Search

Research directly on human embryos has gone through cycles of interest and neglect. The recent revitalization, including the making of 'human developmental biology', depended on fresh supplies of material and demand for medically relevant work. Human studies relied on mice but rejected simple extrapolation from this model mammal. Now, it is time to take stock while scanning the horizon for further change. Will research on human development be facilitated or frustrated? Will comparative approaches bring a greater variety of animal models into the picture? Will human stem-cell-based embryo models secure ever larger roles as exemplars of vertebrate development?, Competing Interests: Competing interests The author declares no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

While model organisms have had many historians, this article places studies of humans, and particularly our development, in the politics of species choice. Human embryos, investigated directly rather than via animal surrogates, have gone through cycles of attention and neglect. In the past 60 years they moved from the sidelines to center stage. Research was resuscitated in anatomy, launched in reproductive biomedicine, molecular genetics, and stem-cell science, and made attractive in developmental biology. I explain this surge of interest in terms of rivalry with models and reliance on them. The greater involvement of medicine in human reproduction, especially through in vitro fertilization, gave access to fresh sources of material that fed critiques of extrapolation from mice and met demands for clinical relevance or "translation." Yet much of the revival depended on models. Supply infrastructures and digital standards, including biobanks and virtual atlases, emulated community resources for model organisms. Novel culture, imaging, molecular, and postgenomic methods were perfected on less precious samples. Toing and froing from the mouse affirmed the necessity of the exemplary mammal and its insufficiency justified inquiries into humans. Another kind of model-organoids and embryo-like structures derived from stem cells-enabled experiments that encouraged the organization of a new field, human developmental biology. Research on humans has competed with and counted on models., (© 2024. The Author(s).)

Following early studies showing no adverse effects, cleavage stage biopsy by zona drilling using acid Tyrode's solution, and removal of single blastomeres for preimplantation genetic testing (PGT) and identification of sex in couples at risk of X-linked disease, was performed by Handyside and colleagues in late 1989, and pregnancies reported in 1990. This method was later used for specific diagnosis of monogenic conditions, and a few years later also for chromosomal structural and/or numerical impairments, thereby establishing a valuable alternative option to prenatal diagnosis. This revolutionary approach in clinical embryology spread worldwide, and several other embryo biopsy strategies developed over three decades in a process that is still ongoing. The rationale of this narrative review is to outline the different biopsy approaches implemented across the years in the workflow of the IVF clinics that provided PGT: their establishment, the first clinical experiences, their downsides, evolution, improvement and standardization. The history ends with a glimpse of the future: minimally/non-invasive PGT and experimental embryo micromanipulation protocols. This grand theme review outlines a timeline of the evolution of embryo biopsy protocols, whose implementation is increasing worldwide together with the increasing application of PGT techniques in IVF. It represents a vade mecum especially for the past, present and upcoming operators and experts in this field to (re)live this history from its dawn to its most likely future., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Recent developments in gene-editing technology have enabled scientists to manipulate the human genome in unprecedented ways. One technology in particular, Clustered Regularly Interspaced Short Pallindromic Repeat (CRISPR), has made gene editing more precise and cost-effective than ever before. Indeed, scientists have already shown that CRISPR can eliminate genes linked to life-threatening diseases from an individual's genetic makeup and, when used on human embryos, CRISPR has the potential to permanently eliminate hereditary diseases from the human genome in its entirety. These developments have brought great hope to individuals and their families, who suffer from genetically linked diseases. But there is a dark side: in the wrong hands, CRISPR could negatively impact the course of human evolution or be used to create biological weaponry. Despite these possible consequences, CRISPR remains largely unregulated due to the United States's outdated regulatory scheme for biotechnology. Moreover, human embryo research, which is likely critical to maximizing the therapeutic applications of CRISPR, is not easily undertaken by scientists due to a number of federal and state restrictions aimed at preventing such research. This Note examines the possible benefits and consequences of CRISPR and discusses the current regulations in both the fields of biotechnology and human embryo research that hamper the government's ability to effectively regulate this technology. Ultimately, this Note proposes a new regulatory scheme for biotechnology that focuses on the processes used to create products using CRISPR, rather than the products themselves, with a focus on enabling ethical research using human embryos to maximize the potential benefits of CRISPR.

The emergence of form and function during mammalian embryogenesis is a complex process that involves multiple regulatory levels. The foundations of the body plan are laid throughout the first days of post-implantation development as embryonic stem cells undergo symmetry breaking and initiate lineage specification, in a process that coincides with a global morphological reorganization of the embryo. Here, we review experimental models and how they have shaped our current understanding of the post-implantation mammalian embryo.

