Retrodictive Disproof of the Onto-Phylogenetic “Just-So Story” and the Role of Narrative in Evolutionary Medicine Noel T. BOAZ, Ph.D., M.D. Anatomy Laboratory, Emory and Henry College School of Health Sciences, Marion, VA 24354, U.S.A. Laboratory of Biological Anthropology and Anatomy, Integrative Centers for Science and Medicine, Martinsville, VA 24112, U.S.A. ABSTRACT. Whereas much of biomedical science relies on the laboratory experiment as its gold-standard methodology to disprove hypotheses, investigations of historical fact in the evolutionary sciences require a time-controlled multidisciplinary approach akin to forensic science that is equally rigorous in disproving its hypotheses. When detractors, scientific and otherwise, disparage paleobiological hypotheses as “untestable” they may use the term “just-so story” pejoratively to dismiss them as fanciful fiction, drawing a comparison with the popular Just-So Stories published by Anglo-Indian author Rudyard Kipling in the early twentieth century. The experimental method tests hypothetical predictions in a uniformitarian empirical framework that is ahistorical and mechanism-focused, while the forensic method tests retrodictions in a uniformitarian empirical framework that is historical and narrative in focus. Both methods are fully compatible with each another, and non-falsified hypotheses must conform with empirical results obtained through either method. A thoroughly tested onto-phylogenetic (“evo-devo”) narrative is an essential component of Evolutionary Medicine, driving research, educational, and clinical advances. Clinical experience amply demonstrates that therapies which ignore evolutionary history and rest solely on ahistorical and mechanistic assumptions lead to less-than-optimal patient outcomes. To operationalize the retrodictive approach an anthropogenic (“human-origins”) matrix is constructed using an array of 9 paradigmatic tools, including rigorous temporal calibration, applied across 7 categories of narrative elements, including environmental context and adaptations, in order to assess hypotheses. Drawing an analogy to Kipling’s unfalsifiable “How the Rhinoceros Got His Skin” (1902) the anthropogenic matrix is used to construct a falsifiable narrative of evolutionary and developmental anatomy of the human integument, with clinical implications.
O2 Levels
CO2 Levels
Earth Impacts
Solar Luminosity
TESTING AN ANTHROPOGENIC ONTO-PHYLOGENETIC HYPOTHESIS (AOPH) Divergence Times (MYA) Eon/Period
S. Kumar, G. Stecher, M. Suleski, and S.B. Hedges, 2017. TimeTree: a resource for timelines, timetrees, and divergence times. Molecular Biology and Evolution 34: 1812-1819, DOI: 10.1093/molbev/msx116.
How the Rhinoceros Got His Skin, U.K. Commemorative Stamp, Centenary of Rudyard Kipling’s Just So Stories, 2002
An anthropogenic onto-phylogenetic hypothesis (AOPH) shares two characteristics with a Kipling-esque “just-so” story (JSS). They are both premised on observable phenomena in the natural world, and they explain the origins of those phenomena by means of a narrative. They differ fundamentally in that an AOPH is constructed to be falsifiable within a scientific hypothetico-deductive paradigm and by its very nature will change as new data become available. The JSS is a non-falsifiable literary creation, despite its author having derived some inspiration from Charles Darwin’s Origin of Species (and also Aesop’s Fables). Its essentially unchangeable nature is shown by Kipling’s (1902) “How the Rhinoceros Got His Skin,” originally a bedtime story for his young daughter. “Taffy” would correct her father if he made the slightest variation in the narrative, giving rise to the appellation “just so” for how the story and others like it had to be told. Kipling intentionally incorporated whimsical incongruities in the stories, which contribute a large part of their allure. He was awarded the Nobel Prize for Literature in 1908. The JSS storyline: A lone “Parsi-man” wearing a resplendent hat (see above) bakes a cake in a cookstove improbably set on an exotic beach somewhere between the Indian Ocean and the Red Sea. A large unmannered rhinoceros emerges from the “altogether uninhabited interior” to gobble up the cake while the angry Parsi watches from a palm tree. He vows revenge. Six weeks later a heat wave forces everyone to the shore to cool off. People undress to go into the water but the rhino, which of course does not wear clothes, takes his skin off, leaving it on the beach. The Parsi sees his chance and rubs stale cake crumbs into the rhino’s skin. When the rhino puts his skin back on, buttoning it up in front, it itches terribly. Distracted so much by the itching that he does not think to unbutton his skin the rhino rubs against a tree, causing his skin to form large folds and rubbing off the buttons. The rhino wanders off in a bad temper and presumably survives to bequeath his unique skin and bad disposition to future generations.
