- Email: [email protected]
Sub-Saharan centralized biorepository for genetic and genomic research
Science of the Total Environment 423 (2012) 210–213
Contents lists available at ScienceDirect
Science of the Total Environment j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c i t o t e n v
Sub-Saharan centralized biorepository for genetic and genomic research Nagla Gasmelseed a, Afrah Awad Elsir a, Pasquale DeBlasio b, Ida Biunno c,⁎ a b c
Department of Molecular Biology, National Cancer Institute University of Gezira, Wadmedani, Sudan BioRep SrL Via Fantoli 16/15 Milano, Italy Institute for Biomedical Technologies-CNR, Via F.lli Cervi 93, 20090 Segrate-Milano, Italy
a r t i c l e
i n f o
Article history: Received 2 December 2009 Received in revised form 19 July 2010 Accepted 19 July 2010 Available online 8 February 2011 Keywords: Biorepository Africa Molecular epidemiology
a b s t r a c t Quality-assessed biomedical samples are essential for academia- and industry driven research on human diseases. The etiologies and the molecular genetic factors relevant in African diseases, including both infections and complex degenerative diseases as well as cancer, need to be studied using well annotated and well-preserved biosamples acquired from native African ethnic groups and compare the results with nonAfrican populations and/or with Afro-Americans. However, a number of difficulties negatively impact on the possibility to obtain clinically annotated biological samples in most Sub-Saharan African countries. This is mainly due to major organizational problems, lack of clinical centres that can dedicate resources to research, as well as lack of facilities in which biomaterials can be properly processed and safely stored. Harmonization of biosample acquisition, storage phenotyping schemes and biocomputer infrastructures are the principal objectives of biological resource centers (BRCs). BRCs comprise biobanks of different formats (collection of blood, DNA, tissues, etc., annotated with medical, environmental, life-style and follow up data) a fundamental tool for molecular epidemiological studies aiming to increase excellence and efficacy of biomedical results, drug development and public health. BRCs provide large and highly controlled biomolecular resources necessary to meet the “omics” scientific platforms. Sudan may be a candidate nation to host such infrastructure, in view of its strategic geographical position and the already existing simple biobanking experiences connected with research groups in Central Sudan. Here, we describe the potential role of biobanks in African genetic studies aiming to dissect the eziopathogenesis of complex diseases in relation to environmental and life-style factors. © 2010 Elsevier B.V. All rights reserved.
1. Introduction There is much to be learned from the study of gene variants implicated in the etiology of diseases in Africans, but comparatively few studies have been conducted thus far on native African ethnic groups (see link to the Online Mendelian Inheritance in Man database; Cavalli-Sforza et al., 1994; Sgaier et al., 2007; Tishkoff et al., 2009). In fact, most research has been performed on non-African populations and on Afro-Americans (Jorde et al., 2001). This is due to the extraordinary difficulties in obtaining clinically annotated human biological samples in most Sub-Saharan African contexts, due logistic and organizational issues, to the rarity of clinical centers, to the lack of trained personnel, and to the almost complete absence of facilities for processing and safe storage of the biosamples. To reconstruct human evolutionary history, to dissect the genetic basis of resistance and susceptibility to diseases, to design better drugs for all people and to understand the basis of complex disorders is necessary, in addition to increase funding and resources, the creation of a global consortium of ⁎ Corresponding author. ITB-CNR, Via Fratelli Cervi 93, 23090 Segrate, Milano, Italy. Tel.: + 39 0226422712; fax: + 39 0226422770. E-mail address: [email protected] (I. Biunno). 0048-9697/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.scitotenv.2010.07.054
Biobanks in Africa (Sgaier et al., 2007). Very recently (23 June 2010), the National Institute of Health (Washington DC) and Welcome Trust (London-UK) announced a partnership to launch a joined project named “Human Hereditary and Health in Africa,” (H3Africa). The project aims to use genomic and clinical tools to identify the genetic and environmental contributions to communicable and non communicable diseases. This huge effort will allow the setting up of various regional or national “biobanks” in order to address common ethical issues, data ownership and data sharing. These biobanks will collect DNA and medical information from hundreds of thousands of African people facilitating genetic epidemiology studies and hopefully uncover gene-environmental interactions by linking together genetic variations to environmental factors. The ultimate goal is to accelerate the discovery of vaccines, drugs and diagnostics. Genetic variations has major implications in medicine and public health since affects disease susceptibility and predisposition to infectious diseases and may provide a better understanding of the universal cancer problems (Cooke and Hill, 2001; Sirugo et al., 2004; Molony, 2005; Menard et al., 2006; Sirugo et al., 2008, 2005; Khoury, 2003). Indeed, the line between normal and pathological variants can be drawn only taking into account ethnic and geographic origin, and should be based on an accurate description of gene/allele frequencies.
