Non-medical or Social egg freezing (oocyte cryopreservation) is currently a controversial topic in Islam, with contradictory fatwas being issued in different Muslim countries. While Islamic authorities in Egypt permit the procedure, fatwas issued in Malaysia have banned single Muslim women from freezing their unfertilized eggs (vitrified oocytes) to be used later in marriage. The underlying principles of the Malaysian fatwas are that (i) sperm and egg cells produced before marriage, should not be used during marriage to conceive a child; (ii) (...) extraction of mature egg cells from single women being unacceptable; and (iii) fertility preservation in anticipation of late marriage is a conjecture that has not yet occurred. Ovarian tissue freezing can potentially be a more Shariah-compliant alternative to social egg freezing, because once the frozen ovarian cortical tissue sections have been re-transplanted back into the woman, mature egg cells can readily be produced, collected, and fertilized by the husband’s sperm only during the period of marriage contract (′akd al-nikāḥ). Unlike accidental mix-ups with frozen eggs, muddling of lineage (nasab) would be automatically avoided in ovarian tissue freezing due to immunological rejection. However, upon critical analysis based on Qawā’id Fiqhiyyah (Islamic Legal Maxims), Maqāṣid-al-Shariah (Higher Objectives of Islamic Law), and Maslaḥah-Mafsadah (benefits versus harmful effects on society), elective ovarian tissue freezing by healthy single women for social reasons would likely be a highly contentious and controversial issue within Muslim communities that may conflict with conservative social-religious norms. This thus needs further debate among Islamic jurists in dialogue with medical doctors and biomedical scientists. (shrink)

In recent years, progress in cancer treatment has greatly increased the chances of recovery. Yet, treatment may have irreversible effects on patients’ fertility. In order to protect future fertility, preservation of ovarian tissue may be offered today even to very young girls, involving a surgical procedure that may be performed by minimally invasive laparoscopy, under general anesthesia. However, in the tragic event of a girl’s death, questions may arise regarding the possible use of the preserved ovarian (...) class='Hi'>tissue by her parents. Should posthumous reproductive use of ovarian tissue without the girl’s prior consent (due to her young age) be considered a violation of her rights? On the other hand, can it be argued that it is in the interest of a child who died young to leave a genetic trace through posthumous reproduction, because genetic continuity is in the interest of every human being? After presenting the relevant clinical facts, we explore the ethical dimensions of this possible practice through an analysis of the interests of the deceased, her parents, and the child that may be born posthumously. (shrink)

The American Journal of Bioethics, Volume 12, Issue 6, Page 46-47, June 2012.

In the USA, one child in 285 children is diagnosed with cancer every year, but thanks to improvements in medicine, the survival rate has reached 80%. However, cancer treatments, such as chemotherapy and radiation, are likely to affect their fertility later in life, limiting their ability to conceive. To reduce this risk, ovarian tissue cryopreservation is a surgical procedure that allows the ovarian tissue to be retrieved and cryopreserved in order to be reimplanted back into the (...) abdomen and restore ovarian function in children who become infertile due to gonadotoxic treatments. A case study published in 2014 offered recommendations to help assess whether such a procedure should be offered to female patients who have not yet entered puberty. This paper will investigate whether, in light of more recent and updated literature, their recommendations may need to be revised. (shrink)

