Election Section

I keep being reminded that the universe, as either the geneticist J. B. S. Haldane or the astronomer Arthur Eddington (or both) said, is not only stranger than we imagine, it’s stranger than we can imagine. And I’m not talking about superstring theory or quantum weirdness here. This is about plain old biology, and the unexpected link between the eastern fox squirrels in my yard and the unfortunate George III of England. It’s not breaking news—the basic facts have been known for quite a while—but it’s just too strange to be left alone with. 

If you saw the 1994 film The Madness of King George, you know the story: verbal tics, erratic behavior (although it’s not in the movie, he had long conversations with trees in the royal gardens), wild lunges at the ladies-in-waiting, brutal treatment regimens, restraints, and so on. It wasn’t until the 1970s that the king’s illness was retrospectively diagnosed by the psychiatrists Ida MacAlpine and Richard Hunter as porphyria, a hereditary disease caused by a chemical defect in the production of hemoglobin. Apart from the psychiatric manifestations, other symptoms—all apparently present in George III’s case—include hypersensitivity to light, abdominal pain, paralysis of the limbs, and urine the color of port wine. The king was part of a line of royal porphyria victims that included Mary Queen of Scots, James I, Anne, his son George IV, his daughter Princess Charlotte, and Frederick the Great of Prussia. I don’t know whether the Windsors have been affected, but they have enough problems of their own.  

The latest twist in the saga of the mad king involves a sample of his hair that surfaced recently among the collections of a London museum. The hair proved to be loaded with arsenic, 300 times the toxic level. Medical detectives concluded that George had ingested the stuff in a popular eighteenth-century nostrum called James’s powders, which contained a compound of antimony and arsenic—and that the buildup of arsenic triggered and aggravated the porphyric attacks. George Washington used it, too, but in smaller doses. 

But what about the squirrels? Eastern fox squirrels seem ubiquitous in Berkeley. They’re not from here; their home range is east of the Mississippi, from which they were introduced to the Bay Area and other parts of California. I haven’t been able to trace the exact origins of the Bay Area population, but the ones in Los Angeles were brought in from Tennessee or thereabouts around 1904 by Civil War and Spanish-American War veterans at the Sawtelle Veteran’s Home—either as pets or as ingredients for the classic Southern dish Brunswick stew. Which is a fate I’ve often wished on the squirrels that raid my bird feeders or dig up the Calochortus bulbs. 

Eastern fox squirrels (so called to distinguish them from the Nayarit fox squirrel of southern Arizona and Mexico) are pretty typical tree squirrels, except for one thing: their bones are pink. Under ultraviolet light, the bones of eastern fox squirrels fluoresce brilliant red.  

In the 1930s, a medical researcher named William J. Turner was looking for possible animal models for human porphyria. Somehow he heard about the fox squirrel and its oddly colored bones. “Although the farmers of Pennsylvania have long known that the bones of the fox-squirrel are red,” Turner wrote in 1937, “it has entirely escaped scientific investigation.” He confirmed the presence of the pigment uroporphyrin I in the squirrels’ systems. Turner, who appears to have been a methodical man, looked at thousands of small mammal skeletons for other examples and found a few pinkish chipmunk remains, but nothing comparable to the fox squirrel situation. He also noted reports of red bones in fetal mammals, including rats, guinea pigs, and rabbits, with the deposit of uroporphyrin I somehow being switched off before birth. 

No one seems to have done anything with the fox squirrel-porphyria connection until the work of Ephraim Levin at Johns Hopkins and Vagn Flyger at the University of Maryland in the 1970s. Their paper explicitly linked the squirrels’ condition with hereditary porphyria in humans and cattle. One common factor was a low level of an enzyme called uroporphyrinogen III cosynthetase, essential to the conversion of porphyrins to hemoglobin, in the red blood cells of fox squirrels and porphyric humans. Levin and Flyger found that eastern gray squirrels, close relatives of eastern fox squirrels, had higher and more stable concentrations of the enzyme. 

But sciurine porphyria, as the researchers called it, doesn’t seem to be a pathological condition. There was no trace of the anemia or skin lesions common to human and bovine subjects with congenital porphyria. And fox squirrels don’t seem sensitive to light; Levin and Flyger pointed out that they’re more active during daylight hours than nonporphyric gray squirrels. They didn’t discuss psychiatric symptoms; if a fox squirrel was demented, I’m not sure how you could tell. The phenomenon seemed to be species-wide and most likely hereditary; although diet or other environmental variables were not ruled out, fox squirrels and gray squirrels eat pretty much the same mix of nuts, fruit, and grain, with the occasional egg or nestling bird. 

Levin and Flyger speculated that somewhere in the 25-million-year history of tree squirrels, a mutation occurred in the fox squirrel line that changed the way their enzymes worked. The condition may have persisted because it was somehow favorable to the squirrels, as sickle-cell trait was to humans in regions with endemic malaria (although it looks like a dominant rather than recessive trait). Or it may have been neutral in its effect and therefore invisible to the process of natural selection, or linked to another trait that was selected for. As far I as can determine, that question remains unanswered. And no one has exhumed George III to see if his royal bones fluoresce red.