In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause the research (...) involves the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

Ten years after the Human Genome Project’s completion the life sciences stand in a moment of uncertainty, transition, and contestation. The postgenomic era has seen rapid shifts in research methodology, funding, scientific labor, and disciplinary structures. Postgenomics is transforming our understanding of disease and health, our environment, and the categories of race, class, and gender. At the same time, the gene retains its centrality and power in biological and popular discourse. The contributors to Postgenomics analyze these ruptures and continuities (...) and place them in historical, social, and political context. Postgenomics, they argue, forces a rethinking of the genome itself, and opens new territory for conversations between the social sciences, humanities, and life sciences. Contributors. Russ Altman, Rachel A. Ankeny, Catherine Bliss, John Dupré, Michael Fortun, Evelyn Fox Keller, Sabina Leonelli, Adrian Mackenzie, Margot Moinester, Aaron Panofsky, Sarah S. Richardson, Sara Shostak, Hallam Stevens. (shrink)

We have synthesized a 582,970-base pair Mycoplasma genitalium genome. This synthetic genome, named M. genitalium JCVI-1.0, contains all the genes of wild-type M. genitalium G37 except MG408, which was disrupted by an antibiotic marker to block pathogenicity and to allow for selection. To identify the genome as synthetic, we inserted "watermarks" at intergenic sites known to tolerate transposon insertions. Overlapping "cassettes" of 5 to 7 kilobases (kb), assembled from chemically synthesized oligonucleotides, were joined by in vitro recombination (...) to produce intermediate assemblies of approximately 24 kb, 72 kb ("1/8 genome"), and 144 kb ("1/4 genome"), which were all cloned as bacterial artificial chromosomes in Escherichia coli. Most of these intermediate clones were sequenced, and clones of all four 1/4 genomes with the correct sequence were identified. The complete synthetic genome was assembled by transformation-associated recombination cloning in the yeast Saccharomyces cerevisiae, then isolated and sequenced. A clone with the correct sequence was identified. The methods described here will be generally useful for constructing large DNA molecules from chemically synthesized pieces and also from combinations of natural and synthetic DNA segments. 10.1126/science.1151721. (shrink)

On September 5, 2020, the International Commission on the Clinical Use of Human Germline Genome Editing, established by the U.S. National Academy of Medicine, the National Academy of Science,...

The Bermuda Principles for DNA sequence data sharing are an enduring legacy of the Human Genome Project. They were adopted by the HGP at a strategy meeting in Bermuda in February of 1996 and implemented in formal policies by early 1998, mandating daily release of HGP-funded DNA sequences into the public domain. The idea of daily sharing, we argue, emanated directly from strategies for large, goal-directed molecular biology projects first tested within the “community” of C. elegans researchers, and were (...) introduced and defended for the HGP by the nematode biologists John Sulston and Robert Waterston. In the C. elegans community, and subsequently in the HGP, daily sharing served the pragmatic goals of quality control and project coordination. Yet in the HGP human genome, we also argue, the Bermuda Principles addressed concerns about gene patents impeding scientific advancement, and were aspirational and flexible in implementation and justification. They endured as an archetype for how rapid data sharing could be realized and rationalized, and permitted adaptation to the needs of various scientific communities. Yet in addition to the support of Sulston and Waterston, their adoption also depended on the clout of administrators at the US National Institutes of Health and the UK nonprofit charity the Wellcome Trust, which together funded 90% of the HGP human sequencing effort. The other nations wishing to remain in the HGP consortium had to accommodate to the Bermuda Principles, requiring exceptions from incompatible existing or pending data access policies for publicly funded research in Germany, Japan, and France. We begin this story in 1963, with the biologist Sydney Brenner’s proposal for a nematode research program at the Laboratory of Molecular Biology at the University of Cambridge. We continue through 2003, with the completion of the HGP human reference genome, and conclude with observations about policy and the historiography of molecular biology. (shrink)

