Ngongas and ecology: on having a worldview

Ngongas provide a metaphor for some of the opportunities and challenges facing the science of ecology and evolution. Ngongas, the traditional healers of the Shona culture, Zimbabwe, fail in the delivery of quality health by today's standards. Their outdated worldview makes most health related issues seem more complicated and more multi-factorial than when viewed through the worldviews of modern medicine. With the wrong worldview, one can work very hard, be very bright and dedicated, and still be ineffective. With the right worldview, one can work much less hard and still be extremely effective. As ecologists, we should be opinionated and possess clearly articulated worldviews for filtering and interpreting information. As ecologists we are also a bit like ngongas – we often fail to provide answers for society's ecological questions and problems, and we excuse ourselves with a belief that ecological systems are too complex and have too many factors. Unlike ngongas, this invites us to pay a lot of attention to promoting and assessing competing worldviews. We should be open-minded to the anomalies in our worldview and the successes of alternative viewpoints. As an admitted ecological ngonga, I discuss the worldview I use in my own research: the Optimization Research Program, a Darwinian research program that uses game theory to conceptualize and understand ecological systems. I use it illustrate how worldviews can synthesize disparate ideas. (I use kin selection and reciprocal altruism as examples.) I use it to show how new ideas and predictions can be generated. (I use root competition in plants and the possibility that increased crop yield may be forthcoming from knowledge of this game.)     

Wrongness,Responsibility, and Conscientious Refusals in Health Care

In this article, I address what kinds of claims are of the right kind to ground conscientious refusals. Specifically, I investigate what conceptions of moral responsibility and moral wrongness can be permissibly presumed by conscientious objectors. I argue that we must permit HCPs to come to their own subjective conclusions about what they take to be morally wrong and what they take themselves to be morally responsible for. However, these subjective assessments of wrongness and responsibility must be constrained in several important ways: they cannot involve empirical falsehoods, objectionably discriminatory attitudes, or unreasonable normative beliefs. I argue that the sources of these constraints are the basic epistemic, relational, and normative competencies needed to function as a minimally decent health‐care professional. Finally, I consider practical implications for my framework, and argue that it shows us that the objection raised by the plaintiffs in Zubik v. Burwell is of the wrong sort.     

Development of the concept of immunologic specificity: IV

We have attempted, in this series of essays on the development of the concept of immunologic specificity, to trace the history of one of the most central ideas in immunology (and indeed in biology in general). The result must be viewed as preliminary and incomplete and as an invitation to others to add, to amend, and even to disprove. Nevertheless, several interesting conclusions may be drawn, which reveal much about the workings of immunology in particular, and perhaps science in general. First, the roots of any important scientific concept (such as that of immunologic specificity) do not grow in isolation; they draw nourishment from many other disciplines. Similarly, the growth of an important concept within a given discipline will have far-reaching implications and fruits for other fields of science. Second, we may note a marked change in the manner in which immunology is currently practiced, compared with that of the end of the last century. The quantum leaps forward in funding, in numbers of scientists, and in masses of crucial data have not been without a certain cost--the substantial reduction in elegant personal style that characterized so many of our scientific forebears, and that makes so pleasant the reading of their reports. Finally, we see again and again how much his philosophical bases and disciplinary upbringing determine a scientist's approach, the questions that he asks, and the type of answers he will accept. Throughout much of immunology's history, as Jerne put it so well (44), cis- and trans-immunologists hardly spoke to one another. Or rather, a cis-immunologist sometimes spoke to a trans-immunologist, but the latter rarely answered! Fortunately, one of the attributes of scientific progress is a merging of these disparate languages, and eventual mutual comprehension.     

What is an organism? An immunological answer

The question, "What is an organism?," formerly considered as essential in biology, has now been increasingly replaced by a larger question, "What is a biological individual?" On the grounds that i) individuation is theory-dependent, and ii) physiology does not offer a theory, biologists and philosophers of biology have claimed that it is the theory of evolution by natural selection that tells us what counts as a biological individual. Here I show that one physiological field, immunology, offers a theory that makes possible a biological individuation based on physiological grounds. I give a new answer to the question of the individuation of an organism by linking together the evolutionary and the immunological approaches to biological individuation.     

