[Medical consent in the era of personalized medicine: Issues and recommendations]. / Le consentement médical à l'ère de la médecine de précision - Enjeux et recommandations.

Free and informed consent as a manifestation of adherence to a therapeutic act in medicine is central to the patient-physician relationship. Despite the medical advances of personalized medicine, it weakens the patient-physician relationship and thus the patient's capacity to consent, due to the increasing complexity of the analysis of available data and the intervention of a large number of specialist physicians in the care trajectory. This article proposes to examine the consequences of personalized medicine on the transmission and nature of information, to rethink the patient-physician relationship and the conditions under which consent is possible. Beyond the impacts of personalized medicine, we believe that the role of the doctor is similar to that of a coordinator capable of ensuring the transmission and coherence of information communicated to patients according to their needs with a view to restoring their understanding of the disease and the therapeutic proposals made to them.

Title: Le consentement médical à l'ère de la médecine de précision - Enjeux et recommandations. Abstract: Le consentement libre et éclairé comme manifestation de l'adhésion à un acte thérapeutique en médecine est central dans la relation patient-médecin. Malgré d'importantes avancées, la médecine de précision fragilise la relation patient-médecin et ainsi la capacité du patient à consentir, du fait de la complexification de l'analyse des données disponibles et de l'intervention de nombreux médecins spécialistes dans la trajectoire des soins. Cet article propose d'interroger les conséquences de la médecine de précision sur la transmission et la nature de l'information, pour repenser la relation patient-médecin et les conditions de possibilité du consentement. Au-delà des impacts de la médecine de précision, nous pensons que le rôle du médecin s'apparente à celui d'un référent capable d'assurer la transmission et la cohérence des informations communiquées aux patients selon ses besoins en vue de restaurer sa compréhension de la maladie et des propositions thérapeutiques qui lui sont faites.

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing.

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices.

[Preimplantation genetic diagnosis (PGD) in the era of predictive medicine]. / Le diagnostic préimplantatoire (DPI) à l'ère de la médecine prédictive.

High speed sequencing is revolutionizing the various genetic tests and in particular preimplantation genetic diagnosis (PGD), opening the doors to an increasingly efficient predictive medicine. PGD itself is not new, and the various legistations have been dealing with it for some twenty years. National ethics committees, for their part, have widely debated antenatal tests in the context of medically assisted procreation. This paper examines the work of these Committees on PGD in three States, France, Belgium and Switzerland, in order to highlight their similarities and differences. The subject has also been raised and discussed in the context of the États généraux de la bioéthique which took place this year in France and, given the progresses made recently, they have echoed certain demands of civil society. However, in France, caution continues to dominate.

Judges' perceptions of expert reports: The effect of neuroscience evidence.

This article explores the impact of neuroscience evidence on how expert reports are perceived and their effects on the decisions made by trial judges. Experimental psychology has demonstrated a number of cognitive effects arising from exposure to neuroimaging data which may bias judgments and lead to (mis)interpretations that can affect decisions. We conducted a study on a sample of 62 Swiss and French judges in order to determine whether their perceptions of the credibility, quality and scientific basis of a psychiatric evaluation of a criminal defendant vary according to whether or not the evaluation includes neuroscientific data. Quantitative analyses were conducted in order to evaluate significant differences between the two conditions (one-way analyses of variance) and moderation and conditional analyses to examine whether the participants' sex and length of professional experience moderated the effect of the conditions. Terminological and thematic analyses were carried out on open questions. Quantitative and qualitative results suggest that the presence of neuroscience data in an expert report affects judges' perceptions of the quality, credibility, and scientificity (reliability, objectivity, scientific basis) of the report, and the persuasiveness of the evidence it provided. Moreover, this phenomenon was stronger in more experienced judges than in less experienced judges.

Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations.

In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients' representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the "actionability" of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.

[Faster, higher, stronger To go where? Transhumanism and yearning for happiness]. / Plus vite, plus haut, plus fort, plus ... Pour aller où Transhumanisme et aspiration au bonheur.

