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Timothy Caulfield,
Stephanie M Fullerton,
Sarah E Ali-Khan,
Laura Arbour,
Esteban G Burchard,
Richard S Cooper,
Billie-Jo Hardy,
Simrat Harry,
Robyn Hyde-Lay,
Jonathan Kahn, [......],
Barbara A Koenig,
Sandra SJ Lee,
Michael Malinowski,
Vardit Ravitsky,
Pamela Sankar,
Stephen W Scherer, Béatrice Séguin,
Darren Shickle,
Guilherme Suarez-Kurtz,
Abdallah S Daar
[show abstract]
[hide abstract]
ABSTRACT: The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such
as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering
an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined
by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and
race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health
in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review
the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action,
including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology
in the media, and drifting or ambiguous definitions of key terms.
Genome Medicine 04/2012; 1(1):1-8.
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Timothy Caulfield,
Stephanie M Fullerton,
Sarah E Ali-Khan,
Laura Arbour,
Esteban G Burchard,
Richard S Cooper,
Billie-Jo Hardy,
Simrat Harry,
Robyn Hyde-Lay,
Jonathan Kahn, [......],
Barbara A Koenig,
Sandra Sj Lee,
Michael Malinowski,
Vardit Ravitsky,
Pamela Sankar,
Stephen W Scherer, Béatrice Séguin,
Darren Shickle,
Guilherme Suarez-Kurtz,
Abdallah S Daar
[show abstract]
[hide abstract]
ABSTRACT: The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.
Genome Medicine 02/2009; 1(1):8.
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[show abstract]
[hide abstract]
ABSTRACT: In 2004, the government of Mexico established the National Institute of Genomic Medicine (INMEGEN), to carry out disease-related genomic studies that will address national health problems and stimulate scientific and technological development by generating new commercial products and services in genomic medicine. Towards this end, INMEGEN is carrying out a large-scale genotyping project to map genomic variation within its own population. The initiative is expected to generate a key resource for local researchers to understand disease susceptibility and variation in drug responses, which will contribute to Mexico's goal of developing public health genomics - a field in which Mexico is proving to be a leader amongst emerging economies.
Nature Reviews Genetics 10/2008; 9 Suppl 1:S5-9. · 38.08 Impact Factor
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ABSTRACT: One potential outcome of investing in genomic medicine is the provision of tools for creating a more cost-effective health-care system. Partly with this aim in mind, Thailand has launched two genotyping initiatives: the Thai SNP Discovery Project and the Thai Centre for Excellence in Life Sciences Pharmacogenomics Project. Together, these projects will help Thailand understand the genomic diversity of its population and explore the role that this diversity has in drug response and disease susceptibility in its population. A major future challenge will be for Thailand to integrate genomic medicine in its relatively young universal health-care system.
Nature Reviews Genetics 10/2008; 9 Suppl 1:S14-9. · 38.08 Impact Factor
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ABSTRACT: This is a historical moment on the path to genomic medicine - the point at which theory is about to be translated into practice. We have previously described human genome variation studies taking place in Mexico, India, Thailand, and South Africa. Such investments into science and technology will enable these countries to embark on the path to the medical and health applications of genomics, and to benefit economically. Here we provide a perspective on the challenges and opportunities facing these and other countries in the developing world as they begin to harness genomics for the benefit of their populations.
Nature Reviews Genetics 10/2008; 9 Suppl 1:S23-7. · 38.08 Impact Factor
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ABSTRACT: India currently has the world's second-largest population along with a fast-growing economy and significant economic disparity. It also continues to experience a high rate of infectious disease and increasingly higher rates of chronic diseases. However, India cannot afford to import expensive technologies and therapeutics nor can it, as an emerging economy, emulate the health-delivery systems of the developed world. Instead, to address these challenges it is looking to biotechnology-based innovation in the field of genomics. The Indian Genome Variation (IGV) consortium, a government-funded collaborative network among seven local institutions, is a reflection of these efforts. The IGV has recently developed the first large-scale database of genomic diversity in the Indian population that will facilitate research on disease predisposition, adverse drug reactions and population migration.
Nature Reviews Genetics 10/2008; 9 Suppl 1:S9-14. · 38.08 Impact Factor
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ABSTRACT: The South African government is committed to science and technology innovation, to establishing a knowledge-based economy and to harnessing life-sciences research for health and economic development. Given the constraints and the early stage of development of the field as a whole in South Africa, we found an impressive amount of research on human genomic variation in this country. Encouragingly, South Africa is beginning to apply genomics to address local health needs, including HIV and tuberculosis (TB) infections. We document a number of initiatives in South Africa that are beginning to study genetic variation within the various local indigenous populations. Other early initiatives focus on pharmacogenetic studies, mutation characterization in individual disease genes and genome-wide association studies. Public engagement in genomic issues is spear-headed by The Africa Genome Education Institute.
