Plant reproduction is vital for species survival, and is also central to the production of food for human consumption. Seeds result from the successful fertilization of male and female gametes, but our understanding of the development, differentiation of gamete lineages and fertilization processes in higher plants is limited. Germ cells in animals diverge from somatic cells early in embryo development, whereas plants have distinct vegetative and reproductive phases in which gametes are formed from somatic cells after the plant (...) has made the transition to flowering and the formation of the reproductive organs. Recently, novel insights into the molecular mechanisms underlying male germ‐line initiation and male gamete development in plants have been obtained. Transcriptional repression of male germ‐line genes in non‐male germ‐line cells have been identified as a key mechanism for spatial and temporal control of male germ‐line development. This review focuses on molecular events controlling male germ‐line development especially, on the nature and regulation of gene expression programs operating in male gametes of flowering plants. BioEssays 29:1124–1132, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

This essay examines the arguments for and against working towards the objective of human germ line engineering for medical purposes. Germ line changes which result as a secondary consequence of other well designed and ethically acceptable manipulations of somatic cells to cure an otherwise fatal disease can be seen as acceptable. More serious objections apply to intentional germ line interventions because of the unacceptability of using a person solely as a vehicle for creating uncertain genetic change (...) in his descendants. It is also morally unacceptable to use the promise of future benefit to experiment on fetuses or embryos when other more effective technologies exist to help parents have healthy children. Using new genetic technologies to select desirable genotypes among gametes is less problematic and affords a promising new technique for avoiding intergenerational harms. Keywords: embryo research, germ line manipulation, intergenerational ethics, secondary germ line effects CiteULike Connotea Del.icio.us What's this? (shrink)

The teratogenic effect of ethanol on human and animal embryos is now well documented. Recent studies have clearly demonstrated that ethanol and related spindle‐acting agents may additionally interfere with normal meiotic chromosome segregation during oocyte maturation, leading to the production of aneuploid embryos. The mode of action, and potential hazard posed by these agents is considered.

The line between Germ-Line genetic therapy and somatic cell is more and more difficult to discern. With new abilities to effect Germ-Line genetic therapy it is less clear why such therapy should not be undertaken. Nonetheless, questions persist as to who is the patient in such therapy and about the extent of discretion that should be allowed prospective parents and the physician/researcher. Keywords: embryo, Germ-Line, patient, somatic therapy CiteULike Connotea Del.icio.us What's this?

Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the stem cells generate tumors (...) in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy. (shrink)

Among emotions, surprise has been extensively studied in psychology. In linguistics, surprise, like other emotions, has mainly been studied through the syntactic patterns involving surprise lexemes. However, little has been done so far to correlate the reaction of surprise investigated in psychological approaches and the effects of surprise on language. This cross-disciplinary volume aims to bridge the gap between emotion, cognition and language by bringing together nine contributions on surprise from different backgrounds - psychology, human-agent interaction, linguistics. Using different (...) methods at different levels of analysis, all contributors concur in defining surprise as a cognitive operation and as a component of emotion rather than as a pure emotion. Surprise results from expectations not being met and is therefore related to epistemicity. Linguistically, there does not exist an unequivocal marker of surprise. Surprise may be either described by surprise lexemes, which are often associated with figurative language, or it may be expressed by grammatical and syntactic constructions. Originally published as a special issue of Review of Cognitive Linguistics 13:2 (2015). (shrink)

Recently, Chinese researchers published the results of their research using a gene-editing technology on abnormal human zygotes. The research team believes this research has prospective clinical application, viz., for gene therapy for?-thalassemia, a white blood cell disorder, and plan to persist with further studies, despite technical problems in this experiment. The research has elicited international criticism from both scientific and bioethics domains, because it innovates beyond the current global consensus against human germ line modification. This paper (...) comments on some ethical issues presented by the research report and concludes that, under present circumstances, the Chinese research team did not meet a standard of scientific responsibility.Bangladesh Journal of Bioethics 2015 Vol.6 (1):22-26. (shrink)

