Life,the universe and everything

The Formal Darwinism project probes the connections between the dynamics of natural selection and the design of organisms. Here, I explain why this work should be of interest to philosophers, arguing that it is the natural development in a long-running scholarly enquiry into the meaning of life. I then review some of my own work which has applied the tools of Formal Darwinism to address issues concerning the units of adaptation in social evolution, leading to a deeper understanding of the adaptation of individual organisms. Finally, I sketch some directions Formal Darwinism to explore beyond the biological sciences, with a focus upon cosmology.     

Again,What the Philosophy of Biology is not

There are many things that philosophy of biology might be. But, given the existence of a professional philosophy of biology that is arguably a progressive research program and, as such, unrivaled, it makes sense to define philosophy of biology more narrowly than the totality of intersecting concerns biologists and philosophers (let alone other scholars) might have. The reasons for the success of the “new” philosophy of biology remain poorly understood. I reflect on what Dutch and Flemish, and, more generally, European philosophers of biology could do to improve the situation of their discipline locally, regionally, and internationally, paying particular attention to the lessons to be learned from the “Science Wars.” This paper grew out of my contribution to the symposium Philosophy of Biology in the Netherlands and Flanders organized by Thomas Reydon and Sabina Leonelli in Amsterdam in February 2004. It is a rather personal reaction to many of the opinions voiced in the quite heated atmosphere of the Symposium. My main concern is to convey an idea of what, according to me, is required to turn “our” philosophy of biology into a more successful enterprise than it currently is. This is motivated by a disconcerting discovery I made at the Symposium: Contrary to my expectations, a sensitivity for the sorts of things that make possible philosophy of biology of the best kind available today seems to be largely lacking in our part of the world. I wish to stress from the outset that although I will be quite polemical at times, this is always intended in the spirit of constructive dialogue.     

The Use and Abuse of Sir Karl Popper

Karl Popper has been one of the few philosophers of sciences who has influenced scientists. I evaluate Popper's influence on our understanding of evolutionary theory from his earliest publications to the present. Popper concluded that three sorts of statements in evolutionary biology are not genuine laws of nature. I take him to be right on this score. Popper's later distinction between evolutionary theory as a metaphysical research program and as a scientific theory led more than one scientist to misunderstand his position on evolutionary theory as a scientific theory. In his later work Popper also introduced what he took to be improvements of evolutionary theory. Thus far these improvements have had almost no influence on evolutionary biology. I conclude by examining the influence of Popper on the reception of cladistic analysis.     

Darwin's artificial selection as an experiment

Darwin used artificial selection (ASN) extensively and variedly in his theorizing. Darwin used ASN as an analogy to natural selection; he compared artificial to natural varieties, hereditary variation in nature to that in the breeding farm; and he also compared the overall effectiveness of the two processes. Most historians and philosophers of biology have argued that ASN worked as an analogical field in Darwin's theorizing. I will argue rather that this provides a limited and somewhat muddled view of Darwinian science. I say "limited" because I will show that Darwin also used ASN as a complex experimental field. And I say "muddled" because, if we concentrate on the analogical role exclusively, we conceive Darwinian science as rather disconnected from contemporary conceptions of "good science". I will argue that ASN should be conceived as a multifaceted experiment. As a traditional experiment, ASN established the efficacy of Darwin's preferred cause: natural selection. As a non-traditional experiment, ASN disclosed the nature of a crucial element in Darwin's evolutionary mechanics: the nature of hereditary variation. Finally, I will argue that the experiment conception should help us make sense of Darwin's comments regarding the "monstrous" nature of domestic breeds traditionally considered to be problematic.     

In search of evolutionary developmental mechanisms: the 30-year gap between 1944 and 1974

The approach I have elected in this retrospective of how I became a student of evo-devo is both biographical and historical, a case study along the lines of Waddington's The Evolution of an Evolutionist ('75), although in my case it is the Evolution of an Evo-devoist. What were the major events that brought me to developmental biology and from there to evo-devo? They were, of course, specific to my generation, to the state of knowledge at the time, and to my own particular circumstances. Although exposed to evolution and embryology as an undergraduate in the 1960s, my PhD and post-PhD research programme lay within developmental biology until the early 1970s. An important formative influence on my studies as an undergraduate was the work of Conrad Hal Waddington (1905-1975), whose writings made me aware of genetic assimilation and gave me an epigenetic approach to my developmental studies. The switch to evo-devo (and my discovery of the existence of the neural crest), I owe to an ASZ (now SICB) symposium held in 1973.     

