Modern Synthesis Research Articles

Radical Retrosynthesis.

In The Logic of Chemical Synthesis, E. J. Corey stated that the key to retrosynthetic analysis was a "wise choice of appropriate simplifying transforms" ( Corey , E. J. ; Cheng , X.-M. The Logic of Chemical Synthesis ; John Wiley : New York , 1989 ). Through the lens of "ideality", chemists can identify opportunities that can lead to more practical, scalable, and sustainable synthesis. The percent ideality of a synthesis is defined as [(no. of construction rxns) + (no. of strategic redox rxns)]/(total no. of steps) × 100. A direct consequence of designing "wise" or "ideal" plans is that new transformations often need invention. For example, if functional group interconversions are to be avoided, one is faced with the prospect of directly functionalizing C-H bonds ( Gutekunst , W. R. ; Baran , P. S. Chem. Soc. Rev. 2011 , 40 , 1976 ; Brückl , T. ; et al. Acc. Chem. Res. 2012 , 45 , 826 ). If protecting groups are minimized, methods testing the limits of chemoselectivity require invention ( Baran , P. S. ; et al. Nature 2007 , 446 , 404 ; Young , I. S. ; Baran , P. S. Nat. Chem. 2009 , 1 , 193 ). Finally, if extraneous redox manipulations are to be eliminated, methods directly generating key skeletal bonds result ( Burns , N. Z. ; et al. Angew. Chem., Int. Ed. 2009 , 48 , 2854 ). Such analyses applied to total synthesis have seen an explosion of interest in recent years. Thus, it is the interplay of aspirational strategic demands with the limits of available methods that can influence and inspire ingenuity. E. J. Corey's sage advice holds true when endeavoring in complex molecule synthesis, but together with the tenets of the "ideal" synthesis, avoiding concession steps leads to the most strategically and tactically optimal route ( Hendrickson , J. B. J. Am. Chem. Soc. 1975 , 97 , 5784 ; Gaich , T. ; Baran , P. S. J. Org. Chem. 2010 , 75 , 4657 ). Polar disconnections are intuitive and underlie much of retrosynthetic logic. Undergraduates exposed to multistep synthesis are often taught to assemble organic molecules through the combination of positively and negatively charged synthons because, after all, opposites attract. Indeed, the most employed two-electron C-C bond forming reactions today are those based upon either classical cross-coupling reactions (e.g., Suzuki, Negishi, or Heck) or polar additions (aldol, Michael, or Grignard). These reactions are the mainstay of modern synthesis and have revolutionized the way molecules are constructed due to their robust and predictable nature. In contrast, radical chemistry is sparsely covered beyond the basic principles of radical chain processes (i.e., radical halogenation). The historical perception of radicals as somewhat uncontrollable species does not help the situation. As a result, synthetic chemists are not prone to make radical-based strategic bond disconnections during first-pass retrosynthetic analyses. Recent interest in the use of one-electron radical cross-coupling (RCC) methods has been fueled by the realization of their uniquely chemoselective profiles and the opportunities they uncover for dramatically simplifying synthesis. In general, such couplings can proceed by relying on the innate preferences of a substrate (innate RCC) or through interception with a mediator (usually a transition metal) to achieve programmed RCC. This Account presents a series of case studies illustrating the inherent strategic and tactical advantages of employing both types of radical-based cross-couplings in a variety of disparate settings. Thematically, it is clear that one-electron disconnections, while not considered to be intuitive, can serve to enable syntheses that are more direct and feature a minimal use of protecting group chemistry, functional group interconversions, and nonstrategic redox fluctuations.