Although the ability to perform gene therapy in human germ-line cells is still hypothetical, the rate of progress in molecular and cell biology suggests that it will only be a matter of time before reliable clinical techniques will be within reach. Three sets of arguments are commonly advanced against developing those techniques, respectively pointing to the clinical risks, social dangers and better alternatives. In this paper we analyze those arguments from the perspective of the client-centered ethos that (...) traditionally governs practice in medical genetics. This perspective clarifies the merits of these arguments for geneticists, and suggests useful new directions for the professional discussion of germ-line gene therapy. It suggests, for example, that the much discussed prospect of germ-line therapy in human pre-embryos may always be more problematic for medical genetics than adult germ-line interventions, even though the latter faces greater technical difficulties. (shrink)

In 1982, the President's Commission produced its report on human gene therapy. One of that report's recommendations was to expand the Recombinant DNA Advisory Committee to the National Institutes of Health to include a subcommittee on human gene therapy. In 1984, the Human Gene Therapy Subcommittee was established, and in 1989 it produced a document—“Points to Consider for Protocols for the Transfer of Recombinant DNA into Human Subjects”—that stated the RAC's position on what sorts of protocols (...) it would approve.In assessing the impact of the President's Commission report, Alexander Capron wrote,[t]he line [the report] drew between somatic cell and germ-line therapies has shaped subsequent discussions and policy formulation. Its conclusion … that somatic cell therapy resembles medical treatment is the basic premise of the RAC subcommittee's “Points to Consider,” while the Commission's view that ethical as well as technical barriers preclude present attempts to alter germ cells continues to be generally accepted by scientists and nonscientists alike. (shrink)

In 1982, the President's Commission produced its report on human gene therapy. One of that report's recommendations was to expand the Recombinant DNA Advisory Committee to the National Institutes of Health to include a subcommittee on human gene therapy. In 1984, the Human Gene Therapy Subcommittee was established, and in 1989 it produced a document—“Points to Consider for Protocols for the Transfer of Recombinant DNA into Human Subjects”—that stated the RAC's position on what sorts of protocols (...) it would approve.In assessing the impact of the President's Commission report, Alexander Capron wrote,[t]he line [the report] drew between somatic cell and germ-line therapies has shaped subsequent discussions and policy formulation. Its conclusion … that somatic cell therapy resembles medical treatment is the basic premise of the RAC subcommittee's “Points to Consider,” while the Commission's view that ethical as well as technical barriers preclude present attempts to alter germ cells continues to be generally accepted by scientists and nonscientists alike. (shrink)

Determinations of the ethical acceptability of genetic therapy have relied on several distinctions in attempts to separate ethically acceptable genetic therapy from those possible therapies that could lead to genetic modifications of future human beings. One distinction that has been proposed is that genetic modifications of human somatic cells is ethically acceptable but that Germ-Line genetics modifications would be ethically objectionable. This paper examines several serious difficulties which call into question the ethical relevance of a somatic/Germ-Line (...) distinction. Keywords: double effect, future generations, Germ-Line modification CiteULike Connotea Del.icio.us What's this? (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. (...) Be- cause the research involves the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

Recent results from studies on animals suggest that functional germ cells may be generated from human pluripotent stem cells, giving rise to three possibilities: research with these so‐called artificial gametes, including fertilization experiments in vitro; their use in vivo for therapy for the treatment of human infertility; and their use in assisted reproductive technologies in vitro. While the legal, philosophical, and ethical questions associated with these possibilities have been already discussed intensively in other countries, the debate in (...) Germany is still at its beginning. A systematic and detailed analysis of the legal framework in Germany is provided with regard to the three possibilities, including the applicable statutory laws as well as the constitutional law. The question emerges as to whether the statutory laws as well as the constitution justify a distinction to be made between embryos of artificial and natural origin. This question is subject to philosophical analysis, discussing the distinction between person and thing, dignity and price, personality and property, and nature and technique. As a result, the criterion of naturalness alone may not be sufficient to differentiate between embryos of natural and artificial origin, and other criteria need to be identified. (shrink)

types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for (...) determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. Keywords: genetic engineering, somatic cells, germ cells, enhancement, eugenics, humanhood CiteULike Connotea Del.icio.us What's this? (shrink)

