Four hidden metamorphosis

This book of biology and medicine shows how diseases such as sickle cell anemia and Duchenne muscular dystrophy are related to the body's adaptation to aerial respiration. This adaptation is operated by a genetic switch substituting a set of fetal proteins for more suitable, regulated, adult isoforms. We discover how fetal or adult metabolic pathways may control the switch, and propose pharmacological treatments to boost the expression of the fetal gene, acting as a "spare wheel" to replace the adult gene when it has mutated. In fact this switch recapitulates a process reminiscent of the evolution of amphibians when they left the water to live in air and on land. The fetus is also an aquatic creature that discovers aerial respiration and the new weight of the body at birth. The blood and muscle proteins will adapt. The metamorphosis is not as evident as for a tadpole, but still as deeply written in our genes. In fact, the switch is our second metamorphosis ; the story started much earlier when a host cell, already surviving in oxygen, incorporated a bacteria, our future mitochondria, that had a more efficient oxidative metabolism. A symbiotic arrangement followed. In the course of development, the most ancient pathways come on stage first, followed by the most recent mitochondrial acquisitions. The developmental maturation of metabolic pathways changes our cells; it is our first metamorphosis. It is involved in apoptosis in diseases such as Alzheimer's and cancer. Since mitochondria had taken on the burden of making ATP, the ancient oxidative mechanism became redundant. Its ATPase evolved, forming acidic compartments that control neurotransmission and thermoregulation. This third metamorphosis is implicated in other diseases (adrenoleucodystrophy). Finally primates, who lost uricase, developed diseases related to the role of uric acid which became their new antioxidant: gout, autism and schizophrenia seem to depend on this last, fourth metamorphosis.