Is germ-line genome modification ethically justified?

As the normative objections to (human) germline genome editing cannot convincingly justify a categorical prohibition of such editing, its present prohibition should be replaced by a strict regulation, i.e. a conditional allowance. If safe and effective, germline genome editing may become a useful reproductive option.</p

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The New Genetics and Informed Consent: Differentiating Choice to Preserve Autonomy

The advent of new genetic and genomic technologies may cause friction with the principle of respect for autonomy and demands a rethinking of traditional interpretations of the concept of informed consent. Technologies such as whole-genome sequencing and micro-array based analysis enable genome-wide testing for many heterogeneous abnormalities and predispositions simultaneously. This may challenge the feasibility of providing adequate pre-test information and achieving autonomous decision-making. At a symposium held at the 11th World Congress of Bioethics in June 2012 (Rotterdam), organized by the International Association of Bioethics, these challenges were presented for three different areas in which these so-called new genetics' technologies are increasingly being applied: newborn screening, prenatal screening strategies and commercial personal genome testing. In this article, we build upon the existing ethical framework for a responsible set-up of testing and screening offers and reinterpret some of its criteria in the light of the new genetics. As we will argue, the scope of a responsible testing or screening offer should align with the purpose(s) of testing and with the principle of respect for autonomy for all stakeholders involved, including (future) children. Informed consent is a prerequisite but requires a new approach. We present preliminary and general directions for an individualized or differentiated set-up of the testing offer and for the informed consent process. With this article we wish to contribute to the formation of new ideas on how to tackle the issues of autonomy and informed consent for (public) healthcare and direct-to-consumer applications of the new genetics

Zoeken naar ‘nevenbevindingen’?: Uitbreiding NIPT moet zorgvuldiger

In a research setting (TRIDENT-2), Dutch pregnant women undergoing prenatal screening for trisomies 21, 18 and 13 with the Non-Invasive Prenatal Test (NIPT), are offered the choice to also receive information about incidental findings. In a recent report, the Health Council of the Netherlands has recommended to retain this option, but to only report those incidental findings that very probably will lead to serious health outcomes for the child. A working group has been appointed to draw up a guideline for this. In this article we argue that actively searching for desired 'incidental findings' in fact amounts to broadening the scope of the screening and that a justification of this choice is still lacking. A core issue is whether the benefits of such broader screening outweigh the drawback of inevitably also generating findings that do not fit in with the aim of the screening: providing meaningful reproductive choices

The scope of prenatal diagnosis for women at increased risk for aneuploidies: views and preferences of professionals and potential users

The increasing number of prenatal diagnostic tests in prenatal screening strategies, raises the question what tests to offer and why. This qualitative study investigated the views and preferences of professionals and potential users regarding four diagnostic test options for women at increased risk for common aneuploidies. Seven focus group sessions were conducted in The Netherlands between October 2009 and June 2010, with various categories of participants (n = 55): professionals engaged in prenatal testing and potential users of this testing (meaning pregnant women and parents of young children). Participants were invited to mention all pros and cons and their preferences regarding four hypothetical diagnostic test options, presented on vignettes: a standard offer of rapid aneuploidy detection, karyotyping or array comparative genomic hybridization, representing a narrow, traditional and broad test, respectively, and the option of individualised choice. Then, a semi-structured group interview was conducted. The data were analysed by the constant comparative method. Participants identified similar test-specific pros and cons but showed different preferences. Users' opinion on what test to offer as a general policy differed from what they would choose themselves. All participants agreed that in theory, users should be enabled to make an informed choice about what test to apply, but they disagreed about the feasibility of this ideal. Standard narrow testing was favoured for its limiting effects on emotional and organisational burdens; individualised choice was preferred for assuring women's decisive influence. The varying opinions reflect different views on what autonomy in the prenatal screening context means, suggest that a single standard test offer is inadequate and that differentiation will be neede