The Island of the Colorblind

Though Gajdusek might have been expected to be sympathetic to the idea of a slow toxin, he argued passionately against it in a sternly titled paper, ‘Cycad Toxicity Not the Cause of High-Incidence ALS⁄Parkinsonism-Dementia on Guam, Kii Peninsula of Japan, or in West New Guinea,’ asserting that such a hypothesis was, first, redundant; second, without precedent; third, without support; and fourth, impossible:

No neurotoxin has been demonstrated to give rise to fatal central nervous system disease, neurological signs and symptoms of which first start to be detectable years after exposure to the neurotoxin has ceased. In fact, we have no example of any toxin producing progressive damage to any organ years after last exposure to the substance…Only hypersensitivity disorders, slow infections, and genetically-timed disorders have given rise to this pattern of long delay.

Spencer, undeterred, saw Gajdusek’s words as a challenge (indeed he has cited them in several of his own papers), and continued to see his task as the search for a new kind of toxin, a new kind of toxic mechanism, hitherto unrecognized in medicine. A great deal of attention was focused, in the sixties and seventies, on carcinogenesis, the appearance of cancers, in some cases, years after an initial exposure to the carcinogen, whether radioactivity, a toxin, or a virus. It had been established, in Kur-land’s original cycad conferences, what a potent carcinogen cycasin was, capable of inducing liver cancers and colon and kidney malformations. It had been observed, moreover, that if infant rats were fed cycasin-high diets, the still-dividing Purkinje cells of the cerebellum might develop bizarre multinucleated forms and ectopic ‘nests,’ and such findings had also been reported, on occasion, in cases of human lytico-bodig.

What then might be the effect of cycasin, Spencer wondered, on adult nerve cells, which are no longer capable of dividing?

He and Glen Kisby have postulated recently that cycasin (or its component, MAM, or methazoxymethanol) may be able to form stable compounds with the DNA in nerve cells (such adduct formation is believed to underlie the overt carcinogenic and teratogenic effects of cycasin elsewhere in the body). This aberrant DNA in the nerve cells, he thinks, could lead to subtly but persistently altered metabolic functions, the nerve cells finally becoming oversensitive to their own neurotransmitters, their own glutamate, so that this itself could act as an excitotoxin. No external agent would be needed to provoke a neurological disaster at this point, for in this pathologically sensitized state, even normal neural functioning would now overexcite neurotransmitter receptor cells and push them toward their own destruction.

The notion of such a gene toxin is not as outlandish as it seemed a decade ago, and Spencer and Kisby have now observed DNA changes in tissue cultures of cells exposed to cycasin which suggest that such a mechanism may be at work in lytico-bodig. Such a gene toxin would actually alter the genetic character of the nerve cells it affected, producing, in effect, a genetically-based form of hypersensitivity disorder.

Now that Spencer was pondering the possible effects of cycasin on adult nerve cells, he had new analyses made of traditionally prepared cycad flours and found (contrary to what John had found earlier) that the Guam samples, even though low in BMAA, contained substantial amounts of cycasin. The highest levels of cycasin, indeed, were found in samples from villages with the greatest prevalence of lytico-bodig, lending strong circumstantial support to the hypothesis of cycasin toxicity.[72]