Prenatal genetic diagnosis with new high-performance technologies such as genomic array adds great complexity to the ethical dilemmas that already exist in current medicine. The main objective of this study was to carry out an analysis and bioethical reflections centred on the outcome associated with the use of the genetic array technique in 185 pregnancies at the Hospital Universitario y Politécnico La Fe (Valencia, Spain). It is an observational, descriptive and cross-sectional study during the years 2014 to 2017, inclusive. (...) We analyse the results and the follow-up of the 185 cases in which this prenatal genetic study was carried out by array technique. Of the 185 prenatal genetic studies carried out, 165 showed no copy number variants (normal result) and in the 20 remaining pregnancies (10.81%), a dose change was detected. Abortion was carried out in 11 cases with pathological and/or probably pathological abnormalities. Of the 165 cases in which no dose variant was detected, an abortion was carried out in 49 cases, which represents 29.7%. The introduction of new genomic analysis techniques to invasive prenatal diagnosis highlights the ethical problems that arise above all in the interpretation of genetic variants detected and genetic counselling, while emphasising the need for correct informed consent and it adds, if possible, more controversy to a subject with great bioethical substance such as abortion. (shrink)

The basic premise of the host‐defense theory is that genomic imprinting, the parent‐of‐origin expression of a subset of mammalian genes, derives from mechanisms originally dedicated to silencing repeated and retroviral‐like sequences that deeply colonized mammalian genomes. We propose that large clusters of tandemly‐repeated C/D‐box small nucleolar RNAs (snoRNAs) or microRNAs represent a novel category of sequences recognized as “genomic parasites”, contributing to the emergence of genomic imprinting in a subset of chromosomal regions that contain them. Such a (...) view is supported by evidence derived from studies of the imprinted snoRNA‐ and/or miRNA‐encoding Dlk1‐Dio3, Snurf‐Snrpn, Sfbmt2, and C19MC domains. While adding a new piece to the challenging puzzle of mammalian genome history, this hypothesis also reinforces the notion that dissecting the features and molecular mechanisms that discriminate between “foreign” and “endogenous” sequences is of crucial importance in the field of mammalian epigenetics. (shrink)

Advances in biochemistry, chemistry and engineering have enabled the development of a new gene expression assay. This ‘chip‐based’ approach utilizes microscopic arrays of cDNAs printed on glass as high‐density hybridization targets. Fluorescent probe mixtures derived from total cellular messenger RNA (mRNA) hybridize to cognate elements on the array, allowing accurate measurement of the expression of the corresponding genes. Array densities of >1,000 cDNAs per cm2 enable quantitative expression monitoring of a large number of genes in a single hybridization. A (...) two‐color fluorescence detection scheme allows rapid and simultaneous differential expression analysis of independent biological samples. Mass‐produced microarrays provide a new tool for genome expression analysis that may revolutionize genetic dissection, drug discovery and human disease diagnostics. (shrink)

The genomics “revolution” is spreading. Originating in the molecular life sciences, it initially affected a number of biomedical research fields such as cancer genomics and clinical genetics. Now, however, a new “wave” of genomic bioinformation is transforming a widening array of disciplines, including those that address the social, historical and cultural dimensions of human life. Increasingly, bioinformation is affecting “human sciences” such as psychiatry, psychology, brain research, behavioural research (“behavioural genomics”), but also anthropology and archaeology (“bioarchaeology”). Thus, bioinformatics is (...) having an impact on how we define and understand ourselves, how identities are formed and constituted, and, finally, on how we (on the basis of these redefined identities) assess and address some of the more concrete societal issues involved in genomics governance in various settings. This article explores how genomics and bioinformation, by influencing research agendas in the human sciences and the humanities, are affecting our self-image, our identity, the way we see ourselves. The impact of bioinformation on self-understanding will be assessed on three levels: (1) the collective level (the impact of comparative genomics on our understanding of human beings as a species), (2) the individual level (the impact of behavioural genomics on our understanding of ourselves as individuals), and (3) the genealogical level (the impact of population genomics on our understanding of human history, notably early human history). This threefold impact will be assessed from two seemingly incompatible philosophical perspectives, namely a “humanistic” perspective (represented in this article by Francis Fukuyama) and a “post-humanistic” one (represented by Peter Sloterdijk). On the basis of this analysis it will be concluded that, rather than focussing on human “enhancement” by adding or deleting genes, genome-oriented practices of the Self will focus on using genomics information in the context of identity-formation. Genomic bioinformation will increasingly be built into our self-images and used in order to tailor and adapt our practices of Self to our “personalised” genome. We will keep working on ourselves, no doubt, not by modifying our genomes, but rather by fine-tuning our behaviour. What we are experiencing is a bioinformatisation of the life-world. Genomics-based technologies will increasingly pervade our daily lives, our autobiographies and narratives, as well as our anthropologies, rather than our genomes as such. (shrink)

