The rise and fall of the adaptive landscape?

The discussion of the adaptive landscape in the philosophical literature appears to be divided along the following lines. On the one hand, some claim that the adaptive landscape is either “uninterpretable” or incoherent. On the other hand, some argue that the adaptive landscape has been an important heuristic, or tool in the service of explaining, as well as proposing and testing hypotheses about evolutionary change. This paper attempts to reconcile these two views.

The rise and fall of surgery for the “floating” kidney

The latter half of the nineteenth century produced a remarkable expansion of surgical practice. Although most of these new techniques and concepts were soundly based, others, such as the movable or floating kidney, were later ridiculed and discredited.In Glasgow Royal Infirmary during the 48 years from 1880, when movable kidney was first mentioned in the annual reports of the hospital, to 1928 472 patients (89% female) were diagnosed as suffering from the condition. Nearly half of them (216) underwent operation and the operative mortality was low. In the first decade of this century an average of 18 cases a year were admitted to the wards of the infirmary. From 1915 to 1920 the number of cases dropped, as did the proportion undergoing operation, but in the 1920s the numbers increased again.In common with other ineffective treatments for imaginary diseases, operations for the movable kidney simply faded away in Britain in the 1930s.     

The new nativism: a commentary on Gary Marcus’s The birth of the mind

Gary Marcus (2004) has written a very interesting book about mental development from a nativist perspective. For the general readership at which the book is largely aimed, it will be interesting because of its many informative examples of the development of cognitive structures and because of its illuminating explanations of ways in which genes can contribute to these developmental processes. However, the book is also interesting from a theoretical point of view. Marcus tries to make nativism compatible with the central arguments that anti-nativists use to attack nativism and with many recent discoveries about genetic activity and brain development. In so doing, he reconfigures the nativist position to a considerable extent. Marcus’s theory is certainly more sophisticated than any version of nativism on the market. However, in our view Marcus ends up reconfiguring the nativist position out of existence. While many of the points that Marcus makes are both interesting and correct, we see no compelling reason to classify his considered position with traditional nativism rather than anti-nativism. More generally, we that think his book points to a general moral: the opposition between nativism and anti-nativism does not help us to understand psycho-developmental issues, and should therefore be abandoned.     

A short history of RubisCO: the rise and fall (?) of Nature's predominant CO2 fixing enzyme

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The harm principle as a mid-level principle?: three problems from the context of infectious disease control

Effective infectious disease control may require states to restrict the liberty of individuals. Since preventing harm to others is almost universally accepted as a legitimate (prima facie) reason for restricting the liberty of individuals, it seems plausible to employ a mid-level harm principle in infectious disease control. Moral practices like infectious disease control support - or even require - a certain level of theory-modesty. However, employing a mid-level harm principle in infectious disease control faces at least three problems. First, it is unclear what we gain by attaining convergence on a specific formulation of the harm principle. Likely candidates for convergence, a harm principle aimed at preventing harmful conduct, supplemented by considerations of effectiveness and always choosing the least intrusive means still leave ample room for normative disagreement. Second, while mid-level principles are sometimes put forward in response to the problem of normative theories attaching different weight to moral principles, employing a mid-level harm principle completely leaves open how to determine what weight to attach to it in application. Third, there appears to be a trade-off between attaining convergence and finding a formulation of the harm principle that can justify liberty-restrictions in all situations of contagion, including interventions that are commonly allowed. These are not reasons to abandon mid-level theorizing altogether. But there is no reason to be too theory-modest in applied ethics. Morally justifying e.g. if a liberty-restriction in infectious disease control is proportional to the aim of harm-prevention, promptly requires moving beyond the mid-level harm principle.     

