ORPHANS BY DESIGN: THE FUTURE OF GENETIC PARENTHOOD

Establishing the nature of genetic parenthood is an important task. This is, firstly, because many people desire that relationship and it is in their interest to know what that is, and secondly, because there is a view that it may incur certain moral obligations between the genetic parent and their child. Many theorists have made attempts to define exactly what genetic parenthood is. I show that these definitions are deficient if they wish to fully capture all reproductive scenarios in ways that are intuitive and/or meaningful. Through a series of cases involving technologies such as cloning and genome editing, we see that in lieu of the traditional two parents, there are possible beings who have no genetic parents, one genetic parent, or many genetic parents. Establishing these cases complicates our understanding of genetic parenthood. From this, we must reconsider current definitions, as well as the usefulness of defining genetic parenthood in these complex cases. Here I do not aim to establish a new definition, but rather to suggest that this complexity makes it necessary to re‐assess the importance of the connection between genetic parenthood and parental obligations and authorities.     

GENETIC TIES: ARE THEY MORALLY BINDING?

Does genetic relatedness define who is a mother or father and who incurs obligations towards or entitlements over children? While once the answer to this question may have been obvious, advances in reproductive technologies have complicated our understanding of what makes a parent. In a recent publication Bayne and Kolers argue for a pluralistic account of parenthood on the basis that genetic derivation, gestation, extended custody and sometimes intention to parent are sufficient (but not necessary) grounds for parenthood. ¹ 1 Bayne, T. & Kolers, A. . Toward A Pluralist Account of Parenthood . Bioethics 2003 ; 17 : 221 – 242 .
Bayne and Kolers further suggest that definitions of parenthood are underpinned by the assumption that ‘being causally implicated in the creation of a child is the key basis for being its parent’. ² 2 Ibid. p. 241.
This paper examines the claim that genetic relatedness is sufficient grounds for parenthood based on a causal connection between genetic parents and their offspring. I argue that parental obligations are about moral responsibility and not causal responsibility because we are not morally accountable for every consequence to which we causally contribute. My account includes the conditions generally held to apply to moral responsibility, i.e. freedom and foreseeability. I argue that parental responsibilities are generated whenever the birth of a child is a reasonably foreseeable consequence of voluntary actions. I consider the implications of this account for third parties involved in reproductive technologies. I argue that under some conditions the obligations generated by freely and foreseeably causing a child to exist can be justifiably transferred to others.     

Generation of an infectious clone of VR-2332, a highly virulent North American-type isolate of porcine reproductive and respiratory syndrome virus

A full-length cDNA clone of the prototypical North American porcine reproductive and respiratory syndrome virus (PRRSV) isolate VR-2332 was assembled in the plasmid vector pOK(12). To rescue infectious virus, capped RNA was transcribed in vitro from the pOK(12) clone and transfected into BHK-21C cells. The supernatant from transfected monolayers were serially passaged on Marc-145 cells and porcine pulmonary alveolar macrophages. Infectious PRRSV was recovered on Marc-145 cells as well as porcine pulmonary macrophages; thus, the cloned virus exhibited the same cell tropism as the parental VR-2332 strain. However, the cloned virus was clearly distinguishable from the parental VR-2332 strain by an engineered marker, a BstZ17I restriction site. The full-length cDNA clone had 11 nucleotide changes, 2 of which affected coding, compared to the parental VR-2332 strain. Additionally, the transcribed RNA had an extra G at the 5' end. To examine whether these changes influenced viral replication, we examined the growth kinetics of the cloned virus in vitro. In Marc-145 cells, the growth kinetics of the cloned virus reflected those of the parental isolate, even though the titers of the cloned virus were consistently slightly lower. In experimentally infected 5.5-week-old pigs, the cloned virus produced blue discoloration of the ears, a classical clinical symptom of PRRSV. Also, the seroconversion kinetics of pigs infected with the cloned virus and VR-2332 were very similar. Hence, virus derived from the full-length cDNA clone appeared to recapitulate the biological properties of the highly virulent parental VR-2332 strain. This is the first report of an infectious cDNA clone based on American-type PRRSV. The availability of this cDNA clone will allow examination of the molecular mechanisms behind PRRSV virulence and attenuation, which might in turn allow the production of second-generation, genetically engineered PRRSV vaccines.     

