Of mice and human embryos: is there an ethically preferred order of preclinical research on new assisted reproductive technologies?

It is widely acknowledged that the responsible introduction of new assisted reproductive technologies (ARTs) requires preclinical safety research, including the use of animal models and human embryos. However, the moral sensitivity of human embryo research has led to regulations and guidance stating that human embryos may only be used for research that cannot also be conducted with animals. We call this the 'use animals first' (UAF) rule. In the field of ART research, this translates into the notion of an ideal chain of consecutive preclinical research steps, where research using human embryos may only be considered as a further step after promising results have been obtained in animals first. This may lead to research ethics committees requiring animal studies that are in fact a waste of time and money, while exposing animals to an infringement of their wellbeing for no good purpose. In this paper, we explore the possible moral arguments behind the UAF-rule and test their validity. We conclude that there are no convincing grounds for upholding this rule and recommend replacing it.

Human embryos from induced pluripotent stem cell-derived gametes: ethical and quality considerations.

Protocols for successful differentiation of male and female gametes from induced pluripotent stem cells have been published. Although culture of precursor cells in a natural microenvironment remains necessary to achieve terminal differentiation, the creation of human preimplantation embryos from induced pluripotent stem cell-derived gametes is technically feasible. Such embryos could provide a solution to the scarcity of human cleavage-stage embryos donated for research. Here, we discuss current technology, major research-related ethical concerns and propose the norms that would assure the quality and reliability of such embryos.

Recommended Ethical Safeguards on Fertilization of Human Germ Cells Derived from Pluripotent Stem Cells Solely for Research Purposes.

Production of human fertilized embryos by using germ cells derived from pluripotent stem cells (PSCs) entails ethical issues that differ fundamentally depending on the aim. If the aim is solely to conduct research, then embryo generation, utilization and destruction must respect for the human embryo as having the innate potential to develop into a human being. If the aim is human reproduction, this technology must never be used to manipulate human life, confuse social order, or negatively affect future generations. Researchers should distinguish the aims and then accordingly establish a consensus on the safeguards needed to proceed with scientifically significant and socially accepted research, or otherwise set a moratorium. Currently, in Japan, germ cell production from human PSCs is permitted, whereas fertilization of these germ cells is not. The Japanese Expert Panel on Bioethics in the Cabinet Office has proposed that all of the following conditions must be met to approve fertilization for research purposes: (1) the research is significant for the life sciences and medicine; (2) the benefits or anticipated benefits are socially accepted; (3) human safety is assured; and (4) safeguards are put in place. If fertilization is ethically approved, I recommend the following safeguards: limitation of the purpose to improving conventional ART as an initial step; permitted culture of human embryos until the appearance of the primitive streak; restriction of the number of embryos produced to the minimum necessary; prohibition of transplantation into a human or animal uterus; and provision of human-derived ova that are not required for ART treatment.

Double-effect reasoning and the conception of human embryos.

Some commentators argue that conception signals the onset of human personhood and that moral responsibilities toward zygotic or embryonic persons begin at this point, not the least of which is to protect them from exposure to death. Critics of the conception threshold of personhood ask how it can be morally consistent to object to the embryo loss that occurs in fertility medicine and research but not object to the significant embryo loss that occurs through conception in vivo. Using that apparent inconsistency as a starting point, they argue that if that embryo loss is tolerable as a way of conceiving children, it should be tolerable in fertility medicine and human embryonic research. Double-effect reasoning shows, by contrast, that conception in vivo is justified even if it involves the death of persons because the motives for wanting children are not inherently objectionable, because the embryo loss that occurs in unassisted conception is not the means by which successful conception occurs, and because the effect of having children is proportionate to the loss involved. A similar outcome holds true for in vitro fertilisation in fertility medicine but not for in vitro fertilisation for research involving human embryos.

How can ethics relate to science? The case of stem cell research.

We live in an era of an important turning point in the relationship between ethics (or, more accurately, bioethics) and science, notably due to both public interest and the gradual tightening of the gap in time between scientific discoveries and ethical reflection. The current bioethics debates of emerging situations (pluripotent stem cells, gene therapy, nanotechnology) have undoubtedly contributed to this change. Today, science happens and bioethics reflects on the possibilities, considers the risks, and advances proposals, which, without being scientific, can also imprint a mark on the path of scientific development. In this article, through the narrative of stem cell research, we will try to illustrate how bringing a bioethical viewpoint to the scientific debate can become a healthy exercise in both ethics and science, especially as narratives shift, as was the case in this field due to the introduction of induced pluripotent stem cells, the advent of which is not easily dissociated from the controversies related to embryo research. We should perhaps welcome this trend as promising for the future relationship between ethics and scientific research, providing a stimulus (and not a block) to the ever-evolving scientific discourse.

Stem cell research on embryonic persons is just.

I argue that embryonic stem cell research is fair to the embryo, even on the assumption that the embryo has attained full personhood and an attendant right to life at conception. This is because the only feasible alternatives open to the embryo are to exist briefly in an unconscious state and be killed or to not exist at all. Hence, one is neither depriving the embryo of an enduring life it would otherwise have had nor is one causing the embryo pain. I also argue that a rational agent in a situation relevantly similar to that of the embryo would consent to such research, and I use this insight to ground two justice-based arguments in favor of this research.

Los pseudoembriones: ¿una inteligibilidad en el límite de nuestra inteligencia? / Pseudo embryos: intelligibility in the limit of our intelligence? / Os pseudo-embriões: uma inteligibilidade no limite de nossa inteligência?