Oncofertility is one of the 9 NIH Roadmap Initiatives, federal grants intended to explore previously intractable questions, and it describes a new field that exists in the liminal space between cancer treatment and its sequelae, IVF clinics and their yearning, and basic research in cell growth, biomaterials, and reproductive science and its tempting promises. Cancer diagnoses, which were once thought universally fatal, now often entail management of a chronic disease. Yet the therapies are rigorous, must start immediately, and in many (...) cases result in premature failure of the body's reproductive ability. In women, this loss is especially poignant; unlike the routine storage of sperm, which is done in men and boys facing similar treatment decisions, freezing oocytes in anticipation of fertility loss is not possible in most cases, and creating an embryo within days of diagnosis raises significant moral, social and medical challenges. Oncofertility is the study of how to harvest ovarian tissue in women facing cancer to preserve their gametes for future use with IVF, thus allowing the decisions about childbearing to be deferred and reproductive choices to be preserved. The research endeavor uses the capacity of the ovarian follicle to produce eggs in vitro . Developing the human follicle to ovulate successfully outside the body is scientifically difficult and ethically challenging. Infertility is linked to long-standing religious and moral traditions, and is intertwined with deeply contentious social narratives about women, families, illness and birth. Is the research morally permissible? Perhaps imperative if understood as a repair from iatrogenic harms? How are considerations of justice central to the work? How will vulnerable subjects be protected? What are the moral implications of the work for women, children and families? What are the implications for society if women could store ovarian tissue as a way of stopping the biological clock? What are the moral possibilities and challenges if eggs can be produced in large quantities from a stored ovarian tissue? (shrink)

The American Journal of Bioethics, Volume 12, Issue 6, Page 50-52, June 2012.

Infertility affects 15 per cent of the world's couples. Research at Edinburgh University has been directed at transplanting fetal ovarian tissue into infertile women, thus enabling them to bear children. Fetal ovary transplantation (FOT) has generated substantial controversy; in fact, one ethicist deemed the procedure 'so grotesque as to be unbelievable' (1). Some have suggested that fetal eggs may harbour unknown chromosomal abnormalities: however, there is no evidence that these eggs possess a higher incidence of genetic anomaly than (...) ova found in a healthy adult female. There is also concern that fetal egg children will be psychologically harmed by the knowledge of their special conceptual status. It will be demonstrated that special conceptual status in and of itself does not determine developmental success. Rather, psychological well-being is dependent upon how the family and child cope with the unique challenges inherent in FOT. Lastly, though considering FOT a legitimate method of family building, given the global population crisis the wisdom of procreational rights will be challenged. Inherent to this challenge is a re-evaluation of the treatment of infertility as a significant disease necessitating remedy. (shrink)

Substantial medical evidence shows that about half of ovarian cancers originate in the fallopian tube. Some medical organizations and clinical articles have suggested opportunistic salpingectomy to reduce the risk of ovarian cancer in patients at average risk of developing it. This entails removing the fallopian tubes at the same time as another procedure that would occur anyway. The authors argue that the principles of totality and double effect can justify such salpingectomies, even though there is a low incidence (...) of ovarian cancer. Since screening tools for ovarian cancer are ineffective and treatment options are poor, the good effect of reducing the risk of death from this type of ovarian cancer can be proportionate to the bad effects of the minor increase in surgical risk over the other procedure, the unintended side effect of infertility, and the removal of normally functioning tissue. The authors conclude that it is within the purview of a patient and physician to determine whether the benefits are proportionate to the risks in a particular case. (shrink)

Although the term commodification is sometimes criticised as imprecise or overused, in fact it has a complex philosophical ancestry and can never be used too much, because the phenomena that it describes are still gaining ground. The issues that commodification raises in relation to reproductive technologies include whether it is wrong to commodify human tissues generally and gametes particularly, and whether the person as subject and the person as object can be distinguished in modern biomedicine. This chapter examines three areas (...) in which commodification is a serious concern for important reproductive technologies: the sale of eggs for IVF and research, the banking of umbilical cord blood, and the use of gestational surrogates both domestically and internationally. Sales of human eggs for IVF or research are frequently disguised as “gifts”, which conceals the very real bodily risks and harms associated with ovarian hyperstimulation and egg harvesting undergone by egg “donors.” Umbilical cord banking is a fast-growing industry, with donated cord blood trading globally at very high prices; women who consent to banking of cord blood ostensibly for the potential future benefit of their child may not be informed of the likelihood that it will be traded in commercial markets or that the method used for harvesting may increase risks of jaundice in their babies. Commercial surrogacy also exploits altruism but in addition involves wrongful sale of babies, particularly in the international context. In each example, the commodification of women’s reproductive labour is masked by the manner in which ‘the lady vanishes’ under a gift model, ignoring the true economic value of their labour. (shrink)