On the use of the Price equation

This paper distinguishes two categories of questions that the Price equation can help us answer. The two different types of questions require two different disciplines that are related, but nonetheless move in opposite directions. These disciplines are probability theory on the one hand and statistical inference on the other. In the literature on the Price equation this distinction is not made. As a result of this, questions that require a probability model are regularly approached with statistical tools. In this paper, we examine the possibilities of the Price equation for answering questions of either type. By spending extra attention on mathematical formalities, we avoid the two disciplines to get mixed up. After that, we look at some examples, both from kin selection and from group selection, that show how the inappropriate use of statistical terminology can put us on the wrong track. Statements that are 'derived' with the help of the Price equation are, therefore, in many cases not the answers they seem to be. Going through the derivations in reverse can, however, be helpful as a guide how to build proper (probabilistic) models that do give answers.     

The parenthood argument

Don Marquis is well known for his future like ours theory (FLO), according to which the killing beings like us is seriously morally wrong because it deprives us of a future we can value. According to Marquis, human fetuses possess a future they can come to value, and thus according to FLO have a right to life. Recently Mark Brown has argued that even if FLO shows fetuses have a right to life, it fails to show that fetuses have a right to use their mother's body, evoking Judith Jarvis Thomson's famous violinist case. In the wake of Brown's conclusion, Marquis presents a new argument—the parenthood argument (PA)—which he believes shows that abortion is seriously morally wrong. Here I argue that the PA fails to show abortion is seriously morally wrong for the same reasons FLO fails to show abortion is seriously morally wrong.     

Authoritative regulation and the stem cell debate

In this paper I argue that liberal democratic communities are justified in regulating the activities of their members because of the inevitable existence of conflicting conceptions of what is considered as morally right. This will often lead to tension and disputes, and in such circumstances, reliance on peaceful or orderly co-existence will not normally suffice. In such pluralistic societies, the boundary between permissible and impermissible activities will be unclear; and this becomes a particular concern in controversial issues which raise specific anxieties and uncertainty. One context that has repeatedly raised issues in this regard is that of biotechnology and, in particular, the recent stem cell debate, on which this paper concentrates. While such developments have the potential to make significant improvements to therapeutic progress, we should also be sceptical because predicting the impact of these developments remains uncertain and complex. For the sake of socio-political stability, it will therefore be necessary to enact and enforce rules which limit these competing claims in public policy but which may not be compatible with what individual moral commitments ideally permit. One way to achieve this is to establish procedural frameworks to resolve potential disputes in the public sphere about what is right, wrong, or permissible conduct. I argue that for one to commit to authoritative regulation, an idea of harm prevention through state intervention is necessary; and that this requires optimum mechanisms of procedure which allow the individual the opportunity to compromise and yet to continue to oppose or fight for changes as demanded by his or her moral position.     

The immune system: a key concept for the history of immunology

The definition of immunology as the science of the immune system that emerged in the 1960s provides a sound basis for both reconstructing its past and constructing its future. The choice of this point in time of course involves important consequences, on the one hand, sociological and institutional, epistemological and conceptual on the other. I will attempt to demonstrate that this perspective allows us to assess the history of immunology in an innovative way while elucidating in the process some of its theoretical paradoxes.     

Where does our behaviour come from?

Conclusion Looking for single causes, whether genetic or environmental, may yield answers of a kind, but little sense of what happens as each individual grows up. The language of nature versus nurture, or genes versus environment, gives only a feeble insight into the processes that I have called developmental cooking. The best that can be said of the nature/nurture split is that it provides a framework for uncovering a few of the genetic and environmental ingredients that generate differences between people. At worst, it satisfies a demand for simplicity in ways that are fundamentally misleading.     

The pro-life argument from substantial identity: a defence

This article defends the following argument: what makes you and I valuable so that it is wrong to kill us now is what we are (essentially). But we are essentially physical organisms, who, embryology reveals, came to be at conception/fertilisation. I reply to the objection to this argument (as found in Dean Stretton, Judith Thomson, and Jeffrey Reiman), which holds that we came to be at one time, but became valuable as a subject of rights only some time later, in virtue of an acquired characteristic. I argue against this position that the difference between a basic, natural capacity and some degree of development of such a capacity is a mere difference in degree, that this position logically implies the denial of equal personal dignity, and that the selection of the required degree of development of a capacity is necessarily arbitrary.     

