In this commentary of Koonin’s target paper, we defend an extended view of CRISPR-Cas immunity by arguing that CRISPR-Cas includes, but cannot be reduced to, defence against nonself. CRISPR-Cas systems can target endogenous elements and tolerate exogenous elements. We conclude that the vocabulary of “defence” and “nonself” might be misleading when describing CRISPR-Cas systems.

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)

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.

The Central Dogma of molecular biology, which holds that DNA makes protein and not the other way around, is as influential as it is controversial. Some believe the Dogma has outlived its usefulness, either because it fails to fully capture the ins-and-outs of protein synthesis (Griffiths and Stotz, 2013; Stotz, 2006), because it turns on a confused notion of information (Sarkar, 2004), or because it problematically assumes the unidirectional flow of information from DNA to protein (Gottlieb, 2001). This paper evaluates (...) an underexplored defense of the Dogma, which relies on the assumption that the Dogma and the Inheritance of Acquired Traits, a principle which dates as far back as Jean Baptiste-Lamarck, are incompatible principles (Smith, 1993; Judson, 1979; Dawkins, 1970; Cobb, 2017; Wilkins, 2002; Graur, 2018). By appealing to empirical evidence in molecular science, I argue that this apparent incompatibility is indeed merely apparent. I conclude by briefly demonstrating how these considerations bear on the topic of conceptual pluralism in the philosophy of science (Stencel and Proszewska, 2018; Lu and Bourrat, 2018). (shrink)

Transhumanism is a movement that advocates for the enhancement of human capabilities through the use of advanced technologies such as genetic enhancement. This article explores the definition, history, and development of transhumanism. Then, it compares the stance on genetic enhancement from the perspectives of bio-conservatism, bio-liberalism, and transhumanism. This article posits that transhuman evolution has twofold implications, allowing for the integration of transhumanist research and evolutionary biology. First, it offers a compelling scientific framework for understanding genetic enhancement, avoiding technological progressivism, (...) and incorporating concepts of evolutionary biology. Second, it represents a new evolutionary paradigm distinct from traditional Lamarckism and Darwinism. It marks the third synthesis of evolutionary biology, offering fresh perspectives on established concepts such as artificial selection and gene-culture co-evolution. In recent decades, human enhancement has captivated not only evolutionary biologists, neurobiologists, psychologists, and philosophers, but also those in fields such as cybernetics and artificial intelligence. In addition to genetic enhancement, other human enhancement technologies, including brain-computer interfaces and brain uploading, are currently under development, which the paradigm of transhuman evolution can better integrate into its framework. (shrink)

Exploration of immune systems in prokaryotes, such as restriction‐modification or CRISPR‐Cas, shows that both innate and adaptive systems possess programmed cell death (PCD) potential. The key outstanding question is how the immune systems sense and “predict” infection outcomes to “decide” whether to fight the pathogen or induce PCD. There is a striking parallel between this life‐or‐death decision faced by the cell and the decision by temperate viruses to protect or kill their hosts, epitomized by the lysis‐lysogeny switch of bacteriophage Lambda. (...) Immune systems and temperate phages sense the same molecular inputs, primarily, DNA damage, that determine whether the cell lives or dies. Because temperate (pro)phages are themselves components of prokaryotic genomes, their shared “interests” with the hosts result in coregulation of the lysis‐lysogeny switch and immune systems that jointly provide the cell with the decision machinery to probe and predict infection outcomes, answering the life‐or‐death question. (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)

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)

In the postgenomic era, interactions between organism and environment are central in disciplines such as epigenetics, medical physiology, and immunology. Particularly in the more "applied" medical fields, an emphasis lies on interactions of the organism with other organisms, that is, other living things. There is, however, a growing amount of research investigating the impact of abiotic triggers on the immune system. While the distinction between biota and abiota features heavily in other contexts, its status is not explicit within immunology. Do (...) immunologists distinguish living from nonliving triggers? In this article, I will carve out whether and in which ways the biotic/abiotic distinction operates in immunology. I will look into responses to biotic and abiotic stressors in plant and invertebrate model species and ask how and why they are conceptually separated. I will trace the reasons by investigating the disciplinary situatedness of immune phenomena and the import of vertebrate immunology when conceptualizing immune responses in other model organisms. I will then investigate how the convergence of biotic and abiotic stress responses in plants and invertebrates adds to the recent philosophical programs advocating an ecological perspective on immune systems. (shrink)

In recent years, immune systems have sparked considerable interest within the philosophy of science. One issue that has received increased attention is whether other phyla besides vertebrates display an adaptive immune system. Particularly the discovery of CRISPR-Cas9-based systems has triggered a discussion about how to classify adaptive immune systems. One question that has not been addressed yet is the transgenerational aspect of the CRISPR-Cas9-based response. If immunity is acquired and inherited, how to distinguish evolutionary from immunological adaptation? To shed light (...) on this issue and obtain conceptual clarity, I will investigate the inheritance of small RNA responses to pathogens in the nematode C. elegans as a further potential instantiation of a transgenerational adaptive immune system. I will explore how to make sense of systems that lie at the crossroads between genetic, immunological, and evolutionary spheres and explore the consequences of a transgenerational perspective on immune systems for immunology and its philosophy. (shrink)

In this commentary of Koonin’s target paper, we defend an extended view of CRISPR-Cas immunity by arguing that CRISPR-Cas includes, but cannot be reduced to, defence against nonself. CRISPR-Cas systems can target endogenous elements and tolerate exogenous elements. We conclude that the vocabulary of “defence” and “nonself” might be misleading when describing CRISPR-Cas systems.

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)