Researchers Focus on Cluster of ALS Cases in Guam
The war was almost over when Dr. Harry M. Zimmerman, a pathologist from Yale, arrived on Guam in 1945 as part of a Navy medical unit.
Five months later, he sent an urgent report to his commanding officer, saying he had seen seven or eight civilians hospitalized with amyotrophic lateral sclerosis. The fatal illness seemed to be shockingly common.
The physician and his colleagues soon calculated that the rate of ALS was 100 times greater on Guam and in some other Western Pacific communities than in the United States. For the last 40 years, scientists, including Zimmerman--now 91 and working at Montefiore Medical Center in New York--have been trying to figure out why.
The largest effort aimed at answering that question--and possibly shedding light on Parkinson’s and Alzheimer’s diseases as well--began recently, when four Guamanians arrived at the Mayo Clinic in Minnesota. There, the four islanders--two dying of ALS and two healthy--spent 10 days having the most advanced tests possible of their blood, brains, muscles and immune systems.
They are the vanguard of 60 Guam residents, half of them ill, who will make the 10,000-mile journey for tests that can’t be done in Guam, says Dr. Leonard Kurland, who is in charge of the two-year study.
ALS, which causes muscle-wasting, paralysis and death, is not the only disease being studied. Many islanders also have symptoms of Parkinson’s disease, such as muscular rigidity and shaking, and of Alzheimer’s disease, with its classic dementia. Most surprising, some Guamanians seem to have all three diseases at once. Thus, solving the Guam puzzle could help unravel larger mysteries.
“If we can show that there is a toxin that can produce these manifestations, it would be important with respect to ALS, Parkinson’s disease and Alzheimer’s,” said Kurland. He has been studying the Guam phenomenon for almost 40 years.
Among the causes that have been proposed are poisoning by the cycad seed, a dangerous palm nut used in cooking in Guam; aluminum toxicity from food sources; an unknown virus; genetic susceptibility, and overdoses of calcium (Guam is on a coral reef, making it easy for abundant calcium to spill into the local water supply).
Kurland began studying the disease in 1953, when, as a young researcher at the National Institute of Mental Health, he happened onto Zimmerman’s classified memo.
In the late 1940s, three naval reserve physicians stationed on the island went looking for more ALS patients and came upon 50. They estimated that the rate was 100 times greater than the average incidence of two cases a year for every 100,000 people.
The highest rate has been observed in Umatec, a village on the southwest shore. In 1954, a study by Kurland and colleagues reported that “one-third to one-fourth of all adult deaths in this village are due to amyotrophic lateral sclerosis.”
Zimmerman, who has also made ALS a lifelong research endeavor, continues to have brain tissue flown in from Guam. He and his colleagues have found strikingly similar alterations in the brains of Guamanians and of mainland Americans who had ALS, Parkinson’s or Alzheimer’s, indicating that each disease is the same in both places.
Researchers believe that an unidentified toxin could be triggering all three disorders, with symptoms changing as a result of the level of exposure.
In addition, the brains of Guamanians who had both ALS and Alzheimer’s symptoms show the nerve-cell tangles that are a hallmark of Alzheimer’s, Kurland and others have found. In the United States, patients with ALS do not have such tangles.
Of the possible causes, the cycad seed has undergone the most intensive study. Before World War II, parts of the cycad tree were eaten or used as medicine by villagers. Much of the tree turned out to be poisonous.
After the war, plant use slowed, and so has the rate of the illness, Kurland said. Now, epidemiologists are finding rates of 50 times higher than normal.
Monkeys fed cycad seeds in studies have developed severe muscle weakness, wasting and dementia-like behaviors, he added. But neither Kurland nor Zimmerman thinks the cycad will turn out to be the culprit. Zimmerman notes that he has studied families where only one member was sick despite sharing the same diet. He thinks there will probably be genetic links.