Schistosome glycoconjugates in host-parasite interplay

Schistosomes are digenetic trematodes which cause schistosomiasis, also known as bilharzia, one of the main parasitic infections in man. In tropical and subtropical areas an estimated 200 million people are infected and suffer from the debilitating effects of this chronic disease. Schistosomes live in the blood vessels and strongly modulate the immune response of their host to be able to survive the hostile environment that they are exposed to. It has become increasingly clear that glycoconjugates of schistosome larvae, adult worms and eggs play an important role in the evasion mechanisms that schistosomes utilise to withstand the immunological measures of the host. Upon infection, the host mounts innate as well as adaptive immune responses to antigenic glycan elements, setting the immunological scene characteristic for schistosomiasis. In this review we summarise the structural data now available on schistosome glycans and provide data and ideas regarding the role that these glycans play in the various aspects of the glycobiology and immunology of schistosomiasis.     

Natural immunoglobulins (contribution to a debate on biomedical education)

Immunology has contributed to biomedical education in many important ways since the creation of scientific medicine in the last quarter of the 19th century. Today, immunology is a major area of biomedical research. Nevertheless, there are many basic problems unresolved in immunological activities and phenomena. Solving these problems is probably necessary to devise predictable and safe ways to produce new vaccines, treat allergy and autoimmune diseases and perform safe transplants. This challenge involves not only technical developments but also changes in attitude, of which the most fundamental is to abandon the traditional stimulus-response perspective in favor of more "systemic" views. Describing immunological activities as the operation of a complex multi connected network, raises biological and epistemological issues not usually dealt with in biomedical education. Here we point to one example of systemic approaches. A new form of immunoblot (Panama blot), by which the reaction of natural immunoglobulins with complex protein mixtures may be analyzed by a special software and multivariate statistics, has been recently used to characterize human autoimmune diseases. Our preliminary data show that Panama blots can also be used to characterize global (systemic) immunological changes in chronic human parasitic diseases, such as malaria and schistosomiasis mansoni, that correlate with the clinical status.     

Correlates of cytotoxic T-lymphocyte-mediated virus control: implications for immunosuppressive infections and their treatment

A very important question in immunology is to determine which factors decide whether an immune response can efficiently clear or control a viral infection, and under what circumstances we observe persistent viral replication and pathology. This paper summarizes how mathematical models help us gain new insights into these questions, and explores the relationship between antiviral therapy and long-term immunological control in human immunodeficiency virus (HIV) infection. We find that cytotoxic T lymphocyte (CTL) memory, defined as antigen-independent persistence of CTL precursors, is necessary for the CTL response to clear an infection. The presence of such a memory response is associated with the coexistence of many CTL clones directed against multiple epitopes. If CTL memory is inefficient, then persistent replication can be established. This outcome is associated with a narrow CTL response directed against only one or a few viral epitopes. If the virus replicates persistently, occurrence of pathology depends on the level of virus load at equilibrium, and this can be determined by the overall efficacy of the CTL response. Mathematical models suggest that controlled replication is reflected by a positive correlation between CTLs and virus load. On the other hand, uncontrolled viral replication results in higher loads and the absence of a correlation between CTLs and virus load. A negative correlation between CTLs and virus load indicates that the virus actively impairs immunity, as observed with HIV. Mathematical models and experimental data suggest that HIV persistence and pathology are caused by the absence of sufficient CTL memory. We show how mathematical models can help us devise therapy regimens that can restore CTL memory in HIV patients and result in long-term immunological control of the virus in the absence of life-long treatment.     

Intention and Moral Enhancement

Recently philosophers have proposed a wide variety of interventions referred to as ‘moral enhancements’. Some of these interventions are concerned with helping individuals make more informed decisions; others, however, are designed to compel people to act as the intervener sees fit. Somewhere between these two extremes lie interventions designed to direct an agent's attention either towards morally relevant issues – hat‐hanging – or away from temptations to do wrong – hat‐hiding. I argue that these interventions fail to constitute genuine moral enhancement because, although they may result in more desirable outcomes – more altruism, more law‐following, and/or less self‐destructive behavior, they ignore a person's intentions, and often what makes an action right or wrong is the intent behind it.     