Ovarian tissue transplantation is an experimental procedure that can be used to treat both infertility and premature menopause. Working within the current legal framework in the USA, I examine whether ovarian tissue should be legally treated like gametes or organs in the case of ovarian tissue transplantation between two women. One option is to base classification upon its intended use: ovarian tissue used to treat infertility would be classified like gametes, and (...) class='Hi'>ovarian tissue used to treat premature menopause would be classified like organs. In the end, however, I argue that this approach will not work because it engenders too many legal, cultural and logistical concerns and that, at least for the near future, we should treat ovarian tissue like gametes. (shrink)

We report on the case of a 2-year-old female, the youngest person ever to undergo ovarian tissue cryopreservation (OTC). This patient was diagnosed with a rare form of sickle cell disease, which required a bone-marrow transplant, and late effects included high risk of future infertility or complete sterility. Ethical concerns are raised, as the patient's mother made the decision for OTC on the patient's behalf with the intention that this would secure the option of biological childbearing in the (...) future. Based on Beauchamp and Childress's principlism approach of respect for autonomy, nonmaleficence, beneficence, and justice, pursing OTC was ethically justified. (shrink)

The Future of Human Reproduction brings together new work, by an international group of contributors from various fields and perspectives, on ethical, social, and legal issues raised by recent advances in reproductive technology. These advances have put us in a position to choose what kindsof children and parents there should be; the aim of the essays is to illuminate how we should deal with these possibilities for choice. Topics discussed include gender and race selection, genetic engineering, fertility treatment, ovarian (...) tissue transfer, and post-menopausal pregnancy. The centralfocus of the volume is the interface between reproductive choice and public regulation. (shrink)

This commentary considers the viability of ovarian tissue cryopreservation (OTC) in the case of an adult who qualified for brain death. Although there has been some success with OTC in achieving pregnancy when the tissue is reimplanted in the original donor, attempting OTC in the case under discussion would have not been medically feasible.

Oncofertility is one of the 9 NIH Roadmap Initiatives, federal grants intended to explore previously intractable questions, and it describes a new field that exists in the liminal space between cancer treatment and its sequelae, IVF clinics and their yearning, and basic research in cell growth, biomaterials, and reproductive science and its tempting promises. Cancer diagnoses, which were once thought universally fatal, now often entail management of a chronic disease. Yet the therapies are rigorous, must start immediately, and in many (...) cases result in premature failure of the body's reproductive ability. In women, this loss is especially poignant; unlike the routine storage of sperm, which is done in men and boys facing similar treatment decisions, freezing oocytes in anticipation of fertility loss is not possible in most cases, and creating an embryo within days of diagnosis raises significant moral, social and medical challenges. Oncofertility is the study of how to harvest ovarian tissue in women facing cancer to preserve their gametes for future use with IVF, thus allowing the decisions about childbearing to be deferred and reproductive choices to be preserved. The research endeavor uses the capacity of the ovarian follicle to produce eggs in vitro. Developing the human follicle to ovulate successfully outside the body is scientifically difficult and ethically challenging. Infertility is linked to long-standing religious and moral traditions, and is intertwined with deeply contentious social narratives about women, families, illness and birth. Is the research morally permissible? Perhaps imperative if understood as a repair from iatrogenic harms? How are considerations of justice central to the work? How will vulnerable subjects be protected? What are the moral implications of the work for women, children and families? What are the implications for society if women could store ovarian tissue as a way of stopping the biological clock? What are the moral possibilities and challenges if eggs can be produced in large quantities from a stored ovarian tissue? (shrink)

The prelims comprise: Why Embryonic Stem Cells? Stem Cells for Organ and Tissue Transplant Immortality A Guarded Welcome for Stem Cell Research The Precautionary Principle The Ethics of ES Cell Research Stem Cells from Early Embryos The Moral Status of the Embryo Lessons from Sexual Reproduction Establishing a Pregnancy by Sexual Reproduction The Incoherence of Current US Federal Law The Symbolic Value of Life ART and Spare Embryos Tissue from Fetuses Doing Something Good is Better than Doing Nothing! (...) Interim Conclusions Genetic Identity Moral Complicity Acknowledgments. (shrink)

