Focus: Personalized Medicine: Tailoring the Treatment of Melanoma: Implications for Personalized Medicine

Oncology has been revolutionized by the ability to selectively inhibit the growth of cancerous cells while ostensibly avoiding the disruption of proteins and pathways necessary for normal cellular function. This paradigm has triggered an explosion of targeted therapies for cancer, creating a burgeoning billion-dollar industry of small molecules and monoclonal antibodies [1]. Largely due to these new treatments, spending on cancer pharmaceuticals has surpassed $100 billion worldwide [2]. In particular, the treatment of melanoma, a deadly and fast-spreading form of skin cancer, has been transformed by these new targeted therapies. In this mini-review, we summarize the progress made in the field of personalized treatment of melanoma, with an emphasis on targeted therapies. We then outline future directions for treatment, including novel cell-mediated therapies and new potential targets.     

Focus: Bioethics: Targeting Representation: Interpreting Calls for Diversity in Precision Medicine Research

Scientists have identified a “diversity gap” in genetic samples and health data, which have been drawn predominantly from individuals of European ancestry, as posing an existential threat to the promise of precision medicine. Inadequate inclusion as articulated by scientists, policymakers, and ethicists has prompted large-scale initiatives aimed at recruiting populations historically underrepresented in biomedical research. Despite explicit calls to increase diversity, the meaning of diversity – which dimensions matter for what outcomes and why – remain strikingly imprecise. Drawing on our document review and qualitative data from observations and interviews of funders and research teams involved in five precision medicine research (PMR) projects, we note that calls for increasing diversity often focus on “representation” as the goal of recruitment. The language of representation is used flexibly to refer to two objectives: achieving sufficient genetic variation across populations and including historically disenfranchised groups in research. We argue that these dual understandings of representation are more than rhetorical slippage, but rather allow for the contemporary collection of samples and data from marginalized populations to stand in as correcting historical exclusion of social groups towards addressing health inequity. We trace the unresolved historical debates over how and to what extent researchers should procure diversity in PMR and how they contributed to ongoing uncertainty about what axes of diversity matter and why. We argue that ambiguity in the meaning of representation at the outset of a study contributes to a lack of clear conceptualization of diversity downstream throughout subsequent phases of the study.     

Focus: Personalized Medicine: Crowdfunding for Personalized Medicine Research

Given the current funding situation of the National Institutes of Health, getting funding for rare disease research is extremely difficult. In light of the enormous potential for research in the rare diseases and the scarcity of research funding, we provide a case study of a novel successful crowdfunding approach at a non-profit organization called Rare Genomics Institute. We partner with biotechnology companies willing to donate their products, such as mouse models, gene editing software, and sequencing services, for which researchers can apply. First, we find that personal stories can be powerful tools to seek funding from sympathetic donors who do not have the same rational considerations of impact and profit. Second, for foundations facing funding restrictions, company donations can be a valuable tool in addition to crowdfunding. Third, rare disease research is particularly rewarding for scientists as they proceed to be pioneers in the field during their academic careers. Overall, by connecting donors, foundations, researchers, and patients, crowdfunding has become a powerful alternative funding mechanism for personalized medicine.     

精准医学基础研究与临床实践的回顾与展望

精准医学是健康卫生和医学科学的发展方向,是发展了一个多世纪的现代医学实践的升级版。本文研究了医学科研和医疗实践的发展趋势,从分子遗传、环境变迁及医疗信息管理等领域,分析和总结了影响精准医学发展的一些因素,提出了精准医学基础研究和临床实践的一些新思路,希望对精准医学的发展、医学科研实践及医疗卫生政策的制定产生积极的影响。     

Focus: Personalized Medicine: Taking Control of Castleman Disease: Leveraging Precision Medicine Technologies to Accelerate Rare Disease Research

