The individuality of mice

Mutant mice simulating human CNS disorders are used as models for therapeutic drug development. Drug evaluation requires a coherent correlation between behavioral phenotype and drug status. Variations in behavioral responses could mask such correlations, a problem highlighted by the three-site studies of Crabbe et al. (1999) and Wahlsten et al. (2003a). Factors contributing to variation are considered, focusing on differences between individual animals. Genetic differences due to minisatellite variation suggest that each mouse is genetically distinct. Effects during gestation, including maternal stress, influence later life behavior; while endocrine exchanges between fetus and parent, and between male and female fetuses dependent on intrauterine position, also contribute. Pre and perinatal nutrition and maternal attention also play a role. In adults, endocrine cyclicity in females is a recognized source of behavioral diversity. Notably, there is increasing recognition that groups of wild and laboratory mice have complex social structures, illustrated through consideration of Crowcroft (1966). Dominance status can markedly modify behavior in test paradigms addressing anxiety, locomotion and aggressiveness, to an extent comparable to mutation or drug status. Understanding how such effects amplify the behavioral spectrum displayed by otherwise identical animals will improve testing.     

The problem of individuality in taxonomy

The ideas of wholeness of superorganism units consist of three constituents: 1) emergeness of properties of the whole; 2) structureness; 3) separability of the whole. Emergeness is a character of both integrated and complex units. Integrated units in strict sense are those that consist of functionally different parts. Species but not super-specific taxa are integrated units. The ideas of unity are based on formula "unity is an aggregation of shape and matter". In taxonomy the idea of archaetype can be used as a shape. Superspecific taxa but not species are recognized as unitary units in taxonomy. Unitary but not integrated units can be considered as individuals.     

The many faces of biological individuality

Biological individuality is a major topic of discussion in biology and philosophy of biology. Recently, several objections have been raised against traditional accounts of biological individuality, including the objections of monism (the tendency to focus on a single individuality criterion and/or a single biological field), theory-centrism (the tendency to discuss only theory-based individuation), ahistoricity (the tendency to neglect what biologists of the past and historians of biology have said about biological individuality), disciplinary isolationism (the tendency to isolate biological individuality from other scientific and philosophical domains that have investigated individuality), and the multiplication of conceptual uncertainties (the lack of a precise definition of “biological individual” and related terms). In this introduction, I will examine the current philosophical landscape about biological individuality, and show how the contributions gathered in this special issue address these five objections. Overall, the aim of this issue is to offer a more diverse, unifying, and scientifically informed conception of what a biological individual is.     

The individuality of artifacts and organisms

Is there any genuine difference between organisms and artifacts? Where and how would we identify such a difference? This paper argues the difference involves the character of their individuality. Unlike an organism, an artifact's individuality is (for the most part) determined by the function that the designer selected in the artifact's production rather than the functional interdependence of its parts. In both cases, individuality is a historical property and in both cases the parts may be functionally interdependent to some extent. However, for artifacts, this interdependence is not what makes it the individual that it is. Instead, the interdependence of its parts is in the service of the functions for which the spear was designed. No such additional purpose or function exists for an organism.     

Post-thymic maturation: young T cells assert their individuality

T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting that the youngest peripheral T cells in both mice and humans comprise a distinct population from their more mature, yet still naive, counterparts. These cells, termed recent thymic emigrants (RTEs), undergo a process of post-thymic maturation that can be monitored at the levels of cell phenotype and immune function. Understanding this final maturation step in the process of generating useful and safe T cells is of clinical relevance, given that RTEs are over-represented in neonates and in adults recovering from lymphopenia. Post-thymic maturation may function to ensure T cell fitness and self tolerance.     

The world of stem cells

Since its beginning, at the turn of the 19th century, biology has been mostly--if not exclusively--analytical. Reductionism has progressively unveiled a series of structures buried into one another like Russian dolls. The study of the genome, the deepest structure of organisms, represents the triumph of reductionism. With the deciphering of the genome and the birth of what is called the 'proteome'--i.e. the study of the proteins and of their interactions--, a new stage appears. To the disorganisation that characterised two centuries of biology, a phase of reconstruction of living organisms is substituted. This is concerned first with interactions of proteins and of cells. In addition, one of the most remarkable tools for this latter research has been provided by embryonic stem cells.     

The glycans of stem cells

Glycans cover all cellular surfaces and, not surprisingly, are involved in many facets of stem cell biology and technology. For instance, coaxing stem cells to either proliferate or differentiate into the specific cell types needed for transplantation requires intricate glycan-dependent modulation of signalling molecules such as FGF-2, Wnt, and Notch. Moreover, owing to their prominent cell-surface localization and lineage-specific signatures, glycan epitopes such as the stage-specific embryonic antigens (Lewis X/SSEA-1, SSEA3-4) and tumor-rejection antigens (TRA1-60, 1-81) are ideally suited for identifying and isolating specific cell types from heterogeneous populations. Finally, the non-human sialic acid Neu5Gc has been detected on the surface of human embryonic stem cells because of metabolic incorporation from animal products used for their culture. Transplantation of Neu5Gc-contaminated cells poses immunological risks due to the presence, in humans, of circulating antibodies recognizing this glycan epitope.     

