Translational Bioethical Decision-Making: Human Brain Organoids as a Case Study.

In an earlier essay, I advocated that translational bioethics uses the public's values, determined through social science, in its analysis of translational science technologies. It may be unclear what those values might be, and whether such a translational ethics would necessarily conclude that cutting edge technologies should not be developed. In this essay, I show the public's values relevant to human brain organoids and argue that a translational bioethics analysis using these values would support continued organoid research.

Understanding the Gap: A Cross-Sectional Survey of ELSI Scholars' Dissemination Practices and Translation Goals.

BACKGROUND: Researchers engaged in the study of the ethical, legal, and social implications (ELSI) of genetics and genomics are often publicly funded and intend their work to be in the public interest. These features of U.S. ELSI research create an imperative for these scholars to demonstrate the public utility of their work and the expectation that they engage in research that has potential to inform policy or practice outcomes. In support of the fulfillment of this "translational mandate," the Center for ELSI Resources and Analysis (CERA), funded by the National Human Genome Research Institute (NHGRI), aims to facilitate community-informed, ELSI research results synthesis and dissemination. However, little is known about how ELSI research scholars define the goals of translation and imagine the intended users of their research findings. METHODOLOGY: We distributed a Qualtrics survey to ELSI scholars that aimed to determine: (1) researchers' expectations for their research findings in relation to policy or practice outcomes, (2) the stakeholder groups researchers believe could benefit from their research findings, and (3) the methods researchers use to foster the uptake of their findings by those stakeholders. RESULTS: Most ELSI researchers surveyed thought there were stakeholders that could benefit from their research findings, including health care professionals, at-risk individuals, patients, and their family members, policy-makers, and researchers/scientists, and expected their research findings to inform the creation or revision of laws, policies, or practice guidelines. Most researchers planned to disseminate findings directly to relevant stakeholders, with fewer expecting dissemination support from research funders, universities, or other entities. CONCLUSION: The broad range of research topics, disciplines, and set of potential end users represented in ELSI reseach complicate the work of a knowledge broker. Nonetheless, the CERA can play an important role in disseminating ELSI results to relevant stakeholders. Further research should explore outreach mechanisms.

Ethics and regulatory considerations for the clinical translation of somatic cell human epigenetic editing.

Altering the human epigenome with gene-editing technology in attempt to treat a variety of diseases and conditions seems scientifically feasible. We explore some of the ethical and regulatory issues related to the clinical translation of human epigenetic editing arguing that such approaches should be considered akin to somatic therapies.

ISSCR's Guidelines for Stem Cell Research and Clinical Translation: Supporting development of safe and efficacious stem cell-based interventions.

The ISSCR's revised Guidelines for Stem Cell Research and Clinical Translation reflect the organization's commitment to opposing premature commercialization of stem cell-based interventions and supporting the development of products that meet stringent ethical, scientific, and regulatory standards. The Guidelines contain five important new recommendations concerning clinical translation of stem cell products.

Ethical, Legal, and Social Issues (ELSI) in Clinical Genetics Research.

ELSI (Ethical, Legal, and Social Issues) is a widely used acronym in the bioethics literature that encompasses a broad range of research examining the various impacts of science and technology on society. In Canada, GE3LS (Genetics, Ethical, Economic, Environmental, Legal, Social issues) is the term used to describe ELSI studies in the context of genetics and genomics research. It is intentionally more expansive in that GE3LS explicitly brings economic and environmental issues under its purview. ELSI/GE3LS research is increasingly relevant in recent years as there has been a greater emphasis on "translational research" that moves genomic discoveries from the bench to the clinic. The purpose of this chapter is to outline a range of ELSI-related work that might be conducted as part of a large scale genetics or genomics research project, and to provide some practical insights on how a scientific research team might incorporate a strong and effective ELSI program within its broader research mandate. We begin by describing the historical context of ELSI research and the development of GE3LS research in the Canadian context. We then illustrate how some ELSI research might unfold by outlining a variety of GE3LS research questions or content domains and the methodologies that might be employed in studying them. We conclude with some practical suggestions about how to build an effective ELSI/GE3LS team and focus within a broader scientific research program.

