed. This includes protocols for collection, appropriate storage, clinical information and confidentiality, training for tissue handling, waste disposal, etc are specified and followed. India has established a biobanking accreditation system as per the international standard ISO 20387. This is open to all biobanks seeking accreditation in India and encourages other biobanks and biorepositories in various fields to demonstrate their competence and credibility globally.
Factors affecting quality of samples
Post mortem delay and cold ischemia time
The interval between the time of death and freezing, known as the Post-Mortem Interval (PMI) should ideally be under 6 hours, to maintain tissue integrity and suitability for research., While a PMI of 4-18 hours has no significant effect on pH of the brain and acts as strong indicator of tissue integrity, extended postmortem delays of >72 adversely affect catecholamine, neuropeptide levels, and proteins which are detrimental for neurodegenerative studies., Unlike research involving animal models wherein the researchers have control over variables such as species, gender, weight, food intake, and others, human research is constrained by several variables such as ethical issues, availability of tissues, pre and postmortem factors, agonal events, treatment, and others that are not possible to control. Notwithstanding these, human material is precious, but these factors have to be taken into account when analysing results. Rapid autopsy programs with very short PMIs within 4–6 hours are ideal but difficult to achieve given the logistics. In tissues obtained following surgeries, the cold ischemia times (from time of cutting off of blood supply to freezing) can be controlled and hence has better preservation of RNA, transcriptome, and genetic information. Studies have found that genes expression changes occur in a tissue-specific manner over same PMI and may affect effect in the biological analysis.
Quality control and quality assurance
This is one of the important factors in tissue banking. The most common factors that alter brain tissue quality are the terminal events preceding death or “agonal” factors (coma, hypoxia, hypotension, hyperthermia, drugs), and long postmortem interval. Measures of quality of tissue include pH and RNA quality, as indicated by the RNA-integrity number., Measurement of tissue pH is easy to perform, and is not influenced by PMI, but dependent on factors such as agonal state and ischemia prior to death. Tissue pH also correlates well with RNA integrity. Quality control measures should also include strict maintenance of freezer temperatures, and minimise free thaw cycles.
Matched cases and controls
Matched controls are extremely critical for deriving accurate and clinically relevant results. Matching should include antemortem factors (age, gender, agonal state, medication and place and time of death is recommended to accommodate seasonal and circadian variations!). Postmortem factors include PMI, tissue storage time, and laterality.
Freeze thaw of tissues
Tissue retrieval for distribution to researchers necessitates a freeze thaw process, a critical factor that affects quality of tissues. Earlier protocols involved freezing entire slices which required long thawing for dissecting out area of interest. But with time, systematic dissection protocols evolved with more than fifty or more brain regions dissected, carefully labelled, and frozen., This will allow more regions to be available for research and importantly minimize the freeze thaw time.
Challenges faced by brain banking
Human tissue is an invaluable source for neuroscience research and will remain so in future. However, this comes with a new set of challenges to overcome. Key ethical issues in biobanking include consent, confidentiality, ownership, and commercialisation issues, feedback to participants and the ethics of re-contact.
The term “informed” consent cannot be applied in principle to biobanking because, at the time of collection, we simply do not know what kind of research we are banking tissues for, and there can be a lag between collection of samples and its use by researchers. Hence the basic tenets required of an informed consent – purpose, methodology, benefits, risks, funding sources, and all the other requirements of informed consent cannot be provided to the participant. There are several types of consent more appropriate in setting of biobanks, each with their own unique advantages and disadvantages.
Blanket consent is the most commonly used form of consent. This is an open consent, that needs to be taken only once, and obviated the need for reconsent for secondary uses, making it very easy for researchers. However, for the participants, there is no option to choose between options and hence offers little protection and no guarantees.
Tiered consent has opt-in opt out options from which participants can choose to provide either blanket permission, or use only related to some aspects of research, sharing of biospecimens/data benefit sharing, etc. The limitation is that there is no avenue for changing their decision. Additionally, it is important to make provision for withdrawal of consent or destruction of samples at any point.