Steps to Retrodictively Disprove an AOPH • •
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1. Construct an Evolutionary Timeline from TimeTree.org for Homo sapiens, showing the geological time scale, evolutionary divergence times as calculated with the molecular clock, and temporally controlled paleoenvironmental parameters (above left). 2. Construct a time-controlled phylogeny with extant comparative organisms showing major genomic and morphological adaptations related to the integument from the Last Universal Common Ancestor (LUCA) to the present. Time is plotted on a logarithmic scale. Divergence dates are means from the Time Tree of Life (www.timetree.org). Extant related organisms are shown along the top row. Major adaptations are indicated in boxes at their respective evolutionary nodes, with references (above right). 3. Dissect a narrative (below left) into 7 elements and critically assess them along a core empirical diagonal of paradigmatic tools (in green below). Following Baconian and Darwinian scientific methods and as still practiced in forensic sciences (see lowermost), all narrative elements must a) agree, b) differ (with explanation), or c) concomitantly vary with the core empirical diagonal.
PARADIGMATIC TOOLS Geochronology
If viewed as a scientific hypothesis a JSS is fallacious based on all four Baconian criteria (see bottom right). Thus it is untestable and unfalsifiable using the anthropogenic matrix proposed here (see right). Science-minded children (unlike “Taffy”) point out to no avail that rhinos do not eat cake, removing their skin would be fatal even if they had opposable thumbs (which they don’t), rubbing like that would injure the skin and would not immediately produce callous-like folds, the crumbs inside would eventually be absorbed, and even if those changes happened they would not be passed on to the rhino’s offspring (that would be inheritance of acquired characters). An adult scientist labeling a colleague’s evolutionary narrative hypothesis a JSS then is undoubtedly globally condemnatory, but not especially specific nor particularly useful in advancing scientific inquiry. Is it possible to re-tell Kipling’s tale about integumentary origins from a human perspective, generating an Anthropogenic Onto-Phylogenetic Hypothesis (AOPH) as a scientific narrative, useful for both research and didactic purposes, and devise reliable scientific criteria to test it?
Shortly after the dawn of the world (some 4.567 thousand million [as we British say for “billion”] years ago), little single-celled LUCA, the Last Universal Common Ancestor of us all, first dressed herself up in a lipid bilayer cell membrane and for the first time clothed her naked RNA. Mother Nature approved and invoked Natural Selection (as I described previously, and somewhat imperfectly, as the “Law of the Jungle”) to ensure that these adaptations were bequeathed to subsequent generations. This most ancient of adaptations was the first approximation of an “integument” between the “altogether uninhabited” organismal interior (no organelles) and the environment. LUCA’s Hadean habitat was a rotten-egg world – sulfurous, hot, dark, oxygenless, clay-lined clefts alongside hydrothermal vents deep in the sea. Bacteria-like descendants of LUCA, Archaean bacteria, began living in stromatolitic colonies over the next billion and a half years, adhering to rocks, covering themselves with a proteinaceous protective film, and producing oxygen as a metabolic byproduct. But bacteria had no manners then and they have no manners now. They just continued proliferating until they polluted the world – with oxygen. What to do? In good time Bacteria began to use the caustic but energy-rich oxygen molecules in their metabolism. Bigger bacterial descendants preyed upon and engulfed the oxygen-users but then made an evolutionary pact with them known as symbiosis. The big bacteria didn’t digest the smaller ones and used the hydrogen electrons left over from the smaller bacteria’s oxygen respiration for their own energy. The smaller bacteria benefitted by living protected inside the larger bacteria’s cell membrane. The little bacteria were the ancestors of the mitochondria who after a billion or more years are still there in our cells today, still producing energy via the electron transport chain. The bigger cell became the first eukaryote and enclosed its DNA-containing nucleus with another membrane layer, the nuclear membrane. Like the bacteria before them the eukaryotes discovered that there was strength in numbers. They clumped together, utilizing the adherens molecules that their ancestors had evolved originally to cling to rocks. They began communicating cell-to-cell with receptor and messenger molecules to produce proteins that promoted the survival not just of themselves but of the aggregate. The genes that had coded for the protective proteinaceous film of their bacterial stromatolite ancestors evolved to produce an actual skin-like covering over all the aggregated cells. Thus did the integument appear as a covering enclosing all the multi-cellular creatures on earth, including our ancestors, the actively moving animals. The integument was so important to animals as they adapted to the many niches in the seas, jungles, mountains, and plains of the earth that Mother Nature bequeathed to multicellular animals one entire embryonic germ layer (the ectoderm) and part of a second layer (the