Although many of the most vexing complications of human pregnancy, including sporadic and recurrent early pregnancy loss, preeclampsia, intrauterine growth restriction, molar pregnancies, and placenta accreta/increta/percreta likely have their origins in very early placental developmental abnormalities, our understanding of these abnormalities remains frustratingly limited. This deficit is inherent to the placenta because access to primary early human gestational tissues is very limited, for ethical and logistical reasons. Comparative placentation among mammalian species reveals the human placenta to be quite unique and limits the utility of animal modelling. In vitro models of human trophoblast differentiation are likewise limited by tissue access, spontaneous differentiation of primary trophoblast cells in culture and the transformation process or neoplastic processes that make stable cell lines immortal. Notable differences in placental development and function among racial groups highlight the need to address social determinants of health when studying early placental development and related pregnancy outcomes. Stem cell-derived models of in vitro trophoblast differentiation, including human embryonic stem cell (hESC)-- and induced pluripotent stem cell (iPSC)-technologies, may provide unique systems in which to reliably study the earliest events in normal and abnormal human placental development.

In Parkinson’s disease, parkinsonism occurs due to the loss of dopaminergic neurons of the substantia nigra. Existing treatments can enhance dopaminergic activity in the brain, but cause adverse effects due to the non-targeted, non-physiologic dopamine delivery, so there is interest in developing regenerative therapies to restore dopaminergic tone in the striatum in a targeted, physiologic manner. Experimental approaches include using viral vectors to deliver genes encoding growth factors or enzymes involved in dopamine synthesis, or to target nucleic acids and gene expression. A number of cell types have been considered potential sources of cell-based therapies for PD and have been trialled in humans and animals, but all have been limited by either poor efficacy, poor graft survival, or logistical barriers. However, stem cells offer a renewable source of dopaminergic cells and hold great promise as potential regenerative treatments, and human trials have begun. Although these treatments remain experimental, some are entering clinical trials and there is hope that they will become available for clinical use in the future.

In Chapter 17, the topic of organismal cloning is described, noting the difference between reproductive and therapeutic cloning. Preformationism and epigenesis (as concepts of development), and the work in the early 1900s that led to the development of the concept of nuclear totipotency, are outlined. As the concept was refined, cells that are pluripotent, multipotent or irreversibly differentiated were described. Cloning using nuclear transfer was first proposed in 1938, and achieved in 1952. More correctly known as somatic cell nuclear transfer (SCNT), the birth of Dolly in 1996 was a milestone in that she was the first mammal to be cloned using a fully differentiated somatic cell as the source of the donor nucleus.

This chapter explores two case histories where American politicians appear to have sided with intense minorities over less-intense majorities. First, I present the case of federal funding for stem cell research in the early 2000s. I find evidence that majorities supported allocating federal health research funds toward research using embryonic stem cells yet federal policy remained stringent for most of the decade. Second, I present the case of firearm regulation following the mass shooting at Sandy Hook Elementary School in 2012. Although large majorities indicated support for new regulation of firearms, no new regulations passed Congress. An intense minority appears to have used costly political action to communicate their strong opposition to new regulations.

The construction of governance frameworks for new health technologies is a complex process for most countries, particularly for developing countries. They must grapple with ‘old’ structures and ways of doing things while striving to plant the seeds of the ‘new’, which will put them on a higher level to promote science as well as access to new drugs and treatments. To achieve these goals, international collaboration is a key element. Argentina issued a regulation for advanced therapy medicinal products at the end of 2018. This chapter describes the objectives and actors involved in that process. It focuses on how internal tensions regarding whether to regulate were solved, considering the regulatory harmonisation process promoted by the European Medicines Agency and the US Food and Drug Administration, and the self-regulatory diversification promoted by China and other countries. Special mention is made of the importance of identifying social values and constructing a vision to guide the exercise of ‘foresight’ in law, which resulted in the design and implementation of the new regulation and governance of the system.