Dynamic consent takes into consideration these limitations. It uses technology to allow participants to decide whether they want to consent to broad consent or consent on a study-by study basis. It is particularly useful for longitudinal studies with multiple samples obtained at different time points. However, it limits participation to only those who have access to the necessary information technology and in India may be costly to implement. There are also logistic problems of having to track and contact participants.
Decline in autopsy rates
Brain banking is dependant upon availability of cadaveric brains, but autopsy rates have seen a steady decline world over.,,,, The foremost cause is the emergence of advanced sensitive diagnostic techniques that offer definitive diagnosis. Another potential reason may be the change in donor and donor families' attitudes and views toward postmortem autopsies and the misinformation surrounding this, with lack of understanding of the long-term benefits. Educating the public on benefits of donation by treating clinicians and promote the philosophy of their donation being regarded as a “gift of hope” needs to be advocated strongly to promote research in neuroscience. A large part of this is also driven by the reluctance of pathologists and clinicians to request autopsies to avoid litigation for a missed diagnosis. This is underscored by the absence of a second Brain Bank in India in the last 25 years. It is the pathologist who has to be a bridge between the clinician and basic scientist. On the one hand, it is essential to educate the medical professionals regarding the benefits of biobanking' for future research and convert biological samples following testing into precious resource for research. On the other hand, it is equally important to enhance public education regarding their rights and privileges via public education, debates, creating awareness, and disseminating information regarding benefits and risks to the community. Soliciting public participation and inputs is critical to develop regulations for protection of research participants.
Commercial use of tissue
It is a long-debated issue about the distribution and utilization of tissue collected from donors and patients in brain bank, to commercial entities. Rigorous ethical evaluation and institutional regulations are in place prior to regulate distribution of the tissues to scientists. However, on the distribution of the tissues to commercial organisations, donors and scientific advisory boards have differing views. Some advocate that donors should be allowed to exercise their choice for sharing their banked specimens for research and development by commercial entities, but the logistic issues, compensation, sharing benefits, etc. are issues that have to be carefully considered.,,
It is important to maintain Biobanks as nonprofit organisations as human tissues are donated as an act of philanthropy for research. The banks are custodians of specimens to ensure there is no commercial exploitation. However running cost of a biobank is high, that includes personnel costs, and costs of acquisition, processing, and preserving specimens, and varies from €10,000 per brain collected in Europe to $15,000 in the US. Some banks incorporate processing costs of specimens into grant budget. The endusers must be made aware that payments are for covering the maintenance of the banks and not for profit making.
Lack of a network system
Research into neurological and neurodegenerative disorders is facilitated by the existence of brain banks. Lack of availability of precious human tissues has led to emergence of consortium of brain banks around the world like the ISBER to facilitate sharing of samples and foster collaborative research studies. Keeping in mind the ethical and privacy concerns surrounding tissues and patient identifiable data, it is important to practice care while building such networks. The development of strategic alliances and connecting brain banks globally has become necessary now more than ever before. There are several inherent issues that arise in consortia such as quality of tissues collected, clinical annotation, mechanism of equitable sharing, data sharing, intellectual property rights sharing, etc., that require harmonizing protocols, stringent quality control measures and data/material sharing agreements and at same time ensure demand for quality tissues that will allow rapid advances in research into neurological disorders are met., The emergence of bio-banks in India are influenced by several factors such as interests of pathologists and clinicians, religious beliefs, limited funding available, and importantly difficulties in transport across the country maintaining cold chain. But now with support of Indian Council of Medical Research, NIMHANS has sought to establish satellite Brain Banks Network India initiative by helping two Institutes PGIMER Chandigarh and AIIMS Bhubaneswar. To set up satellite Brain banks. This network will be a stepping stone in expanding the network and provide necessary fillip for neuroscience research in India. However, networking these banks with international banks will necessitate development of not only uniform, globally accepted SOP's for exchange of specimens, and data with the scientific community but also an internationally accepted Code of Conduct.