In addition to the aim of mapping and sequencing one human's genome, the Human Genome Project also intends to characterise the genetic diversity of the world's peoples. The Human Genome Diversity Project raises political, economic and ethical issues. These intersect clearly when the genomes under study are those of indigenous peoples who are already subject to serious economic, legal and/or social disadvantage and discrimination. The fact that some individuals associated with the project have made dismissive comments about (...) indigenous peoples has confused rather than illuminated the deeper issues involved, as well as causing much antagonism among indigenous peoples. There are more serious ethical issues raised by the project for all geneticists, including those who are sympathetic to the problems of indigenous peoples. With particular attention to the history and attitudes of Australian indigenous peoples, we argue that the Human Genome Diversity Project can only proceed if those who further its objectives simultaneously: respect the cultural beliefs of indigenous peoples; publicly support the efforts of indigenous peoples to achieve respect and equality; express respect by a rigorous understanding of the meaning of equitable negotiation of consent, and ensure that both immediate and long term economic benefits from the research flow back to the groups taking part. (shrink)

On June 26, 2000, President Clinton, together with Francis Collins and Craig Venter, solemnly announced, from the East Room of the White House, that the grand effort to sequence the human genome, the Human Genome Project (HGP), was rapidly nearing its completion. Symbolism abounded. The event was framed as a crucial marker in the history of both humanity and knowledge by explicitly connecting the completion of the HGP with a number of already acknowledged and established scientific highlights. Tensions (...) abounded as well, however, notably between competing metaphors. In the course of the HGP, metaphors had become crucially important in framing and conveying what the HGP was really about. They had proved themselves to be of key importance when it came to defining and explaining the project’s significance for both science and society. Powerful images and metaphors had been deployed in order to secure unprecedented amounts of funding, on the one hand by comparing the HGP to other big technoscientific projects such as space travel, high energy physics, the atomic bomb and a territorial mapping exercise, and on the other hand through the suggestion that, once we have our “blueprint”, “code of codes”, “parts list”, etc. available, cancer genes will no longer have a place to hide. This article sets out to analyze this clash of metaphors, firmly embedded within the HGP but culminating at the press conference, arguing that the June 2000 event is even reminiscent of a somewhat similar event, depicted by a famous altarpiece, ‘The adoration of the Lamb’, on display in Ghent Cathedral and finished more than five centuries before. (shrink)

Two major reports in the UK and USA have recently sanctioned as ethically acceptable genome editing of future generations for the treatment of serious rare inherited conditions. This marks an important turning point in the application of recombinant DNA techniques to humans. The central question this paper addresses is how did it became possible for human genetic engineering (HGE) of future generations to move from an illegitimate idea associated with eugenics in the 1980s to a concrete proposal sanctioned by (...) scientists and bioethicists in 2020? The paper uses the concept of a regime of normativity to understand the co-evolution and mutual shaping of technology, imaginaries, norms and governance processes in debates about HGE in the USA and UK. It will be argued that interlinked discursive, institutional, political and technological changes have made proposals for the use of genome editing in the genetic engineering of future generations both “thinkable” and legitimate. (shrink)

Gyngell and colleagues consider that the recent Nuffield Council report does not go far enough: heritable genome editing is not just justifiable in a few rare cases; instead, there is a moral imperative to undertake it. We agree that there is a moral argument for this, but in the real world it is mitigated by the fact that it is not usually possible to ensure a better life. We suggest that a moral imperative for HGE can currently only be (...) concluded if one first buys into an overly deterministic view of a genome sequence, and the role of variation within in it, in the aetiology of the disease: most diseases cannot simply be attributed to specific genetic variants that we could edit away. Multiple, poorly understood genetic and environmental factors interact to influence the expression of diseases with a genetic component, even well understood ‘monogenic’ disorders. Population-level genome analyses are now demonstrating that many genetic ’mutations' are much less predictive than previously thought 1. Furthermore, HGE might introduce new risks just as it reduces old ones; or remove protections not yet clearly delineated. (shrink)

On October 1, 1988, thirty-five years after co-discovering the structure of the DNA molecule, Dr. James Watson launched an unprecedented experiment in American science policy. In response to a reporter's question at a press conference, he unilaterally set aside 3 to 5 percent of the budget of the newly launched Human Genome Project to support studies of the ethical, legal, and social implications of new advances in human genetics. The Human Genome Project (HGP), by providing geneticists with the (...) molecular maps of the human chromosomes that they use to identify specific human genes, will speed the proliferation of a class of DNA-based diagnostic and risk-assessment tests that already create professional ethical and health-policy challenges for clinicians. “The problems are with us now, independent of the genome program, but they will be associated with it,” Watson said. “We should devote real money to discussing these issues.” By 1994, the “ELSI program” (short for “Ethical, Legal, and Social Implications”) had spent almost $20 million in pursuit of its mission, and gained both praise and criticism for its accomplishments. (shrink)