Castleman disease (CD) is a rare and heterogeneous disorder characterized by lymphadenopathy that may occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric), the latter typically occurring secondary to excessive proinflammatory hypercytokinemia. While a cohort of multicentric Castleman disease (MCD) cases are caused by Human Herpes Virus-8 (HHV-8), the etiology of HHV-8 negative, idiopathic MCD (iMCD), remains unknown. Breakthroughs in “omics” technologies that have facilitated the development of precision medicine hold promise for elucidating disease pathogenesis and identifying novel therapies for iMCD. However, in order to leverage precision medicine approaches in rare diseases like CD, stakeholders need to overcome several challenges. To address these challenges, the Castleman Disease Collaborative Network (CDCN) was founded in 2012. In the past 3 years, the CDCN has worked to transform the understanding of the pathogenesis of CD, funded and initiated genomics and proteomics research, and united international experts in a collaborative effort to accelerate progress for CD patients. The CDCN’s collaborative structure leverages the tools of precision medicine and serves as a model for both scientific discovery and advancing patient care.     

Science in the Service of Patients: Lessons from the Past in the Moral Battle for the Future of Medical Education

Medical schools instill a classic moral standoff in which the responsibility for the betterment of the patient stands at odds with the responsibility for the betterment of society. In critical ways, the latter, in the form of a robust research and technology-driven enterprise, has taken precedence over the former, resulting in harm to patients and individual dignity. This tradeoff can be traced to Abraham Flexner, the father of American medical education. In the wake of the Flexner report, American medicine set out on a course of exponential scientific advancement, but the mistreatment of research subjects and the erosion of the doctor-patient relationship in a health care system that is increasingly unaffordable, complex, and impersonal suggest that such progress has come at a price. Recent efforts by medical schools to emphasize humanism in their curricula and admissions processes have shown promise in orienting the values of academic medicine toward the individual patient’s well-being.     

Social Responsibility and the State's Duty to provide Healthcare: An Islamic Ethico‐Legal Perspective

The United Nations Educational, Scientific and Cultural Organization's (UNESCO) Declaration on Bioethics and Human Rights asserts that governments are morally obliged to promote health and to provide access to quality healthcare, essential medicines and adequate nutrition and water to all members of society. According to UNESCO, this obligation is grounded in a moral commitment to promoting fundamental human rights and emerges from the principle of social responsibility. Yet in an era of ethical pluralism and contentions over the universality of human rights conventions, the extent to which the UNESCO Declaration can motivate behaviors and policies rests, at least in part, upon accepting the moral arguments it makes. In this essay I reflect on a state's moral obligation to provide healthcare from the perspective of Islamic moral theology and law. I examine how Islamic ethico‐legal conceptual analogues for human rights and communal responsibility, ?uqūq al‐’ibād and far? al‐kifāyah and other related constructs might be used to advance a moral argument for healthcare provision by the state. Moving from theory to application, I next illustrate how notions of human rights and social responsibility were used by Muslim stakeholders to buttress moral arguments to support American healthcare reform. In this way, the paper advance discourses on a universal bioethics and common morality by bringing into view the concordances and discordances between Islamic ethico‐legal constructs and moral arguments advanced by transnational health policy advocates. It also provides insight into applied Islamic bioethics by demonstrating how Islamic ethico‐legal values might inform the discursive outputs of Muslim organizations.     

Personalized diagnostics and biosensors: a review of the biology and technology needed for personalized medicine

Abstract

Exploiting the burgeoning fields of genomics, proteomics and metabolomics improves understanding of human physiology and, critically, the mutations that signal disease susceptibility. Through these emerging fields, rational design approaches to diagnosis, drug development and ultimately personalized medicine are possible. Personalized medicine and point-of-care testing techniques must fulfill a host of constraints for real-world applicability. Point-of-care devices (POCDs) must ultimately provide a cost-effective alternative to expensive and time-consuming laboratory tests in order to assist health care personnel with disease diagnosis and treatment decisions. Sensor technologies are also expanding beyond the more traditional classes of biomarkers – nucleic acids and proteins – to metabolites and direct detection of pathogens, ultimately increasing the palette of available techniques for the use of personalized medicine. The technologies needed to perform such diagnostics have also been rapidly evolving, with each generation being increasingly sensitive and selective while being more resource conscious. Ultimately, the final hurdle for all such technologies is to be able to drive consumer adoption and achieve a meaningful medical outcome for the patient.     

