The US Food and Drug Administration’s final Guidance for Industry on the regulation of transgenesis in animal agriculture has paved the way for the commercialization of genetically engineered (GE) farm animals. The production-related diseases associated with extant breeding technologies are reviewed, as well as the predictable welfare consequences of continued emphasis on prolificacy at the potential expense of physical fitness. Areas in which biotechnology could be used to improve the welfare of animals while maintaining profitability are explored along with (...) regulatory schema to improve agency integration in GE animal oversight. (shrink)

In this article, we examine the ethical implications of human transgenesis by considering the phenomenon in its larger evolutionary context. After clarifying the concept of transgenesis, we show that rather than unprecedented or unnatural, transgenesis is a common aspect of the evolutionary process that has likely affected all extant living animals, humans included. Additionally, we demonstrate that human transgenesis is technically feasible and that the moral barriers to it are mostly based on irrational fears premised on (...) distorted and unrealistic views of “human nature”. Furthermore, we suggest that transgenically modifying persons might be morally preferable to relying blindly on the “natural lottery”, and that it is possible to do so in an ethical and responsible manner. (shrink)

Gene therapy has emerged from the idea of inserting a wild‐type copy of a gene in order to restore the proper expression and function of a damaged gene. Initial efforts have focused on finding the proper vector and delivery method to introduce a corrected gene to the affected tissue or cell type. Even though these first attempts are clearly promising, seveal problems remain unsolved. A major problem is the influence of chromatin structure on transgene expression. To overcome chromatin‐dependent repressive transgenic (...) states, researchers have begun to use chromatin regulatory elements to drive transgene expression. Insulators or chromatin boundaries are able to protect a transgene against chromatin position effects at their genomic integration sites, and they are able to maintain transgene expression for long periods of time. Therefore, these elements may be very useful tools in gene therapy applications for ensuring high‐level and stable expression of transgenes. BioEssays 26:796–807, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The Sleeping Beauty transposon system is a nonviral DNA transfer tool capable of efficiently mediating transposition‐based, stable integration of DNA sequences of choice into eukaryotic genomes. Continuous refinements of the system, including the emergence of hyperactive transposase mutants and novel approaches in vectorology, greatly improve upon transposition efficiency rivaling viral‐vector‐based methods for stable gene insertion. Current developments, such as reversible transgenesis and proof‐of‐concept RNA‐guided transposition, further expand on possible applications in the future. In addition, innate advantages such as lack (...) of preferential integration into genes reduce insertional mutagenesis‐related safety concerns while comparably low manufacturing costs enable widespread implementation. Accordingly, the system is recognized as a powerful and versatile tool for genetic engineering and is playing a central role in an ever‐expanding number of gene and cell therapy clinical trials with the potential to become a key technology to meet the growing demand for advanced therapy medicinal products. (shrink)

Cyberfeminism and Artificial Life examines construction, manipulation and re-definition of life in contemporary technoscientific culture. It takes a critical political view of the concept of life as information, tracing this through the new biology and the changing discipline of artificial life and its manifestation in art, language, literature, commerce and entertainment. From cloning to computer games, and incorporating an analysis of hardware, software and 'wetware', Sarah Kember demonstrates how this relatively marginal field connects with, and connects up global networks of (...) information systems. As well as offering suggestions for the evolution of [cyber]feminism in Alife environments, the author identifies the emergence of posthumanism; an ethics of the posthuman subject mobilized in the tension between cold war and post-cold war politics, psychological and biological machines, centralized and de-centralized control, top-down and bottom-up processing, autonomous and autopoietic organisms, cloning and transgenesis, species-self and other species. Ultimately, this book aims to re-focus concern on the ethics rather than on the 'nature' of life-as-it-could-be. (shrink)

