Exploiting cellular-developmental evolution as the scientific basis for preventive medicine

Department of Pediatrics, David Geffen School of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Los Angeles, California 90502, United States.
Medical Hypotheses (Impact Factor: 1.07). 02/2009; 72(5):596-602. DOI: 10.1016/j.mehy.2008.09.057
Source: PubMed


In the post-genomic era, we must make maximal use of this technological advancement to broaden our perspective on biology and medicine. Our understanding of the evolutionary process is undermined by looking at it retrospectively, perpetuating a descriptive rather than a mechanistic approach. The reintroduction of developmental biologic principles into evolutionary studies, or evo-devo, allows us to apply embryologic cell-molecular biologic principles to the mechanisms of phylogeny, obviating the artificial space and time barriers between ontogeny and phylogeny. This perspective allows us to consider the continuum between the proximate and ultimate causes of speciation, which was unthinkable when looked at from the descriptive perspective. Using a cell-cell interactive 'middle-out' approach, we have gained insight to the evolution of the lung from the swim bladder of fish based on gene regulatory networks that generate both lung ontogeny and phylogeny, i.e. decreased alveolar size, decreased alveolar wall thickness, and increased alveolar wall strength. Vertical integration of cell-cell interactions predicts the adaptivity and maladaptivity of the lung, leading to novel insights for chronic lung disease. Since we have employed principles involved in all of development, this approach is amenable to all biologic structures, functions, adaptations, maladaptations, and diseases, providing an operational basis for preventive medicine.

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Available from: Virender Rehan, Aug 04, 2014
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    • "We have previously shown that viewing lung ontogeny and phylogeny from the common denominator of cell-cell interactive paracrine signaling reveals that they are one and the same mechanism of morphogenesis, suggesting that time is superfluous to understanding vertebrate evolution (Torday and Rehan 2009a, 2009b, 2009c). The time variable is an artifact of descriptive biology. "
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    ABSTRACT: This article offers a novel, enlightened concept for determining the mechanism of evolution. It is based on homeostasis, which distinguishes life from non-life and as such is the universal mechanism for the evolution of all living organisms. This view of evolution is logical, mechanistic, non-scalar, predictive, testable, and falsifiable, and it illuminates the epistemological relationships between physics and biology, ontogeny and phylogeny, development and aging, ultimate and proximate causation, health and disease. In addition to validating Haeckel's biogenetic law and Lamarckian epigenetics, reflecting the enabling value of the cellular approach, this perspective also expresses the evolutionary process at the cell-molecular level, since the mechanism of cell communication itself is universal in biology, in keeping with a Kuhnian paradigm shift. This approach may even elucidate the nature and evolution of consciousness as a manifestation of the cellular continuum from unicellular to multicellular life. We need such a functional genomic mechanism for the process of evolution if we are to make progress in biology and medicine. Like Copernican heliocentrism, a cellular approach to evolution may fundamentally change humankind's perceptions about our place in the universe.
    Perspectives in Biology and Medicine 01/2013; 56(4):455-84. DOI:10.1353/pbm.2013.0038 · 0.48 Impact Factor
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    • "Normal lung development is the result of a functionally interconnected series of cell-molecular steps. This sequence of biologic events has been positively selected for evolutionarily over biologic time and space [1], resulting in optimal gas exchange mediated by alveolar homeostasis [2]. Elsewhere we have suggested that chronic lung disease (CLD) causes simplification of the lung in a manner consistent with the reversal of the evolutionary process [3, 4]. "
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    ABSTRACT: In the postgenomic era, we need an algorithm to readily translate genes into physiologic principles. The failure to advance biomedicine is due to the false hope raised in the wake of the Human Genome Project (HGP) by the promise of systems biology as a ready means of reconstructing physiology from genes. like the atom in physics, the cell, not the gene, is the smallest completely functional unit of biology. Trying to reassemble gene regulatory networks without accounting for this fundamental feature of evolution will result in a genomic atlas, but not an algorithm for functional genomics. For example, the evolution of the lung can be "deconvoluted" by applying cell-cell communication mechanisms to all aspects of lung biology development, homeostasis, and regeneration/repair. Gene regulatory networks common to these processes predict ontogeny, phylogeny, and the disease-related consequences of failed signaling. This algorithm elucidates characteristics of vertebrate physiology as a cascade of emergent and contingent cellular adaptational responses. By reducing complex physiological traits to gene regulatory networks and arranging them hierarchically in a self-organizing map, like the periodic table of elements in physics, the first principles of physiology will emerge.
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