Human cloning: can it be made safe?

There are continued claims of attempts to clone humans using nuclear transfer, despite the serious problems that have been encountered in cloning other mammals. It is known that epigenetic and genetic mechanisms are involved in clone failure, but we still do not know exactly how. Human reproductive cloning is unethical, but the production of cells from cloned embryos could offer many potential benefits. So, can human cloning be made safe?     

Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum.

Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions.     

La majorité des couples procréant par don de sperme envisagent d’informer l’enfant de son mode de conception, mais la plupart souhaitent le maintien de l’anonymat du donneur

Semen donation is anonymous by law since 1994 in France but has been abolished in various countries. We present the results of a study that has been conducted in 14 Cecos in 2006, including 534 couples who were waiting for the assisted procreation, were under treatment, or had already at least one child with donor semen. The results were very similar between men and women and in the various groups. Over 90% of the men and the women are in agreement with donors’ anonymity and less than 10% would like the law to be changed on this point. Approximately 25% of them would give up their parental project if the law was going to change. Almost one-third would like information on the semen donor, mainly on his health, to be transmitted to themselves and to the children. The couples who plan to become parents through semen donation make a clear distinction between donor anonymity and child disclosure on its conception circumstances.     

USE OR REFUSE REPRODUCTIVE GENETIC TECHNOLOGIES: WHICH WOULD A ‘GOOD PARENT’ DO?

A number of authors have objected to potential parents' use of reproductive genetic technologies on the grounds that the use of these technologies reflects a morally problematic attitude toward parenting. More specifically, proponents of this view have argued that such a choice is inconsistent with the unconditional acceptance that lies at the heart of praiseworthy parental attitudes. This paper offers a rebuttal of this view by arguing that it is possible for a parent to exhibit unconditional acceptance of the child herself without accepting each of that child's traits. If this is true, the use of reproductive genetic technologies does not inherently undermine appropriate parental attitudes. Further, by working to change some of a child's specific traits, a parent may instead exemplify an aspirational aspect of praiseworthy parenting and so demonstrate appropriate parental attitudes.     

Unexpected ancestry of Populus seedlings from a hybrid zone implies a large role for postzygotic selection in the maintenance of species

In the context of potential interspecific gene flow, the integrity of species will be maintained by reproductive barriers that reduce genetic exchange, including traits associated with prezygotic isolation or poor performance of hybrids. Hybrid zones can be used to study the importance of different reproductive barriers, particularly when both parental species and hybrids occur in close spatial proximity. We investigated the importance of barriers to gene flow that act early vs. late in the life cycle of European Populus by quantifying the prevalence of homospecific and hybrid matings within a mosaic hybrid zone. We obtained genotypic data for 11 976 loci from progeny and their maternal parents and constructed a Bayesian model to estimate individual admixture proportions and hybrid classes for sampled trees and for the unsampled pollen parent. Matings that included one or two hybrid parents were common, resulting in admixture proportions of progeny that spanned the whole range of potential ancestries between the two parental species. This result contrasts strongly with the distribution of admixture proportions in adult trees, where intermediate hybrids and each of the parental species are separated into three discrete ancestry clusters. The existence of the full range of hybrids in seedlings is consistent with weak reproductive isolation early in the life cycle of Populus. Instead, a considerable amount of selection must take place between the seedling stage and maturity to remove many hybrid seedlings. Our results highlight that high hybridization rates and appreciable hybrid fitness do not necessarily conflict with the maintenance of species integrity.     

