Faith-based perspectives on the use of chimeric organisms for medical research

Efforts to advance our understanding of neurodegenerative diseases involve the creation chimeric organisms from human neural stem cells and primate embryos—known as prenatal chimeras. The existence of potential mentally complex beings with human and non-human neural apparatus raises fundamental questions as to the ethical permissibility of chimeric research and the moral status of the creatures it creates. Even as bioethicists find fewer reasons to be troubled by most types of chimeric organisms, social attitudes towards the non-human world are often influenced by religious beliefs. In this paper scholars representing eight major religious traditions provide a brief commentary on a hypothetical case concerning the development and use of prenatal human–animal chimeric primates in medical research. These commentaries reflect the plurality and complexity within and between religious discourses of our relationships with other species. Views on the moral status and permissibility of research on neural human animal chimeras vary. The authors provide an introduction to those who seek a better understanding of how faith-based perspectives might enter into biomedical ethics and public discourse towards forms of biomedical research that involves chimeric organisms.     

Genetic modification of animals in the next century

Since the initial demonstration in 1982 of profound phenotypic effects stemming from the expression of a single transgene, genetic engineering has revolutionized fundamental biological and biomedical research. The application of transgenic technology to farm animals has held the promise of being able to improve animal agriculture significantly and has resulted in a new industry, i.e., the successful expression of foreign proteins in the mammary gland for the pharmaceutical industry. Work over the last few years in model species (e.g., the mouse) and new technical developments such as cloning have now set the stage for the initial application of transgenic technology for the improvement of farm animals. Major limitations that remain are the lack understanding of which genes we should transfer in order to alter quantitative production traits usefully and the low efficiency of producting transgenic founders. Furthermore, more research is needed concerning the consequences and potential problems arising from the integration of transgenes into populations with varying genetic backgrounds. Recent advances suggest that within the first decade of the 21 st century the first transgenic animals will become available to the livestock industry, with acceptance depending upon their cost versus their potential economic benefit to the producers.     

IMPACT OF ALGAL RESEARCH IN AQUACULTURE

Algal aquaculture worldwide is estimated to be a $5–6 billion U.S. per year industry. The largest portion of this industry is represented by macroalgal production for human food in Asia, with increasing activity in South America and Africa. The technical foundation for a shift in the last half century from wild harvest to farming of seaweeds lies in scientific research elucidating life histories and growth characteristics of seaweeds with economic interest. In several notable cases, scientific breakthroughs enabling seaweed-aquaculture advances were not motivated by aquaculture needs but rather by fundamental biological or ecological questions. After scientific breakthroughs, development of practical cultivation methods has been accomplished by both scientific and commercial-cultivation interests. Microalgal aquaculture is much smaller in economic impact than seaweed cultivation but is the subject of much research. Microalgae are cultured for direct human consumption and for extractable chemicals, but current use and development of cultured microalgae is increasingly related to their use as feeds in marine animal aquaculture. The history of microalgal culture has followed two main paths, one focused on engineering of culture systems to respond to physical and physiological needs for growing microalgae and the other directed toward understanding the nutritional needs of animals—chiefly invertebrates such as mollusks and crustaceans—that feed upon microalgae. The challenge being addressed in current research on microalgae in aquaculture food chains is to combine engineering and nutritional principles so that effective and economical production of microalgal feed cultures can be accomplished to support an expanding marine animal aquaculture industry.     

Ethical, legal, and social aspects of farm animal cloning in the 6th Framework Programme for Research

Cloned livestock have potential importance in the provision of improved medicine as well as in the development of livestock production. The public is, however, increasingly concerned about the social and ethical consequences of these advances in knowledge and techniques. There is unevenness throughout Europe in different Member States' attitudes to research into livestock cloning. Although there is EU legislation controlling the use of animals for research purposes, there is no legislation specifically governing cloning in livestock production. The main EU reference is the 9th Opinion of the European Group on Ethics, which states "Cloning of farm animals may prove to be of medical and agricultural as well as economic benefit. It is acceptable only when the aims and methods are ethically justified and when carried out under ethical conditions." The ethical justification includes the avoidance of suffering, the use of the 3Rs principle and a lack of better alternatives. The Commission addresses these issues in the 6th Framework Programme by promoting the integration of ethical, legal and social aspects in all proposals where they are relevant, by fostering ethical awareness and foresight in the proposals, by encouraging public dialogue, and by supporting specific actions to promote the debate. Research must respect fundamental ethical principles, including animal welfare requirements.     