A case for more curiosity-driven basic research

Having been selected to be among the exquisitely talented scientists who won the Sandra K. Masur Senior Leadership Award is a tremendous honor. I would like to take this opportunity to make the case for a conviction of mine that I think many will consider outdated. I am convinced that we need more curiosity-driven basic research aimed at understanding the principles governing life. The reasons are simple: 1) we need to learn more about the world around us; and 2) a robust and diverse basic research enterprise will bring ideas and approaches essential for developing new medicines and improving the lives of humankind.When I was a graduate student, curiosity-driven basic research ruled. Studying mating-type switching in budding yeast, for example, was exciting because it was an interesting problem: How can you make two different cells from a single cell in the absence of any external cues? We did not have to justify why it is important to study what many would now consider a baroque question. Scientists and funding agencies alike agreed that this was an exciting biological problem that needed to be solved. I am certain that all scientists of my generation can come up with similar examples.Open in a separate windowAngelika AmonSince the time I was a graduate student, the field of biological research has experienced a revolution. We can now determine the genetic makeup of every species in a week or so and have an unprecedented ability to manipulate any genome. This revolution has led to a sense that we understand the principles governing life and that it is now time to apply this knowledge to cure diseases and make the world a better place. While applying knowledge to improve lives and treat diseases is certainly a worthwhile endeavor, it is important to realize that we are far from having a mechanistic understanding of even the basic principles of biology. What the genomic revolution brought us are lists, some better than others. We now know how many coding genes define a given species and how many protein kinases, GTPases, and so forth there are in the various genomes we sequenced. This knowledge, however, does not even scratch the surface of understanding their function. When I browse the Saccharomyces cerevisiae genome database (my second-favorite website), I am still amazed how many genes there are that have not even been given a name.To me the most important achievement the new genome-sequencing and genome-editing technologies brought us is that nearly every organism can be a model organism now. We can study and manipulate the processes that most fascinate us in the organisms in which they occur, with the exception, of course, of humans. Thus, I believe that the golden era of basic biological research is not behind us but in front of us, and we need more people who will take advantage of the tools that have been developed in the past three decades. I am therefore hoping that many young people will chose a career in basic research and find an exciting question to study. The more of us there are, the more knowledge we will acquire, and the higher the likelihood we will discover something amazing and important. There is so much interesting biology out there that we should strive to understand. Some of my favorite unanswered questions are: What are the biological principles underlying symbiosis and how did it evolve? Why is sleep essential? Why do plants, despite an enormous regenerative potential, never die of cancer? Why do brown bears, despite inactivity, obesity, and high levels of cholesterol, exhibit no signs of atherosclerosis? How do sharks continuously produce teeth?One could, of course, argue that the knowledge we have accumulated over the past 50 years provides a reasonable framework, and it is now time to leave basic science and model organisms behind and focus on what matters—curing diseases, developing methods to produce energy, cleaning up the oceans, preventing global warming, building biological computers, designing organisms, or engineering whatever the current buzz is about. Like David Botstein, who eloquently discussed the importance of basic research in these pages in 2012 (Botstein, 2012 ), I believe that the notion that we already know enough is wrong and the current application-centric view of biology is misguided. Experience has taught us over and over that we cannot predict where the next important breakthrough will be emerge. Many of the discoveries that we consider groundbreaking and that have brought us new medicines or improved our lives in other ways are the result of curiosity-driven basic research. My favorite example is the discovery of penicillin. Alexander Fleming, through the careful study of his (contaminated) bacterial plates, enabled humankind to escape natural selection. More recent success stories such as new cures for hepatitis C, the human papillomavirus vaccine, the HIV-containment regimens, or treatments for BCR-ABL induced chronic myelogenous leukemia have also only been possible because of decades of basic research in model organisms that taught us the principles of life and enabled us to acquire the methodologies critical to develop these treatments. Although work from my own lab on the causes and consequences of chromosome mis-segregation in budding yeast has not led to the development of new treatments, it has taught us a lot about how an imbalanced karyotype, a hallmark of cancer, affects the physiology of cancer cells and creates vulnerabilities in cancer cells that could represent new therapeutic targets.These are but a few examples for why it is important that we scientists must dedicate ourselves to the pursuit of basic knowledge and why we as a society must make funding basic research a priority. Achieving the latter requires that we scientists tell the public about the importance of what we are doing and explain the potential implications of basic research for human health. At the same time, it will be important to manage expectations. We must explain that not every research project will lead to the development of new medicines and that we cannot predict where the next big breakthroughs will materialize. We must further make it clear that this means we have to fund a broad range of basic research at a healthy level. Perhaps a website that collects examples of how basic research has led to breakthroughs in medicine could serve as a showcase for such success stories, bringing the importance of what we do to the public.While conducting research to improve the lives of others is certainly a worthy motivation, it is not the main reason why I get up very early every morning to go to the lab. To me, gaining an understanding of a basic principle in the purest Faustian terms is what I find most rewarding and exciting. Designing and conducting experiments, pondering the results, and developing hypotheses as to how something may work is most exciting, the idea that I, or nowadays the people in my lab, may be (hopefully) the first to discover a new aspect of biology is the best feeling. It is these rare eureka moments, when you first realize how a process works or when you discover something that opens up a new research direction, that make up for all the woes and frustrations that come with being an experimental scientist in an expensive discipline.For me, having a career in curiosity-driven basic research has been immensely rewarding. It is my hope that basic research remains one of the pillars of the American scientific enterprise, attracting the brightest young minds for generations to come. We as a community can help to make this a reality by telling people what we do and highlighting the importance of our work to their lives.     