N. Gasmelseed et al. / Science of the Total Environment 423 (2012) 210–213
The annotation of millions of single nucleotide polymorphisms (SNPs) within the genome, facilitated by the completion of the Human Genome Project, the development of ultrahigh-throughput genotyping, small molecule detection methods and powerful software to analyze the mass of data that is generated will make possible the discovery of the allelic and biological variants that underlie complex diseases (such as cardiovascular, cancer, diabetes, communicable and non communicable diseases, tuberculosis and AIDS); (Sgaier et al., 2007; Collins, 2001; Guttmacher, 2002). Large-scale analyses of genes (genomics), proteins (proteomics), and metabolites (metabolomics) have been undertaken thanks to the availability of well-annotated human biological samples provided by biological resource centers (BRC) (Troyer, 2008). BRCs follow the best practices guidelines released by The International Society for Biological and Environmental Repositories (ISBER) (2005) and the National Cancer Institute's Office of Biorepositories and Biospecimen Research (Ozerskay, 2008). Well-designed geographically-based BRCs offer the opportunity to: (1), assess population prevalence of specific genes and variants; (2) simplify the search for molecular markers; (3), improve targeted drug discovery and development for disease management; (4), refine strategies for disease prevention; (5), provide the data necessary for evidence-based decision-making (Blatt, 2000). Biological samples (wet tissues, frozen and paraffin-embedded tissues, glass slides, blood, serum and urine) from both diseased and unaffected individuals should be cryopreserved with a quality as close as possible to the initial quality (i.e., quality at sampling). The promise of genomic research has drawn attention on the highly sensitive category of information contained in the genes and on how to inform donors correctly. In fact, serious scientific and social questions regarding the protection of the rights of people whose samples are in the biobank, the identification and access of such samples, the privacy and confidentiality of genomic information, civil liberties, patenting and commercialization of biosamples, and, finally, proprietary rights. These issues largely remain un-resolved (Cambon-Thomsen, 2003; Hoffman, 2009). 2. Potentials of a biological resource center (BRC) in the Sudan Sudan, the largest country in Africa, may reflect the African nation in which develop a BRC. Sudan besides being the largest country in Africa is characterized by a strategic geographical position linking the Arab world to Sub-Saharan Africa. It shares borders with nine countries and holds within its borders an admixture of populations and cultures. Indeed, Sudan is one of the most ethnically and linguistically diverse country in the world, with nearly 600 ethnic groups speaking over 400 languages and dialects. Some smaller ethnic and linguistic groups have disappeared due to migration, migrants often forget their native tongue when they move to an area dominated by another language. Some linguistic groups were absorbed by accommodation others by conflict. Arabic is the lingua franca but despite the use of English by many elites, most Sudanese are multilingual. Sudan is a multicultural country where hundreds of tribes live together: the Nubians in the north, Bija in the east, Kababish, Baggara and Nuba in the west Nuer and Dinke in the south. The environment ranges from damp rainy in the south, to desert in the northern areas. Despite being the 17th fastest-growing economy in the world with new economic policies and infrastructure investments, Sudan still faces remarkable socio-economic problems, as it must rise from a very low level per capita income. Rich mineral resources are available in Sudan which includes: petroleum, natural gas, gold, silver, chrome, asbestos, manganese, gypsum, mica, zinc, iron, lead, uranium, copper kaolin, cobalt, granite, nickel and tin. Agriculture production remains Sudan's most important sector, employing 80% of the workforce, but most farms remain rain-fed and susceptible to droughts. Unfortunately, outside urban areas, little health care is available. Control of communicable diseases dominates the health
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scene with high vulnerability to disease outbreaks. Large parts of Sudan's population suffer from poor hygiene, bad infrastructure and bad water quality. Common diseases include malaria, dysentery and other gastrointestinal disorders, and tuberculosis. Bilharziasis is a major problem for people along the White and Blue Niles, African Trypanosomiasis, sleeping sickness, is widespread in the south. Meningitis, measles, whooping cough, infectious hepatitis, syphilis and gonorrhea are also relatively common. Some regions have problems of seasonal undernourishment, and malnutrition is still a problem in some areas. Malnutrition is widespread outside the central Nile corridor because of population displacement from war and recurrent droughts; these factors, together with a scarcity of medicines, make diseases difficult to control. Child immunization against most major childhood diseases, however, had risen to