A few ethical issues in translational research for medicinal products discovery and development.

The results obtained with basic research showing significant therapeutic promise are often not translated into clinical applications. The purpose of translational research is to favour the transition of basic research to application at the patient's bedside, and from here to routine clinical practice (without excluding the opposite pathway, in which the evidence generated by clinical practice helps to guide research). Although translational research can provide patients with valuable therapeutic resources, it is not risk-free. The most significant ethical issues in translational research on medicinal products derive from the risk of the intention to shorten the timeframes for the application of the results of the research making the scientific methods adopted and the regulatory requisites to be satisfied along the long path from the bench to the patient's bedside less rigorous. This is also relevant during pandemics when shortening the timeline from basic research to bedside is even more crucial. It is therefore necessary to establish defined and agreed requisites in order to guarantee the ethicality of translational research, by promoting the good of individuals and minimising the risks.

Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics.

INTRODUCTION: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. OBJECTIVE: To analyze the Código Infarto protocol from the perspective of translational bioethics. METHOD: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. RESULTS: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. CONCLUSION: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

INTRODUCCIÓN: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. OBJETIVO: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. MÉTODO: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. RESULTADOS: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. CONCLUSIÓN: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Surgical Translational Research May Be Forward or Reverse.

The classic concept of translational research can be described as a bench-to-bedside approach. Reverse translational research, bedside-to-benchtop, also may have a place. Under some circumstances, innovative clinicians may develop new techniques in advance of basic science research. A recent example of the success of reverse translational research is shoulder superior capsular reconstruction. Theoretically, new surgical techniques are ideally first tested ex vivo, but this does not guarantee clinical success, and in some cases, experienced, specialized surgeon-scientists can modify existing techniques and perform novel interventions with little risk to patients. Benefits of reverse translational research include a shorter time from innovation to application, and real, not theoretical, determination of clinical outcome. If a reverse approach is warranted, strict adherence to bioethical principles is required, including cooperation with ethics committees, institutional review boards, trial registration, and informed consent. Translational research can be bidirectional.

Science at Warp Speed: Medical Research, Publication, and Translation During the COVID-19 Pandemic.

In response to the COVID-19 pandemic, there has been a rapid growth in research focused on developing vaccines and therapies. In this context, the need for speed is taken for granted, and the scientific process has adapted to accommodate this. On the surface, attempts to speed up the research enterprise appear to be a good thing. It is, however, important to consider what, if anything, might be lost when biomedical innovation is sped up. In this article we use the case of a study recently retracted from the Lancet to illustrate the potential risks and harms associated with speeding up science. We then argue that, with appropriate governance mechanisms in place (and adequately resourced), it should be quite possible to both speed up science and remain attentive to scientific quality and integrity.

Improving the trustworthiness, usefulness, and ethics of biomedical research through an innovative and comprehensive institutional initiative.

The reproducibility crisis triggered worldwide initiatives to improve rigor, reproducibility, and transparency in biomedical research. There are many examples of scientists, journals, and funding agencies adopting responsible research practices. The QUEST (Quality-Ethics-Open Science-Translation) Center offers a unique opportunity to examine the role of institutions. The Berlin Institute of Health founded QUEST to increase the likelihood that research conducted at this large academic medical center would be trustworthy, useful for scientists and society, and ethical. QUEST researchers perform "science of science" studies to understand problems with standard practices and develop targeted solutions. The staff work with institutional leadership and local scientists to incentivize and support responsible practices in research, funding, and hiring. Some activities described in this paper focus on the institution, whereas others may benefit the national and international scientific community. Our experience, approaches, and recommendations will be informative for faculty leadership, administrators, and researchers interested in improving scientific practice.

Ethical Aspects of Translating Research with Human Pluripotent Stem Cell Products into Clinical Practice: A Stakeholder Approach.

