Advancing primatology through ethical and scientific perspectives on rhesus monkey (Macaca mulatta) cloning.

A critical turning point was reached in research with the recent success in cloning rhesus monkeys (Macaca mulatta), a major advancement in primatology. This breakthrough marks the beginning of a new age in biomedical research, ushered by improved somatic cell nuclear transfer techniques and creative trophoblast replacement strategies. The successful cloning of rhesus monkeys presents the possibility of producing genetically homogeneous models that are highly advantageous for studying complex biological processes, testing drugs, and researching diseases. However, this achievement raises important ethical questions, particularly regarding animal welfare and the broader ramifications of primate cloning. Approaching the future of primate research with balance is critical, as the scientific world stands on the brink of these revolutionary breakthroughs. This paper aims to summarise the consequences, ethical challenges and possible paths forward in primatology arising from rhesus monkey cloning.

25th ANNIVERSARY OF CLONING BY SOMATIC-CELL NUCLEAR TRANSFER: Cloning, mitochondrial replacement and genome editing: 25 years of ethical debate since Dolly.

The birth of Dolly the sheep in 1996 elicited a tsunami of commentaries, both in the popular media and academic journals, including responses to the prospect of human reproductive cloning. Much of the anxiety expressed over this imagined consequence of Dolly's genesis revealed fundamental concerns about us losing our commitments to certain ethical goods, such as human dignity, or even 'what it means to be human'. Over the last 25 years, the focus of much of the ethical debate over human biotechnology has slowly shifted towards other genetic technologies that aim to influence inheritance, such as mitochondrial replacement techniques (MRT) and heritable genome editing. Genome editing, in particular, is a technology with multiple fields of application, actual and potential, in research and innovation. This review suggests that many of the fundamental concerns about the possibility of human reproductive cloning that were precipitated by Dolly persist today in the arguments of those who oppose MRT and any use of heritable human genome editing (HHGE). Whilst it is not accepted here that an understanding of human nature and dignity alone can demonstrate the ethical unacceptability of such assisted reproductive technologies, there are themes of justice, which extend into our relationships with animals, that demand continued wide-ranging examination and public dialogue. While Dolly has cast a long shadow over such discussions, this review suggests that the general existential angst over human uses of biotechnology that she came to symbolise is neither compulsory nor a reliable guide for how to think about biotechnologies today.

Sharpening the cutting edge: additional considerations for the UK debates on embryonic interventions for mitochondrial diseases.

In October 2015 the UK enacted legislation to permit the clinical use of two cutting edge germline-altering, IVF-based embryonic techniques: pronuclear transfer and maternal spindle transfer (PNT and MST). The aim is to use these techniques to prevent the maternal transmission of serious mitochondrial diseases. Major claims have been made about the quality of the debates that preceded this legislation and the significance of those debates for UK decision-making on other biotechnologies, as well as for other countries considering similar legislation. In this article we conduct a systematic analysis of those UK debates and suggest that claims about their quality are over-stated. We identify, and analyse in detail, ten areas where greater clarity, depth and nuance would have produced sharper understandings of the contributions, limitations and wider social impacts of these mitochondrial interventions. We explore the implications of these additional considerations for (i) the protection of all parties involved, should the techniques transfer to clinical applications; (ii) the legitimacy of focussing on short-term gains for individuals over public health considerations, and (iii) the maintenance and improvement of public trust in medical biotechnologies. We conclude that a more measured evaluation of the content and quality of the UK debates is important and timely: such a critique provides a clearer understanding of the possible, but specific, contributions of these interventions, both in the UK and elsewhere; also, these additional insights can now inform the emerging processes of implementation, regulation and practice of mitochondrial interventions.

Algunas consideraciones sobre la transferencia mitocondrial: ¿un nuevo problema para la bioética? / Some thoughts on the mitochondrial transfer: a new issue for bioethics? / Algumas considerações sobre a transferência mitocondrial: um novo problema para a bioética?

En febrero de 2015 el Reino Unido dio el primer paso para la aprobación de la transferencia mitocondrial como técnica terapéutica. Teóricamente, gracias a eso será posible para muchas mujeres engendrar descendencia libre de patologías asociadas a defectos mitocondriales. Sin embargo, esta práctica enfrenta severas dudas desde un punto de vista ético. Entre las objeciones destacan: su estrecha vinculación con la clonación humana; la alteración de los genes de la línea germinal; la modificación de la identidad del ser humano al que dará lugar; la destrucción de embriones humanos que envuelve, o el elevado riesgo que encierra para la salud del ser humano resultante. En este texto se analiza la solvencia de todas estas objeciones de forma crítica, resaltando las fortalezas de algunas de ellas. En particular, se aboga por una restricción cuidadosa del uso de esta técnica, que promueva el empleo de alternativas más respetuosas con la salud del futuro ser humano.

