Eugene V. Koonin argues that fundamental research of CRISPR-Cas mechanisms has illuminated “fundamental principles of genome manipulation.” Koonin's discussion provides important philosophical insights for how we should understand the significance of CRISPR-Cas systems. Yet the analysis he provides is only part of a larger story. There is also a human element to the CRISPR-Cas story that concerns its development as a technology. Accounting for this part of CRISPR's history reveals that the story Koonin provides requires greater nuance. I'll show how (...) CRISPR-Cas technologies are not “natural” genome editing systems, but artifacts of human ingenuity. Furthermore, I'll argue that the story of CRISPR-Cas is not “primarily about research into fundamental biological mechanisms”, but is instead about the intertwining of applied and fundamental research programs. (shrink)

Koonin argues that CRISPR-Cas systems present the best-known case in point for Lamarckian evolution because they satisfy his proposed criteria for the specific inheritance of acquired adaptive characteristics. We see two interrelated issues with Koonin’s characterization of CRISPR-Cas systems as Lamarckian. First, at times he appears to confuse an account of the CRISPR-Cas system with an account of the mechanism it employs. We argue there is no evidence for the CRISPR-Cas system being “Lamarckian” in any sense. Second, it is unclear (...) whether the mechanism is more “Lamarckian” than many other forms of genetic change already well-characterized in Darwinian terms. We present three conceptually distinct senses in which the mechanism of IAC may be considered Lamarckian and argue that only the strongest sense of goal-directed IAC would be difficult to accommodate in a Darwinian account. As the CRISPR-Cas mechanism does not qualify as “Lamarckian” in this strong sense, we argue there is no conceptual value in calling it “Lamarckian”. Finally, we suggest that CRISPR-Cas systems do hold the potential for genuinely non-Darwinian, directed evolution in a way that Koonin did not discuss, involving their potential use as a human gene-editing tool. (shrink)

Koonin, in an article in this issue, claims that CRISPR–Cas systems are mechanisms for the inheritance of acquired adaptive characteristics, and that the operation of such systems comprises a “Lamarckian mode of evolution.” We argue that viewing the CRISPR–Cas mechanism as facilitating a form of “directed mutation” more accurately represents how the system behaves and the history of neoDarwinian thinking, and is to be preferred.

In his insightful review, Eugene V. Koonin discusses various aspects of CRISPR-Cas systems with a strong focus on their qualities as "adaptive immune systems". The CRISPR-Cas system is most famous for its application as a gene-editing tool. Koonin provides a deeper insight into its biological function in bacteria, which is to immunize the cell against parasite DNA. I shall comment on one issue discussed in the text, in two steps. First, I shall elaborate on CRISPR-Cas systems and their supposed Lamarckian (...) character. Criteria for calling biological phenomena genuinely Lamarckian will be narrowed down and then applied to the CRISPR-Cas system, considering interference-driven spacer acquisition as an instantiation of a truly Lamarckian paradigm. Second, I shall consider whether Lamarckian and "canonical" instances of inheritance are a case of theoretical pluralism, being two non-reducible, yet interconnected paradigms. (shrink)

The main objective of immunology is to establish why and when an immune response occurs, that is, to determine a criterion of immunogenicity. According to the consensus view, the proper criterion of immunogenicity lies in the discrimination between self and nonself. Here we challenge this consensus by suggesting a simpler and more comprehensive criterion, the criterion of continuity. Moreover, we show that this criterion may be considered as an interpretation of the immune 'self'. We conclude that immunologists can continue to (...) speak of the self, provided that they admit that the self/nonself discrimination is not an adequate criterion of immunogenicity. (shrink)

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point (...) for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (shrink)

In his target article, Koonin discusses the insights into the evolution of bacterial genomes provided by the CRISPR-Cas system. This evolved defense system is based on intrinsic processes of genome engineering which, as he argues, enable Lamarckian inheritance. In this commentary I discuss some historical and conceptual issues that pertain to Koonin’s analysis of this aspect of the CRISPR-Cas system, extending and qualifying his discussion.

This is one of the first books in a new series that will publish the very best work in the philosophy of biology. The series will be non-sectarian in character, will extend across the broadest range of topics, and will be genuinely interdisciplinary. The Immune Self is a critical study of immunology from its origins at the end of the nineteenth century to its contemporary formulation. The book offers the first extended philosophical critique of immunology, in which the function of (...) the term 'self' that underlies the structure of current immune theory is analysed. However, this analysis is carefully integrated into a broad survey of the major scientific developments in immunology, a discussion of their historical context, and a review of the conceptual arguments that have moulded this sophisticated modern science. (shrink)

In Darwinism's Struggle for Survival Jean Gayon offers a philosophical interpretation of the history of theoretical Darwinism. He begins by examining the different forms taken by the hypothesis of natural selection in the nineteenth century and the major difficulties which it encountered, particularly with regard to its compatibility with the theory of heredity. He then shows how these difficulties were overcome during the seventy years which followed the publication of Darwin's Origin of Species, and he concludes by analysing the major (...) features of the genetic theory of natural selection, as it developed from 1920 to 1960. This rich and wide-ranging study will appeal to philosophers and historians of science and to evolutionary biologists. (shrink)

This is one of the first books in a new series that will publish the very best work in the philosophy of biology. The series will be non-sectarian in character, will extend across the broadest range of topics, and will be genuinely interdisciplinary. The Immune Self is a critical study of immunology from its origins at the end of the nineteenth century to its contemporary formulation. The book offers the first extended philosophical critique of immunology, in which the function of (...) the term 'self' that underlies the structure of current immune theory is analysed. However, this analysis is carefully integrated into a broad survey of the major scientific developments in immunology, a discussion of their historical context, and a review of the conceptual arguments that have moulded this sophisticated modern science. (shrink)

The Limits of the Self, will be essential reading for anyone interested in the definition of biological individuality and the understanding of the immune system.

In 1809--the year of Charles Darwin's birth--Jean-Baptiste Lamarck published Philosophie zoologique, the first comprehensive and systematic theory of biological evolution. The Lamarckian approach emphasizes the generation of developmental variations; Darwinism stresses selection. Lamarck's ideas were eventually eclipsed by Darwinian concepts, especially after the emergence of the Modern Synthesis in the twentieth century. The different approaches--which can be seen as complementary rather than mutually exclusive--have important implications for the kinds of questions biologists ask and for the type of research they conduct. (...) Lamarckism has been evolving--or, in Lamarckian terminology, transforming--since Philosophie zoologique's description of biological processes mediated by "subtle fluids." Essays in this book focus on new developments in biology that make Lamarck's ideas relevant not only to modern empirical and theoretical research but also to problems in the philosophy of biology. Contributors discuss the historical transformations of Lamarckism from the 1820s to the 1940s, and the different understandings of Lamarck and Lamarckism; the Modern Synthesis and its emphasis on Mendelian genetics; theoretical and experimental research on such "Lamarckian" topics as plasticity, soft (epigenetic) inheritance, and individuality; and the importance of a developmental approach to evolution in the philosophy of biology. The book shows the advantages of a "Lamarckian" perspective on evolution. Indeed, the development-oriented approach it presents is becoming central to current evolutionary studies--as can be seen in the burgeoning field of Evo-Devo. Transformations of Lamarckism makes a unique contribution to this research. (shrink)