A critique is made of Bernard Rollin''s examination of the ethics of cloning adult mammalian cells. The primary concern is less to propound an anticloning or procloning position than to call for full exploration of the ethical complexities before a rush to judgment is made. Indeed, the ethical examination in question rushes toward an ethical position in such a way that does not appear consistent with Rollin''s usual methodology. By extending this methodology – which entails full weighing of (...) benefits and costs – it becomes apparent that there are real potential risks to this type of cloning in both animals and humans, besides the possible benefits, and that the scientific, political, philosophical, and broader academic communities should explore these risks and benefits extensively. Rollin''s usual methodological call for hesitation before risks would translate into hesitation before the ethical risks of adult mammalian cell cloning instead of his paper''s curiously laissez-faire stance. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 12.3 (2002) 305-323 [Access article in PDF] Scope Note 41 Bioethics and Cloning, Part I Susan Cartier Poland and Laura Jane Bishop This is Part One of a two part Scope Note on Bioethics and Cloning. Part Two will be published in the December 2002 issue of the Kennedy Institute of Ethics Journal and as a separate reprint. Contents For Parts 1 (...) And 2 Part 1Part 2I.History of the ScienceI.Ethical PerspectivesII.Historical CommentaryII.Religious PerspectivesIII.Animal WelfareIII.Fiction and FilmIV.Laws and Legal Literature"Clone" is a collective noun (I, Stewart 1997, p. 771). A collective noun names a group and is composed of individual members, such as "herd" or "flock." Derived from the Greek kl¯on for twig or slip, "clone" was first used in biology to describe the aggregate of asexually produced progeny of an individual, either naturally occurring or man-made; the definition later expanded to mean a group of genetically identical members who originate from a single ancestor. Thus, a clone is a group that results from the process of asexual reproduction.In nature, cloning occurs either by parthenogenesis (reproduction without fertilization) or by fission (embryo splitting). In a pioneering experiment in 1952, Robert Briggs and Thomas J. King (I, 1952), cancer researchers at the Institute for Cancer Research (today part of the Fox Chase Cancer Center) in Philadelphia, demonstrated on frogs another method of cloning by transplanting nuclei into enucleated cells, a technique called "nuclear transplantation," which John B. Gurdon and colleagues (I, 1958, 1975) used to create clones of frogs.Then, in the late 1970s and early 1980s, two back-to-back frauds in cloning occurred. First, the cloning of a human described by American science journalist David Rorvik in the 1978 book In His Image was called a hoax by a court in [End Page 305] 1982. Second, the cloning of three mice, announced by German wunderkind Karl Illmensee to scientific circles in 1979 (and to the public in 1981), could not be proven to be true, according to convincing evidence by McGrath and Solter (I) published in 1984.With their pronouncement that mammalian cloning was impossible, McGrath and Solter essentially stopped cloning research and funding for such biological research. So by the mid-1980s, instead of further investigating cloning, developmental biologists studied embryology related to in vitro fertilization, while molecular biologists studied recombinant DNA under the newly relaxed NIH guidelines. These two strands of scientific investigation came together in the work of Ian Wilmut, who created in vitro embryos using nuclear transplantation to reproduce genetically engineered cattle. Wilmut was seeking a way to increase the successful birth rate when, in the 1990s, he produced identical twin sheep, Megan and Morag, cloned from an embryonic cell, followed by another sheep, Dolly, cloned from an adult cell. The birth of a mammal from an embryo whose genetic material came from an adult cell firmly re-established the possibility of cloning from adults. Prior to Dolly's birth, scientists believed that adult cells lost the ability to dedifferentiate—i.e., to become unspecialized—and so could not direct the development of an embryo through to birth.The 1997 announcement of Dolly's birth initiated the present widespread discussion of cloning. Because of its potentially vast applications across human health, medicine, agriculture, and business/economics, cloning raises a host of issues including those concerning: genetics and genetic engineering, patenting, animal rights and/or animal welfare (especially for transgenic, research, or cloned animals), organ transplantation, reproduction, eugenics, pharmacology (drug production using transgenic animals), research practices, informed consent, stem cell research, women's rights, children's rights, parental rights and responsibilities, and theology and philosophy. It fosters questions about the meaning and purpose of life, the limits of human powers to intervene in research and therapy, and what it means to be human or animal. In addition, environmentalists and organic farmers raise concerns about the effect of novel animals and plants on the environment, while nutritionists and the lay public wonder... (shrink)

To clone humans is deliberately to generate two or more individuals who share the same nuclear deoxyribonucleic acid. Using animals, researchers have performed two basic types of cloning that will eventually yield commercial benefits. Embryo twinning involves separating the individual cells of an embryo and allowing each to cleave for later transfer to a uterus. Cloning by nuclear transfer involves removing the nuclei from embryonic cells or fetal or adult somatic cells and fusing those nuclei with enucleated (...) donor egg cells. Although for the purposes of commercial biotechnology these techniques do not raise undue concern when attempted with animals, embryo twinning, embryo nuclear transfer, fetal somatic cell nuclear transfer, and adult somatic cell nuclear transfer all provoke intense ethical discussions when considered for human use. (shrink)

