The mutation's surprising frequency and peculiar fondness for those of Irish, British, and Scandanavian heritage offers a unique opportunity for scientists and historians to study how the world of our ancestors may have shaped the landscape of modern disease. Researchers look to DNA analysis to solve a lingering biohistorical puzzle: Is the hemochromatosis gene common because it is an unintended consequence of natural selection, or because it is a relatively fresh glitch in the human genome with little time to spread to other regions?

Out of this tradition of sickness rises a story of medical progress -- and uncertainty -- involving an atom, the wanderlust of ancient peoples, the appetite of a caveman, and a possible legacy of the Black Death. Casadaban's tragic death at the hands of an infamous microbe challenges a theory that the hemochromatosis gene became common because it protected its owners from the plague.

In this search for the origin of one of the world's most common genetic diseases, emerging research in evolutionary medicine raises new questions about our history, development, and future as a species.

***

As elements go, iron is a fickle and mischievous companion. Essential to life, yet impulsive, promiscuous, and destructive when allowed to roam unescorted, it poses a tremendous engineering challenge to human tissues.

Iron readily exchanges electrons with other elements. Indispensable to oxygen transport and metabolism, this property may also cause disease if iron participates in unsanctioned electron exchanges that produce free radicals -- an evanescent and particularly hot-blooded family of compounds that damage cells and DNA. As a result, all organisms dependent on iron -- from primitive bacteria to mammals -- go to great lengths to safely transport and store this potentially poisonous payload. Under normal conditions, this meticulously coordinated system functions beautifully. However, in those who absorb more iron than average, the extra influx eventually overwhelms this transport and storage system. Eventually, rogue iron escapes its minders and chemical mischief ensues.

In spite of its proclivity for drama, we owe our lives to this metal. In fact, its value and scarcity over the course of human evolution may be reflected in the body's selfish tendency to hold on to it. The kidneys and gut are much less fond of sodium, potassium, calcium, and magnesium, as we can easily excrete these metals when they accumulate in excess. We have no such way to rid ourselves of iron. Some believe this may be a thrifty adaptation to an ancient world where meat from the butcher or blood from the hospital weren't a short car ride away.

***

Dr. Armand Tosseau [Wikimedia Commons] Dr. Armand Tosseau [Wikimedia Commons]

In 1865, Dr. Armand Trosseau described a previously unrecognized illness involving the peculiar triad of skin bronzing, cirrhosis, and diabetes. A French internist, Dr. Trosseau was a legendary diagnostician and educator. His name remains familiar to modern students of medicine, though not for this first case report of hemochromatosis. He is more famously associated with Trosseau's syndrome, a disorder of blood clotting found in patients with a lurking gastrointestinal cancer. Not long after giving the first lecture on hemochromatosis, Dr. Trosseau discovered a painful, pale, inflammatory rash on his own left leg, heralding an underlying blood clot. Ironically, it was the very phlegmasia alba dolens of his own eponymous syndrome. Shortly thereafter, he succumbed to gastric cancer -- having named, diagnosed, and suffered from its syndrome of inappropriate clotting. An ironic end for the first physician to study iron-overload.