Certain kinds of medical treatment are often held to be morally unacceptable because they are an 'interference with nature'. I suggest a way in which we can make sense of such ideas. We can make significant choices only against a background of conditions which we regard as 'natural', and these will typically include such facts as those of birth and death, of youth and age, and of sexual relations. I argue, however, that such ideas, though intelligible, do not establish any (...) valid moral objection to, for instance, the use of ovarian tissue for assisted conception. (shrink)

Background Chemotherapy and/or radiotherapy treatments may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of therapies on future reproductive autonomy are a major concern. While a few options are open to post-pubertal patients, the only immediate option currently open to pre-pubertal girls is cryopreservation of ovarian tissue and subsequent transplantation. The aim of the study was to address a current gap in knowledge (...) regarding the offer of fertility preservation by Ovarian Tissue Cryopreservation for prepubescent girls with cancer, and to explore current practices and attitudes of Canadian, French and Moroccan pediatric heme oncologists. The comparative perspective is relevant since legal frameworks surrounding fertility preservation and funding offered by the healthcare system vary greatly. Methods An online survey was sent to the 45 pediatric oncology centers in Canada, France and Morocco. Results A total of 39 centers responded. OTC is offered by almost all pediatric heme oncologists in France, very few in Canada, and none in Morocco. For pediatric hematologists/oncologists who do not propose fertility preservation in Canada, the reasons are: the technique is still experimental, it is not available locally and cost of the technique for the family. 97% of Canadian and 100% of Moroccan pediatric hematologists/oncologists think OTC should be funded by the healthcare system as it is in France and in the province of Quebec in Canada. Conclusions The results of this study show tremendous diversity in the provision of OTC across countries, whereby its offer is correlated with legislation and funding. We argue that the current reality, in which this technology is often not offered to families, raises ethical issues related to justice and equity of access, as well as informed consent and future reproductive autonomy. (shrink)

In a landmark Fatwa, Saudi Arabia’s highest religious authority—The Council of Senior Scholars—declared the Islamic permissibility of oocyte cryopreservation. The fatwa sanctioned the retrieval, preservation, and future use of oocytes, ovarian tissue, and whole ovaries from cancer patients receiving gonadotoxic interventions. Although momentous, the fatwa’s specification of cancer patients effectively rendered this technology unavailable to others to whom it may be similarly beneficial, including patients with other medical conditions or patients seeking elective cryopreservation. This article argues in favor (...) of widening reproductive choices through expanded access to oocyte cryopreservation in Saudi Arabia—regardless of the underlying cause of infertility—on three grounds: the technology’s compliance with Islamic law, as a matter of fairness in medical practice, and as a means to support the well-being and flourishing of Saudi women within the context of a national societal and economic transformation strategy closely linked to their success. (shrink)

In 2003, The Guardian newspapers ran an article with the headline, “Prospect of babies from unborn mothers.” A team of Israeli researchers had been attempting to grow viable eggs from the ovarian tissue of aborted fetuses for use in fertility treatments such as IVF. The rhetoric of “unborn mothers” poses new challenges to the liberal feminist discourse of personhood. How do we articulate the ethical issues involved in harvesting eggs from an aborted fetus, without resurrecting the debate over (...) whether this fetus is a full-fledged person with, for example, rights to non-interference or freedom from harm? Can we coherently defend a woman’s right to terminate pregnancy without relinquishing a feminist position from which to critique the use of aborted fetuses in certain experimental procedures? In short, what happens when the “new” discourse of reproductive technology intersects with the “old” discourse of abortion? (shrink)