Revamping the Metaphysics of Ethnobiological Classification

Ethnobiology has a long tradition of metaphysical debates about the “naturalness,” “objectivity,” “reality,” and “universality” of classifications. The work of Brent Berlin has been especially influential in developing a “convergence metaphysics” that explains cross-cultural similarities of knowledge systems through shared recognition of objective discontinuities in nature. Despite its influence on the development of the field, convergence metaphysics has largely fallen out of favor as contemporary ethnobiologists tend to emphasize the locality and diversity of classificatory practices. The aim of this article is twofold. First, I provide a historical account of the rise and fall of convergence metaphysics in ethnobiology. I show how convergence metaphysics emerged as an innovative theoretical program in the wake of the “cognitive revolution” and the “modern evolutionary synthesis” but failed to incorporate both theoretical insights and political concerns that gained prominence in the 1980s and 1990s. Second, I develop a positive proposal of how to engage with metaphysical issues in ethnobiology. By integrating traditional research on convergence of classifications with more nuanced accounts of distinctly local categories, a revamped metaphysics of ethnobiological classification can make substantial contributions to debates about ontological difference in anthropology and about the relation between applied and theoretical ethnobiology.

Assimiliating an Associative Trait: from Eco-Physiology to Epigenetics

The possible evolutionary significance of epigenetic memory and codes is a key problem for extended evolutionary synthesis and biosemiotics. In this paper, some less known original works are reviewed which highlight theoretical parallels between current evolutionary epigenetics, on the one hand, and its predecessors in the eco-physiology of higher nervous activity, on the other. Recently, these areas have begun to converge, with first evidence now indicating the possibility of transgenerational epigenetic inheritance of conditional associations in the mammalian nervous system, and related findings in other taxa. This can serve as an interesting example of evolutionary code-making, where the molecular mechanisms underlying arbitrary associations between stimuli involve lasting changes in gene expression that may be transmitted epigenetically across generations, and which in some cases could be further assimilated into the genome over subsequent evolution. Although preliminary, such epigenetic scenarios would also offer an interesting, if so far overlooked parallel to earlier research carried out by one of I.P. Pavlov’s leading students, acad. P.K. Anokhin, and his colleagues, but also by eminent eco-physiologists of the time, several of whom offered arguments for the possibility of unconditional reflexes representing evolutionarily later, specialized, and reduced forms of associative reflexes, from which they may be derived. Although discarded under the growing dominance of modern synthesis, these early epigenetic investigations may deserve renewed attention in the modern context, and if further confirmed, could open essentially new perspectives on the morphofunctional evolution of the nervous system.

Tris(dibenzylideneacetone)dipalladium: New Life of the Old Synthon for Pd(0) atom

The history of a unique stable and soluble complex Pd2(dba)3 has been considered starting with the classical oxidative addition and finishing by the modern synthesis of Pd nanoclusters catalysts absorbed on the carbon and non-carbon polymer supports.

What’s wrong with the modern evolutionary synthesis? A critical reply to Welch (2017)

Welch (Biol Philos 32(2):263–279, 2017) has recently proposed two possible explanations for why the field of evolutionary biology is plagued by a steady stream of claims that it needs urgent reform. It is either seriously deficient and incapable of incorporating ideas that are new, relevant and plausible or it is not seriously deficient at all but is prone to attracting discontent and to the championing of ideas that are not very relevant, plausible and/or not really new. He argues for the second explanation. This paper presents a twofold critique of his analysis: firstly, the main calls for reform do not concern the field of evolutionary biology in general but rather, or more specifically, the modern evolutionary synthesis. Secondly, and most importantly, these calls are not only inspired by the factors, enumerated by Welch, but are also, and even primarily, motivated by four problematic characteristics of the modern synthesis. This point is illustrated through a short analysis of the latest reform challenge to the modern synthesis, the so-called extended evolutionary synthesis. We conclude with the suggestion that the modern synthesis should be amended, rather than replaced.

Macroevolutionary Freezing and the Janusian Nature of Evolvability: Is the Evolution (of Profound Biological Novelty) Going to End?