approximately 60% by the late 1990s from very low rates in earlier decades. The research priorities in Sudan are on infectious diseases although diabetes, thyroid disease and cancer are not to be underscored. The objective of this brief paper is to identify the challenges in the realization of a “BRC” infrastructure in Sudan and formulate professional and scientific view on the social, ethical and economical issues that provide an impact on data storage and human biobanking practices for biomedical research in Sudan. A biorepository initiative in the Sudan would be justified by the fact that presently small disease- and geographically-oriented biobanks already exist in Central Sudan. These biobanks have been motivated by specific studies and are concentrated in two research institutes in Khartoum, i.e., the “Institute of Endemic Diseases” and the “Tropical Medicine Research Institute” and one in Wadmedani, i.e., the “National Cancer Institute” (NCI). Questionnaires about the objectives of the presently held collections, the types of specimens currently stored, qualification and training of the personnel working in the biobank, procedures applied, participation in international biobanking networks, data sharing of the stored samples were distributed to research institutes. Table 1 summarizes the collections, their locations, the disease phenotypes and the type of biological specimens stored. These Institutes have a local ethical committee for the evaluation and approval of research proposals and are linked to the National Ethical Committee network within the Federal Ministry of Health. The role of this Committee is to evaluate and eventually approve specific programs of research such as: multi-states studies within the Sudan federal state, international research collaborations, and drug or vaccine experimental trials. Ethical consent may represent a problem in establishing and maintaining a biobank in Sudan, due to the lack of proper legal approval or consent by local ethical committees. The task of providing ethical and legal guidance could therefore be assumed by the National Ethical Committee, in conjunction with the existing local Committees at the three major research institutes in Khartoum and Wadmedani. 3. Scientific, ethical procedures and donor confidentiality The genome based science we are exposed today, has placed huge attention on the highly sensitive category of information contained in genes. Polymorphic markers (SNPs) are related to gene function and play a role in the understanding of the origin of common diseases, the response of individuals to treatments and to the development of new therapeutic molecules. Serious scientific and social questions regarding the protection of the rights of people whose samples are in the biobank, the identification and access of the samples, privacy and confidentiality of the genomic information, civil liberties, patenting and commercialization of the biosamples and finally proprietary rights are still highly debatable arguments (Human Genetic Commission, http://www.dh.gov.uk/en/publicationsandstatistics/publications/publicationspolicyandguidance/dh_4009988 (accessed 24 October 2008). Informed consent has become the standard way of legitimising medical interventions and protects individual privacy. Biobanks due
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N. Gasmelseed et al. / Science of the Total Environment 423 (2012) 210–213
Table 1 Biomedical collections currently present in the Sudan (ND: not determined number). No. Institute and location
1-
2-
3-
Type of sample collected
Whole blood, serum, plasma, cells, paraffinembedded tissue and fresh tissue Institute of Endemic Diseases, Whole blood, serum, plasma University of Khartoum, Khartoum
National Cancer Institute, University of Gezira, Wadmedani
Tropical Medicine Research Institute, National Research Center, Ministry of Science and Research Technology, Khartoum
Whole Blood, serum, Plasma buffy coat
Capacity of shares samples
Types Freezer and backup power
Cell pellets, 1500 whole blood, samples DNA, serum are stores and plasma
50% of sharing samples with international institutions
DNA, serum, plasma
25% of the total samples were share with International Institution 25% of the total samples were share with International Institution
Three freezer −20 °C Two freezer −80 °C In addition to −4 °C Liquid nitrogen containers with automatic generator Two −20 °C one −80 °C and one −40 °C Electronic generator and Liquid nitrogen
No. of currently stored and processed samples
Disease phenotype
Type of stored biological specimens
Malaria, non Hodgkin's lymphoma, breast cancer, nasopharyngeal carcinoma schistosomiasis, tuberculosis, HBV and HCV infection, hepatocellular carcinoma. Infectious diseases (malaria, tuberculosis leishmaniasis, etc.), cancers
Schistosomiasis, malaria, cancer
ND Whole blood, serum, plasma puffy coat and parasites