In February 2015 the United Kingdom took the first step towards the adoption of mitochondrial transfer as a therapeutic technique. Theoretically, it will make it possible for many women to get rid of pathologies associated with mitochondrial defects. However, this practice has been subjected to severe doubts from an ethical standpoint. Among these objections, we could highlight the following: its close association with human cloning; the alteration of the germline genes; the modification in the identity of the human being involved; the destruction of human embryos; or the high risk to the health of the human being. In this text we will analyze these objections critically, highlighting the strength of all of them. As a result, we will call for a careful restriction of the use of this technique, and the promotion of the use of alternative options much more respectful of the human future.

Em fevereiro de 2015 o Reino Unido deu o primeiro passo para a aprovação da transferência mitocondrial como técnica terapêutica. Teoricamente, graças a isso será possível a muitas mulheres engendrar descendência livre de patologias associadas a defeitos mitocondriais. No entanto, esta prática enfrenta severas dúvidas a partir de um ponto de vista ético. Entre as objeções destacam: sua estreita vinculação com a clonagem humana; a alteração dos genes da linha germinal; a modificação da identidade do ser humano ao qual dará lugar; a destruição de embriões humanos que envolve, ou o elevado risco que encerra para a saúde do ser humano resultante. Neste texto se analisa a solvência de todas estas objeções de forma crítica, ressaltando as fortalezas de algumas delas. Em particular, se advoga por uma restrição cuidadosa do uso desta técnica, que se promova o emprego de alternativas mais respeitosas com a saúde do futuro ser humano.

"Mitochondrial Replacement" Technologies and Human Germline Nuclear Modification.

In 2015 the United Kingdom became the first jurisdiction to approve "mitochondrial replacement techniques" (MRT), thereby dropping prohibitions against creating human embryos with a permanently altered genetic make-up for purposes of reproduction. MRT is a misnomer because in fact it is the nucleus of the oocyte of the woman who wants a genetically related child that is transferred to the enucleated oocyte of a woman paid to undergo IVF to provide the oocyte. MRT thus constitutes nuclear transfer, which is prohibited by criminal sanctions under sections of laws on reproductive cloning in Canada, the United States, Australia, and European countries that regulate assisted reproduction. By adopting policies permitting the use of MRT, the United Kingdom has become the first jurisdiction to counteract an international consensus prohibiting germline modification. Analyses of the legal, ethical, and societal implications of MRT in assisted human reproduction are essential.

Human somatic cell nuclear transfer and reproductive cloning: an Ethics Committee opinion.

This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer and cloning," last published in Fertil Steril 2012;98:804-7.

Rendered invisible? The absent presence of egg providers in U.K. debates on the acceptability of research and therapy for mitochondrial disease.

Techniques for resolving some types of inherited mitochondrial diseases have recently been the subject of scientific research, ethical scrutiny, media coverage and regulatory initiatives in the UK. Building on research using eggs from a variety of providers, scientists hope to eradicate maternally transmitted mutations in mitochondrial DNA by transferring the nuclear DNA of a fertilised egg, created by an intending mother at risk of transmitting mitochondrial disease, and her male partner, into an enucleated egg provided by another woman. In this article we examine how egg providers for mitochondrial research and therapy have been represented in stakeholder debates. A systematic review of key documents and parliamentary debates shows that the balance of consideration tilts heavily towards therapeutic egg providers; research egg providers have been ignored and rendered invisible. However, mapping the various designations of therapeutic egg providers shows that their role is so heavily camouflaged that they have only an absent presence in discussions. We explore this puzzling ambivalence towards egg providers whose contributions are necessary to the success of current mitochondrial research and proposed therapies. We suggest that labels that diminish the contributions of egg providers serve certain governance objectives in managing possible future claims about, and by, therapeutic egg providers. We demonstrate that the social positioning of research egg providers is entangled within that of therapeutic egg providers which means that the former can also never receive their due recognition. This article contributes to the wider literature on the governance of new technological interventions.

The ethics of stem cells revisited.