Ethical and legal concerns
Availability of tissues for research is strongly dependent on ethical, legal, and social issues (ELSIs), as well as on the cultural and religious backgrounds of each country.
Due to the relative novelty of the science of postmortem removal and use of human tissues for scientific research, the governing laws are often lacking or ambiguous in different countries. According to the Convention on Human Rights and Biomedicine, every person has the right of autonomy over his or her body. Particularly in India, there are only rules that govern organ transplantation (Transplantation of Human Organs Act) but there are none to govern tissues/organs harvested for research. The Indian Government is in the process of reviewing its stand on honouring the Living Will and respect the autonomous decision of donors. Till date, in India, the next of kin have absolute authority over the deceased and even if the deceased, during life, willed their organs for research, the next of kin have the authority to overrule this. Hence a written informed consent from next kin is the only legally recognised document to permit retrieval and storage of organs/issues for research. In cases of medico-legal autopsies carried out as mandated by the legal system, it becomes further complicated to obtain informed consents. Legal regulations concerning postmortem organ harvesting for research are still in its infancy and many countries also lack a stipulated code of conduct that would be binding in such cases.
All the brain banks should operate in accordance with the guidelines encoded in Helsinki declaration (World Medical Association Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects (1964)) and Ethics in Science and New Technologies in respect of Human Tissue Banking (Council of Europe Opinion of the European Group on Ethics in Science and New Technologies to the European Commission. Ethical Aspects of Human Tissue Banking, 21st July 1998) and the Nuffield Council on Bioethics (http://www.nuffieldbioethics.org). Brain Banks must be run on non-profit basis. The Indian Council of Medical Research has now come up with well-formed guidelines for biobanking. https://naitik.gov.in/DHR/resources/app_srv/DHR/global/pdf/downloads/Handbook_on_ICMR_Ethical_Guidelines.pdf).
Evolution of the human brain tissue repository in India
In a country like India, sociocultural, geographic factors, ethnic issues influence the spectrum of disorders prevalent here in that maybe distinct from the Western countries. For example, the concept of consanguineous marriages and genetic inbreeding prevalent in some cultural communities especially in Southern India, can predispose to inborn errors of metabolism and other inherited disorders manifesting as Lafora body disease, Wilson's disease, etc. A form of leukodystrophy is common to Aggarwal community and a high prevalence of PD in Parsi community. India is also home to several infections such as tuberculosis and cysticercosis. Disorders such as madras pattern of Motor Neuron Disease was described from India. Autoimmune disorders like Neuromyelitis optica are prevalent in Asian countries like India and Japan. These significant differences in prevalence of diseases, in contrast to West, makes it critical to have a Brain Bank in India that to provide well annotated and characterised tissues for neuroscientists in India to conduct research on diseases prevalent in India. This gap was discussed during the “Brain Storming Session in Neurobiology”, conducted at National Institute of Mental Health and Neurosciences (NIMHANS) in 1985. Since the concept of a “Bio-banking” was very new to the neurologists and neurosurgeons in the country at the time, a mammoth effort was required to convince the funding agencies for the need of a Human Brain Bank in the country. It took nearly a decade of concerted effort from Dr SK Shankar and with the assistance of Prof. P. N. Tandon, an eminent Neurosurgeon and a clinical neuroscientist, the Human Brain Tissue Repository (HBTR) as a National Research Facility at the National Institute of mental Health & Neurosciences in 1995. It was jointly funded by Department of Biotechnology, Department of Science and Technology and Indian Council of Medical Research, Government of India for five years and was subsequently taken over by NIMHANS administration. The prime objective of the Human Brain Bank is to facilitate research in various branches of Neurosciences to help understanding the pathogenesis of neurological disorders of importance to India, so that effective treatment strategies can be evolved.
