Ethics of modifying the mitochondrial genome

Recent preclinical studies have shown the feasibility of specific variants of nuclear transfer to prevent mitochondrial DNA disorders. Nuclear transfer could be a valuable reproductive option for carriers of mitochondrial mutations. A clinical application of nuclear transfer, however, would entail germ-line modification, more specifically a germ-line modification of the mitochondrial genome. One of the most prominent objections against germ-line modification is the fear that it would become possible to alter 'essential characteristics' of a future person, thereby possibly violating the child's right to an open future. As only the nuclear DNA would contain the ingredients for individual characteristics, modification of the mtDNA is often considered less controversial than modification of the nuclear DNA. This paper discusses the tenability of this dichotomy. After having clarified the concept of germ-line modification, it argues that modification of the mtDNA is not substantively different from modification of the nuclear DNA in terms of its effects on the identity of the future person. Subsequently the paper assesses how this conclusion affects the moral evaluation of nuclear transfer to prevent mtDNA disorders. It concludes that the moral acceptability of germ-line modification does not depend on whether it alters the identity of the future child-all germ-line modifications do-but on whether it safeguards the child's right to an open future. If nuclear transfer to prevent mtDNA disorders becomes safe and effective, then dismissing it because it involves germ-line modification is unjustified

Met het oog op de toekomst : voortplantingstechnologie, erfelijkheidsonderzoek en ethiek

Dit proefschrift betreft de ethiek van voortplantingstechnologie en erfelijkheidsonderzoek. Een boek over dit thema kan uiteraard op verschillende manieren worden opgezet. Om praktische redenen koos ik voor een opzet waarbij ik zoveel mogelijk gebruik kon maken van lopende onderzoeksprojecten binnen het Instituut voor Gezondheidsethiek. Het boek kreeg zodoende de structuur van 'capita selecta': een samenvoeging van afzonderlijk geconcipieerde, zelfstandig leesbare, hoofdstukken. Het verbindende thema - de 'rode draad' - is de verantwoordelijkheid van de arts, meer in het bijzonder de voortplantingsarts en de hulpverlener die betrokken is bij erfelijkheidsvoorlichting en - onderzoek: wat is in de verschillende contexten verantwoord handelen? Hoe krijgt 'goed hulpverlenerschap' hier gestalte?' Dat deze vraag urgent is in de context van de moderne voortplantingstechnologic, waar men voortdurend wordt geconfronteerd met nieuwe technieken en toepassingen, behoeft geen betoog. Door welke morele overwegingen zou de arts zich moeten laten leiden als de technologische imperatief geen betrouwbare gids is? (In hoeverre) mag of moet de arts zich bijvoorbeeld iets gelegen laten liggen aan de belangen van het eventuele toekomstige kind? De inhoud van 'goed hulpverlenerschap' staat ook voortdurend tcr discussie op het dynamische terrein van erfelijkheidsvoorlichting en -onderzoek: aan de orde is niet alleen de attitude van de betreffende hulpverleners, maar ook hun verantwoordelijkheid in concrete conflictsituaties

ESHRE task force on ethics and law 15: Cross-border reproductive care

This paper analyses the ethical aspects of cross-border reproductive care. Ethical questions are raised by some of the main reasons of cross-border travelling, i.e. law evasion and unequal access to treatment. The phenomenon also generates possible conflicts linked to the responsibility of the professionals. Three points are discussed: the moral obligation of the physician to refer the patient, his/her duty to provide information and counselling and the acceptability of fee-splitting. The recommendations focus on measures to reduce or limit the number of patients that have to travel abroad and on steps to guarantee the safety and quality of the treatment wherever it is provided

The catalytic oxidation of organic contaminants in a packed bed reactor

The catalytic oxidation of several hydrocarbons was studied over noble metal and metal oxide catalysts. A fast empirical method was developed to determine the minimum operating temperature required to guarantee complete conversion of the hydrocarbon.\ud \ud The influence of the operating parameters such as the inlet concentration and residence time, as well as the chemical character of the component to be oxidized, have been investigated. The results can be described satisfactorily by a simple isothermal, plug flow reactor model and first-order reaction kinetics. In the case of simultaneous oxidation of different components a significant mixture effect was not observed. The presence of water in the feed did significantly inhibit the oxidation of alkanes.\ud \ud Of the applied catalysts, Pt was the most effective for the combustion of the alkenes, whereas Pd showed a higher activity for the oxidation of alkanes

A leap of faith? An interview study with professionals on the use of mitochondrial replacement to avoid transfer of mitochondrial diseases

