by Oliver Sacks
She had not had any medication for several hours when we stopped by, and she was in an ‘off’ state, sitting completely motionless in a chair, her head bent, almost jammed, on her chest, only her eyes still capable of any movement. There was extreme rigidity in all her limbs. Her voice was very soft, flat, almost inaudible, and devoid of any animation or expression. She drooled constantly.
John introduced us, and I took her hand and squeezed it gently She could not speak, but she smiled back, her eyes crinkling, and I could feel a faint squeeze in response.
With a conspiratorial wink to Euphrasia, I said to John, ‘I’ll show you something – or Euphrasia will.’ I managed, with some difficulty, to get her to her feet. Walking backward in front of her, holding her gnarled hands, cueing her all the time, I was able to guide her, with tiny, tottering steps, to the garden just outside. There was a rock garden in the form of a little hill, with irregular ledges and slopes. ‘Okay,’ I said to Euphrasia, pointing to a rock, ‘climb over this, you’re on your own – go!’ To John’s horror, and the nuns’, I took my hands off her, and let her go. But Euphrasia, who had been almost incapable of movement on the flat, featureless floor of the dayroom, lifted her leg high, and stepped boldly over the rock, and then over another one, and another, up to the top of the rock garden, without difficulty. She smiled, and climbed down again, as surefootedly as she had gone up. As soon as she reached the level ground, she was as helpless as before. John looked rather stunned at this, but Euphrasia still had a ghost of a smile on her lips – she was not in the least surprised at all. And had she been capable of speaking, she might have said, like so many of my post-encephalitic patients, ‘If only the world consisted of stairs!’
It was two o’clock, the nun said, time for her medicine. She brought Euphrasia, now sitting in the dayroom once again, a tiny white pill with some water. Fourteen minutes after receiving her L-DOPA – we timed this, as if waiting for a chemical reaction, or explosion – she suddenly jumped to her feet with such energy her chair fell over backward, hurtled along the corridor, and burst into lively, even rambunctious, conversation, bursting with all the things she had wanted to say, but could not while she was frozen. This was not just a disappearance of her parkinsonism, her motor problems, but a transformation of her senses, her feelings, her whole demeanor. I had not seen anything like this in more than twenty years, and was both stunned (though I had half expected her to show such a reaction) and a bit nostalgic – Euphrasia especially reminded me of my postencephalitic patient Hester, in whom there was a similar, instantaneous transformation, with no intermediary state, no warming-up period whatever.
But it was not a wholly simple ‘awakening’ for Euphrasia, any more than it had been for hyperbolic Hester. For along with the motor animation, the liveliness, the playfulness, which suddenly came on her, there came a tendency to wisecrack, to tic, to sudden lookings and touchings, to tossing and darting, to jabbing and lunging – a dozen strange impulsions, a drivenness of body and mind. There was this tremendous rush of life, of extravagant activation, both healthy and pathological, and then, twenty minutes later, a re-descent into her original state, coupled with repeated yawning, a sudden complete lethargy.
‘What do you think of that, eh?’ asked John, at my side, eagerly. ‘Remind you of anything?’
When he is not seeing patients, John teaches at the Guam Memorial Hospital in Tamuning and does research in his laboratory there. He has lobbied hard for more research funding to be put into local facilities, and would like to establish a complete center on the island for investigating the lytico-bodig, with sophisticated neuropathology equipment and facilities for MRI scans and other brain imaging. At present, many of these studies have to be done on the mainland, while much of the epidemiological work – interviewing patients and piecing together extensive family trees – as well as basic clinical and lab work of various kinds, is done here on the island.
He showed me into his lab; he had something special he wanted me to see. ‘Let me show you these slides, Oliver,’ said John, waving me over to a microscope. I looked through the eyepiece, under low power first, and saw pigmented cells, symmetrically arranged in a V.
‘Substantia nigra,’ I said. ‘Many of the cells are pale and depigmented. There’s a lot of glial reaction, and bits of loose pigment.’ I shifted to a higher power, and saw a huge number of neurofibrillary tangles, densely staining, convoluted masses, harshly evident within the destroyed nerve cells. ‘Do you have samples of cortex, hypothalamus, spinal cord?’ John handed these to me, I looked at them one after another – all were full of neurofibrillary tangles.