After reading Savulescu and colleagues,1 one ought to be in no doubt that human heritable genome editing is a ‘moral imperative’: to cure disease, reduce inequalities, improve public health and protect future generations. They make this argument repeatedly and in no uncertain terms. Yet are they right to do so? I am certainly not against developing HGE or exploring its possibilities. Instead, I aim to sound a cautionary note in relation to claims about its technological potential and how we (...) frame arguments on this basis. The ‘moral imperative’ argument has been made many times, since well before the advent of genome editing, by the present authors and others. It generally rests on a number of preconditions, implicit or explicit: that HGE will be safe, effective, cost-efficient and equitably available. Now, many bioethicists would take no issue with, indeed have supported,5 the proposition that, once all of these conditions are satisfied, HGE is something we have good moral reasons to pursue. At this pivotal moment for global science, ethics and governance, however, we need equally to be concerned with the technology’s immediate future trajectory: whether and how we can reach the point of satisfying these conditions. In this context, the MIA is something of a distraction; at worst, it may even be corrosive and damaging. Consider first the argument from evolutionary fitness, that HGE is morally required to counteract the supposed ‘genetic deterioration’ produced by medically enabled ‘survival of the weak’, that makes …. (shrink)

This article traces the rapid progression of policy pertaining to human genome germline modifications using genome editing. It provides an overview of how one fertility physician implemented and advertised experimental techniques as part of his fertility clinic services, examines US law and policy, and assesses the impact of rhetoric influencing global policy and interpretation of the law. This article provides an in-depth examination of the medical rationale driving the acceptance of genome editing human embryos in two contexts: (...) to cure disease and treat infertility. It describes complexities in genomics and outlines risks currently associated with genome editing, asserting the available evidence fails to demonstrate genome editing constitutes a curative therapy. (shrink)

Hastings Center Report, Volume 52, Issue 2, Page 10-14, March‐April 2022.

This paper examines three possible justifications for original ACMG recommendations to return incidental findings from whole exome or genome sequencing independent of patient preferences. The first two potential justifications, based on a patient's authentic values, then on harms to others, are founding lacking as a basis of justification for these recommendations. The third, grounded in analogous professional practices, might serve as a potential justification if several controversies can be avoided. However, given the nature of these controversies and the need (...) to instill public trust in this newly emerging science, the paper finds that updated ACMG recommendations that recognize opt-out rights on behalf of patients is the most prudent, and justifiable, approach. (shrink)

Review of Francoise Baylis, Altered Inheritance: CRISPR and the Ethics of Human Genome Editing (2019).

The chromodomain is a highly conserved sequence motif that has been identified in a variety of animal and plant species. In mammals, chromodomain proteins appear to be either structural components of large macromolecular chromatin complexes or proteins involved in remodelling chromatin structure. Recent work has suggested that apart from a role in regulating gene activity, chromodomain proteins may also play roles in genome organisation. This article reviews progress made in characterising mammalian chromodomain proteins and emphasises their emerging role in (...) the regulation of gene expression and genome organisation. BioEssays 22:124–137, 2000. ©2000 John Wiley & Sons, Inc. (shrink)

This paper reports our analysis of the ELSI Virtual Forum: 30 Years of the Genome: Integrating and Applying ELSI Research, an online meeting of scholars focused on the ethical, legal, and social implications (ELSI) of genetics and genomics.

An important mechanism for the evolution of phenotypic complexity, diversity and innovation, and the origin of novel gene functions is the duplication of genes and entire genomes. Recent phylogenomic studies suggest that, during the evolution of vertebrates, the entire genome was duplicated in two rounds (2R) of duplication. Later, ∼350 mya, in the stem lineage of ray‐finned (actinopterygian) fishes, but not in that of the land vertebrates, a third genome duplication occurred—the fish‐specific genome duplication (FSGD or 3R), (...) leading, at least initially, to up to eight copies of the ancestral deuterostome genome. Therefore, the sarcopterygian (lobe‐finned fishes and tetrapods) genome possessed originally only half as many genes compared to the derived fishes, just like the most‐basal and species‐poor lineages of extant fishes that diverged from the fish stem lineage before the 3R duplication. Most duplicated genes were secondarily lost, yet some evolved new functions. The genomic complexity of the teleosts might be the reason for their evolutionary success and astounding biological diversity. BioEssays 27:937–945, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

