Disease

This paper examines what it is for a condition to be a disease. It falls into two sections. In the first I examine the best existing account of disease (as proposed by Christopher Boorse) and argue that it must be rejected. In the second I outline a more acceptable account of disease. According to this account, by disease we mean a condition that it is a bad thing to have, that is such that we consider the afflicted person to have been unlucky, and that can potentially be medically treated. All three criteria must be fulfilled for a condition to be a disease. The criterion that for a condition to be a disease it must be a bad thing is required to distinguish the biologically different from the diseased. The claim that the sufferer must be unlucky is needed to distinguish diseases from conditions that are unpleasant but normal, for example teething. Finally, the claim that for a condition to be a disease it must be potentially medically treatable is needed to distinguish diseases from other types of misfortune, for example economic problems and legal problems.     

The evolutionary stability of automimicry

Internal defences such as toxins cannot be detected from a distance by a predator, and are likely to be costly to produce and maintain. Populations of well-defended prey may therefore be vulnerable to invasion from rare 'cheater' mutants that do not produce the toxin themselves but obtain some protection from their resemblance to their better defended conspecifics (automimicry). Although it is well established that well-defended and weakly defended morphs may coexist stably in protected dimorphisms, recent theoretical work suggests that such dimorphisms would not be resistant to invasion by novel mutants with defence levels intermediate to those present. Given that most defences (including toxins) are likely to be continuous traits, this implies that automimicry may tend to be a transitory phenomenon, and thus less likely to explain variation in defence levels in nature. In contrast to this, we show that automimicry can also be evolutionarily stable for continuous traits, and that it may evolve under a wide range of conditions. A recently developed geometric method allows us to determine directly from a trade-off curve whether an evolutionarily stable defence dimorphism is at all possible, and to make some qualitative inferences about the ecological conditions that may favour it.     

COMPETENCE,PRACTICAL RATIONALITY AND WHAT A PATIENT VALUES

According to the principle of patient autonomy, patients have the right to be self‐determining in decisions about their own medical care, which includes the right to refuse treatment. However, a treatment refusal may legitimately be overridden in cases where the decision is judged to be incompetent. It has recently been proposed that in assessments of competence, attention should be paid to the evaluative judgments that guide patients' treatment decisions. In this paper I examine this claim in light of theories of practical rationality, focusing on the difficult case of an anorexic person who is judged to be competent and refuses treatment, thereby putting themselves at risk of serious harm. I argue that the standard criteria for competence assess whether a treatment decision satisfies the goals of practical decision‐making, and that this same criterion can be applied to a patient's decision‐guiding commitments. As a consequence I propose that a particular understanding of practical rationality offers a theoretical framework for justifying involuntary treatment in the anorexia case.     

Unravelling phenotypic plasticity -- why should we bother?

The ability of a genotype to change its phenotype was once considered rather a nuisance -- making it difficult to define a genotype. This led to the idea that there was a problem called 'instability'. But quite early it was recognized that stability was under genetic control, and was a character like other attributes of an individual. From this realization came the idea that there were two sides to the character of 'instability', and that the ability to change could be important. This ability was thus given the title of 'plasticity'. Once recognized, it became clear from surveys of different species and populations that plasticity can (i) be a complex character, and (ii) be selected to fit species to the particular demands of different environments. For plants, which cannot meet variations in environment like animals by behavioural responses, phenotypic plasticity can be very important. Plants should therefore be valuable tools for unravelling the mechanisms of plasticity whilst also demonstrating its contribution to fitness experimentally. We ought also to be able to demonstrate that appropriate genetic variability is available through which complex responses can be built up by selection. Genes must exist not only to determine character means, but also to determine character response, which adds interesting complexity to our ideas about evolution.     

