(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)

This article explores the ethical principles of prescribing in Sickle Cell Disease. The first two sections of the article provide detailed scientific justification for the last section of the manuscript, which explores and discusses the ethical principles.

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

"Dying in the City of Blues: Sickle Cell Anemia and the Politics of Race and Health" by Keith Wailoo is reviewed.

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)

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)

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)

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)

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)

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.

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)

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...

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). 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.

(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.

(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.

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)

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)

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)

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)

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. While this would on the surface appear to be a straightforward medical decision, it is not. One must weigh the benefits of preventing permanent brain (...) damage against the risks of infection from transfused blood, iron overload, which is the result of the frequent transfusions, and rare transfusion reactions. (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)

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)

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)

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)

The COVID-19 pandemic has impacted almost every aspect of daily life, from whether and where people work, to their ability to easily obtain necessities like flour and toilet paper. Healthcare has b...

A case study concerning a 27-year-old African American female with sickle cell anemia who requests specific medication is presented. Hospital team members should do their best to treat the patient and form their judgments based on her clinical data and medical and social history.

(2013). Pain, Chronic Pain, and Sickle Cell Chronic Pain. The American Journal of Bioethics: Vol. 13, No. 4, pp. 14-16. doi: 10.1080/15265161.2013.768859.

Sickle cell haemoglobin polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, in solution , onto existing polymers . When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time :591–610, 611–631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model . Here, we compare the simulated outputs to experimental progress curves . Within 10% from start, average root mean (...) square deviation between simulated and experimental curves is 0.04 ± 0.01 . Conversely, for complete progress curves, averaged rms is 0.48 ± 0.04. This figure is improved to 0.13 ± 0.01 by adjusting heterogeneous pathway parameters : the nucleus stability , and the fraction of polymer surface available for nucleation , from 5e−7, to 13 . Similar results are obtained at 37°C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process. (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)

Community based participatory research is an effective tool in engaging under-represented minorities in research. To be successful, CBPR must be culturally sensitive, re...

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.

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)

The work of Bruno Latour has animated debates in sociology, anthropology and philosophy over several decades, while attracting criticisms of the ontological, epistemological and political implications of his focus on networks. This article takes a particular depth example – the case of the genetic condition of sickle cell – and, drawing upon anthropological, archaeological and sociological evidence of the sickle cell body in history, appraises early, and later, Latourian ideas. The article concludes that while methodologically useful (...) in drawing attention to the complicated links of humans, animals and things, concerns remain about Latourian ontological claims. Limitations include an empiricist failure to account for absence; an insufficiently robust conception of emergence; an unwarranted curtailment of counterfactual human knowledge; a lack of concern for serial ‘undeserving losers’; a tendency to accord excessive freedoms to human actors; and a lack of a conception of how things may be considered as agents rather than actants. (shrink)

There are no national recommendations for routine screening for sickle cell trait, nor is there guidance on whether or how to notify donors that they might be tested or identified as having sickle cell trait. As a result, the organizations that collect blood have implemented variable policies about whether and how to inform prospective donors of the possible screening and discovery of this noncommunicable condition. The question of what they should do is related to the broader (...) question of how to handle incidental and secondary findings. In a recent report, the Presidential Commission for the Study of Bioethical Issues outline a framework for handling such findings in the clinical, research, and direct‐to‐consumer contexts. While the commission's report did not directly address incidental and secondary findings in the public health context of blood donation, it made several overarching recommendations that apply in all contexts where such findings might arise. This essay outlines the special issues raised by discovering sickle cell trait in blood donation and considers the implications of the commission's framework for that problem. (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...