Recombinant DNA technology will soon allow physicians an opportunity to carry out both somatic cell- and Germ-Line gene therapy. While somatic cell gene therapy raises no new ethical problems, gene therapy of gametes, fertilized eggs or early embryos does raise several novel concerns. The first issue discussed here relates to making a distinction between negative and positive eugenics; the second issue deals with the evolutionary consequences of lost genetic diversity. In distinguishing between positive and negative eugenics, the (...) concept of malady is applied as a definitional criterion for identifying genetic disorders that could qualify for Germ-Line therapy. Because gene replacement techniques are currently unavailable for humans, and because even if they were possible the number of people involved would be quite small, the loss of diversity concern seems moot. Finally, we dissuss the issue of iatrogenic disorders associated with gene therapy and discuss several ‘real world considerations.’. (shrink)

This essay develops a framework for thinking about the moral basis for the commodification of human reproductive materials. It argues that selling and buying gametes and genes is morally acceptable although there should not be a market for zygotes, embryos, or genomes. Also a market in gametes and genes should be regulated in order to address concerns about the adverse social consequences of commodification.

Technical, ethical, and social questions of germ-line gene interventions have been widely discussed in the literature. The majority of these discussions focus on planned interventions executed on the nuclear DNA (nDNA). However, human cells also contain another set of genes that is the mitochondrial DNA (mtDNA). As the characteristics of the mtDNA grossly differ from those of nDNA, so do the social, ethical, psychological, and safety considerations of possible interventions on this part of the genetic substance.

Technical, ethical, and social questions of germ-line gene interventions have been widely discussed in the literature. The majority of these discussions focus on planned interventions executed on the nuclear DNA (nDNA). However, human cells also contain another set of genes that is the mitochondrial DNA (mtDNA). As the characteristics of the mtDNA grossly differ from those of nDNA, so do the social, ethical, psychological, and safety considerations of possible interventions on this part of the genetic substance.

In lieu of an abstract, here is a brief excerpt of the content:Human Gene TherapyMary Carrington Coutts (bio)On September 14, 1990, researchers at the U.S. National Institutes of Health (NIH) performed the first approved gene therapy procedure on a four-year-old girl named Ashanti DeSilva. Born with a rare genetic disease, severe combined immune deficiency (SCID), Ashanti lacked a healthy immune system and was extremely vulnerable to infection. Children with SCID usually develop overwhelming infections and rarely survive to adulthood; even (...) a common childhood illness like chicken pox is life-threatening. Ashanti led a cloistered existence, avoiding contact with people outside her family, remaining in the sterile environment of her home, and battling frequent illnesses with massive amounts of antibiotics.In Ashanti's gene therapy procedure, her own white blood cells were genetically modified and then infused back into her bloodstream. Laboratory tests show that the therapy has strengthened Ashanti's immune system. She no longer has recurrent colds, has been allowed to attend school, and has been immunized against whooping cough. This gene therapy procedure is not a cure, however. The genetically-treated white blood cells only survive for a few months and must then be replaced, but Ashanti's future is much brighter because of the new therapy (VI, Thompson [The First] 1993).Although this simplified description of Ashanti's gene therapy procedure sounds like a happy ending, it is little more than an optimistic chapter in a long story. The road to the first approved gene therapy procedure was rocky and fraught with controversy. The biology of human gene therapy is very complex, and there are still many techniques that need to be developed and diseases that need to be understood more fully before gene therapy is well established. The public policy debate surrounding the possible use of genetically engineered material in human subjects is equally complex. Major participants in the debate come from the fields of biology, government, law, medicine, philosophy, politics, and religion, each bringing different views to the discussion.In studying the ethics of gene therapy, one should draw a distinction between [End Page 63] therapy on somatic (non-reproductive) cells and germ (reproductive) cells. Only the germ cells carry the genes that will be passed on to the next generation. Reactions to gene therapy have varied widely. Some commentators on gene therapy object to any form of genetic manipulation, no matter how well-intentioned (VI, Rifkin 1983). Another reaction is to allow the use of somatic-cell therapy, but not to approve the use of germ-line therapy, which could have unforeseeable effects on future generations. A different stance is that, with proper regulation and safeguards, germ-line gene therapy is a logical extension of the progress made to date and that it is an ethically acceptable procedure.TechniquesTo date, 43 research protocols have been approved for somatic-cell gene therapy in the United States. The techniques employed in each protocol vary, but in general a virus is used as a "vector" to insert the desired gene into the DNA of the patient's cells, in order to compensate for a defective gene. For Ashanti's gene therapy, this technique involved obtaining white blood cells and introducing properly functioning genes into as many of the cells as possible. The normal genes were delivered through the use of a specially-engineered virus.Although similar techniques are used in germ-line gene therapy, the procedure is more difficult. There are two basic ways to perform germ-line gene therapy: (1) to treat a preimplantation embryo that carries a serious genetic defect before its implantation in the mother, which necessitates the use of in vitro fertilization techniques; or (2) to treat the germ cells (sperm or egg cells) of afflicted adults so that the genetic defects would not be passed on to their offspring, which requires the technical expertise to delete the defective gene and insert a properly functioning replacement. Because of the complexity of the procedures involved and the attendant ethical controversy, germ-line therapy is not currently performed.Candidate Diseases for Gene TherapyAt present, gene therapy is likely to be most successful in treating diseases that are caused by single-gene defects and has been approved for treating diseases such... (shrink)