The human genome contains about 30,000 genes, each creating several transcripts per gene. Transcript structures and expression are studied by high‐throughput transcriptomic techniques using microarrays. Generally, transcripts are not directly operating molecules, but are translated into functional proteins, post‐translationally modified by proteolysis, glycosylation, phosphorylation, etc., sometimes with great functional impact. Proteins need to be analyzed by proteomic techniques, less suited for high‐throughput. Two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE), separating thousands of proteins has developed slowly over the past quarter of a century. (...) This technique is now quite reproducible and suitable for differential proteomics, comparing normal and diseased cells/tissues revealing differentially regulated proteins. 2D‐PAGE is combined with protein‐identification methods, currently mass spectrometry (MS), which has been significantly improved over the last decade. Other proteomic techniques studying protein–protein interactions are now either established or still being developed, such as peptide or protein arrays, phage display, and the yeast two‐hybrid system. The strengths and weaknesses of these techniques are discussed. BioEssays 26:901–915, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The phenomenal proliferation of scientific studies into the nature of induced pluripotent stem (iPS) cells following publication of the findings of Takahashi and Yamanaka little more than 2 years ago, have significantly expanded our understanding of cellular mechanisms relating to cell lineage, differentiation, and proliferation. While the full potential of iPS cell lineages for both scientific tool and therapeutic applications is as yet unclear, findings from several lines of investigation suggests that multipotential and terminally differentiated cells from an array of (...) cell types are competent to undergo epigenetic reprogramming to a pluripotential state. The nature of this pluripotential state appears to be similar to, but not identical with that previously described for embryonic stem (ES) cells. Understanding the nature of this induced reprogrammed state will be critical to determining the full potential of iPS cells. Recently, this issue has been examined through an integrated analysis of the genome in fully and partially reprogrammed iPS cell lineages. These results provide a window onto the temporal components of reprogramming and suggest mechanisms by which the efficacy of reprogramming can be enhanced. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Human Genome Research in an Interdependent WorldAlexander Morgan Capron (bio)This has been the year of agenda-setting conferences for the ambitious ELSI (ethical, legal and social issues) program of the Human Genome Project (HGP). But of the dozen or more major meetings of this sort held across the country, the one held at the National Institutes of Heakh (NIH) in Bethesda, MD, June 2-4, 1991, was distinctive in several respects.1As (...) its name implies, "Human Genome Research in an Interdependent World" was a global look at the issues raised by gene mapping and sequencing. Unlike previous conferences, however, this meeting looked beyond a comparative analysis of clinical and domestic legal issues, and concentrated on topics that may require responses on a truly international level if they are to be successfully resolved.The meeting's organizers gathered an impressive group of more than seventy participants from fifteen countries, including the first significant contingent of Soviet and Japanese scientists, physicians, and philosophers at an ELSI meeting. In addition to talks by the heads of the genome projects in the Soviet Union, Japan, and the United States, the meeting was keynoted by Dr. James Wyngaarden, director general of the Human Genome Organization (HUGO), and I had the honor of serving as its general chairman.The goal of the meeting was to consider an array of issues that scientists, philosophers, and lawyers from around the world suggested might have international significance, with an eye to deciding three things: (1) Does the issue deserve further attention? (2) Is the issue best addressed in an international or domestic context? and (3) Do structures exist to which the issue can be referred for resolution? In the final sessions, the entire group debated proposed resolutions on the various topics and narrowed the list needing further, intensive exploration.To provide an international framework for this process, the conference [End Page 247] established a Global Steering Committee on Ethical and Social Issues in Genome Research, which will coordinate the efforts of several task forces charged with refining the tentative resolutions adopted by the conference participants on June 4. The task forces are expected to be able to complete work on some topics by the time of the steering committee's first meeting, which was described by one participant as a "check point," probably within the coming year; on other topics, the task forces will provide interim reports and arrange to continue their analysis. Several topics—less complex or more embryonic—were referred directly to the steering committee. On all issues, a major objective will be to ascertain what existing or newly created structure or structures are capable of implementing the group's recommendations and then to monitor the issue to ensure that appropriate implementation is occurring.Issues to be Explored by Task ForcesInsurance and EmploymentWhile individuals may derive medically useful information from the expanded range of genetic tests that will flow from the HGP, they could also be harmed if test results become a basis for discrimination. An area of particular concern at the conference in Bethesda was whether genetic information should be used to decide eligibility for employment or the scope and cost of health and life insurance. The complexity of this issue is increased as barriers to worker migration fall (especially in Europe) and as more firms carry on business internationally. Furthermore, questions arise about the limits of required testing and whether individuals may decline to be informed of the results of tests.The task force will not only gather information on practices and legal standards throughout the world—especially in light of the differences among nations with regard to the linkage of employment and various forms of insurance—but will also examine international anti-discrimination laws as a possible means of supplementing domestic statutes and regulations. As a starting point, the Bethesda meeting agreed on a set of principles for the task force to refine.2ForensicsAlthough their legal status is not fully resolved, DNA tests are being used increasingly in judicial proceedings and civil and criminal investigations as a highly probative means to identify people. Most forensic uses of "DNA fingerprints" are domestic, but international cooperation among investigative bodies... (shrink)

Noninvasive, prenatal whole genome sequencing may be a technological reality in the near future, making available a vast array of genetic information early in pregnancy at no risk to the fetus or mother. Many worry that the timing, safety, and ease of the test will lead to informational overload and reproductive consumerism. The prevailing response among commentators has been to restrict conditions eligible for testing based on medical severity, which imposes disputed value judgments and devalues those living with eligible conditions. (...) To avoid these difficulties, we propose an unrestricted testing policy, under which prospective parents could obtain information on any variant of known significance after a careful informed consent process that uses an interactive decision aid to deliver a mandatory presentation on the purposes, techniques, and limitations of genomic testing, as well as optional resources for reflection and consultation. This process would encourage thoughtful, informed deliberation... (shrink)

The rise of genomic technologies has catalyzed shifts in the health care landscape through the commercialization of genome sequencing and testing services in the genomics marketplace. The development of consumer genomics into a growing array of information technologies aimed at collecting, curating, and broadly sharing personal data and biological materials reconstitutes the meaning of health and reframes patients into biocitizens. In this context, the good biocitizen is expected to assume personal responsibility for health through consumption of genomic information (...) and acquiescence to public and private efforts at data surveillance and aggregation. These shifts raise fundamental questions about how competing interests of the public, the state, and corporate entities will be reconciled and what trade‐offs are demanded for the promise of precision health. (shrink)

