Cloning humans,cloning literature: genetics and the imagination deficit

Abstract

After the birth of Dolly, media stories on cloning were replete with references to well-known science fiction plots. This essay criticizes the ‘imagination deficit’ of scientists and journalists, first by problematizing the uncritical adoption of attenuated science fiction plots in the media coverage of Dolly, and second, by proposing to look at more expansive science fiction novels that carefully examine issues such as uniqueness and identity in relation to the new genetics.     

Amphibian and mammal somatic-cell cloning: different species, common results?

Since the production of Dolly the sheep cloning methods for somatic cells have been thoroughly described and are becoming routine. However, the rate at which live clones are produced remains low in all mammalian species tested so far. Remarkably, irrespective of the cloning protocol or the donor-cell type, all clones display common abnormalities, particularly in the placenta. The process is also complicated by early mortality of somatic-cell clones and the founder mammalian clone, Dolly the sheep, died in February 2003 aged six years. Based on published data and on our own experience, our view is that mammalian somatic-cell cloning and the pioneer nuclear-transfer data from amphibians have much in common. We suggest that the only way to improve nuclear reprogramming is to modify the chromatin structure of somatic cells before nuclear transfer, to provide the oocyte with a chromosomal structure that is more compatible with the natural reprogramming machinery of the oocyte.     

Language and values in the human cloning debate: a web-based survey of scientists and christian fundamentalist pastors

Over the last seven years, a major debate has arisen over whether human cloning should remain legal in the United States. Given that this may be the ‘first real global and simultaneous news story on biotechnology’ (Einsiedel et al., 2002, p. 313), nations around the world have struggled with the implications of this newly viable scientific technology, which is often also referred to as somatic cell nuclear transfer. Since the successful cloning of Dolly the sheep in 1997, and with increasing media attention paid to the likelihood of a successful human reproductive clone coupled with research suggesting the medical potential of therapeutic cloning in humans, members of the scientific community and Christian fundamentalist leaders have become increasingly vocal in the debate over U.S. policy decisions regarding human cloning (Wilmut, 2000). Yet despite a surfeit of public opinion polls and widespread opining in the news media on the topic of human cloning, there have been no empirical studies comparing the views of scientists and Christian fundamentalists in this debate (see Evans, 2002a for a recent study of opinion polls assessing religion and attitudes toward cloning).

In order to further investigate the values that underlie scientists' and Christian fundamentalist leader's understanding of human cloning, as well as their differential use of language in communicating about this issue, we conducted an open-ended, exploratory survey of practicing scientists in the field of molecular biology and Christian fundamentalist pastors. We then analyzed the responses from this survey using qualitative discourse analysis. While this was not necessarily a representative sample (in quantitative terms, see Gaskell & Bauer, 2000) of each of the groups and the response rate was limited, this approach was informative in identifying both commonalities between the two groups, such as a focus on ethical concerns about reproductive cloning and the use of scientific terminology, as well as significant differences including concerns over ‘playing God’ for the Christian pastors, focus on therapeutic cloning by scientists, and subtle but informative differences between the two groups in their use of scientific terminology and their interpretations of human cloning as scientific progress.     

Dolly's Deceiving Perfection: Biotechnology, Animal Welfare, and Ethics

New biotechnological inventions demand a different way of monitoring experiments for possible nonhuman animal welfare problems. Only with such a monitoring system in place will review committees be able to render good judgments on new experiments. Nuclear transfer cloning serves as a clear example. In February 1997, the Roslin Institute, situated in Edinburgh, United Kingdom, amazed the world with the birth of Dolly, the healthy, cloned sheep generated from the cell nucleus of the udder of an adult sheep. Although Dolly seems to be in good condition, cloned lambs and calves produced by nuclear transfer have generally been characterized as having a high birth weight, various anatomical and physiological abnormalities, and a low survival rate. Although these symptoms have been observed only in part of the clones, their severity shows a considerable risk of compromised animal welfare following a cloning experiment.     

Human cloning: category, dignity, and the role of bioethics

Human cloning has been simultaneously a running joke for massive worldwide publicity of fringe groups like the Raelians, and the core issue of an international movement at the United Nations in support of a treaty to ban the use of cloning techniques to produce a child (so called reproductive cloning). Yet, even though debates on human cloning have greatly increased since the birth of Dolly, the clone sheep, in 1997, we continue to wonder whether cloning is after all any different from other methods of medically assisted reproduction, and what exactly makes cloning an 'affront to the dignity of humans.' Categories we adopt matter mightily as they inform but can also misinform and lead to mistaken and unproductive decisions. And thus bioethicists have a responsibility to ensure that the proper categories are used in the cloning debates and denounce those who try to win the ethical debate through well-crafted labels rather than well-reasoned argumentations. But it is as important for bioethicists to take a position on broad issues such as human cloning and species altering interventions. One 'natural question' would be, for example, should there be an international treaty to ban human reproductive cloning?     