In a macroevolutionary timescale, evolvability itself evolves. Lineages are sorted based on their ability to generate adaptive novelties, which leads to the optimization of their genotype-phenotype map. The system of translation of genetic or epigenetic changes to the phenotype may reach significant horizontal and vertical complexity, and may even exhibit certain aspects of learning behaviour. This continuously evolving semiotic system probably enables the origin of complex yet functional and internally compatible adaptations. However, it also has a second, “darker”, side. As was pointed out by several authors, the same process gradually reduces the probability of the origination of significant evolutionary novelties. In a similar way to the evolution of societies, teachings, or languages, in which the growing number of internal linkages gradually solidifies their overall structure and the structure or interpretation of their constitutive elements, the evolutionary potential of lineages decreases during biological evolution. Possible adaptations become limited to small “peripheral” modifications. According to the Frozen Evolution theory, some of the proximate causes of this “macroevolutionary freezing” are more pronounced or present exclusively in sexual lineages. Sorting based on the highest (remaining) evolvability probably leads to the establishment of certain structural features of complex organisms, e.g. the modular character of their development and morphology. However, modules also “macroevolutionary freeze” whereas the hypothetical “thawing” of modules or their novel adaptive combinations becomes rarer and rarer. Some possible ways out of this dead end include the rearrangement of individual development, e.g. neoteny, radical simplification, i.e. sacculinization, and transition to a higher level of organization, e.g. symbiosis or symbiogenesis. The evolution of evolvability is essentially a biosemiotic process situated at the intersection of the genocentric modern synthesis and the evo-devo-centric extended synthesis. Therefore, evolvability may eventually connect these three not necessarily contradictory approaches.

The Problem with Too Much Fidelity to the Modern Synthesis When Explaining the Origins and Evolution of the Social Universe

Religion emerged as a cognitive capacity and behavioral propensity by virtue of Darwinian natural selection on hominins and then humans to become more social and group oriented. The capacity to be religious is only a modest extension of the Darwinian selection on cognitive, emotional, and interpersonal propensities of all great apes and, hence, early hominins. However, other forms of natural selection need to be added to the explanation of why religion became institutionalized in early human societies, why religious organizations arise and die from competition, and why violence is so often a part of religious revolution. These additional types of natural selection do not obviate Darwinian selection on the human brain, but they become a necessary supplement to Darwinian analysis if the early institutionalization and subsequent evolution of religion are to be more fully explained.

Combined morphological and phylogenomic re-examination of malawimonads, a critical taxon for inferring the evolutionary history of eukaryotes.

Modern syntheses of eukaryote diversity assign almost all taxa to one of three groups: Amorphea, Diaphoretickes and Excavata (comprising Discoba and Metamonada). The most glaring exception is Malawimonadidae, a group of small heterotrophic flagellates that resemble Excavata by morphology, but branch with Amorphea in most phylogenomic analyses. However, just one malawimonad, Malawimonas jakobiformis, has been studied with both morphological and molecular-phylogenetic approaches, raising the spectre of interpretation errors and phylogenetic artefacts from low taxon sampling. We report a morphological and phylogenomic study of a new deep-branching malawimonad, Gefionella okellyi n. gen. n. sp. Electron microscopy revealed all canonical features of ‘typical excavates’, including flagellar vanes (as an opposed pair, unlike M. jakobiformis but like many metamonads) and a composite fibre. Initial phylogenomic analyses grouped malawimonads with the Amorphea-related orphan lineage Collodictyon, separate from a Metamonada+Discoba clade. However, support for this topology weakened when more sophisticated evolutionary models were used, and/or fast-evolving sites and long-branching taxa (FS/LB) were excluded. Analyses of ‘–FS/LB’ datasets instead suggested a relationship between malawimonads and metamonads. The ‘malawimonad+metamonad signal’ in morphological and molecular data argues against a strict Metamonada+Discoba clade (i.e. the predominant concept of Excavata). A Metamonad+Discoba clade should therefore not be assumed when inferring deep-level evolutionary history in eukaryotes.

