(2013). Sickle Cell Disease and the “Difficult Patient” Conundrum. The American Journal of Bioethics: Vol. 13, No. 4, pp. 3-10. doi: 10.1080/15265161.2013.767954.

Sickle cell disease is an autosomal recessive hemoglobinopathy found mainly in populations of African and Mediterranean descent, including approximately 100,000 Americans. It is also very common in Spanish-speaking regions of Central America, South America, and parts of the Caribbean, in Saudi Arabia, and in India and Sri Lanka. The disorder is characterized most commonly by lifelong recurrent unpredictable vaso-occlusive pain that may be disabling, and by chronic tissue damage and organ dysfunction. There are several genotypes of the (...) disease. Although SCD pain frequency generally varies between genotypes, it also varies between subjects even within genotype. It may worsen from childhood to adulthood. It may vary by gender. Its location, timing, and severity may be unpredictable.Until recently, pain in SCD had been characterized as episodes that were acute, periodic, and relatively rare. Crises were viewed as usually associated with hospitalization. Many patients utilized hospital or emergency care for pain once per year or less, so painful episodes in SCD were called vaso-occlusive “crises.”. (shrink)

Background Noninvasive prenatal testing (NIPT) designed to screen for fetal genetic conditions, is increasingly being implemented as a part of routine prenatal care screening in the United States (US). However, these advances in reproductive genetic technology necessitate empirical research on the ethical and social implications of NIPT among populations underrepresented in genetic research, particularly Black women with sickle cell disease (SCD).Methods Forty (N = 40) semi-structured interviews were conducted virtually with Black women in the US (19 participants (...) with SCD; 21 participants without SCD) from June 2021 to January 2022. We employed a qualitative approach to examine the study participants’ perceptions of the potential advancement of NIPT for screening SCD in the fetus. Data were analyzed using NVivo 12 qualitative software.Results The themes revealed the complexities involving the intersectional lived experiences of SCD, prenatal care, lack of synergy among health providers, and NIPT decision-making. The results further revealed that even when Black women have shared commonalities in their lived experiences while navigating SCD and motherhood, their perceptions of NIPT screening technologies are divergent.Conclusion Expanding the ethical discourse on the social implications of NIPT is critical to fully elucidate how Black women perceive NIPT’s utility, particularly as NIPT advances to screen for SCD in the fetus. Neglecting to include Black women with genetic conditions in empirical studies on NIPT may contribute to ongoing health inequities and limit and constrain reproductive choices among Black women with and without SCD. (shrink)

Sickle cell disease describes an inherited group of blood disorders that affect the lives of more than 4 million people around the globe. More than 43 million additional people are believed t...

In a recent article, Marilyn Baffoe-Bonnie offers three arguments for conducting CRISPR/Cas9 biotechnology research to cure sickle-cell disease (SCD) based on addressing historical and current injustices in SCD research and care. I show that her second and third arguments suffer from roughly the same defect, which is that they really argue for something else rather than for conducting CRISPR/Cas9 research in particular. For instance, the second argument argues that conducting this gene therapy research would improve the relationship (...) between SCD sufferers (who are mostly of African descent) and health care providers. But really what is essential in improving this relationship is for those providers to genuinely care and be concerned, and this could be lacking even with the CRISPR research being done. Indeed, this relationship could be improved even without that research being done, as long as there is genuine concern. Thus, this argument actually argues for the need for genuine concern. As for the third argument, one (of two) problems arises because it claims that CRISPR research for SCD should be pursued because the benefits would be shared by even non-research-participants, as non-participants would be encouraged. However, this argues for any research for SCD, not for CRISPR research in particular. I conclude that a better justice-based argument will use only Baffoe-Bonnie’s first argument, which is based on historic neglect of an actual cure for SCD (going beyond merely management or transplant therapies). (shrink)