'Crook' pipettes: embryonic emigrations from agriculture to reproductive biomedicine

While cloning, stem cells, and regenerative medicine are often imagined in a futurial idiom--as expectations, hype, hope and promises--this article approaches the remaking of genealogy in such contexts from a historical route. Through a series of somewhat disparate historical connections linking Australian sheep to the development of clinical IVF and the cloning of Dolly at the Roslin Institute in Scotland in 1996, this article explores the linkages through which agriculture, embryology, and reproductive biomedicine are thickly intertwined. Key to this examination is not only the history of experimental sheep breeding, and its somewhat unexpectedly genealogical connections to (Australian) national identity ('wool in the veins'), but also the re-emergence of a distinctive frontier ethos in the context of assisted conception, and later human embryonic stem cell derivation. I have set this scene of genealogical interconnection against the criss-crossing traffic between Britain and Australia, and the wool trade, to emphasise the importance of global, as well as local, connections in the bloodlines of animals such as Dolly. In sum, this article examines the idea of the 'biological frontier' by exploring its histories as a means to offset the assumption that this frequently encountered idiom describes a future that is, or must be, by definition, unknown and unknowable.     

Animal breeding in the age of biotechnology: the investigative pathway behind the cloning of Dolly the sheep

History and Philosophy of the Life Sciences - This paper addresses the 1996 cloning of Dolly the sheep, locating it within a long-standing tradition of animal breeding research in Edinburgh. Far...     

Cloning of Homo sapiens? No!

Animal cloning by nuclear transplantation was first developed in the northern leopard frog, Rana pipiens. It was soon extended to other amphibian species and within time, to various mammalian species. The production of a cloned sheep (Dolly) from an adult nuclear donor reawakened interest in human cloning. Nuclear transfer for the production of animal clones has served experimental biology well. Nonetheless, the potential burden of developmental hazards, scientists and funds diverted from more needy causes, as well as the potential assault on the concept of family has led the author to oppose human cloning.     

Abortion rhetoric in American news coverage of the human cloning debate

Abstract

The issue of human cloning has received intense media and political attention since the cloning of Dolly the sheep was announced in 1997. This research explores the discursive basis for support and opposition to human cloning by examining the role of abortion-related rhetoric in constructing the concept of human cloning within the American press. An in-depth content analysis of human cloning news coverage was conducted on a sample of articles collected from the mainstream press as well as advocacy publications with either a pro-science or Christian fundamentalist orientation. Statistically significant differences were found indicating an important role for abortion rhetoric in the human cloning debate. This expansion of abortion rhetoric into the domain of science policy portends a unique and growing problem for resolving bioethical debates within American politics over the future development of biomedical technologies such as human cloning.     

Technical advances and pitfalls on the way to human cloning

There exists a widespread consensus that the cloning of human beings to term would be detrimental to both the mother and child and of little value to society. However, the ambition of a few organisations and the recent advances in cellular and molecular technologies that led to the cloning of Dolly the sheep, for example, have meant that such a procedure will be possible if not illegal in the near future. The science associated with the cloning technologies practiced in other mammalian species reported to date provide important advances in our understanding of how cells function during early developmental processes and commit themselves to specific developmental pathways. However, many technological insufficiencies remain. Both technological advances and several of the associated insufficiencies are outlined in this review.     

Specific genetic modifications of domestic animals by gene targeting and animal cloning

The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large livestock species until the successful creation of the first mammalian clone "Dolly" the sheep. The combination of the technologies for gene targeting of somatic cells with those of animal cloning made it possible to introduce specific genetic mutations into domestic animals. In this review, the principles of gene targeting in somatic cells and the challenges of nuclear transfer using gene-targeted cells are discussed. The relevance of gene targeting in domestic animals for applications in bio-medicine and agriculture are also examined.     

Cloning humans, cloning literature: genetics and the imagination deficit

After the birth of Dolly, media stories on cloning were replete with references to well-known science fiction plots. This essay criticizes the 'imagination deficit' of scientists and journalists, first by problematizing the uncritical adoption of attentuated science fiction plots in the media coverage of Dolly, and second, by proposing to look at more expansive science fiction novels that carefully examine issues such as uniqueness and identity in relation to the new genetics.     