Mary Shelley's Frankenstein is 200 years old and remains relevant to 21st-century scientific experimentation. Molecular biologists today have become especially bold in their attempts to cure diseases while remaining mindful of the real dangers of their research. Scientists presumably share an abiding concern about producing uncontrollable mutations in people, animals, and the wider environment, yet a sense of urgency appears to inform the current scientific willingness to take risks, especially in the realm of embryology and germ-line modification. This willingness to go more boldly than before could be influenced by the unprecedented ability of such gene-cutting technologies as CRISPR to make immediate and lasting improvements to persons suffering from certain diseases and other physical malignancies, but also by an acculturated sense that such persons deserve to participate more fully in broader society.

Germany is an interesting case with respect to the governance of reprogenetics. It has a strong profile in the technosciences and high aims regarding the global bioeconomy, yet her regulation of human genetics, reproductive medicine and embryo research has for a long time been rather restrictive. German biopolitical exceptionalism has often been explained by reference to Catholicism and the legacy of the Nazi past. The Germans, so goes the common story, have learnt the lessons of history and translated them into unconditional respect for human dignity, which in turn translates into unconditional protection of human life, including the human embryo, and the firm repudiation of any eugenic distinction between 'life worth to live' and 'life not worth to live'. This, however, is not the whole story. Alongside deontological strictness we find another strand of governing body politics and reprogenetics in Germany, the rule-and-exception model, running from the mid-1970s abortion law via the 2002 Stem Cell Act to the 2011 regulation of pre-implantation genetic diagnosis. In contrast to the former, that strongly draws on Kant and his concept of human dignity, the latter bears resemblances to Carl Schmitt's concept of state of exception. The article will show that the rule-and-exception model builds the exception into the rule and transforms the meaning and mandate of ethics, namely from safeguarding ethical standards to deciding about the exception. Given that the exception has now tended to become the rule, the question is whether the lessons of history will govern German reprogenetics for much longer., (© 2016 John Wiley & Sons Ltd.)

In October 2011 the Court of Justice of the European Union pronounced the sentence in the case Brüstle v. Greenpeace. This sentence resolves the preliminary ruling interposed by the Bundesgerichtshof. The object of the preliminary ruling was the interpretation of the expression "human embryos", on 44/98/CE Guideline, in order to resolve the litigation between Brüstle, a German neurobiologist, and Greenpeace. Brüstle have patented a process for obtaining stem cells using cells originally extracted from human embryos, Greenpeace have filed a lawsuit against this patent. The article analyzes the meaning of this sentence in the light of the discrimination of the pre-implantation embryos in Spanish law. The content of the Biopatent Guideline, the Opinions of the European Group on Ethics of Science and New Technologies related to it, the EUJC verdict and the Conclusions of the General Advocate are analyzed. We will pay special attention to the final verdict given on November 27, 2012, by the German Federal Court of Justice. The paper also considers the repercussion of Brüstle case at the European level, examining the activity of the European Parliament, in the frame of the discussion of the program Horizon 2020, and the citizen's initiative "One of us". At the Spanish level, the paper underlines the need to reform the laws of Human Assisted Reproduction and of Biomedical Investigation.

Oocyte development is the end result of a sophisticated biological process that is hormonally regulated and produced by highly specialized cellular lines that differentiate in early embryo/fetal development. Embryo development is initially regulated by maternal transcripts until replaced by embryonic genomic expression. Then, an assortment of hormones and local environmental factors in various concentrations along the reproductive tract (e.g. fallopian tube, endometrial lining) provide the protection, nutrients and means of communication for the embryo to implant and develop. Both oocytes and embryos are susceptible to environmental, occupational and lifestyle exposures that can exert direct toxic effects and disrupt hormones. While some exposures may produce reversible changes, others, especially those damaging germinal cells in utero or during prepuberty, may result in permanent sequelae that continue in future generations. This article reviews the main factors that affect female fertility and their possible influence on human reproduction. Some lifestyles, xeno-oestrogens and heavy metals are already known to compromise female reproductive function. Nonetheless, many questions remain and little is known about the effect of many other factors on female fertility., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