Community Members' Engagement with and Involvement in Genomic Research: Lessons to Learn from the Field

In this paper, we describe the potential role laypersons on ethics committees can play in ensuring community concerns are addressed in the design and implementation of genomic research. We draw inferences from the outcome of an empirical study of the impact of training of laypersons to address community engagement issues in ethics review of research protocol. While this paper does not advocate a particular solution, it describes the importance of community engagement in genomic research, the current limitations there are in engaging communities in the design of these research projects and how communities can be indirectly engaged in the design and implementation of genomic research through the engagement of laypersons on ethics committees. However, to ensure that these laypersons can play this role, their capacity needs to be built to play this role appropriately. There is evidence to show that where resources are invested in building the capacity of laypersons to play their role as community ‘watchdogs’ in research, they play this role aptly. Community engagement is important in genomic research as genomic researchers will increasingly require community perspectives in critical ethics decision making.     

European Electronic Personal Health Records initiatives and vulnerable migrants: A need for greater ethical,legal and social safeguards

The effective collection and management of personal data of rapidly migrating populations is important for ensuring adequate healthcare and monitoring of a displaced peoples’ health status. With developments in ICT data sharing capabilities, electronic personal health records (ePHRs) are increasingly replacing less transportable paper records. ePHRs offer further advantages of improving accuracy and completeness of information and seem tailored for rapidly displaced and mobile populations. Various emerging initiatives in Europe are seeking to develop migrant‐centric ePHR responses. This paper highlights their importance and benefits, but also identifies a number of significant ethical, legal and social issues (ELSI) and challenges to their design and implementation, regarding (1) the kind of information that should be stored, (2) who should have access to information, and (3) potential misuse of information. These challenges need to be urgently addressed to make possible the beneficial use of ePHRs for vulnerable migrants in Europe.     

The Vulnerability of Study Participants in the Context of Transnational Biomedical Research: From Conceptual Considerations to Practical Implications

Outsourcing clinical trials sponsored by pharmaceutical companies from industrialized countries to low‐ (middle)‐income countries – summarized as transnational biomedical research (TBR) – has lead to many concerns about ethical standards. Whether study participants are particularly vulnerable is one of those concerns. However, the concept of vulnerability is still vague and varies in its definition. Despite the fact that important international ethical guidelines such as the Declaration of Helsinki by the World Medical Association or the Ethical Guidelines for Biomedical Research Involving Human Subjects by the Council of International Organizations of Medical Sciences refer to vulnerability as ethical principle, each of their approaches are different. To overcome these shortcomings, we analyze and unite different approaches of vulnerability and develop practical criteria in order to operationalize the concept especially for the context of TBR. These criteria refer to the context of a study as well as the characteristics and the current living situation of study participants. Based on a case study of an HIV‐vaccine‐trial conducted in India we demonstrate how those criteria can be applied in a retrospective way to identify potential ethical conflicts. The criteria can also indicate a prospective function for ethical pre‐assessment. For this, we provide an outlook for three major topics: 1. Vulnerability as a normative concept: Different ways of protection; 2. The relevance of transparency and 3. Vulnerability as an instrument to increase decision participation of human subjects.     

Focus: Preventive Medicine: Race,Racism, and the Policy of 21st Century Medicine

This perspective describes three new policies passed at the November 2020 Special Meeting of the American Medical Association House of Delegates. These policies (1) denounce racism as a public health threat; (2) call for the elimination of race as a proxy for ancestry, genetics, and biology in medical education, research, and clinical practice; and (3) decry racial essentialism in medicine. We also explore the social and institutional context leading to the passage of these policies, which speak directly to the harmful legacy of racism in America, and its insidious impact on the healthcare system.     