The availability of new cellular technologies, such as human-induced pluripotent stem cells have opened possibilities to significantly ‘humanise’ the biology of experimental and model organisms in laboratory settings. With greater quantities of genetic sequences being manipulated and advances in embryo and stem cell technologies, it is increasingly possible to replace animal tissues and cells with human tissues and cells. The resulting chimeric embryos and organisms are used to support basic research into human biology. This chapter investigates these transformations in the area of interspecies mammalian chimera. The chapter will explore how human-animal chimeras become objects of regulatory controversy and agreement depending on the concepts, tools and materials used to make them. The final sections of the chapter provide some reflections on the future of chimera-based research for human health, which, as we argue, calls forth a reassessment of regulatory boundaries between human subjects and experimental animals. We argue that interspecies research poses pressing questions for the regulatory structures of biomedicine, especially health research regulation systems’ capacity to simultaneously care for and realign the human and animal vulnerabilities at stake within interspecies chimera research and therapeutic applications.

The traditional notion of the embryo as the developmental phase in which, starting from an undisputable origin (egg, seed) the outline of the bodily architecture of a multicellular organism is shaped, deserves critical discussion. Development does not necessarily have a recognizable starting point. Some of the cells deriving from the zygote may not contribute to the embryo. There are significant differences between the early developmental stages of animals and plants. In animals, at the end of embryonic development the entire structure of the organism is almost always delineated. In plants, the seedling formed during the so-called embryonic development contains only the shoot with the first leaves and the radicle, while the entire structure of the plant, including almost all the leaves and all the flowers, will form from groups of stem cells generated through the entire life of the plant. Development does not necessarily produce an increasing division of labour. Development is not necessarily irreversible. Individual organs are not the products of a distinct developmental process. Differences between species do not always increase progressively from the egg on.

Knowledge and understanding of the appearance of normal bone marrow (BM) and therefore normal haematopoiesis is essential for both general pathologists and specialist haematopathologists. It is only once normal cytology and histology is understood that abnormalities can be identified and defined, leading to the accurate diagnosis of pathologies seen in the BM.

The rapid advance of research in stem cells has opened the door for their potential use in cell-based therapies to treat neurological conditions some of them incurable to date. Encouraging studies in animal models are moving into early phase clinical trials that hold realistic promise for the future. However, important ethical challenges remain as stem cells are translated from preclinical research to the clinical realm.Translation of stem cell–based therapies must be framed within a rigorous scientific and ethical process. This framework extends to the continuum of basic science in the laboratory, subsequent animal studies to the execution of early and late phase clinical trials in humans.Neurosurgery will play a fundamental role in the stem cell therapies of the future. New neurosurgical techniques and instruments will be developed for the delivery of stem cells to single or multiple targets within the CNS. Neurosurgeon’s roles will expand as stem cells move from clinical trials to effective potential therapies. This chapter will review selected stem cell ethical issues, that may inform and guide the practicing neurosurgeon in a rapidly moving field of great scientific promise, as well as ethical challenges

In France, civil law provisions on research involving human subjects, on donation and use of human body parts, and on medically assisted reproduction – originally developed between 1988 and 1994 and generally referred to as loi de bioéthique (law on bioethics) – specify whether and under which statutory conditions activities potentially leading to human germline genome modification can be undertaken. International law, including European law, poses further conditions. This chapter explores legislative and regulatory constraints on this type of research in France, analyzing how they developed over time to reach their present state. We will show that, in France, it is prohibited to create a human embryo solely for research purposes; that, however, research activities on supernumerary embryos and human embryonic stem cells are possible upon authorization by the national agency on biomedicine; but that, nevertheless, alterations to the genome of an embryo under circumstances that allow the modifications to pass on to future generations (i.e. through a successful pregnancy) are strictly prohibited. A peculiar feature of French legislation in this domain is that the law on bioethics is regularly updated in light of new technological or scientific developments, and as a result of a national public consultation held at least every five years. In 2018 one such rounds of public consultation took place, and a report summarizing its outcome is now being considered as the basis for possible legislative reform – including in the domain of genetic engineering. While it is not possible to anticipate future legislative developments, the report signals some degree of openness in the French civil society regarding the use of genetic engineering and genome editing, at least in the context of research.