For the first time in the history of civilization, humans have procured the power to rewrite nature's book of life. Following the discovery of CRISPR and other key scientific developments at the dawn of the twenty-first century, humankind has-for better or worse-reached the Rubicon of precise genetic manipulation, which existed only in science fiction until now. Those familiar with genome editing understand its colossal power and potential to become a global transformative agent that surpasses the impact of electricity, the atomic (...) bomb, or the Internet. REWRITING NATURE is an interdisciplinary odyssey through the law, science, and policy of genome editing-the most significant breakthrough of our generation. The volume addresses a critical need to bridge gaps between law, science, and policy, and challenges the conventional, false dichotomy frequently associated with mutually exclusive normative roles for science and law. Through exploration of heuristic inquiries into an array of interdisciplinary fields, the book seeks to ignite thoughtful dialogues about authentic-rather than manufactured or sensationalized-issues raised by the technology. This timely resource is intended for keen audiences focused on venturing beyond the headlines and talking points to develop a deeper understanding of the prospects and challenges of genome editing. (shrink)

Linear chromosomes shorten in every round of replication. In Drosophila, telomere‐specialized long interspersed retrotransposable elements (LINEs) belonging to the jockey clade offset this shortening by forming head‐to‐tail arrays at Drosophila telomere ends. As such, these telomeric LINEs have been considered adaptive symbionts of the genome, protecting it from premature decay, particularly as Drosophila lacks a conventional telomerase holoenzyme. However, as reviewed here, recent work reveals a high degree of variation and turnover in the telomere‐specialized LINE lineages across Drosophila. There (...) appears to be no absolute requirement for LINE activity to maintain telomeres in flies, hence the suggestion that the telomere‐specialized LINEs may instead be neutral or in conflict with the host, rather than adaptive. (shrink)

Interferon stimulated gene 15 (ISG15) encodes a ubiquitin‐like protein that is highly induced upon activation of interferon signaling and cytoplasmic DNA sensing pathways. As part of the innate immune system ISG15 acts to inhibit viral replication and particle release via the covalent conjugation to both viral and host proteins. Unlike ubiquitin, unconjugated ISG15 also functions as an intracellular and extra‐cellular signaling molecule to modulate the immune response. Several recent studies have shown ISG15 to also function in a diverse array of (...) cellular processes and pathways outside of the innate immune response. This review explores the role of ISG15 in maintaining genome stability, particularly during DNA replication, and how this relates to cancer biology. It puts forth the hypothesis that ISG15, along with DNA sensors, function within a DNA replication fork surveillance pathway to help maintain genome stability. (shrink)

Noninvasive, prenatal whole genome sequencing may be a technological reality in the near future, making available a vast array of genetic information early in pregnancy at no risk to the fetus or mother. Many worry that the timing, safety, and ease of the test will lead to informational overload and reproductive consumerism. The prevailing response among commentators has been to restrict conditions eligible for testing based on medical severity, which imposes disputed value judgments and devalues those living with eligible conditions. (...) To avoid these difficulties, we propose an unrestricted testing policy, under which prospective parents could obtain information on any variant of known significance after a careful informed consent process that uses an interactive decision aid to deliver a mandatory presentation on the purposes, techniques, and limitations of genomic testing, as well as optional resources for reflection and consultation. This process would encourage thoughtful, informed deliberation by prospective parents before deciding whether or how to use NIPW. (shrink)

Tumour‐associated genetic changes frequently involve DNA translocation or deletion. Many of these events will have arisen from initial genomic damage, induced by either the activity of endogenous metabolic processes or from exposure to environmental genotoxic agents. Although initial genomic damage will have been widely distributed, tumorigenic events are confined to certain DNA target sites. Furthermore, within these target sites there appear to be regions of preferential DNA rearrangement, and examination of these sites implies that the location and extent (...) of such rearrangement may be influenced by DNA primary and secondary structure rather than simply by the point of damage. We selectively review evidence relating to DNA structures that may predispose certain regions of the genome to damage‐induced rearrangement, and discuss the possible role of interstitial, inverted telomere‐like sequence arrays in promoting chromosomal events of a type known to be associated with some human and animal tumours. (shrink)

In this post‐sequencing era, geneticists can focus on functional genomics on a much larger scale than ever before. One goal is the discovery and elucidation of the intricate genetic networks that co‐ordinate transcriptional activation in different regulatory circuitries. High‐throughput gene expression measurement using DNA arrays has thus become routine strategy. This approach, however, does not directly identify gene loci that belong to the same regulatory group; e.g., those that are bound by a common (set of) transcription factor(s). Working in (...) yeast, two groups have recently published an elegant method that could circumvent this problem, by combining chromatin immunoprecipitation and DNA microarrays.(1,2) The method is likely to provide a powerful tool for the dissection of global regulatory networks in eukaryotic cells. BioEssays 23:473–476, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

What is the status of the dichotomy proposed and the nosological validity of the contrasting pathologies described in the target article? How plausibly can dysregulated imprinting explain the array of features described, compared with other genetic models? We believe that considering alternative models is more likely to lead in the long term to the correct classification and explanation of the component behaviours.

We are living through one of the greatest scientific revolutions in history: the “information revolution” in genetics. The revolution is leading to a deep understanding of biological processes and is uncovering the molecular basis of many human diseases and susceptibilities. It is also confronting society with a vast array of choices, and presenting each individual with the question of what knowledge to seek and how to act on that knowledge, My purpose is to discuss the scientific foundations of this revolution (...) and to foreshadow its consequences.The current scientific revolution has perhaps one appropriate historical precedent: the chemical revolution that followed Dmitri Mendeleev's key insight in 1869 that the elements could be organized in a simple periodic table. (shrink)

We are living through one of the greatest scientific revolutions in history: the “information revolution” in genetics. The revolution is leading to a deep understanding of biological processes and is uncovering the molecular basis of many human diseases and susceptibilities. It is also confronting society with a vast array of choices, and presenting each individual with the question of what knowledge to seek and how to act on that knowledge, My purpose is to discuss the scientific foundations of this revolution (...) and to foreshadow its consequences.The current scientific revolution has perhaps one appropriate historical precedent: the chemical revolution that followed Dmitri Mendeleev's key insight in 1869 that the elements could be organized in a simple periodic table. (shrink)

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)