to the nature of their research, to use the biological material need a “broad consent” which requires less specific information then “strict consent” forms (Beskow and Dean, 2008; Hansson et al., 2006; Hoffman, 2009). To fulfill long term research projects using new technology, new perspectives and new research questions, biobank research requires a revision of the presently used consent forms keeping in mind that to renew consents is costly especially if the donors are anonymous or deceased (Meslin, 2004). 4. Conclusions and discussion Research activities have traditionally been performed in non-African populations thus liming the knowledge of the genetic basis of diseases in Africa. Certainly the comparisons of the genetics, genomics and epigenetics between Africans and African descendants leaving outside of Africa, can lead to the identification of those environmental risk factors that influence the universal problems of cancer (Sgaier et al., 2007). Epidemiological genetic studies require a shared set of DNA resources, the establishment of an African genetic database and large bio-collections (Ginsburg et al., 2008). In Sudan, biobanking (DNA, blood and cells) started only recently (in this decade) and for research purposes only. As established through questionnaire responses, all the research institutes presently involved do not have cryopreservation standard operating procedure (SOPs), supplier qualification, personnel training, control and quality systems. An internal sample tracking procedure was developed based on excel-spread sheets. However, the status of the collections is not well known and most laboratories that bank DNA have no written policies or agreements regarding their activities. Furthermore, little information is available to guide researchers in selecting the most appropriate specimens for epidemiologic studies and surveys. In general, there is still concern regarding validity of informed consent, safeguard of samples and data privacy. Obtaining informed consent for the collection and storage, as well as future research use of biospecimens is challenging, as potentially complex and controversial information must clearly be communicated. A major challenge for biobanking in Sudan is also the economical situation. Since managing of large bio-collections requires implementation of standards and guidelines (two-dimensional and nanobarcodes and customized electronic databases to assure efficient management of large sample collections and tracking results of data analyses), a single academic investigator or a small research consortium cannot govern the samples alone. Thus major investment is necessary for new equipments and for renewal of old ones, for the training of human resources dedicated to biobanking activities, and for the coverage of operational costs
ND
Five freezer −20 °C three freezer −80 °C In addition to Liquid nitrogen containers
(electricity, liquid nitrogen, reagents, maintenance, etc.). Cost recovery policies should also be contemplated. In conclusion then, there is an increasing awareness on the importance of doing genetic research in African settings. This urges international coordinated actions to expedite the development of adequate infrastructures and the training of African scientists to lead and promote research in Africa. It is an accepted hypothesis that centralization and standardization of biobanking activities will facilitate international collaborations, define restrictions and limit the dis-use of the biosamples for research. Indeed the governments of several countries, including United Kingdom (www.ukbiobank.ac.uk), Iceland (www.decode.com), Estonia (www.genomics.ee), Singapore, and Sweden, as well as medical centers in the United States, have made commitments to create centralized banking facilities on a national scale. In Africa this effort is still in its infancy. It is un-realistic and, to say the least, logistically unfeasible, to think that all African countries would agree in storing their biological resources in a single “continental African biorepository.” National or regional biobanks are a first key step, as exemplified by the DNA biobank in The Gambia (Sirugo et al., 2004), a Wellcome Trust-financed project. Outside of Africa, examples that could be considered as models are the Indian National Biobank (Sgaier et al., 2007); The Chinese Kadoorie study (Chen et al., 2005) and The Mexico City Prospective bank (Tapia-Conyer et al., 2006). However, a number of initiatives from developed countries are in progress to sponsor the creation of a global consortium of biobanks committed to aid biobanking in developing countries (Morel et al., 2005). Indeed, recently was announced the H3Africa project, a $38 M effort between NIH and Wellcome Trust to create a repository in Africa for biological sample collection of native Africans, will provide participants with examination and screening tests, will train African researchers abroad with the prospective to return to their home country and establish or enhance research facilities. This project will promote strong collaborations between African Institutions, USA, Europe and with other parts of the world. Acknowledgements We would like to thank the following: Prof. Moawia Mukhtar Institute of Endemic Diseases (IED), University of Khartoum; Dr Intisar Erayh, Director, Tropical Medicine Research Institute (TMRI), National Research Institute; and the Ministry of Scientific Research and Technology (Khartoum). This collaborative work was partly financed by a grant from the Italian government to IB and PDB (MURFIRB nRBIP064CRT).