The role of vocal individuality in conservation

Identifying the individuals within a population can generate information on life history parameters, generate input data for conservation models, and highlight behavioural traits that may affect management decisions and error or bias within census methods. Individual animals can be discriminated by features of their vocalisations. This vocal individuality can be utilised as an alternative marking technique in situations where the marks are difficult to detect or animals are sensitive to disturbance. Vocal individuality can also be used in cases were the capture and handling of an animal is either logistically or ethically problematic. Many studies have suggested that vocal individuality can be used to count and monitor populations over time; however, few have explicitly tested the method in this role. In this review we discuss methods for extracting individuality information from vocalisations and techniques for using this to count and monitor populations over time. We present case studies in birds where vocal individuality has been applied to conservation and we discuss its role in mammals.     

The culture of neural stem cells

A stem cell has three important features. Firstly, the ability of self‐renewal: making identical copies of itself. Secondly, multipotency, generating all the major cell lineages of the host tissue (in the case of embryonic stem cells—pluripotency). Thirdly, the ability to generate/regenerate tissues. Thus, the study of stem cells will help unravel the complexity of tissue development and organisation, and will also have important clinical applications. Neural stem cells (NSCs) are present during embryonic development and in certain regions of the adult central nervous system (CNS). Mobilizing adult NSCs to promote repair of injured or diseased CNS is a promising approach. Since NSCs may give rise to brain tumor, they represent in vitro models for anti‐cancer drug screening. To facilitate the use of NSCs in clinical scenarios, we need to explore the biology of these cells in greater details. One clear goal is to be able to definitively identify and purify NSCs. The neurosphere‐forming assay is robust and reflects the behavior of NSCs. Clonal analysis where single cells give rise to neurospheres need to be used to follow the self‐renewal and multipotency characteristics of NSCs. Neurosphere formation in combination with other markers of NSC behavior such as active Notch signaling represents the state of the art to follow these cells. Many issues connected with NSC biology need to be explored to provide a platform for clinical applications. Important future directions that are highlighted in this review are; identification of markers for NSCs, the use of NSCs in high‐throughput screens and the modelling of the central nervous development. There is no doubt that the study of NSCs is crucial if we are to tackle the diseases of the CNS such as Parkinson's and Alzheimer's. J. Cell. Biochem. 106: 1–6, 2009. © 2008 Wiley‐Liss, Inc.     

The individuality thesis (3 ways)

I spell out and update the individuality thesis, that species are individuals, and not classes, sets, or kinds. I offer three complementary presentations of this thesis. First, as a way of resolving an inconsistent triad about natural kinds; second, as a phylogenetic systematics theoretical perspective; and, finally, as a novel recursive account of an evolved character (individuality). These approaches do different sorts of work, serving different interests. Presenting them together produces a taxonomy of the debates over the thesis, and isolates ways it has been (and may continue to be) productive. This goes to the larger point of this paper: a defense of the individuality thesis in terms of its utility, and an update of it in light of recent theoretical developments and empirical work in biology.     

The therapeutic potential of stem cells

In recent years, there has been an explosion of interest in stem cells, not just within the scientific and medical communities but also among politicians, religious groups and ethicists. Here, we summarize the different types of stem cells that have been described: their origins in embryonic and adult tissues and their differentiation potential in vivo and in culture. We review some current clinical applications of stem cells, highlighting the problems encountered when going from proof-of-principle in the laboratory to widespread clinical practice. While some of the key genetic and epigenetic factors that determine stem cell properties have been identified, there is still much to be learned about how these factors interact. There is a growing realization of the importance of environmental factors in regulating stem cell behaviour and this is being explored by imaging stem cells in vivo and recreating artificial niches in vitro. New therapies, based on stem cell transplantation or endogenous stem cells, are emerging areas, as is drug discovery based on patient-specific pluripotent cells and cancer stem cells. What makes stem cell research so exciting is its tremendous potential to benefit human health and the opportunities for interdisciplinary research that it presents.     

The clinical potential of stem cells

Stem cells are defined by their capacity for self-renewal and multilineage differentiation, making them uniquely situated to treat a broad spectrum of human diseases. For example, because hematopoietic stem cells can reconstitute the entire blood system, bone marrow transplantation has long been used in the clinic to treat various diseases. Similarly, the transplantation of other tissue-specific stem cells, such as stem cells isolated from epithelial and neural tissues, can treat mouse disease models and human patients in which epithelial and neural cells are damaged. An alternative to tissue-specific stem cell therapy takes advantage of embryonic stem cells, which are capable of differentiating into any tissue type. Furthermore, nuclear transfer, the transfer of a post-mitotic somatic cell nucleus into an enucleated oocyte, creates a limitless source of autologous cells that, when combined with gene therapy, can serve as a powerful therapeutic tool.