Language and values in the human cloning debate: a web-based survey of scientists and Christian fundamentalist pastors

Over the last seven years, a major debate has arisen over whether human cloning should remain legal in the United States. Given that this may be the 'first real global and simultaneous news story on biotechnology' (Einsiedel et al., 2002, p.313), nations around the world have struggled with the implications of this newly viable scientific technology, which is often also referred to as somatic cell nuclear transfer. Since the successful cloning of Dolly the sheep in 1997, and with increasing media attention paid to the likelihood of a successful human reproductive clone coupled with research suggesting the medical potential of therapeutic cloning in humans, members of the scientific community and Christian fundamentalist leaders have become increasingly vocal in the debate over U.S. policy decisions regarding human cloning (Wilmut, 2000). Yet despite a surfeit of public opinion polls and widespread opining in the news media on the topic of human cloning, there have been no empirical studies comparing the views of scientists and Christian fundamentalists in this debate (see Evans, 2002a for a recent study of opinion polls assessing religion and attitudes toward cloning). In order to further investigate the values that underlie scientists' and Christian fundamentalist leader's understanding of human cloning, as well as their differential use of language in communicating about this issue, we conducted an open-ended, exploratory survey of practicing scientists in the field of molecular biology and Christian fundamentalist pastors. We then analyzed the responses from this survey using qualitative discourse analysis. While this was not necessarily a representative sample (in quantitative terms, see Gaskell & Bauer, 2000) of each of the groups and the response rate was limited, this approach was informative in identifying both commonalities between the two groups, such as a focus on ethical concerns about reproductive cloning and the use of scientific terminology, as well as significant differences including concerns over 'playing God' for the Christian pastors, focus on therapeutic cloning by scientists, and subtle but informative differences between the two groups in their use of scientific terminology and their interpretations of human cloning as scientific progress.     

Effect of ectoparasites on quality of pickled skins and their impact on the tanning industries in Amhara regional state,Ethiopia

Five groups of 20 infested skins with different ectoparasites and different levels of infestation and two groups of negative control skins from sheep and goats were examined for their corresponding defects at the pickled or wet blue stage of processing in tanneries. In addition, an analysis of skin defects was made from randomly selected processed skins at Kombolcha and Dessei tanneries. The prevalence of ‘ekek’ (cockle) at the pickled stage in Damalina ovis and Melophagus ovinus-infested sheep skins were 100 and 95%, respectively. Pickled goat skins affected by sarcoptic mange and Linognathus spp. were 100 and 0% positive for ‘ekek’ (cockle) lesion, respectively. The prevalence in control sheep and goat skins were 15 and 0%, respectively. There was a strong association (p < 0.05) between ‘ekek’ and infestation with M. ovinus and D. ovis in sheep and sarcoptic mange in goats. Follow-up of randomly selected 1000 pickled sheep skins and 1000 wet blue goat skins revealed that 71% of pickled sheep and 42% of wet blue goat skins had ‘ekek’ lesions. As the proportion of ‘ekek’ increased, the quality of graded skins decreased both in sheep and goats. Both on pickled sheep and wet blue goat skins, scratch and scars were found to have a strong association (p < 0.05) with ‘ekek’. The annual economic loses in 2002/2003 due to ‘ekek’ at the two tanneries was estimated to be 1.6 million USD for pickled sheep and 0.6 million USD for wet blue goat skins.     

A reliable, noninvasive technique for spindle imaging and enucleation of mammalian oocytes

Factors affecting the efficiency of animal cloning remain to be elucidated. Enucleation of recipient oocytes is a critical step in cloning procedures and typically is performed by aspirating a portion of the cytoplasm underlying the first polar body. Enucleation is evaluated using epifluorescence after Hoechst staining for DNA, which may disrupt functions of the cytoplast, especially mitochondria. Mitochondrial DNA in Dolly and other cloned sheep has been shown to derive exclusively from recipient oocytes. Not only might evaluation of the aspirated karyoplast portion inadequately reflect the state of the cytoplast, it is also time consuming. Here we report a reliable, noninvasive technique for spindle imaging and enucleation of oocytes using a new microscope, the Pol-Scope. The efficiency of enucleation was 100%, and only 5.5% of the oocytes' mitochondria entered the karyoplast upon Pol-Scope-directed removal of the spindle. Moreover, Pol-Scope imaging of spindles and micromanipulation did not compromise the developmental competence of reconstituted oocytes and cytoplasts.     

Analysis of telomere length in Dolly, a sheep derived by nuclear transfer

We have used a (TTAGGG) oligonucleotide probe to demonstrate that ovine telomeres are composed of (TTAGGG) repeat arrays and to compare the terminal restriction fragment lengths of sheep derived by natural mating and nuclear transfer. Here we show that ovine somatic telomeres decrease in length with age, and that Dolly, derived by the transfer of 6-year-old adult somatic nucleus, exhibits diminished terminal restriction fragment lengths. The decrease is consistent with the age of the donor tissue and telomere erosion during in vitro culture. Nuclear transfer does not restore telomere lengths. Dolly otherwise appears physiologically and phenotypically normal for her breed and age. We further report on apparent telomere lengthening in sheep, occurring during the first year in naturally derived lambs.     