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Contents lists available at ScienceDirect
Science of the Total Environment j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c i t o t e n v
Sub-Saharan centralized biorepository for genetic and genomic research Nagla Gasmelseed a, Afrah Awad Elsir a, Pasquale DeBlasio b, Ida Biunno c,⁎ a b c
Department of Molecular Biology, National Cancer Institute University of Gezira, Wadmedani, Sudan BioRep SrL Via Fantoli 16/15 Milano, Italy Institute for Biomedical Technologies-CNR, Via F.lli Cervi 93, 20090 Segrate-Milano, Italy
a r t i c l e
i n f o
Article history: Received 2 December 2009 Received in revised form 19 July 2010 Accepted 19 July 2010 Available online 8 February 2011 Keywords: Biorepository Africa Molecular epidemiology
a b s t r a c t Quality-assessed biomedical samples are essential for academia- and industry driven research on human diseases. The etiologies and the molecular genetic factors relevant in African diseases, including both infections and complex degenerative diseases as well as cancer, need to be studied using well annotated and well-preserved biosamples acquired from native African ethnic groups and compare the results with nonAfrican populations and/or with Afro-Americans. However, a number of difficulties negatively impact on the possibility to obtain clinically annotated biological samples in most Sub-Saharan African countries. This is mainly due to major organizational problems, lack of clinical centres that can dedicate resources to research, as well as lack of facilities in which biomaterials can be properly processed and safely stored. Harmonization of biosample acquisition, storage phenotyping schemes and biocomputer infrastructures are the principal objectives of biological resource centers (BRCs). BRCs comprise biobanks of different formats (collection of blood, DNA, tissues, etc., annotated with medical, environmental, life-style and follow up data) a fundamental tool for molecular epidemiological studies aiming to increase excellence and efficacy of biomedical results, drug development and public health. BRCs provide large and highly controlled biomolecular resources necessary to meet the “omics” scientific platforms. Sudan may be a candidate nation to host such infrastructure, in view of its strategic geographical position and the already existing simple biobanking experiences connected with research groups in Central Sudan. Here, we describe the potential role of biobanks in African genetic studies aiming to dissect the eziopathogenesis of complex diseases in relation to environmental and life-style factors. © 2010 Elsevier B.V. All rights reserved.
1. Introduction There is much to be learned from the study of gene variants implicated in the etiology of diseases in Africans, but comparatively few studies have been conducted thus far on native African ethnic groups (see link to the Online Mendelian Inheritance in Man database; Cavalli-Sforza et al., 1994; Sgaier et al., 2007; Tishkoff et al., 2009). In fact, most research has been performed on non-African populations and on Afro-Americans (Jorde et al., 2001). This is due to the extraordinary difficulties in obtaining clinically annotated human biological samples in most Sub-Saharan African contexts, due logistic and organizational issues, to the rarity of clinical centers, to the lack of trained personnel, and to the almost complete absence of facilities for processing and safe storage of the biosamples. To reconstruct human evolutionary history, to dissect the genetic basis of resistance and susceptibility to diseases, to design better drugs for all people and to understand the basis of complex disorders is necessary, in addition to increase funding and resources, the creation of a global consortium of ⁎ Corresponding author. ITB-CNR, Via Fratelli Cervi 93, 23090 Segrate, Milano, Italy. Tel.: + 39 0226422712; fax: + 39 0226422770. E-mail address: [email protected] (I. Biunno). 0048-9697/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.scitotenv.2010.07.054
Biobanks in Africa (Sgaier et al., 2007). Very recently (23 June 2010), the National Institute of Health (Washington DC) and Welcome Trust (London-UK) announced a partnership to launch a joined project named “Human Hereditary and Health in Africa,” (H3Africa). The project aims to use genomic and clinical tools to identify the genetic and environmental contributions to communicable and non communicable diseases. This huge effort will allow the setting up of various regional or national “biobanks” in order to address common ethical issues, data ownership and data sharing. These biobanks will collect DNA and medical information from hundreds of thousands of African people facilitating genetic epidemiology studies and hopefully uncover gene-environmental interactions by linking together genetic variations to environmental factors. The ultimate goal is to accelerate the discovery of vaccines, drugs and diagnostics. Genetic variations has major implications in medicine and public health since affects disease susceptibility and predisposition to infectious diseases and may provide a better understanding of the universal cancer problems (Cooke and Hill, 2001; Sirugo et al., 2004; Molony, 2005; Menard et al., 2006; Sirugo et al., 2008, 2005; Khoury, 2003). Indeed, the line between normal and pathological variants can be drawn only taking into account ethnic and geographic origin, and should be based on an accurate description of gene/allele frequencies.
