Affordable Pricing of CRISPR Treatments is a Pressing Ethical Imperative.

Casgevy, the world's first approved CRISPR-based cell therapy, has been priced at $2.2 million per patient. Although this hefty price tag was widely anticipated, the extremely high cost of this and other cell and gene therapies poses a major ethical issue in terms of equitable access and global health. In this Perspective, we argue that lowering the prices of future CRISPR therapies is an urgent ethical imperative. Although we focus on Casgevy as a case study, much of our analysis can be extrapolated to the controversies over affordable access to other gene and cell therapies. First, we explain why this first-of-its-kind CRISPR therapy might be so expensive. We then analyze the ethical issues of equity and global health of early CRISPR treatments. Next, we discuss potential solutions to lower the prices of CRISPR gene therapies. We conclude that the approval of CRISPR transforms our obligations of justice and compels us to bring future gene therapies to the maximum possible number of patients with serious genetic diseases at affordable prices.

Human stem-cell-derived embryo models: When bioethical normativity meets biological ontology.

The use of human stem-cell-derived embryo models in biomedical research has recently sparked intense bioethical debates. In this article, we delve into the ethical complexities surrounding these models and advocate for a deeper exploration of their biological ontology to discuss their bioethical normativity. We examine the ethical considerations arising from the implementation of these models, emphasizing varying viewpoints on their ethical standing and the ethical obligations associated with their development and utilization. We contend that a nuanced comprehension of their biological ontology is crucial for navigating these ethical quandaries. Furthermore, we underscore the indispensability of interdisciplinary cooperation among bioethicists, biologists, and philosophers to unravel the complex interplay between biological ontology and the normative framework of bioethics. Moreover, this article introduces a novel combinatorial approach to resolve the ethical dilemma surrounding these models. We propose a distinction between models that closely emulate natural embryos, based on the status of synthetic embryos, and those capable of reproducing specific dimensions of embryonic development. Such differentiation allows for nuanced ethical considerations while harnessing the value of these models in scientific research, paving the way for a more comprehensive ethical framework in the context of evolving biotechnologies.

Why whole body gestational donation must be rejected: a response to Smajdor.

Anna Smajdor's proposal of whole body gestational donation (WBGD) states that female patients diagnosed as brain-dead should be considered for use as gestational donors. In this response, Smajdor's proposal is rejected on four different accounts: (a) the debated acceptability of surrogacy despite women's autonomy, (b) the harm to dead women ́s interests, (c) the interests of the descendants, and (d) the symbolic value of the body and interests of relatives. The first part argues that WBGD rests on a particular conception of the instrumentalization of bodies that cannot be circumvented simply by the patient's consent and relinquished autonomy. The second part argues the importance of avoiding any harm to dead women's interests. The third part identifies the importance of the interest of the foetus in the light of Procreative-Beneficence principle that Smajdor overlooks. And finally, the fourth part considers the symbolic value of the human body and the interest of relatives. The main goal of this commentary is not to show that WBGD cannot be implemented; rather, it is to show that there are not any good arguments in favour of doing so.

Synthetic embryos: a new venue in ethical research.

In brief: Two independent groups have reported the development of 'artificial embryos'. Those are in vitro models made of mouse embryonic stem cells, without the need for egg or sperm, and grown ex utero without requiring implantation. This system might open new venues in bioethical research if human cells show the ability to replicate this system. Abstract: The recent publications reported in 2022 reveal the possibility of obtaining mouse embryos without the need for egg or sperm. These 'artificial embryos' can recapitulate some stages of development ex utero - from neurulation to organogenesis - without implantation. Synthetic mouse embryos might serve as a valuable model to gain further insights into early developmental stages. Indeed, it is expected for these models to be replicated by employing human cells. This promising research raises ethical issues and expands the horizon of ethics in regard to the development of the human embryo. From this point of view, we state some of the new open venues for bioethical research.

Germline Gene Editing: The Gender Issues.