On Sunday morning, 23 February 1997, the world awoke to a technological advance that shook the foundations of biology and philosophy. On that day, we were introduced to Dolly, a 6-month-old lamb that had been cloned directly from a single cell taken from the breast tissue of an adult donor. Perhaps more astonished by this accomplishment than any of their neighbors were the scientists who actually worked in the field of mammalian genetics and embryology. Outside the lab where (...) the cloning had actually taken place, most of us thought it could never happen. Oh, we would say that perhaps at some point in the distant future, cloning might become feasible through the use of sophisticated biotechnologies far beyond those available to us now. But what many of us really believed, deep in our hearts, was that this was one biological feat we could never master. New lifemust have its origins in an embryo formed through the merger of gametes from a mother and father. It was impossible, we thought, for a cell from an adult mammal to become reprogrammed, to start all over again, to generate another entire animal or person in the image of the one born earlier. (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)

Stem cell research is very promising. The use of human embryos has been confronted with objections based on ethical and religious positions. The recent production of reprogrammed adult (induced pluripotent) cells does not – in the opinion of scientists – reduce the need to continue human embryonic stem cell research. So the debate continues.Islam always encouraged scientific research, particularly research directed toward finding cures for human disease. Based on the expectation of potential benefits, Islamic teachings permit and (...) support human embryonic stem cell research. The majority of Muslim scholars also support therapeutic cloning. This permissibility is conditional on the use of supernumerary early pre-embryos which are obtained during infertility treatment in vitro fertilization (IVF) clinics. The early pre-embryos are considered in Islamic jurisprudence as worthy of respect but do not have the full sanctity offered to the embryo after implantation in the uterus and especially after ensoulment.In this paper the Islamic positions regarding human embryonic stem cell research and therapeutic cloning are reviewed in some detail, whereas positions in other religious traditions are mentioned only briefly.The status of human embryonic stem cell research and therapeutic cloning in different countries, including the USA and especially in Muslim countries, is discussed. (shrink)

In 2001, the U.S. House of Representatives passed the "Human Cloning Prohibition Act" and President Bush announced his decision to allow only limited research on existing stem cell lines but not on "embryos." In contrast, the U.K. has explicitly authorized "therapeutic cloning." Much more will be said about bioethical, legal, and social implications, but subtleties of the science and careful definitions of terms have received much less consideration. Legislators and reporters struggle to discuss "cloning," "pluripotency," "stem (...) cells," and "embryos," and whether "adult" are preferable to "embryonic" stem cells as research subjects. They profess to abhor "copying humans" or "killing embryos." Do they know what they are talking about? Do we? This paper explores the historical, philosophical, and scientific contexts that inform this heated discussion. (shrink)

This paper addresses the 1996 cloning of Dolly the sheep, locating it within a long-standing tradition of animal breeding research in Edinburgh. Far from being an end in itself, the cell-nuclear transfer experiment from which Dolly was born should be seen as a step in an investigative pathway that sought the production of medically relevant transgenic animals. By historicising Dolly, I illustrate how the birth of this sheep captures a dramatic redefinition of the life sciences, when in (...) the 1970s and 1980s the rise of neo-liberal governments and the emergence of the biotechnology market pushed research institutions to show tangible applications of their work. Through this broader interpretative framework, the Dolly story emerges as a case study of the deep transformations of agricultural experimentation during the last third of the twentieth century. The reorganisation of laboratory practice, human resources and institutional settings required by the production of transgenic animals had unanticipated consequences. One of these unanticipated effects was that the boundaries between animal and human health became blurred. As a result of this, new professional spaces emerged and the identity of Dolly the sheep was reconfigured, from an instrument for livestock improvement in the farm to a more universal symbol of the new cloning age. -/- . (shrink)

Someday soon (if it hasn't happened in secret already), a human will be cloned, and mankind will embark on a scientific and moral journey whose destination cannot be foretold. In Copycats: The Science and Ethics of Cloning, Arlene Judith Klotzko describes the new world of possibilities that can be glimpsed over the horizon. In a lucid and engaging narrative, she explains that the technology to create clones of living beings already exists, inaugurated in 1996 by Dolly the sheep, the (...) first mammal cloned from a single adult cell. Dolly is the culmination of a long scientific quest to understand the puzzle of our development from one cell into a complex organism--the outcome of a "fantastic experiment" envisioned six decades before her birth. Scientists have since cloned mice, cows, goats, pigs, rabbits and cats. Using the same laboratory tools and techniques, they are trying to grow an embryo, cloned from a single cell of a human being. Their goal is not to make copies of existing people, but to design therapies for currently untreatable diseases and the afflictions of old age. Our fascination with cloning is about much more than science and its extraordinary medical implications. In riveting prose, full of illusions to art, music and the cinema, Klotzko shows why the prospect of human cloning triggers our dearest hopes and especially our darkest fears, forcing us to ponder anew what it means to be human. And what it would be like to have "a clone of your own.". (shrink)

Patents recognize economic right and are important for both individual and social economic benefit. Nonetheless, mere economic right does not eliminate the requirement for moral assessment when adjudicating intellectual property claims, especially in the case of claims associated with applications of biomedical technology [e.g., somatic cell nuclear transfer methods]. This is so for applications for patent in the case of live-born animal clones, as governed in the setting of the judicial system of the USA. Here recent federal court (...) decisions in the USA are reviewed, and the ethical ambiguities of this judicial review are engaged in light of the current prohibitions on human reproductive cloning. It is concluded that the legal proscription of patents on animal clones bodes well for human accountability to present and future generations in the event of human reproductive cloning. (shrink)