Advancements in science and technology have not only brought hope to humankind to produce disease-free offspring, but also offer possibilities to genetically enhance the next generation’s traits and capacities. Human genetic enhancement, however, raises complex ethical questions, such as to what extent should it be allowed? It has been a great challenge for humankind to develop robust ethical guidelines for human genetic enhancement that address both public concerns and needs. We believe that research about public concerns is necessary prior to (...) developing such guidelines, yet the issues have not been thoroughly investigated in many countries, including Malaysia. Since the novel often functions as a medium for the public to express their concerns, this paper explores ethical concerns about human genetic enhancement expressed in four Malay science fiction novels namely Klon, Leksikon Ledang, Transgenesis Bisikan Rimba and Transgenik Sifar. Religion has a strong influence on the worldview of the Malays therefore some concerns such as playing God are obviously religious. Association of the negative image of scientists as well as the private research companies with the research on human genetic enhancement reflects the authors’ concerns about the main motivations for conducting such research and the extent to which such research will benefit society. (shrink)

I examine the process and outcomes of animal genetic manipulation (‘transgenesis’) with reference to its morally salient features. I consider several objections to transgenesis. I examine and reject the alleged intrinsic wrongness of ‘deliberate genetic sequence alteration’, as I do the notion that transgenesis may lead to human genetic manipulation. I examine the alleged wrongness of killing inherent in transgenesis, and suggest that the concept of ‘replaceability’ successfully justifies such killing, although not for entities deemed to (...) possess ‘personhood’. I examine ‘significant suffering’ associated with transgenesis and propose the radical conclusion that, although it would be wrong to prohibit animal genetic manipulation per se, utilitarians ought to support a ‘default prohibition’ on transgenic experiments that entail significant suffering. (shrink)

Recent developments in studies of sperm‐mediated gene transfer (SMGT) now provide solid ground for the notion that sperm cells can act as vectors for exogenous genetic sequences. A substantive body of evidence indicates that SMGT is potentially useable in animal transgenesis, but also suggests that the final fate of the exogenous sequences transferred by sperm is not always predictable. The analysis of SMGT‐derived offspring has shown the existence of integrated foreign sequences in some cases, while in others stable modifications (...) of the genome are difficult to detect. The appearance of SMGT‐derived modified offspring on the one hand and, on the other hand, the rarity of actual modification of the genome, suggest inheritance as extrachromosomal structures. Several specific factors have been identified that mediate distinct steps in SMGT. Among those, a prominent role is played by an endogenous reverse transcriptase of retrotransposon origin. Mature spermatozoa are naturally protected against the intrusion of foreign nucleic acid molecules; however, particular environmental conditions, such as those occurring during human assisted reproduction, can abolish this protection. The possibility that sperm cells under these conditions carry genetic sequences affecting the integrity or identity of the host genome should be critically considered. These considerations further suggest the possibility that SMGT events may occasionally take place in nature, with profound implications for evolutionary processes. BioEssays 27: 551–562, 2005. © 2005 Wiley periodicals, Inc. (shrink)

Ecological developmental biology (eco‐devo) explores the mechanistic relationships between the processes of individual development and environmental factors. Recent studies imply that some of these relationships have deep evolutionary origins, and may even pre‐date the divergences of the simplest extant animals, including cnidarians and sponges. Development of these early diverging metazoans is often sensitive to environmental factors, and these interactions occur in the context of conserved signaling pathways and mechanisms of tissue homeostasis whose detailed molecular logic remain elusive. Efficient methods for (...) transgenesis in cnidarians together with the ease of experimental manipulation in cnidarians and sponges make them ideal models for understanding causal relationships between environmental factors and developmental mechanisms. Here, we identify major questions at the interface between animal evolution and development and outline a road map for research aimed at identifying the mechanisms that link environmental factors to developmental mechanisms in early diverging metazoans.Also watch the Video Abstract. (shrink)