N. Gasmelseed et al. / Science of the Total Environment 423 (2012) 210–213
The annotation of millions of single nucleotide polymorphisms (SNPs) within the genome, facilitated by the completion of the Human Genome Project, the development of ultrahigh-throughput genotyping, small molecule detection methods and powerful software to analyze the mass of data that is generated will make possible the discovery of the allelic and biological variants that underlie complex diseases (such as cardiovascular, cancer, diabetes, communicable and non communicable diseases, tuberculosis and AIDS); (Sgaier et al., 2007; Collins, 2001; Guttmacher, 2002). Large-scale analyses of genes (genomics), proteins (proteomics), and metabolites (metabolomics) have been undertaken thanks to the availability of well-annotated human biological samples provided by biological resource centers (BRC) (Troyer, 2008). BRCs follow the best practices guidelines released by The International Society for Biological and Environmental Repositories (ISBER) (2005) and the National Cancer Institute's Office of Biorepositories and Biospecimen Research (Ozerskay, 2008). Well-designed geographically-based BRCs offer the opportunity to: (1), assess population prevalence of specific genes and variants; (2) simplify the search for molecular markers; (3), improve targeted drug discovery and development for disease management; (4), refine strategies for disease prevention; (5), provide the data necessary for evidence-based decision-making (Blatt, 2000). Biological samples (wet tissues, frozen and paraffin-embedded tissues, glass slides, blood, serum and urine) from both diseased and unaffected individuals should be cryopreserved with a quality as close as possible to the initial quality (i.e., quality at sampling). The promise of genomic research has drawn attention on the highly sensitive category of information contained in the genes and on how to inform donors correctly. In fact, serious scientific and social questions regarding the protection of the rights of people whose samples are in the biobank, the identification and access of such samples, the privacy and confidentiality of genomic information, civil liberties, patenting and commercialization of biosamples, and, finally, proprietary rights. These issues largely remain un-resolved (Cambon-Thomsen, 2003; Hoffman, 2009). 2. Potentials of a biological resource center (BRC) in the Sudan Sudan, the largest country in Africa, may reflect the African nation in which develop a BRC. Sudan besides being the largest country in Africa is characterized by a strategic geographical position linking the Arab world to Sub-Saharan Africa. It shares borders with nine countries and holds within its borders an admixture of populations and cultures. Indeed, Sudan is one of the most ethnically and linguistically diverse country in the world, with nearly 600 ethnic groups speaking over 400 languages and dialects. Some smaller ethnic and linguistic groups have disappeared due to migration, migrants often forget their native tongue when they move to an area dominated by another language. Some linguistic groups were absorbed by accommodation others by conflict. Arabic is the lingua franca but despite the use of English by many elites, most Sudanese are multilingual. Sudan is a multicultural country where hundreds of tribes live together: the Nubians in the north, Bija in the east, Kababish, Baggara and Nuba in the west Nuer and Dinke in the south. The environment ranges from damp rainy in the south, to desert in the northern areas. Despite being the 17th fastest-growing economy in the world with new economic policies and infrastructure investments, Sudan still faces remarkable socio-economic problems, as it must rise from a very low level per capita income. Rich mineral resources are available in Sudan which includes: petroleum, natural gas, gold, silver, chrome, asbestos, manganese, gypsum, mica, zinc, iron, lead, uranium, copper kaolin, cobalt, granite, nickel and tin. Agriculture production remains Sudan's most important sector, employing 80% of the workforce, but most farms remain rain-fed and susceptible to droughts. Unfortunately, outside urban areas, little health care is available. Control of communicable diseases dominates the health
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scene with high vulnerability to disease outbreaks. Large parts of Sudan's population suffer from poor hygiene, bad infrastructure and bad water quality. Common diseases include malaria, dysentery and other gastrointestinal disorders, and tuberculosis. Bilharziasis is a major problem for people along the White and Blue Niles, African Trypanosomiasis, sleeping sickness, is widespread in the south. Meningitis, measles, whooping cough, infectious hepatitis, syphilis and gonorrhea are also relatively common. Some regions have problems of seasonal undernourishment, and malnutrition is still a problem in some areas. Malnutrition is widespread outside the central Nile corridor because of population displacement from war and recurrent droughts; these factors, together with a scarcity of medicines, make diseases difficult to control. Child immunization against most major childhood diseases, however, had risen