Elegant, suggestive, and clarifying, Lewis Thomas's profoundly humane vision explores the world around us and examines the complex interdependence of all things. Extending beyond the usual limitations of biological science and into a vast and wondrous world of hidden relationships, this provocative book explores in personal, poetic essays to topics such as computers, germs, language, music, death, insects, and medicine. Lewis Thomas writes, "Once you have become permanently startled, as I am, by the realization that we are a social species, (...) you tend to keep an eye out for the pieces of evidence that this is, by and large, good for us.". (shrink)

For nearly two centuries, developmental biologists have known that body organs are derived from distinct germ layers. They have argued that adult stem cells formed in one of these, mesoderm for example, cannot give rise to cells that originate in another. We disagree. An exception to this “rule” has been described in crayfish recently. In this species, hemocytes appear to replenish neurogenic cells. This may happen in humans as well. In women who were given male bone marrow‐derived cells, Y (...) chromosome positive cheek cells and brain neurons were detected. While repopulation of these tissues by bone marrow derived cells may not occur normally, and while it does not appear to be terribly efficient, the phenomenon should be studied in more detail. Perhaps cells in the marrow could be used to regenerate tissues elsewhere. (shrink)

Germ cells are cross-roads of development and evolution. They define the origin of every new generation and, at the same time, represent the biological end-product of any mature organism. Germ cells are endowed with the following capacities: to store a self-descriptive program, to accumulate a protein-synthesizing machinery, and to incorporate enough nourishment to sustain embryonic development. To accomplish this goal, germ cells do not simply unfold a pre-determined program or realize a sole instructive role. On the contrary, (...) due to the complexity of their cytoarchitecture and the nature of the soma-to-germ interactions, they are heavily involved in processes of sign recognition and meaningful tissue exploration. At each stage of their inward migration, germ plasma membranes act as semiotic interfaces allowing cells to interact with the surrounding extracellular milieu and experience the compatibility of selected developmental sequences. The question of which signaling pathways are activated at each developmental stage does not result from a strictly predetermined program instructing germ cell stemness. Rather, each developmental sequence is an open-ended semiotic relationship explored and gradually defined during evolution by the context-dependency of specific cell-to-cell interactions. In this way, any structural and functional novelty that has emerged in the course of germ cell interactions may be interpreted as an exaptation fixed in the species genome in response to specific environmental constraints. (shrink)

The rationale of patents on transgenic organisms leads to the startling notion of the human qua infringement. The moral reasons by which we may tenably reject such notion are not conclusive as to human life forms outside the body. A close look at recombinant DNA experimentation reveals ingenious processes, but not entities that the body lacks. Except for artificial genes, the genes of biotechnology are found on chromosomes, albeit nonconsecutively, and their uninterrupted transcripts appear in messenger RNA. An (...) enhanced form of protection for ingenious processes, the human methods patent, is proposed and defended as a replacement for product patents. The proposed patent would pertain to biotechnology manufacturing and genetic intervention in somatic and germ cells. A counterpart could govern nonhuman life forms. It is argued that compulsory licensing protections should be a condition of such patent. Contrary to the conservative assumption that statutory sobriquets suffice, the reckoning of what qualifies as a patentable ingenious process will continue to require systematic scientific guidance. (shrink)