Human germline gene editing constitutes an extremely promising technology; at the same time, however, it raises remarkable ethical, legal, and social issues. Although many of these issues have been largely explored by the academic literature, there are gender issues embedded in the process that have not received the attention they deserve. This paper examines ways in which this new tool necessarily affects males and females differently-both in rewards and perils. The authors conclude that there is an urgent need to include these gender issues in the current debate, before giving a green light to this new technology.

COVID-19, the Immune System, and Organic Disability.

Despite the availability of safe vaccines against SARS-CoV-2, some people will remain vulnerable because they will not be vaccinated. Who are these non-vaccinated people? We can distinguish two groups: (i) persons who cannot be vaccinated for clinical reasons and who, despite having been vaccinated, have not achieved immunity; (ii) persons who voluntarily refuse to get vaccinated. These groups have in common an immune system that will make them vulnerable to COVID-19. The reasons for their vulnerability and the ethical judgment they deserve are different; the solutions offered to them are also different. In the case of those who voluntarily avoid vaccination, States are not compromised to introduce new protective policies. In the case of people who remain involuntarily vulnerable, instead, the response should be articulated on the same rules and principles that inform the social model of disability because they will live with an organic disability.

Digital Covid Certificates as Immunity Passports: An Analysis of Their Main Ethical, Legal, and Social Issues.

Digital COVID certificates are a novel public health policy to tackle the COVID-19 pandemic. These immunity certificates aim to incentivize vaccination and to deny international travel or access to essential spaces to those who are unable to prove that they are not infectious. In this article, we start by describing immunity certificates and highlighting their differences from vaccination certificates. Then, we focus on the ethical, legal, and social issues involved in their use, namely autonomy and consent, data protection, equity, and international mobility from a global fairness perspective. The main conclusion of our analysis is that digital COVID certificates are only acceptable if they meet certain conditions: that they should not process personal data beyond what is strictly necessary for the aimed goals, that equal access to them should be guaranteed, and that they should not restrict people's autonomy to access places where contagion is unlikely. We conclude that, if such conditions are guaranteed, digital COVID certificates could contribute to mitigating some of the most severe socioeconomic consequences of the pandemic.

[Prioritization of health resources in contexts of scarcity. SESPAS Report 2022]. / Priorización de recursos sanitarios en contextos de escasez. Informe SESPAS 2022.

The COVID-19 pandemic has been a clinical challenge, but also a legal and bioethical one. These three fundamental pillars are developed in the approach to prioritizing health resources in pandemic, clinical criteria, corresponding legal framework and applicable ethical principles. Initially, clinical criteria were applied to identify patients with the best survival prognosis, combining a clinical evaluation and the use of short-term and long-term prognostic variables. But the decision to prioritize the care of one patient over another has a legal-political burden, which poses a risk of falling into discrimination since fundamental rights are at stake. The prioritization criteria must be based on principles that reflect as a vehicle philosophy that which we have constitutionally assumed as a social and democratic State of Law, which did not respond to utilitarianism but to personalism. Any philosophy of resource distribution must bear in mind the scientific and constitutional perspective and, with them, those of fundamental rights and bioethical principles. In the prioritization of resources, ethical principles must be consolidated such as respect for the human dignity, the principle of necessity (equal need, equal access to the resource), the principle of equity (which advises prioritizing the most vulnerable population groups), transparency (fundamental in society's trust) and the principle of reciprocity (which requires protecting the sectors of the population that take more risks), among others.

Shifting to a model of donor conception that entails a communication agreement among the parents, donor, and offspring.