De-extinction and the conception of species

Developments in genetic engineering may soon allow biologists to clone organisms from extinct species. The process, dubbed “de-extinction,” has been publicized as a means to bring extinct species back to life. For theorists and philosophers of biology, the process also suggests a thought experiment for the ongoing “species problem”: given a species concept, would a clone be classified in the extinct species? Previous analyses have answered this question in the context of specific de-extinction technologies or particular species concepts. The thought experiment is given more comprehensive treatment here. Given the products of three de-extinction technologies, twenty-two species concepts are “tested” to see which are consistent with the idea that species may be resurrected. The ensuing discussion considers whether or not de-extinction is a conceptually coherent research program and, if so, whether or not its development may contribute to a resolution of the species problem. Ultimately, theorists must face a choice: they may revise their commitments to species concepts (if those concepts are inconsistent with de-extinction) or they may recognize de-extinction as a means to make progress in the species problem.     

The golden age of biochemical research in photosynthesis

The perspectives and enthusiasms recorded in this review describe the events I witnessed and, in small ways, contributed to. Two great rewards emerged from my experiences – the pleasure of doing experiments and the great wealth of friendships with students and colleagues. As a graduate student, phenomena appeared at the bench before me which clarified the coupling of electron transport to ATP synthesis. My first PhD graduate student measured concentrations of pyridine nucleotides in chloroplasts and his results have been often confirmed and well used. All of the many graduate students who followed contributed to our understanding of photosynthesis. I have taken much pleasure from documenting the details of photosynthetic phosphorylation and electron transport in cyanobacteria. Studies of the `c' type cytochromes in these organisms continue to fascinate me. My experiences in government in its efforts to promote research are unusual, perhaps unique. A rare event outside the laboratory – a natural bloom of cyanobacteria – stimulated new thoughts and special opportunities for laboratory science. Photosynthesis seems magisterial in its shaping of our planet and its biology and in the details of its cleverness that were revealed in the time of my witness. This revised version was published online in June 2006 with corrections to the Cover Date.     

Do we need a ‘theory’ of development?

Edited by Alessandro Minelli and Thomas Pradeu, Towards a Theory of Development gathers essays by biologists and philosophers, which display a diversity of theoretical perspectives. The discussions not only cover the state of art, but broaden our vision of what development includes and provide pointers for future research. Interestingly, all contributors agree that explanations should not just be gene-centered, and virtually none use design and other engineering metaphors to articulate principles of cellular and organismal organization. I comment in particular on the issue of how to construe the notion of a ‘theory’ and whether developmental biology has or should aspire to have theories, which four of the contributions discuss in detail while taking opposing positions. Beyond construing a theory in terms of its empirical content (established knowledge about biological phenomena), my aim is to shift the focus toward the role that theories have for guiding future scientific theorizing and practice. Such a conception of ‘theory’ is particularly important in the context of development, because arriving at a theoretical framework that provides guidance for the discipline of developmental biology as a whole is more plausible than a unified representation of development across all taxa.     

Phylogenetic approaches for studying diversification

Estimating rates of speciation and extinction, and understanding how and why they vary over evolutionary time, geographical space and species groups, is a key to understanding how ecological and evolutionary processes generate biological diversity. Such inferences will increasingly benefit from phylogenetic approaches given the ever‐accelerating rates of genetic sequencing. In the last few years, models designed to understand diversification from phylogenetic data have advanced significantly. Here, I review these approaches and what they have revealed about diversification in the natural world. I focus on key distinctions between different models, and I clarify the conclusions that can be drawn from each model. I identify promising areas for future research. A major challenge ahead is to develop models that more explicitly take into account ecology, in particular the interaction of species with each other and with their environment. This will not only improve our understanding of diversification; it will also present a new perspective to the use of phylogenies in community ecology, the science of interaction networks and conservation biology, and might shift the current focus in ecology on equilibrium biodiversity theories to non‐equilibrium theories recognising the crucial role of history.     