Stem cells constitute one of the most promising tools for regenerative medicine. Thus, it seems morally compelling to explore all the sources that might provide us with them. However, some of these sources, such as somatic cell nuclear transfer, embryo destruction, or even induced pluripotency obtained by reprogramming have raised deep ethical issues. The aim of this paper is to reflect on the stem cell ethical debate at the current moment through an analysis of the academic literature. It will also provide an analysis of the ethical implications of the most relevant scientific advances that have happened in recent months or those which seem about to merge.

Clinical and ethical implications of mitochondrial gene transfer.

Inherited diseases caused by mitochondrial gene (mtDNA) mutations affect at least 1 in 5000-10,000 children and are associated with severe clinical symptoms. Novel reproductive techniques designed to replace mutated mtDNA in oocytes or early embryos have been proposed to prevent transmission of disease from parents to their children. Here we review the efficacy and safety of these approaches and their associated ethical and regulatory issues.

The commercialization of human eggs in mitochondrial replacement research.

After the development of induced pluripotent stem cells (IPSCs) in 2007, the pressure to commercialize women's eggs for stem cell research could have been expected to lessen. However, the pressure to harvest human eggs in large quantities for research has not diminished; rather, it has taken different directions, for example in germline mitochondrial research. Yet there has been little acknowledgement of these technologies' need for human eggs, the possible risks to women and the ethical issues concerning potential exploitation. Rather, there has been a renewed campaign to legalize payment for eggs in research, although the actual scientific advances are at best modest. This article shows why a market in women's eggs is ethically problematic in terms of the doctor's duty to do no harm and the limitations of 'informed' consent.

[IPS an ethical paradigm for biomedical research]. / Las IPS Paradigma Ético de la Investigación Biomédica.

One of the greatest advances in molecular and cell biology was the discovery of the Induced Pluripotent Stem cells (iPS) in mice, by Shinya Yamanka and his team in 2006. The possibility that these cells can be generated also in humans opens up unexpected ways of development for biomedicine. Its main contribution is the creation of a strong protocol that takes into account three major advances in biology such as; nuclear transfer techniques, the discovery of transcription factors associated with pluripotency and the isolation of mouse embryonic stem cells. A protocol that can be easily replicated in other laboratories to have the oportunity to design tests that allow modeling of many incurable diseases, drug testing for human cells or explore the possibilities of autologous transplants of tissues or organs. Yamanaka ethical motivation to find an alternative to embryonic stem cells (ES) and prevent the destruction of embryos produced by In Vitro Fertilization techniques (IVF), has proved to be a research model, in which the intuition of the ethical principles and its application in advanced biotechnology projects, has meant the opening of a whole new way of understanding the biology of embryonic development. It is clear that development, biologically understood (puede ser también ″treated″; tratado), is not a one-way street. The possibilities to deepen into the foundations of molecular biology and genetics, along with the expectations of its clinical applications have earned Yamanka the Nobel Prize in Medicine 2012, along with another great scholar Sir John Gurdon, discoverer of nuclear transfer techniques.

[The embryonic stem cells research. Example of biotechnology progress under extra-scientific pressure]. / La Investigación con Células Troncales Embrionarias. Ejemplo de Progreso Biotecnológico bajo Presiones Extracientíficas.

The possibility to isolate, cultivate, preserve, characterize and differentiate Human Embryonic Stem Cells (ES) discovered by James Thomson and his colleagues in 1998 was a milestone in the history of Stem Cell Research. Immediately after this discovery many speculations were made about the therapeutic possibilities of ES, motivated by ideological, political and economic aspects. The episode made clear the lack of scientific rationality and ethics when assessing realities as meaningful as those of human embryos obtained by in vitro fertilization techniques (IVF) or human eggs. Therapeutic Cloning as a promise to produce ″tailored″ Stem Cells reported by Hwang and his team in 2004, ended up being a scandal within the scientific community. The technical difficulties and ethical controversies that arose from obtaining ES were insurmountable. In 2010 only two clinical trials were reported using these cells. Those trials were abandoned in late 2011 arguing financial reasons. The discovery of Induced Pluripotent Stem Cell (iPS) in 2006 in mice and in 2007 in humans, represented the possibility of obtaining pluripotent stem cells without the need to destroy embryos. Today, the absence of clinical trials using ES, caused by financial difficulties as a result of its ineffectiveness, anticipates that the use of ES will be limited to certain experimental controls. Probably, the main contribution of Embryonic Stem Cells will be the understanding that biomedical research should follow an ethically and rationally based rigorous method that cannot be ignore.

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.

Human somatic cell nuclear transfer and cloning.

This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer (cloning)," last published in Fertil Steril 2000;74:873-6.