The article investigates the validity of two different versions of the slippery slope argument construed in relation to human gene therapy: the empirical and the conceptual argument. The empirical version holds that our accepting somatic cell therapy will eventually cause our accepting eugenic medical goals. The conceptual version holds that we are logically committed to accepting such goals once we have accepted somatic cell therapy. It is argued that neither the empirical nor the conceptual version of the (...) argument can provide a conclusive moral reason for banning somatic cell therapy. According to a third interpretation, referred to as the arbitrary result argument, the many apparent similarities between somatic cell therapy and eugenic-based human genetic engineering drive us to make principled choices concerning what differences and similarities between the two practices should be regarded as morally (ir)relevant. Decisions of this kind are likely to have unpredictable moral consequences. Thus formulated, the slippery slope argument has much plausibility. One objects to somatic cell therapy not so much because of what is at the bottom of the slope on which it lies, but because it is on a slope of which one does not know what is at the bottom. While the arbitrary result argument does not provide a conclusive reason for prohibiting human gene therapy, it reminds of a very important thing: when making bioethical decisions, we should be as specific and as consistent as possible about our basic moral and medical concepts. (shrink)

Despite widespread agreement that it would be ethical to use somatic cell gene therapy to correct serious diseases, there is still uneasiness on the part of the public about this procedure. The basis for this concern lies less with the procedure's clinical risks than with fear that genetic engineering could lead to changes in human nature. Legitimate concerns about the potential for misuse of gene transfer technology justify drawing a moral line that includes corrective germline therapy but excludes (...) enhancement interventions in both somatic and germline contexts. Keywords: somatic cell, germ line, genetic diseases, genetic engineering, humanness, enhancement, eugenics CiteULike Connotea Del.icio.us What's this? (shrink)

The February 1997 announcement of the birth of Dolly, the sheep cloned from a mammary cell of an adult ewe, has drawn attention to the growing ability to select, alter, or otherwise manipulate the genome of offspring. Prior to Dolly, ethical discussion of genes in reproduction had focused on negative selection: carrier screening, prenatal diagnosis, and abortion or embryo discard. After Dolly, ethical debate will have to consider the direct or positive use of genetic selection or alteration technology.The principal (...) use of genetic selection techniques in human reproduction likely will be to treat or prevent disease in offspring. In the future, however, such techniques might also be used to enhance or even diminish expected characteristics of progeny. Techniques to accomplish these goals are likely to include: selection of the nuclear genome, as occurs in somatic cell cloning; chromosomal transplants; or direct insertion or deletion of specific genes. (shrink)

The February 1997 announcement of the birth of Dolly, the sheep cloned from a mammary cell of an adult ewe, has drawn attention to the growing ability to select, alter, or otherwise manipulate the genome of offspring. Prior to Dolly, ethical discussion of genes in reproduction had focused on negative selection: carrier screening, prenatal diagnosis, and abortion or embryo discard. After Dolly, ethical debate will have to consider the direct or positive use of genetic selection or alteration technology.The principal (...) use of genetic selection techniques in human reproduction likely will be to treat or prevent disease in offspring. In the future, however, such techniques might also be used to enhance or even diminish expected characteristics of progeny. Techniques to accomplish these goals are likely to include: selection of the nuclear genome, as occurs in somatic cell cloning; chromosomal transplants; or direct insertion or deletion of specific genes. (shrink)

:Any space program involving long-term human missions will have to cope with serious risks to human health and life. Because currently available countermeasures are insufficient in the long term, there is a need for new, more radical solutions. One possibility is a program of human enhancement for future deep space mission astronauts. This paper discusses the challenges for long-term human missions of a space environment, opening the possibility of serious consideration of human enhancement and a (...) fully automated space exploration, based on highly advanced AI. The author argues that for such projects, there are strong reasons to consider human enhancement, including gene editing of germ line and somatic cells, as a moral duty. (shrink)

The application of genetic editing techniques for the prevention or cure of disease is a highly promising tool for the future of humanity. However, its implementation contains a number of ethical and legal challenges that should not be underestimated. On this basis, some sectors have already asked for a veto on any intervention that modifies the human germ line, while supporting somatic line editing. In this paper, I will support that this suggestion makes no sense at all, because (...) the somatic/germ line disjunctive has no moral relevance and, therefore, it should not play any role in legal terms. I will provide a number of reasons to hold this assumption, such as the non‐sacred nature of the germ line, the difference between germ line and human genome modification, or the moral importance of the presence of a will to create modified descendants. While doing so, I will provide some examples of the different approaches to germ line editing adopted by different regulations so as to demonstrate that, contrary to what is sometimes stated, a general ban on this practice is not the rule, but the exception. Additionally, I will show how alternative options which currently exist, such as a selective ban based on criteria different to the germ line/somatic line distinction, match better with the need to conciliate research needs and legitimate ethical concerns. Finally, I will introduce some further suggestions to this same purpose. (shrink)