BACKGROUND: Some persons conceived with donor gametes react negatively when they found their birth via donor conception. They request access to information about and seek to communicate with the donor. However, some countries mandate donor anonymity. Other countries allow donor-conceived persons to access donor information, but they can only use this access if their parents have disclosed donor conception to them. We investigated a thorny issue of donor conception: whether donor conception should be shifted from an anonymous basis to a non-anonymous basis. METHODS: We review the issues and concerns regarding donor conception. We then consider the impact of direct-to-consumer genetic testing on donor conception, as well as the influence of donor conception on offspring's identity and the potential of different types of donors. To discuss the future policy of donor conception, the policies on the anonymity of gamete donors were investigated using publicly-available documents in 15 countries. RESULTS: The aim of mandating donor anonymity is to protect the privacy of the donor and intended parents. However, the diffusion of direct-to-consumer genetic testing may make it impossible to maintain anonymity. Birth via donor conception shapes the offspring's identity, and the donor may further influence the development of offspring's identity through communications. It remains important to disclose donor conception to donor-conceived offspring and to provide them with donor information. However, that information might be insufficient for some donor-conceived persons. Here are benefits to having open-identity donors and known donors. Such donors can make an agreement with the parents regarding future communication with the offspring, although both sides should respect privacy. Subsequent counseling for all parties involved can result in better tripartite communication agreements. CONCLUSIONS: In sum, ethical and practical issues that complicate donor anonymity are driving a shift to non-anonymous donor conception, in which all parties come to a communication agreement. To pave the way for such a donor conception system, transitional measures can be put into place. For countries that already adopted non-anonymous donor conception, ensuring the communication agreements is important to protect the rights of parents, donor, and offspring.

Mandatory vaccination and the 'seat belt analogy' argument: a critical analysis in the context of the Covid-19 pandemic.

The seat belt analogy argument is aimed at furthering the success of coercive vaccination efforts on the basis that the latter is similar to compulsory use of seat belts. However, this article demonstrated that this argument does not work so well in practice due to several reasons. The possibility of saving resources in health care does not usually apply in our societies, and the paternalist mentality that contributed to the implementation of seat belt-wearing obligation was predominant 30 years ago, but it does not apply at this moment. Furthermore, the risk/benefit analysis is totally different in both scenarios. In the case of seat belts, there is no way to discriminate between the users. In the case of vaccines, individuals present with unique circumstances that may differ substantially from those of another and might be foreseen a priori. This means that an analysis must be performed individually before vaccination is imposed. Finally, one must keep in mind that seat belts are often the only way in which we can protect third parties against a tragic hit by the occupant of another vehicle and are very efficient tools for this purpose. Vaccines, in contrast, do not always create sterilising immunity and are definitely not the only way by which we can avoid spreading a virus; immunity certificates, isolation, or even confinement may also serve as viable methods to achieve this purpose.

Bioethical Concerns During the COVID-19 Pandemic: What Did Healthcare Ethics Committees and Institutions State in Spain?

Objectives: Each new wave of the COVID-19 pandemic invites the possible obligation to prioritize individuals' access to vital resources, and thereby leads to unresolved and important bioethical concerns. Governments have to make decisions to protect access to the health system with equity. The prioritization criteria during a pandemic are both a clinical and legal-administrative decision with ethical repercussion. We aim to analyse the prioritization protocols used in Spain during the pandemic which, in many cases, have not been updated. Method: We carried out a narrative review of 27 protocols of prioritization proposed by healthcare ethics committees, scientific societies and institutions in Spain for this study. The review evaluated shared aspects and unique differences and proffered a bioethical reflection. Results: The research questions explored patient prioritization, the criteria applied and the relative weight assigned to each criterion. There was a need to use several indicators, being morbidity and mortality scales the most commonly used, followed by facets pertaining to disease severity and functional status. Although age was initially considered in some protocols, it cannot be the sole criterion used when assigning care resources. Conclusions: In COVID-19 pandemic there is a need for a unified set of criteria that guarantees equity and transparency in decision-making processes. Establishing treatment indications is not the aim of such criteria, but instead prioritizing access to care resources. In protocols of prioritization, the principle of efficiency must vary according to the principle of equity and the criteria used to guarantee such equity.

Immunity passports, fundamental rights and public health hazards: a reply to Brown et al.

