Projecting terrestrial biodiversity intactness with GLOBIO 4

Scenario‐based biodiversity modelling is a powerful approach to evaluate how possible future socio‐economic developments may affect biodiversity. Here, we evaluated the changes in terrestrial biodiversity intactness, expressed by the mean species abundance (MSA) metric, resulting from three of the shared socio‐economic pathways (SSPs) combined with different levels of climate change (according to representative concentration pathways [RCPs]): a future oriented towards sustainability (SSP1xRCP2.6), a future determined by a politically divided world (SSP3xRCP6.0) and a future with continued global dependency on fossil fuels (SSP5xRCP8.5). To this end, we first updated the GLOBIO model, which now runs at a spatial resolution of 10 arc‐seconds (~300 m), contains new modules for downscaling land use and for quantifying impacts of hunting in the tropics, and updated modules to quantify impacts of climate change, land use, habitat fragmentation and nitrogen pollution. We then used the updated model to project terrestrial biodiversity intactness from 2015 to 2050 as a function of land use and climate changes corresponding with the selected scenarios. We estimated a global area‐weighted mean MSA of 0.56 for 2015. Biodiversity intactness declined in all three scenarios, yet the decline was smaller in the sustainability scenario (?0.02) than the regional rivalry and fossil‐fuelled development scenarios (?0.06 and ?0.05 respectively). We further found considerable variation in projected biodiversity change among different world regions, with large future losses particularly for sub‐Saharan Africa. In some scenario‐region combinations, we projected future biodiversity recovery due to reduced demands for agricultural land, yet this recovery was counteracted by increased impacts of other pressures (notably climate change and road disturbance). Effective measures to halt or reverse the decline of terrestrial biodiversity should not only reduce land demand (e.g. by increasing agricultural productivity and dietary changes) but also focus on reducing or mitigating the impacts of other pressures.     

Impacts of soil temperature,phenology and plant community composition on invertebrate herbivory in a natural warming experiment

Species and community-level responses to warming are well documented, with plants and invertebrates known to alter their range, phenology or composition as temperature increases. The effects of warming on biotic interactions are less clearly understood, but can have consequences that cascade through ecological networks. Here, we used a natural soil temperature gradient of 5–35°C in the Hengill geothermal valley, Iceland, to investigate the effects of temperature on plant community composition and plant–invertebrate interactions. We quantified the level of invertebrate herbivory on the plant community across the temperature gradient and the interactive effects of temperature, plant phenology (i.e. development stage) and vegetation community composition on the probability of herbivory for three ubiquitous plant species, Cardamine pratensis, Cerastium fontanum and Viola palustris. We found that the percentage cover of graminoids and forbs increased, while the amount of litter decreased, with increasing soil temperature. Invertebrate herbivory also increased with soil temperature at the plant community level, but this was underpinned by different effects of temperature on herbivory for individual plant species, mediated by the seasonal development of plants and the composition of the surrounding vegetation. This illustrates the importance of considering the development stage of organisms in climate change research given the variable effects of temperature on susceptibility to herbivory at different ontogenetic stages.     

Early Warning Signals for Rate-induced Critical Transitions in Salt Marsh Ecosystems

Ecosystems - Intertidal ecosystems are important because of their function as coastal protection and ecological value. Sea level rise may lead to submergence of salt marshes worldwide. Salt marshes...     