Toward a cross-species neuroscientific understanding of the affective mind: do animals have emotional feelings?

Do we need to consider mental processes in our analysis of brain functions in other animals? Obviously we do, if such BrainMind functions exist in the animals we wish to understand. If so, how do we proceed, while still retaining materialistic-mechanistic perspectives? This essay outlines the historical forces that led to emotional feelings in animals being marginalized in behavioristic scientific discussions of why animals behave the way they do, and why mental constructs are generally disregarded in modern neuroscientific analyses. The roots of this problem go back to Cartesian dualism and the attempt of 19th century physician-scientists to ground a new type of medical curriculum on a completely materialistic approach to body functions. Thereby all vitalistic principles were discarded from the lexicon of science, and subjective experience in animals was put in that category and discarded as an invalid approach to animal behavior. This led to forms of rigid operationalism during the era of behaviorism and subsequently ruthless reductionism in brain research, leaving little room for mentalistic concepts such as emotional feelings in animal research. However, modern studies of the brain clearly indicate that artificially induced arousals of emotional networks, as with localized electrical and chemical brain stimulation, can serve as "rewards" and "punishments" in various learning tasks. This strongly indicates that animal brains elaborate various experienced states, with those having affective contents being easiest to study rigorously. However, in approaching emotional feelings empirically we must pay special attention to the difficulties and vagaries of human language and evolutionary levels of control in the brain. We need distinct nomenclatures from primary (unconditioned phenomenal experiences) to tertiary (reflective) levels of mind. The scientific pursuit of affective brain processes in other mammals can now reveal general BrainMind principles that also apply to human feelings, as with neurochemical predictions from preclinical animal models to self-reports of corresponding human experiences. In short, brain research has now repeatedly verified the existence of affective experience-various reward and punishment functions-during artificial arousal of emotional networks in our fellow animals. The implications for new conceptual schema for understanding human/primate affective feelings and how such knowledge can impact scientific advances in biological psychiatry are also addressed.     

Past, present and future strategies to study the genetics of body weight regulation.

Genetic advances have made remarkable progress towards our understanding of body weight regulation. Much of our current knowledge has come from the cloning and characterisation of the genes responsible for obesity syndromes in the mouse, and the identification of homologous mutations causing rare forms of obesity in humans. Gene targeting experiments in mice have been instrumental in confirming the importance of many genes in the aetiology of obesity, and the existence of a fundamental physiological pathway that controls energy balance is becoming clear. The genetic determinants that underlie common forms of human obesity are largely polygenic, with most genes producing small effects. Thus, elucidating the many genetic determinants of obesity is a current challenge for modern geneticists. Despite the inherent difficulties, progress has been made through linkage/association studies and a genetic map of quantitative trait loci for human obesity is beginning to emerge. Obesity research is now very much in a transition period. Not so long ago, access to high throughput screening, as well as microarray and proteomic techniques, was prohibitively expensive and available only to the few. In recent years, these technologies have become more accessible to the larger scientific community and, in this paper, we will discuss how such technological advances are likely to drive the next wave of progress in obesity research. For example, large-scale mutagenesis screens in rodents coupled with high throughput screening are likely to emerge as important technologies for identifying genes previously unexpected to be involved in body weight regulation. Furthermore, applications of microarray and proteomic techniques will further refine our understanding of currently known peptides as well as identify novel pathways and molecules which are involved in energy homeostasis.     

Science and technology of farm animal cloning: state of the art

Details of the first mammal born after nuclear transfer cloning were published by Steen Malte Willadsen in 1986. In spite of its enormous scientific significance, this discovery failed to trigger much public concern, possibly because the donor cells were derived from pre-implantation stage embryos. The major breakthrough in terms of public recognition has happened when Ian Wilmut et al. [Wilmut, I., Schnieke, A.E., McWhir, J., Kind, A.J., Campbell, K.H., 1997. Viable offspring derived from fetal és adult mammalian cells. Nature 385, 810-813] described the successful application of almost exactly the same method, but using the nuclei of somatic cells from an adult mammal, to create Dolly the sheep. It has become theoretically possible to produce an unlimited number of genetic replicates from an adult animal or a post-implantation foetus. Since 1997 a number of different species including pigs, goats, horses, cats, etc. have been cloned with the somatic cell nuclear transfer technique. Although the technology still has relatively low success rates and there seems to be substantial problems with the welfare of some of the cloned animals, cloning is used both within basic research and the biomedical sector. The next step seems to be to implement cloning in the agricultural production system and several animals have been developed in this direction. This article reviews the current state of the art of farm animal cloning from a scientific and technological perspective, describes the animal welfare problems and critically assess different applications of farm animal cloning. The scope is confined to animal biotechnologies in which the use of cell nuclear transfer is an essential part and extends to both biomedical and agricultural applications of farm animal cloning. These applications include the production of genetically identical animals for research purposes, and also the creation of genetically modified animals. In the agricultural sector, cloning can be used as a tool within farm animal breeding. We do not intend to give an exhaustive review of the all the literature available; instead we pinpoint issues and events pivotal to the development of current farm animal cloning practices and their possible applications.     