The localization of estrogen receptors on human osteoblasts

Attempts to identify estrogen target cells in bone by immunocytochemistry using antibodies to the receptor have proved to be controversial. The aim of this study was therefore to determine whether immunogold labeling can be used as a technique for the localization of estrogen receptors (ER) on a human osteoblast-like cell line. The aim was also to determine the distribution of ER on the cell surface by using a scanning electron microscope (SEM) and intracellularly by using a transmission electron microscope (TEM). Labeling of the cytoplasmic material was seen around areas that appeared to be a disrupted plasma membrane. No nuclear or perinuclear labeling could be detected. The conclusion can be made that SEM immunogold labeling combined with TEM can be regarded as a practical technique for localizing ER on human osteoblasts. This article clearly demonstrated that osteoblast-like cells do express ER at low levels and that, although cytoplasmic immunoreactivity could be detected, no, nuclear or perinuclear labeling was found.     

Compulsory moral bioenhancement should be covert

Some theorists argue that moral bioenhancement ought to be compulsory. I take this argument one step further, arguing that if moral bioenhancement ought to be compulsory, then its administration ought to be covert rather than overt. This is to say that it is morally preferable for compulsory moral bioenhancement to be administered without the recipients knowing that they are receiving the enhancement. My argument for this is that if moral bioenhancement ought to be compulsory, then its administration is a matter of public health, and for this reason should be governed by public health ethics. I argue that the covert administration of a compulsory moral bioenhancement program better conforms to public health ethics than does an overt compulsory program. In particular, a covert compulsory program promotes values such as liberty, utility, equality, and autonomy better than an overt program does. Thus, a covert compulsory moral bioenhancement program is morally preferable to an overt moral bioenhancement program.     

What is this stuff called fitness?

This paper considers a variety of attempts to define fitness in such a way as to defend the theory of evolution by natural selection from the criticism that it is a circular argument. Each of the definitions is shown to be inconsistent with the others. The paper argues that the environment in which an animal evolves can be defined only with respect to the properties of the phenotype of the animal and that it is therefore not illuminating to try to explain the phenotypic properties of the animal in terms of adaptation to an environment that is defined by those very properties. Furthermore, since there is no way that the environment can be defined independently of the presence of the animal there is no way that the quality of an animal can be assessed; and there can be no objective criteria by whichany form of selection can be carried out, therefore there can be no criteria by whichnatural selection can be carried out. It is proposed that fitness is nothing more than the production of offspring, that this is a phenotypic property like all the others, and if it is heritable then the offspring of the parents that produce the most offspring will themselves produce the most offspring, and that in principle it is impossible to account for this in terms of the other phenotypic properties of the fittest animals except by circular argument. Differential rates of reproduction are the causes of evolution and the phenotypic causes are strictly inexplicable.     

Workshop on algal polysaccharides

Summary This workshop was an impromptu event, but the fact that a number of interesting problems were identified by the participants from the floor may indicate that it is worth repeating. If it is to be repeated, however, it is important that notice be given, and that the scope of the workshop be defined in advance, so that participants can be better informed and bring supporting data. The best approach would be to identify a convenor and define the scope of the workshop prior to the first circular for the next Seaweed Symposium; invitations could then be issued by the convenor for specific topics and data, and a very brief program could be issued with the third circular. Such a procedure may very well allow the identification of new areas for research.     

A review about nothing: Are apolar cavities in proteins really empty?

Cavities within proteins that are strictly apolar typically appear to be empty. It has been suggested, however, that water molecules may be present within such cavities but are too disordered to be seen in conventional crystallographic analyses. In contrast, it is argued here that solvent mobility will be limited by the size of the cavity and for this reason high‐occupancy solvent in cavities of typical volume should be readily detectable using X‐ray crystallography. Recent experimental studies of cavity hydration are reviewed. Such studies are consistent with theoretical predictions that it is energetically unfavorable to have a single water molecule in an apolar cavity. As apolar cavities become larger, a point is reached where it is favorable to have the cavity occupied by a cluster of mutually H‐bonded water molecules. The exact size of such a cavity in a protein is yet to be verified.     