Rethinking the life sciences

The life sciences are at loggerheads with society and neither much trusts the other. To unleash the full potential of molecular life science, a new contract with society and more organized ways of doing research are needed.Suppose that an international group of scientists presents a 15-year, €750 million research programme to unravel the molecular mechanisms of metabolic syndrome, a disorder implicated in obesity, type 2 diabetes, cardiovascular diseases, cancer and other diseases. The results from this project will neither replace obvious preventive measures—such as reducing food intake or increasing exercise—nor will it magically generate pharmaceutical treatments. Instead, the research aims to gain a systems-level understanding of metabolic syndrome that could lead to more effective prevention schemes, improved food quality, improved early diagnosis of people with higher risk, and better therapies and drugs. From an economic point of view, this is an excellent investment, as the costs of obesity and its co-morbidities in the European Union are estimated to increase to €100 billion per year in 2030 [1]. If the proposed research project helped to lower the costs by only 10%, it would generate a considerable return on investment.Sadly, such a project would be unlikely to receive funding. The reason is not because it would be scientifically unrealistic or unfeasible, or because society does not want to support expensive research programmes. The Manhattan Project to develop the atomic bomb, the Large Hadron Collider at CERN to identify the Higgs boson and the European Southern Observatory in Chile are all examples of large-scale research programmes that are publicly funded. Rather, the life sciences suffer from a unique set of problems that have developed in the past decades and would prevent such a project receiving popular support and funding. This article explores why this is the case and how modern life sciences could contribute more to society. Specifically, we argue that two areas need rethinking: the embedding of the life sciences in society and the way that research is organized.There are more than seven billion humans on this planet who need food, energy and health care, and life science research has a huge potential to address these needs. However, critics point out that many of the promises made by life scientists in the past have still not materialized. One example is the promises made to justify the US $3 billion spent on the Human Genome Project. It was supposed to provide a ‘blueprint of life'' that would quickly lead to new approaches for curing diseases. In the end, however, despite its success at generating new research fields and knowledge, the Human Genome Project has not (yet) lived up to its promises.…critics point out that many of the promises made by life scientists in the past have still not materializedWorse still, some critics perceive the life sciences as a problem that is creating physical and moral hazards. Rather than writing a blank cheque to allow scientists to pursue their research goals, governments are increasingly demanding control over the direction and application of research. This approach tends to reward short-term applications of scientific resources to help solve societal problems. Moreover, the success of projects has to be demonstrated at the application stage, before any of the research has even begun, which is fundamentally incompatible with the trial-and-error processes at the heart of creative research. Long-term, in-depth investments in research have become unpopular. Ironically, this ‘short-termism'' undermines the potential of the life sciences to be realized. Life sciences and society seem to be in a dead-lock.The life sciences must therefore regain the trust of society. This cannot be done merely by emphasizing academic freedom and the autonomy of science, or by promoting the so-called ‘cornucopia'' of science and technology, implying that both bring only precious gifts. It is also not useful to suggest that morals should follow scientific and technological developments rather than shape them. It is equally counterproductive when scientists deny taking responsibility for how their findings are applied after they leave the laboratory. As Ravetz [2] famously remarked: “Scientists claim credit for penicillin, while Society takes the blame for the Bomb”. In reality, the definition of ends is always influenced by the available means.One approach to restore the trust between the life sciences and society is to create platforms that allow for open and symmetrical dialogue. Fortunately, we do not have to start from scratch, as the recent discussions about responsible research and innovation (RRI; [3,4,5]) have already begun this process. According to René von Schomberg, policy officer at the European Commission, Directorate-General for Research, RRI is “a transparent, interactive process by which societal actors and innovators become mutually responsive to each other with a view to the (ethical) acceptability, sustainability and societal desirability of the innovation process and its marketable products” [5]. An example is the EU ‘Code of conduct for responsible nanosciences and nanotechnologies research''. The concept is also expected to have a major role in the upcoming EU Framework Programme for Research and Innovation ‘Horizon 2020'', and national research councils in the UK, Norway and the Netherlands are supporting initiatives under this heading. The National Nanotechnology Initiative in the USA heralds ‘responsible development'', and the Presidential Commission on the Study of Bioethical Issues recommends ‘responsible stewardship'' and ‘prudent vigilance'' in relation to synthetic biology.