Whole genome sequencing and SNP genotyping arrays can paint strikingly different pictures of demographic history and natural selection. This is because genotyping arrays contain biased sets of pre‐ascertained SNPs. In this short review, we use comparisons between high‐coverage whole genome sequences of African hunter‐gatherers and data from genotyping arrays to highlight how SNP ascertainment bias distorts population genetic inferences. Sample sizes and the populations in which SNPs are discovered affect the characteristics of observed variants. We find that (...) SNPs on genotyping arrays tend to be older and present in multiple populations. In addition, genotyping arrays cause allele frequency distributions to be shifted towards intermediate frequency alleles, and estimates of linkage disequilibrium are modified. Since population genetic analyses depend on allele frequencies, it is imperative that researchers are aware of the effects of SNP ascertainment bias. With this in mind, we describe multiple ways to correct for SNP ascertainment bias. (shrink)

Genomes of higher eukaryotes contain abundant non‐coding repeated sequences whose overall biological impact is unclear. They comprise two categories. The first consists of retrotransposon‐derived elements. These are three major families of retroelements (LINEs, SINEs and LTRs). SINEs are clustered in gene‐rich regions and are found in promoters of genes while LINEs are concentrated in gene‐poor regions and are depleted from promoters. The second class consists of non‐coding tandem repeats (satellite DNAs and TTAGGG arrays), which are associated with mammalian centromeres, (...) heterochromatin and telomeres. Terminal TTAGGG arrays are involved in telomere capping and satellite DNAs are located in heterochromatin, which is implicated in transcription silencing by gene repositioning (relocalization). It is unknown whether interstitial TTAGGG sequences, which are present in many vertebrates, have a function. Here, evidence will be presented that retroelements and TTAGGG arrays are involved in regulation of gene expression. Retroelements can provide binding sites for transcription factors and protect promoter CpG islands from repressive chromatin modifications, and may be also involved in nuclear compartmentalization of transcriptionally active and inactive domains. Interstitial telomere‐like sequences can form dynamically maintained three‐dimensional nuclear networks of transcriptionally inactive domains, which may be involved in transcription silencing like classic heterochromatin. BioEssays 30:338–348, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis is now a first line test for children with multiple birth defects, children with intellectual impairment, and children with an unusual constellation of symptoms that do not fit with a (...) known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides. (shrink)

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis is now a first line test for children with multiple birth defects, children with intellectual impairment, and children with an unusual constellation of symptoms that do not fit with a (...) known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides. (shrink)

During the last few months, several pioneer genome‐wide transcriptomic, proteomic and metabolomic studies have revolutionised the understanding of bacterial biological processes, leading to a picture that resembles eukaryotic complexity. Technological advances such as next‐generation high‐throughput sequencing and high‐density oligonucleotide microarrays have allowed the determination, in several bacteria, of the entire boundaries of all expressed transcripts. Consequently, novel RNA‐mediated regulatory mechanisms have been discovered including multifunctional RNAs. Moreover, resolution of bacterial proteome organisation (interactome) and global protein localisation (localizome) have unveiled an (...) unanticipated complexity that highlights the significance of protein multifunctionality and localisation in the cell. Also, analysis of a complete bacterial metabolic network has again revealed a high fraction of multifunctional enzymes and an unexpectedly high level of metabolic responses and adaptation. Altogether, these novel approaches have permitted the deciphering of the entire physiological landscape of one of the smallest bacteria, Mycoplasma pneumoniae. Here, we summarise and discuss recent findings aimed at defining the blueprint of any prokaryote. (shrink)

The advent of new genetic and genomic technologies may cause friction with the principle of respect for autonomy and demands a rethinking of traditional interpretations of the concept of informed consent. Technologies such as whole‐genome sequencing and micro‐array based analysis enable genome‐wide testing for many heterogeneous abnormalities and predispositions simultaneously. This may challenge the feasibility of providing adequate pre‐test information and achieving autonomous decision‐making. At a symposium held at the 11th World Congress of Bioethics in June 2012 (Rotterdam), organized (...) by the International Association of Bioethics, these challenges were presented for three different areas in which these so‐called ‘new genetics’ technologies are increasingly being applied: newborn screening, prenatal screening strategies and commercial personal genome testing. In this article, we build upon the existing ethical framework for a responsible set‐up of testing and screening offers and reinterpret some of its criteria in the light of the new genetics. As we will argue, the scope of a responsible testing or screening offer should align with the purpose(s) of testing and with the principle of respect for autonomy for all stakeholders involved, including (future) children. Informed consent is a prerequisite but requires a new approach. We present preliminary and general directions for an individualized or differentiated set‐up of the testing offer and for the informed consent process. With this article we wish to contribute to the formation of new ideas on how to tackle the issues of autonomy and informed consent for (public) healthcare and direct‐to‐consumer applications of the new genetics. (shrink)

The advent of new genetic and genomic technologies may cause friction with the principle of respect for autonomy and demands a rethinking of traditional interpretations of the concept of informed consent. Technologies such as whole-genome sequencing and micro-array based analysis enable genome-wide testing for many heterogeneous abnormalities and predispositions simultaneously. This may challenge the feasibility of providing adequate pre-test information and achieving autonomous decision-making. At a symposium held at the 11th World Congress of Bioethics in June 2012 (Rotterdam), organized (...) by the International Association of Bioethics, these challenges were presented for three different areas in which these so-called ‘new genetics’ technologies are increasingly being applied: newborn screening, prenatal screening strategies and commercial personal genome testing. In this article, we build upon the existing ethical framework for a responsible set-up of testing and screening offers and reinterpret some of its criteria in the light of the new genetics. As we will argue, the scope of a responsible testing or screening offer should align with the purpose(s) of testing and with the principle of respect for autonomy for all stakeholders involved, including (future) children. Informed consent is a prerequisite but requires a new approach. We present preliminary and general directions for an individualized or differentiated set-up of the testing offer and for the informed consent process. With this article we wish to contribute to the formation of new ideas on how to tackle the issues of autonomy and informed consent for (public) healthcare and direct-to-consumer applications of the new genetics. (shrink)