STUDY QUESTION: What are the opinions of professionals in the field of genetics, reproductive science and metabolic diseases on the development of mitochondrial replacement technologies to be used in the context of medically assisted reproduction? SUMMARY ANSWER: Although concerns regarding safety remain, interviewees supported the development of nuclear transfer techniques to help women who are at risk of transferring a mitochondrial DNA disease to their offspring conceive a genetically related child. WHAT IS KNOWN ALREADY: Technological developments in the field of nuclear transfer have sparked new interest in the debate on the acceptability of the use of donor oocytes to prevent the transmission of mitochondrial diseases. For example, in the UK, extensive public consultations have been done to investigate whether such techniques would allow the passing of a law that involves making changes to a human oocyte or embryo before transfer to a woman's body. Until now, continental European countries seem to await the outcome of the British debate before themselves considering the arguments for and against this technology. STUDY DESIGN, SIZE, AND DURATION: We interviewed 12 professionals from Belgium and The Netherlands. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We conducted 12 interviews with fertility specialists, scientists, clinical geneticists, a pediatrician specialized in metabolic diseases and a specialist in metabolic diseases. The profiles of the interviewees varied but all had experience with mitochondrial diseases, either in treating patients or in providing counseling to patients or to prospective parents. The interviews were conducted face-to-face and took 30-45 min. The language of the interviews was Dutch. We analyzed the transcript of these interviews using QSR NVIVO 10 software to extract themes and categories. MAIN RESULTS AND THE ROLE OF CHANCE: This study has shown that, although amongst the professionals we interviewed there was support for the development and deployment of nuclear transfer, this support does not necessarily correspond to uniform opinions about the importance of having a genetically own child or the contribution of mitochondrial DNA to essential characteristics of an individual. LIMITATIONS, REASONS FOR CAUTION: In translating the quotes from Dutch to English some of the linguistic nuances may have been lost. We only interviewed 12 individuals, in two countries, whose view may not be representative of existing values and opinions that may be held by professionals worldwide on this matter. To further explore the issue at hand, a subsequent investigation of the opinions of people affected by mitochondrial diseases and of the general public is necessary. WIDER IMPLICATIONS OF THE FINDINGS: With this study we have demonstrated there is in principle support for the nuclear transfer technique from Dutch and Belgian professionals. Further research, both scientific and ethical, is needed to define the modalities of its possible introduction in the fertility clinic