…‘short-termism'' undermines the potential of the life sciences to be realizedThe starting point of RRI is that society, science, technology and morality comprise a single system. If one component changes, the others are also affected. The traditional division of labour—science provides knowledge and instruments, whilst society determines values and application—therefore does not work anymore. Life scientists have to acknowledge and accept that society is co-shaping their agenda. Scientists should also realise that vice versa they co-shape society, rather than just offering knowledge and tools. In other words, science and society co-evolve [6]. Bringing life sciences and society closer together requires the concerted efforts of life scientists, social scientists, ethicists, legal experts, economists, policy-makers, market parties and laypeople.Research and technology are rational activities at the micro level. Science is superior to other methods for creating reliable, testable knowledge, and technology is unmatched in providing solutions to many problems. But both tend to become irrational at higher levels of organization—we drive highly sophisticated cars and still get stuck in traffic jams, nuclear waste remains a huge problem for generations to come, and knowledge and technology have enabled increasingly lethal weaponry. Science and technology therefore need moral guidelines—such as ‘the precautionary principle''—to direct what kind of knowledge is worth pursuing and should be applied, why and for whom. This is a one-sided view, however, that ignores the perspective of the scientific method. As science proceeds by trial and error, it must be fundamentally open to pursue any avenue of knowledge. As such, new scientific insight and technological opportunities can often necessitate a reappraisal of established morals. Keeping science, technology and morality in contact with each other requires more than rules and prohibitions that can be ticked off on a form. It needs a culture of attentiveness and reflection to avoid tunnel vision whilst allowing flexibility and improvisation to learn from mistakes and change course if needed.During the past two decades, many experiments in public understanding, awareness and participation in science and technology have been conducted. In the Netherlands, for instance, this has included science cafes, citizen panels [7], nation-wide public debates about nuclear energy [8], biotechnology and food in 2001 [9], and public participation (http://www.nanopodium.nl). It is yet to be determined how effective these efforts have been. Appreciating that science and technology, as well as society and morality, constitute parts of a larger system demands skills, institutions and procedures that have not as yet been adequately developed. Indeed, many scientists continue to adhere to a ‘knowledge deficit'' model of public outreach that has scientists ‘explaining'' scientific developments to an audience that is perceived to be ignorant at best and technophobic at worst. On the other hand, NGOs have sometimes hijacked discussions by simply being ‘against'', rather than contributing to the debate in an open and constructive manner. Another problem is that the life sciences are poorly organized. They lack an organization that represents the community and can professionalize the relationship between society and life sciences.What are the requirements for developing responsibly the relationship between society and the life sciences? First, it is important that scientists are explicit about the trial-and-error character of research, and are honest and transparent about the results they expect, rather than inducing unrealistic expectations. Laypeople should be made aware of how the life sciences function and what they might achieve. It is also important that citizens understand that science produces theories that can be corroborated to some degree rather than absolute certainties, and that technology offers solutions that can do both more or less than expected. This should also make clear that the distinction between fundamental science and applied technology is both real and illusionary. It is real because it is important to allow space for unfettered curiosity. It is illusionary because even the most ‘fundamental'' research is usually embedded in a general normative vision about its possible use. Moreover, even truly applied research can generate new fundamental insight.Second, it is important to engage societal actors as early as possible in the research enterprise, so that they can determine the research agenda rather than be confronted with final results and products. A specific suggestion would be to attach a ‘layman advisory board'' to large research programmes. Although the tasks of such boards should be defined carefully to avoid tying them up in minutiae, such boards can help to enhance the involvement of society in the life sciences. Engaging interested individuals and stakeholders early on in the process and offering them an opportunity to influence the research agenda would help to foster a constructive attitude.These boards should put the definitions, visions and goals of scientific research to the social test and set research priorities accordingly. Research is inevitably conducted with reference to priorities—such as advancing knowledge, improving public health, economic development and military use—but setting these priorities exceeds the authority of science. We need social scientists, philosophers, lawyers, policy-makers, politicians, companies, opinion-makers, NGOs and patient organizations to discuss with life scientists how scientific results can be developed to benefit society. For example, because knowledge can be viewed as an economically valuable resource, we have to consider whether intellectual property laws are adequate to deal with new forms of knowledge. The ongoing debate about the legal and moral problems of intellectual property [10] also highlights issues of fairness and justice. How will science and technology influence prevailing ideas about the meaning of a ‘healthy life''? How much do we value physical and mental health, how much are we willing to invest in this value, and how will society react to choices made by individuals? The life sciences are creating enormous data collections about individuals, which raises issues about access, privacy, ownership and consent. Discussing these issues would neither put the life sciences in a strait jacket nor would it curtail curiosity-driven research. On the contrary, we should be more