Good practice in medicine and biology: scientific integrity needs global bioethics.

We consider scientific integrity to constitute a new theory of morality of science, in a very specific deontological sense. Indeed, at least in practice, scientific integrity extends beyond scientific concerns, seeking to develop specific moral duties and/or procedures based on general moral values and/or standards, leading to common moral frameworks for usual scientific practices. This is, of course, necessary. Contemporary history has shown us only too well that usual scientific practices need common moral frameworks, especially in medicine and biology. However, like scientific practices, and medical and biological practices in particular, the persistence of certain moral values and/or standards and the priority attributed to them, can change significantly, due to changes in society, people, the times and/or environments, and they may be under strong tension. We therefore believe that a new theory of ethics of science, in a very specific teleological sense, may be required in this case, particularly in medicine and biology, in addition to scientific integrity. This ethical theory, through research, professionals and structures in ethics of science also called medical ethics, research ethics or bioethics in the fields of medicine and biology, should seek to identify and find specific ethical solutions to these tensions, applicable at a particular place and time, based on common ethical purposes and/or consequences. As a result, these specific ethical solutions may, or may not, lead to an evolution of common moral frameworks, which may, or may not, be developed on the basis of scientific integrity. In the fields of medicine and biology, this ethical theory is closely related to another theory, global bioethics, but with a number of new conceptual and methodological developments.

Cancer and COVID-19: ethical issues concerning the use of telemedicine during the pandemic.

The lockdown imposed in France during the first wave of the COVID-19 pandemic wreaked havoc with access to healthcare. From March 2020 onwards, the oncologists of Foch Hospital, like many others at hospitals throughout the world, were obliged to adapt to the new conditions, including, in particular, the impossibility of seeing patients in classic consultations for the diagnosis and treatment of cancer. Patients with cancer are particularly susceptible to this new virus, due to their immune status, and this made it difficult to carry out standard hospital visits for these patients. Some patients refused to come to the hospital, whereas the doctors decided, for others, that consultation conditions at the hospital were not sufficiently safe, with sanitary measures that had yet to be precisely defined. Telemedicine was one of the adaptations adopted during this period. This mode of consultation was little used before the pandemic, for various reasons, and reimbursement was not automatic. This new approach proved to have limitations as well as advantages, as demonstrated by our empirical ethics research study, a retrospective qualitative survey of the doctors of the oncology and supportive care departments of Foch Hospital, performed during July 2021. The interview grid was based on the studies on telemedicine, oncology, COVID-19 and empirical ethics available at the time. Based on the experience gained in this domain during the first wave of the epidemic, which hit France between March and June 2020, we identified three eligibility criteria for consultations in telemedicine: the consultation concerned should not be the first consultation, the patient should be a known patient that the doctor trusts not to minimize the description of symptoms, and the results of the patient's evaluations and examinations must be good. It may be appropriate to continue the use of teleconsultation in the future, provided that these criteria are respected.

From a voluntary vaccination policy to mandatory vaccination against COVID-19 in cancer patients: an empirical and interdisciplinary study in bioethics.

BACKGROUND: At the start of 2021, oncologists lacked the necessary scientific knowledge to adapt their clinical practices optimally when faced with cancer patients refusing or reluctant to be vaccinated against COVID-19, despite the marked vulnerability of these patients to severe, and even fatal forms of this new viral infectious disease. Oncologists at Foch Hospital were confronted with this phenomenon, which was observed worldwide, in both the general population and the population of cancer patients. METHODS: Between April and November 2021, the Ethics and Oncology Departments of Foch Hospital decided to investigate this subject, through an empirical and interdisciplinary study in bioethics. Our scientific objective was to try to identify and resolve the principal bio-ethical issues, with a view to improving clinical practices in oncology during future major pandemics of this kind, from a highly specific bio-ethical standpoint (= quality of life/survival). We used a mainly qualitative methodological approach based on questionnaires and interviews. RESULTS: In April 2021, 29 cancer patients refused or were reluctant to be vaccinated (5.6%; 29/522). Seventeen of these patients said that making vaccination mandatory would have helped them to accept vaccination. In October 2021, only 10 cancer patients continued to maintain their refusal (1.9%; 10/522). One of the main reasons for the decrease in refusals was probably the introduction of the "pass sanitaire" (health pass) in July 2021, which rendered vaccination indispensable for many activities. However, even this was not sufficient to convince these 10 cancer patients. CONCLUSION: We identified a key bio-ethical issue, which we then tried to resolve: vaccination policy. We characterized a major tension between "the recommendation of anti-COVID-19 vaccination" (a new clinical practice) and "free will" (a moral value), and the duty to "protect each other" (a moral standard). Mandatory vaccination, at least in France, could resolve this tension, with positive effects on quality of life (i.e. happiness), or survival, in cancer patients initially refusing or reluctant to be vaccinated, but only if collective and individual scales are clearly distinguished.