Animal models to study Mycobacterium tuberculosis and HIV co-infection

Mycobacterium tuberculosis(M.tb) and human immunodeficiency virus(HIV) co-infection has become a public health issue worldwide. Up to now, there have been many unresolved issues either in the clinical diagnosis and treatment of M.tb/HIV coinfection or in the basic understanding of the mechanisms for the impairments to the immune system by interactions of these two pathogens. One important reason for these unsolved issues is the lack of appropriate animal models for the study of M.tb/HIV coinfection. This paper reviews the recent development of research on the animal models of M.tb/HIV co-infection, with a focus on the non-human primate models.     

Editor's introduction to the Journal of Applied Animal Welfare Science

Animal welfare names a science in which investigators ask the general question: What are the capacities, sensibilities, needs, and interests of animals as they relate to their welfare? The objects of study in this emerging field are exclusively animals other than humans. Numerous contexts give rise to this interest in nonhuman animal welfare: The intensification of the use of animals since World War II, particularly on the farm and in the laboratory. The development of moral philosophies that establish nonhuman animals as objects of moral consideration. The advances in science in fields that have added to our understanding of animals, such as cognitive ethology. Advances in technology that give us more direct access to human physiology and psychology and undercut the tradition of using animal models. The success of the contemporary animal rights movement in placing the issue of the treatment of animals before the public.     

Genomics at the origins of agriculture,part one

The causes and consequences of the Neolithic revolution represent a fundamental problem for anthropological inquiry. Traditional archeological evidence, ethnobotanical remains, artifacts, and settlement patterns have been used to infer the transition from foraging to primary food production. Recent advances in genomics (the study of the sequence, structure, and function of the genome) has enhanced our understanding of the process of plant and animal domestication, revealed the impact that adaptation to agriculture has had on human biology, and provided clues to the pathogens and parasites thought to have emerged during the Neolithic. Genomic analysis provides insights into the complexity of the process of domestication that may not be apparent from the physical remains of bones and seeds, and allows us to measure the impact that the shift to primary food production had on the human genome. Questions related to the location and the process of domestication can be answered more fully by analyzing the genomes of the plants and animals brought under human control. The spread of the agriculture package (plants, animals, and technology) by cultural diffusion or demic expansion can also be investigated through this approach. Whether dissemination by farmers or the diffusion of farming knowledge and technology was the source of the Neolithic expansion, this process should be revealed by the patterh of genetic and linguistic diversity and language found from centers of agricultural Neolithic development. In addition, a number of pathogens that were previously thought to have been transmitted from domesticated species to human now appear to have been present in foragers long before the agricultural revolution took place. Furthermore, we now have evidence that humans were the source of the transmission of some parasites to domesticated animals. For all of these reasons, data from genomic studies are providing a more complete understanding of the origins of agriculture, a critical hallmark in human evolution.     