worried about the current situation, in which governments set the agenda by choosing which areas are funded without consulting the life sciences community or other stakeholders.The sequencing of the human genome and the rapid development of new technologies and research fields—genomics, proteomics, advanced light microscopy, bioinformatics, systems biology and synthetic biology—have not yet paid off in terms of highly visible applications that provide a significant benefit to society. However, there are many examples of progress both scientifically and clinically, such as the ongoing Encyclopaedia of DNA Elements project (ENCODE; http://encodeproject.org), the stratification of patients for anti-cancer therapies based on molecular markers or the creation of genetically modified disease-resistant plants. Notwithstanding, applying the new technologies made scientists realize that biological systems are much more complex than anticipated. The multi-layered and multi-scale complexity of cells, organisms and ecosystems is a huge challenge for research in terms of generating, analysing and integrating enormous amounts of data to gain a better understanding of living systems at all levels of organization.However, and remarkably, the life sciences have not adapted accordingly to tackle bigger challenges with larger teams comparable with their colleagues in physics and astronomy. Most research is still carried out by small groups or collaborations that are woefully inadequate to address the full complexity of living systems. This type of research is grounded in the history of molecular biology when scientists focused on individual genes, proteins and metabolic pathways. Scientists hope that many small discoveries and advances made by many individual research groups will eventually add up to a more complete picture, an approach that clearly does not work and must change. The new challenge is to systematically acquire and integrate comprehensive data sets on the huge number of components at the cellular level and that of tissues, organs and complete organisms. This requires the life sciences to scale up their research efforts into larger projects.The putative research programme described at the beginning of this paper could help to reduce the health and economic burden of metabolic syndrome. This multifactorial disorder is an excellent example of the complex interplay between organs, tissues, cells, molecules, lifestyle, genetic factors, age and stress. Unravelling this daunting but finite complexity requires a major and well-coordinated effort. It would have to combine diverse skills and disciplines, including biology, chemistry, medicine, mathematics, physics and engineering. Similar considerations are true for research into areas such as cancer, Alzheimer disease or the development of efficient biofuels. Why, then, are we not making the necessary investments? The answer to this question has four components that we address below: scaling and management of research programmes, the academic culture and funding.First, one could argue that many national and European research programmes already focus on many aspects of metabolic syndrome. Together, they probably represent an investment of several hundred million Euros. So why spend another €750 million? The problem is that the results from individual research efforts simply do not add up due to a lack of standardization in regard to experiments, the use of model systems and protocols. Given the complexity of the disease, defining standard operation protocols (SOPs) is not a trivial task and requires a considerable research effort. However, experience shows that developing SOPs should be an integral part of larger research programmes. Moreover, SOPs change as our knowledge increases. SOPs can only be effective and stimulate research in the context of a sufficiently large and receptive research community, dedicated to a common well-defined research goal. An example of the successful development and implementation of SOPs in a ‘learning-by-doing'' setting is the German Virtual Liver Network (VLN) programme (http://www.virtual-liver.de). Obviously, a considerable fraction of the €750 million should come from regrouping and readjusting existing research in the field of metabolic syndrome.Second, we have remarkably little experience in managing concerted large-scale research efforts in the life sciences in the range of €100–1,000 million. The Human Genome Project cost US $3 billion. However, genomes are just DNA sequences, and it is relatively easy to define SOPs and integrate the contributions of many research groups. In terms of research management it was relatively straightforward compared with, for instance, a metabolic syndrome programme, which would have many more dimensions and components. It would require a highly coordinated approach, as the experiments of the participating research groups from different institutes and countries are strongly interdependent and the results must add up to a larger picture.To keep such a complex research programme on track, on time and within budget, strategic decisions will inevitably need to be made at a central level, rather than by individual researchers. A serious risk is that scaling-up coordinated research efforts will result in excessive bureaucracy and inflexibility that could kill creativity. Avoiding this problem is a major challenge. The life sciences could learn here from large, long-term projects in other fields, such as high-energy physics, astronomy and ecology. An instructive example is the Census of Marine Life programme [11] that successfully measured the diversity, distribution and abundance of marine life in the oceans over ten years. It involved 80 countries and 640 institutions and had a budget of US $650 million [12]. A recent overview and analysis of large-scale research efforts in the life sciences has been presented and discussed in [13,14,15].A third aspect is academic culture, which cherishes freedom, independence and competition and will not necessarily mesh well with the idea of large, tightly managed research programmes. Even so, research institutions will probably