French-style genetics v. 2.0: The "e-CohortE" project.

In the digital age, a genetics cohort has become much more than a simple means of determining the cause of a disease. Two-sided markets, of which 23andMe, Ancestry DNA and MyHeritage are the best known, have showed this perfectly over the last few years: a cohort has become a means of producing massive amounts of data for medical, scientific and commercial exploitation, and for genetic use in particular. French law does not currently allow these foreign private companies to develop on French national territory and also forbids the creation of similar entities in France. However, at least in theory, this same law does not preclude the creation of new types of cohorts in France inspired by the success of two-sided markets but retaining features specific to the French healthcare management system. We propose an optimal solution for France, for genomic studies associated with multi-subject questionnaires, still purely theoretical for the moment: the development, with no need for any change in the law, of France's own version of "Genetics v.2.0": "e-CohortE."

Genetic Data, Two-Sided Markets and Dynamic Consent: United States Versus France.

Networks for the exchange and/or sharing of genetic data are developing in many countries. We focus here on the situations in the US and France. We highlight some recent and remarkable differences between these two countries concerning the mode of access to, and the storage and use of genetic data, particularly as concerns two-sided markets and dynamic consent or dynamic electronic informed consent (e-IC). This brief overview suggests that, even though the organization and function of these two-sided markets remain open to criticism, dynamic e-IC should be more widely used, especially in France, if only to determine its real effectiveness.

Molecular Tumor Boards: Ethical Issues in the New Era of Data Medicine.

The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with "genomic medicine" nor with "precision medicine", but with "data medicine" (DM) (big data, data mining). The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The "transformation" of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision of care. Molecular tumor boards (MTB) are one response to these changes and are now providing better access to next-generation sequencing (NGS) and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent (IC) documents at all academic medical centers and to introduce dynamic and electronic informed consent (e-IC).

23andMe: a new two-sided data-banking market model.

BACKGROUND: Since 2006, the genetic testing company 23andMe has collected biological samples, self-reported information, and consent documents for biobanking and research from more than 1,000,000 individuals (90% participating in research), through a direct-to-consumer (DTC) online genetic-testing service providing a genetic ancestry report and a genetic health report. However, on November 22, 2013, the Food and Drug Administration (FDA) halted the sale of genetic health testing, on the grounds that 23andMe was not acting in accordance with federal law, by selling tests of undemonstrated reliability as predictive tests for medical risk factors. Consumers could still obtain the genetic ancestry report, but they no longer had access to the genetic health report in the United States (US). However, this did not prevent the company from continuing its health research, with previously obtained and future samples, provided that consent had been obtained from the consumers concerned, or with health reports for individuals from other countries. Furthermore, 23andMe was granted FDA authorization on February 19, 2015, first to provide reports about Bloom syndrome carrier status, and, more recently, to provide consumers with "carrier status" information for 35 genes known (with high levels of confidence) to cause disease. DISCUSSION: In this Debate, we highlight the likelihood that the primary objective of the company was probably two-fold: promoting itself within the market for predictive testing for human genetic diseases and ancestry at a low cost to consumers, and establishing a high-value database/biobank for research (one of the largest biobanks of human deoxyribonucleic acid (DNA) and personal information). By dint of this marketing approach, a two-sided market has been established between the consumer and the research laboratories, involving the establishment of a database/DNA biobank for scientific and financial gain. We describe here the profound ethical issues raised by this setup.

Ancient origin of somatic and visceral neurons.