mesoderm) for its development. The integument became the largest organ in the vertebrate body, serving as an impenetrable barrier in our fishy ancestors between their internal milieu and the surrounding waters. As our amphibian forebears moved onto the land, their still-moist respiring skin helped them catch their breath as they wriggled away from predators. Those too slow to escape the jaws of doom, however, did not die in vain, for the integument’s noxious toxins provided a bitter reminder to any predator the next time it contemplated dining on one of their fellows. Among the descendent, fully terrestrial amniotes the integument became a major barrier to water loss made possible by a dry non-living layer of epidermal cells sealed by corneodesmosomes, the stratum corneum. But 300 million years ago was a time of snow and ice and again the integument helped our ancestors survive. Hair evolved to insulate the body of mammal-like reptiles from the cold. When large reptiles, the dinosaurs, took over diurnal niches, a furry integument proved to be a valuable exaptation for their tiny nocturnal cousins, the warm-blooded mammals, who had to stay warm while they scurried around during the hours of darkness. Mammals sensed the environment around them via whiskers (integumentary hairs on the face), communicated via smell and cooled themselves off via integumentary sweat glands, and even fed their offspring with nutritious secretions from female integumentary glands that came to be known in humans as “breasts.” As the Cenozoic Era dawned some 65 million years ago a group of diurnal, tree-living mammals, the primates, adorned themselves in a stunning array of patterns and colors of skin and pelage, communicating everything from receptivity to mating to group membership. Paradoxically, human-like primates largely divested themselves of their integumentary hairy raiment in order to cool off (similar to my earlier discussion of this topic relative to the rhinoceros [op cit.]). Environmental desiccation 5 to 6 million years ago forced them to adapt to a sweaty, bipedal life on the open ground. Increased ultraviolet radiation on naked skin, however, disrupted folate metabolism in australopithecine mothers, leading to many neurological birth defects fatal to their newborns, until protective dark skin evolved in early Homo some 1.2 million years ago. Variably melanic integument has been the norm for the human species ever since, with skin color rapidly evolving a lighter hue in those people migrating to sunlightdeprived higher latitudes (to allow adequate Vitamin D production in the skin) and evolving rapidly to darker skin in people moving back towards the Equator (to prevent ultraviolet radiation skin injury and folate deficiency). Despite a remarkable lability in human skin color and its lack of correlation with any fundamental genetic difference between groups or individuals, humans still today generally retain the ancient primate response to an individual’s visible integument as intrinsic to membership in a particular “race.” The long and tortuous evolutionary history of the human integument holds many insights into contemporary human health, running the gamut across an astounding array of skin maladies from autoimmune diseases such as pemphigus, to viral infections such as shingles, to bacterial infections such as impetigo, to genetic malformations such as ichthyosis, and to manifestations of underlying pathologies in other systems such as jaundice.
NARRATIVE ELEMENTS
How Humans Got Their Skin: An Anthropomorphized but Disprovable AOPH as Rudyard Kipling May Have Told It
Time Frame
Paleoecology / Astrobiology Paleoclimatology / Paleontology
Molecular Systematics / Comparative Biochemistry
Evo-Devo / Integrative Biology
Comparative Anatomy
Comparative Physiology
Anthropology / Evolutionary Anthropogeny Medicine / Comparative Pathology
Place / Environment
Action / Significant Events
Players / Actors
Experimental /Comparative Organisms from this Stage
Significance – Adaptation Bequeathed to Human Lineage
Clinical / Research Correlates
“I worked on true Baconian principles, and without any theory collected facts on a wholesale scale…” - Charles Darwin, Autobiography Sir Francis Bacon – Novum Organum (1620) Holder, C.F. 1892 Charles Darwin, His Life and Work. New York: Putnam.
Bacon's method of empirical (“inductive”) reasoning requires careful, systematic observations necessary to produce quality facts. • Common fallacies (“idola menti”), i.e. 1) preconceptions (tribus), 2) personal predilections (specus), 3) wordplay (fori), and 4) dogma (theatric), must be avoided • In investigating the cause (“form nature”) of a phenomenon one or more axioms (“first vintage” hypotheses) can be generalized from the facts, but not beyond what the facts truly demonstrate. • Methods of isolating and further investigating the form nature include 1) Agreement, 2) Difference, and 3) Concomitant Variation • New axioms can be deduced from existing data or incrementally from additional data • Specific types of facts can be particularly useful, such as negative instances, exceptional instances, and data from experiments [Bacon reputedly died after an experiment attempting to preserve a dead rabbit by freezing] • The whole process is repeated in a stepwise fashion to build an increasingly complex base of knowledge • Form nature, the cause of phenomena, is always supported by observed facts and empirical data.