Nature Reviews Genetics 10/2008; 9 Suppl 1:S19-23. · 38.08 Impact Factor
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ABSTRACT: The notion that developing countries must wait for the developed world to make advances in science and technology that they later import at great cost is being challenged. We have previously argued that developing countries can harness human genetic variation to benefit their populations and economies. Based on our empirical studies of large-scale population genotyping projects in Mexico, India and Thailand, we describe how these resources are being adopted to improve public health and create knowledge-based economies. A significant additional benefit is building the capacity for scientific research and internalizing advances in technology, whatever their source.
Nature Reviews Genetics 07/2008; 9(6):487-93. · 38.08 Impact Factor
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Science 07/2006; 312(5780):1602-3. · 31.20 Impact Factor
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ABSTRACT: Idiosyncratic drug reactions (IDRs) cause significant morbidity and mortality. In an animal model of IDRs, 50-80% of Brown Norway rats exposed to D-penicillamine develop an autoimmune syndrome after several weeks of treatment. The symptoms of the IDR are similar to that observed in humans who take D-penicillamine. The mechanism of this reaction is unknown, and no effective biomarkers have been identified to predict susceptibility. We postulate that cell stress caused by drugs is required to initiate the response. We used a high-throughput approach to identify factors that might represent danger signals by profiling hepatic gene expression 6 h after dosing with D-penicillamine (150 mg/kg). Our results show that the drug-treated animals cluster into two distinct groups. One group exhibits substantial expression changes relative to control animals. The most significantly altered transcripts have a role in stress, energy metabolism, acute phase response, and inflammation. We used quantitative reverse transcriptase polymerase chain reaction to measure transcript levels in liver biopsies of 33 rats and found that resistant animals cluster together. This "resistant" cluster of animals contains 87.5% (7/8) resistant animals but only 48% (12/25) "sensitive" animals. This separation is statistically significant at the p = 0.01 level.
Chemical Research in Toxicology 09/2005; 18(8):1193-202. · 3.78 Impact Factor
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ABSTRACT: The D-penicillamine autoimmune syndrome observed in Brown Norway (BN) rats is similar to an idiosyncratic reaction seen in some patients. We have previously shown that 2 weeks of low dose (5 mg/day) D-penicillamine pretreatment completely prevented all clinical signs of autoimmunity normally observed in 60-80% of rats treated with high dose (20 mg/day) D-penicillamine. We demonstrated that this tolerance is immune-mediated; tolerance to D-penicillamine is long lasting, we can adoptively transfer splenocytes from tolerant rats into slightly irradiated naive syngeneic recipients, and rats exposed to low dose D-penicillamine produce tolerogenic cytokines [Masson, M. J., and Uetrecht, J. P. (2004) Tolerance induced by low dose D-penicillamine in the brown norway rat model of drug-induced autoimmunity is immune-mediated. Chem. Res. Toxicol. 17, 82-94]. The aim of this study was to provide further understanding of the cells that are responsible for transferring tolerance and to assess the presence of regulatory T cells in the spleen of tolerant animals. We cotransferred T cells or splenocytes depleted of T cells from tolerant BN rats with splenocytes from naive BN rats into lightly irradiated syngeneic recipients. We found that neither tolerant splenocyte subpopulation could completely prevent clinical signs of autoimmunity. These results demonstrate that immune tolerance to D-penicillamine-induced autoimmunity may require both antigen presenting cells and T cells.
Chemical Research in Toxicology 11/2004; 17(10):1299-302. · 3.78 Impact Factor
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ABSTRACT: Idiosyncratic drug reactions pose a significant clinical threat and hamper drug development. The idiosyncratic nature of these reactions has made mechanistic studies exceedingly difficult, and yet without a better understanding of the mechanisms involved it is unlikely that much progress can be made in dealing with the problem. Several working hypotheses have been used to study these reactions, but none fits all of the characteristics that are observed. Borrowed from immunology, the danger hypothesis has most recently been used to explain several characteristics of these reactions. The present review describes the danger hypothesis and compares it with previous hypotheses to determine how well each fits with the observed characteristics of the reactions.
Slow progress in the field continues and it is important to use new observations, such as identifying T cells that recognize drugs in the absence of reactive metabolite formation, to test and refine the working hypotheses. However, the development of animal models of idiosyncratic drug reactions as well as progress in basic immunology and genomics are likely to accelerate progress in this area in the near future.
No one model fits the characteristics of all idiosyncratic drug reactions; however, the danger model provides a new perspective and suggests avenues of research that have the potential to increase our ability to predict and prevent such reactions significantly.
Current Opinion in Allergy and Clinical Immunology 09/2003; 3(4):235-42. · 4.11 Impact Factor
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Timothy Caulfield,
Stephanie M Fullerton,
Sarah E Ali-Khan,
Laura Arbour,
Esteban G Burchard,
Richard S Cooper,
Billie-Jo Hardy,
Simrat Harry,
Robyn Hyde-Lay,
Jonathan Kahn, [......],
Barbara A Koenig,
Sandra SJ Lee,
Michael Malinowski,
Vardit Ravitsky,
Pamela Sankar,
Stephen W Scherer, Béatrice Séguin,
Darren Shickle,
Guilherme Suarez-Kurtz,
Abdallah S Daar
[show abstract]
[hide abstract]
ABSTRACT: The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.