This article reports a historical study of factors influencing the achievement of clinical preimplantation genetic diagnosis (PGD) in 1990, 22 years after its first demonstration in animals. During the 1970s, research on PGD continued in large farm animals, but serious interest in human PGD was not evident until 1986. First, interest in PGD during the 1970s waned with the advent of prenatal testing, which for gynaecologists was clinically more familiar, technically simpler and ethically less challenging than IVF. Indeed, IVF was viewed with widespread suspicion until the first IVF births in 1978. Second, interest in clinical PGD was stimulated by the UK Parliamentary reaction against human embryo research that greeted the Warnock Report in 1984. This hostility led scientists to initiate a pro-research campaign, further galvanized in 1985 by MP Enoch Powell's bid to ban such research. However, while Powell abhorred embryo research, he approved of PGD, a stance that divided the anti-research lobby. Accordingly, the campaigners for research emphasized that it was needed to achieve PGD. Powell demanded evidence of such projects and PGD research increased from 1986. It is concluded that UK political debates on embryo research played a critical role in stimulating the achievement of clinical PGD. Human pregnancies following preimplantation genetic diagnosis (PGD) for embryo sex were announced in 1990, 22 years after the technique was pioneered in animals. PGD in humans required not only technological advances, such as IVF and sensitive diagnostic tests, but also the motivation to develop and apply them. Our historical analysis shows that, although research on PGD continued in large farm animals during the 1970s, and techniques of the required sensitivity were developed on mouse embryo models, interest in clinical PGD was not evident until 1986. Two factors stimulated this sudden change in motivation. First, interest in PGD was depressed during the 1970s by the advent of prenatal diagnostic techniques, which for gynaecologists were clinically, technically and ethically less challenging than IVF. IVF was then regarded with a suspicion that only started to wane in the early 1980s following the first IVF births. Second, the UK Parliamentary reaction against human embryo research that greeted the Warnock Report in 1984 provided a positive stimulus to clinical PGD by prompting scientists to form a pro-research lobby, which was further galvanized in early 1985 by MP Enoch Powell's almost-successful bid to ban human embryo research. We show that while Powell abhorred embryo research, he approved of PGD, a stance that fractured the unity of the anti-research lobby. Accordingly, the pro-research lobby emphasized that embryo research was needed to achieve PGD. Powell demanded evidence of such projects, thereby, we argue, stimulating PGD research from 1986. Our evidence shows that UK political debates about PGD played a critical role in stimulating the achievement of PGD clinically., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The idea that biomedical research can be influenced by political events implies a teleological basis indicating that scientific achievements occur because there is a political need. Such a concept appears to have been the reason PGD was fast-tracked to emerge as a biomedical achievement well before its due date, occurring at a time when human embryology was still struggling to reach a reasonable level of efficiency and become adopted as a clinically relevant advance around the world. One story underlying the historical achievement of the HFE Act 1990, enabling regulated embryo research, steps outside the firm ground of biomedical science and encourages the idea that Reproductive BioMedicine Online should embrace a further section enabling articles dealing with 'History, politics and personalities' where these influence biomedical research., (Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical 'Studies on Human Reproduction'. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology., Methods: The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision., Results: We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants' high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support., Conclusions: This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research.

Stem cell research has enormous potential to advance knowledge about many diseases but poses critical ethical issues. Many countries and U.S. states have developed policies concerning this area that over time will surely evolve, yet certain underlying ethical principles and tensions will no doubt continue to remain key. Overall, the basic ethical principles of autonomy, beneficence, nonmalfeasance, and justice are crucial but have been viewed, interpreted, and applied differently by policy makers and others. Controversies remain concerning what degree of respect eggs and embryos should receive; whether egg donors should be compensated, and if so, how much; what exactly to include in informed consent; and how to ensure appropriate oversight by institutional review boards and embryonic stem cell research oversight committees. This article addresses these areas and ways of approaching them, to adhere to important ethical principles, while helping to advance research that has the potential to help innumerable patients., (Thieme Medical Publishers.)

This essay describes the approach and early results of the collaborative Embryo Project and its on-line encyclopedia (http://embryo.asu.edu). The project is based on a relational database that allows federated searches and inclusion of multiple types of objects targeted for multiple user groups. The emphasis is on the history and varied contexts of developmental biology, focusing on people, places, institutions, techniques, literature, images, and other aspects of study of embryos. This essay introduces the ways of working as well as the long-term goals of the project. We invite others to join the effort, both in this particular project and in joining together in digital collection, archiving, and knowledge generation at the borders of biology and history.

Regenerative medicine has been endorsed in Spain as a strategic, interdisciplinary topic to boost biomedical research. Special programs have been developed to promote collaborative research efforts among Spanish basic, applied, translational, and clinical researchers. Here, we present what we consider Spain's main current assets in this area.