The prevention and eradication of smallpox: a commentary on Sloane (1755) ‘An account of inoculation’

Sir Hans Sloane''s account of inoculation as a means to protect against smallpox followed several earlier articles published in Philosophical Transactions on this procedure. Inoculation (also called ‘variolation’) involved the introduction of small amounts of infectious material from smallpox vesicles into the skin of healthy subjects, with the goal of inducing mild symptoms that would result in protection against the more severe naturally acquired disease. It began to be practised in England in 1721 thanks to the efforts of Lady Mary Wortley Montagu who influenced Sloane to promote its use, including the inoculation of the royal family''s children. When Edward Jenner''s inoculation with the cow pox (‘vaccination’) followed 75 years later as a safer yet equally effective procedure, the scene was set for the eventual control of smallpox epidemics culminating in the worldwide eradication of smallpox in 1977, officially proclaimed by WHO in 1980. Here, we discuss the significance of variolation and vaccination with respect to scientific, public health and ethical controversies concerning these ‘weapons of mass protection’. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

A Delicate Adjustment: Wallace and Bates on the Amazon and “The Problem of the Origin of Species”

For over a century it has been believed that Alfred Russel Wallace and Henry Walter Bates set out for the Amazon in 1848 with the aim of “solving the problem of the origin of species”. Yet this enticing story is based on only one sentence. Bates claimed in the preface to his 1863 book that Wallace stated this was the aim of their expedition in an 1847 letter. Bates gave a quotation from the letter. But Wallace himself never endorsed or repeated this story. Many writers have acknowledged that this letter still survives. Yet the wording is different from that quoted by Bates and the letter says nothing of an expedition. It is argued that the sentence given by Bates is not a genuine quotation from this or any other Wallace letter but was modified by Bates to promote his own reputation. More significantly, this leads to the conclusion that there was a very sudden and dramatic shift in the way species were thought of and discussed after Darwin’s Origin of species appeared. Something called “the problem of the origin of species” (and similar variants) never occurred before Darwin’s book but exploded in frequency immediately after it. A profound change in how species origins were discussed happened which no one seemed to notice.     

The enigma of the rise of angiosperms: can we untie the knot?

Multiple hypotheses have been put forward to explain the rise of angiosperms to ecological dominance following the Cretaceous. A unified scheme incorporating all these theories appears to be an inextricable knot of relationships, processes and plant traits. Here, we revisit these hypotheses, categorising them within frameworks based on plant carbon economy, resistance to climatic stresses, nutrient economy, biotic interactions and diversification. We maintain that the enigma remains unresolved partly because our current state of knowledge is a result of the fragmentary nature of palaeodata. This lack of palaeodata limits our ability to draw firm conclusions. Nonetheless, based on consistent results, some inferences may be drawn. Our results indicate that a complex multidriver hypothesis may be more suitable than any single‐driver theory. We contend that plant carbon economy and diversification may have played an important role during the early stages of gymnosperms replacement by angiosperms in fertile tropical sites. Plant tolerance to climatic stresses, plant nutrition, biotic interactions and diversification may have played a role in later stages of angiosperm expansion within temperate and harsh environments. The angiosperm knot remains partly tied, but to unravel it entirely will only be feasible if new discoveries are made by scientific communities.     

Effects of Whaling on the Structure of the Southern Ocean Food Web: Insights on the “Krill Surplus” from Ecosystem Modelling

The aim of this study was to examine the ecological plausibility of the “krill surplus” hypothesis and the effects of whaling on the Southern Ocean food web using mass-balance ecosystem modelling. The depletion trajectory and unexploited biomass of each rorqual population in the Antarctic was reconstructed using yearly catch records and a set of species-specific surplus production models. The resulting estimates of the unexploited biomass of Antarctic rorquals were used to construct an Ecopath model of the Southern Ocean food web existing in 1900. The rorqual depletion trajectory was then used in an Ecosim scenario to drive rorqual biomasses and examine the “krill surplus” phenomenon and whaling effects on the food web in the years 1900–2008. An additional suite of Ecosim scenarios reflecting several hypothetical trends in Southern Ocean primary productivity were employed to examine the effect of bottom-up forcing on the documented krill biomass trend. The output of the Ecosim scenarios indicated that while the “krill surplus” hypothesis is a plausible explanation of the biomass trends observed in some penguin and pinniped species in the mid-20^th century, the excess krill biomass was most likely eliminated by a rapid decline in primary productivity in the years 1975–1995. Our findings suggest that changes in physical conditions in the Southern Ocean during this time period could have eliminated the ecological effects of rorqual depletion, although the mechanism responsible is currently unknown. Furthermore, a decline in iron bioavailability due to rorqual depletion may have contributed to the rapid decline in overall Southern Ocean productivity during the last quarter of the 20^th century. The results of this study underscore the need for further research on historical changes in the roles of top-down and bottom-up forcing in structuring the Southern Ocean food web.     