Human DNA can be cloned as yeast artificial chromosomes (YACs), each of which contains several hundred kilobases of human DNA. This DNA can be manipulated in the yeast host using homologous recombination and yeast selectable markers. In relatively few steps it is possible to make virtually any change in the cloned human DNA from single base pair changes to deletions and insertions. In order to study the function of the cloned DNA and the effects of the changes (...) made in the yeast, the human DNA must be transferred back into mammalian cells. Recent experiments indicate that large genes can be transferred from the yeast host to mammalian cells in tissue culture and that the genes are transferred intact and are expressed. Using the same methods it may soon be possible to transfer YAC DNA into the mouse germ line so that the expression and function of genes cloned in YACs can be studied in developing and adult mammalian animals. (shrink)

Any suggestion of altering the genetic makeup of human beings through gene therapy is quite likely to provoke a response involving some reference to a 'slippery slope'. In this article the author examines the topography of two different types of slippery slope argument, the logical slippery slope and the rhetorical slippery slope argument. The logical form of the argument suggests that if we permit somatic cell gene therapy then we are committed to accepting germ line gene therapy (...) in the future because there is no logically sustainable distinction between them. The rhetorical form posits that allowing somatic cell therapy now will be taking the first step on a slippery slope which will ultimately lead to the type of genocide perpetrated by the Nazis. The author tests the validity of these lines of argument against the facts of human gene therapy and concludes that because of their dependence on probabilities that cannot be empirically proven they should be largely disregarded in the much more important debate on moral line-drawing in gene therapy. (shrink)

The rationale for pursuing the development and use of Germ-Line selection and modification techniques is examined in this essay. The argument is put forth that it is the moral obligation of the medical profession to make available to the public any technology that can cure or prevent pathology leading to death and disability, in both the present and future generations. Society should pursue the development of strategies for preventing or correcting, at the Germ-Line level, genetic features that will (...) lead to, or enhance, pathological conditions. Because prenatal screening and even early embryo screening and selection can prevent only a subset of known genetic disorders, direct genetic intervention is the only way in which certain couples can exercise their rights to reproductive health. Finally, the arguments most often raised against the pursuit of and use of methods for Germ-Line intervention shall be discussed. Keywords: Germ-Line therapy, pre-implantation embryo screening gamete modification, risk and uncertainty CiteULike Connotea Del.icio.us What's this? (shrink)

Explains how and why laws against human germline modification will do more harm than good.

As the potential for the first human trials of somatic cell gene therapy nears, two ethical issues are examined: (1) problems of moral choice for members of institutional review boards who consider the first protocols, for parents, and for the clinical researchers, and the special protections that may be required for the infants and children to be involved, and (2) ethical objections to somatic cell therapy made by those concerned about a putative inevitable progression of genetic knowledge (...) from therapy to mass genetic engineering in human reproduction. The author's viewpoint is that a consensus exists on the required moral approach to somatic cell therapy, but that no moral approach yet exists for experiments beyond this level, especially in the germline cells of human beings. Keywords: gene therapy, somatic cells, germ cells, institutional review boards, genetic engineering CiteULike Connotea Del.icio.us What's this? (shrink)

More than thirty-four years after the United States Supreme Court initially recognized a woman’s constitutional right to choose whether or not to terminate a pregnancy (at least within the first two trimesters) in its landmark abortion decision Roe v. Wade, the issue of whether women ought to have this right continues to affect public debate. Presidential candidates are asked about the issue, and potential Supreme Court nominees and their prior judicial decisions, academic writings, and speeches are thoroughly scrutinized for any (...) inkling of how they would likely rule in a future case on the issue. Perhaps even more important is the way the debate over this issue has impacted federal funding for stem cell research in the United States. Because of moral concerns regarding the personhood status and level of dignity owed to the human embryo as a form of human life, in September of 1999, the National Bioethics Advisory Commission recommended against providing federal funding for the use and derivation of embryonic stem (ES) cells and embryonic germ (EG) cells except when obtained from “cadaveric fetal tissue” or “embryos remaining after infertility treatment.” In this article, I will suggest that the abortion debate and its offshoots into embryonic medical research persist because of a failure to properly separate human personhood from human biology. I will argue further that a proper analysis of the problem will not only enlighten the abortion and fetal tissue research debate, but will have implications for end-of-life issues as well. (shrink)