The dangers of euthanasia and dementia: how Kantian thinking might be used to support non-voluntary euthanasia in cases of extreme dementia

Some writers have argued that a Kantian approach to ethics can be used to justify suicide in cases of extreme dementia, where a patient lacks the rationality required of Kantian moral agents. I worry that this line of thinking may lead to the more extreme claim that euthanasia is a proper Kantian response to severe dementia (and similar afflictions). Such morally treacherous thinking seems to be directly implied by the arguments that lead Dennis Cooley and similar writers to claim that Kant might support suicide. If rationality is the only factor in valuing a human life, then the loss of that rationality (however such loss might be defined) would allow us to use essentially utilitarian thinking in order to support non-voluntary euthanasia, since the patients themselves would no longer be moral agents that demand respect.     

Block Fitness

There are three related criteria that a concept of fitness should be able to meet: it should render the principle of natural selection non-tautologous and it should be explanatory and predictive. I argue that for fitness to be able to fulfill these criteria, it cannot be a property that changes over the course of an individual's life. Rather, I introduce a fitness concept--Block Fitness--and argue that an individual's genes and environment fix its fitness in such a way that each individual's fitness has a fixed value over its lifetime.     

Making the case for human life extension: personal arguments

In the close to medium future, the life sciences might permit a vast extension of the human life span. I will argue that this is a very desirable development for the individual person. The question whether death is a harm to the dying is irrelevant here. All it takes is that being alive is good for the living person and not being alive is not good for anyone. Thus, living persons who expect to live on happily are rationally required to want to stay alive. Eventual uncertainty whether it will be possible to be happy in the future provides no objection, but rather an incentive to try. This view, however, may be naive in assuming that persons are unchanging entities that exist separately from their psychological information. Objections have been derived from reductionistic views that value our future experiences in a way that declines with time, so that there will be a future point beyond which only negligible value accrues. If we adopt such a view, then we cannot now be concerned to have experiences beyond that point. I argue that these arguments fail to take into account all the reasons we might have to be concerned for the future and all kinds of such concern that come from them. The adoption of a plausible reductionistic account can arguably weaken our concern for the future and certainly change its quality in important ways. But this provides no objection to the desire to live forever, nor to live at all.     

Sanctions and mutualism stability: when should less beneficial mutualists be tolerated?

Why do mutualists perform costly behaviours that benefit individuals of a different species? One of the factors that may stabilize mutualistic interactions is when individuals preferentially reward more mutualistic (beneficial) behaviour and/or punish less mutualistic (more parasitic) behaviour. We develop a model that shows how such sanctions provide a fitness benefit to the individuals that carry them out. Although this approach could be applied to a number of symbioses, we focus on how it could be applied to the legume‐rhizobia interaction. Specifically, we demonstrate how plants can be selected to supply preferentially more resources to (or be less likely to senesce) nodules that are fixing more N₂ (termed plant sanctions). We have previously argued that appreciable levels of N₂ fixation by rhizobia are only likely to be selected for in response to plant sanctions. Therefore, by showing that plant sanctions can also be favoured by natural selection, we are able to provide an explanation for the stability of the plant‐legume mutualism.     

Suffering at the end of life

In the end‐of‐life context, alleviation of the suffering of a distressed patient is usually seen as a, if not the, central goal for the medical personnel treating her. Yet it has also been argued that suffering should be seen as a part of good dying. More precisely, it has been maintained that alleviating a dying patient’s suffering can make her unable to take care of practical end‐of‐life matters, deprive her of an opportunity to ask questions about and find meaning in and for her existence, and detach her from reality. In this article, I argue that the aims referred to either do not support suffering or are better served by alleviating it. When the aims would be equally well served by enduring suffering and relieving it, the latter appears to be the preferable option, given that the distress a patient experiences has no positive intrinsic value. Indeed, as the suffering can be very distressing, it may not be worth bearing even if that was the best way to achieve the aims: the distress can sometimes be bad enough to outbalance the worth of achieving the goals. Having considered an objection to the effect that a patient can have a self‐regarding moral duty to endure the distress she faces at the end of life, I conclude that the burden of proof is on the side of those who maintain that the suffering experienced at the end of life ought to be endured as a part of dying well.     

