The principles and practice of human evolution research: Are we asking questions that can be answered?

The research agenda of paleoanthropology involves many topics and methodologies. Fossil specimens are allocated to species, and those species are assigned to the hominin clade. After that we want to know how they are related to each other, what they ate, how much they weighed, how smart they were, etc. We also want to know about the origin of particular attributes of hominins, such as our delayed growth and development, bipedalism, and language. The data available to answer these complex questions are confounded by fragmentary fossil specimens, small sample sizes, limited opportunities for controlled experimentation, and the inherent limitations of historical data. Also, because many traits are effectively unique to hominins, even observational comparative studies are inevitably limited in what they can tell us, if not impossible to conduct. We explore how these limitations should, but often do not, constrain the questions that paleoanthropologists should attempt to answer.     

The case for studying tadpole autecology,with comments on strategies to study other small,fast-moving animals in nature

Two of the most fundamental questions in tadpole biology, also applicable to most small, under-studied organisms are: (1) ‘Why are they built the way they are?’ and (2) ‘Why do they live where they do?’ Regrettably, despite significant progress in most aspects of tadpole biology, the answers to these questions are not much better now than they were in the last century. We propose that an autecological approach, that is the careful observation of individuals and how they interact with the environment, is a potential path towards a fuller understanding of tadpole ecomorphology and evolution. We also discuss why more attention should be given to studying atypical tadpoles from atypical environments, such as torrential streams, water-filled cavities of terrestrial plants and wet rock surfaces neighbouring streams. Granted, tadpoles are rare in these settings, but in those unusual habitats the physical environments can be well described and characterized. In contrast, the more common ponds where tadpoles are found are typically too structurally complex to be easily delineated. This makes it difficult to know exactly what individual tadpoles are doing and what environmental parameters they are responding to. Our overall thesis is that to understand tadpoles we must see exactly what they are doing, where they are doing it, and how they are doing it. This takes work, but we suggest it is feasible and could greatly advance our understanding of how anuran larvae have evolved. The same strategies for studying tadpoles that we encourage here can be applied to the study of many other small and fast-moving animals.     

Creative Ignorance

To secure the public trust, risk analysts should divorce themselves from the philosophy of probabilism and the language of probability. Given the antecedent conditions, the chance of an outcome is either one or zero. Values between one and zero must be based on something other than the conditions and are misleading. Probabilism holds that the same conditions produce varying outcomes and assigns fractional probabilities to each of the outcomes. Probabilists conclude this by ignoring the differences between the antecedent conditions. When probabilists do not know if an outcome can or cannot occur, they conclude that it can. As epidemiologists seldom, if ever, know the particular conditions, they conclude that individuals within large populations are at risk to the same degree. Indeed, the less they know about us as individuals, the more at risk the public becomes. Not knowing the conditions, probabilists base their calculations on their ignorance of the conditions. Using one and zero equivocally, philosopher mathematicians tailored the language of probability to the philosophy of probabilism. With it, they convinced players who, given the conditions, cannot win that they could. Epidemiologists employ it to convince persons who, given the conditions, are not at risk that they are.     

How is a tissue built?

Tissues change in many ways in the period that they are part of a living organism. They are created in fairly repeatable structural patterns, and we know that the patterns are due to both the genes and the (mechanical) environment, but we do not know exactly what part or percentage of a particular pattern to consider the genes, or the environment, responsible for. We do not know much about the beginning of tissue construction (morphogenesis) and we do not know the methods of tissue construction. When the tissue structure is altered to accommodate a new loading, we do not know how the decision is made for the structural reconstruction. We do know that tissues grow or reconstruct themselves without ceasing to continue with their structural function, but we do not understand the processes that permit them to accomplish this. Tissues change their structures to altered mechanical environments, but we are not sure how. Tissues heal themselves and we understand little of the structural mechanics of the process. With the objective of describing the interesting unsolved mechanics problems associated with these biological processes, some aspects of the formation, growth, and adaptation of living tissues are reviewed. The emphasis is on ideas and models. Beyond the objective is the hope that the work will stimulate new ideas and new observations in the mechanical and chemical aspects of developmental biology.     