Nuclear cloning,stem cells,and genomic reprogramming

The generation of adult animals by nuclear cloning from adult donor cells is extremely inefficient, with most clones dying soon after implantation. In contrast, cloning from embryonic stem cell donor nuclei is significanty more efficient than from adult donor cells. However, regardless of donor cell type, all clones that survive to birth and beyond suffer serious phenotypic and gene expression abnormalities. All available evidence is consistent with the notion that the anomalous phenotypes of cloned animals are caused by faulty epigenetic reprogramming of the donor nucleus. Faulty reprogramming appears to be caused by the cloning process itself as well as by the epigenetic state of the donor nucleus. In contrast to reproductive cloning, faulty reprogramming of the donor nucleus does not tend to interfere with the application of nuclear transfer technology for therapeutic purposes (therapeutic cloning).     

Human infertility, reproductive cloning and nuclear transfer: a confusion of meanings

The Chief Medical Officer of Health of the United Kingdom has recommended that the 1990 Human Fertilisation and Embryology Act should be amended to allow cloning in humans for research purposes only. He also recommended that: "The transfer of an embryo created by cell nuclear replacement into the uterus of a woman (so called 'reproductive cloning') should remain a criminal offence" (recommendation 7, Ref. 1). This recommendation implies that nuclear replacement and cloning are the same. They are not. Nuclear transfer constitutes reproductive cloning only when the individual created is genetically identical to the nuclear donor. In this paper, we describe a possible future use of nuclear transfer for the treatment of infertile individuals. The treatment yields an individual that receives approximately equal genetic contributions from each parent. We use this example to illustrate how semantic confusion might lead to plausibly moral and justifiable treatments being legally banned. In doing so, we hope to encourage a more accurate and informed use of language in science, law and politics, so that legislation is properly informed by science and achieves what it intends. BioEssays 23:359-364, 2001.     

Parent development

Today's parents tend to be overwhelmed with advice from many sources. In his role as family counselor, the pediatrician must understand and consider the emotional development of parents in relation to their child's development; otherwise, his advice and counsel do not "take" and he becomes tired and frustrated and angry. PARENTS PROGRESS THROUGH DEFINITE STAGES OF DEVELOPMENT: Stage 1: Learning the cues-the struggle of the parents to interpret the infant's needs. Stage 2: Learning to accept growth and development-the parent learning to accept some loss of control of the toddler. Stage 3: Learning to separate-the parent learning to allow the child to develop independently. Stage 4: Learning to accept rejection, without deserting-the struggle of the parents not to intrude and yet to be there when needed. Stage 5: Learning to build a new life having been thoroughly discredited by one's teenager-the parent learning to live independently while the teenager struggles to develop his own identity.The pediatrician who is accepting, sensitive and a good listener and who keeps in mind that parents as well as children have capacities for growth and development, will be a potent factor in promoting good parent-child relationships and many times more effective in dealing with the child in health and disease.     

Practical aspects of donor cell selection for nuclear cloning

Choosing the right nuclear donor is the most critical decision in cloning by nuclear transfer (NT), or nuclear cloning, because the cloned animal will be a genetic copy of the donor cell genome used for NT. Both donor cell type and cell cycle stage are important methodological parameters and influence nuclear cloning efficiency. Cloning, however, is a multi-step procedure and the exact contribution of the nuclear donor to overall cloning success must be determined in comparative studies. This requires strict standardization of isolation, purification, and culture protocols, and application of stringent identification criteria in order to obtain a homogenous donor cell population. In all these respects, the standards in the cloning field are currently poor. The aim of this review is to provide a brief guideline for the major practical aspects of donor cell selection, cell cycle synchronization and preparation for NT.     

Asymmetric nuclear reprogramming in somatic cell nuclear transfer?

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.     