The organization of eukaryotic genomes as chromatin provides the framework within which regulated transcription occurs in the nucleus. The association of DNA with chromatin proteins required to package the genome into the nucleus is, in general, inhibitory to transcription, and therefore provides opportunities for regulated transcriptional activation. Granting access to the cis‐acting elements in DNA, a prerequisite for any further action of the trans‐acting factors involved, requires the establishment of local heterogeneity of chromatin and, in some cases, extensive remodeling of (...) nucleosomal structures. Challenging problems relate to the establishment of this heterogeneity at the level of the single nucleosome and to the mechanisms that operate when nucleosomal arrays are reorganized. Recent developments indicate that chromatin reconstitution in cell‐free systems allows the biochemical analysis of the interplay between transcription factors and chromatin components that brings about regulated transcription. (shrink)

Potential applications of genome editing in assisted reproductive technology (ART) raise a vast array of strong opinions, emotional reactions and divergent perceptions. Acknowledging the need for caution and respecting such reactions, we observe that at least some are based on either a misunderstanding of the science or misconceptions about the content and flexibility of the existing legal frameworks. Combining medical, legal and ethical expertise, we present and discuss regulatory responses at the national, European and international levels. The discussion has an (...) EU starting point and is meant as a contribution to the general international regulatory debate. Overall, this paper concludes that gene editing technologies should not be regulated autonomously. Rather, potential uses should be regulated under general, existing frameworks and where applicable by reference to sufficiently equivalent technologies and techniques already subject to specific regulation. To be clear, we do not argue for the hasty introduction of gene editing as a reproductive treatment option in the immediate future. We call for caution with regard to overreaching moratoria and prohibitions that will also affect basic research. We recommend flexible regulations that allow for further responsible research into the potential development of the technology. We call for an open and inclusive debate and argue that scientific communication should claim a more prominent role to counter the danger of widespread misinformation. A high level of transparency and accuracy should guide scientific communication while simultaneously global‐scale responsibility and governance should be fostered by promoting cross‐disciplinary thinking and multi‐level stakeholder involvement in legal and regulatory processes. (shrink)

Potential applications of genome editing in assisted reproductive technology (ART) raise a vast array of strong opinions, emotional reactions and divergent perceptions. Acknowledging the need for caution and respecting such reactions, we observe that at least some are based on either a misunderstanding of the science or misconceptions about the content and flexibility of the existing legal frameworks. Combining medical, legal and ethical expertise, we present and discuss regulatory responses at the national, European and international levels. The discussion has an (...) EU starting point and is meant as a contribution to the general international regulatory debate. Overall, this paper concludes that gene editing technologies should not be regulated autonomously. Rather, potential uses should be regulated under general, existing frameworks and where applicable by reference to sufficiently equivalent technologies and techniques already subject to specific regulation. To be clear, we do not argue for the hasty introduction of gene editing as a reproductive treatment option in the immediate future. We call for caution with regard to overreaching moratoria and prohibitions that will also affect basic research. We recommend flexible regulations that allow for further responsible research into the potential development of the technology. We call for an open and inclusive debate and argue that scientific communication should claim a more prominent role to counter the danger of widespread misinformation. A high level of transparency and accuracy should guide scientific communication while simultaneously global‐scale responsibility and governance should be fostered by promoting cross‐disciplinary thinking and multi‐level stakeholder involvement in legal and regulatory processes. (shrink)

The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non‐coding genome. Recent advances in epigenomic profiling have uncovered non‐coding gene proximal promoters and distal enhancers of transcription genome‐wide. Extension of promoter‐associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3‐BD), is a signature of constitutive (...) expression of cell‐type‐specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3‐BDs over oncogenes is a cancer‐specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super‐enhancers (SE), by proto‐oncogenes results in the presence of H3K4me3‐BDs over the gene body. Therefore, H3K4me3‐BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers. (shrink)

Neurobiology studies mechanisms of cell signalling. A key question is how cells recognise specific signals. In this context, olfaction has become an important experimental system over the past 25 years. The olfactory system responds to an array of structurally diverse stimuli. The discovery of the olfactory receptors (ORs), recognising these stimuli, established the olfactory pathway as part of a greater group of signalling mechanisms mediated by G-protein-coupled receptors (GPCRs). GPCRs are the largest protein family in the mammalian genome and involved (...) in numerous fundamental physiological processes. The OR family exhibits two characteristics that make them an excellent model system to understand GPCRs: its size and the structural diversity of its members. Research on the OR binding site investigates what amino acid sequences determine the receptor-binding capacity. This promises a better understanding of how the basic genetic makeup of GPCRs relates to their diversification in ligand-binding capacities. (shrink)

It has become increasingly clear that there is a vast array of microorganisms on and in the human body, known collectively as the human microbiome. Our microbiomes are extraordinarily complex, and this complexity has been linked to human health and well-being. Given the complexity and importance of our microbiomes, we struggle with how to think about them. There is a long list of competing metaphors that we use to refer to our microbiomes, including as an “organ” containing our “second genome,” (...) as a “symbiont” in the human “holobiont,” and as an ecological “community” in the human “ecosystem,” among others. Each of these makes different assumptions about the fundamental biology of the human-microbe system, with important implications for how we choose to study microbiomes, and the therapies we envision for correcting microbiome-linked disorders. We believe that it is time to move beyond metaphors, and we propose a scientifically pluralist approach that focuses on characterizing fundamental biological properties of microbiomes such as heritability, transmission mode, rates of dispersal rates, and strength of local selection. Such an approach will allow us to break out of the confines of narrow conceptual frameworks, and to guide the exploration of our complexity as chimeric beings. (shrink)