‘So this is what lytico-bodig looks like,’ I said, ‘neurofibrillary degeneration everywhere!’
‘Yes,’ said John, ‘that’s very typical. Here’s another case – have a look at this.’ I went over it as before; the findings were very similar, and there was much the same distribution of tangles.
‘All the lytico-bodig cases look like this?’ I asked.
‘Actually, Oliver’ – John smiled broadly – ’what you’re looking at now isn’t lytico-bodig at all. It’s your disease, it’s postencephalitic parkinsonism – these slides were sent to me by Sue Daniel in London.’
‘I haven’t done much pathology since I was a resident,’ I said, ‘and I’m no expert – but I can’t tell them apart.’
John grinned, pleased. ‘Here, I have some more slides for you.’ I looked at this new series, starting with the substantia nigra, the midbrain, moving up and down from there.
‘I give up,’ I said, ‘I can’t tell whether it’s lytico-bodig or post-encephalitic parkinsonism.’
‘Neither,’ said John. ‘This is my disease, progressive supranuclear palsy. In fact, it’s from one of the original cases we described in 1963 – even then we wondered about its similarity to post-encephalitic parkinsonism. And now we look at the Guam disease…and all three look virtually the same.
‘Sue Daniel and Andrew Lees and their colleagues at the Parkinson’s Brain Bank have wondered whether these diseases are, in fact, related – perhaps even the same disease, a viral one, which could take three different forms.
‘These are very similar to the neurofibrillary tangles to be found in Alzheimer’s disease,’ John went on, ‘though in Alzheimer’s there are not as many, and they occur in a different distribution. So we have tangles – like little tombstones in the nervous system – in four major neurodegenerative diseases. Perhaps the tangles contain vital clues to the process of neu-rodegeneration, or perhaps they are relatively nonspecific neural reactions to disease – we don’t know.’
As we got back in his car to return to Umatac, John continued to sketch the history of the lytico-bodig. Another dimension was added to the problem as the 1960s advanced, and a curious change was observed in the natural history of the disease: cases of bodig, which had been much rarer than cases of lytico in the 1940s and early ‘50s, now came more and more to outnumber them. And the age of onset was also increasing – there were no more teenage cases (like the nineteen-year-old youth with lytico whom Kurland had seen), and almost no cases in their twenties.
But why should a single disease present itself chiefly as lytico in one decade, and then predominantly as bodig the next? Did this have something to do with age? – bodig patients, by and large, were a decade older than those with lytico. Did it have something to do with dose – could it be that the most severely exposed patients had their motor neurons knocked out in the 1950s, producing an ALS-like syndrome; whereas those exposed to less of the agent (whatever it was) were then caught by the slower effects of this on the brain, which might cause parkinsonism or dementia? Would most patients with lytico, were they to survive long enough, go on to develop bodig years later? (This, of course, was an impossible question, because lytico in its acute form cuts short the course of life. But Tomasa, still alive after twenty-five years of lytico, showed not a trace of bodig.) All of these questions were posed – but none of them could be answered.
Kurland had always felt that the possibility of cycad toxicity, however odd it seemed, should be investigated as carefully as possible, and to this end, he had organized, with Whiting, a series of major conferences starting in 1963 and continuing for a decade. The first of these were full of excitement, hopes of a breakthrough, and brought together botanists, nutritionists, toxicologists, neurologists, pathologists, and anthropologists to present research from all over the world. One constituent of cycad seeds was cycasin, a glycoside which had been isolated in the 1950s, and this was now reported to have a remarkable range of toxic effects. Large doses caused death from acute liver failure; smaller doses might be tolerated by the liver, but later gave rise to a variety of cancers. While cycasin did not seem to be toxic to adult nerve cells, it was one of the most potent carcinogens known.
There was renewed excitement when another compound found in cycad seeds was isolated – an amino acid, beta-2V-methylamino-levoalanine (BMAA), very similar in structure to the neurotoxic amino acid beta-N-oxalylamino-levoalanine (BOAA), which was known to cause the paralysis of neuro-lathyrism. Was BMAA, then, the cause of lytico-bodig? It had been administered in many animal experiments, John said, but none of the animals developed anything like lytico-bodig.