The Imagined Child: Ambiguity and Agency in Australian Intercountry Adoption

The adoption by Australian couples of children from ‘overseas’ involves claborate processes of bureaucratic assessment, approval and ‘parent education’. This paper explores adults' notions of ‘child’(ren) from ‘overseas’, which help shape and constitute such social processes, not only with couples seeking to adopt, but also with those cultural brokers who assess, regulate and ‘educate’ couples pursuing adoption, such as social workers and psychologists. The ways in which the adoptive ‘child’ is imagined and anticipated by counsellors and would‐be parents alike are explored through ethnographic data from South Australia. However, the proclivities of prospective adoptive parents to imagine their child‐to‐be are attenuated by certain social knowledge in relation to countries of origin. This leads to an exploration of ambiguities and tensions between the intercountry adoptive child as a tabula rasa and as a culturally and historically constituted person. The significance of ambiguities and contradictions for the child's agency and identities is highlighted, within the context of certain social policies around adoption. The chronological age of the child at the time of ‘allocation’ to its adoptive parents is considered as constituting a cultural fulcrum, upon which the identity and situational significance of the ‘origins’ of the child are deemed to subsequently turn.     

Behavior of meiotic chromosomes in Pinus wallichiana, P. strobus and their hybrid and nrDNA localization in pollen mother cells of the hybrid by using FISH

The complete process of meiosis was investigated in Pinus wallichiana, P. strobus and their artificial hybrid （F1） using microsporocytes. It is revealed that there were slightly lower chiasma frequency, lower ring bivalent frequency, lower meiotic index and distinctly higher frequency of aberrance （chromosomal bridges, fragments or micronuclei） in pollen mother cells （PMCs） of the hybrid （F1） than those of the parental species, which showed a certain degree of differentiation between homologous chromosomes of the two parents. However, relatively higher frequency of ring bivalents and higher meiotic index in all the three entities indicate the great stability of genomes of parental species, and the differentiation of genomes between the two parents must have been slight. Total nineteen signal loci of 18S rDNA were observed in nine bivalents of the hybrid （F1）, among which one bivalent bears two loci, while the others have only one. It is suggested that distinct differentiation at genetic level existed in homologous chromosomes of the two parental species, whereas only slight differentiation at karyotypic and genomic levels take place between the parent species.     

Enjeux psychosociaux du don de sperme: le point de vue des couples

The French national debate, which took place during the review of bioethical laws, concerns the issue of anonymity of gametes donations, among other questions. More specifically, the debate was focused on sperm donations in which numerous arguments have advocated for a partial opening of sperm donor’s anonymity. But what about couples who are implicated in donation programs? What do they want? What sort of practical changes occur for receiving couples in countries which take away the donor’s anonymity? Our article presents some results of recent social psychological research conducted on a significant sample of French receiving couples. Results focus as much on their experience and their intention to share the secret of conception through sperm donation, as on specific aspects of this type of donation and its defining legislative principles in France. Finally, we question the organizing principles of their stand regarding donator’s anonymity and the convergence of parental strategies in dissident legal frameworks, through the lens of international scientific literature.     

Exploring the Relation of Harsh Parental Discipline with Child Emotional and Behavioral Problems by Using Multiple Informants. The Generation R Study

Parental harsh disciplining, like corporal punishment, has consistently been associated with adverse mental health outcomes in children. It remains a challenge to accurately assess the consequences of harsh discipline, as researchers and clinicians generally rely on parent report of young children''s problem behaviors. If parents rate their parenting styles and their child''s behavior this may bias results. The use of child self-report on problem behaviors is not common but may provide extra information about the relation of harsh parental discipline and problem behavior. We examined the independent contribution of young children''s self-report above parental report of emotional and behavioral problems in a study of maternal and paternal harsh discipline in a birth cohort. Maternal and paternal harsh discipline predicted both parent reported behavioral and parent reported emotional problems, but only child reported behavioral problems. Associations were not explained by pre-existing behavioral problems at age 3. Importantly, the association with child reported outcomes was independent from parent reported problem behavior. These results suggest that young children''s self-reports of behavioral problems provide unique information on the effects of harsh parental discipline. Inclusion of child self-reports can therefore help estimate the effects of harsh parental discipline more accurately.     