As the #1 topic in bioethics, cloning has made big news since Dolly's announced birth in 1998. In a new book building on his classic Who's Afraid of Human Cloning?, pioneering bioethicist Gregory E. Pence continues to advocate a reasoned view of cloning. Beginning with his surreal experiences as an expert witness before Congressional and California legislative committees, Pence analyzes the astounding recent progress in animal cloning; the coming surprises about human cloning; the links (...) between animal, stem cell, and human cloning; embryo politics; and other hot topics like artificial wombs and transgenic animals. -/- Pence rebuts the growing chorus of naysayers headed by Leon Kass, chairman of the President's Council on Bioethics, who attack the biomedical sciences, and explains why cloning will save endangered species and beloved pets, and help future children and people with degenerative diseases. (shrink)

A common feature of scientific and ethical debates is that clones are generally described and understood as “copies” or, more specifically defined, as “genetic copies.” The attempt of this paper is to question this widespread definition. It first argues that the terminology of “clone as copy” can only be understood as a metaphor, and therefore, a clone is not a “genetic copy” in a strict literal sense, but in a figurative one. Second, the copy metaphor has a normative component that (...) is problematic in the context of descriptive science and may support or indicate the ethically relevant phenomenon of objectification of animals. In order to support the argument against the common conception of a clone as a copy, the biotechnological principles of somatic cell nuclear transfer cloning will be examined. On this basis, it will be shown that the metaphor is valid because of similarities between the phenotype, the genotype, or the nuclear DNA sequence of the clone and its progenitor by using three prominent levels of comparison. Focusing on the process of SCNT, it will be shown that cloning as copying or doubling has to be redefined for scientific purposes because it is neither necessary nor does it fit to the biotechnological principles of cloning. It is more accurate to understand SCNT cloning as a process of splitting rather than of doubling or copying. In the second part, a deconstructivist analysis based on Jacques Derrida’s description in Positions will reveal the normative potential of the original–copy dichotomy. I will be showing that it includes an asymmetrical power structure between the original and the copy and that this structure can be reversed or at least considered unstable. Therefore, arguments that build on that metaphor must be reconsidered. Moreover, the analysis reveals that applying a terminology to humans and animals that is commonly used for things becomes the language of objectification. Two selected examples, fungibility and violability, based on Martha Nussbaum’s notion of objectification will support the thesis of objectification, display its normative consequences, and put the clone as a copy metaphor in a broader range of ethically questionable research tendencies. (shrink)

Certain events settle themselves in the collective memory of humankind where they keep functioning for decades as points of reference for future generations. The announcement of the successful cloning of Dolly was such an event. Every one of us will remember this thought-provoking occasion or will, at least, be confronted with the extended media coverage of this breakthrough in medical science. Immediately, world leaders reacted and the question was raised how long it would take before the shepherd was cloned. (...) More important is the sequel to this medical breakthrough: the successful Dolly experiment led to the possibility of human embryonic and adult stem cell research. In 2000, the Pontifical Academy for Life took a position on this additional and innovative research. At the same time, understanding these technological innovations takes a lot of time as a result of the immense scientific complexity of these new technologies. In this article, we want to clarify the technological possibilities as well as the moral, theological and ethical issues involved. To some, it seems that humans usurped the Divine Creator's place and, by doing this, crossed a border. To others, this medical breakthrough is in line with previous reproductive technological innovations. (shrink)

Since the first successful attempt to clone a dog in 2005, dogs have been cloned by Somatic Cell Nuclear Transfer for a variety of purposes. One of these is to clone dogs as companion animals. In this paper we discuss some of the ethical implications that cloning companion dogs through SCNT encompasses, specifically in relation to human–dog relationships, but also regarding animal welfare and animal integrity. We argue that insofar as we understand the relationship with our (...) companion dogs as one of friendship, the meaningfulness of cloning a companion dog is seriously questionable. Cloning may both disrupt the uniqueness of the relationship, as the shared history underlying the relationship can neither be repeated nor copied, and it may violate the meaning we attribute to friendship, as the notion of singularity inherent in our understanding of friendship is incompatible with the replaceability embedded in the practice of cloning. We further argue that the application of cloning technology to companion dogs can be interpreted as a violation of the integrity of dogs on at least two accounts: negative welfare implications associated with the cloning process, and the instrumentalisation of the dog inherent in cloning. (shrink)

Many countries or jurisdictions have legally banned human cloning or are in the process of doing so. In some countries, including France and Singapore, reproductive cloning of humans is a criminal offence. In 2005, the United Nations adopted a ‘Declaration on Human Cloning’, which calls for a universal ban on human cloning. The debate on human reproductive cloning seems to have drawn to a close. However, since reproductive cloning of mammals has become routine in (...) several countries, there is reason to believe that at some point in the future, humans will be cloned too. Moreover, even if reproductive cloning will not be possible in the near future, cloning for research and therapeutic purposes is likely to be. -/- This entry describes the most important areas of disagreement regarding the ethics of cloning. I will focus on human cloning (as opposed to animal cloning), since human cloning has been the focus of the cloning debate. (shrink)

The possibility of human reproductive cloning has led some bioethicists to suggest that potentiality-based arguments for fetal moral status become untenable, as such arguments would be committed to making the implausible claim that any adult somatic cell is itself a potential person. In this article I defend potentiality-based arguments for fetal moral status against such a reductio. Starling from the widely-held claim that the maintenance of numerical identity throughout successive changes places constraints on what a given entity (...) can plausibly be said to have the potential to become, I argue that the cell reprogramming that takes place in reproductive cloning is such that it produces a new individual, and so adult somatic cells cannot be potential persons. (shrink)