In many bilaterian phyla, appendages are morphological traits that characterise the identity of the various body parts. In pterygote insects, wings are dorsal appendages on the thorax. The famous “bithorax” fly created by Ed Lewis is the emblematic example of the role of Hox genes.1 Now, Tomoyasu et al.,2 using classical genetics, transgenesis and RNAi, have examined the function of thoracic Hox genes in the beetle Tribolium castaneum. Beetles have rigid elytra in place of the first pair of wings. (...) Instead of the expected transformation of the elytron into a wing, loss of Hox genes' function leads to the homeotic transformation of the second pair of dorsal appendages, the wings, into elytra. This has important consequences for the way that we see the role of Hox genes in development and evolution. BioEssays 27:673–675, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

Herpes simplex virus (HSV)‐derived vectors are currently being developed for the introduction of foreign DNA into neurons. HSV vectors can facilitate a range of molecular studies on postmitotic neurons and may ultimately be used for somatic cell gene therapy for certain neurologic diseases. In this article, the salient features of the pathogenesis and molecular biology of HSV relevant to its use as a vector are described, along with an overview of the methods used to derive these vectors. The accomplishments which (...) have been made to date using the HSV vector system are discussed, with emphasis on the issues of this technology which remain to be addressed. HSV has the potential to be a most useful tool for neuronal cell transgenesis and it is likely that important neurobiological questions will be answered using this vector system. (shrink)

Throughout art history, numerous artists have explored connections to science. In the society of today, the relationship between art and biology has been acquiring special visibility. Moreover, the current importance given to science and technology by today’s public opinion directly drives an increased awareness about the relationship between art and science. The public has been eagerly following breakthroughs in scientific research, albeit with mixed feelings: simultaneously awe, hope and fear for its potential misuse. Such awareness about biological sciences and biotechnology (...) has been having an increasing influence over artists, where the artist is no longer a mere observer of the scientific research and not quite a science researcher, but rather an art researcher. This particular position has led to the development of strategies to promote the exploration of possibilities deriving from a cross-talk between artists and scientists. This is a new art practice, based on a ‘risk-based’ situation; a timeless research strategy to develop new methods of practice, new media and new ways to manipulate materials for artistic expression. This is art research. During the twentieth century, the key scientific advances – such as the discovery of the DNA structure, in vitro fertilization, transgenesis or the sequencing of the human genome (in the twenty-first century) – were perceived by society in diverse ways. The progressive incorporation of those concepts by society itself led to a point where biology and the medical sciences became the most promising areas of science. It is therefore not surprising that those same scientific disciplines have marked the development of the artistic discourse in a tremendous fashion, as well as also influencing all other areas of the contemporary society. Furthermore, these artworks explore new media, described as ‘moist’ in that they integrate dry in silico computer components with wet living biological systems. (shrink)

The zona pellucida is an extracellular coat that surrounds mammalian eggs and early embryos. This insoluble matrix separates germ from somatic cells during folliculogenesis and plays critical roles during fertilization and early development. The mouse and human zona pellucida contain three glycoproteins (ZP1 or ZPB, ZP2, ZP3), the primary structures of which have been deduced by molecular cloning. Targeted mutagenesis of endogenous mouse genes and transgenesis with human homologues provide models to investigate the roles of individual zona components. Collectively, (...) the genetic data indicate that no single mouse zona pellucida protein is obligatory for taxon‐specific sperm binding and that two human proteins are not sufficient to support human sperm binding. An observed post‐fertilization persistence of mouse sperm binding to “humanized” zona pellucida correlates with uncleaved ZP2. These observations are consistent with a model for sperm binding in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2. BioEssays 26:29–38, 2004. Published 2003 Wiley Periodicals, Inc. (shrink)

This article takes as its starting point and its main problematic the status of evolution as a ‘sterile belief’ in contemporary technoscientific culture. Focusing in particular on the role of evolution across the boundaries of art and science in the contexts of artificial life and transgenic engineering, it offers a critique of the belief in evolutionary possibility as an abstract process. The lack of what François Jacob refers to as a dialogue between the possible and the actual is seen to (...) account for the sterility of evolutionary possibility and for its status as myth. In particular, evolutionary possibility recalls the myth of metamorphoses, the conservatism of which is demonstrated in an analysis of two art/science works - Galápagos by Karl Sims and Genesis by Eduardo Kac. Lacking a dialogue with the actual, metamorphic evolutionary possibility here becomes self-referential and produces nothing new. Rather than a rejection of evolution per se, this article takes up Jacob’s critique of its over-extension by showing how this operates in two works representing the fields of artificial life and transgenesis respectively. (shrink)