Somatic cell nuclear transfer: infinite reproduction of a unique diploid genome

In mammals, a diploid genome of an individual following fertilization of an egg and a spermatozoon is unique and irreproducible. This implies that the generated unique diploid genome is doomed with the individual ending. Even as cultured cells from the individual, they cannot normally proliferate in perpetuity because of the "Hayflick limit". However, Dolly, the sheep cloned from an adult mammary gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables us to produce offspring without germ cells, that is, to "passage" a unique diploid genome. Animal cloning has also proven to be a powerful research tool for reprogramming in many mammals, notably mouse and cow. The mechanism underlying reprogramming, however, remains largely unknown and, animal cloning has been inefficient as a result. More momentously, in addition to abortion and fetal mortality, some cloned animals display possible premature aging phenotypes including early death and short telomere lengths. Under these inauspicious conditions, is it really possible for SCNT to preserve a diploid genome? Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear transfer ES cells (ntES) more efficiently, which can preserve the eternal lifespan for the "passage" of a unique diploid genome. Further, new somatic cloning technique using histone-deacetylase inhibitors has been developed which can significantly increase the previous cloning rates two to six times. Here, we introduce SCNT and its value as a preservation tool for a diploid genome while reviewing aging of cloned animals on cellular and individual levels.     

On Cloning: Advocating History of Biology in the Public Interest

Cloning – the process of creating a cell, tissue line or even a complete organism from a single cell – or the strands that led to the cloning of a mammal, Dolly, are not new. Yet the media coverage of Dolly's inception raised a range of reactions from fear or moral repulsion, to cautious optimism. The implications for controlling human reproduction were clearly in the forefront, though many issues about animals emerged as well. On topics of public interest such as cloning, historians of biology have the opportunity to make a unique contribution. Such debates are often aired as if they have no precedents, either in biology or in the ethical, moral, and social concerns arising in the public arena. The technology leading to Dolly draws on strands of research going back to the 1890s, and the cycle of public response has been repeated often in the past century. What can we learn from examining these events historically, and how can we – or should we even try – to inform public opinion? I think we should try and will outline briefly some of the ways that can work.     

Characterization of MTNR1A gene in terms of genetic variability in a panel of subtemperate and subtropical Indian sheep breeds

Seasonality of animals is an important adaptive trait for successful survival and production during limited food availability and extreme environmental conditions. Photoperiodic changes in day length are utilized by these seasonal animals as an important environmental cue for regulating their annual rhythms of reproduction cycles. Melatonin is an important hormone which is secreted by the pineal gland in proportion to darkness and its effect is mediated by melatonin receptor subtypes, principally MTNR1A. In the present study, polymorphism in the coding sequence at two important SNPs (C606T and G612A), known to be markers for out of season breeding in sheep were studied by PCR-RFLP in a panel of four breeds of sheep from subtemperate and subtropical arid conditions, respectively. The frequencies of ‘G’ and ‘A’ alleles with reference to G612A SNP did not differ considerably among all the breeds of sheep. Frequency of ‘T’ allele of the C606T SNP was found to be dominantly higher in subtemperate sheep breeds in comparison to subtropical sheep breeds. Identified SNPs in the coding region were mostly synonymous and did not lead to any change in conformation of the MTNR1A receptor protein.     

Somatic cell nuclear transfer: Past, present and future perspectives

It is now over a decade since the birth, in 1996, of Dolly the first animal to be produced by nuclear transfer using an adult derived somatic cell as nuclear donor. Since this time similar techniques have been successfully applied to a range of species producing live offspring and allowing the development of transgenic technologies for agricultural, biotechnological and medical uses. However, though applicable to a range of species, overall, the efficiencies of development of healthy offspring remain low. The low frequency of successful development has been attributed to incomplete or inappropriate reprogramming of the transferred nuclear genome. Many studies have demonstrated that such reprogramming occurs by epigenetic mechanisms not involving alterations in DNA sequence, however, at present the molecular mechanisms underlying reprogramming are poorly defined. Since the birth of Dolly many studies have attempted to improve the frequency of development, this review will discuss the process of animal production by nuclear transfer and in particular changes in the methodology which have increased development and survival, simplified or increased robustness of the technique. Although much of the discussion is applicable across species, for simplicity we will concentrate primarily on published data for cattle, sheep, pigs and mice.