Anticipating in vitro gametogenesis: Hopes and concerns for IVG among diverse stakeholders.

In vitro gametogenesis (IVG), the reconstitution of germ cell development in vitro, is an emerging stem cell-based technology with profound implications for reproductive science. Despite researchers' long-term goals for future clinical applications, little is currently known about the views of IVG held by the stakeholders potentially most affected by its introduction in humans. We conducted focus groups and interviews with 80 individuals with lived experience of infertility and/or LGBTQ+ family formation in the US, two intersecting groups of potential IVG users. Respondents expressed hope that IVG would lead to higher reproductive success than current assisted reproductive technology (ART), alleviate suffering associated with ART use, and promote greater social inclusion, while expressing concerns predominantly framed in terms of equity and safety. These findings underscore the importance of sustained engagement with stakeholders with relevant experience to anticipate the implications of IVG for research and clinical translation.

Human embryo models made from pluripotent stem cells are not synthetic; they aren't embryos, either.

Embryo models are potentially highly impactful for human health research because their development recapitulates otherwise inaccessible events in a poorly understood area of biology, the first few weeks of human life. Casual reference to these models as "synthetic embryos" is misleading and should be approached with care and deliberation.

Physiological costs of undocumented human migration across the southern United States border.

Political, economic, and climatic upheaval can result in mass human migration across extreme terrain in search of more humane living conditions, exposing migrants to environments that challenge human tolerance. An empirical understanding of the biological stresses associated with these migrations will play a key role in the development of social, political, and medical strategies for alleviating adverse effects and risk of death. We model physiological stress associated with undocumented migration across a commonly traversed section of the southern border of the United States and find that locations of migrant death are disproportionately clustered within regions of greatest predicted physiological stress (evaporative water loss). Minimum values of estimated evaporative water loss were sufficient to cause severe dehydration and associated proximate causes of mortality. Integration of future climate predictions into models increased predicted physiological costs of migration by up to 34.1% over the next 30 years.

A planetary health perspective on synthetic methionine.

Methionine is an amino acid that humans and farm animals must derive from food. This metabolite, a tightly regulated resource in ecosystems, has become a mass commodity in the global economy, with well over 1 million tons being produced annually from petroleum to fortify livestock feed. Viewed from the standpoint of planetary health, anthropogenic methionine synthesis is an important enabler of low-cost animal protein production, with interdependent but unexamined effects on human health and ecosystems. At a time when agrochemical engineering is shifting the way sulphur is assimilated and moves up our food chain, research suggests that dietary methionine restriction alone captures many healthspan benefits noted with calorie restriction. As such, methionine synthesis is an excellent exemplar of planetary scale anthropogenic activity that manifests at the molecular scale of cellular metabolism, with potential systemic effects on human health. In this Personal View we establish the scale and historical trajectory of the methionine industry and provide a preliminary model for tracing this amino acid through the food supply into the human body. We draw together insights across disparate publications of applied animal agriculture, human nutrition, and biomedical research to call for cross-disciplinary dialogue on responsible use of methionine-augmentation technologies.

Heritable changeability: Epimutation and the legacy of negative definition in epigenetic concepts.

Epigenetic concepts are fundamentally shaped by a legacy of negative definition, often understood by what they are not. Yet the function and implication of negative definition for scientific discourse has thus far received scant attention. Using the term epimutation as exemplar, we analyze the paradoxical like-but-unlike structure of a term that must simultaneously connect with but depart from genetic concepts. We assess the historical forces structuring the use of epimutation and like terms such as paramutation. This analysis highlights the positive characteristics defining epimutation: the regularity, oxymoronic temporality, and materiality of stable processes. Integrating historical work, ethnographic observation, and insights from philosophical practice-oriented conceptual analysis, we detail the distinctive epistemic goals the epimutation concept fulfils in medicine, plant biology and toxicology. Epimutation and allied epigenetic terms have succeeded by being mutation-like and recognizable, yet have failed to consolidate for exactly the same reason: they are tied simultaneously by likeness and opposition to nouns that describe things that are assumed to persist unchanged over space and time. Moreover, negative definition casts the genetic-epigenetic relationship as an either/or binary, overshadowing continuities and connections. This analysis is intended to assist practitioners and observers of genetics and epigenetics in recognizing and moving beyond the conceptual legacies of negative definition.

Heavy Metal Toxicity in Armed Conflicts Potentiates AMR in A. baumannii by Selecting for Antibiotic and Heavy Metal Co-resistance Mechanisms.

Acinetobacter baumannii has become increasingly resistant to leading antimicrobial agents since the 1970s. Increased resistance appears linked to armed conflicts, notably since widespread media stories amplified clinical reports in the wake of the American invasion of Iraq in 2003. Antimicrobial resistance is usually assumed to arise through selection pressure exerted by antimicrobial treatment, particularly where treatment is inadequate, as in the case of low dosing, substandard antimicrobial agents, or shortened treatment course. Recently attention has focused on an emerging pathogen, multi-drug resistant A. baumannii (MDRAb). MDRAb gained media attention after being identified in American soldiers returning from Iraq and treated in US military facilities, where it was termed "Iraqibacter." However, MDRAb is strongly associated in the literature with war injuries that are heavily contaminated by both environmental debris and shrapnel from weapons. Both may harbor substantial amounts of toxic heavy metals. Interestingly, heavy metals are known to also select for antimicrobial resistance. In this review we highlight the potential causes of antimicrobial resistance by heavy metals, with a focus on its emergence in A. baumanni in war zones.

Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark.

The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies.

Environmental Politics of Reproduction.

What constitutes "human reproduction" is under negotiation as its biology, social nature, and cultural valences are increasingly perceived as bound up in environmental issues. This review maps the growing overlap between formerly rather separate domains of reproductive politics and environmental politics, examining three interrelated areas. The first is the emergence of an intersectional environmental reproductive justice framework in activism and environmental health science. The second is the biomedical delineation of the environment of reproduction and development as an object of growing research and intervention, as well as the marking off of early-life environments as an "exposed biology" consequential to the entire life span. Third is researchers' critical engagement with the reproductive subject of environmental politics and the lived experience of reproduction in environmentally dystopic times. Efforts to rethink the intersections of reproductive and environmental politics are found throughout these three areas.

It is what it eats: Chemically defined media and the history of surrounds.

The cultivation of living organs, cells, animals, and embryos in the laboratory has been central to the production of biological knowledge. Over the twentieth century, the drive to variance control in the experimental setting led to systematic efforts to generate synthetic, chemically defined substitutes for complex natural foods, housing, and other substrates of life. This article takes up the history of chemically defined media with three aims in mind. First, to characterize patterns of decontextualization, tinkering, and negotiation between life and experimenter that occur across disparate histories of cultivation. Second, to highlight the paradoxical historicity of cultivated organisms generated to be freed from context, as they incorporate and embody the purified amino acids, vitamins, plastics, and other artificial supports developed in the name of experimental control. Third, to highlight the figure-ground reversal that occurs as these cells and organisms are reconsidered as accidentally good models of life in industrialized conditions of pollution and nutrient excess, due to the man-made nature of their surrounds. Methodologically, the history of surrounds is described as an epigenetic approach that focuses on the material relations between different objects and organisms previously considered quite separately, from explanted organs to bacteria to plant cells to rats to human embryos.

Antibiotic Resistance and the Biology of History.

Beginning in the 1940s, mass production of antibiotics involved the industrial-scale growth of microorganisms to harvest their metabolic products. Unfortunately, the use of antibiotics selects for resistance at answering scale. The turn to the study of antibiotic resistance in microbiology and medicine is examined, focusing on the realization that individual therapies targeted at single pathogens in individual bodies are environmental events affecting bacterial evolution far beyond bodies. In turning to biological manifestations of antibiotic use, sciences fathom material outcomes of their own previous concepts. Archival work with stored soil and clinical samples produces a record described here as 'the biology of history': the physical registration of human history in bacterial life. This account thus foregrounds the importance of understanding both the materiality of history and the historicity of matter in theories and concepts of life today.

How The Genome Got a Life Span.

In the space of little more than a decade, ideas of the human genome have shifted significantly, with the emergence of the notion that the genome an individual changes with development, age, disease, environmental inputs, and time. This paper examines the emergence of the genome with a life span, one that experiences drift, instability and mutability, and a host of other temporal changes. We argue that developments in chromatin biology have provided the basis for this genomic embodiment of experience and exposure. We analyze how time has come to matter for the genome through chromatin, providing analysis of examples in which the human life course is being explored as a set of material changes to chromatin. A genome with a lifespan aligns the molecular and the experiential in new ways, shifting ideas of life stages, their interrelation, and the temporality of health and disease.

Creeping, drinking, dying: the cinematic portal and the microscopic world of the twentieth-century cell.

Film scholars have long posed the question of the specificity of the film medium and the apparatus of cinema, asking what is unique to cinema, how it constrains and enables filmmakers and audiences in particular ways that other media do not. This question has rarely been considered in relation to scientific film, and here it is posed within the specific context of cell biology: What does the use oftime-based media such as film coupled with the microscope allow scientists to experience that other visualization practices do not? Examining three episodes in the twentieth-century study of the cell, this article argues that the apparatus ofmicrocinematography constitutes what might be thought of as a technical portal to another world, a door that determines the experience of the world that lies on the other side of it. In this case, the design of apparatuses to capture time-lapsed images enabled the acceleration of cellular time, bringing it into the realm of human perception and experience. Further, the experience of the cellular temporal world was part of a distinct kind of cell biology, one that was focused on behavior rather than structure, focused on the relation between cells, and between the cell and its milieu rather than on cell-intrinsic features such as chromosomes or organelles. As such, the instruments and technical design of the microcinematographic apparatus may be understood as a kind of materialized epistemology, the history of which can elucidate how cinema was and is used to produce scientific knowledge.

Food as exposure: Nutritional epigenetics and the new metabolism.

Nutritional epigenetics seeks to explain the effects of nutrition on gene expression. For social science, it is an area of life science whose analysis reveals a concentrated form of a wider shift in the understanding of food and metabolism. Rather than the chemical conversion of food to energy and body matter of classic metabolism, food is now also a conditioning environment that shapes the activity of the genome and the physiology of the body. It is thought that food in prenatal and early postnatal life impacts adult-onset diseases such as diabetes and heart disease; exposure to food is seen as a point of potential intervention in long-term health of individuals and populations. This article analyzes how food has become environment in nutritional epigenetics, with a focus on the experimental formalization of food. The experimental image of human life generated in rodent models, it is argued, generates concepts of food as a form of molecular exposure. This scientific discourse has profound implications for how food is perceived, manufactured and regulated, as well as for social theories and analyses of the social body that have a long history of imbrication with scientific models of metabolism.