Human embryonic stem cell research promises an increased understanding of the molecular process underlying cell differentiation. Transplantation of embryonic stem cells or their derivatives may, in the future, offer therapies for human diseases. In this Committee Opinion, American College of Obstetricians and Gynecologists (ACOG) Committee on Ethics presents an ethical framework for examining issues surrounding research using preimplantation embryos and proposes ethical guidelines for such research. The Committee acknowledges the diversity of opinions among ACOG members and affirms that no physician who finds embryo research morally objectionable should be required or expected to participate in such research. The Committee supports embryo research within 14 days after evidence of fertilization but limits it according to ethical guidelines. The Committee recommends that cryopreserved embryos be the preferred source for research but believes that the promise of somatic cell nuclear transfer is such that research in this area is justified. The Committee opposes reproductive cloning. Intended parents for whom embryos are created should give informed consent for the disposition for any excess embryos. The donors of gametes or somatic cells used in the creation of such tissue should give consent for donation of embryos for research. Potential research projects should be described to potential donors as much as possible. Donation of embryos for stem cell research requires specific consent. The Committee believes that compensation for egg donors for research is acceptable, consistent with American Society for Reproductive Medicine guidelines.

In August 2004, Stojkovic and Murdoch from the University of Newcastle upon Tyne, UK, were granted the UK's first license to create human embryonic stem cells (hESCs) using cell nuclear replacement. While this news made headlines around the globe, a spokesman for the German Ministry of Research warned scientists in his country of the illegality of advising their English colleagues on hESC research. Meanwhile, US Members of Congress had asked President Bush to revoke his decision to limit federal funding to research on a limited number of hESC lines created before 9 August, 2001 (a decision that he confirmed in July 2006, while nonfederally funded research on hESC continues to be unrestricted). In Israel, where hESC research is legal and has never been a contested political issue, a bioethicist argued that, in light of the potential to alleviate human suffering, "banning research is against human dignity". How can such striking differences in the regulation of hESC research be explained?

The aim of regenerative medicine is to reconstruct tissue that has been lost or pathologically altered. Therapeutic cloning seems to offer a method of achieving this aim; however, the ethical debate surrounding human therapeutic cloning is highly controversial. Artificial parthenogenesis-obtaining embryos from unfertilised eggs-seems to offer a way to sidestep these ethical pitfalls. Jacques Loeb (1859-1924), the founding father of artificial parthenogenesis, faced negative public opinion when he published his research in 1899. His research, the public's response to his findings, and his ethical foundations serve as an historical argument both for the communication of science and compromise in biological research.

Training in genetics in Edinburgh in the 1950s led to a PhD on the developmental biology of mouse embryos with unusual chromosomal complements. Fundamental aspects of reproduction under study included ovulation induction, oocyte maturation and embryonic growth to blastocysts. It led to the introduction of embryo stem cells, preimplantation genetic diagnosis, the exact timing of human oocyte maturation in vitro and studies on fertilising human eggs in vitro to alleviate human infertility. My work was helped by studies on sperm capacitation and the physiology of fertilization in domestic and laboratory species by Thibault, Dauzier, Austin, Chang, Yanagimachi and others. I met Charles Thibault at a meeting in Cambridge U.K. where he criticised the work of Moricard, and then frequently on lecture circuits. Impressed by his grandeur but not his doubts about human IVF, Steptoe and I initiated human embryo transfers and the birth of Louise Brown. Details of her pregnancy had to be confidential to reduce the risks of abortion associated with the intrusion of numerous newsmen chasing the story. I was compelled to withold this information at a meeting in Paris in the late 1960s when I had to leave early to return to UK. This omission annoyed Thibault and led to our celebrated quarrel. I felt he failed to appreciate the complexity, the implications of this pregnancy and an astonishing future. So much was at stake, including IVF, stem cells and preimplantation diagnosis to help millions of patients. Some months later, our dispute was ended even if somewhat formally. Nevertheless it is a pleasure to recall how we shared so much in common. I still admire him as an inspiration to many colleagues and students, and a father figure in French agricultural research.

Since its inception, the Health Council of the Netherlands has included normative aspects in its reports. Over the past decades, ethics and rights have received increasing attention, particularly since the establishment of the Standing Committee on Medical Ethics and Health Law in 1977. In particular, the ethical implications of bio-molecular life sciences (genetic counselling, genetic screening, research with human embryos) have been discussed in the Council's publications. The Council has also been involved from an early stage in the euthanasia discussion. It is accepted that policy advice concerning scientific developments implies normative considerations. However, the extent to which the Council's role is simply to highlight these considerations or to present conclusions remains a recurring question. In the latter case, priority is often given to the principle of respect for autonomy, while underestimating the significance of solidarity.