In the September 19th New Yorker, mail (under this title) from Arthur P. Grollman, M.D. (Distinguished Professor of Pharmacological Sciences, Stony Brook University School of Medicine):
Elif Batuman, in her piece on kidney disease in the Balkans, describes various theories addressing the etiology of the disease Balkan endemic nephropathy, or ben (“Poisoned Land,” August 12th & 19th). Over the past fifty years, many of the hypotheses Batuman mentions have been eliminated by rigorous scientific research. The crucial exception, and now the most widely accepted cause, is aristolochic acid, an environmental toxin from seeds of the aristolochia plant, which has been shown to be present in the kidney and urothelial tissues of patients with ben. We believe that aristolochic acid contaminates wheat grain, which is likely the primary route of toxin ingestion in the Balkans.
On the genus (from Wikipedia):
Aristolochia is a large plant genus with over 500 species. Collectively known as birthworts, pipevines or Dutchman’s pipes, they are the namesake of the family (Aristolochiaceae). They are widespread and occur in the most diverse climates.
… The common names “Dutchman’s pipe” and “pipevine” (e.g. common pipevine, A. durior) are an allusion to old-fashioned meerschaum pipes at one time common in the Netherlands and northern Germany. “Birthwort” (e.g. European birthwort A. clematitis) refers to these species’ flower shape, resembling a birth canal. Some reference books state that the scientific name Aristolochia was developed from Ancient Greek aristos (άριστος) “best” + locheia (λοχεία), “childbirth” or “childbed,” [hence “well-born”] but according to an ancient tradition recorded in the first century BCE by Cicero the plant was named for the otherwise unknown individual with the common Greek name Aristolochos, who had learned from a dream that it was an antidote for snake bites. [The OED provides only the first etymology.]
… The species A. clematitis was highly regarded as a medicinal plant since the ancient Egyptians, Greeks and Romans, and on to until the Early Modern era; it also plays a role in traditional Chinese medicine. Due to its resemblance to the uterus, the doctrine of signatures held that “birthwort” was useful in childbirth. A preparation was given to women upon delivery to expel the placenta, as noted by the herbalist Dioscurides in the first century CE. Despite its presence in ancient medicine, Aristolochia is known to contain the lethal toxin aristolochic acid.
A. clematitis, which has escaped from cultivation into the wild in many places (including Britain).
Grollman’s letter continues:
As Batuman writes, it has been proposed that the designation ben be changed to aristolochic acid nephropathy (aan), a formal identifier that is critically important, as it would provide the impetus to change agricultural practices, thereby preventing contamination of crops. As an extension from the aristolochia research in the Balkan countries, another vital educational mission is now in progress in China and Taiwan, where aristolochia herbs are widely used for medicinal purposes. Taiwan has the highest incidence of upper-urinary-tract cancer in the world, characterized by the mutational signature of ben. Indeed, the traditional use of this family of highly nephrotoxic and carcinogenic herbs represents a significant problem for global public health. The example of aristolochia’s toxicities, unrecognized for centuries because of the long time between ingestion and the development of cancer, should give us pause.
So, an unsuspected source of toxin, a plant that not only grows wild in many places but has also long been employed in folk medicine. Shudder.