La investigación científica ha posibilitado nuevas esperanzas en la curación de diversas patologías provocadas por procesos degenerativos o por daño directo sobre órganos y tejidos. Una de las líneas de estudio más prometedoras es la utilización de células pluripotenciales, siendo su fuente principal los embriones obtenidos en las técnicas de fertilización asistida. Mas los cuestionamientos éticos respecto a la utilización y destrucción de ellos ha llevado al ingenio humano a desarrollar entidades que semejan embriones pero que no lo serían esencialmente. Si esto fuera cierto, su utilización para obtener esas valiosas células no sería objetable. Estos pseudoembriones desafían a nuestra inteligencia a establecer su verdadero estatuto ontológico. Este trabajo busca reflexionar sobre la dificultad para aplicar los distintos criterios que utiliza nuestra inteligencia para identificar o no, en una serie de entidades naturales y creadas por el hombre, la presencia de un individuo humano con todos sus derechos y dignidad.

Scientific research has made possible new hopes for the cure of diverse pathologies provoked by degenerative processes or by direct damage on organs and tissues. One of the fields of study most promising is the use of pluripotential cells, being their main origin embryos obtained by assisted reproduction techniques. But, the ethical questioning with respect to their use and destruction has guided human talent to develop entities similar to embryos, but not essentially. If this were true, their use to obtain these valuable cells will not be ethically objectionable. These pseudo embryos challenge our intelligence to establish their true ontological statute. This article reflects about the difficulty in applying the different criteria that our intelligence uses to identify or not the presence of a human being with all his/her rights and dignity in a series of natural and created by man entities.

A investigação científica tem possibilitado novas esperanças na cura de diversas patologias provocadas por processos degenerativos ou por dano direto sobre órgãos e tecidos. Uma das linhas de estudo mais promissoras é a utilização de células pluripotenciais, sendo sua fonte principal os embriões obtidos nas técnicas de fertilização assistida. Mas os questionamentos éticos a respeito da utilização e destruição deles tem levado a engenhosidade humana a desenvolver entidades que se assemelham a embriões, mas que não seriam essencialmente. Se isto for certo, sua utilização para obter essas valiosas células não seria objetável. Estes pseudo-embriões desafiam a nossa inteligência a estabelecer seu verdadeiro estatuto ontológico. Este trabalho busca refletir sobre a dificuldade para aplicar os distintos critérios que utiliza a nossa inteligência para identificar ou não, numa série de entidades naturais e criadas pelo homem, a presença de um indivíduo humano com todos os seus direitos e dignidade.

Complicity in stem cell research: the case of induced pluripotent stem cells.

Many who object to human embryonic stem cell (hESC) research because they believe it involves complicity in embryo destruction have welcomed induced pluripotent stem cell (iPSC) research as an ethical alternative. This opinion article aims to show that complicity arguments against hESC research are prima facie inconsistent with accepting iPSC research as it is currently done. Those who oppose hESC research on grounds of complicity should either (i) oppose iPSC research as well, (ii) advocate a radical change in the way iPSC research is done, (iii) demonstrate that complicity arguments against iPSC research are weaker than those against hESC research or (iv) reject complicity arguments against both hESC and iPSC research, either by adopting a more limited conception of complicity that allows acceptance of some hESC research, or by accepting that destroying embryos for important scientific research is not wrong.

A libertarian perspective on the stem cell debate: compromising the uncompromisible.

The present paper attempts to forge a compromise between those who maintain that stem cell research is out-and-out murder of young helpless human beings and those who favor this practice. The compromise is predicated upon the libertarian theory of private property rights. Starting out with the premise that not only the fetus but even the fertilized egg is a human being, with all rights thereto, it offers a competition between those who fertilize eggs for research and those who wish to adopt them. If and only if the former win this competition will they be allowed to use these very young human beings for the purposes they have constructed them. This is justified on grounds of avoiding child abuse.

Creating embryos for use in stem cell research.

In this paper I will address whether the restriction on the creation of human embryos solely for the purpose of research in which they will be used and destroyed in the creation of human stem cell lines is ethically justified. Of course, a cynical but perhaps accurate reading of the new Obama policy is that leaving this restriction in place was done for political, not ethical, reasons, in light of the apparent public opposition to creating embryos for use in this research. But the issue of whether the restriction is ethically justified remains important, even if only for another day in the policy arena.

Translating stem cell research: challenges at the research frontier.

This paper will address the translation of basic stem cell research into clinical research. While "stem cell" trials are sometimes used to describe established practices of bone marrow transplantation or transplantation of primary cells derived from bone marrow, for the purposes of this paper, I am primarily focusing on stem cell trials which are far less established, including use of hESC derived stem cells. The central ethical challenges in stem cell clinical trials arise in frontier research, not in standard, well-established areas of research.

[Does 2009 mark a revival of embryonic stem cells?]. / ¿Resucitan al inicio del 2009 las células troncales procedentes de embriones?

The legal possibility of using federal funds to work with embryonic cells and destroy embryos started on March 2009 in the USA. It has nothing to do with regenerative therapies. It is directed to create banks with human cells, banks directed by a few scientists involved in biotechnology enterprises connected with centers of in vitro reproduction. They pursue the use of ad hoc human embryos for biomedical research. The idea of using cell lines derived from embryos is quite spread, and even the idea of obtaining new lines of this type to validate reprogrammed somatic pluripotential cells, the so called iPS cell (induced pluripotent stem), without destroying embryos or using ovules. This type of cells is indeed of great value in medical research and it is opening new possibilities in Cell Therapy. Recent data are analyzed and considerations are advanced encouraging rational alternatives to eliminate embryonic cells in the evaluation of iPS cells.