In their recent article, Brown et al analyse several ethical aspects around immunity passports and put forward some recommendations for implementing them. Although they offer a comprehensive perspective, they overlook two essential aspects. First, while the authors consider the possibility that immunological passports may appear to discriminate against those who do not possess them, the opposite viewpoint of immune people is underdeveloped. We argue that if a person has been tested positive for and recovered from COVID-19, becoming immune to it, she cannot be considered a hazard to public health and, therefore, the curtailment of her fundamental rights (eg, the right to freedom of movement) is not legitimate. Second, they omit that vaccine distribution will create similar problems related to immunity-based licenses. Vaccine certificates will de facto generate a sort of immunity passport. In the next phases of the pandemic, different immunity statuses will be at stake, because the need to identify who can spread COVID-19 is unavoidable. If a person does not pose a threat to public health because she cannot spread the infection, then her right to freedom of movement should be respected, regardless of how she acquired that immunity.

Human Dignity and Gene Editing: Additional Support for Raposo's Arguments.

The aim of the present paper is to reinforce some of the affirmations made by Vera Lucia Raposo in a recent paper published by the Journal of Bioethical Inquiry. According to her, germline gene editing does not violate human dignity at all. This article offers some complementary ideas supporting her statement. In particular, four main arguments are stressed. Firstly, not only is the idea of human dignity unclear, but the idea of the human genome suffers from a general lack of concreteness, which has dramatic consequences for the debate. Secondly, it is highlighted that if we believe that the immutability of the human genome underpins human dignity, then it should be our duty to use the tools of genetic modification to reverse any accidental changes that occur in nature. Thirdly, it is showed that if the alteration of germline constitutes an attack on human dignity, then we should also refrain from performing medical practices such as chemotherapy, which cause precisely this effect. Finally, we argue that modification of germline is not contrary to human dignity but an excellent expression of our autonomy.

Gene editing and disabled people: a response to Felicity Boardman.

Is the germline gene editing (GEE) of embryos with disabling conditions a moral obligation? According to a recent editorial by F. Broadmann, there are strong reasons to hold the opposite, since "such a focus on the benefit to individual embryos is to overlook the broader societal changes that genome editing will signal, as well as the potential negative impacts on existing persons with genetic conditions". This paper is aimed at rebuking these arguments by invoking the human dignity principle.

Should we have a right to refuse diagnostics and treatment planning by artificial intelligence?

Should we be allowed to refuse any involvement of artificial intelligence (AI) technology in diagnosis and treatment planning? This is the relevant question posed by Ploug and Holm in a recent article in Medicine, Health Care and Philosophy. In this article, I adhere to their conclusions, but not necessarily to the rationale that supports them. First, I argue that the idea that we should recognize this right on the basis of a rational interest defence is not plausible, unless we are willing to judge each patient's ideology or religion. Instead, I consider that the right must be recognized by virtue of values such as social pluralism or individual autonomy. Second, I point out that the scope of such a right should be limited at least under three circumstances: (1) if it is against a physician's obligation to not cause unnecessary harm to a patient or to not provide futile treatment, (2) in cases where the costs of implementing this right are too high, or (3) if recognizing the right would deprive other patients of their own rights to adequate health care.

Is the 'serious' factor in germline modification really relevant? A response to Kleiderman, Ravitsky and Knoppers.

Should we use human germline genome modification (HGGM) only when serious diseases are involved? This belief is the underlying factor in the article written by Kleiderman, Ravitsky and Knoppers to which I now respond. In my opinion, the answer to this question should be negative. In this paper, I attempt to show that there are no good reasons to think that this technology should be limited to serious diseases once it is sufficiently proven to be safe and efficient. In fact, opting otherwise would negatively harm human beings' right to the highest standard of health that unmodified embryos could promote. Therefore, the issue should not be so much to define adequately what a serious disease is, but rather to elucidate whether this concept should play any role beyond the context of preimplantation genetic testing (PGT). This paper argues that we should not accept the similarity between technologies such as PGT and HGGM because they face different challenges and offer totally different possibilities. Therefore, we are in urgent need to build a completely new ethical architecture that covers the application of germline editing in human embryos. As a part of that process, a much deeper debate on the necessity of distinguishing different disease types is required.