This paper investigates continuities and changes in the definition of sickle cell disease in 1950s Brazil, taking into account that diseases have a history and are recognized as such according to the knowledge and perceptions available in a certain historical period and specific location. In the post-war era, new diagnostic tools, inheritance theories and, in particular, discussions on the concepts of race and racial relations, both nationally and internationally, were changing previous racialist and racist views. Nonetheless, the (...) Brazilian medical interpretations of sickle cell disease continued to racialize it and even use deep-rooted racist formulations to explain its symptoms or the existence of the disease. It is argued that the celebration of racial mixture and racial democracy might have concealed racist presumptions biasing the study of sickle cell disease. Although race as a biological concept gradually gave way to other genetic expressions, in Brazilian medical papers on sickle cell disease, race continued to influence the interpretation of the disease, along with the persistence of concepts of heredity through blood mixture. (shrink)

CRISPR/Cas9 is quickly becoming one of the most influential biotechnologies of the last five years. Clinical trials will soon be underway to test whether CRISPR/Cas9 can edit away the genetic mutations that cause sickle cell disease (SCD). This article will present the background of CRISPR/Cas9 gene editing and SCD, highlighting research that supports the application of CRISPR/Cas9 to SCD. While much has been written on why SCD is a good biological candidate for CRISPR/Cas9, less has been written (...) on the ethical implications of including SCD in CRISPR/Cas9 research. This article will argue that there is a strong case in favor of including SCD. Three benefits are achieving distributive justice in research, continuing to repair the negative relationship between patients with SCD and the health‐care system, and benefit‐sharing for those who do not directly participate in CRISPR/Cas9 research. Opponents will argue that SCD is a risky candidate, that researchers will not find willing participants, and that the burden of SCD is low. Of this set of arguments, the first gives pause. However, on balance, the case in favor of including SCD in CRISPR/Cas9 research is stronger than the case against. Ultimately, this article will show that the historic and sociopolitical injustices that impede progress in treating and curing SCD can be alleviated through biotechnology. (shrink)

(2013). Intractable Difficulties in Caring for People With Sickle Cell Disease. The American Journal of Bioethics: Vol. 13, No. 4, pp. 22-24. doi: 10.1080/15265161.2013.767959.

International health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants’ perspectives, including social forms of benefit and harm, and the influence of access to care. To inform (...) research practice locally, and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status. (shrink)

Historical accounts of sickle cell disease tend to emphasize either its theoretical role in catalyzing the field of medical genetics or its clinical and social significance in representing the health-care disparities experienced by African Americans. This essay bridges these narratives by focusing on the discovery of sickle cells in marginalized Arabic-speaking communities of Yemen and Turkey in the 1950s. As in North America, sickle cell research in the Middle East unfolded along the social fractures (...) of race. The essay analyzes how British, Turkish, and Arab geneticists attempted to create evolutionary hypotheses that reconciled historical and sociological boundaries between white and African, Arab and Turk. As the parameters of Turkish and Arab nationalism shifted in the Cold War–era Middle East, so did the favored explanatory narratives for the presence of sickle cells in different communities, which assigned different degrees of importance to African ancestry, socially enforced endogamy, and evolutionary adaptations to malaria. (shrink)

Volume 20, Issue 8, August 2020, Page 46-49.

Sickle cell disease is a debilitating illness that affects quality of life and life expectancy for patients. In Cameroon, it is now possible to opt for termination of an affected pregnancy where the fetus is found to be affected by SCD. Our earlier studies found that, contrary to the views of Cameroonian physicians, a majority of parents with their children suffering from SCD would choose to abort if the fetuses were found to be affected. What have not (...) yet been investigated are the views of people suffering from/living with SCD. We used a quantitative sociological method, with administered structured questionnaires, to study the attitudes of adult patients suffering from SCD on prenatal genetic diagnosis and possible TAP. The majority of the 89 participants were urban dwellers , women , Christian and single , with a secondary/tertiary education . The majority would consider PND for SCD; almost half would reject TAP while 40.9% would consider it. Respondents who rejected TAP claimed mostly ethical reasons while those who found TAP acceptable cited fear of having an affected child and the poor quality of the affected child's health . Cameroonian patients with SCD are generally supportive of PND and a remarkably high number of patients living with SCD reported that they would consider terminating a pregnancy based on their assessment of the future well-being of the child. Research is required to investigate the burden of SCD on families and their quality of life. (shrink)

(2013). Disrespectful Care in the Treatment of Sickle Cell Disease Requires More Than Ethics Consultation. The American Journal of Bioethics: Vol. 13, No. 4, pp. 12-14. doi: 10.1080/15265161.2013.768857.