Contribution of HBTR as a tissue resource centre
In the past 25 years since its inception (1995–2020), there has been significant and noteworthy contribution to the scientific advancement utilizing the archived material at the Human Brain Bank. These observations have an impact on various fields of neuroscience including neurochemistry, neurodegenerative, and developmental disorders, neuropsychiatry and neuroinfections, helping to make inroads into unravelling pathogenesis of numerous disorders that are of significance in the country. Over the past 25 years, the HBTR has supported nearly 60 research projects funded by national and international agencies, with 73 publications in national and international journals and contribution to several text books/monographs based on the research carried out utilizing the material. The relatively normal 'disease free' controls from cases of road traffic accidents have served as a valuable source for biochemical, molecular biological, and proteogenomic studies.
The Dept of Health Research, ICMR-funded establishment of a Centre for Advanced Research for Innovation in Mental Health and Neurosciences, to develop Neuroscience Educational Material for popularizing neuroscience and promote cadaver organ donation. A 'Histological Atlas of the Common Infections of the CNS' with a CD containing the Text and Photographs was prepared and distributed among the medical colleges teaching postgraduate students of pathology, microbiology, and neurology.
In addition, a Creutzfeldt Jakob Disease (CJD) registry was set up to record all cases of CJD in India, and obtain epidemiological data of this rare and fatal neurodegenerative disease over last 3 decades. The registry has recorded 109 with clinical details (unpublished data). Indigenous test for 14-3-3 has been developed by Department of Neurochemistry for the first time in India.
| Future of Brain Banking – A Road Map|| |
Brain banks being nonprofit establishments often face financial difficulties. As more biobanks come up in India, there will be new challenges to face and there will be a need for constant revision in guidelines regulating biobanks. Governance, should be guided by transparency and accountability, with independent committees for oversight at each step of collection, distribution, research, and requirements for consent. It is very important to enhance public education regarding their rights and privileges and get their participation and inputs to develop regulations and policies to facilitate research and protect participants as bankers are mere custodians of tissues, but the donors are the owners. In a recent ''biorights'' movement, patients, and their advocates raising pertinent questions over their rights with respect to benefits, compensation return of information regarding results etc. Indian advocacy laws pertaining to these matters are to be resolved.
The final goal is to provide necessary impetus for discovering markers for early diagnosis, determine prognosis and develop innovative treatment modalities and prevention for human diseases. Keeping the future in mind, it is imperative to overcome obstacles to move forward. This requires that medical professionals, clinicians as well as the public understand the advantages of brain banking and biobanking for research and convert biological waste into invaluable resources for scientific research. This will be the greatest “gift of hope” that we can offer for the future generations to overcome hitherto untreatable disorders such as dementias.
The Human Brain Tissue Repository (Brain Bank) owes its existence to the dedicated team of staff in Human Brain Tissue Repository and Mortuary of Department of Neuropathology, National Institute of Mental Health & Neurosciences, Bangalore. The authors also wish to gratefully acknowledge the support of all the clinicians and researchers who have contributed to the success of the Brain Bank as well as the NIMHANS administration and funding support from ICMR, Departments of Biotechnology and Science & technology (DBT, DST), Govt of India for initial funding and support. The authors acknowledge funding from ICMR for Brain Bank Network India Initiative project (Sanction order No. No. SWG/Neuro/40/Centre 1/2020-NCD-I, (RFC.No. NCD/NTF/8/2021-22 dated 17.08.2021). Most importantly, we gratefully acknowledge the selfless donations of patients and their families for their “gift of hope” to neuroscience research. The authors also acknowledge the technical assistance of Ms Aparajita Chatterjee, former JSO, HBTR, Department of neuropathology, NIMHANS, Bangalore.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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S K Shankar
Former Emeritus Professor, Department of Neuropathology, Founder and Former Co-Ordinator, Human Brain Tissue Repository (Brain Bank), National Institute of Mental Health and Neurosciences, Bangalore - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None