Complex diseases involve both a genetic component and a response to environmental factors or lifestyle changes. Recently, genome-wide association studies (GWAS) have succeeded in identifying hundreds of polymorphisms that are statistically associated with complex diseases. However, the association is usually weak and none of the associated allelic forms is either necessary or sufficient for the disease occurrence. We argue that this promotes a network view, centred on functional redundancy. We adapted reliability theory to the concerned sub-network, modelled as a parallel (...) array of functional modules. In our model, as long as one module remains active, the function correlated with the respective disease is ensured and disease does not occur. Genetic factors reduce the initial number of available modules while environment, contingent surroundings, personal history, epigenetics, and some intrinsic stochasticity influence their persistence time. This model reproduces age-specific incidence curves and explains the influence of environmental changes. It offers a new paradigm, according to which disease occurs due to a lack of functional elements, depending on many idiosyncratic factors. Genetic risk assessed from GWAS is only a statistical notion with no direct interpretation at the individual level. However, genomic profiling could be useful at population level in devising models to guide decisions in health care policy. (shrink)

Technology shapes every aspect of human experience and it is the primary driver of social and ecological change. Given this, it is surprising that we spend so little time studying, analyzing, and evaluating new technologies. Occasionally, an issue grabs public attention--for example, the use of human embryonic stem cells in medical research or online file sharing of music and movies. However, these are the exceptions. For the most part, we enthusiastically embrace each new technology and application with little critical reflection (...) on how it will impact our lives and our world. What is more, when an issue raised by an emerging technology is attended to, we often lack the language, concepts, and critical perspectives to thoroughly address it. The aim of this textbook is to introduce students and other readers to the ethical issues associated with a broad array of emerging technologies--including nanotechnology, synthetic genomics, robotics, genetic engineering, geoengineering, synthetic meat, virtual reality, information technologies, sex selection, and many more--and to help them develop analytical skills and perspectives for effectively evaluating novel technologies and applications. (shrink)

In this article we examine the history of the production of microarray technologies and their role in constructing and operationalizing views of human genetic difference in contemporary genomics. Rather than the “turn to difference” emerging as a post-Human Genome Project phenomenon, interest in individual and group differences was a central, motivating concept in human genetics throughout the twentieth century. This interest was entwined with efforts to develop polymorphic “genetic markers” for studying human traits and diseases. We trace the technological, methodological (...) and conceptual strategies in the late twentieth century that established single nucleotide polymorphisms as key focal points for locating difference in the genome. By embedding SNPs in microarrays, researchers created a technology that they used to catalog and assess human genetic variation. In the process of making genetic markers and array-based technologies to track variation, scientists also made commitments to ways of describing, cataloging and “knowing” human genetic differences that refracted difference through a continental geographic lens. We show how difference came to matter in both senses of the term: difference was made salient to, and inscribed on, genetic matter, as a result of the decisions, assessments and choices of collaborative and hybrid research collectives in medical genomics research. (shrink)

It is hypothesized that human faces judged to be attractive by people possess two features—averageness and symmetry—that promoted adaptive mate selection in human evolutionary history by way of production of offspring with parasite resistance. Facial composites made by combining individual faces are judged to be attractive, and more attractive than the majority of individual faces. The composites possess both symmetry and averageness of features. Facial averageness may reflect high individual protein heterozygosity and thus an array of proteins to which parasites (...) must adapt. Heterozygosity may be an important defense of long-lived hosts against parasites when it occurs in portions of the genome that do not code for the essential features of complex adaptations. In this case heterozygosity can create a hostile microenvironment for parasites without disrupting adaptation. Facial bilateral symmetry is hypothesized to affect positive beauty judgments because symmetry is a certification of overall phenotypic quality and developmental health, which may be importantly influenced by parasites. Certain secondary sexual traits are influenced by testosterone, a hormone that reduces immunocompetence. Symmetry and size of the secondary sexual traits of the face (e.g., cheek bones) are expected to correlate positively and advertise immunocompetence honestly and therefore to affect positive beauty judgments. Facial attractiveness is predicted to correlate with attractive, nonfacial secondary sexual traits; other predictions from the view that parasite-driven selection led to the evolution of psychological adaptations of human beauty perception are discussed. The view that human physical attractiveness and judgments about human physical attractiveness evolved in the context of parasite-driven selection leads to the hypothesis that both adults and children have a species-typical adaptation to the problem of identifying and favoring healthy individuals and avoiding parasite-susceptible individuals. It is proposed that this adaptation guides human decisions about nepotism and reciprocity in relation to physical attractiveness. (shrink)

Emerging evidence suggests that DNA topology plays an instructive role in cell fate control through regulation of gene expression. Transcription produces torsional stress, and the resultant supercoiling of the DNA molecule generates an array of secondary structures. In turn, local DNA architecture is harnessed by the cell, acting within sensory feedback mechanisms to mediate transcriptional output. MYC is a potent oncogene, which is upregulated in the majority of cancers; thus numerous studies have focused on detailed understanding of its regulation. Dissection (...) of regulatory regions within the MYC promoter provided the first hint that intimate feedback between DNA topology and associated DNA remodeling proteins is critical for moderating transcription. As evidence of such regulation is also found in the context of many other genes, here we expand on the prototypical example of the MYC promoter, and also explore DNA architecture in a genome-wide context as a global mechanism of transcriptional control. Torsional stress, and supercoiling generated by transcription, shape the topology of DNA. Furthermore, the resultant secondary DNA structures and their interacting partners provide feedback to regulate gene expression. Emerging evidence suggests these mechanisms, identified through analysis of the MYC promoter, are applicable genome-wide. (shrink)

Two reports have shown that mammalian artificial chromosomes (MAC) can be constructed from cloned human centromere DNA and telomere repeats, proving the principle that chromosomes can form from naked DNA molecules transfected into human cells. The MACs were mitotically stable, low copy number and bound antibodies associated with active centromeres. As a step toward second-generation MACs, yeast and bacterial cloning systems will have to be adapted to achieve large MAC constructs having a centromere, two telomeres, and genomic copies of (...) mammalian genes. Available construction techniques are discussed along with a new P1 artificial chromosome (PAC)-derived telomere vector (pTAT) that can be joined to other PACs in vitro, avoiding a cloning step during which large repetitive arrays often rearrange. The PAC system can be used as a route to further define the optimal DNA elements required for efficient MAC formation, to investigate the expression of genes on MACs, and possibly to develop efficient MAC-delivery protocols. BioEssays 1999;21:76–83. © 1999 John Wiley & Sons, Inc. (shrink)