This study examines how low-income African American mothers of children with sickle cell disease cope with the reproductive implications of having passed a genetic disease on to their children. Based on in-depth interviews with 29 African American mothers, I found that most mothers knew about SCD prior to having a child with the disease; many knew they were carriers of the sickle cell trait. In explaining why this knowledge did not lead them to (...) alter their reproductive behaviors, mothers invoked a theme of medical mismanagement; that is, they said the genetic screening programs for SCD did not provide them with enough medical knowledge about the disease. The implication that adequate knowledge about SCD would have affected their childbearing choices, however, is contradicted by their subsequent reproductive behaviors. I argue that the SCD diagnosis threatened motherhood, an important cultural value among low-income African American women, and that they protected their reproductive autonomy by obfuscating SCD medical knowledge. (shrink)

(2013). Not Your Typical Frequent Flyer: Overcoming Mythology in Caring for Sickle Cell Disease Patients. The American Journal of Bioethics: Vol. 13, No. 4, pp. 18-20. doi: 10.1080/15265161.2013.767963.

Crediting scientific discovery for prolonging life is pervasive in biomedical histories of the genetic blood disorder, sickle cell disease. This includes the preventive strategies, such as newborn screening, that have underwritten the success of its life-extending interventions. Newborn screening is a technology that relies not only upon intact health infrastructures but also expertise and enhanced vigilance on the part of caregivers to anticipate complications while they are still open to circumvention. This paper posits that even after overcoming (...) institutional barriers to make newborn screening equitably available, care and vigilance are resources that are themselves subject to what I term anticipatory politics, where structural conditions also stratify expectations for the future, including the affective appeal of medical innovations. This paper elaborates the paradigm of anticipatory politics through an ethnographic examination of newborn screening to connect the comprehensive care practices that have improved survival for sickle cell disease, and as the burden of mortality shifts to young adulthood, to expose how those who are resourced to care for these futures preferentially stand to benefit from preventive interventions. (shrink)

(2013). The “Difficult Patient” Conundrum in Sickle Cell Disease in Kenya: Complex Sociopolitical Problems Need Wide Multidimensional Solutions. The American Journal of Bioethics: Vol. 13, No. 4, pp. 20-22. doi: 10.1080/15265161.2013.767960.

The Inforare project aims to set up a system for the sharing of clinical and familial data, in order to study how genes are related to the severity of sickle cell disease. While the computerisation of clinical records represents a valuable research goal, an ethical framework is necessary to guarantee patients' protection and their rights in this developing field. Issues relating to patient information during the Inforare study were analysed by the steering committee. Several major concerns were (...) discussed by the committee and formalised in the patients' information letter: educating patients to aid the recruitment of family members, rules of confidentiality and the disclosure of aggregate, individual and unexpected research results. This paper presents the main issues addressed. (shrink)

Gene therapies to treat sickle cell disease are in development and are expected to have high costs. The large eligible population size — by far, the largest for a gene therapy — poses daunting budget challenges and threatens to exacerbate health disparities for Black patients, who make up the vast majority of American sickle cell patients.

Sickle cell anemia is a disease characterized by abnormal hemoglobin structure. There is a mutation in the beta-globin gene that changes the sixth amino acid from glutamic acid to valine causing the mutated hemoglobin to polymerize reversibly when deoxygenated to form a gelatinous network of fibrous polymers that stiffen and distort the red blood cell membrane. This leads to episodes of microvascular vasoocclusion and premature RBC destruction leading to hemolytic anemia. For reasons that are unclear, some (...) children develop a large artery vasculopathy involving the intracranial arteries supplying the brain.The risk of stroke for a child with SCD is many times greater than that of a healthy child without SCD or heart disease. There is a technique that allows the identification of the children with SCD who have high risk even within this relatively high-risk group. And there is a highly effective preventive treatment. (shrink)