Modelling the Effects of Selection Temperature and Mutation on the Prisoner’s Dilemma Game on a Complete Oriented Star

This paper models the prisoner’s dilemma game based on pairwise comparison in finite populations on a complete oriented star (COS). First, we derive a linear system on a COS for calculating the corresponding fixation probabilities that imply dependence of the selection temperature and mutation. Then we observe and analyze the effects of two parameters on fixation probability under different population sizes. In particular, it is found through the experimental results that (1) high mutation is more sensitive to the fixation probability than the low one when population size is increasing, while the opposite is the case when the number of cooperators is increasing, and (2) selection temperature demotes the fixation probability.     

Refinements of and commentary on the silver staining techniques of Fernández-Galiano

The original ammoniacal silver carbonate staining technique and subsequent modification developed by Fernández-Galiano are useful for investigating ciliate protozoan systematics and/or ciliate cortical structure and morphogenesis. The technique is complicated, however, by both uncertainties arising from the need to count drops of reagents and subjective control of the staining intensity. I have resolved these complications by defining volumes of reagents rather than using drops and by defining a range of staining times. I also comment on various steps of the techniques. My techniques are simplified and refined to produce consistent, high quality staining results.     

Hormones for life? Behind the rise and fall of a hormone remedy (Gonadex) against sterility in the Swedish welfare state

In 1948 the pharmaceutical company Leo launched a placental hormonal preparation, called Gonadex, in Sweden. During a press conference, and in commercials and newspapers, it was said that Gonadex could cure sterility as well as many other problems related to the endocrine system. The remedy was described as effective and pure, with no side effects whatsoever. For several reasons, Gonadex was looked upon as a 'Swedish triumph'. Inspired by research on 'mediation', conducted within the field of social studies of pharmaceutical drugs, the present essay explores the political and scientific visions and values behind Gonadex; the propaganda for and marketing of Gonadex; the mediated image of Gonadex in the press; the reception by the medical profession, and finally the hopes and fears of the women who tried (or wanted to try) Gonadex. The essay argues that the public image of Gonadex was 'oversell' of hormone therapy, and that it was shaped by the way endocrinologists at Karolinska Hospital, notably Professor Axel Westman, mediated between Leo, the mass media, and the consumers when, and even before, Gonadex was introduced to the market.     

Marketing data: Has the rise of impact factor led to the fall of objective language in the scientific article?

Genetic association studies have become an important part of our scientific landscape. This commentary discusses some basic scientific issues which should be considered when reporting and evaluating such studies including SNP Discovery, Genotyping and Haplotype Analysis; Population Size, Matching of Cases and Controls, and Population Stratification; Phenotype Definition and Multiple Related Phenotypes; Multiple Testing; Replication; Genome-wide Association Studies (GWAS); and the Role of Functional Studies. All of these elements are important in evaluating such studies and should be carefully considered when these studies are conceived and carried out.     

The influence of spin-labeled fluorene compounds on the assembly and toxicity of the aβ peptide

Background

The deposition and oligomerization of amyloid β (Aβ) peptide plays a key role in the pathogenesis of Alzheimer''s disease (AD). Aβ peptide arises from cleavage of the membrane-associated domain of the amyloid precursor protein (APP) by β and γ secretases. Several lines of evidence point to the soluble Aβ oligomer (AβO) as the primary neurotoxic species in the etiology of AD. Recently, we have demonstrated that a class of fluorene molecules specifically disrupts the AβO species.