Should we change the human genome? The most general arguments against changing the human genome are here in focus. Distinctions are made between positive and negative gene therapy, between germ-line and somatic therapy, and between therapy where the intention is to benefit a particular individual (a future child) and where the intention is to benefit the human gene-pool.Some standard arguments against gene-therapy are dismissed. Negative somatic therapy is not controversial. Even negative, germ-line therapy is endorsed, (...) if the intention is to cure a certain individual (a future child). In rare cases, positive therapy on somatic cells may be warranted. Germ-line therapy may become a valuable method of preventing harm, through genetic vaccination. If safe methods evolve, it is harmless (though vain), to try to achieve more ambitious goals. Prospective parents should not be prevented from exercising this harmless kind of parental authority. (shrink)

Germ cell segregation and gamete production are developmental problems that all sexually reproducing species must solve in order to survive. Many people are familiar with the complex social structures of some insect species, where specialised castes of adult insects perform specific tasks, one of which is usually to guard the sexually reproductive queen. The parasitic wasp Copidosoma floridanum adds another level of complexity to the caste system: a fertilised egg produces both sterile, short‐lived “soldier” larvae and “reproductive” larvae (...) that complete metamorphosis to produce sexually reproductive adults. How two morphologically and functionally distinct larval castes are produced by genetically identical groups of cells developing under the same environmental conditions is a baffling problem. A recent paper suggests that differential germ cell segregation during embryogenesis may be an event both necessary and sufficient for caste determination.1 BioEssays 26:1263–1267, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Sex determination in the germ line may either rely on cell‐autonomous genetic information, or it may be imposed during development by inductive somatic signals. In Drosophila, both mechanisms contribute to ensure that germ cells are oogenic when differentiating in females and spermatogenic when differentiating in males. Some of the genes that are involved in germ line sex determination have been identified. In other species, including vertebrates, inductive signals are commonly used to determine the sex of (...) class='Hi'>germ cells. (shrink)

In the debate regarding the different possibilities for gene therapy, it is presupposed that the manipulations are limited to the nuclear genome (nDNA). Given recent advances in genetics, mitochondrial genome (mtDNA) and diseases must be considered as well. In this paper, we propose a three dimensional framework for the ethical debate of gene therapy where we add the genomic type (nDNA vs. mtDNA) as a third dimension to be considered beside the paradigmatic dimensions of target cell (somatic vs. (...) class='Hi'>germ-line) and purpose (therapeutic vs. enhancement). Somatic gene therapy can be viewed today as generally accepted, and we review t he contemporary arguments surrounding it on the basis of bioethical-pragmatic, socio-political and deontological classifications. Many of the supposed ethical questions of somatic gene therapy today are not new; they are well-known issues of research ethics. We also critically summarize the different international perspectives and the German ethical discussion regarding manipulations of germ-line cells. (shrink)

Acute starvation can have long-term consequences that are mediated through epigenetic change. Some of these changes are affected by the activity of AMP-activated protein kinase, a master regulator of cellular energy homeostasis. In Caenorhabditis elegans, the absence of AMPK during a period of starvation in an early larval stage results in developmental defects following their recovery on food, while many of them become sterile. Moreover, the loss of AMPK during this quiescent period results in transgenerational phenotypes that can become progressively (...) worse with each successive generation. Our recent data describe a chromatin-based mechanism of how AMPK mediates adjustment to acute starvation in the germ cells, however, the heritable aspect of this AMPK mutant phenotype remains unresolved. Here, we explore how AMPK might affect this process and speculate how the initial transcription that occurs in the germ cells may adversely affect subsequent germline gene expression and/or genomic integrity. AMPK protects germ cell integrity during acute starvation by blocking inappropriate transcription. How these aberrant transcripts cause transgenerational defects is unclear. AMPK likely regulates germline integrity at multiple levels through several targets. The authors speculate here how AMPK disruption during starvation could result in the observed defects seen at each generation. (shrink)