The author, a member of the U.S.President's Council on Bioethics, discussesethical issues raised by human cloning, whetherfor purposes of bringing babies to birth or forresearch purposes. He first argues that everycloned human embryo is a new, distinct, andenduring organism, belonging to the speciesHomo sapiens, and directing its owndevelopment toward maturity. He then distinguishesbetween two types of capacities belonging toindividual organisms belonging to this species,an immediately exerciseable capacity and abasic natural capacity that develops over time. He argues that it is (...) the second type ofcapacity that is the ground for full moralrespect, and that this capacity (and itsconcomitant degree of respect) belongs tocloned human embryos no less than to adulthuman beings. He then considers and rejectscounter-arguments to his position, includingthe suggestion that the capacity of embryos isequivalent to the capacity of somatic cells,that full human rights are afforded only tohuman organisms with functioning brains, thatthe possibility of twinning diminishes themoral status of embryos, that the fact thatpeople do not typically mourn the loss of earlyembryos implies that they have a diminishedmoral status, that the fact that earlyspontaneous abortions occur frequentlydiminishes the moral status of embryos, andthat his arguments depend upon a concept ofensoulment. He concludes that if the moralstatus of cloned human embryos is equivalent tothat of adults, then public policy should bebased upon this assumption. (shrink)

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. (shrink)

What makes something an embryo—as opposed to what is actually, and not just in biotech parlance, a collection of cells? This question has come to the fore in recent years with proposals for producing embryonic stem cells for research. While some of those opposed to use of standard embryonic stem cells emphasise that adult cells have a clinical track record, others argue that there may be further benefits obtainable from cells very like those of embryos, provided such cells can (...) be derived in new ways. Rather than deriving them in ways that kill or otherwise endanger a living human embryo, they could be obtained from an entity that merely resembles a human embryo sufficiently closely for its cells to be of use. Such an entity might be created after introducing genetic changes to an ovum before it is activated by, for example, a cloning-type procedure, such that a gene essential to embryogenesis will be either absent, blocked in its expression, or overexpressed.1,2 The claim is that the ovum could be made to give rise to embryonic stem cells—mere living parts—without ever giving rise to a whole embryo, who is killed to obtain them. Whereas cloning “proper” winds back the specialisation of the cell nucleus to a point where a whole embryo is formed who has not yet specialised its cells, oocyte-assisted reprogramming , it is claimed, would wind back the specialisation merely to an intermediate point at which no embryo is created. Other methods proposed for deriving pseudoembryonic cells include parthenogenesis, in which an ovum is activated without a sperm, or even the insertion of an adult cell nucleus.1MORAL STATUS OF THE EMBRYOIn this paper, I assume that a genuine …. (shrink)

On 5 July 1996 a sheep named Dolly was born in Scotland, the result of the transfer of the nucleus of an adult mammary tissue cell to the enucleated egg cell of an unrelated sheep, and gestation in a third, surrogate mother sheep. Although for the past ten years scientists have routinely cloned sheep and cows from embryo cells, this was the first cloning experiment that apparently succeeded using the nucleus of an adult cell.

Every body cell of an animal or human being contains the same complete set of genes. In theory any of these cells can be used to start a new embryo. The technique has been employed in the case of frogs. The nucleus is taken out of a body cell of a frog and implanted in an enucleated frog's egg. The resulting egg cell is stimulated to develop into a normal frog, and will be an exact copy (...) of that frog which provided the nucleus with all the genetic information. In normal sexual reproduction, two parents each contribute half their genes, but in the case of cloning, one parent passes on all his or her genes. (shrink)

As the debates over cloning and stem cell research indicate, issues raised by biotechnology combine research into the genetic sciences, perspectives and contexts articulated by the social sciences, and the ethical and anthropological concerns of philosophy. Consequently, I argue that intervening in the debates over biotechnology requires supra-disciplinary critical philosophy and social theory to illuminate the problems and their stakes. In addition, debates over cloning and stem cell research raise exceptionally important challenges to bioethics and a (...) democratic politics of communication. (shrink)

The recent successful conversion of adult cells into induced pluripotent stem (iPS) cells through direct reprogramming opens a new chapter in the study of disease and the development of regenerative medicine. It also provides a historic opportunity to turn away from the ethically problematic use of embryonic stem cells isolated through the destruction of human embryos. Moreover, because iPS cells are patient specific, they render therapeutic cloning unnecessary. To maximize therapeutic benefit, adult stem cell research will (...) need to be pursued in parallel with studies using iPS cells. Among the four alternative methods presented by the President’s Council on Bioethics, direct reprogram- ming is the most ethically acceptable. Nonetheless, iPS cells are tainted by their association with the human embryonic stem cell lines, derived in the past, which will be required for their validation. This concern is one that can be resolved. Human iPS cells will serve to stem the tide of human embryonic stem cell research, changing it and diverting stem cell research in a more ethical direction. (shrink)

