Parasites and molecular biology

The Editors wish to thank Prof. Thomas Seebeck for coordinating this multi-author review     

Directed evolution of enzymes for biocatalysis and the life sciences

Engineering the specificity and properties of enzymes and proteins within rapid time frames has become feasible with the advent of directed evolution. In the absence of detailed structural and mechanistic information, new functions can be engineered by introducing and recombining mutations, followed by subsequent testing of each variant for the desired new function. A range of methods are available for mutagenesis, and these can be used to introduce mutations at single sites, targeted regions within a gene or randomly throughout the entire gene. In addition, a number of different methods are available to allow recombination of point mutations or blocks of sequence space with little or no homology. Currently, enzyme engineers are still learning which combinations of selection methods and techniques for mutagenesis and DNA recombination are most efficient. Moreover, deciding where to introduce mutations or where to allow recombination is actively being investigated by combining experimental and computational methods. These techniques are already being successfully used for the creation of novel proteins for biocatalysis and the life sciences.Received 8 June 2004; received after revision 22 July 2004; accepted 2 August 2004     

Mass spectrometry-based proteomics in the life sciences

Over the last 20 years, mass spectrometrybased proteomics has become an indispensable tool in the cellular and molecular life sciences. This has been enabled by the soft ionisation techniques of electrospray and matrix-assisted laser desorption-ionisation, which allow the gentle ionisation and vaporisation of large, thermally labile biomolecules. Innovative instrumentation designs and biochemical strategies have brought success in the large-scale identification and quantification of proteins, as well as the characterisation of their complexes and post-translational modifications. This review describes the instrumentation used for proteomics research. It presents an overview of the current applications of mass spectrometry-based proteomics to the cellular and molecular life sciences, and discusses challenges that exist for research in the future.Received 7 January 2005; accepted 27 January 2005     

Kant and the scope of analogy in the life sciences

In the present paper I investigate the role that analogy plays in eighteenth-century biology and in Kant's philosophy of biology. I will argue that according to Kant, biology, as it was practiced in the eighteenth century, is fundamentally based on analogical reflection. However, precisely because biology is based on analogical reflection, biology cannot be a proper science. I provide two arguments for this interpretation. First, I argue that although analogical reflection is, according to Kant, necessary to comprehend the nature of organisms, it is also necessarily insufficient to fully comprehend the nature of organisms. The upshot of this argument is that for Kant our understanding of organisms is necessarily limited. Second, I argue that Kant did not take biology to be a proper science because biology was based on analogical arguments. I show that Kant stemmed from a philosophical tradition that did not assign analogical arguments an important justificatory role in natural science. Analogy, according to this conception, does not provide us with apodictically certain cognition. Hence, sciences based on analogical arguments cannot constitute proper sciences.     

The algorithmic turn in conservation biology: Characterizing progress in ethically-driven sciences

As a discipline distinct from ecology, conservation biology emerged in the 1980s as a rigorous science focused on protecting biodiversity. Two algorithmic breakthroughs in information processing made this possible: place-prioritization algorithms and geographical information systems. They provided defensible, data-driven methods for designing reserves to conserve biodiversity that obviated the need for largely intuitive and highly problematic appeals to ecological theory at the time. But the scientific basis of these achievements and whether they constitute genuine scientific progress has been criticized. We counter by pointing out important inaccuracies about the science and rejecting the apparent theory-first focus. More broadly, the case study reveals significant limitations of the predominant epistemic-semantic conceptions of scientific progress and the considerable merits of pragmatic, practically-oriented accounts.     

Adipokinetic hormones: cell and molecular biology

Adipokinetic hormones AKH I (pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH₂) and AKH II (pGlu-Leu-Asn-Phe-Ser-Trp-Gly-Thr-NH₂) are synthesized by neurosecretory cells (NSC) of the corpora cardiaca (CC) in the locust,Schistocerca gregaria. These NSC constitute a homogeneous peptide factory as each cell synthesizes both AKH I and AKH II. This homogeneity makes the CC an excellent system in which to study aspects of neuropeptide biosynthesis. This report summarizes recent findings on AKH inactivation and metabolism, as well as on AKH prohormone processing and biosynthesis.     

Kant on anatomy and the status of the life sciences

This paper contributes to recent interest in Kant's engagement with the life sciences by focusing on one corner of those sciences that has received comparatively little attention: physical and comparative anatomy. By attending to remarks spread across Kant's writings, we gain some insight into Kant's understanding of the disciplinary limitations but also the methodological sophistication of the study of anatomy and physiology. Insofar as Kant highlights anatomy as a paradigmatic science guided by the principle of teleology in the Critique of the Power of Judgment, a more careful study of Kant's discussions of anatomy promises to illuminate some of the obscurities of that text and of his understanding of the life sciences more generally. In the end, it is argued, Kant's ambivalence with regard to anatomy gives way to a pessimistic conclusion about the possibility that anatomy, natural history, and, by extension, the life sciences more generally might one day become true natural sciences.     