Radical Diazidation of Alkenes: Cu/Fe/Mn Catalysis and Electrochemical Support

AbstractThe synthetic routes for C‐N3 bond formation through a radical mechanism with the use of transition metals provide efficient diazide products, which can be further applied in many transformations to synthesize various valuable nitrogen‐containing compounds of pharmaceutical interest. The reported methods evidence stoichiometric heavy metals and toxic reagents (as N3‐source) and generally exhibit a limited substrate scope. However, the electrochemical diazidations are found to be environmentally friendly and very simple, while also providing a highly efficient way to synthesize 1,2‐diazide derivatives. Moreover, they provide a smart alternative for easy access to 1,2‐diamines, which can be used for future modern syntheses.

‘Great is Darwin and Bergson his poet’: Julian Huxley's other evolutionary synthesis

SUMMARYIn 1912, Julian Huxley published his first book The Individual in the Animal Kingdom which he dedicated to the then world-famous French philosopher Henri Bergson. Historians have generally adopted one of two attitudes towards Huxley's early encounter with Bergson. They either dismiss it entirely as unimportant or minimize it, deeming it a youthful indiscretion preceding Huxley's full conversion to Fisherian Darwinism. Close biographical study and archive materials demonstrate, however, that neither position is tenable. The study of the Bergsonian elements in play in Julian Huxley's early works fed into Huxley's first ideas about progress in evolution and even his celebrated theories of bird courtship. Furthermore, the view that Huxley rejected Bergson in his later years needs to be revised. Although Huxley ended up claiming that Bergson's theory of evolution had no explanatory power, he never repudiated the descriptive power of Bergson's controversial notion of the élan vital. Even into the Modern Synthesis period, Huxley represented his own synthesis as drawing decisively on Bergson's philosophy.

Natural Selection and Pangenesis: The Darwinian Synthesis of Evolution and Genetics.

Since the end of the 19th century, Lamarck's name has been tightly linked to the notion of the inheritance of acquired characters. Darwin regarded Lamarck as a great zoologist and a forerunner of evolution, and repeatedly expressed the opinion that "natural selection has been the main but not the exclusive means of modification." The original Darwinism not only includes natural selection, but also the inheritance of acquired characters and mutation. Neo-Darwinism considers natural selection as the one controlling process of evolution, but denies the inheritance of acquired characters. Lysenkoism accepts the inheritance of acquired characters and graft hybridization, but denies the significance of Malthusism and Mutationism. It has been suggested that the "modern synthesis", which evolved from neo-Darwinism, needs a rethink. I propose that there is a need to go back to Darwin's own synthesis which combined his theory of evolution by natural selection with his theory of heredity and variation - Pangenesis.

Organic chemistry: Theory, reactivity, mechanisms in modern synthesis

Organic chemistry: Theory, reactivity, mechanisms in modern synthesis

The economy of nature: the structure of evolution in Linnaeus, Darwin, and the modern synthesis

We argue that the economy of nature constitutes an invocation of structure in the biological sciences, one largely missed by philosophers of biology despite the turn in recent years toward structural explanations throughout the philosophy of science. We trace a portion of the history of this concept, beginning with the theologically and economically grounded work of Linnaeus, moving through Darwin’s adaptation of the economy of nature and its reconstitution in genetic terms during the first decades of the Modern Synthesis. What this historical case study reveals, we argue, is a window into the shifting landscape of the explanatory and ontic uses of structural concepts. In Linnaeus, the economy of nature has both ontic and explanatory import; in Darwin the ontic and explanatory aspects start to come apart (with the explanatory aspect being foregrounded); and finally, in the Modern Synthesis, the economy of nature is replaced by the conceptual toolkit of population genetics, the structural elements of which are nearly entirely explanatory. Having traced a historical trajectory of structural concepts that moves from an ontic formulation to an increasingly explanatory one, we conclude by outlining some insights for structural realism.

Unmodern Synthesis: Developmental Hierarchies and the Origin of Phenotypes.

