Examines the processes of scientific creativity and discovery, and proposes a model of scientific development.

Two conundrums puzzle COVID‐19 investigators: 1) morbidity and mortality is rare among infants and young children and 2) rates of morbidity and mortality exhibit large variances across nations, locales, and even within cities. It is found that the higher the rate of pneumococcal vaccination in a nation (or city) the lower the COVID‐19 morbidity and mortality. Vaccination rates with Bacillus Calmette–Guerin, poliovirus, and other vaccines do not correlate with COVID‐19 risks, nor do COVID‐19 case or death rates correlate with number (...) of people in the population with diabetes, obesity, or adults over 65. Infant protection may be due to maternal antibodies and antiviral proteins in milk such as lactoferrin that are known to protect against coronavirus infections. Subsequent protection might then be conferred (and correlate with) rates of Haemophilus influenzae type B (Hib) (universal in infants) and pneumococcal vaccination, the latter varying widely by geography among infants, at‐risk adults, and the elderly. Also see the video abstract here https://youtu.be/GODBYRbPL00. (shrink)

I propose a T‐cell receptor (TcR)‐based mechanism by which immunity mediates both “genetic self” and “microbial self” thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross‐reactivity with “self,” resulting in selection for a TcR repertoire mimicking “genetic self.” Second, evolution has selected for a “microbial self” that mimics “genetic self” so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel mechanism for (...) modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR‐microbiome mimicry “holoimmunity” to denote immune tolerance to the “holobiont self.” Logically, microbiome‐host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross‐react with host antigens producing “holoautoimmunity.”. (shrink)

The purpose of this article is to integrate two outstanding problems within the philosophy of science. The first concerns what role aesthetics plays in scientific thinking. The second is the problem of how logically testable ideas are generated (the so-called "psychology of research" versus "logic of (dis)proof" problem). I argue that aesthetic sensibility is the basis for what scientists often call intuition, and that intuition in turn embodies (in a literal physiological sense) ways of thinking that have their own meta-logic. (...) Thus, aesthetics is a form of cognition. Scientists think not in equations or words or other logical abstractions, but emotionally and sensually, using visual and aural images, kinesthetic and other proprioceptive feelings, sensations, patterns, and analogies. These aesthetic forms of thinking have their own logics that I call "synosia", from the root words synaesthesia (a combining of senses) and gnosis, "to know". Synosia denotes understanding that integrates feeling that one knows with feeling what one knows. Eminent scientists universally describe an explicitly secondary process in which such personal knowledge must be "translated" into a formal language, such as words or equations, in order to be communicated to other people. Many of the unsolved problems that philosophers of science (as well as psychologists and artificial intelligence researchers) have had in making sense of scientific thinking have arisen from confusing the form and content of the final translations with the hidden means by which scientific insights are actually achieved. (shrink)

We hypothesize that life began not with the first self‐reproducing molecule or metabolic network, but as a prebiotic ecology of co‐evolving populations of macromolecular aggregates (composomes). Each composome species had a particular molecular composition resulting from molecular complementarity among environmentally available prebiotic compounds. Natural selection acted on composomal species that varied in properties and functions such as stability, catalysis, fission, fusion and selective accumulation of molecules from solution. Fission permitted molecular replication based on composition rather than linear structure, while fusion (...) created composomal variability. Catalytic functions provided additional chemical novelty resulting eventually in autocatalytic and mutually catalytic networks within composomal species. Composomal autocatalysis and interdependence allowed the Darwinian co‐evolution of content and control (metabolism). The existence of chemical interfaces within complex composomes created linear templates upon which self‐reproducing molecules (such as RNA) could be synthesized, permitting the evolution of informational replication by molecular templating. Mathematical and experimental tests are proposed. BioEssays 28: 399–412, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

The idea behind this special theme journal issue was to continue the work we have started with the INBIOSA initiative (www.inbiosa.eu) and our small inter-disciplinary scientific community. The result of this EU funded project was a white paper (Simeonov et al., 2012a) defining a new direction for future research in theoretical biology we called Integral Biomathics and a volume (Simeonov et al., 2012b) with contributions from two workshops and our first international conference in this field in 2011. The initial impulse (...) for this effort was given a year earlier by a publication of one of the guest editors of this issue (Simeonov, 2010) in this journal. This time we wish to provide a broader forum and more space to elaborate in detail some of the most interesting concepts we have encountered in our discussions, as well as to invite some new contributions of particular interest in the field. Another goal we had in mind was to collect and review as many provocative perspectives as possible on the same key topic we are interested before making a decision to follow a more focused notion that would lead to a funded research program. Therefore we welcomed the generous suggestion of Professor Denis Noble, FRS, who is also editor of this journal to prepare a special theme issue entitled: “Can biology create a profoundly new mathematics and computation?” It has taken a while to invite and collect the contributions. Most of them had a couple of revision cycles and adjustments after having been thoroughly discussed with colleagues, incl. the editors of this issue. We think that the result we have obtained at the end is a satisfactory one, since we succeeded to integrate a diversity of original, but sometimes controversial and mutually excluding concepts organized within chapters of a self-contained volume. The task of compiling all this was not easy at all. Despite our efforts to position the articles of different authors and themes in a way allowing their easy comprehension and relation to each other within the individual chapters, some of them still require a sort of introduction to dissolve possible ambiguities. This is what we are going to do in the following few paragraphs with the hope that the reader (and some of the authors) would excuse our failures. (shrink)

The origin of homochirality in molecules characterizing living systems has remained a mystery since Pasteur's recognition of the problem some 150 years ago.2-5 Most theories also assume that homochirality emerged in one class of molecules (e.g. ribose) from which it was enriched in other molecules (e.g. amino acids) as well.2-5 I propose a novel, experimentally testable hypothesis describing a process by which selective chirality in amino acids and ribonucleotides emerged simultaneously and hand-in-hand with the origin and directionality of the genetic (...) code within a system of interactions involving amino acids, peptides, nucleotide bases, their sugars and polynucleotides. BioEssays 29:689–698, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Severe COVID‐19 is often accompanied by coagulopathies such as thrombocytopenia and abnormal clotting. Rarely, such complications follow SARS‐CoV‐2 vaccination. The cause of these coagulopathies is unknown. It is hypothesized that coagulopathies accompanying SARS‐CoV‐2 infections and vaccinations result from bacterial co‐infections that synergize with virus‐induced autoimmunity due to antigenic mimicry of blood proteins by both bacterial and viral antigens. Coagulopathies occur mainly in severe COVID‐19 characterized by bacterial co‐infections with Streptococci, Staphylococci, Klebsiella, Escherichia coli, and Acinetobacter baumannii. These bacteria express unusually (...) large numbers of antigens mimicking human blood antigens, as do both SARS‐CoV‐2 and adenoviruses. Bacteria mimic cardiolipin, prothrombin, albumin, and platelet factor 4 (PF4). SARS‐CoV‐2 mimics complement factors, Rh antigens, platelet phosphodiesterases, Factors IX and X, von Willebrand Factor (VWF), and VWF protease ADAMTS13. Adenoviruses mimic prothrombin and platelet factor 4. Bacterial prophylaxis, avoidance of vaccinating bacterially infected individuals, and antigen deletion for vaccines may reduce coagulopathy risk. Also see the video abstract here: https://youtu.be/zWDOsghrPg8. (shrink)