Carson Strong has argued that if human cloning were safe it should be available to some infertile couples as a matter of ethics and law. He holds that cloning by somatic cell nuclear transfer should be available as a reproductive option for infertile couples who could not otherwise have a child genetically related to one member of the couple. In this analysis, Strong overlooks an important category of people to whom his argument might apply, couples he has (...) not failed to consider elsewhere. In this discussion, however, Strong refers exclusively to opposite sex couples facing obstacles such as surgically removed ovaries and the inability to produce sperm. In fact, however, there are many adult couples who, while fertile in and of themselves, are not fertile as couples. This group includes not only opposite sex couples but coupled same sex partners as well. I believe the defenses Strong offers regarding the use of SCNT by opposite sex infertile couples would extend to same sex couples for two reasons. First, some same sex couples might face the inability to have a genetically related child, and second, Strong's arguments ultimately ground a general defense of SCNT independent of the question of a couple's fertility. (shrink)

This paper queries why we are more reluctant to perform stem cell research on human than on nonhuman embryos, given their remarkable similarities together with the former's greater promise for addressing human illnesses. I begin by examining two leading arguments for prohibiting stem cell research on human embryos. The first type of argument suggests that we should not interfere with the potential for human life. This argument, advanced in different ways by both utilitarians and religious believers, inadequately grapples (...) with the moral complexities raised by current technologies, such as IVF and cloning. Moreover, it fails to address the significant adverse effects of human overpopulation to both human and nonhuman well-being. The second line of argument addressed here suggests that we are morally prohibited from "playing God." This argument overlooks the various ways in which we do—indeed, we must—make life and death decisions. Further, the argument rests on an undefended assumption that we are only prohibited from making such decisions with regard to human life, while remaining free to make such decisions with regard to animals without apparent moral qualms. On the contrary, I argue that, from a fully ethical Darwinian standpoint, we must treat both human and nonhuman life with respect. Far from requiring us to abstain from difficult moral decision making, an attitude of respect toward all life requires human willingness to take responsibility for making difficult—indeed, sometimes excruciating—moral decisions. (shrink)

No comprehensive theory of development is available yet. Traditionally, we regard the development of animals as a sequence of changes through which an adult multicellular animal is produced, starting from a single cell which is usually a fertilized egg, through increasingly complex stages. However, many phenomena that would not qualify as developmental according to these criteria would nevertheless qualify as developmental in that they imply nontrivial (e.g., non degenerative) changes of form, and/or substantial changes in gene expression. (...) A broad, comparative approach is badly needed. In the Cnidaria, for example, even the boundary between generations is problematic. Describing their life cycle in terms of metagenesis (alternation between polyp generation and medusa generation) or in terms of metamorphosis (polyp as larva or juvenile) are matters of semantics more than biology. The life cycle of other metazoans, described in textbooks in terms of larva-to-adult metamorphosis, is hardly different from a typical metagenetic life cycle of cnidarians. This applies to holometabolous insects and to marine invertebrates like sea urchins, where most of the larval cells are discarded at metamorphosis. The uncertain temporal and spatial boundaries of individual development are also shown by the widespread lack of a strict correspondence between adult and mature. A comprehensive theory of development should start with a zero principle of “developmental inertia,” corresponding to an indeterminate local self-perpetuation of cell-level dynamics. Indeterminate growth, scale-invariance, segmentation, and regeneration provide examples of developmental dynamics close to that. (shrink)

On 25 April 2002, the German Parliament has passed a strict new law referring to stem cell research. This law took effect on July 1, 2002. The so-called embryonic Stem Cell Act ( Stammzellgesetz — StZG ) permits the import of embryonic stem (ES) cells isolated from surplus IvF-embryos for research reasons. The production itself of ES cells from human blastocysts has been prohibited by the German Embryo Protection Act of 1990, with the exception of the use of (...) ES cells which exist already. The debate on the legitimate use of ES cells escalated, after the main German research funding agency, the Deutsche Forschungsgemeinschaft (DFG), unexpectedly published new guidelines recommending are stricted use of human ES cells for research. Meanwhile, the debate has ethically dividedsociety, political parties, government and church members into a group supporting and a group rejecting ES cell research. The arguments in favour of such a research can be summarized as arguments derived from a new ethics ofhealing calling for a therapeutic imperative, whereas the arguments against can be summarized as arguments violating the fundamental principle of human dignity as they imply the destruction of human embryos. This article willtry to present and evaluate various ethical arguments founded on the latest biological and medical data on the potential use of stem cell technologies. It will finally come to the conclusion that ES cell research is opposed to human dignity, since the procedures of isolating ES cells require the destruction and instrumentalization of human embryos. Human embryos are human beings at a very early stage of their development, fully possessing the ability of completing their development. At this very early stage, human embryos are extremely dependent and fragile, and thus vulnerable corporealities. Vulnerability and human dignity demand the protection of the embryo's corporeal integrity. Hence, this essay will try to propagate research with adult stem(AS) cells, a procedure which does not require the destruction of human embryos; with regard to the necessary plasticity, it should be emphasized that AS cells very much resemble ES cells. (shrink)

This thematic issue addresses questions of constraints on the evolution of form—physical, biological, and technical. Here, form is defined as an embodiment of a specific structure, which can be hierarchically different yet emerge from the same processes. The focus of this contribution is about how developmental biology and paleontology can be better integrated and compared in order to produce hypotheses about the evolution of form. The constraints on current EvoDevo research stem from the disconnect in the focus of study for (...) developmental geneticists and evolutionary morphologists; the former being interested in early developmental events at a molecular level in a model animal, the latter in late developmental events or comparison between adult forms, at a structural level in non-model animals. In order to truly integrate information from both fields in our understanding of evolutionary processes, morphology needs to be reintegrated in the study of gene expression, and its time frame needs to be extended beyond early developmental stages. Gene expression in non-model organisms also needs to be studied in order to gain perspective into primitive patterning at evolutionary nodes. Hypotheses formed by the comparison of expression patterns and morphologies seen in extant species can then be tested against forms found in the fossil record, coming closer to understanding the mechanisms underlying evolution. (shrink)