to approximately 60% by the late 1990s from very low rates in earlier decades. The research priorities in Sudan are on infectious diseases although diabetes, thyroid disease and cancer are not to be underscored. The objective of this brief paper is to identify the challenges in the realization of a “BRC” infrastructure in Sudan and formulate professional and scientific view on the social, ethical and economical issues that provide an impact on data storage and human biobanking practices for biomedical research in Sudan. A biorepository initiative in the Sudan would be justified by the fact that presently small disease- and geographically-oriented biobanks already exist in Central Sudan. These biobanks have been motivated by specific studies and are concentrated in two research institutes in Khartoum, i.e., the “Institute of Endemic Diseases” and the “Tropical Medicine Research Institute” and one in Wadmedani, i.e., the “National Cancer Institute” (NCI). Questionnaires about the objectives of the presently held collections, the types of specimens currently stored, qualification and training of the personnel working in the biobank, procedures applied, participation in international biobanking networks, data sharing of the stored samples were distributed to research institutes. Table 1 summarizes the collections, their locations, the disease phenotypes and the type of biological specimens stored. These Institutes have a local ethical committee for the evaluation and approval of research proposals and are linked to the National Ethical Committee network within the Federal Ministry of Health. The role of this Committee is to evaluate and eventually approve specific programs of research such as: multi-states studies within the Sudan federal state, international research collaborations, and drug or vaccine experimental trials. Ethical consent may represent a problem in establishing and maintaining a biobank in Sudan, due to the lack of proper legal approval or consent by local ethical committees. The task of providing ethical and legal guidance could therefore be assumed by the National Ethical Committee, in conjunction with the existing local Committees at the three major research institutes in Khartoum and Wadmedani. 3. Scientific, ethical procedures and donor confidentiality The genome based science we are exposed today, has placed huge attention on the highly sensitive category of information contained in genes. Polymorphic markers (SNPs) are related to gene function and play a role in the understanding of the origin of common diseases, the response of individuals to treatments and to the development of new therapeutic molecules. Serious scientific and social questions regarding the protection of the rights of people whose samples are in the biobank, the identification and access of the samples, privacy and confidentiality of the genomic information, civil liberties, patenting and commercialization of the biosamples and finally proprietary rights are still highly debatable arguments (Human Genetic Commission, http://www.dh.gov.uk/en/publicationsandstatistics/publications/publicationspolicyandguidance/dh_4009988 (accessed 24 October 2008). Informed consent has become the standard way of legitimising medical interventions and protects individual privacy. Biobanks due
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Table 1 Biomedical collections currently present in the Sudan (ND: not determined number). No. Institute and location
1-
2-
3-
Type of sample collected
Whole blood, serum, plasma, cells, paraffinembedded tissue and fresh tissue Institute of Endemic Diseases, Whole blood, serum, plasma University of Khartoum, Khartoum
National Cancer Institute, University of Gezira, Wadmedani
Tropical Medicine Research Institute, National Research Center, Ministry of Science and Research Technology, Khartoum
Whole Blood, serum, Plasma buffy coat
Capacity of shares samples
Types Freezer and backup power
Cell pellets, 1500 whole blood, samples DNA, serum are stores and plasma
50% of sharing samples with international institutions
DNA, serum, plasma
25% of the total samples were share with International Institution 25% of the total samples were share with International Institution
Three freezer −20 °C Two freezer −80 °C In addition to −4 °C Liquid nitrogen containers with automatic generator Two −20 °C one −80 °C and one −40 °C Electronic generator and Liquid nitrogen
No. of currently stored and processed samples
Disease phenotype
Type of stored biological specimens
Malaria, non Hodgkin's lymphoma, breast cancer, nasopharyngeal carcinoma schistosomiasis, tuberculosis, HBV and HCV infection, hepatocellular carcinoma. Infectious diseases (malaria, tuberculosis leishmaniasis, etc.), cancers
Schistosomiasis, malaria, cancer
ND Whole blood, serum, plasma puffy coat and parasites