Members of the transforming growth factor beta (TGFβ) family are pleiotropic cytokines with key roles in tissue morphogenesis and growth. TGFβ1, TGFβ2 and TGFβ3 are abundant in mammalian reproductive tissues, where development and cyclic remodelling continue in post‐natal and adult life. Potential roles for TGFβ have been identified in gonad and secondary sex organ development, spermatogenesis and ovarian function, immunoregulation of pregnancy, embryo implantation and placental development. However, better tools must now be employed to map more precisely essential (...) functions and the regulatory networks governing their activity. Gene ablation and transgenic models are expected to provide novel insights into distinct physiological activities for each TGFβ isoform in normal reproductive function and reproductive pathologies. It is also necessary to consider the mechanisms controlling TGFβ activation from latent precursor forms, and receptor and binding protein expression. Smad intracellular signalling circuitry and modulation by environmental stimuli through cross‐talk with other signal transduction pathways will further constrain TGFβ action. This review examines existing evidence for TGFβ1, TGFβ2 and TGFβ3 regulation of male and female reproductive biology, and highlights prospects for future research. BioEssays 24:904–914, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Given an equal sex ratio at conception, the excess of human males at birth can only be explained by greater loss of females during pregnancy. It is proposed that the bias against females during human development is the result of a greater degree of genetic and metabolic “differentness” between female embryos and maternal tissues than for similarly aged males, and that successful implantation and placentation represents a threshold dichotomy, where the acceptance threshold shifts depending on maternal condition, especially stress. Right (...) and left ovaries are not equal, and neither are the eggs and follicular fluid that they produce, and it is further hypothesized that during times of stress, the implantation threshold is shifted sufficiently to favor survival of females, most likely those originating from the right ovary, and that this, rather than simply a greater loss of males, explains at least some of the variability in the human sex ratio at birth. (shrink)

The ovarian reserve defines female reproductive lifespan, which in humans spans decades. The ovarian reserve consists of oocytes residing in primordial follicles arrested in meiotic prophase I and is maintained independent of DNA replication and cell proliferation, thereby lacking stem cell‐based maintenance. Largely unknown is how cellular states of the ovarian reserve are established and maintained for decades. Our recent study revealed that a distinct chromatin state is established during ovarian reserve formation in mice, uncovering a (...) novel window of epigenetic programming in female germline development. We showed that an epigenetic regulator, Polycomb Repressive Complex 1 (PRC1), establishes a repressive chromatin state in perinatal mouse oocytes that is essential for prophase I‐arrested oocytes to form the ovarian reserve. Here we discuss the biological roles and mechanisms underlying epigenetic programming in ovarian reserve formation, highlighting current knowledge gaps and emerging research areas in female reproductive biology. (shrink)

Ex-vivo tissue engineering is a quickly developing medical technology aiming to regenerate tissue through the introduction of an ex-vivo created tissue construct instead of restoring the damaged tissue to some level of functionality. Tissue engineering is considered by some as a new medical paradigm. We analyse this claim and identify tissue engineering’s fundamental characteristics, focusing on the aim of the intervention and on the complexity and continuity of the process. We inquire how these features (...) have an impact not only on the scientific research itself but also on the ethical evaluation of this research. We suggest that viewing tissue engineering as a new medical paradigm allows us to develop a wider perspective for successful investigation instead of focusing on isolated steps of the tissue engineering process in an anecdotal way, which may lead to an inadequate ethical evaluation. We argue that the concept of tissue engineering as a paradigm may benefit the way we address the ethical challenges presented by tissue engineering. (shrink)

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

More and more areas of medicine involve subjects donating tissues to another — blood, organs, bone marrow, sperm, ova and embryos can all be transferred from one person to another. Within the technical frameworks of biomedicine, such fragments are generally treated as detachable things, severed from social identity once they are removed from a particular body. However an abundant anthropological and sociological literature has found that, for donors and patients, human tissues are not impersonal. They retain some of the values (...) of personhood and identity, and their incorporation often has complex effects on embodied identity. This article draws on feminist philosophy of the body to think through the implications of some of these practices. Specifically, it draws on the idea of intercorporeality, wherein the body image is always the effect of embodied social relations. While this approach is highly productive for considering the stakes involved in tissue transfer, it is argued that the concept of body image has been too preoccupied with the register of the visual at the expense of introceptive data and health/illness events. Empirical data around organ transplant and sperm donation are used to demonstrate that the transfer of biological fragments involves a profound kind of intercorporeality, producing identifications and disidentifications between donors and recipients that play out simultaneously at the immunological, psychic and social levels. (shrink)

Health research is increasingly being conducted on a global scale, particularly in the developing world to address leading causes of morbidity and mortality. While research interest has increased, building scientific capacity in the developing world has not kept pace. This often leads to the export of human tissue (defined broadly) from the developing to the developed world for analysis. These practices raise a number of important ethical issues that require attention.