This paper focuses on sickle cell anemia and thalassemia as case studies of genetic disease in America. Before the 1950s, these two diseases were perceived by many physicians as closely related (indeed, by some, as indistinguishable). Sickle cell anemia was defined by most American physicians as a Mendelian dominant disorder specific to African-Americans. As such, it could be 'spread' by any individual parent 'carrier' through reproduction. This view of the disease fed into (and was (...) supported by) prevalent social concerns about miscegenation and, more generally, the dangers inherent in 'negro blood'. A particularly thorny problem for American physicians was how to explain cases of 'sickle cell anemia in white patients'. The paper examines how views about race, blood, and Mendelian genetics informed broader debates about the nature of hereditary disease and social relations in America from 1910 to 1950. (shrink)

This article presents the epistemological issues related to the implementation and exploitation of data produced within the framework of a transdisciplinary project on young sickle cell patients in Guadeloupe. The use of the theoretical model of the Human Development Model – Disability Creation Process aims to apprehend the reciprocal interactions between the biomedical effects of the pathology and lifestyle habits, breaking with medical readings of the disability. Based on an inclusive approach, this model reintroduces individual factors in interaction (...) with the physical and social environment, in the study of the performance of everyday activities and social roles. The resulting reflection on transdisciplinarity concerns both the operationalization of the survey protocol and the modalities of processing research data. How to avoid the dispersion or simple coexistence of the latter? By contributing to their integration, the HDM-DPC offers a framework likely to promote applications and benefits for patients. The transdisciplinary approach aims societal benefits, in particularly improved inclusion in all spheres of their social life and aims to examine the epistemological foundations of a transdisciplinary study of sickle cell disease, favoring a socio-anthropological approach. (shrink)

BackgroundThe potential contribution of community engagement to addressing ethical challenges for international biomedical research is well described, but there is relatively little documented experience of community engagement to inform its development in practice. This paper draws on experiences around community engagement and informed consent during a genetic cohort study in Kenya to contribute to understanding the strengths and challenges of community engagement in supporting ethical research practice, focusing on issues of communication, the role of field workers in 'doing ethics' on (...) the ground and the challenges of community consultation.MethodsThe findings are based on action research methods, including analysis of community engagement documentation and the observations of the authors closely involved in their development and implementation. Qualitative and quantitative content analysis has been used for documentation of staff meetings and trainings, a meeting with 24 community leaders, and 40 large public and 70 small community group meetings. Meeting minutes from a purposive sample of six community representative groups have been analysed using a thematic framework approach.ResultsField workers described challenges around misunderstandings about research, perceived pressure for recruitment and challenges in explaining the study. During consultation, leaders expressed support for the study and screening for sickle cell disease. In community meetings, there was a common interpretation of research as medical care. Concerns centred on unfamiliar procedures. After explanations of study procedures to leaders and community members, few questions were asked about export of samples or the archiving of samples for future research.ConclusionsCommunity engagement enabled researchers to take account of staff and community opinions and issues during the study and adapt messages and methods to address emerging ethical challenges. Field workers conducting informed consent faced complex issues and their understanding, attitudes and communication skills were key influences on ethical practice. Community consultation was a challenging concept to put into practice, illustrating the complexity of assessing information needs and levels of deliberation that are appropriate to a given study. (shrink)

In 1949, Linus Pauling and collaborators published in Science a paper provocatively titled: 'Sickle cell anemia, a molecular disease'. What was actually meant by 'molecular disease'? We interpret the concept of molecular disease in the frame of the traditional positions about the nature of diseases: the ontological and the physiological positions. We conclude that the physiological does not give an adequate account of what molecular diseases are. The ontological position, when correctly reinterpreted, leads to an (...) understanding of molecular diseases where the macromolecule is seen as a symptom or as a part of a mechanism leading to the symptoms of the disease. We then show that the concept of molecular disease leads to a particular view of therapy, emphasizing eugenics as a way of eliminating disease. On the individual level, this concept leads to an increased power of diagnosis, and especially predictive diagnosis, but has little therapeutic consequence. Lastly, we examine how this concept of disease unifies two contemporary classifications of diseases, one based on the location of the diseases, the other on the cause of the diseases. (shrink)