The interface of natural theology and science in the ethology of W. H. Thorpe

Conclusion It should be clear by now the extent to which many features of Thorpe's interpretation of animal behavior and of the animal mind rested, at bottom, not simply on conventional scientific proofs but on interpretive inferences, which in turn rested on a willingress to make extensions of human experience to animals. This, in turn, rested on his view of evolution and his view of reality. And these were governed by his natural theology, which was the fundamental stratum of his intellectual experience.Contrary to the scientific ethos, which restricts theory choice to scientific issues alone, Thorpe's career suggests that the actual reasons for theory choice among scientists often are not limited to science, but are multiple and may sometimes be difficult to discover. It is largely because Thorpe took a public part in the natural theology enterprise that we can know something about his religious beliefs and so can see their probable influence on his scientific decisions. Similar beliefs of other scientists are sometimes harder to get at. Most may be practically beyond discovery, for the ethos of science has discouraged public professions of personal belief in relation to scientific work.¹⁰¹ Yet does it seem plausible that, for example, the restriction of self-consciousness to humans by some scientists is a purely scientific decision?¹⁰² Surely not, any more than that the strong influence of natural theology on Thorpe's thought means that he was not a good scientist. His natural theology may have led him into incautious enthusiasms regarding the animal mind — such as the potential if unrealizable linguistic ability of chimpanzees — through a bias in favor of the continuity of emergents in a progressive evolutionary system, just as it led him to advocate animal consciousness long before the recent upsurge of interest, but the scientific integrity of his work overall is unimpeachable. And yet, that work is not comprehensible historically as science alone. Personal philosophy must not be discounted in writing the history of recent science. This somewhat obvious conclusion (obvious to historians of science) needs emphasis, for we are still prone to think that the sciences of our own time provide their own internal dynamic that is in itself sufficient to account for their content and development.     

Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine

Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications.     

The cryobiology of spermatozoa

The impact of successful cryopreservation of spermatozoa can be found in many fields, including agriculture, laboratory animal medicine, and human assisted reproduction, providing a cost-effective and efficient method to preserve genetic material for decades. The success of any cryobiologic protocol depends critically on understanding the fundamentals that underlie the process. In this review, we summarize the biophysical fundamentals critical to much of the research in sperm cryobiology, provide a synopsis of the development of sperm cryobiology as a discipline, and present the current state and directions for future research in sperm cryobiology in the three major areas outlined above—agriculture, laboratory animal medicine, and human clinical assisted reproduction. There is much room for new research, both empiric and fundamental, in all areas, including refinement of mathematical models, optimization of cryoprotective agent addition and removal procedures for spermatozoa from many species, development of effective, efficient, and facile cryopreservation protocols and freezing containers for agricultural sperm cryopreservation, and tailoring cryopreservation protocols for individual human samples.     

Future prospectives on animal biotechnology

Abstract

Farm animal reproduction is entering the era of embryo engineering ‐ a part of the new biotechnology revolution that has been sweeping the nation during the early 1980s. This comes at a time when the $70 billion livestock industry is hard‐pressed for survival. Not since the commercial development of artificial insemination (AI) techniques in the 1950s has any new technical research development caused such a stir in the livestock community. The genetic impact of artificial insemination (AI) in the cattle industry these last 40 years cannot be questioned. Nearly three‐fourths of the dairy cattle in the United States are now being artificially inseminated. Also, commercial processing of bull semen has been and still is a major agribusiness success story, grossing millions of dollars annually. With the development of embryo transfer (ET) technology in the mid‐1970s, animal reproduction again entered a new age of technical advancement. It appears that AI and embryo methodology are just the beginning of a new age in animal reproduction technology. Recent developments in molecular biology and genetic engineering now offer a new dimension in research and development for future application to seed stock farm animals. New molecular technologies will most certainly change the traditional approach to animal breeding, thus allowing the livestock producer to select breeding stock on genotype rather than phenotype. In the future, researchers will be able to study whole animal biology to a depth never before dreamed using molecular biology.     

Prions: where do we stand 20 years after the appearance of bovine spongiform encephalopathy?

Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) identified twenty years ago in the British cattle herds. Creutzfeldt-Jakob disease (CJD) is a TSE that occurs in humans. In 1996, scientists found a possible link between BSE and a new variant of CJD (vCJD). The fact that the non conventional infectious agent of TSE, named prions, could cross the species barrier from cattle to human through meat consumption, raised a tremendous concern for public safety in Europe. This led to the development in the following two decades of substantial and expensive measures to contain BSE and prevent its transmission to humans. In parallel, scientific programs have been funded to progress through the comprehension of the physiopathology of these fatal disorders. In Europe, the BSE epidemics is now ending and the number of cases is decreasing thanks to the strict control of animal foodstuff that was the main source of prion contamination. Only a small number of vCJD have been detected, however, additional concerns have been raised recently for public safety as secondary transmission of CJD through medical procedure and blood transfusion is possible. In addition, the possibility that the BSE was transmitted to other animals including small ruminants is also worrisome. Research efforts are now focussing on decontamination and ante mortem diagnosis of TSE to prevent animal and human transmission. However, needs for fundamental research are still important as many questions remain to be addressed to understand the mechanism of prion transmission, as well as its pathogenesis.     