Experimental therapies with embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs) are steadily gaining ground in clinical practice. The implementation of such novel high-risk/high-potential treatments calls for proper safeguards for the interests of the public and, most importantly, of research participants directly affected by the design and outcomes of trials. We argue that the active involvement of stakeholders in decision-making is ethically required. Public and patient involvement is a necessary prerequisite for dealing responsibly with high-risk/high-potential clinical research such as stem-cell research. Moreover, there is an urgent need for public debate, regionally and globally, about the present and future value of such types of research. A stakeholder approach that pays attention to all of the people and institutions involved, including patients and their organizations, will guide the translational process and maintain the public's trust in such a rapidly evolving scientific field.

The Progression of Regenerative Medicine and its Impact on Therapy Translation.

Despite regenerative medicine (RM) being one of the hottest topics in biotechnology for the past 3 decades, it is generally acknowledged that the field's performance at the bedside has been somewhat disappointing. This may be linked to the novelty of these technologies and their disruptive nature, which has brought an increasing level of complexity to translation. Therefore, we look at how the historical development of the RM field has changed the translational strategy. Specifically, we explore how the pursuit of such novel regenerative therapies has changed the way experts aim to translate their ideas into clinical applications, and then identify areas that need to be corrected or reinforced in order for these therapies to eventually be incorporated into the standard-of-care. This is then linked to a discussion of the preclinical and postclinical challenges remaining today, which offer insights that can contribute to the future progression of RM.

Ethical, Legal and Regulatory Issues of Paediatric Translational Research. Call for an Adequate Model of Governance.

The lack of paediatric medicines, including innovative and advanced ones, is a long-lasting and well-known problem at European and international levels. Despite the existing legal frameworks and incentives, children remain deprived of many kinds of therapy because of challenges faced in appropriately study and tailoring medicinal and other products for them. In this context, the necessity to foster paediatric research addressing unsolved and uncovered issues within a 'translational approach' has appeared. This article, after having clarified the concept of translational research in the perspective of the establishment of a European paediatric research infrastructure (RI), will identify and point out ethical, legal and regulatory issues particularly relevant in a children's rights perspective. It concludes asking for the setting up of an adequate model of governance within a future RI, including adequate and independent ethical oversight and a pluridisciplinary common service dealing with ethical, legal and societal issues relevant for children.

Translational Research-For the Individual and the Community.

The potential for translational research to improve human health is unprecedented, as the integration of genetic health risks with other data influencing health provides substantial opportunities for improvement. However, how integrating these data sources in a fair, unbiased and appropriate way without reinforcing pre-existing assumptions requires thoughtful implementation. Furthermore, integration of new technologies requires assessment of needs and benefits for the individual balanced with community needs and goals. Thus, examination of values, goals and implicit assumptions through transparent, authentic engagement of individuals and communities is essential.

A few ethical issues in translational research for gene and cell therapy.

BACKGROUND: Although translational research for drug development can provide patients with valuable therapeutic resources it is not without risk, especially in the early-phase trials that present the highest degree of uncertainty. With the extraordinary evolution of biomedical technologies, a growing number of innovative products based on human cells and gene therapy are being tested and used as drugs. Their use on humans poses several challenges. METHODS: In this work, we discuss some ethical issues related to gene and cell therapies translational research. We focus on early-phase studies analysing the regulatory approach of Europe and the United States. We report the current recommendations and guidelines of international scientific societies and European and American regulatory authorities. RESULTS: The peculiarity of human cell- or tissue-based products and gene therapy has required the development of specific regulatory tools that must be continually updated in line with the progress of the research. The ethics of translational research for these products also requires further considerations, particularly with respect to the specificity of the associated risk profiles. CONCLUSIONS: An integrated ethical approach that aims for transparency and regulation of development processes, the support of independent judgment in clinical trials and the elimination of unregulated and uncontrolled grey areas of action are necessary to move gene and cell therapy forward.