Toward synthetic life: Biomimetic synthetic cell communication

Engineering synthetic minimal cells provide a controllable chassis for studying the biochemical principles of natural life, increasing our understanding of complex biological processes. Recently, synthetic cell engineering has enabled communication between both natural live cells and other synthetic cells.A system such as these enable studying interactions between populations of cells, both natural and artificial, and engineering small molecule cell communication protocols for a variety of basic research and practical applications. In this review, we summarize recent progress in engineering communication between synthetic and natural cells, and we speculate about the possible future directions of this work.     

合成生物学伦理、法律与社会问题探讨

合成生物学是以基因组学、系统生物学知识和分子生物学技术为基础,综合了科学与工程的一门新兴交叉学科。它使生命科学和生物技术研发进入了以人工设计、合成自然界中原本不曾出现的人造生命体系,以及对这些人工体系进行体内、体外优化,或利用这些人造生命体系研究自然生命规律为目标的新时代。然而,合成生物学研究在迅速发展、表现出巨大潜力和应用前景的同时,也引发了社会各界对相关社会、伦理、安全,以及知识产权等问题的重视与讨论。就世界各国针对合成生命对传统意义上生命概念的挑战、合成生物学产品存在的潜在风险危害、合成生物学研究的风险评估与监管等问题进行回顾综述和相关探讨。     

The emergence of shape: notions from the study of the Drosophila tracheal system

The generation of bodies and body parts with specific shapes and sizes has been a longstanding issue in biology. Morphogenesis in general and organogenesis in particular are complex events that involve global changes in cell populations in terms of their proliferation, migration, differentiation and shape. Recent studies have begun to address how these synchronized changes are controlled by the genes that specify cell fate and by the ability of cells to respond to extracellular cues. In particular, a notable shift in this research has occurred owing to the ability to address these issues in the context of the whole organism. For such studies, the Drosophila tracheal system has proven to be a particularly appropriate model. Here, my aim is to highlight some ideas that have arisen through our studies, and those from other groups, of Drosophila tracheal development. Rather than providing an objective review of the features of tracheal development, I intend to discuss some selected notions that I think are relevant to the question of shape generation.     

Five Classic Articles in Public Health

In this brief review, Dr. Jonathan Borak comments on five seminal papers that helped shape the fields of epidemiology and public health. These papers include Hill’s criteria for inferring causality; the first proof of the multistage theory of cancer; the first evidence that subclinical lead exposures can cause neurobehavioral impairment in children; a simple yet robust study that had a major influence on setting current air pollution policies; and a landmark review of the general public’s perception of risk in relation to actual public health hazard.Dr. Jonathan Borak is a Clinical Professor of Epidemiology and Public Health at the Yale School of Public Health, Clinical Professor of Internal Medicine at the Yale School of Medicine, and Director of the Yale Interdisciplinary Risk Assessment Forum. In this article, Dr. Borak provides his perspective on five publications that significantly influenced the study and practice of epidemiology and public health. This article is the first in a series that will identify and provide commentary on the top five seminal papers published in a field related to biology and medicine.A former student, a member of the Yale Journal of Biology and Medicine’s Editorial Board, reminded me of a comment I made in class. I had described a particular assigned reading as “one of those classic articles” that should be read by everyone studying public health. Okay, he challenged me, what other “classic articles” were on my list? And so began the following: my short list of five articles that represent “must reading” for all students in public health.First, note that I do not speak for public health in general, a field of great breadth of interest and activity, but only the narrower slice, including toxicology, risk assessment, and related interests. Also, I was principally concerned to identify articles that provide models of critical thinking, addressed issues of substantial public health importance, and served as stepping stones for subsequent research and the formulation of public health policy. I also wanted to include articles that were observational and opportunistic, i.e., based on real world observations and available data, not complex laboratory models.My five choices below include: 1) a landmark presentation of criteria for inferring causality from observational data (Hill 1965); 2) a thought experiment based on the re-analysis of publicly available cancer mortality data, which shaped the fields of cancer biology and risk assessment (Armitrage & Doll, 1954); 3) an early study of the effects of lead exposure in school children (Needleman, 1979); 4) a study of the impact of air pollution on children’s health, which was enabled by a fortuitous labor dispute that shuttered a polluting steel mill (Ransom & Pope, 1992); and, 5) a critical literature review of cognitive psychology research that shaped our understanding about how public health risks are perceived (Slovic, 1987).     