Age‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase (...) in phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis. (shrink)

The controversies in Bristol, Alder Hey and elsewhere in the UK surrounding the removal and retention of human tissue and organs have led to extensive law reform in all three UK legal systems. This paper reports a short study of the reactions of a range of health professionals to these changes. Three main areas of ethical concern were noted: the balancing of individual rights and social benefit; the efficacy of the new procedures for consent; and the helpfulness for professional (...) practice of the new legislation and regulation. Recognition of these concerns may help in forging a new partnership between professionals and patients and their families. (shrink)

Historically, studies of the role of endogenous hormones in developmental differentiation of the sexes have suggested that mammalian sexual differentiation is mediated primarily by testicular androgens, and that exposure to androgens in early life leads to a male brain as defined by neuroanatomy and behavior. The female brain has been assumed to develop via a hormonal default mechanism, in the absence of androgen or other hormones. Ovarian hormones have significant effects on the development of a sexually dimorphic cortical structure, (...) the corpus callosum, which is larger in male than in female rats. In the females, removal of the ovaries as late as Day 16 increases the cross-sectional area of the adult corpus callosum. Treatment with low-dose estradiol starting on Day 25 inhibits this effect. Female callosa are also enlarged by a combination of daily postnatal handling and exogenous testosterone administered prior to Day 8. The effects of androgen treatment are expressed early in development, with males and testosterone-treated females having larger callosa than control females as early as Day 30. The effects of ovariectomy do not appear until after Day 55. These findings are more consistent with other evidence of a later sensitive period for ovarian feminization as compared to androgenic masculinization. (shrink)

Testicular tissue cryopreservation aims to preserve the future option of genetic reproduction for prepubescent cancer patients who are at risk of infertility as a result of their cancer therapies. This technology is experimental and currently only offered in the research context. As TTCP moves towards becoming more widely available, it is imperative that healthcare providers recognize the complex ethical issues surrounding this technology. This scoping review study identifies and assesses the range and depth of ethical concerns related to this (...) testicular tissue cryopreservation technology. At present, no such scoping review of ethical concerns exists in the TTCP literature. The forty-three full-text articles included in this study yielded twenty-two different ethical considerations discussed in relation to TTCP. It was observed that these ethical considerations fit within a mainstream Principlism approach to bioethics. Accordingly, there are ethical gaps in the TTCP literature that can be identified with alternative moral lenses. In particular, it was found that ethical concerns related to context and relational aspects of identity were absent in nearly all ethical examinations of TTCP. Furthermore, only 9 per cent of articles reviewed in this study focused primarily on the ethics of TTCP, thus demonstrating a need for further in depth ethical analyses of this technology. The results of this study are important for supporting the ethical provision of TTCP and can contribute to policy and guideline development. The findings of this study demonstrate the need for greater depth and diversity in analyses of ethical considerations related to this technology. (shrink)

Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non‐model organisms has revealed that a common set of genes underlie tooth‐forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints (...) act in parallel to shape the tooth throughout development. Here recent advances in understanding dental development from these studies are reviewed and important gaps that can be filled through continued application of evolutionary and biomechanical approaches are discussed. (shrink)