Non-therapeutic genetic testing in childhood presents a “myriad of ethical questions”; questions which are discussed and resolved in professional policy and position statements. In this paper we consider an underdiscussed but strongly influential feature of policy-making, the role of selective case and exemplar in the production of general recommendations. Our analysis, in the tradition of rhetoric and argumentation, examines the predominate use of three particular disease exemplar to argue for or against particular genetic tests. We discuss the influence these (...) choices have on the type and strength of subsequent recommendations. We argue that there are lessons to be drawn about how genetic diseases are conceptualised and we caution against the geneticisation of medical policy making. (shrink)

How is a disease contracted, and how does it progress through the body? Answers to these questions are fundamental to understanding both basic biology and medicine. Advances in the biomedical sciences continue to provide more tools to address these fundamental questions and to uncover questions that have not been thought of before. Despite these major advances, we are still facing conceptual and technical challenges when learning about the etiology of disease, especially for genetic diseases. In this review, we (...) illustrate this point by discussing the causal links between molecular mechanisms and systems-level phenotypes in molecular diseases. We begin with an examination of sickle cell anemia, and how mechanisms of the disease have been comprehended over the last century. While sickle cell anemia involves a mutation in a single protein in a single cell type, other diseases involve mutations in networks with many protein interactions and in diverse cell types. We introduce the challenges that result from these differences and illustrate the current obstacles by discussing the RASopathies, a recently discovered class of developmental syndromes that result from mutations in signaling networks. Methods to study mutant genotypes that lead to mutant phenotypes are discussed, particularly the use of model organisms and mutant proteins to study protein interactions that may be important for development of disease. These studies will point toward the future of diagnosing and treating genetic disease. (shrink)

Common monogenic genetic diseases, ones that have unexpectedly high frequencies in certain populations, have attracted a great number of conflicting evolutionary explanations. This paper will attempt to explain the mystery of why two particularly extensively studied common genetic diseases, Tay Sachs disease and cystic fibrosis, remain evolutionary mysteries despite decades of research. I review the most commonly cited evolutionary processes used to explain common genetic diseases: reproductive compensation, random genetic drift (in the context of founder effect), and especially heterozygote (...) advantage. The latter process has drawn a particularly large amount of attention, having so successfully explained the elevated frequency of sickle cell anemia in malaria-endemic areas. However, the empirical evidence for heterozygote advantage in other common genetic diseases is quite weak. I introduce and illustrate the significance of a hierarchy of genetic disease phenomena found within the genetic disease explanations, which include the phenomena: single mutation variants of a common genetic disease, single genetic diseases, and classes of diseases with related phenotypic effects. I demonstrate that some of the confusion over the explanations of common genetic diseases can be traced back to confusions over which phenomena are being explained. I proceed to briefly evaluate the existing evidence for two common human genetic diseases: Tay Sachs disease and cystic fibrosis. The above considerations will ultimately shed light on why these diseases’ evolutionary explanations remain so deeply unresolved after so such a great volume of research. (shrink)

Public investments in genomic and precision medicine have begun to yield clinically useful interventions, most recently, for example, two new, FDA-approved gene therapies for sickle cell disease (F...

An eighteen‐year‐old with sickle cell disease was admitted to the pediatric hematology service at his local children's hospital for management of an acute pain crisis, one of many such admissions. He had a good relationship with his primary hematologist and primary nurse, but with other health care providers, there was evident friction. Sometimes, he was simply rude, rolling over and pretending to sleep in response to questions about his symptoms. When frustrated or convinced that his pain was (...) not being addressed appropriately, he was prone to yelling and cursing at his nurses. After members of the health care team complained, their supervisor decided to transfer the patient to an adult general medicine service. Reasons cited for the transition included the stressful work environment created by the patient's actions, his refusal to follow directives from staff (although he was generally adherent to treatment), and the hypothetical harm to other young patients who might witness his behavior. Was this a just outcome? Is it ever permissible to deny access to pediatric care to a patient whose best interests would be served by it? Can access be withheld for “bad” behavior, and can transfer of care be wielded as a punishment? (shrink)