This paper traces the history of the Animal Research Station, Cambridge from its establishment in 1932 to its closure in 1986. The author worked there for forty years and was Director from 1979. Originally set up as a field station for Cambridge University’s School of Agriculture, the Station was expanded after World War II as the Agricultural Research Council’s Unit of Animal Reproduction. Beginning with semen and artificial insemination, research at the Station soon embraced superovulation and embryo transfer (...) in farm animals. Many other technologies were also developed here, including IVF in pigs, cloning by nuclear transplantation of early embryonic cells, and the first genetically modified farm animals in Britain. This account recalls the Directors of the Station and their research teams together with details of their pioneering contribution to reproductive biology. (shrink)

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS (...) class='Hi'>cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes. (shrink)

Regeneration capabilities are found in most or all animals. Whether regeneration is part of the development of an animal or a distinct phenomenon independent of development is a debatable question. If we consider regeneration as a process belonging to development, similarly to embryogenesis or metamorphosis, the existence of regenerative capabilities in adults can be seen as an argument in favor of the theory that development continues throughout the life of animals. Here I perform a comparative analysis of regeneration versus (...) “classical” developmental processes in animals in order to determine to what extent these processes are inclusive or distinct. I identify the existence of regeneration-specific processes, i.e., processes that occur during the regeneration, but not the initial development, of a given structure. In addition, I find that seemingly similar processes acting during development and regeneration may have differential molecular and cellular bases. I thus conclude that there are significant differences between regeneration processes in adult animals and developmental processes occurring during earlier phases of the life cycle. The existence of regenerative capabilities in adult animals can therefore not be used as an argument in favor of the idea that development spans the whole life. (shrink)

Five partly successive and partly overlapping framings have dominated the public debate about human embryonic stem cells since they first were “derived” a decade ago. Geron Corporation staged the initial framings as 1) basic research and 2) medical hope, but these two were immediately refuted and opposed by 3) bioethical concerns, voiced by influential politicians and leaders of opinion. Thereafter, the research community presented adult stem cells and therapeutic cloning as 4) techno-fix solutions supposed to bypass these ethical (...) concerns. And in recent years, 5) institutional limitations to and hurdles within the university–industrial complex (such as patentability, misconduct and fraud) have attracted more attention. The article purifies the arguments and points out the interests and institutions behind the five framings. It also discusses their interplay and finally addresses the question of what happened to the stem cells? (shrink)

This article is concerned with the problem of the relation between the genetic information contained in the DNA and the emergence of visible structure in multicellular animals. The answer is sought in a reappraisal of the data of experimental embryology, considering molecular, cellular and organismal aspects. The presence of specific molecules only confers a tissue identity on the cells when their concentration exceeds the threshold of differentiation. When this condition is not fulfilled the activity of the genes that code for (...) the specific molecules in question only confers on them a histogenetic potency, i.e. the capacity to form the corresponding tissue in further development (or to transdifferentiate to that tissue). The progressive restriction of histogenetic potencies during development reflects the irreversible repression of more and more genes. The establishment of a given tissue identity under the influence of an inducing tissue (or a morphogenetic hormone) is only possible when the cells have acquired the competence to respond. Tissue differentiation proceeds progressively during development thanks to the cytoplasmic memory that cells retain collectively (or sometimes individually) of the items of information successively registered by their ancestors cells. The increasing complexity of visible structure emerging during development results only from the progression of tissue differentiation. This involves continual exchange of information among the cells and leads to (1) cell displacements and rearrangements, particularly during organogenesis and (2) extreme diversification of cell individualities within tissues, particularly during postembryonic growth. A mutation (just as a teratogenic factor) evokes an anomaly that is localized in both space and time because it alters a certain aspect of cell behaviour (particularly cell surface adhesiveness or mitotic activity) at the time when this is involved in the establishment of a particular structural trait. Neither the organization of the adult nor the modalities of development are encoded in the DNA. The automatic concatenation of cell interactions in the embryo and the structural amplification it entails is conditioned by the specific biochemical composition of the cytoplasm of the egg and by the heterogeneous distribution of its inclusions. (shrink)

As a moral philosopher, the perspective I will take in this chapter is one of argumentation and informed judgment about two main questions: whether individuals should ever choose to conduct human embryonic stem cell research, and whether the law should permit this type of research. I will also touch upon a secondary question, that of whether the government ought to pay for this type of research. I will discuss some of the main arguments at stake, and explain how the (...) ethical conflict over these questions differs from the political conflict over them. I will be guided throughout by the assumption that the unique scientific and clinical promise of human embryonic stem cell research is significant. Those who have doubts about this assumption should consult other chapters in this volume in which the issue is addressed directly. I begin with one of the basic facts relevant to the ethical issue of stem cell research: you and I, along with everybody else we know, developed out of clumps of primordial cells, which happen to be the very same clumps that serve as the source for human embryonic stem cells in the laboratory. Let us call these “source cells” for short, since they can be used in this way. Each individual has developed into whatever she is now out of a one-celled animal, which then became a blastocyst, a multi-celled human embryo. These blastocysts are partly made up of an inner mass of cells, and the body of every adult person has developed out of this inner mass. It is this very same clump from the inner part of the blastocyst that consists of source cells for human embryonic stem 1 cell research. These cells can be extracted and grown into a laboratory specimen of extraordinary interest to scientists. Before discussing the significance of the fact that all humans originate from these source cells, it is useful to begin by asking some perhaps rather simple-minded questions about how any one of us knows this fact to be true in the first place. How do I know that I developed from a single cell, and then a blastocyst? In my own case, the main way I know this is that other people have told me so.. (shrink)