to the nature of their research, to use the biological material need a “broad consent” which requires less specific information then “strict consent” forms (Beskow and Dean, 2008; Hansson et al., 2006; Hoffman, 2009). To fulfill long term research projects using new technology, new perspectives and new research questions, biobank research requires a revision of the presently used consent forms keeping in mind that to renew consents is costly especially if the donors are anonymous or deceased (Meslin, 2004). 4. Conclusions and discussion Research activities have traditionally been performed in non-African populations thus liming the knowledge of the genetic basis of diseases in Africa. Certainly the comparisons of the genetics, genomics and epigenetics between Africans and African descendants leaving outside of Africa, can lead to the identification of those environmental risk factors that influence the universal problems of cancer (Sgaier et al., 2007). Epidemiological genetic studies require a shared set of DNA resources, the establishment of an African genetic database and large bio-collections (Ginsburg et al., 2008). In Sudan, biobanking (DNA, blood and cells) started only recently (in this decade) and for research purposes only. As established through questionnaire responses, all the research institutes presently involved do not have cryopreservation standard operating procedure (SOPs), supplier qualification, personnel training, control and quality systems. An internal sample tracking procedure was developed based on excel-spread sheets. However, the status of the collections is not well known and most laboratories that bank DNA have no written policies or agreements regarding their activities. Furthermore, little information is available to guide researchers in selecting the most appropriate specimens for epidemiologic studies and surveys. In general, there is still concern regarding validity of informed consent, safeguard of samples and data privacy. Obtaining informed consent for the collection and storage, as well as future research use of biospecimens is challenging, as potentially complex and controversial information must clearly be communicated. A major challenge for biobanking in Sudan is also the economical situation. Since managing of large bio-collections requires implementation of standards and guidelines (two-dimensional and nanobarcodes and customized electronic databases to assure efficient management of large sample collections and tracking results of data analyses), a single academic investigator or a small research consortium cannot govern the samples alone. Thus major investment is necessary for new equipments and for renewal of old ones, for the training of human resources dedicated to biobanking activities, and for the coverage of operational costs
ND
Five freezer −20 °C three freezer −80 °C In addition to Liquid nitrogen containers
(electricity, liquid nitrogen, reagents, maintenance, etc.). Cost recovery policies should also be contemplated. In conclusion then, there is an increasing awareness on the importance of doing genetic research in African settings. This urges international coordinated actions to expedite the development of adequate infrastructures and the training of African scientists to lead and promote research in Africa. It is an accepted hypothesis that centralization and standardization of biobanking activities will facilitate international collaborations, define restrictions and limit the dis-use of the biosamples for research. Indeed the governments of several countries, including United Kingdom (www.ukbiobank.ac.uk), Iceland (www.decode.com), Estonia (www.genomics.ee), Singapore, and Sweden, as well as medical centers in the United States, have made commitments to create centralized banking facilities on a national scale. In Africa this effort is still in its infancy. It is un-realistic and, to say the least, logistically unfeasible, to think that all African countries would agree in storing their biological resources in a single “continental African biorepository.” National or regional biobanks are a first key step, as exemplified by the DNA biobank in The Gambia (Sirugo et al., 2004), a Wellcome Trust-financed project. Outside of Africa, examples that could be considered as models are the Indian National Biobank (Sgaier et al., 2007); The Chinese Kadoorie study (Chen et al., 2005) and The Mexico City Prospective bank (Tapia-Conyer et al., 2006). However, a number of initiatives from developed countries are in progress to sponsor the creation of a global consortium of biobanks committed to aid biobanking in developing countries (Morel et al., 2005). Indeed, recently was announced the H3Africa project, a $38 M effort between NIH and Wellcome Trust to create a repository in Africa for biological sample collection of native Africans, will provide participants with examination and screening tests, will train African researchers abroad with the prospective to return to their home country and establish or enhance research facilities. This project will promote strong collaborations between African Institutions, USA, Europe and with other parts of the world. Acknowledgements We would like to thank the following: Prof. Moawia Mukhtar Institute of Endemic Diseases (IED), University of Khartoum; Dr Intisar Erayh, Director, Tropical Medicine Research Institute (TMRI), National Research Institute; and the Ministry of Scientific Research and Technology (Khartoum). This collaborative work was partly financed by a grant from the Italian government to IB and PDB (MURFIRB nRBIP064CRT).
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