In mammals, a network of cellular circadian clocks organizes physiology and behavior along the 24‐h day cycle. The traditional hierarchical model of circadian clock organization with a central pacemaker and peripheral slave oscillators has recently been challenged by studies combining tissue‐specific mouse mutants with transcriptome analyses. First, a surprisingly small number of tissue rhythms are lost when only local clocks are ablated and, second, transcriptional circadian rhythms appear to be regulated by a complex mix of local and systemic (...) factors. As reviewed here, these findings suggest a more integrated model of clock network interaction with the central pacemaker as the main source of behavioral and systemic–physiological rhythms and peripheral clocks controlling some local rhythms while at the same time acting as gatekeepers that temporally adjust cellular responses to external stimuli. (shrink)

Cancer is the second leading cause of death in developed countries, making it a global public health problem. In this scenario, early detection is the key to successful treatment. Tissue biopsy, the current gold standard for cancer diagnosis, offers reliable results, but it is feasible only when the mass becomes detectable. On the other hand liquid biopsy, a promising experimental system, not yet implemented within clinical practice, allows early detection as its functioning relies on the analysis of body fluids. (...) Yet, its results are less reliable if compared to those of tissue biopsy as, for instance, false positives and false negatives might occur. Despite technical features, the tradeoff between a reliable diagnosis available at a later time and a potentially less reliable diagnosis available at an early stage poses significant ethical challenges in the clinical scenario which involve, among other aspects, informed consent, communication, and patient-physician encounter. (shrink)

Khalafzai, Rida Usman The legalization of egg donation for medical research has resulted in the use of assisted reproductive techniques for the creation of embryos for research. This carries significant risks for the women undergoing these procedures and has brought humankind to a major ethical and moral crossroads.

One important sense of 'global ethics' concerns the applied ethical issues arising in the context of economic globalisation. This article contends that we are beginning to witness the economic commodification and, concomitantly, the globalisation, of human tissue and the human genome. Policy-makers and local research ethics committees need to be aware that the relevant ethical questions are no longer confined to their old national or subnational context. A shift from questions of personal autonomy and identity can therefore be expected-towards (...) the more problematic issues of justice, exploitation and distribution. Here we can learn from the distinctions drawn in legal philosophy, such as the notion of property as a 'bundle' of rights, from which we may choose rights favouring the interests of vulnerable populations. We may also wish to apply the distinctions drawn by Calabresi and Melamed between pure property rules, modified alienability rules, and pure non-property regimes. Global ethics also concerns issues of value disparity across cultures, directing our attention to the moral beliefs of indigenous peoples, for example, whose DNA or tissue is increasingly of commercial importance. In examining case examples from Tonga and Aotearoa/new Zealand, I will consider the impact of indigenous belief systems and of neo-colonialism on indigenous peoples' perceptions of Western researchers. It is clear that many indigenous peoples reject both the pure property system and any modifications, insisting on a pure non-property regime. How can they then be protected in a globalised market system that so far favours the opposite end of the spectrum? (shrink)

There are complex unresolved ethical, legal and social issues related to the use of human tissues obtained in the course of research or diagnostic procedures and retained for further use in research. The question of intellectual property rights over commercially viable products or procedures that are derived from these samples and the suitability or otherwise of participants relinquishing their rights to the samples needs urgent attention. The complexity of these matters lies in the fact that the relationship between intellectual property (...) rights and ownership or rights pertaining to the samples on which the intellectual property right is based may either be overlooked or taken for granted. What equally makes the matter complex is that samples may be obtained from participants in developing countries and exported to developed countries for analysis and research. It is important for research ethics committees to tread carefully when reviewing research protocols that raise such issues for purposes of ensuring that appropriate benefit sharing agreements, particularly with developing countries, are in place.This paper attempts to analyse the key questions related to ownership and intellectual property rights in commercially viable products derived from human tissue samples. Patent law is used as a point of reference as opposed to other forms of intellectual property rights such as industrial designs because it is the right that most inventors apply for in respect of human tissue-related inventions. The key questions are formulated following a systematic analysis of peer reviewed journal articles that have reported original investigations into relevant issues in this field. Most of the cases and reported studies that are referred to in this paper do not directly deal with HIV/AIDS research but the underlying principles are helpful in HIV/AIDS research as well. Pertinent questions, which members of ethics review committees should focus on in this regard are discussed and suggestions on appropriate approaches to the issues are proposed in the form of specific questions that an ethics review committee should consider. Specific recommendations regarding areas for further research and action are equally proposed. (shrink)