Regenerative medicine promises to greatly impact on human health by improving repair outcomes in a range of tissues and injury contexts. Successful therapies will rely on identifying both intrinsic and extrinsic biological circuits that control wound healing, proliferation, cell survival, and developmental cell fate. Animals such as the zebrafish and the salamander display powerful examples of near‐perfect regeneration and scar‐free healing in a range of injury contexts not attained in mammals. By studying regeneration in a range of highly (...) regenerative species that maintain regenerative potential throughout life, many instructive and permissive factors have been identified that could assist in the development of regenerative therapies. This review highlights some of the recent observations in immune regulation, epigenetic regulation, stem cell mobilization, and regenerative signatures that have improved our understanding of the regenerative process. Potential opportunities in harnessing this knowledge for future translation into the clinic are discussed. (shrink)

Despite the progress achieved over the last decade after the birth of the first cloned mammal, the efficiency of reproductive cloning remains invariably low. However, research aiming at the use of nuclear transfer for the production of patient‐tailored stem cells for cell/tissue therapy is progressing rapidly. Yet, reproductive cloning has many potential implications for animal breeding, transgenic research and the conservation of endangered species. In this article we suggest that the changes in the epi‐/genotype observed in (...) cloned embryos arise from unbalanced nuclear reprogramming between parental chromosomes. It is probable that the oocyte reprogramming machinery, devised for resident chromosomes, cannot target the paternal alleles of somatic cells. We, therefore, suggest that a reasonable approach to balance this asymmetry in nuclear reprogramming might involve the transient expression in donor cells of chromatin remodelling proteins, which are physiologically expressed during spermatogenesis, in order to induce a male‐specific chromatin organisation in the somatic cells before nuclear transfer. BioEssays 30:66–74, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

Like most bilaterian animals, the annelid Platynereis dumerilii generates the majority of its body axis in an anterior to posterior temporal progression with new segments added sequentially. This process relies on a posterior subterminal proliferative body region, known as the "segment addition zone" (SAZ). We explored some of the molecular and cellular aspects of posterior elongation in Platynereis, in particular to test the hypothesis that the SAZ contains a specific set of stem cells dedicated to posterior elongation.We cloned and characterized (...) the developmental expression patterns of orthologs of 17 genes known to be involved in the formation, behavior, or maintenance of stem cells in other metazoan models. These genes encode RNA-binding proteins(e.g., tudor, musashi, pumilio) or transcription factors(e.g., myc, id, runx) widely conserved in eumetazoans. Most of these genes are expressed both in the migrating primordial germ cells and in overlapping ring-like patterns in the SAZ, similar to some previously analyzed genes(piwi, vasa). The SAZ patterns are coincident with the expression of proliferation markers cyclin B and PCNA. EdU pulse and chase experiments suggest that new segments are produced through many rounds of divisions from small populations of teloblast-like posterior stem cells. The shared molecular signature between primordial germ cells and posterior stem cells in Platynereis thus corresponds to an ancestral "stemness" program. (shrink)

The larval arms of echinoid plutei are used for locomotion and feeding. They are composed of internal calcite skeletal rods covered by an ectoderm layer bearing a ciliary band. Skeletogenesis includes an autonomous molecular differentiation program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal plate for the blastocoel, and a patterning of the differentiated skeletal units that requires molecular cues from the overlaying ectoderm. The arms represent a larval feature that arose in the echinoid lineage during the (...) Paleozoic and offers a subject for the study of gene co-option in the evolution of novel larval features. We isolated new molecular markers in two closely related but differently developing species, Heliocidaris tuberculata and Heliocidaris erythrogramma. We report the expression of a larval arm-associated ectoderm gene tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase. Tetraspanin localizes to the animal half of blastula stage H. tuberculata and then undergoes a restriction into the putative oral ectoderm and future location of the postoral arms, where it continues to be expressed at the leading edge of both the postoral and anterolateral arms. In H. erythrogramma, its expression initiates in the animal half of blastulae and expands over the entire ectoderm from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the PMCs postgastrulation and localized to the leading edge of the growing larval arms of H. tuberculata but do not exhibit coordinated expression in H. erythrogramma larvae. The tight spatiotemporal regulation of these genes in H. tuberculata along with other ontogenetic and phylogenetic evidence suggest that pluteus arms are novel larval organs, distinguishable from the processes of skeletogenesis per se. The dissociation of expression control in H. erythrogramma suggest that coordinate gene expression in H. tuberculata evolved as part of the evolution of pluteus arms, and is not required for larval or adult development. (shrink)

What appeared to be the most momentous scientific advance of 2005 is currently under siege. In June, the prestigious journal Science published an article by the South Korean scientist Woo-Suk Hwang and an international team of co-authors describing how they had developed what were, in effect, “made to order†lines of human stem cells cloned from an adult. Although the scientific validity of their research is now the subject of several separate investigations, it is no less important to examine (...) its ethical implications. (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)