compete to participate in goal-oriented, large-scale research programmes. In fact, this is largely similar to the way most research is funded presently, for instance, through the Framework Programmes of the European Commission, except that the total collective effort is scaled up by one to two orders of magnitude. Moreover, as large-scale efforts involve longer timescales of between 10 and 15 years, it would offer a more stable basis of financing research. However, as the cooperation between parties and their interdependency will need to increase, participating research institutes and consortia will be held much more accountable for their contribution to the overall goals. ‘Take-the-money-and-run'' is no longer an option. This will obviously require explicit agreements between a programme director and participating institutions.In addition, academic institutions should rethink their criteria for selecting and promoting researchers. The impact factor, h-factor and citation scores [16] will have to be abandoned or modified as large-scale research efforts with an increasing number of multi-author publications will decrease their ability to assess individuals. Consequently, less emphasis will be put on first or last authorships, whilst project and team management skills might become more relevant.Academic freedom and creativity will be just as essential to a collective research enterprise as it is to small projects and collaborations. Large-scale research programmes will create new scientific questions and challenges, but they will not tell investigators how to address these. Academics will be free to choose how to proceed within the programme. Moreover, researchers will benefit from tapping into well-structured, large, knowledge bases, and they will have early access to the relevant data of others. Hence, being part of a large, well-organized research community brings benefits that might compensate for a perceived decrease in independence. Again, all of this depends strongly on how a large-scale programme is organized and managed, including the distribution of responsibilities, data-sharing policies and exchanges of expertise. Competition will probably remain part of the scientific endeavour, but it is important that it does not hamper collaboration and data sharing.Whilst we stress the need for larger-scale research efforts in the life sciences to have an impact on society, we also want to acknowledge the crucial role of classical curiosity-driven research programmes. It is essential to develop a reasonable and effective balance between different types of research in life sciences.A fourth issue is the lack of adequate funding mechanisms for international, large-scale research efforts. Given the ambiguous relationship between the life sciences and society—as argued in the first part of this essay—this problem can only be solved if life scientists convince policy-makers, funders and politicians that research can significantly contribute to solving societal problems and at reasonable costs. If not, life sciences will not flourish and society will not profit. As argued above, research efforts should be scaled to the complexity of the systems they intend to investigate. There are only a few problem-focused research programmes with a volume of more than €50 million. The VLN, funded to the tune of €43 million over five years by the German ministry for education and research, comes close. Its aim is to deliver a multi-scale representation of liver physiology, integrating data from the molecular, cellular and organ levels. The VLN involves 69 principal investigators dispersed throughout Germany and is headed by a director who is responsible for keeping the programme on track and on time. Issues such as standardization, division of responsibilities between the director and principal investigators, and decision-making procedures are tackled as the programme develops.If it is possible to rekindle the trust between society and the life sciences, will society be more willing to fund expensive, large-scale research programmes? Previous examples of publicly funded scientific and technological programmes in the multi-billion Euro range are the Large Hadron Collider, the Apollo programme and the Human Genome Project. Amazingly, none of these contributed directly to human well-being, although the Human Genome Project did make such promises. Hence, a life science programme that targets a crucial societal problem convincingly, such as metabolic syndrome, should have a fair chance of being acceptable and fundable.The above four issues must be addressed before the life sciences can successfully tackle major societal problems. It will need action from the research community itself, which is painfully lacking an organization to speak on behalf of life scientists and that can take the lead in discussions, internally and between society and science. Any such organization could learn from other areas, such as high-energy physics (CERN), astronomy (European Southern Observatory) and space research (European Space Agency). It would be tremendously helpful if a group of life scientists would get this issue on the agenda. This paper is meant to stimulate that process.In summary, we argue that if society wants to benefit from what the modern life sciences have to offer, we must act on two parallel tracks. One is to bring the life sciences closer to society and accept that society, science and morality are inseparable. The other is to rethink how we organize research in the life sciences. Both tracks create major challenges that can only be tackled successfully if the life sciences get organized and create a body that can lead the debate. At a more fundamental level, we need to decide what type of knowledge we want to acquire and why. Clearly, the value of generating knowledge for the sake of knowledge itself is important, but it must constantly be balanced with the values of society, which requires a dialogue between researchers and society.? Open in a separate windowTsjalling SwierstraOpen in a separate windowNiki VermeulenOpen in a separate windowJohan BraeckmanOpen in a separate windowRoel van Driel     