Advantages and clinical applications of natural killer cells in cancer immunotherapy

The past decade has witnessed a burgeoning of research and further insight into the biology and clinical applications of natural killer (NK) cells. Once thought to be simple innate cells important only as cytotoxic effector cells, our understanding of NK cells has grown to include memory-like responses, the guidance of adaptive responses, tissue repair, and a delicate paradigm for how NK cells become activated now termed “licensing” or “arming.” Although these cells were initially discovered and named for their spontaneous ability to kill tumor cells, manipulating NK cells in therapeutic settings has proved difficult and complex in part due to our emerging understanding of their biology. Therapies involving NK cells may either activate endogenous NK cells or involve transfers of exogenous cells by hematopoietic stem cell transplantation or adoptive cell therapy. Here, we review the basic biology of NK cells, highlighting characteristics which make NK cells particularly useful in cancer therapies. We also explore current treatment strategies that have been used for cancer as well as discuss potential future directions for the field.     

Twenty years of research on primordial germ cells.

Just twenty years ago I was preparing a research project centred on establishing methods for the isolation and culture of mouse primordial germ cells (PGCs). The project had been suggested to me by Anne McLaren and was to be developed at the Medical Research Council (MRC) "Mammalian Development Unit" in London under the direction of Anne herself. At that time I was a young postdoctoral researcher at the Institute of Histology and Embryology of the University of Rome "La Sapienza" and did not imagine that my decision to be involved in this project would signal a profound switch in my scientific life. From then on my research would mostly concentrate on primordial germ cell biology. I feel like saying that the modern history of mammalian primordial germ cells began twenty years ago at the MRC Mammalian Development Unit under Anne McLaren's impulse. It is not surprising that among the most active researchers in the last twenty years in studying mammalian primordial germ cells, three, namely Chris Wylie, Peter Donovan and myself, began their studies under Anne McLaren's guidance. Over the years, Anne's suggestions and encouragement were always precious for my studies and her presence marked my most important findings on PGC biology. She often invited me to present the results obtained in my laboratory to workshops and congresses. In the present article some of these results particularly influenced by Anne's teaching and suggestions will be briefly reviewed.     

What is life?

Background

Many traditional biological concepts continue to be debated by biologists, scientists and philosophers of science. The specific objective of this brief reflection is to offer an alternative vision to the definition of life taking as a starting point the traits common to all living beings.

Results and Conclusions

Thus, I define life as a process that takes place in highly organized organic structures and is characterized by being preprogrammed, interactive, adaptative and evolutionary. If life is the process, living beings are the system in which this process takes place. I also wonder whether viruses can be considered living things or not. Taking as a starting point my definition of life and, of course, on what others have thought about it, I am in favor of considering viruses as living beings. I base this conclusion on the fact that viruses satisfy all the vital characteristics common to all living things and on the role they have played in the evolution of species. Finally, I argue that if there were life elsewhere in the universe, it would be very similar to what we know on this planet because the laws of physics and the composition of matter are universal and because of the principle of the inexorability of life.

     

Adventures in vascular biology: a tale of two mediators

I would like to thank the Royal Society for inviting me to deliver the Croonian Lecture. In so doing, the Society is adding my name to a list of very distinguished scientists who, since 1738, have preceded me in this task. This is, indeed, a great honour.For most of my research career my main interest has been the understanding of the normal functioning of the blood vessel wall and the way this is affected in pathology. During this time, our knowledge of these subjects has grown to such an extent that many people now believe that the conquering of vascular disease is a real possibility in the foreseeable future.My lecture concerns the discovery of two substances, prostacyclin and nitric oxide. I would like to describe the moments of insight and some of the critical experiments that contributed significantly to the uncovering of their roles in vascular biology. The process was often adventurous, hence the title of this lecture. It is the excitement of the adventure that I would like to convey in the text that follows.     

Finding a niche

Although I always knew I wanted to be a scientist, I didn't know I would become a cell biologist. Events in life that you would never have predicted can greatly impact your career trajectory. I have learned to let those events take me in new directions. Following a desire to investigate an understudied area of cell biology, I have found a niche. In this area, my lab is poised to contribute significantly toward understanding the fundamental molecular mechanisms underlying polarized plant cell growth.