A History of Animal Welfare Science

Human attitudes to animals have changed as non-humans have become more widely incorporated in the category of moral agents who deserve some respect. Parallels between the functioning of humans and non-humans have been made for thousands of years but the idea that the animals that we keep can suffer has spread recently. An improved understanding of motivation, cognition and the complexity of social behaviour in animals has led in the last 30 years to the rapid development of animal welfare science. Early attempts to define welfare referred to individuals being in harmony with nature but the first usable definition incorporated feelings and health as part of attempts to cope with the environment. Others considered that welfare is only about feelings but it is argued that as feelings are mechanisms that have evolved they are a part of welfare rather than all of it. Most reviews of welfare now start with listing the needs of the animal, including needs to show certain behaviours. This approach has used sophisticated studies of what is important to animals and has replaced the earlier general guidelines described as freedoms. Many measures of welfare are now used and indicate how good or how poor the welfare is. Naturalness is not a part of the definition of welfare but explains why some needs exist. In recent years, welfare has become established as one of various criteria used to decide on whether a system is sustainable because members of the public will not accept systems that cause poor welfare. The study of welfare has become part of the scientific basis upon which important political decisions are made.     

Compassion for animals in the laboratory: impairment or refinement of research methodology?

There are now signs in the United States as well as in Europe that the importance of a positive human-nonhuman animal relationship in research laboratories is appreciated more seriously. In addition to knowledge and skills, primary attributes of animal research personnel must be feelings of compassion and sensitivity toward animals to safeguard the reliability of scientific research data.     

Farm Animal Production: Changing Agriculture in a Changing Culture

Western attitudes toward animals have undergone a gradual evolution during recent centuries, driven by the scientific recognition that humans and many other species share a common anatomical template, a common phylogenetic ancestry, and certain similarities in their social and emotional lives. This evolving view has been accompanied by a heightened popular respect for animals, which has caused increasing opposition to the relatively utilitarian treatment of animals in modern farming. Western culture also tends to venerate the pastoralist image of humans caring diligently for animals, and North Americans tend to venerate the agrarian life-style of farm families living in harmony with domestic animals and the land. These positive images, which have traditionally lent legitimacy to animal agriculture, have been diminished by changes in production methods during recent decades. The resulting debate between critics and defenders of modern animal production has led to widespread confusion and concern about how animal agriculture affects animal welfare, human health, the environment, and world food security. To resolve this situation will require research to create an accurate understanding of the diverse effects of modern animal agriculture, together with measures to harmonize agricultural practices with changing public values.     

Hormonal regulation of fertility in domestic farm species

The diverse techniques used to successfully regulate reproduction in domestic farm species involve both the direct and indirect manipulation of the endocrine system. Rapid advances in our understanding of the endocrine control of reproduction provides for an expansion and improvement of the techniques available to control fertility. A failure to appreciate even subtle species differences in physiological control mechanisms frequently limits the success of otherwise effective treatments. Changes in the social environment, acting through pheromonal signals, and changes in the physical environment such as light and temperature, may be effective in regulating reproductive function. Likewise changes in suckling intensity and nutritional availability can be used to alter the fertility and fecundity of farm species. Direct intervention to modify reproductive activity is practised at all stages of the reproductive cycle. The range of compounds currently used exert their effects at all levels of the reproductive axis and may promote or inhibit the synthesis and release of hormones, as well as their action in target tissues. Regulation of the bioavailability of hormones has also proved to be an effective means of controlling fertility. In contrast to the application of fertility control in the human and in non-domesticated species, in the socio-economic climate of the modern animal husbandry industry, long term control of the timing of reproductive activity may be as economically important as an increase in fertility or fecundity.     

The future of aging therapies

Advances in understanding aging processes and their consequences are leading to the development of therapies to slow or reverse adverse changes formerly considered to be "normal" aging and processes that underlie multiple age-related conditions. Estimating the effectiveness of candidate aging therapies, whose effects on human aging may require many years to determine, is a particular challenge. Strategies for identifying candidate interventions can be developed through multiple approaches, including the screening of molecular targets and pathways in vitro and in animal models, informed as well by evidence from human genetic and epidemiologic data. A number of recently established programs and networks can serve as resources for such research. For all these research approaches, from in vitro molecular studies to clinical trials, contributions of cell and molecular biology are crucial and offer the prospect of therapeutic advances that address fundamental biological processes as well as the clinically important challenges of aging.