On November 26, 2018, the world awoke to the news that genome editing had for the first time been used to create genetically modified human beings. He Jiankui, a scientist then employed by Southern University of Science and Technology of China, Shenzhen, announced via social media and the popular press that he had performed genome editing on embryos with the aim of disrupting the CCR5 gene in order to induce immunity to HIV, implanted the embryos, and that twin (...) girls had been born.In the wake of this announcement, arguments, claims, and accusations flew. Most commentators declared He's actions "irresponsible," pointing to various statements by scientific organizations agreeing that human embryo genome editing was... (shrink)

Conley and colleagues (2023) explore how calls for broad public engagement (PE) in the case of heritable human genome editing are being put into action, reviewing the activities of five different i...

A common account sees the human genome sequencing project of the 1990s as a “natural outgrowth” of the deciphering of the double helical structure of DNA in the 1950s. The essay aims to complicate this neat narrative by putting the spotlight on the field of human chromosome research that flourished at the same time as molecular biology. It suggests that we need to consider both endeavors – the human cytogeneticists who collected samples and looked down the microscope and the (...) molecular biologists who probed the molecular mechanisms of gene function – to understand the rise of the human genome sequencing project and the current genomic practices. In particular, it proposes that what has often been described as the “molecularization” of cytogenetics could equally well be viewed as the turn of molecular biologists to human and medical genetics – a field long occupied by cytogeneticists. These considerations also have implications for the archives that are constructed for future historians and policy makers. (shrink)

With the advent of CRISPR gene-editing technology, designer babies have become a reality. Françoise Baylis insists that scientists alone cannot decide the terms of this new era in human evolution. Members of the public, with diverse interests and perspectives, must have a role in determining our future as a species.

A common account sees the human genome sequencing project of the 1990s as a “natural outgrowth” of the deciphering of the double helical structure of DNA in the 1950s. The essay aims to complicate this neat narrative by putting the spotlight on the field of human chromosome research that flourished at the same time as molecular biology. It suggests that we need to consider both endeavors – the human cytogeneticists who collected samples and looked down the microscope and the (...) molecular biologists who probed the molecular mechanisms of gene function – to understand the rise of the human genome sequencing project and the current genomic practices. In particular, it proposes that what has often been described as the “molecularization” of cytogenetics could equally well be viewed as the turn of molecular biologists to human and medical genetics – a field long occupied by cytogeneticists. These considerations also have implications for the archives that are constructed for future historians and policy makers. (shrink)

While the 1970's have been called the environmental years, the 1990's could be seen as the genome years. As the challenge to map and to sequence the human genome mobilized the scientific community, risks and benefits of information and uses that would derive from this project have also raised ethical issues at the international level. The particular interest of the 1997 UNESCO Declaration relies on the fact that it emphasizes both the scientific importance of genetics and the appropriate (...) reinforcement of human rights in this area. It considers the human genome, at least symbolically, as the common heritage of humanity. (shrink)

The fundamental Hennigian principle, grouping solely on synapomorphy, is seldom used in modern phylogenetics. In the submitted paper, we apply this principle in reanalyzing five datasets comprising 197 complete plastid genomes (plastomes). We focused on the latter because plastome-based DNA sequence data gained dramatic popularity in molecular systematics during the last decade. We show that pattern-cladistic analyses based on complete plastid genome sequences can successfully resolve affinities between plant taxa, simultaneously simplifying both the genomic and analytical frameworks of phylogenetic (...) studies. We developed “Matrix to Newick” (M2N), a program to represent the standard molecular alignment of plastid genomes in the form of trees or relationships directly. Thus, massive plastome-based DNA sequence data can be successfully represented in a relational form rather than as a standard molecular alignment. Application of methods of median supertree construction (the Average Consensus method has been used as an example in this study) or Maximum Parsimony analysis to relational representations of plastome sequence data may help systematist to avoid the complicated assumption-based frameworks of Maximum Likelihood or Bayesian phylogenetics that are most used today in massive plastid sequence data analyses. We also found that significant amounts of pure genomic information that typically accommodate the majority of current plastid phylogenomic studies can be effectively dropped by systematists if they focus on the pattern-cladistics or relational analyses of plastome-based molecular data. The proposed pattern-cladistic approach is a powerful and straightforward heuristic alternative to modern plastome-based phylogenetics. (shrink)