To know or not to know? Genetic ignorance, autonomy and paternalism

This paper examines some arguments which deny the existence of an individual right to remain ignorant about genetic information relating to oneself--often referred to as 'a right to genetic ignorance' or, more generically, as 'a right not to know'. Such arguments fall broadly into two categories: 1) those which accept that individuals have a right to remain ignorant in self-regarding matters, but deny that this right can be extended to genetic ignorance, since such ignorance may be harmful to others, particularly those to whom one is genetically related (the 'harm to others objection') and 2) those which contend that, even if genetic ignorance is only self harming, it is not something to which individuals can rationally or morally claim to have a 'right' at all, since they defend their claims on autonomy-respecting grounds and ignorance is inimical to autonomy (the 'incoherence objection'). I argue that defenders of a right not to know have some plausible responses to the 'harm to others objection', they and their opponents reach an impasse in which both sides are left voicing concerns about the paternalistic implications of the other's point of view. I conclude that defenders of a right not to know would, therefore, advance their position further by analysing it in terms of values other than those of autonomy and rights.     

The molecular mosaic of regulated cell death in the cardiovascular system

Cell death is now understood to be a highly regulated process that contributes to normal development and tissue homeostasis, alongside its role in the etiology of various pathological conditions. Through detailed molecular analysis, we have come to know that all cells do not always die in the same way, and that there are at least 7 processes involved, including: apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and autophagy-mediated cell death. These processes act as pieces in the mosaic of cardiomyocyte cell death, which come together depending on context and stimulus. This review details each individual process, as well as highlights how they come together to produce various cardiac pathologies. By knowing how the pieces go together we can aim towards the development of efficacious therapeutics, which will enable us to prevent cardiomyocyte loss in the face of stress, both reducing mortality and improving quality of life.     

A Food Scare a Day: Why Aren't We Better at Managing Dietary Risk?

Does the existence of food scares mean that we are bad at risk management? Not necessarily. New information brings new risks to the forefront or puts known risks into a new perspective. But in some cases food scares do indicate poor risk management. There are two key problems that explain why we are not better at managing dietary risks. The first is an imbalance of effort among the three components of risk analysis: we have Hummer risk assessment, Yugo risk management, and tricycle risk communication. The second problem is inadequate risk management. The cases of risks from mad cow disease and dioxins illustrate how the quality of risk management is affected by what we do not know well enough, what we know too well, and what we have not tried to find out. Better risk management requires a two-tier approach: (1) generate broad and shallow information on risks, health outcomes, incentives, options, benefits, and costs (Toyota Prius Hybrid risk management to be used everyday) and (2) generate narrow and in-depth information on high priority risks (Hummer risk assessment to be used sparingly).     

Cell groups reveal structure of stimulus space

An important task of the brain is to represent the outside world. It is unclear how the brain may do this, however, as it can only rely on neural responses and has no independent access to external stimuli in order to “decode” what those responses mean. We investigate what can be learned about a space of stimuli using only the action potentials (spikes) of cells with stereotyped—but unknown—receptive fields. Using hippocampal place cells as a model system, we show that one can (1) extract global features of the environment and (2) construct an accurate representation of space, up to an overall scale factor, that can be used to track the animal's position. Unlike previous approaches to reconstructing position from place cell activity, this information is derived without knowing place fields or any other functions relating neural responses to position. We find that simply knowing which groups of cells fire together reveals a surprising amount of structure in the underlying stimulus space; this may enable the brain to construct its own internal representations.     