The question of whether the modern evolutionary synthesis requires an extension has recently become a topic of discussion, and a source of controversy. We suggest that this debate is, for the most part, not about the modern synthesis at all. Rather, it is about the extent to which genetic mechanisms can be regarded as the primary determinants of phenotypic characters. The modern synthesis has been associated with the idea that phenotypes are the result of gene products, while supporters of the extended synthesis have suggested that environmental factors, along with processes such as epigenetic inheritance, and niche construction play an important role in character formation. We argue that the methodology of the modern evolutionary synthesis has been enormously successful, but does not provide an accurate characterization of the origin of phenotypes. For its part, the extended synthesis has yet to be transformed into a testable theory, and accordingly, has yielded few results. We conclude by suggesting that the origin of phenotypes can only be understood by integrating findings from all levels of the organismal hierarchy. In most cases, parts and processes from a single level fail to accurately explain the presence of a given phenotypic trait.

The sociobiology of genes: the gene's eye view as a unifying behavioural-ecological framework for biological evolution.

Although classical evolutionary theory, i.e., population genetics and the Modern Synthesis, was already implicitly 'gene-centred', the organism was, in practice, still generally regarded as the individual unit of which a population is composed. The gene-centred approach to evolution only reached a logical conclusion with the advent of the gene-selectionist or gene's eye view in the 1960s and 1970s. Whereas classical evolutionary theory can only work with (genotypically represented) fitness differences between individual organisms, gene-selectionism is capable of working with fitness differences among genes within the same organism and genome. Here, we explore the explanatory potential of 'intra-organismic' and 'intra-genomic' gene-selectionism, i.e., of a behavioural-ecological 'gene's eye view' on genetic, genomic and organismal evolution. First, we give a general outline of the framework and how it complements the-to some extent-still 'organism-centred' approach of classical evolutionary theory. Secondly, we give a more in-depth assessment of its explanatory potential for biological evolution, i.e., for Darwin's 'common descent with modification' or, more specifically, for 'historical continuity or homology with modular evolutionary change' as it has been studied by evolutionary developmental biology (evo-devo) during the last few decades. In contrast with classical evolutionary theory, evo-devo focuses on 'within-organism' developmental processes. Given the capacity of gene-selectionism to adopt an intra-organismal gene's eye view, we outline the relevance of the latter model for evo-devo. Overall, we aim for the conceptual integration between the gene's eye view on the one hand, and more organism-centred evolutionary models (both classical evolutionary theory and evo-devo) on the other.

Time for a Change: Topical Amendments to the Medical Model of Disease

There is a conceptual crisis in the biomedical sciences that is particularly salient in psychopathology research. Underlying the crisis is a controversy that pertains to the current medical model of disease that largely draws from causal-mechanistic explanations. The bedrock of this model is the analysis of biological part-dysfunctions that aims at unequivocally defining a pathological condition and demarcating it from its neighboring entities. This endeavor has led to a quest for physiological, biochemical, and genetic signatures. Yet, so far there is little evidence for reliable biomarkers for any mental disorder. The contemporary biomedical paradigm largely ignores historical, dynamic, and system-level aspects—a view that has contributed much to the conceptual disjunction of the patient as a person from his/her disease. Notwithstanding the impressive progress in the biomedical sciences, increasingly more critics question whether the constituting framework is sufficient to convey a comprehensive understanding of illnesses, especially mental illnesses. Thus, the medical model urgently requires an update. But rather than revamping it by methodological advancements, it will be necessary to critically review its philosophical roots. The most problematic issues that require reworking are: the preponderance of the biostatistical theory; the undue decoupling of physiological from evolutionary explanations of function; the clinging to the Modern Synthesis (if etiological aspects are ever considered); and the neglect of dynamic and system-level properties. The proposed overhaul requires the heeding of historical explanations that draw from the Extended Evolutionary Synthesis as well as systems biology approaches for tackling multilevel and dynamic phenomena of complex systems.