Human beings desire to become better. Education and development of tools have helped them to reach this goal for many a time. But what is the ultimate goal? A classical answer is: to be happy. Till now, the result has not been very convincing, but transhumanism has recently taken responsibility for this project, giving us hope to be happy and to live longer. However, will we become more human or posthuman? Transhumanists hesitate between both, but think after all that no limit should be laid down in advance. Consequently, nothing is sacred in human nature and changing it raises no moral concern. Saying this, transhumanism puts itself inside an old tradition, claiming that the value of a human being does not consist in his humanity but in the fact that he is a person, that is a being endowed with reason - reason being the source of all progresses. Consequently, there is a continuity between humanism and transhumanism, and we have good reasons to hope for a bright future. However, the life in our contemporary societies, where everything goes faster and stronger, does not seem to go in this direction. Will transhumanism be able to correct our mistakes? To succeed, it should also aim at human moral enhancement, a hope for some, but a nightmare for others.

Fostering responsible research with genome editing technologies: a European perspective.

In this consensus paper resulting from a meeting that involved representatives from more than 20 European partners, we recommend the foundation of an expert group (European Steering Committee) to assess the potential benefits and draw-backs of genome editing (off-targets, mosaicisms, etc.), and to design risk matrices and scenarios for a responsible use of this promising technology. In addition, this European steering committee will contribute in promoting an open debate on societal aspects prior to a translation into national and international legislation.

Can Neuroscience Contribute to Practical Ethics? A Critical Review and Discussion of the Methodological and Translational Challenges of the Neuroscience of Ethics.

Neuroethics is an interdisciplinary field that arose in response to novel ethical challenges posed by advances in neuroscience. Historically, neuroethics has provided an opportunity to synergize different disciplines, notably proposing a two-way dialogue between an 'ethics of neuroscience' and a 'neuroscience of ethics'. However, questions surface as to whether a 'neuroscience of ethics' is a useful and unified branch of research and whether it can actually inform or lead to theoretical insights and transferable practical knowledge to help resolve ethical questions. In this article, we examine why the neuroscience of ethics is a promising area of research and summarize what we have learned so far regarding its most promising goals and contributions. We then review some of the key methodological challenges which may have hindered the use of results generated thus far by the neuroscience of ethics. Strategies are suggested to address these challenges and improve the quality of research and increase neuroscience's usefulness for applied ethics and society at large. Finally, we reflect on potential outcomes of a neuroscience of ethics and discuss the different strategies that could be used to support knowledge transfer to help different stakeholders integrate knowledge from the neuroscience of ethics.

The metaphysical lessons of synthetic biology and neuroscience.

In this paper, I examine some important metaphysical lessons that are often presented as derived from two new scientific disciplines: synthetic biology and neuroscience. I analyse four of them: the nature of life, the existence of a soul (the mind-body problem), personhood, and free will. Many caveats are in order, and each 'advance' or each case should be assessed for itself. I conclude that a main lesson can nevertheless be learned: in conjunction with modern science, neuroscience and synthetic biology allow us to enrich old metaphysical debates, to deepen and even renew them. In particular, it becomes less and less plausible to consider life, mind, person, and agency as non-natural or non-physical entities.

Human dignity as a component of a long-lasting and widespread conceptual construct.

For some decades, the concept of human dignity has been widely discussed in bioethical literature. Some authors think that this concept is central to questions of respect for human beings, whereas others are very critical of it. It should be noted that, in these debates, dignity is one component of a long-lasting and widespread conceptual construct used to support a stance on the ethical question of the moral status of an action or being. This construct has been used from Modernity onward to condemn slavery and torture as violations of human dignity. In spelling it out, we can come to a better understanding of what "dignity" means and become aware that there exists a quite useful place for this notion in our ethical thought, albeit a modest one.

Changing the brain, changing the society: clinical and ethical implications of neuromodulation techniques in neurology and psychiatry.

New neurotechnologies for modulating brain functions are becoming increasingly powerful and applicable to diverse diseases, but raise new questions for clinicians, ethicists, policy makers, and laymen. This issue of Brain Topography gathers several papers exploring the clinical and ethical implications of several invasive and noninvasive neuromodulation approaches. The opportunities and challenges associated with the emergence of neuro-engineering solutions to brain research and brain repair require a close dialogue between multiple disciplines, as well as open discussion with the general public.

Neuromodulation in the service of moral enhancement.