Alcohol Drinking Cessation and the Risk of Laryngeal and Pharyngeal Cancers: A Systematic Review and Meta-Analysis

Objective

To evaluate the effect of alcohol cessation on the risk of developing laryngeal and pharyngeal cancers, combining available evidence in the scientific literature in a meta-analysis.

Methods

A systematic literature review was conducted, and a meta-analysis was applied on the retrieved studies. The generalised least squares method was used to estimate the trend from dose-response data to assess changes in the risks of laryngeal and pharyngeal cancers after drinking cessation.

Results

A total of 9 case-control studies were included in the meta-analysis (4 and 8 estimates for laryngeal and pharyngeal cancers, respectively). On average, alcohol drinking cessation was associated with a 2% yearly reduction in the risk of developing laryngeal and pharyngeal cancers. There was a considerable heterogeneity between the studies of pharyngeal cancer, but this was mostly due to two studies. The increased risk of laryngeal and pharyngeal cancers caused by alcohol was reversible; the time periods until the risks became equal to those of never drinkers were 36 (95% CI 11–106) and 39 (95% CI 13–103) years, respectively. Moreover, 5 years of drinking cessation was associated with a reduction of around 15% in the alcohol-related elevated risk of laryngeal and pharyngeal cancers.

Conclusion

Although a long time period is required to completely eliminate the alcohol-related elevated risk of laryngeal and pharyngeal cancers, a substantial risk reduction can be seen in the short term (5–10 years), and drinking cessation should therefore be encouraged to reduce the incidence of these cancers.     

An Evaluation of Plotless Sampling Using Vegetation Simulations and Field Data from a Mangrove Forest

In vegetation science and forest management, tree density is often used as a variable. To determine the value of this variable, reliable field methods are necessary. When vegetation is sparse or not easily accessible, the use of sample plots is not feasible in the field. Therefore, plotless methods, like the Point Centred Quarter Method, are often used as an alternative. In this study we investigate the accuracy of different plotless sampling methods. To this end, tree densities of a mangrove forest were determined and compared with estimates provided by several plotless methods. None of these methods proved accurate across all field sites with mean underestimations up to 97% and mean overestimations up to 53% in the field. Applying the methods to different vegetation patterns shows that when random spatial distributions were used the true density was included within the 95% confidence limits of all the plotless methods tested. It was also found that, besides aggregation and regularity, density trends often found in mangroves contribute to the unreliability. This outcome raises questions about the use of plotless sampling in forest monitoring and management, as well as for estimates of density-based carbon sequestration. We give recommendations to minimize errors in vegetation surveys and recommendations for further in-depth research.     

Early Life Stress and Physical and Psychosocial Functioning in Late Adulthood

Background

Severe stress experienced in early life may have long-term effects on adult physiological and psychological health and well-being. We studied physical and psychosocial functioning in late adulthood in subjects separated temporarily from their parents in childhood during World War II.

Methods

The 1803 participants belong to the Helsinki Birth Cohort Study, born 1934–44. Of them, 267 (14.8%) had been evacuated abroad in childhood during WWII and the remaining subjects served as controls. Physical and psychosocial functioning was assessed with the Short Form 36 scale (SF-36) between 2001 and 2004. A test for trends was based on linear regression. All analyses were adjusted for age at clinical examination, social class in childhood and adulthood, smoking, alcohol intake, physical activity, body mass index, cardiovascular disease and diabetes.

Results

Physical functioning in late adulthood was lower among the separated men compared to non-separated men (b = −0.40, 95% confidence interval [95% CI]: −0.71 to −0.08). Those men separated in school age (>7 years) and who were separated for a duration over 2 years had the highest risk for lower physical functioning (b = −0.89, 95% CI: −1.58 to −0.20) and (b = −0.65, 95% CI: −1.25 to −0.05), respectively). Men separated for a duration over 2 years also had lower psychosocial functioning (b = −0.70, 95% CI: −1.35 to −0.06). These differences in physical and psychosocial functioning were not observed among women.

Conclusion

Early life stress may increase the risk for impaired physical functioning in late adulthood among men. Timing and duration of the separation influenced the physical and psychosocial functioning in late adulthood.     

A new mutation in MT-ND1 m.3928G>C p.V208L causes Leigh disease with infantile spasms

New mutations in mitochondrial DNA encoded genes of complex I are rarely reported. An infant developed Leigh disease with infantile spasms. Complex I enzyme activity was deficient and response to increasing coenzyme Q concentrations was reduced. Complex I assembly was intact. A new mutation in MT-ND1 m.3928G>C p.V208L, affecting a conserved amino acid in a critical domain, part of the coenzyme Q binding pocket, was present at high heteroplasmy. The unaffected mother did not carry measurable mutant mitochondrial DNA, but concern remained for gonadal mosaicism. Prenatal testing was possible for a subsequent sibling. The ND1 p.V208L mutation causes Leigh disease.