Biogeography and Biotic Assembly of Indo-Pacific Corvoid Passerine Birds

The archipelagos that form the transition between Asia and Australia were immortalized by Alfred Russel Wallace's observations on the connections between geography and animal distributions, which he summarized in what became the first major modern biogeographic synthesis. Wallace traveled the island region for eight years, during which he noted the marked faunal discontinuity across what has later become known as Wallace's Line. Wallace was intrigued by the bewildering diversity and distribution of life he discovered. But even today we ask ourselves how species formed within the region and why they are not evenly distributed. Biogeography, phylogeny, dispersal, biotic interactions, and abiotic factors affect the assembly of diversity. On the basis of a decade of research on the ecology, evolution, and systematics of corvoid passerine birds, we summarize what we have learned about the biogeography and assembly of island bird diversity. Corvoid passerine birds include nearly 800 species and 2,300 named taxa and thus represent a large, well-described, and globally distributed clade. Understanding the processes influencing biodiversity in this group is certain to deepen our general understanding of ecology and evolution in the context of biogeography and faunal assembly.

J. B. S. Haldane's passage to India: reconfiguring science.

In 1957, John Burdon Sanderson (JBS) Haldane (1892-1964), the world's leading population geneticist, committed political radical and one of the three 'founders' of neo-Darwinian 'Modern Synthesis' of twentieth century biology (Sarkar 1995; Haldane 1932; Cain 2009; Smocovitis 1996), ostentatiously renounced both his British citizenship and his prestigious chair at University College London. In a decisively and very public anti-imperial gesture, ostensibly played out as a reaction to the Suez crisis (although his discontent was simmering for quite some time), Haldane, and his partner, geneticistHelen Spurway (1917-1977), turned their backs on Britain and set off to India to offer their considerable scientific prestige, their inexhaustible organisational abilities, along with their leading Journal of Genetics, behind the efforts to build a 'modern', democratic India emerging out of the ashes of colonial rule. Haldane's support of independent India was a major triumph for the new state, itself in the midst of negotiating a fine balance between rapid modernization through science and technology and an postcolonial respect for traditional 'non-Western' values. Although his time in India was short, Haldane's few years in India were marked by a frenzied engagement with the new India, its science, its government and its culture (Rao 2013).

Haldane's The causes of evolution and the Modern Synthesis in evolutionary biology.

This paper argues that Haldane's The causes of evolution was the most important founding document in the emergence of the received view of evolutionary theory which is typically referred to as the Modern Synthesis. Whether or not this historical development is characterized as a synthesis (which remains controversial), this paper argues the most important component of the emergence of the received view consisted of showing how the formal rules of Mendelian inheritance are based on (or emerge from) the material basis of heredity established by classical genetics primarily through the experimental work on Drosophila genetics of the Morgan school in the 1910s and 1920s. This is one of the most important achievements of Haldane's book. Thus this paper rejects both (i) the view that the synthesis was a unification of biometry and Mendelism and (ii) the claim that it arose from work primarily done in the late 1930s and 1940s by naturalists rather than theoretical population and classical experimental geneticists.

Hierarchy Theory of Evolution and the Extended Evolutionary Synthesis: Some Epistemic Bridges, Some Conceptual Rifts

Contemporary evolutionary biology comprises a plural landscape of multiple co-existent conceptual frameworks and strenuous voices that disagree on the nature and scope of evolutionary theory. Since the mid-eighties, some of these conceptual frameworks have denounced the ontologies of the Modern Synthesis and of the updated Standard Theory of Evolution as unfinished or even flawed. In this paper, we analyze and compare two of those conceptual frameworks, namely Niles Eldredge’s Hierarchy Theory of Evolution (with its extended ontology of evolutionary entities) and the Extended Evolutionary Synthesis (with its proposal of an extended ontology of evolutionary processes), in an attempt to map some epistemic bridges (e.g. compatible views of causation; niche construction) and some conceptual rifts (e.g. extra-genetic inheritance; different perspectives on macroevolution; contrasting standpoints held in the “externalism–internalism” debate) that exist between them. This paper seeks to encourage theoretical, philosophical and historiographical discussions about pluralism or the possible unification of contemporary evolutionary biology.