Human enhancement is a much debated topic in the bioethical literature. Human beings have long tried to improve their capacities and their performances through training and with the aid of tools; but more recently new means have come to the fore, such as drugs and biotechnological devices, especially in the domain of bodily strength and cognitive powers. Moral enhancement has been more seldom discussed. However, this question has recently been hotly debated between two philosophers, Thomas Douglas and John Harris. Douglas claims that modulating certain ugly emotions directly would consist in moral progress-directly, that is, without using cognitive means like persuasion or deliberation. Harris makes three objections against this thesis: such a direct neuromodulation would be inefficacious, would put our liberty in jeopardy and would lead to a moral decline. In this paper, I examine the third argument: with direct modulation, we risk intervening too much or too little, inducing an inappropriate emotion or an inappropriate level of an otherwise appropriate emotion-two upshots that will put morality in jeopardy. I conclude that the validity of this objection depends on several meta-ethical positions: if you are a rationalist or think that intentionality and consciousness are at the core of morality, you will agree with Harris, but if you are a sentimentalist or someone for whom results count, you will disagree. Here as elsewhere, ethical questions cannot be divorced from meta-ethical ones.

Defeating the argument from hubris.

Biotechnologies - synthetic biology in particular - are sometimes blamed for playing God or manifesting hubris, that is, for evincing the vicious attitude of transcending the limits of human agency. In trying to create living organisms, we would adopt an attitude that is immoral for human beings. In this article, I want to show that this blame is unwarranted. I distinguish two aspects of the argument, which claims that it is impossible for human beings to create life and immoral to attempt it. I argue that if we adopt a conception of what life consists of in agreement with the scientific world view, there is no place for hubris. Finally, I maintain that even if we accept a non-scientific conception of life (a vitalist or a supernatural one), we are not in a position to formulate the blame against synthetic biologists because what they do cannot contravene this vitalist or supernaturalist view.

Hearing the implant debate: therapy or cultural alienation?

Cochlear implants are devices that allow deaf people to hear. Consequently, implanting them in children seems to be a very beneficent intervention. However, some deaf parents have opposed it in the name of the preservation of their culture. For them, deafness is a rich culture with its own language (signing), and implanting their children will prevent them from being members of their parents' culture. For the same reason, other deaf parents have asked for PGD (preimplantation genetic diagnoses) and embryo selection in order to have deaf children. Several arguments can be given in favour of the attitude and of the requests of deaf parents; nevertheless, I conclude that, ultimately, they cannot be morally supported because deafness is a true handicap in our civilization of information.

Ethical Considerations in Mouse Experiments.

Mice count morally because they can be harmed. This raises a moral issue in animal experimentation. Three main ethical attitudes towards animals are reviewed here. The Kantian view denies moral value to animals because they lack reason. The second view, by Singer, considers animals as sentient creatures (i.e., able to suffer). Finally, Regan considers that animals are subjects of their own life; they are autonomous and therefore have moral rights. Singer is a reformist and allows animal experimentation under certain conditions. Regan is abolitionist, saying that animals have moral rights that cannot be negotiated. Current animal protection legislation strives to put in balance the human and animal interests to decide whether an animal experiment is morally justified or not. An ethical evaluation process is conducted based on the harm-benefit assessment of the experiment. The researcher has to implement the 3Rs (Replacement, Reduction, Refinement) to minimize the harms to the animals and make sure that the outcomes are scientifically significant and that the quality of the science is high, in order to maximize benefits to humans and animals. Curr. Protoc. Mouse Biol. 1:155-167. © 2011 by John Wiley & Sons, Inc.

[Humanness can be said in many ways]. / L'humanité se dit de multiples manières.

The recent debates on human enhancement ask the question whether enhancing our capabilities is morally desirable. In a sense, the answer is straightforward: to enhance, that is to make things better, is, by definition, a good thing. However, to enhance has a special meaning in the present debates: it consists in going beyond our "natural" capabilities. Is it then still a good thing? To answer this question, it is necessary to ask what is the value of the goods we pursue through enhancement, and this is only possible in the context of a conception of human flourishing. There exist several conceptions of human flourishing; each demands that we improve ourselves in certain directions, depending on the various excellences and on the ideal of the person they promote. But are all means permissible to this effect? Of course not. A set of normative principles is suggested in order to determine which means are permissible. The result of this is that technological and biotechnological means raise no particular problem.

Moral status revisited: the challenge of reversed potency.

Moral status is a vexing topic. Linked for so long to the unending debates about ensoulment and the morality of abortion, it has recently resurfaced in the embryonic stem cell controversy. In this new context, it should benefit from new insights originating in recent scientific advances. We believe that the recently observed capability of somatic cells to return to a pluripotential state (a capability we propose to name 'reversed potency') in a controlled manner requires us to modify the traditional concept of moral status and to consider it as referring not only to intrinsic properties (like 'to possess reason' or 'to be a person'), but also to extrinsic or relational ones.