Cycad neurotoxin, consumption of flying foxes, and ALS/PDC disease in Guam

To the Editor:

The Cox and Sacks’ hypothesis on the century-old mysterious neurodegenerative disease of Guam was quite interesting.1 Vigorous epidemiologic and etiologic investigations by the National Institute of Neurological Disorders and Stroke for the past 50 years were mainly research by exclusion. Many hypotheses were postulated and then discarded due to negative results. These included genetic2-4⇓⇓ (before the age of molecular genetics) as well as environmental risk factors such as zoonoses and viral and prion infections.5-7⇓⇓ Whiting and Kurland at NIH extensively investigated food practices of the native Chamorros. They launched six International Conferences of Cycad Toxicity from 1962 to 1974.8 Amazingly, the cycad neurotoxic has been haunting those phytotoxin investigators over the past four decades, even though cycad was proved beyond a doubt to be epileptogenic, carcinogenic, and hepatotoxic, but not neurotoxic.8

Some 15 years later in 1987, Spencer’s BMAA experiment on the monkey surprised the neuroscience world.9 The July 31 issue of Science editorialized: “a combination of dogged determination and inspired science appeared to have solved the mystery of a brain disease in Guam… .” It was an instant sensation of hope and fervor in the history of ALS research. In fact, it was the old cycad story revisited with a monkey experiment using megadose of synthetic BMAA. Had Spencer used BMAA extracted from Cycad circinalis seeds from Guam, the monkey would have had to consume 40 kg of seeds a day, which is impossible. The neuropathology was that of subacute chemical encephalitis, not formation of pathognomonic neurofibrillary tangles. No lab throughout the world could reproduce his experiment10-12⇓⇓ and Spencer had to retract his paper from Science …