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.