Louise Brown's birth in 1978 heralded a new era not just in reproductive technology, but in the relationship between science, cells, and society. For the first time, human embryos could be created, selected, studied, manipulated, frozen, altered, or destroyed, outside the human body. But with this possibility came a plethora of ethical questions. Is it acceptable to destroy a human embryo for the purpose of research? Or to create an embryo with the specific purpose of destroying it for research? In (...) an attempt to construct ethical and legal frameworks for the new era of cellular reprogramming, legislators and ethicists have tried to distinguish between different kinds of biological entity. We treat cells differently depending on whether they are human or animal, somatic cells or gametes, and on whether they are embryos or not. But this approach to the ethics of cellular reprogramming is doomed to failure for the simple reason that cellular reprogramming in itself destroys the distinctions that the law requires to function. In this article, we explore the historical trajectory of cellular reprogramming and its relationship with ethics and society. We suggest that the early hype of embryo research has not obviously fulfilled expectations, but since new avenues of research are continuously opening, it is hard to say definitely that these promises have been broken. We explore the forthcoming challenges posed by the creation of DNA from scratch in the laboratory, and the implications of this for understandings of identity, privacy, and reproduction. We conclude that while ethics used to seek answers in biological facts, this is no longer possible, and a new approach is required. (shrink)

Anuran amphibian metamorphosis is an immunologically interesting period. For the investigator, it provides an unusual opportunity for analyzing both humoral regulation of the immune response and the development and maintenance of self‐tolerance. Some of the questions one can ask are: Why don't immunocompetent larvae destroy antigenically disparate adult cells as they differentiate within them during metamorphosis? Do the dramatic hormonal changes occurring during this period regulate immunological function? How do animals in metamophorsis protect themselves from their immunologically hostile environment?

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 national identity , 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. (shrink)

Taste cells respond to a wide variety of chemical stimuli: certain ions are perceived as salty (Na+) or sour (H+); other small molecules are perceived as sweet (sugars) and bitter (alkaloids). Taste has evolutionary value allowing animals to respond positively (to sweet carhohydrates and salty NaCl) or aversively (to bitter poisons and corrosive acids). Recently, some of the proteins involved in taste transduction have been cloned. Several different G proteins have been identified and cloned from taste tissue: gustducin is a (...) taste cell specific G protein closely related to the transducins. Work is under way to clone additional components of the taste transduction pathways. The combination of electrophysiology, biochemistry and molecular biology is being used to characterize taste receptor cells and their sensory transduction mechanisms. (shrink)

Anamniote animals, such as fish and amphibians, are able to regenerate damaged CNS nerves following injury, but regeneration in the mammalian CNS tracts, such as the optic nerve, does not occur. However, severed adult mammalian retinal axons can regenerate into peripheral nerve segments grafted into the brain and this finding has emphasized the importance of the environment in explaining regenerative failure in the adult mammalian CNS. Following lesions, regenerating axons encounter the glial cells, oligodendrocytes and astro‐cytes, and their (...) derivatives, respectively myelin and the astrocytic scar. Experiments to investigate the influence of these components on axon growth in culture have revealed cell‐surface and extracellular matrix molecules that inhibit axon extension and growth cone motility. Structural and functional characterization of these ligands and their receptors is underway, and may solve the interesting neurobiological conundrum posed by the failure of mammalian CNS regeneration. Simultaneously, this might allow new possibilities for treatment of the severe clinical disabilities resulting from injury to the brain and spinal cord. (shrink)

Cloning is a biological technique of producing any required number of individuals with identical properties as the parent organism from a single cell of the latter. Cloning of protozoa, plants and lower animals meets with no moral objections, but the as yet hypothetical but increasingly more realistic prospect of cloning human beings appears to be highly objectionable. The analysis of the arguments used in the discussion of cloning indicates that mass-scale or repeated replication of human (...) individuals is unacceptable. Such a practice would probably trigger an avalanche of psychological problems connected with the diluted identity of the cloned offspring, a possible social stigmatization of the clones and the negative effects of a narrowing of the genetic pool of the human species which would limit its ability of biological adaptation to the varying conditions of the environment. (shrink)

Scientific research and ethics -- Ethical theory and decision making -- Data acquisition and management -- Mentoring and professional relationship -- Collaboration in research -- Authorship -- Publication and peer review -- Misconduct in research -- Intellectual property -- Conflicts of interest and scientific objectivity -- The use of animals in research -- The use of human subjects in research -- The use of vulnerable subjects in research -- Genetics, cloning, and stem cell research -- International research.

A large, diverse sample of adults was interviewed about their conception of the ontological and functional properties of the mind as compared to the soul. The existence of the mind was generally tied to the human lifecycle of conception, birth, growth and death, and was primarily associated with cognitive as opposed to spiritual functions. In contrast, the existence of the soul was less systematically tied to the lifecycle and frequently associated with spiritual as opposed to cognitive functions. Participants were also (...) asked about three ethical issues: stem cell research, life support for patients in a persistent vegetative state and cloning. As expected, participants' beliefs about the ontology and function of the soul were linked to their judgments about these ethical issues whereas their beliefs about the mind were unrelated. Overall, the findings show that many adults do not espouse a simple body-mind dualism, and any tendency toward such dualism is unlikely to explain their beliefs in an afterlife. Instead, afterlife beliefs appear to be associated with the idea of an immaterial essence, potentially dissociable from the biology of life and death. (shrink)