Dilemas bioéticos en torno a la experimentación psicológica en los inicios de la vida / Bioethical dilemmas around psychological experimentation in early life

El documental "Three Identical Strangers" realizado por el cineasta británico Tim Wardle (2018) y traducido al castellano como "Vidas separadas" nos llega como un producto más a ser consumido desde la plataforma Netflix. Nos entrega diferentes testimonios y abre problemas bioéticos que resultan interesantes para su tratamiento y debate. En el presente escrito desplegaré cuatro ejes de problematización en torno al documental: a) la investigación y experimentación con seres humanos; b) el derecho a la identidad de los niños adoptados; c) el debate natura nurtura que hoy se desarrolla fuertemente en el ámbito de las ciencias naturales a propósito de la epigenética y d) el debate sobre las relaciones de parentesco en niños y niñas nacidos por donación de gametos que buscan el encuentro con sus hermanos genéticos.

The documentary "Three Identical Strangers" made by British filmmaker Tim Wardle (2018) and translated into Spanish as "Separate lives" comes to us as one more product to be consumed from the Netflix platform. It gives us different testimonies and opens up bioethical problems that are interesting for its treatment and debate. In this writing I will deploy four axes of problematization around the documentary: a) research and experimentation with human beings; b) the right to identity of adopted children; c) the natural nurture debate that today is strongly developed in the field of natural sciences regarding epigenetics and d) the debate on kinship relationships in boys and girls born by donation of gametes who seek to meet their genetic siblings.

Conducting epigenetics research with refugees and asylum seekers: attending to the ethical challenges.

An increase in global violence has forced the displacement of more than 70 million people, including 26 million refugees and 3.5 asylum seekers. Refugees and asylum seekers face serious socioeconomic and healthcare barriers and are therefore particularly vulnerable to physical and mental health risks, which are sometimes exacerbated by immigration policies and local social discriminations. Calls for a strong evidence base for humanitarian action have encouraged conducting research to address the barriers and needs of refugees and asylum seekers. Given the role of epigenetics factors to mediate the effect of psychological and environmental exposures, epigenetic modifications have been used as biomarkers for life adversity and disease states. Therefore, epigenetic research can be potentially beneficial to address some of the issues associated with refugees and asylum seekers. Here, we review the value of previous and ongoing epigenetic studies with traumatized populations, explore some of the ethical challenges associated with epigenetic research with refugees and asylees and offer suggestions to address or mitigate some of these challenges. Researchers have an ethical responsibility to implement strategies to minimize the harms and maximize the short and long-term benefits to refugee and asylee participants.

RNA modifications as a common denominator between tRNA and mRNA.

Recent studies underscore RNA modifications as a novel mechanism to coordinate expression and function of different genes. While modifications on the sugar or base moieties of tRNA are well known, their roles in mRNA regulation are only starting to emerge. Interestingly, some modifications are present in both tRNA and mRNA, and here we discuss the functional significance of these common features. We describe key modifications that are present in both RNA types, elaborate on proteins that interact with them, and indicate recent works that identify roles in communicating tRNA processes and mRNA regulation. We propose that as tools are developed, the shortlist of features that are common between types of RNA will greatly expand and proteins that interact with them will be identified. In conclusion, the presence of the same modification in both RNA types provides an intersect between tRNA processes and mRNA regulation and implies a novel mechanism for connecting diverse cellular processes.

A conserved RNA degradation complex required for spreading and epigenetic inheritance of heterochromatin.

Heterochromatic domains containing histone H3 lysine 9 methylation (H3K9me) can be epigenetically inherited independently of underlying DNA sequence. To gain insight into the mechanisms that mediate epigenetic inheritance, we used a Schizosaccharomyces pombe inducible heterochromatin formation system to perform a genetic screen for mutations that abolish heterochromatin inheritance without affecting its establishment. We identified mutations in several pathways, including the conserved and essential Rix1-associated complex (henceforth the rixosome), which contains RNA endonuclease and polynucleotide kinase activities with known roles in ribosomal RNA processing. We show that the rixosome is required for spreading and epigenetic inheritance of heterochromatin in fission yeast. Viable rixosome mutations that disrupt its association with Swi6/HP1 fail to localize to heterochromatin, lead to accumulation of heterochromatic RNAs, and block spreading of H3K9me and silencing into actively transcribed regions. These findings reveal a new pathway for degradation of heterochromatic RNAs with essential roles in heterochromatin spreading and inheritance.

Blurring the germline: Genome editing and transgenerational epigenetic inheritance.

Sperm, eggs and embryos are made up of more than genes, and there are indications that changes to non-genetic structures in these elements of the germline can also be inherited. It is, therefore, a mistake to treat phrases like 'germline inheritance' and 'genetic inheritance' as simple synonyms, and bioethical discussion should expand its focus beyond alterations to the genome when considering the ethics of germline modification. Moreover, additional research on non-genetic inheritance draws attention to a variety of means whereby differences can be inherited in offspring generations that do not rely on differences in germline structures. Research on these diverse forms of inheritance challenges the notion that there is some special form of ethical concern that falls on germline interventions in general, and on interventions to the nuclear genome within the germline in particular.

Epigenetics: ethics, politics, biosociality.