Stem cell research has important implications for medicine. The source of stem cells influences their therapeutic potential, with stem cells derived from early-stage embryos remaining the most versatile. Somatic cell nuclear transfer (SCNT), a source of embryonic stem cells, allows for understandings about disease development and, more importantly, the ability to yield embryonic stem cell lines that are genetically matched to the somatic cell donor. However, SCNT requires women to donate eggs, which involves injection of ovulation-inducing hormones and egg retrieval (...) through laparoscopy or transvaginal needle aspiration. Risks from this procedure are fiercely debated, most notably risk of ovarian hyperstimulation syndrome (OHSS). This review examines risk of OHSS resulting from oocyte donation. We conclude that risk posed by OHSS in egg donation is not significant enough to warrant undue concern, and much of this can be eliminated when proper precautions are taken. This bears relevance to the future of stem cell research policymaking. (shrink)

We have rapidly gained insights into the presence and function of T lymphocytes in non‐lymphoid tissues, the tissue‐resident memory T (TRM) cells. The central pillar of adaptive immunity has been expanded from classic central memory T cells giving rise to progeny upon reinfection and effector memory cells circulating through the blood and patrolling the tissues to include TRM cells that reside and migrate inside solid organs and tissues. Their development and maintenance have been studied in detail, providing exciting clues (...) on how their unique properties used to fight infections may benefit therapies against solid tumors. We provide an overview of CD8 TRM cells and the properties that make them of interest for vaccination and cancer therapies. (shrink)

Three-dimensional ‘bioprinting’ is under development, which may produce living human organs and tissues to be surgically implanted in patients. Like tissue engineering and regenerative medicine generally, the process of bioprinting potentially disrupts experience of the human body by redefining understandings of, and becoming actualised in new practices and regimes in relation to, the body. The authors consider how these novel sociotechnical imaginaries may emerge, having regard to law’s contribution to, as well as its possible transformation by, the process of (...) 3D bioprinting. The authors draw on Gilbert Simondon and corporeal, material feminists to account for these disruptions as ‘ontogenetic,’ in the sense that technology can produce new ontologies or beings. The authors focus namely on ontogenesis, individuation and the pre-individual forces that comprise, and yet remain inexhausted by, the process of 3D bioprinting. The authors argue legal phenomena are pre-individual forces that ‘in-form’ ontogenesis. These pre-individual forces are indistinguishable from those implicated in the individuation of the body’s physical form; thereby, the individuation of the bodily material through 3D bioprinting may be expressive and generative of sociolegal phenomena, at least as those relate to the body. The authors conclude that 3D bioprinting shores up conventional, liberal conceptions in law of the human body as individual, bounded and primarily contractual. Three-dimensional bioprinting may introduce ontological difference to the extent it promises and realises a new temporality of the human as a species- and legal-subject, although such a development would only seem to expand, rather than attenuate, a biopolitical regime. (shrink)

Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT‐mediated NAD+ biosynthesis, together with its key downstream mediator, namely the NAD+‐dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue‐dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, (...) such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT‐mediated NAD+ biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD+ biology. (shrink)

Following new scientific evidence, removal of the fallopian tubes or the ovaries, or both, are options for reducing the risk of ovarian cancer. This paper examines the new scientific evidence on the origin of ovarian cancer and argues that the removal of fallopian tubes or ovaries in high-risk patients for the purpose of reducing risk of cancer is not intrinsically disordered. Although a present and serious pathology may not exist, this removal constitutes an indirect sterilization, because the immediate (...) and primary effect is the reduction in risk of a pathological condition. This effect occurs immediately, directly, and effectively, and sterilization is a secondary effect. The paper then reflects on the subsequent inadequacy of the language of “present and serious pathology” given the new evidence on ovarian cancer. National Catholic Bioethics Quarterly 14.1 : 67–79. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal (...) class='Hi'>tissue from induced abortion slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)