Aristolochic acid, endemic nephropathy, and a great biological detective story

Aristolochia clematitisI know it is bad form to tell the solution of a mystery at the beginning of the story, but the solution is only the beginning. It is the story of the path to the solution that I find so interesting. The mystery, or actually mysteries, was the cause of endemic nephropathy (a horrible renal disease that was killing entire Baltic farming families) and if this disease had any connection to the nephropathies associated with some herbal supplements. The symptoms of the ailments were very similar, but on the surface it was not obvious how the two diseases could be related. It took literally years of detective work, collaborations and advancements in biological research techniques to find the connection, and that connection turns out to be aristolochic acid. The herbal remedies contained Aristolochia fanghi, an herb used in Chinese medicines, and the Baltic families were unintentionally consuming Aristolochia clematitis, which grew as weeds in their wheat fields. Both plant species were poisoning people who consumed them with aristolochic acid - one via their herbal weight-loss remedies and the other as a contaminant in their bread. I was tipped off to this fascinating biological detective story by a great article I saw in The Scientist entitled “Manna from Hell” which described the work of Arthur Grollman et al., which includes epidemiology, mutation, cancer and a lot of insightful observation. I’ve referenced his paper and an herbal supplement paper below, and you can find The Scientist article by searching on the title of the article at their site. I recommend checking these articles out if you too like a great biological detective story!

1. A.P. Grollman et al., “Aristolochic acid and the etiology of endemic (Balkan) nephropathy,” Proc Natl Acad Sci, 104:12129-34, 2007.Grollman, A.P., Shibutani, S., Moriya, M., Miller, F., Wu, L., Moll, U., Suzuki, N., Fernandes, A., Rosenquist, T., Medverec, Z., Jakovina, K., Brdar, B., Slade, N., Turesky, R.J., Goodenough, A.K., Rieger, R., Vukelic, M., Jelakovic, B. (2007). Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proceedings of the National Academy of Sciences, 104(29), 12129-12134. DOI: 10.1073/pnas.0701248104

2. J.L. Nortier et al., “Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fanghi),” N Engl J Med, 342:1686-92, 2000.

3. Aristolochia clematitis image of found 021408 at