The right to genetic ignorance confirmed

One of the much debated issues around the evolving human genetics is the question of the right to know versus the right not to know. The core question of this theme is whether an individual has the right to know about her own genetic constitution and further, does she also have the right to remain in ignorance. Within liberal traditions it is usually held that people, if they so wish, have the right to all the knowledge available about themselves. This right is based on the value of autonomy or on the right of self-determination, and it is sometimes partly justified as a countermeasure to the authorities' control over people. I do not wish to deny the right to genetic knowledge (about oneself). I think that its existence is self-evident. The argument I want to put forth in this paper is that in liberal societies we should acknowledge people's right to remain in ignorance as well. The only reason for not doing this would be that grave harm to others would follow if people were allowed to make these seemingly self-regarding decisions. Arguments presented against the right to ignorance are twofold. First there are those arguing against the right to ignorance on the grounds of harm to others, that is, philosophers who do not deny people's right to ignorance in self-related matters but wish to state that genetic ignorance causes harm to others, and this is one of the most commonly accepted reason for restricting people's freedom. The other line of argument flows from the Kantian view that not even merely self-regarding foolishness (in the eyes of others) should be allowed.     

Possible Roles for Cognin in Chick Embryo Neural Retina

In this review, we discuss current information about a cell-cellrecognition protein present in chick embryo neural retina. Thisprotein, retina cognin, has cell adhesion or aggregation promotingpropertiesin vitro. We discuss five questions. First, what isretina cognin (R-cognin)? Second, what do we know about cogninin chick retina? We discuss its histological distribution inretina and how that distribution changes during embryonic andearly post-hatching development. Third, where is cognin withincells? We review light microscopy evidence for its localizationin plasma membranes of somas and neurites of selected retinalneurons as an intrinsic membrane protein. Fourth, how is cognindistributed in membranes? We summarize evidence that cogninmight not be uniformly distributed over cellsurfaces and thatit might bind to specific proteins on the surfaces of otherretina cells. From the available information, we ask what wecan deduce about cognin's biological role in the neural retina.     

Conflicting demands on a modern healthcare service: Can Rawlsian justice provide a guiding philosophy for the NHS and other socialized health services?

We explore whether a Rawlsian approach might provide a guiding philosophy for the development of a healthcare system, in particular with regard to resolving tensions between different groups within it. We argue that an approach developed from some of Rawls’ principles – using his ‘veil of ignorance’ and both the ‘difference’ and ‘just savings’ principles which it generates – provides a compelling basis for policy making around certain areas of conflict. We ask what policies might be made if those making them did not know if one was patient, doctor, nurse or manager – in this generation or the next. We first offer a brief summary of Rawls’ approach and how we intend to extrapolate from it. We examine how this adapted Rawlsian framework could be applied to specific examples of conflict within healthcare; we demonstrate how this framework can be used to develop a healthcare service which is both sustainable (in its training and treatment of staff, and in encouraging research and innovation) and open (to protect the powers and opportunities of those using the health service). We conclude that while Rawls’ approach has previously been rejected as a means to address specific healthcare decisions, an adapted veil of ignorance can be a useful tool for the consideration of how a just health service should be constructed and sustained. Turning the theoretical into the practical (and combining Rawls’ thought experiment with Scanlonian contractarianism), managers, doctors, patients, carers and nurses could come together and debate conflicting issues behind a hypothetical veil.     

Cognition in insects

A traditional view of cognition is that it involves an internal process that represents, tracks or predicts an external process. This is not a general characteristic of all complex neural processing or feedback control, but rather implies specific forms of processing giving rise to specific behavioural capabilities. In this paper, I will review the evidence for such capabilities in insect navigation and learning. Do insects know where they are, or do they only know what to do? Do they learn what stimuli mean, or do they only learn how to behave?     

Cognition in insects

A traditional view of cognition is that it involves an internal process that represents, tracks or predicts an external process. This is not a general characteristic of all complex neural processing or feedback control, but rather implies specific forms of processing giving rise to specific behavioural capabilities. In this paper, I will review the evidence for such capabilities in insect navigation and learning. Do insects know where they are, or do they only know what to do? Do they learn what stimuli mean, or do they only learn how to behave?     