What kind of world do we want to live in? It’s rare that we ask this question of ourselves, and even rarer that we get to do so with others. In Altered Inheritance: CRISPR and the Ethics of Human Genome Editing, Francoise Baylis encourages us to keep this question in the forefront of our minds as we think about whether, when, or how to edit the human genome. She is neither an “enthusiastic proponent nor a staunch opponent” of (...) heritable human genome editing. She is, however, very clear that the ethics of human genome editing is not the domain of scientists, ethicists, or elites. Her thesis is that all of us must think together about what our collective future should look like, and then consider whether and how... (shrink)

Inclusive fitness theory provides conditions for the evolutionary success of a gene. These conditions ensure that the gene is selfish in the sense of Dawkins (The selfish gene, Oxford University Press, Oxford, 1976): genes do not and cannot sacrifice their own fitness on behalf of the reproductive population. Therefore, while natural selection explains the appearance of design in the living world (Dawkins in The blind watchmaker: why the evidence of evolution reveals a universe without design, W. W. Norton, New York, (...) 1996), inclusive fitness theory does not explain how. Indeed, Hamilton’s rule is equally compatible with the evolutionary success of prosocial altruistic genes and antisocial predatory genes, whereas only the former, which account for the appearance of design, predominate in successful organisms. Inclusive fitness theory, however, permits a formulation of the central problem of sociobiology in a particularly poignant form: how do interactions among loci induce utterly selfish genes to collaborate, or to predispose their carriers to collaborate, in promoting the fitness of their carriers? Inclusive fitness theory, because it abstracts from synergistic interactions among loci, does not answer this question. Fitness-enhancing collaboration among loci in the genome of a reproductive population requires suppressing alleles that decrease, and promoting alleles that increase the fitness of its carriers. Suppression and promotion are effected by regulatory networks of genes, each of which is itself utterly selfish. This implies that genes, and a fortiori individuals in a social species, do not maximize inclusive fitness but rather interact strategically in complex ways. It is the task of sociobiology to model these complex interactions. (shrink)

Altered Inheritance is essential reading for anyone interested in genome editing and its ethical and social implications. Current genome editing technologies are rapidly making science fiction a reality. Indeed, it is a marvelous time for genetics, largely due to CRISPR-Cas tools being adopted in research and commercial sectors. While scientists were able to alter DNA for over thirty years, CRISPR offers faster, cheaper, and more accurate methods to remove, add, or alter genes. Applications abound, with researchers working to (...) develop therapies to treat a wide range of genetic disorders. However, as Françoise Baylis so aptly states, although “CRISPR shows great promise for therapeutic use, it raises thorny ethical... (shrink)

Background Forward-looking, democratically oriented governance is needed to ensure that human genome editing serves rather than undercuts public values. Scientific, policy, and ethics communities have recognized this necessity but have demonstrated limited understanding of how to fulfill it. The field of bioethics has long attempted to grapple with the unintended consequences of emerging technologies, but too often such foresight has lacked adequate scientific grounding, overemphasized regulation to the exclusion of examining underlying values, and failed to adequately engage the public. (...) Methods This research investigates the application of scenario planning, a tool developed in the high-stakes, uncertainty-ridden world of corporate strategy, for the equally high-stakes and uncertain world of the governance of emerging technologies. The scenario planning methodology is non-predictive, looking instead at a spread of plausible futures which diverge in their implications for different communities’ needs, cares, and desires. Results In this article we share how the scenario development process can further understandings of the complex and dynamic systems which generate and shape new biomedical technologies and provide opportunities to re-examine and re-think questions of governance, ethics and values. We detail the results of a year-long scenario planning study that engaged experts from the biological sciences, bioethics, social sciences, law, policy, private industry, and civic organizations to articulate alternative futures of human genome editing. Conclusions Through sharing and critiquing our methodological approach and results of this study, we advance understandings of anticipatory methods deployed in bioethics, demonstrating how this approach provides unique insights and helps to derive better research questions and policy strategies. (shrink)

As genomic science has evolved, so have policy and practice debates about how to describe and evaluate the ways in which genomic information is treated for individuals, institutions, and society. The term genetic exceptionalism, describing the concept that genetic information is special or unique, and specifically different from other kinds of medical information, has been utilized widely, but often counterproductively in these debates. We offer genomic contextualism as a new term to frame the characteristics of genomic science in the debates. (...) Using stasis theory to draw out the important connection between definitional issues and resulting policies, we argue that the framework of genomic contextualism is better suited to evaluating genomics and its policy-relevant features to arrive at more productive discussion and resolve policy debates. (shrink)