Adipokinetic hormones: cell and molecular biology.

Adipokinetic hormones AKH I (pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2) and AKH II (pGlu-Leu-Asn-Phe-Ser-Trp-Gly-Thr-NH2) are synthesized by neurosecretory cells (NSC) of the corpora cardiaca (CC) in the locust, Schistocerca gregaria. These NSC constitute a homogeneous 'peptide factory' as each cell synthesizes both AKH I and AKH II. This homogeneity makes the CC an excellent system in which to study aspects of neuropeptide biosynthesis. This report summarizes recent findings on AKH inactivation and metabolism, as well as on AKH prohormone processing and biosynthesis.     

The protein meta-structure: a novel concept for chemical and molecular biology

The ultimate goal of bioinformatics or computational chemical biology is the sequence-based prediction of protein functionality. However, due to the degeneracy of the primary sequence code there is no unambiguous relationship. The degeneracy can be partly lifted by going to higher levels of abstraction and, for example, incorporating 3D structural information. However, sometimes even at this conceptual level functional ambiguities often remain. Here a novel conceptual framework is described (the protein meta-structure). At this level of abstraction, the protein structure is viewed as an intricate network of interacting residues. This novel conception offers unique possibilities for chemical (molecular) biology, structural genomics and drug discovery. In this review some prototypical applications will be presented that serve to illustrate the potential of the methodology.     

Snake venom components and their applications in biomedicine

Snake envenomation is a socio-medical problem of considerable magnitude. About 2.5 million people are bitten by snakes annually, more than 100,000 fatally. However, although bites can be deadly, snake venom is a natural biological resource that contains several components of potential therapeutic value. Venom has been used in the treatment of a variety of pathophysiological conditions in Ayurveda, homeopathy and folk medicine. With the advent of biotechnology, the efficacy of such treatments has been substantiated by purifying components of venom and delineating their therapeutic properties. This review will focus on certain snake venom components and their applications in health and disease. Received 6 July 2006; received after revision 14 August 2006; accepted 28 September 2006     

Kant and the nature of matter: Mechanics,chemistry, and the life sciences

Kant believed that the ultimate processes that regulate the behavior of material bodies can be characterized exclusively in terms of mechanics. In 1790, turning his attention to the life sciences, he raised a potential problem for his mechanically-based account, namely that many of the operations described in the life sciences seemed to operate teleologically. He argued that the life sciences do indeed require us to think in teleological terms, but that this is a fact about us, not about the processes themselves. Nevertheless, even were we to concede his account of the life sciences, this would not secure the credentials of mechanics as a general theory of matter. Hardly any material properties studied in the second half of the eighteenth century were, or could have been, conceived in mechanical terms. Kant's concern with teleology is tangential to the problems facing a general matter theory grounded in mechanics, for the most pressing issues have nothing to do with teleology. They derive rather from a lack of any connection between mechanical forces and material properties. This is evident in chemistry, which Kant dismisses as being unscientific on the grounds that it cannot be formulated in mechanical terms.     

100 years of radiobiology: Implications for biomedicine and future perspectives

The development of radiobiology from the very early detection of the biological action of X-rays to the knowledge of today is described in sections on radiation chemistry and biochemistry, mutation and cancer induction, and embryonic damage, as well as the dependence of radiation response on radiation quality and temporal dose distribution (repair) and the interaction with other factors. For medicine radiobiology serves as a basis for radiotherapy and radiological protection. The effect of very low doses, and their possible biopositive effect (hormesis and adaptive response), is also discussed, as are the health hazard of radon, health risks after the Chernobyl accident, and space radiobiology. The radiobiology of the future will be concerned with biomolecular and genetic implications, problems of damage and repair, and connected problems like hormesis.     

Analogical reflection as a source for the science of life: Kant and the possibility of the biological sciences

In contrast to the previously widespread view that Kant's work was largely in dialogue with the physical sciences, recent scholarship has highlighted Kant's interest in and contributions to the life sciences. Scholars are now investigating the extent to which Kant appealed to and incorporated insights from the life sciences and considering the ways he may have contributed to a new conception of living beings. The scholarship remains, however, divided in its interest: historians of science are concerned with the content of Kant's claims, and the ways in which they may or may not have contributed to the emerging science of life, while historians of philosophy focus on the systematic justifications for Kant's claims, e.g., the methodological and theoretical underpinnings of Kant's statement that living beings are mechanically inexplicable. My aim in this paper is to bring together these two strands of scholarship into dialogue by showing how Kant's methodological concerns (specifically, his notion of reflective judgment) contributed to his conception of living beings and to the ontological concern with life as a distinctive object of study. I argue that although Kant's explicit statement was that biology could not be a science, his implicit and more fundamental claim was that the study of living beings necessitates a distinctive mode of thought, a mode that is essentially analogical. I consider the implications of this view, and argue that it is by developing a new methodology for grasping organized beings that Kant makes his most important contribution to the new science of life.