Probabilistic computation by neuromine networks

In this paper, we address the question, can biologically feasible neural nets compute more than can be computed by deterministic polynomial time algorithms? Since we want to maintain a claim of plausibility and reasonableness we restrict ourselves to algorithmically easy to construct nets and we rule out infinite precision in parameters and in any analog parts of the computation. Our approach is to consider the recent advances in randomized algorithms and see if such randomized computations can be described by neural nets. We start with a pair of neurons and show that by connecting them with reciprocal inhibition and some tonic input, then the steady-state will be one neuron ON and one neuron OFF, but which neuron will be ON and which neuron will be OFF will be chosen at random (perhaps, it would be better to say that microscopic noise in the analog computation will be turned into a megascale random bit). We then show that we can build a small network that uses this random bit process to generate repeatedly random bits. This random bit generator can then be connected with a neural net representing the deterministic part of randomized algorithm. We, therefore, demonstrate that these neural nets can carry out probabilistic computation and thus be less limited than classical neural nets.     

ADDICTION AND AUTONOMY: CAN ADDICTED PEOPLE CONSENT TO THE PRESCRIPTION OF THEIR DRUG OF ADDICTION?

It is often claimed that the autonomy of heroin addicts is compromised when they are choosing between taking their drug of addiction and abstaining. This is the basis of claims that they are incompetent to give consent to be prescribed heroin. We reject these claims on a number of empirical and theoretical grounds. First we argue that addicts are likely to be sober, and thus capable of rational thought, when approaching researchers to participate in research. We reject behavioural evidence purported to establish that addicts lack autonomy. We present an argument that extrinsic forces must be irresistible in order to make a choice non-autonomous. We argue that heroin does not present such an irresistible force. We make a case that drug-oriented desires are strong regular appetitive desires, which do not compromise consent. Finally we argue that an addict's apparent desire to engage in a harmful act cannot be construed as evidence of irrational or compulsive thought. On these arguments, a sober heroin addict must be considered competent, autonomous and capable of giving consent. More generally, any argument against legalisation of drugs or supporting infringement of the liberty of those desiring to take drugs of addiction must be based on considerations of harm and paternalism, and not on false claims that addicts lack freedom of the will.     

Misplaced Paternalism and other Mistakes in the Debate over Kidney Sales

Erik Malmqvist defends the prohibition on kidney sales as a justifiable measure to protect individuals from harms they have not autonomously chosen. This appeal to ‘group soft paternalism’ requires that three conditions be met. It must be shown that some vendors will be harmed, that some will be subject to undue pressure to vend, and that we cannot feasibly distinguish between the autonomous and the non‐autonomous. I argue that Malmqvist fails to demonstrate that any of these conditions are likely to obtain. His argument involves two common errors. First, he, like many, proceeds on a mistaken understanding of how to assess harm. What matters is not the balance of costs and benefits of vending, but a comparison of potential vendors’ welfare across two possible courses of action. Second, Malmqvist's concerns about third‐party pressure are predicated on an empirically unrealistic understanding of the operation of a regulated market. A widely underappreciated fact is that kidney sales will be relatively rare, and most who try to vend will be unable to. Because pressure on another to vend will not result in the desired outcome, few will exert it.     

Biomimetics of Campaniform Sensilla： Measuring Strain from the Deformation of Holes

We present a bio-inspired strategy for designing embedded strain sensors in space structures. In insects, the campaniform sensillum is a hole extending through the cuticle arranged such that its shape changes in response to loads. The shape change is rotated through 90° by the suspension of a bell-shaped cap whose deflection is detected by a cell beneath the cuticle. It can be sensitive to displacements of the order of 1 nm. The essential morphology, a hole formed in a plate of fibrous composite mate- rial, was modelled by Skordos et al. who showed that global deformation of the plate （which can be flat, curved or a tube） induces higher local deformation of the hole due to its locally higher compliance. Further developments reported here show that this approach can be applied to groups of holes relative to their orientation. , The morphology of the sensillum in insects suggests that greater sensitivity can be achieved by arranging several holes in a regular pattern; that if the hole is oval it can be ＂aimed＂ to sense specific strain directions; and that either by controlling the shape of the hole or its relationship with other holes it can have a tuned response to dynamic strains. We investigate space applications in which novel bio-inspired strain sensors could successfully be used.