The mode and timing of germ-cell specification has been studied in diverse organisms, however, the molecular mechanism regulating germ-cell-fate determination remains to be elucidated. In some model organisms, maternal germ-cell determinants play a key role. In mouse embryos, some germ-line-specific gene products exist as maternal molecules and play critical roles in a pluripotential cell population at preimplantation stages. From those cells, primordial germ cells (PGCs) are specified by extracellular signaling mediated by (...) tissue, as well as cell–cell interaction during gastrulation. Thus, establishment of germ-cell lineage in mammalian embryos appears to be regulated by a multistep process, including formation and maintenance of a pluripotential cell population, as well as specification of PGCs. PGCs can be generated from pluripotential embryonic stem (ES) cells in a simple monolayer culture in which tissue interaction does not occur. This raises the possibility that ES cells, as well as, possibly, pluripotential cells in preimplantation embryos, are more closely related to the PGC precursors than pluripotential cells after implantation. BioEssays 27:136–143, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Egg or sperm? The mechanism of sexual fate decision in germ cells has been a long‐standing issue in biology. A recent analysis identified foxl3 as a gene that determines the sexual fate decision of germ cells in the teleost fish, medaka. foxl3/Foxl3 acts in female germline stem cells to repress commitment into male fate (spermatogenesis), indicating that the presence of mitotic germ cells in the female is critical for continuous sexual fate decision of germ cells in (...) medaka gonads. Interestingly, foxl3 is found in most vertebrate genomes except for mammals. This provides the interesting possibility that the sexual fate of germ cells in mammals is determined in a different way compared to foxl3‐possessing vertebrates. Considering the fact that germline stem cells are the cells where foxl3 begins to express and sexual fate decision initiates and mammalian ovary does not have typical germline stem cells, the mechanism in mammals may have been co‐evolved with germline stem cell loss in mammalian ovary. (shrink)

Ramathal et al. have employed an elegant xenotransplantation technique to study the fate of human induced pluripotent stem cells (hiPSCs) from fertile males and from males carrying Y chromosome deletions of the azoospermia factor (AZF) region. When placed in a mouse testis niche, hiPSCs from fertile males differentiate into germ cell‐like cells (GCLCs). Highlighting the crucial role of cell autonomous factors in male sterility, hiPSCs derived from azoospermic males prove to be less successful under similar circumstances. (...) Their studies argue that the agametic “Sertoli cell only” phenotype of two of the AZF deletions likely arises from a defect in the maintenance of germline stem cells (GSCs) rather than from a defect in their specification. These observations underscore the importance of the dialogue between the somatic niche and its inhabitant stem cells, and open up interesting questions concerning the functioning of the somatic niche and how it communicates to the GSCs. (shrink)

Germ-line genetic interventions, like all medicine, can present opportunities to remove suffering, save and prolong human life, and support the conditions for successful human performance. Like all medicine, these interventions also present risks that reflect fallen humans’ age-old egocentric ambition to secure their health and improve their quality of life by relying exclusively on their own power, wisdom, and technical means. Moreover, man has always been tempted to overstep Divine prohibitions and to disregard his own calling to (...) become deified by grace. Wherever man succumbs to such tendencies, this inescapably leads to a disruption of the vital relationship between man and God. The legitimacy of the intervention itself depends on the theological status of the genome. Orthodox theology recognizes that the human genome, just as everything else that is created, must be understood in terms of its relationship to God. This consideration, however, does not mean that it can be idolized or is therefore untouchable. Interventions and alterations can be accepted within the constraints set by God, as formulated in the theology of creative logoi of beings in the teaching of the Fathers of the Church, and thus in view of man’s divine vocation. The Christian acceptability or inacceptability of human germ-line gene therapy depends directly on the extent to which it accords with an Orthodox spiritual life, or else hinders such a life. In this sense, this intervention can be examined in the same way as the application of all medical knowledge. When this is used to relieve pain and is motivated by selfless love for one’s neighbor, then it can be considered God’s gift to humankind. When, however, it becomes an absolute and attempts to usurp the presence of God in human life, then use becomes abuse and modern man faces yet another form of idolatry, even though more refined than earlier forms. (shrink)