We report on the case of a 2-year-old female, the youngest person ever to undergo ovarian tissue cryopreservation (OTC). This patient was diagnosed with a rare form of sickle cell disease, which required a bone-marrow transplant, and late effects included high risk of future infertility or complete sterility. Ethical concerns are raised, as the patient's mother made the decision for OTC on the patient's behalf with the intention that this would secure the option of biological childbearing in (...) the future. Based on Beauchamp and Childress's principlism approach of respect for autonomy, nonmaleficence, beneficence, and justice, pursing OTC was ethically justified. (shrink)

Sickle cell anemia (SCA) is a major genetic disease with the greatest burden in sub-Saharan Africa. To try to help reduce this burden, some churches in Nigeria conduct premarital sickle cell hemoglobin screening and refuse to conduct weddings when both individuals are identified as carriers of sickle cell trait. This paper explores the ethical challenges involved in such denials. We assess whether churches have the right to decline to marry adults who understand the (...) risks and still prefer to get married, and whether couples should be denied church weddings based on the risk that their child may suffer from sickle cell anemia. We examine the moral and ethical dimensions of such denials and explore the underlying socio-cultural context involving the purpose of marriage and the meaning of the wedding ceremony in societies where premarital screening is one of the few tools available to reduce the risk of having children with SCA. The potential role of the church is also examined against the background of church beliefs, the duty of the church to its members and its role in reducing the suffering of its members and /or their children. We argue that the church should impose these burdens on couples only if doing so promotes a sufficiently compelling goal and there is no less burdensome way to achieve it. We then argue that the goal of reducing the number of individuals in Nigeria who have SCA is compelling. However, testing earlier in life offers a less burdensome and potentially even more effective means of achieving this goal. This suggests that, advocating for earlier screening and helping to support these programs, would likely better promote the church’s own goals of helping its parishioners, increasing the number of church weddings, and reducing the burden of SCA in Nigeria. (shrink)

BackgroundLow literacy of study participants in Sub - Saharan Africa has been associated with poor comprehension during the consenting process in research participation. The concerns in comprehension are far greater when consenting to participate in genomic studies due to the complexity of the science involved. While efforts are made to explore possibilities of applying genomic technologies in diseases prevalent in Sub Saharan Africa, we ought to develop methods to improve participants’ comprehension for genomic studies. The purpose of this study was (...) to understand different approaches that can be used to seek consent from individuals with low literacy in Sub-Saharan African countries in genomic research to improve comprehension.MethodsUsing qualitative study design, we conducted focus-group discussions, in-depth interviews and participant observations as data collection methods. This study was embedded in a hospital based genomic study on Sickle Cell Disease at Muhimbili National Hospital in Tanzania. Thematic content analysis was used to analyse the transcripts and field notes.ResultsFindings from this study show that literacy level has little influence on understanding the research details. According to the participants of this study, the methods used to provide information, the language, and time spent with the study participants were the key factors influencing understanding. The availability of group sessions held before individual consent to allow for a detailed questions and answers format was agreed to be the best method to facilitate the comprehension.ConclusionThe quality of the consenting process of participants will be influence by a number of factors. The type of research consented for, where the research will be implemented and who are the potential study participants are amongst the factors that need to be assessed during the consenting. Measures to improve participants’ comprehension need to be developed when consenting participants with low literacy level in genomic studies. (shrink)

Debates over adaptationism can be clarified and partially resolved by careful consideration of the ‘grain’ at which evolutionary processes are described. The framework of ‘adaptive landscapes’ can be used to illustrate and facilitate this investigation. We argue that natural selection may have special status at an intermediate grain of analysis of evolutionary processes. The cases of sickle-cell disease and genomic imprinting are used as case studies.