From the earliest days of the Human Genome Project, the holy grail of genomics was the ability to perform whole-genome sequencing quickly, accurately, and relatively inexpensively so that the benefits of genomics would be widely available in clinical settings. Although the mythical $1,000 genome sequence seemed elusive for many years, next-generation sequencing technologies and other recent advances clearly indicate that inexpensive whole-genome sequencing is at hand.Whole-genome sequencing has demonstrable value in elucidating the genetic etiology of (...) rare disorders, in identifying atypical variants in common diseases, in determining pharmacogenomically appropriate drugs and dosages, in performing tumor genome sequencing, and in aiding other clinical applications for the diagnosis and treatment of individuals who are symptomatic or whose family health history places them at substantial risk. Undoubtedly, the clinical applications of wholegenome sequencing will increase in the future. (shrink)

The anticipation of ethical issues that may arise with the clinical use of genomic technologies is crucial to envision their future implementation in a manner sensitive to local contexts. Yet, populations in low- and middle-income countries are underrepresented in studies that aim to explore stakeholders’ perspectives on the use of such technologies. Within the framework of a research project entitled “Personalized medicine in the treatment of epilepsy”, we sought to increase inclusiveness by widening the reach of our survey, inviting neurologists (...) from around the world to share their views and practices regarding the use of whole-genome sequencing in clinical neurology and its associated ethics. We discuss herein the compelling scientific and ethical reasons that led us to attempt to recruit neurologists worldwide, despite the lack, in many low- or middle-income countries, of access to genomic technologies. Recruitment procedures and their results are presented and discussed, as well as the barriers we faced. We conclude that inclusive recruitment remains a challenging, albeit necessary and legitimate, endeavour. (shrink)

Replication protein A (RPA) is the main eukaryotic single‐stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here, we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology‐mediated end (...) joining or the formation of hairpin structures that are substrates for structure‐selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity. (shrink)

the recent announcement of the claimed births of CRISPR-edited babies has prompted both widespread condemnation and calls by leading scientists for a moratorium on any further germline genome editing for reproductive purposes. Concurrently, national and international bodies are calling for the development of robust guidelines and requirements that will identify permissible conditions under which such GGE efforts may proceed. As detailed recommendations to navigate this unique terrain are under development, we suggest an approach that begins with identifying serious concerns (...) about social exclusion and social justice that arise... (shrink)

As evidenced by high-throughput sequencers, genomic technologies have recently undergone radical advances. These technologies enable comprehensive sequencing of personal genomes considerably more efficiently and less expensively than heretofore. These developments present a challenge to the conventional framework of biomedical ethics; under these changing circumstances, each research project has to develop a pragmatic research policy. Based on the experience with a new large-scale project—the Genome Science Project—this article presents a novel approach to conducting a specific policy for personal genome (...) research in the Japanese context. In creating an original informed-consent form template for the project, we present a two-tiered process: making the draft of the template following an analysis of national and international policies; refining the draft template in conjunction with genome project researchers for practical application. Through practical use of the template, we have gained valuable experience in addressing challenges in the ethical review process, such as the importance of sharing details of the latest developments in genomics with members of research ethics committees. We discuss certain limitations of the conventional concept of informed consent and its governance system and suggest the potential of an alternative process using information technology. (shrink)

The regulatory mechanism which ensures that eukaryotic chromosomes replicate precisely once per cell cycle is a basic and essential cellular property of eukaryotes. This fundamental aspect of DNA replication is still poorly understood, but recent advances encourage the view that we may soon have a clearer picture of how this regulation is achieved. This review will discuss in particular the role of proteins in the minichromosome maintenance (MCM) family, which may hold the key to understanding how DNA is replicated once, (...) and only once, per cell cycle. (shrink)

Synthetic Biology and Renewal of the Ethics of the Research. From the Genome Editing to Organoids of the Brains In this paper I will address the philosophical and scientific impact brought up by “synthetic biology” from the beginning of embryogeny to the fabrication of organoids, to analyze how this paradigm shift impacts on our definition of what a good life is, or should be, in rehabilitation a dialog between sciences and philosophy.