Focus: Preventive Medicine: Pre-Participation Screening of Athletes: Primary Health Care Physicians’ Knowledge,Experience, and Approach in Turkey

Pre-participation screening (PPS) is crucial for assessing the competitive athletes since their risk of sudden death is higher than non-athletes. In Turkey, PPS is performed at the primary health care setting by primary care physicians (PCPs) who are family medicine specialists (FMSs) or general practitioners (GPs). Although there are national guidelines, there is no legal regulation for this process. This study aims to evaluate PCPs’ knowledge, experience, and approach about PPS. We prepared an online survey for PCPs and used non-probabilistic sampling. PPS attitudes and practices were analyzed and compared according to factors such as experience, education, and being GP or FMS. Of the 214 PCPs included in the study, 39.3% were female. The mean age was 44.9 years (SD:8.88). The average work experience was 7.9 years. Most participants were aware of their authorization to perform PPS (89.7%) and had previously prepared it (90.2%). However, 6.5% of them felt confident in performing PPS. Only 13.1% were aware of the guidelines. Almost 25% of the participants stated being informed about the subject at some part of their career, but this did not affect the confidence or referral decisions. In addition to medical history and physical examination, further testing was considered necessary by 96.3% of the participants. Significantly more tests were ordered by GPs than FMSs (p=0.026 and p=0.011, respectively). The accurate referral decision ratio was 59.3%, without difference between FMSs and GPs (p=0.216). We found that awareness of the guidelines was low among PCPs who lack confidence in PPS. These factors collectively increased the tendency for unnecessary further testing and referral. Therefore, the PPS implementation into medical school and residency curriculums and national legal regulation for the process is a necessity in Turkey.     

药物临床前研究与转化医学——实验动物的应用与动物实验

本文讨论了药物临床前研究与实验动物和动物模型之间的关系,探讨了实验动物和动物模型在新药研发过程中实现转化研究的要求和条件.讨论了实验动物质量对新药研发的影响,分析了实验动物质量的影响因素;讨论了实验动物模型的主要类型和特点,分析了进行实验动物模型研究的要点和要求;分析了动物模型与新药研发过程中实现转化研究的条件,提出加强转化研究需要实验动物和动物模型研究的支撑.     

The intersection of social determinants of health,the microbiome,and health outcomes in immigrants: A scoping review

In the present scoping review, we explore whether existing evidence supports the premise that social determinants of health (SDoH) affect immigrant health outcomes through their effects on the microbiome. We adapt the National Institute on Minority Health and Health Disparities' research framework to propose a conceptual model that considers the intersection of SDoH, the microbiome, and health outcomes in immigrants. We use this conceptual model as a lens through which to explore recent research about SDoH, biological factors associated with changes to immigrants' microbiomes, and long-term health outcomes. In the 17 articles reviewed, dietary acculturation, physical activity, ethnicity, birthplace, age at migration and length of time in the host country, socioeconomic status, and social/linguistic acculturation were important determinants of postmigration microbiome-related transformations. These factors are associated with progressive shifts in microbiome profile with time in host country, increasing the risks for cardiometabolic, mental, immune, and inflammatory disorders and antibiotic resistance. The evidence thus supports the premise that SDoH influence immigrants' health postmigration, at least in part, through their effects on the microbiome. Omission of important postmigration social-ecological variables (e.g., stress, racism, social/family relationships, and environment), limited research among minoritized subgroups of immigrants, complexity and inter- and intra-individual differences in the microbiome, and limited interdisciplinary and biosocial collaboration restrict our understanding of this area of study. To identify potential microbiome-based interventions and promote immigrants' well-being, more research is necessary to understand the intersections of immigrant health with factors from the biological, behavioral/psychosocial, physical/built environment, and sociocultural environment domains at all social-ecological levels.     

Finding A Seat at the Table Together: Recommendations for Improving Collaboration between Social Work and Bioethics

Social work and bioethics are fields deeply committed to cross‐disciplinary collaboration to do their respective work. While scholars and practitioners from both fields share a commitment to social justice and to respecting the dignity, integrity and the worth of all persons, the overlap between the fields, including shared values, has received little attention. The purpose of this article is to describe the ways in which greater collaboration between the two fields can broaden their scope, enrich their scholarship, and better ground their practice. We describe the potential for realizing such benefits in two areas – health care ethics consultation and social inequalities in health – arguing that the fields both complement and challenge one another, making them ideal partners for the interdisciplinary inquiry and problem‐solving so often called for today in health and health care.