New genetic technologies and their applications in biomedicine have important implications for social identities in contemporary societies. In medicine, new genetics is increasingly important for the identification of health and disease, the imputation of personal and familial risk, and the moral status of those identified as having genetic susceptibility for inherited conditions. There are also consequent transformations in national and ethnic collective identity, and the body and its investigation is potentially transformed by the possibilities of genetic investigations and modifications (including (...) the highly controversial terrains of reproductive technologies and the use of human embryos in biomedical research). The papers in this volume, drawn from an international array of authors, address these issues from a variety of national, disciplinary and empirical standpoints. An informative read for postgraduates and professionals in the fields of sociology, social anthropology, science and technology studies, and environmental studies, the chapters comprise empirically based and theoretically informed discussions of key sociological, anthropological, political and ethical issues. Using the resources of a wide range of social science disciplines to provide a comparative approach to complex issues, this superb collection explores the local and global consequences of the new genetics, and analyzes the social implications of these advances for identity formation in a period of rapid social change. (shrink)

Drosophila telomeres comprise DNA sequences that differ dramatically from those of other eukaryotes. Telomere functions, however, are similar to those found in telomerase‐based telomeres, even though the underlying mechanisms may differ. Drosophila telomeres use arrays of retrotransposons to maintain chromosome length, while nearly all other eukaryotes rely on telomerase‐generated short repeats. Regardless of the DNA sequence, several end‐binding proteins are evolutionarily conserved. Away from the end, the Drosophila telomeric and subtelomeric DNA sequences are complexed with unique combinations of proteins (...) that also modulate chromatin structure elsewhere in the genome. Maintaining and regulating the transcriptional activity of the telomeric retrotransposons in Drosophila requires specific chromatin structures and, while telomeric silencing spreads from the terminal repeats in yeast, the source of telomeric silencing in Drosophila is the subterminal arrays. However, the subterminal arrays in both species may be involved in telomere–telomere associations and/or communication. BioEssays 30:25–37, 2008. © 2007 Wiley Periodicals, Inc. (shrink)

Introduction of human plasma protein genes into the mouse genome to produce transgenic mice furnishes an in vivo model for correlating chromosomal DNA sequences with developmental and tissue‐specific expression. The liver produces an array of plasma proteins that circulate throughout the body contributing to homeostasis. Non‐hepatic tissue sites of synthesis have been identified where a local provision of plasma proteins in needed. Analysis of expression of human plasma protein genes in ageing transgenic mice appears especialy promising in identifying DNA sequences (...) that respond to environmental adversities such as inflammatory factors, hormonal changes and metal toxicity. The results indicate that human genes encoding and controlling liver plasma proteins serve as useful models for studying genetic regulation in the background of development and ageing. (shrink)

This paper, addressed to both philosophers of science and stem cell biologists, aims to reduce the obscurity of and disagreements over the nature of stemness. The two most prominent current theories of stemness—the entity theory and the state theory—are both biologically and philosophically unsatisfactory. Improved versions of these theories are likely to converge. Philosophers of science can perform a much needed service in clarifying and formulating ways of testing entity and state theories of stemness. To do so, however, philosophers should (...) acquaint themselves with the latest techniques and approaches employed by bench scientists, such as the use of proteomics, genome-wide association studies, and ChIP-on-chip arrays. An overarching theme of this paper is the desirability of bringing closer together the philosophy of science and the practice of scientific research. (shrink)

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)‐based “active genetic” elements developed in 2015 bypassed the fundamental rules of traditional genetics. Inherited in a super‐Mendelian fashion, such selfish genetic entities offered a variety of potential applications including: gene‐drives to disseminate gene cassettes carrying desired traits throughout insect populations to control disease vectors or pest species, allelic drives biasing inheritance of preferred allelic variants, neutralizing genetic elements to delete and replace or to halt the spread of gene‐drives, split‐drives with the core constituent (...) Cas9 endonuclease and guide RNA (gRNA) components inserted at separate genomic locations to accelerate assembly of complex arrays of genetic traits or to gain genetic entry into novel organisms (vertebrates, plants, bacteria), and interhomolog based copying systems in somatic cells to develop tools for treating inherited or infectious diseases. Here, we summarize the substantial advances that have been made on all of these fronts and look forward to the next phase of this rapidly expanding and impactful field. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Alzheimer's Disease, Mild Cognitive Impairment, and the Biology of Intrinsic AgingThomas B. L. Kirkwood (bio)Keywordsaging, Alzheimer’s disease, genetic mutation, mild cognitive impairment, telomereThe article by Gaines and Whitehouse (2006) raises key questions about the uncertain relationship between (i) the intrinsic, "normal" aging process, and (ii) the clinicopathologic states represented by the labels of Alzheimer's disease (AD) and mild cognitive impairment (MCI). This short commentary offers a perspective on this (...) debate that is drawn from a consideration of underlying biological mechanisms.Because age is unquestionably the greatest single risk factor associated with AD and MCI, I begin by asking what we know about the intrinsic processes of aging. The central feature of current understanding of intrinsic aging is that it consists of the gradual, lifelong accumulation of a wide variety of molecular and cellular faults that begins very early in life and eventually leads to overt functional impairments resulting in age-related frailty, disability, and disease (Kirkwood 2005). This is an essentially bottom-up process. A strong consensus has emerged in recent years that there is no active program for aging and that there are no genetic factors that have evolved specifically to cause aging or age-related diseases. Unquestionably, there are genes that influence susceptibility to disease and even length of life, but these genes are genes for maintenance and repair functions, not for aging. It is the limitation in the past evolutionary pressure to invest in greater longevity than was required, within an environment where life was usually truncated by hazards such as starvation, injury, or infection, that means that our maintenance systems—good as they are—are insufficient to keep us going indefinitely. Added to this is the idea that there are probably also genes that program processes that are good for the young organism, but which may in later life have harmful effects. Processes like inflammation and apoptosis, which are seen to occur extensively in aged tissues, including brain, surely evolved to help cope with infection and cellular damage arising earlier in life. That they are called into play in aged tissues is a direct, but secondary, consequence of accumulated damage.With this general framework to understand the intrinsic biology of aging, let us now ask what we might expect a priori for the aging of an organ such [End Page 79] as the brain. Although we cannot pretend complete ignorance of how the brain actually does age, our enquiry can be based entirely on data from other organ systems, so we can develop our predictions about brain aging without prejudice.Aging begins very early during human development, faults accumulating from the first stages of embryonic development. Each time a cell divides, each of the daughter cells is likely to acquire a few new mutations. We know this from the estimates for the error rate in DNA replication and the size of the human genome. It is confirmed by direct evidence that at individual gene loci where mutations have been measured, mutation frequency increases with age (Morley 1998; Vijg 2000). In addition to replication errors, DNA is damaged on a daily basis to a very considerable degree by agents such as reactive oxygen species (free radicals), which are formed as byproducts of normal cellular metabolism. Although most of this damage is corrected by repair, the repair mechanisms themselves are not error free and additional mutations accumulate through this route. If a mutation is lethal to the cell, the cell dies and thus the mutation is eliminated. However, the majority of mutations are nonlethal, either because the mutation is recessive and the cell carries an intact gene copy on the other chromosome, because the gene is not currently required, or because the mutation produces only a delayed deleterious effect. Examples of genes that produce delayed deleterious effects include the genes responsible for familial AD. It is interesting to reflect that on statistical grounds alone, it is almost certain that each of us carries a randomly determined fraction of cells in our brains that bear amyloid precursor protein or presenilin mutations associated with AD. We also carry a heterogeneous array of random mutations that compromise essential cell maintenance functions. How many such... (shrink)