BACKGROUND: A key to understanding the evolution of the nervous system on a large phylogenetic scale is the identification of homologous neuronal types. Here, we focus this search on the sensory and motor neurons of bilaterians, exploiting their well-defined molecular signatures in vertebrates. Sensorimotor circuits in vertebrates are of two types: somatic (that sense the environment and respond by shaping bodily motions) and visceral (that sense the interior milieu and respond by regulating vital functions). These circuits differ by a small set of largely dedicated transcriptional determinants: Brn3 is expressed in many somatic sensory neurons, first and second order (among which mechanoreceptors are uniquely marked by the Brn3+/Islet1+/Drgx+ signature), somatic motoneurons uniquely co-express Lhx3/4 and Mnx1, while the vast majority of neurons, sensory and motor, involved in respiration, blood circulation or digestion are molecularly defined by their expression and dependence on the pan-visceral determinant Phox2b. RESULTS: We explore the status of the sensorimotor transcriptional code of vertebrates in mollusks, a lophotrochozoa clade that provides a rich repertoire of physiologically identified neurons. In the gastropods Lymnaea stagnalis and Aplysia californica, we show that homologues of Brn3, Drgx, Islet1, Mnx1, Lhx3/4 and Phox2b differentially mark neurons with mechanoreceptive, locomotory and cardiorespiratory functions. Moreover, in the cephalopod Sepia officinalis, we show that Phox2 marks the stellate ganglion (in line with the respiratory--that is, visceral--ancestral role of the mantle, its target organ), while the anterior pedal ganglion, which controls the prehensile and locomotory arms, expresses Mnx. CONCLUSIONS: Despite considerable divergence in overall neural architecture, a molecular underpinning for the functional allocation of neurons to interactions with the environment or to homeostasis was inherited from the urbilaterian ancestor by contemporary protostomes and deuterostomes.

Bio-ethical issues in oncology during the first wave of the COVID-19 epidemic: A qualitative study in a French hospital.

BACKGROUND: Using a specific bioethical theory (=global bioethics) and method (=a posteriori), we try here to identify and evaluate the bio-ethical issues raised by the COVID-19 pandemic, and possible solutions, to improve the management of cancer patients at the hospital in future pandemics, before the emergence of vaccines or scientifically validated treatments. MATERIALS & METHODS: Our work is based primarily on the clinical experience of three oncologists from the oncology department of Foch Hospital in France, who were on the frontline during the first wave of the epidemic. We compared their perceptions with published findings, to complete or nuance their views. RESULTS: Three bio-ethical issues were identified, and possible solutions to these problems were evaluated: (1) scientific evidence versus lack of time → the creation of emergency multidisciplinary team meetings (MTM); (2) healthcare equality versus lack of resources → the development of telemedicine; (3) individual liberties versus risk of contamination → role of cancer patients' associations, psychologists and bioethicists. CONCLUSION: We consider the creation of an emergency MTM, in particular, in addition to a true ethics committee with real competence in bioethics, to be a first solution that would be easy to implement in hospitals in many countries.

Bioethics after the COVID-19 pandemic: More research, fewer committees?

In the face of the pandemic, bioethics, once again, proved its scientific utility. In France, in particular, the academic approach (= peer-reviewed, scientific publications, etc.) should be given priority over the institutional approach (= public surveys, public meetings, etc.), in hospitals, research institutes, universities, and companies, with the professionalization that this would imply (i.e. bioethicists).

Creation and use of organoids in biomedical research and healthcare: the bioethical and metabioethical issues.

In the field of bioethics, scientific articles have already been published, and have highlighted relatively pluralist reflections concerning the creation and use of organoids. This plurality, rather than simply reflecting the complexity of the subject, may also be a consequence of the multiple theoretical and practical frameworks applied. Moreover, the creation and use of organoids in biomedical research and healthcare is probably in its infancy. This phenomenon is likely to increase in amplitude. Bioethics may be able to provide it with an effective and pertinent moral meaning, provided that a veritable metabioethical reflection is developed in parallel, that is, a reflection on bioethics itself, to provide scientists and clinicians with the best possible assistance in their everyday practice.

Systemic Modelling in Bioethics.

We present here a new method for bioethics: systemic modelling. In this method, the complex phenomenon being studied (e.g. personalized medicine, genetic testing, gene therapy, genetically modified organisms) is modelled as a whole, to shed light on its organization and functioning, and major (bio)ethical issues and solutions for their resolution are then identified. This systemic modelling method is ideal for use in the identification of solutions, rather than their validation, with other methods then used to test the solutions found. We provide a description and reproducible instructions for the application of systemic modelling in bioethics, together with a brief example of the application of this method to the study of the impact of personalized medicine on French society.