How to build an information gathering and processing system: lessons from naturally and artificially intelligent systems

Imagine a situation in which you had to design a physical agent that could collect information from its environment, then store and process that information to help it respond appropriately to novel situations. What kinds of information should it attend to? How should the information be represented so as to allow efficient use and re-use? What kinds of constraints and trade-offs would there be? There are no unique answers. In this paper, we discuss some of the ways in which the need to be able to address problems of varying kinds and complexity can be met by different information processing systems. We also discuss different ways in which relevant information can be obtained, and how different kinds of information can be processed and used, by both biological organisms and artificial agents. We analyse several constraints and design features, and show how they relate both to biological organisms, and to lessons that can be learned from building artificial systems. Our standpoint overlaps with Karmiloff-Smith (1992) in that we assume that a collection of mechanisms geared to learning and developing in biological environments are available in forms that constrain, but do not determine, what can or will be learnt by individuals.     

Wild chimpanzees inform ignorant group members of danger

The ability to recognize other individuals' mental states-their knowledge and beliefs, for example-is a fundamental part of human cognition and may be unique to our species. Tests of a "theory of mind" in animals have yielded conflicting results. Some nonhuman primates can read others' intentions and know what others see, but they may not understand that, in others, perception can lead to knowledge. Using an alarm-call-based field experiment, we show that chimpanzees were more likely to alarm call in response to a snake in the presence of unaware group members than in the presence of aware group members, suggesting that they recognize knowledge and ignorance in others. We monitored the behavior of 33 individuals to a model viper placed on their projected travel path. Alarm calls were significantly more common if the caller was with group members who had either not seen the snake or had not been present when alarm calls were emitted. Other factors, such as own arousal, perceived risk, or risk to receivers, did not significantly explain the likelihood of calling, although they did affect the call rates. Our results suggest that chimpanzees monitor the information available to other chimpanzees and control vocal production to selectively inform them.     

Mechanistic reasoning and informed consent

Evidence‐based medicine (EBM) proponents have argued that mechanistic evidence concerning medical treatments should be considered secondary to evidence derived from randomized controlled trials (RCTs). One common criticism of RCTs is that they often do not yield results that are generalizable to clinical practice, and that for clinical practice application, mechanistic evidence is needed. However, proponents of EBM have argued that mechanistic reasoning is often unreliable and thus not very useful. Here we suggest an important role of mechanistic explanation that has been left out of this discussion entirely, namely, its importance in a patient’s decision of whether or not to take certain drugs. We argue that in certain cases, knowing how a treatment works is just as important for the patient as knowing whether it does. In this paper, we explore how and why giving patients mechanistic information can be an important factor in obtaining informed consent for medical treatment, focusing on the example case of hormonal contraceptives.     

Social Awareness in Monkeys

Tests of self-awareness in nonhuman primates have to date beenconcerned almost entirely with the recognition of an animal'sreflection in a mirror. By contrast, we know much less aboutnon-human primates' perception of their place within a socialnetwork, or of their understanding of themselves as individualswith unique sets of social relationships. Here we review evidencethat monkeys who fail the mirror test may nonetheless behaveas if they recognize themselves as distinct individuals, eachof whom occupies a unique place in society and has a specificset of relations with others. A free-ranging vervet monkey,baboon, or macaque recognizes other members of his group asindividuals. He also recognizes matrilineal kin groups, lineardominance rank orders, and behaves as if he recognizes his ownunique place within them. This sense of "social self" in monkeys,however, is markedly different from self-awareness in humans.Although monkeys may behave in ways that accurately place themselveswithin a social network, they are unaware of the knowledge thatallows them to do so: they do not know what they know, cannotreflect on what they know, and cannot become the object of theirown attention.     

Molecular and cell biology of cystic fibrosis.

The questions emerged in better focus: we need to know, definitively, what CFTR is and what it does. We need to know how mutant CFTR expression leads to the relentless lung disease that takes the lives of the patients. We need to know how the different mutations in CFTR behave functionally. Much more information is needed on the pathways for ion transport in the airways in order for us to consider therapeutic alternatives. Better information on CFTR expression, particularly in the lung, would greatly facilitate consideration of pathophysiology as well as gene therapy. Many of these questions can be attacked by imaginative use of the tools already in hand. The need is urgent. The wondrous scientific advancements of the last five years and the additional money being spent on CF research have bought no dramatic increase in life expectancy for the patients. Every day, three more succumb.