Can binocular rivalry reveal neural correlates of consciousness?

This essay critically examines the extent to which binocular rivalry can provide important clues about the neural correlates of conscious visual perception. Our ideas are presented within the framework of four questions about the use of rivalry for this purpose: (i) what constitutes an adequate comparison condition for gauging rivalry''s impact on awareness, (ii) how can one distinguish abolished awareness from inattention, (iii) when one obtains unequivocal evidence for a causal link between a fluctuating measure of neural activity and fluctuating perceptual states during rivalry, will it generalize to other stimulus conditions and perceptual phenomena and (iv) does such evidence necessarily indicate that this neural activity constitutes a neural correlate of consciousness? While arriving at sceptical answers to these four questions, the essay nonetheless offers some ideas about how a more nuanced utilization of binocular rivalry may still provide fundamental insights about neural dynamics, and glimpses of at least some of the ingredients comprising neural correlates of consciousness, including those involved in perceptual decision-making.     

Emergency Contraceptives and the Beginning of Human Animals

Emergency contraceptives may sometimes prevent implantation, thereby causing the death of the embryo. According to some positions contrary to abortion, because the embryo is a human animal, there are usually decisive moral reasons not to use them. In this article, I will show that objecting to the use of emergency contraceptives on those grounds is unjustified. If organisms are real existents, then according to the most plausible conception of what is required for a group of cells to compose one, the embryo cannot qualify as a single organism. On the other hand, if organisms are virtual objects, then whether or not the embryo qualifies as one is morally irrelevant. I conclude that even if those positions are right about the morality of abortion, they are not entitled to oppose the use of emergency contraceptives.     

Can we help addicts become more autonomous? Inside the mind of an addict

I examine the impact of addiction on autonomy in terms of the standard literature on addiction--referred to also as 'substance dependence.' Then in terms of the criteria for substance dependence, by developing a set of practical strategies to help people with addictions think more clearly, I test the idea of whether addicts can be helped to become more autonomous. Given that unsuccessful attempts to quit constitute part of the criteria of substance dependence, I look at what goes wrong when people try to quit using a substance. The subjective experience of addiction is an important aid in understanding addiction and first person accounts and literary characterisations of addiction provide insight into the addict's mind and assist us in deciding whether addicts can be helped to become more autonomous.     

AFRICAN AND WESTERN MORAL THEORIES IN A BIOETHICAL CONTEXT

The field of bioethics is replete with applications of moral theories such as utilitarianism and Kantianism. For a given dilemma, even if it is not clear how one of these western philosophical principles of right (and wrong) action would resolve it, one can identify many of the considerations that each would conclude is relevant. The field is, in contrast, largely unaware of an African account of what all right (and wrong) actions have in common and of the sorts of factors that for it are germane to developing a sound response to a given bioethical problem. My aim is to help rectify this deficiency by first spelling out a moral theory grounded in the mores of many sub-Saharan peoples, and then applying it to some major bioethical issues, namely, the point of medical treatment, free and informed consent, standards of care and animal experimentation. For each of these four issues, I compare and contrast the implications of the African moral theory with utilitarianism and Kantianism, my overall purposes being to highlight respects in which the African moral theory is distinct and to demonstrate that the field should take it at least as seriously as it does the Western theories.     

Schistosome immunology: more questions than answers

The past 30 years have seen research on the immunology of schistosomiasis move to encompass studies of responses in naturally exposed human populations, in addition to the studies in animal model systems. While animal systems still retain an important place in research on the immunology of schistosomiasis, recent debate has centred on aspects of human immunological responses that may or may not be associated with resistance or susceptibility to infection. In this article, Paul Hagan, Patricia Ndhlovu and David Dunne take stock of the present state of knowledge and offer their views on prospects for the future.