Dr Sydney Brenner has played a major, and unique, role in biology during the past 40 years. His contributions have ranged from key work on the structure of the genetic code and the existence of mRNA through the development of Caenorhabditis elegans as a key model system in developmental biology to genomic analysis and function in vertebrates. BioEssays went to interview Dr Brenner at his home in the cathedral city of Ely, England, on the significance of the genome projects (...) for human biology, in particular, and for biology, in general. (shrink)

Horizontal transfer (HT) is the transmission of genetic material between non‐mating species, a phenomenon thought to occur rarely in multicellular eukaryotes. However, many transposable elements (TEs) are not only capable of HT, but have frequently jumped between widely divergent species. Here we review and integrate reported cases of HT in retrotransposons of the BovB family, and DNA transposons, over a broad range of animals spanning all continents. Our conclusions challenge the paradigm that HT in vertebrates is restricted to infective long (...) terminal repeat (LTR) retrotransposons or retroviruses. This raises the possibility that other non‐LTR retrotransposons, such as L1 or CR1 elements, believed to be only vertically transmitted, can horizontally transfer between species. Growing evidence indicates that the process of HT is much more general across different TEs and species than previously believed, and that it likely shapes eukaryotic genomes and catalyses genome evolution. (shrink)

Chromatin composition differs across the genome, with distinct compositions characterizing regions associated with different properties and functions. Whereas many histone modifications show local enrichment over genes or regulatory elements, marking can also span large genomic intervals defining broad chromatin domains. Here we highlight structural and functional features of chromatin domains marked by histone modifications, with a particular emphasis on the potential roles of H3K27 methylation domains in the organization and regulation of genome activity in metazoans. Chromatin domains are (...) extended genomic regions defined by the continuous enrichment of a given histone modification. Here, we review recent work highlighting the presence of chromatin domains in multiple species, their structural aspects in the context of chromatin architecture, and their potential role on the regulation of genome activity. (shrink)

It is essential for scientists to introduce their research in a comprehensible manner and to communicate with colleagues in the same/different fields and with the public. As genome research requires the massive expenditure of public funds, and raises ethical, legal, and social issues, genome scientists have communicated extensively with the public. In addition, they have established interdisciplinary collaborations that resulted in the creation of a new research field known as bioinformatics.We examined the history of communication activities involving Japanese (...) genome scientists between 1989 and 2005 using extensive literature surveys and interviews. We found that genome researchers went through much trial and error, particularly with respect to collaborative interdisciplinary efforts, and although they early on recognized the necessity of communicating with colleagues in different fields, it was not until the introduction of a large governmental research budget, the Millennium Project (2000 - 2004), that individual researchers began to be actively engaged in communication activities. In conclusion, to facilitate the participation of scientists in communication activities, researchers who are acquainted with different research fields, community, and society should proactively function as coordinators of interdisciplinary programs or mediators of collaborative research. It is also of primal importance to present to scientists the advantage of dialogue with society scientifically and to design effective communication programs that provide researchers with such opportunities. (shrink)

Over the past few years, developments in the science of precise editing of human genomes using CRISPR-Cas9 have led many countries that lack specific laws in this area, such as South Africa, to contemplate legal reform. Thaldar et al. recently published five principles to guide legal reform in SA on heritable genome editing. In a similar vein, concerns about the global impact of human germline genome editing have led to calls for a global regulatory mechanism. This is what (...) the World Health Organization has tried to achieve with the recently published ‘Draft governance framework for human genome editing’. In this article, we compare the policies proposed by the draft framework to the current SA legal position, as well as the five guiding principles. The article concludes that SA law is in need of reform in order to meet the global standards that the draft framework seems to be moving towards. (shrink)

Chromosomal rearrangements frequently occur at specific places (“hot spots”) in the genome. These recombination hot spots are usually separated by 50–100 kb regions of DNA that are rarely involved in rearrangements. It is quite likely that there is a correlation between the above‐mentioned distances and the average size of DNA loops fixed at the nuclear matrix. Recent studies have demonstrated that DNA loop anchorage regions can be fairly long and can harbor DNA recombination hot spots. We previously proposed that (...) chromosomal DNA loops may constitute the basic units of genome organization in higher eukaryotes. In this review, we consider recombination between DNA loop anchorage regions as a possible source of genome evolution. (shrink)

I greatly appreciate the open peer commentary authors’ thoughtful engagement with my proposal to include a Citizens’ Jury (CJ) at the level of the International Commission when exploring ethical re...

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical (...) and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. (shrink)