The creation of transgenic animals has application in the following areas of pharmaceutical and biomedical research: the production of biopharmaceuticals for human use; the production of organs for xenotransplantation; and the generation of animal models for human genetic diseases. Nuclear transfer technology offers a more precise and efficient way of performing genetic modification and creating transgenic animals than the more traditional method of pronuclear microinjection. This paper will review nuclear transfer as ameans of producing transgenic animals; introduce advantages nuclear transfer (...) technology offers in the field of animal transgenesis; and highlight some of the animal welfare issues and ethical concerns raised by the generation and use of transgenic animals in the aforementioned fields of study. Finally, the influence of objectifying language and terminology used to describe transgenic animals will be considered, and the impact of phrases such as “living bioreactor” and “spare part supplier” examined. (shrink)

There has been a long-standing opposition to genetically modified organisms worldwide. Some studies have tried to identify the deep-lying philosophical, conceptual as well as psychological motivations for this opposition. Philosophical essentialism, psychological essentialism, and vitalism have been proposed as possible candidates. I approach the plausibility of the claim that these notions are related to GMO opposition from a historical perspective. Vitalism and philosophical essentialism have been associated with anti-GMO stance on account of their purported hostility to species and organismic mutability. (...) I show that vitalism has often been associated to various mutabilist theories, whereas the case for philosophical essentialism as motivating GMO opposition depends on the now discredited Essentialism Story that had constructed essentialism as a predominant view in pre-Darwinian science. Further, as philosophical essentialism taken seriously is incompatible with the reality of genetic engineering, it is unlikely to be a reason for opposition. Psychological essentialism, involving an instinctive repulsion from the practice of manipulating what is thought to be the essence of living beings, is a more likely reason for resistance to transgenesis. Yet even here, historical considerations are crucial. Not only lay people tend to essentialize genes, but scientists themselves can be shown to have been complicit in essentialist tendencies. From the advent of modern genetics, the imagery of the all-powerful genes, often depicted by scientists themselves metaphorically as material counterparts of the now obsolete vitalistic agent, has permeated the language of leading scientific figures, whose influence in shaping public opinion should not be downplayed. Enthusiasm for genetic engineering and the abhorrence from it might both derive from the same unrealistic image of the essential gene, the revision of which thus holding out the hope for transcending the present impasse of the GMO controversy. (shrink)

The common autoimmune disease type 1 diabetes provides a paradigm for the genetic analysis of multifactorial disease. Disease occurrence is attributable to the interaction with the environment of alleles at many loci interspersed throughout the genome. Their mapping and identification is difficult because the disease-associated alleles occur almost as commonly in patients as in healthy individuals; even the highest-risk genotypes bestow only modest risks of disease. The identification of common quantitative trait loci (QTL) in autoimmune disease and in other common (...) disorders, therefore,requires a very close marriage of genetics and biology. Two QTLs have been identified in human type 1 diabetes: the major histocompatibility complex HLA class II loci and a promoter polymorphism of the insulin gene. The evidence for their primary roles in disease aetiology demonstrates the necessity of combined studies of genetics and biology. Their functions and interaction underpin an emerging picture of the basic causes of the disease and direct analyses towards other candidate genes and pathways. The genetic tools used for QTL identification include transgenesis and gene knockouts, whole genome scanning for linkage, mouse congenic strains, linkage disequilibrium mapping, and the establishment of ancestral haplotypes among disease-associated chromosomes. BioEssays 1999;21:164–174. © 1999 John Wiley & Sons, Inc. (shrink)