Background: Epigenetics is a burgeoning field of contemporary biosciences, which has attracted a lot of interest both in biomedical and in social sciences. Sources of data: Unsystematic literature analysis and retrospective mapping of highly cited work (source: Web of Science core collection) in the social sciences and humanities engaging with epigenetics. Areas of agreement: Epigenetics poses no new ethical issue over and above those discussed in relation to genetics. Areas of controversy: However, it encourages a different framing and reflexivity on some of the commonly held categories in the moral uptake of scientific discoveries. Growing points: Epigenetics presents us with normative questions that touch upon privacy, responsibility for individual health and for the well-being of future generations, as well as matters of health justice and equality of opportunities. Areas timely for developing research: Epigenetic thinking could help us adjust and refine the problem frames and categories that inform our ethical and political questions with a complex biosocial description of situations, of persons or actions.

Effects of Cadmium Exposure on DNA Methylation at Imprinting Control Regions and Genome-Wide in Mothers and Newborn Children.

BACKGROUND: Imprinted genes are defined by their preferential expression from one of the two parental alleles. This unique mode of gene expression is dependent on allele-specific DNA methylation profiles established at regulatory sequences called imprinting control regions (ICRs). These loci have been used as biosensors to study how environmental exposures affect methylation and transcription. However, a critical unanswered question is whether they are more, less, or equally sensitive to environmental stressors as the rest of the genome. OBJECTIVES: Using cadmium exposure in humans as a model, we aimed to determine the relative sensitivity of ICRs to perturbation of methylation compared to similar, nonimprinted loci in the genome. METHODS: We assayed DNA methylation genome-wide using bisulfite sequencing of 19 newborn cord blood and 20 maternal blood samples selected on the basis of maternal blood cadmium levels. Differentially methylated regions (DMRs) associated with cadmium exposure were identified. RESULTS: In newborn cord blood and maternal blood, 641 and 1,945 cadmium-associated DMRs were identified, respectively. DMRs were more common at the 15 maternally methylated ICRs than at similar nonimprinted loci in newborn cord blood (p=5.64×10-8) and maternal blood (p=6.22×10-14), suggesting a higher sensitivity for ICRs to cadmium. Genome-wide, Enrichr analysis indicated that the top three functional categories for genes that overlapped DMRs in maternal blood were body mass index (BMI) (p=2.0×10-5), blood pressure (p=3.8×10-5), and body weight (p=0.0014). In newborn cord blood, the top three functional categories were BMI, atrial fibrillation, and hypertension, although associations were not significant after correction for multiple testing (p=0.098). These findings suggest that epigenetic changes may contribute to the etiology of cadmium-associated diseases. CONCLUSIONS: We analyzed cord blood and maternal blood DNA methylation profiles genome-wide at nucleotide resolution in individuals selected for high and low blood cadmium levels in the first trimester. Our findings suggest that ICRs may be hot spots for perturbation by cadmium, motivating further study of these loci to investigate potential mechanisms of cadmium action. https://doi.org/10.1289/EHP2085.

MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women.

BACKGROUND: Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mineral density and microarchitectural deterioration of bone tissue, resulting in bone fragility and low-trauma fractures. Imaging techniques are routinely used to detect low bone mass; however, they are unable to identify deterioration of bone quality. Recently, microRNAs have emerged as regulators of bone remodelling and potentially also as a new class of sensitive biomarkers of bone health to aid in diagnosis and treatment monitoring of osteoporosis. METHODS: To identify new plasma-based biomarkers associated with osteoporosis we analyzed microRNAs isolated from plasma samples of 74 postmenopausal women divided into osteoporotic (N = 17) and control groups (N = 57). A prior microRNA screening was performed where a few showed promise for further analysis. Quantitative polymerase chain reaction was used to investigate differences in expression of let-7d-5p, let-7e-5p, miR-30d-5p, miR-30e-5p, miR-126-3p, miR-148a-3p, miR-199a-3p, miR-423-5p and miR-574-5p between the two groups. Furthermore, correlation analysis between microRNA expression levels and patient bone mineral density measurements and fracture risk assessment tool (FRAX) as well as trabecular bone scores were performed. RESULTS: Expression of miR-148a-3p was significantly higher (p = 0.042) in the osteoporotic patient group compared to the controls. In addition, we identified correlations between miR-126-3p (ρ = 0.253, p = 0.032) and 423-5p (ρ = -0.230, p = 0.049) and parameters of bone quality and quantity. CONCLUSION: The results from our study, together with the functional role of miR-148a-3p in bone suggest that this microRNA could be considered as a potential new plasma-based biomarker for pathological changes associated with osteoporosis.

Single-cell multimodal profiling reveals cellular epigenetic heterogeneity.

Sample heterogeneity often masks DNA methylation signatures in subpopulations of cells. Here, we present a method to genotype single cells while simultaneously interrogating gene expression and DNA methylation at multiple loci. We used this targeted multimodal approach, implemented on an automated, high-throughput microfluidic platform, to assess primary lung adenocarcinomas and human fibroblasts undergoing reprogramming by profiling epigenetic variation among cell types identified through genotyping and transcriptional analysis.

The ghost in our genes: legal and ethical implications of epigenetics.

Epigenetics is one of the most scientifically important, and legally and ethically significant, cutting-edge subjects of scientific discovery. Epigenetics link environmental and genetic influences on the traits and characteristics of an individual, and new discoveries reveal that a large range of environmental, dietary, behavioral, and medical experiences can significantly affect the future development and health of an individual and their offspring. This article describes and analyzes the ethical and legal implications of these new scientific findings.