Methodology/Principal Findings

To achieve a better understanding of the mechanism of action of this disruptive ability, we extend the application of electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels in the Aβ peptide to investigate the binding and influence of fluorene compounds on AβO structure and dynamics. In addition, we have synthesized a spin-labeled fluorene (SLF) containing a pyrroline nitroxide group that provides both increased cell protection against AβO toxicity and a route to directly observe the binding of the fluorene to the AβO assembly. We also evaluate the ability of fluorenes to target multiple pathological processes involved in the neurodegenerative cascade, such as their ability to block AβO toxicity, scavenge free radicals and diminish the formation of intracellular AβO species.

Conclusions

Fluorene modified with pyrroline nitroxide may be especially useful in counteracting Aβ peptide toxicity, because they posses both antioxidant properties and the ability to disrupt AβO species.     

Deciphering death: a commentary on Gompertz (1825) ‘On the nature of the function expressive of the law of human mortality,and on a new mode of determining the value of life contingencies’

In 1825, the actuary Benjamin Gompertz read a paper, ‘On the nature of the function expressive of the law of human mortality, and on a new mode of determining the value of life contingencies’, to the Royal Society in which he showed that over much of the adult human lifespan, age-specific mortality rates increased in an exponential manner. Gompertz''s work played an important role in shaping the emerging statistical science that underpins the pricing of life insurance and annuities. Latterly, as the subject of ageing itself became the focus of scientific study, the Gompertz model provided a powerful stimulus to examine the patterns of death across the life course not only in humans but also in a wide range of other organisms. The idea that the Gompertz model might constitute a fundamental ‘law of mortality’ has given way to the recognition that other patterns exist, not only across the species range but also in advanced old age. Nevertheless, Gompertz''s way of representing the function expressive of the pattern of much of adult mortality retains considerable relevance for studying the factors that influence the intrinsic biology of ageing. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

The early evolution of land plants,from fossils to genomics: a commentary on Lang (1937) ‘On the plant-remains from the Downtonian of England and Wales'

During the 1920s, the botanist W. H. Lang set out to collect and investigate some very unpromising fossils of uncertain affinity, which predated the known geological record of life on land. His discoveries led to a landmark publication in 1937, ‘On the plant-remains from the Downtonian of England and Wales’, in which he revealed a diversity of small fossil organisms of great simplicity that shed light on the nature of the earliest known land plants. These and subsequent discoveries have taken on new relevance as botanists seek to understand the plant genome and the early evolution of fundamental organ systems. Also, our developing knowledge of the composition of early land-based ecosystems and the interactions among their various components is contributing to our understanding of how life on land affects key Earth Systems (e.g. carbon cycle). The emerging paradigm is one of early life on land dominated by microbes, small bryophyte-like organisms and lichens. Collectively called cryptogamic covers, these are comparable with those that dominate certain ecosystems today. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

The precautionary principle: a double edged sword?

There is no doubt that the introduction of quality system principles and regulation to blood and tissue services in the 1990’s has brought about significant improvements in the control of processes and the quality of products being released for patient care. But, as regulation extends into new areas of cellular and tissue therapy, it is perhaps time to review the regulatory paradigm within which we work, and the principles that underpin it. At what point do the costs of regulation exceed the benefits to be gained? At what point to regulations cease to yield measurable benefits to patient care and safety at all, but instead become simply a burden on service providers and businesses, and ultimately the community as a whole? And is there a point at which regulation actually compromises patient care and safety, or the development of new technologies? In the early stages of regulation, there is demonstrable cost-benefit as assessed by product quality and patient outcomes. However, there is inevitably a “law of diminishing returns”, whereby the degree of improvement that can be achieved decreases and the cost of achieving that benefit increases. What has not yet been determined is whether, as regulations and regulators become more precise and more demanding, there remains a measurable net cost benefit over time, or whether there is a point at which the cost of further improvement matches, or even exceeds, the benefits to be gained. A key underpinning of the regulatory philosophy is the “Precautionary Principle”. This paper will focus on the application of the Precautionary Principle in the area of blood and tissues, which encompasses the burgeoning field of cellular therapies.