L’entretien psychologique systématique pour les couples optant pour l’IAD: huit ans d’expérience clinique dans une législation prévoyant la levée de l’anonymat du donneur

A law on medically assisted procreation was implemented in Switzerland in 2001. This law is subordinate to the well-being of the child and stipulates that only married couples can benefit from donor insemination (DI). Furthermore, a child who was conceived with donor sperm may obtain access to information including the identity of the donor on reaching adulthood, at age 18. The law also specifies that psychological assistance must be offered before, during, and after treatment. For the past 12 years, the Unit of Reproductive Medicine and the Center of Medically Assisted Procreation in Lausanne employ a concept of psychological assistance adjusted to each couple’s needs, called “ressource counselling”. In preparation for DI, specific questions are examined, such as “Should the child be informed about the donor insemination, should others be informed, if so, how and when?” These questions may also be discussed in a group setting specific for couples concerned with DI. Our experience shows that systematic counselling helps couples in finding their own path through the delicate subjects of secrecy, attachment, and the rights of a child to be informed of his/her genetic links.     

Patterns of child fosterage in rural northern Thailand

Evolutionary theory guides an investigation of foster parent selection in two northern Thai villages with different biosocial environments: one village has high levels of labour migration and divorce, and growing numbers of parental death due to HIV/AIDS, while the other village has lower migration, divorce and parental mortality levels. Focus groups examine mothers' and fathers' motivations and ideals regarding foster caretaker selection, and quantitative family surveys examine real fostering outcomes: specifically, the laterality (matrilateral versus patrilateral) and genetic distance of the foster caretakers of all ever-fostered children in these two villages. As predicted, in environments of high marital stability and paternity certainty, parents seem to prefer close genetic kin from either side as foster parents for their children. In low marital stability and paternity certainty environments, parents trust their own lateral kin, regardless of genetic distance, over close genetic kin from the other side. The striking exception to this pattern, however, occurs in the case of parental death, in which case children are fostered to the deceased parent's kin, regardless of the child's sex or other factors. In general, the foster parents for girls are selected with more care, reflecting the daughter/female preference expected in traditionally matrilineal, matrilocal societies. An ordered decision-making pathway for foster parent selection is proposed, taking into consideration the key factors of (a) the circumstances driving the fostering decision, (b) the gender of the child, (c) the gender of the key decision-making parent, and (d) the degree of marital and population fluidity (and subsequent, paternity certainty) in the village.     

Genome-wide analysis of abnormal H3K9 acetylation in cloned mice

Somatic nuclear transfer is a cloning technique that shows great promise in the application to regenerative medicine. Although cloned animals are genetically identical to their donor counterparts, abnormalities in phenotype and gene expression are frequently observed. One hypothesis is that the cause of these abnormalities is due to epigenetic aberration. In this report, we focused our analysis on the acetylation of histone H3 at lysine9 (H3K9Ac). Through the use of whole genome tiling arrays and quantitative PCR, we examined this epigenetic event and directly compared and assessed the differences between a cloned mouse (C1) and its parental nuclear donor (D1) counterpart. We identified 4720 regions of chromosomal DNA that showed notable differences in H3K9Ac and report here many genes identified in these hyper- and hypo-acetylated regions. Analysis of a second clone (C2) and its parental donor counterpart (D2) for H3K9Ac showed a high degree of similarity to the C1/D1 pair. This conservation of aberrant acetylation is suggestive of a reproducible epigenetic phenomenon that may lead to the frequent abnormalities observed in cloned mice, such as obesity. Furthermore, we demonstrated Crp which was identified as a hyper-acetylated gene in this study is related to the body mass, suggesting that Crp is a possible candidate of a cause for the abnormal obesity in cloned mice. In this, one of the first reports describing genome-wide epigenetic aberration between parental and nuclear transfer-cloned mammals, we propose that aberrant acetylation of histones (H3K9Ac) flanking promoter regions highly correlates with gene-expression and may itself be an epigenetic change that accounts for variable expression patterns observed in cloned animals.