Effectively addressing ethical issues in precision medicine research in Africa requires a holistic social contract that integrates biomedical knowledge with local cultural values and Indigenous knowledge systems. Drawing on African epistemologies such as ubuntu and ujamaa and on our collective experiences in genomics and big data research for sickle cell disease, hearing impairment, and fragile X syndrome and the project Public Understanding of Big Data in Genomics Medicine in Africa, we envision a transformative shift in health research (...) data governance in Africa that could help create a sense of shared responsibility between all stakeholders in genomics and data‐driven health research in Africa. This shift includes proposing a social contract for genomics and data science in health research that is grounded in African communitarianism such as solidarity, shared decision‐making, and reciprocity. We make several recommendations for a social contract for genomics and data science in health, including the coproduction of genomics knowledge with study communities, power sharing between stakeholders, public education on the ethical and social implications of genetics and data science, benefit sharing, giving voice to data subjects through dynamic consent, and democratizing data access to allow wide access by all research stakeholders. Achieving this would require adopting participatory approaches to genomics and data governance. (shrink)

would like for them to know that I am in pain or this part of my body hurts or the other part hurts — that I am not lying about it. To examine me and to cut down on the pain….And help me out.Patient with Sickle Cell Disease, Focus Group ParticipantPain in the United States is widely recognized to be undertreated; however, the capacity to treat pain has never been greater. The causes of this undertreatment are varied. (...) As we focus on pain and why it is too often ineffectively treated, we also discover that this undertreatment afflicts some more than others. What divides the some from the others isn't limited to one factor, but one particularly disturbing factor is race and ethnicity. Racial and ethnic minority populations are at higher risk for oligoanalgesia, or the ineffective treatment of pain. Only through further study of the differences in pain treatment based on race and ethnicity can we develop strategies to reduce the disparities in care. (shrink)

I gave remarks at the Third International Summit on Human Genome Editing in London, UK on the first day for the section titled, “Sickle Cell Disease: A Case Study Affecting Millions.” It did not es...

While researching my 2001 book on sickle cell disease, I became aware of the politics of pain. In that malady—a painful disorder associated with African Americans and characterized by frequent infections and recurring painful “crises”—the politics of pain recognition and adequate relief intersect not only with drug concerns, but also with American racial politics. One cannot understand fully the history of sickle cell patients without understanding politics on two levels: the macropolitics of race in America (...) and the micropolitics of medicinal encounters. How these two kinds of politics collided in clinical decision-making about diagnosis, treatment, and pain management has long been a focus of my scholarship—not... (shrink)

The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in response to (...) the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD defi- ciency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not (...) been inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

For over four decades, knowledge that symptoms of some inherited diseases can be prevented or reduced via early detection and treatment in newborns has underpinned state-funded screening programs in most developed countries. Conditions for which newborn screening is now a recognized preventative public health initiative include phenylketonuria, congenital hypothyroidism, and, more recently, cystic fibrosis and sickle cell disorder. The use of tandem mass spectrometry to detect conditions such as amino-acidopathies and fatty-acid oxidation defects is also becoming increasingly prevalent. (...) a. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal tissue from induced abortion (...) slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)

Advances in understanding genetic disorders have been rapid in the last few years and with them the need and desire for genetic counselling have grown. Almost simultaneously, particularly in the USA, several large screening programmes have been initiated to screen large numbers of people who may be carriers of such deleterious genes as those of Tay-Sachs disease and sickle cell anaemia. The authors of this paper, clinical medical students at University College Hospital, London, spent some time studying (...) the ethical issues raised. The first part of their study, which is not published here, relates to the biochemistry of certain genetic disorders, so leading up to the aspect of the subject which must concern readers of this journal, genetic counselling. At present genetic counselling is generally the province of the medical practitioner working with clinical biochemists, and in this paper their function is described and how programmes of screening for carriers are designed. Whether the subjects of the screening tests are found to be 'innocent' or 'guilty' psychological problems confront them, and of these the genetic counsellor must be aware. In fact the range of ethical problems raised by such counselling is wide and can only be sketched in this article. (shrink)

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