The United Kingdom is a leader in genomics research, and the presence of numerous types of biobanks and the linking of health data and research within the UK evidences the importance of biobank-based research in the UK. There is no biobank-specific law in the UK and research on biobank materials is governed by a confusing set of statutory law, common law, regulations, and guidance documents. Several layers of applicable law, from European to local, further complicate an understanding of privacy protections. (...) Finally, biobanks frequently contain data in addition to the samples; the legal framework in the UK generally differentiates between data and samples and the form of the data affects the applicability of legal provisions. Biobanks must be licensed by the Human Tissue Authority; certain projects must be reviewed by Research Ethics Committees, and all projects are encouraged to be reviewed by them. Data Access Committees in biobanks are also common in the UK. While this confusing array of legal provisions leaves privacy protections in biobanking somewhat unclear, changes at the EU level may contribute to harmonization of approaches to privacy. (shrink)

The unprecedented development of medical informatics is constantly transforming the concept of expertise in medical sciences in a way that has far-reaching consequences for both the theory of knowledge and the philosophy of informatics. Deep medicine is based on the assumption that medical diagnosis should take into account the wide array of possible health factors involved in the diagnostic process, such as not only genome analysis alone, but also the metabolome (analysis of all body metabolites important for e.g. drug-drug interactions), (...) microbiome (i.e. analysis of all bodily microorganisms interacting with host cells) or exposome (analysis of all environmental factors triggering potentially harmful cell mutations, such as UV radiation, heavy metals, various carcinogens, etc.). Deep data analysis is of tantamount importance for personalized diagnosis but, at the same time, hardly achievable by a regular human being. However, adequately designed artificial intelligence (e.g. a deep neural network) can undeniably be of great help for finding correlations between symptoms and underlying diseases. Nowadays AI applies to nearly every aspect of medicine, starting from the data analysis of scientific literature, through the diagnostic process, to the act of communication between physicians and their patients. Medical image processing algorithms greatly enhance the chances of successful recognition of melanoma or intestinal polyps. Communication tools designed for physicians use techniques known from social media to provide users with an opportunity to consult the case with colleagues from the same discipline. Natural language processing tools significantly improve doctor-patient communication by the automation of note-taking. Is this enough to support the claim that the non-epistemic competences in medicine are becoming more and more important? Can we attribute expertise only to a person? How is medical informatics changing the way most people usually understand human-computer interactions? (shrink)

The rapid sequencing of entire genomes based in large measure on a DNA cloning procedure, the polymerase chain reaction (PCR), has opened new frontiers in the discovery process for novel therapeutic agents. DNA cloning is a basic tool in genomics and it has been used for over a decade. Drug discovery is currently focused on the identification of gene databases, gene arrays and protein arrays aimed at therapeutic modulation of disease-related genes—which require procedures that may involve cloning techniques. (...) Currently, cloning for pharmacologic products is most applicable in the preclinical area of drug discovery. For example, the identification of specific receptor subtypes occurred via cloning whereas traditional pharmacologic approaches that use agonists and antagonists may have failed to separate binding affinities. Successful therapeutic agents where cloning played vital role resulted in the development of synthetic insulin, growth hormone, erythropoiten and other tissue factors in blood products, Vaccines may be another successful application derived from cloning. Another area where cloning can make a significant impact upon human therapeutics is that this technique may provide a new source of cells for tissue engineering and transplantation. Stem cells, and in particular, embryonic stem cells can differentiate into other cell types such as hepatocytes and neurons to provide normal products for hepatic and neurological diseases. However, the use of cloning embryonic stem cells introduces important ethical, medical and legal issues which require that leaders in government, academic, and religious groups be fully educated in these applications. A close working relationship among these diverse groups is needed to respond wisely to the introduction of new therapeutic opportunities while at the same time providing protection for the individual and the public at large from unethical practises. (shrink)