Anti-predator adaptations and strategies in the Lepidoptera

This thesis examines visual anti-predator strategies employed by the Lepidoptera. I examine key aspects of pattern and behaviour and how they relate to the reduction of an individual’s predation risk. Symmetrical patterns have been found to be easier to remember and pick out, suggesting that symmetry is beneficial to aposematic displays. This suggests that symmetry may be maladaptive in cryptic patterning and asymmetry beneficial. In Chapter one, I report the results of a field experiment using artificial prey and wild birds to investigate how asymmetry and symmetry affect the efficiency of cryptic patterning to reduce predation. I found that asymmetry does not affect predation rate, in agreement with previous work. Yet, there is still the problem of how to mesh this with the potentially conflicting conclusions of symmetry studies. Chapter two examines aspects of the intimidation hypotheses of Lepidopteran eyespots. These address the generally larger and more centrally placed spots found on Lepidopteran wings and state that they startle or intimidate predators, providing time for escape. While it is agreed that eyespots intimidate or startle predators, the mechanism has not been agreed. There are two competing lines of thought 1) that ‘eyespots’ intimidate because they resemble the eyes of the predators’ own predators and 2) that it is the conspicuous colouration of the pattern that induces the startle or avoidance behaviour. The first experiment utilised artificial prey with differing ‘directions of gaze’ in a field setting. If purely conspicuous patterns direction of gaze should have no influence on prey survival. The results indicate that patterns imitating staring or upward gazes provide the greatest protection, suggesting that in some cases eyespots may be being perceived as eyes and not simply as conspicuous patterns. I wanted to see if it would be possible to find a way in which to measure or quantify the reaction of an animal to ‘real’ eyes, in order to compare it to the reaction to eyespots. Recent trials investigating human reactions to eye contact suggested a computer based method may be possible. In this second experiment we examined whether the direct gaze of a predator might produce a measurable effect in human subjects. I was not able find any effect, but it is unclear as to whether this is due to problems with the experimental set up. In Chapter three I investigate a factor often over looked in the study of crypsis, that of the behavioural adaptations that can enhance its efficiency. The larvae of the early thorn moth (Selenia dentaria) masquerade as twigs, using both colouration and behaviour adaptations. I compared the angle at which the larvae rested, to the angle at which real twigs deviate from the main stem. The results found that the larvae showed variation in their angle of rest and do not appear to match the angle of real twigs on the host tree. This result suggests that perfectly matching the angles of real twigs is not necessary to twig mimicry. While carrying out this experiment it was noticed that a breeze appeared to increase larval activity and induced a ‘swaying’ behaviour. This led me to examine whether mimic species may utilise the visual ‘noise’ produced by windy conditions to camouflage movement. Firstly, a small ‘proof of concept’ pilot was carried out, followed by a larger study using 2 different twig mimic species. The study involved measuring movement and swaying behaviour in 3 conditions (still air, wind setting 1 and 2). The results suggest that cryptic and mimetic lepidopteran species may use windy conditions to camouflage their movements and that some species may employ specialised ‘swaying’ behaviours. Cryptic species are limited in opportunities to move between foraging sites without increasing detection by predators, therefore, any adaptation that might reduce detection is extremely advantageous. In Chapter four I examine how conspicuousness and colouration are affected by living in a group, particularly in relation to other group members. A field experiment using groups of artificial prey, with differing densities and group sizes was used to explore the effect of group size and density on the predation risk and detectibility of cryptic prey. My results show that, as expected, larger groups are more likely to be detected, but that the increase is much slower than a linear increase. This suggests that groups must increase considerably in size before any individual group member will suffer increased predation risk. The second experiment examines the ‘oddity effect’ and how it affects predation. This hypothesises that when confronted by grouped prey, predators can increase their kill rate by concentrating their efforts on capturing unusual or ‘odd’ prey, a strategy that reduces the ‘confusion effect’. A field experiment was conducted with groups composed of differing proportions of two artificial cryptic prey types. Groups with odd individuals did not suffer an increase in conspicuousness and were not attacked more often. However, once located and attacked the groups did suffer a greater predation rate. Odd individuals were predated at a greater rate than normal individuals and the rate did not change as more or less odd individuals were added to the group. A computer based ‘game’ was used to further investigate the oddity effect. The results from the initial run of the game appeared to show strong evidence for the oddity effect, with a further significant increase in this effect when attention is split between foraging for prey and scanning for predators. To be confident of this result the experiment was repeated with the ‘odd’ and ‘normal’ seed patterns reversed. The new data set strongly suggested that much of the effect seen in the previous experiment was due to a difference in pattern visibility between the two seed patterns. Nevertheless, the results indicated that selecting odd seeds is quicker than selecting normal seeds. The results from both the field and computer trials suggest that preference for odd prey may improve predator foraging speed and efficiency. Chapter five investigates whether cryptic and non-defended prey could reduce their predation risk by grouping with aposematic and defended prey. This was tested using artificial prey in a field setting. My results show that undefended non-aposematic prey can benefit by grouping with aposematic prey with no evidence that predation rates for aposematic prey were adversely affected by this association. If confirmed this might illuminate the origins of Batesian mimicry. I have investigated a range of anti-predator adaptations and strategies in the Lepidoptera and in particular pattern elements and use of crypsis and aposematic displays. These anti-predator strategies are important in that they modify predation rate and so directly influence the evolution of species. While I have been able to provide evidence for some current hypotheses, in many respects my results demonstrate that there is still a lot to learn about visual anti-predatory strategies

Follow-up in the field of reproductive medicine : an ethical exploration

Research question: What ethical implications, issues and concerns play a role in conducting follow-up studies of children born after assisted reproductive technologies (ART)? Design: Literature study and relevant experiences of academic medical centres in Brussels, Belgium, and Maastricht, the Netherlands were used to identify and analyse the most pertinent ethical implications, issues and concerns. Results: According to recommendations from the European Society of Human Reproduction and Embryology, follow-up (ideally long term) of children conceived through medically assisted reproduction (MAR) should be an integral part of introducing new ART. With potentially risky new ART on the horizon, these recommendations need to be taken more seriously. Apart from practical barriers, such as funding, challenges for follow-up include securing active involvement of families of children conceived through MAR, starting with parents of young children, and ideally involving consenting adolescents and adults during a large part of their lives, possibly even into the next generation. Conclusions: From an ethical viewpoint, the most pertinent issues include the proportionality of the inevitable burdens and risks for families of children conceived through MAR, and the implications of the principle of respect for autonomy. The proportionality requirement is most critical when it concerns incompetent children, who should not be included in research with more than minimal burdens and risks if there is no reasonable expectation of benefit for themselves. With respect for autonomy, we argue that, when seeking voluntary consent for participating in followup studies that meet the condition of proportionality, professionals may encourage members of families of children conceived through MAR to partake in follow-up research