Meanwhile there were two further discoveries of an epidemiological sort. In 1962 Carleton Gajdusek, who had been working on the cause of kuru, a fatal neurological disease in eastern New Guinea (work for which he was later awarded a Nobel Prize), now found an endemic lytico-bodig – like condition among the Auyu and Jakai people on the southern coastal plain of western New Guinea.65 This proved indeed to be an extraordinarily ‘hot’ focus, for the incidence of disease here was more than 1,300 per 100,000, and thirty percent of those affected were under the age of thirty. At about the same time, in Japan, Kiyoshi Kimura and Yoshiro Yase discovered a third focus of a lytico-bodig – like disease on the Kii Peninsula of the island of Honshu. But in neither of these places did they find any cycads.
With these new findings, and the inability to produce an animal model of the disease, the plausibility of the cycad hypothesis seemed to fade. ‘The cycad proponents thought they had it,’ said John, somewhat wistfully. ‘They thought that they’d cracked the lytico-bodig, and it was a real loss to let the cycad hypothesis go. Especially as they had nothing to replace it; they were left with a sort of conceptual vacuum.’ By 1972 only Kurland continued to consider it a possibility, but for most of the researchers, the cycad hypothesis had died, and attention turned elsewhere.
John had arranged to take me that evening to a Japanese restaurant in Agana. With our huge tourist trade, he said, we get the best Japanese food in the world here, outside Japan. As we sat down and studied the enormous, exotic menus before us, I was interested to see fugu, puffer fish, listed; it was ten times as expensive as anything else on the menu.
‘Don’t try it!’ said John, adamantly. ‘You have a one in two hundred chance of being poisoned – the chefs are highly trained, but sometimes they make a mistake, leave a trace of skin or viscera on the fish. People like to play Russian roulette with the stuff, but I think there are better ways to die. Tetrodotoxin – a ghastly way to go!’
On Guam, John continued, warming to his theme, the most common form of toxic seafood illness was ciguatera poisoning – ’It’s so common here, we just call it fish poisoning.’ Ciguatoxin is a powerful neurotoxin produced by a tiny organism, a dinoflagellate called Gambierdiscus toxicus, which lives among the algae that grow in channels on the coral reefs. Herbivorous fish feed on the algae, and carnivorous fish in turn feed on them, so the toxin accumulates in large, predatory fish like snapper, grouper, surgeonfish, and jack (all of which I saw on the menu). The ciguatoxin causes no illness in fish – they seem to thrive on it – but it is very dangerous to mammals, and to man. John is something of an expert on this. ‘I first saw it when I was working in the Marshall Islands twenty years ago – a fourteen-year-old boy, who became totally paralyzed, with respiratory paralysis as well, after eating a grouper. I saw hundreds of cases in those days. There were fifty-five different species of fish we found which could carry the ciguatoxin. There is no way a fisherman can tell whether a particular fish is toxic, and no way of preparing or cooking it that will deactivate the toxin.
‘At one point,’ he added, ‘people wondered if the lytico might be caused by some similar kind of fish poisoning – but we’ve never found any evidence of this.’
Thinking of the delectable sushi I had looked forward to all day, I was conscious of a horripilation rippling up my spine. ‘I’ll have chicken teriyaki, maybe an avocado roll – no fish today,’ I said.
‘A wise choice, Oliver,’ said John. ‘I’ll have the same.’
We had just started eating when the lights went out. A groan – ’Not again!’ – went around the restaurant, and the waiters quickly produced candles, which they lit. ‘They seem very well prepared for power outages,’ I said.
‘Sure,’ said John, ‘we have them all the time, Oliver. They’re caused by the snakes.’
‘What?’ I said. Did I mishear? Was he mad? I was startled, and for an instant wondered if he had somehow eaten some poison fish after all, and was beginning to hallucinate.
‘Sounds odd, doesn’t it? We have millions of these brown, tree-climbing snakes everywhere – the whole island is overrun by them. They climb the telephone poles, get into the substations, through the ducts, into the transformers, and then, pfft! We have another outage. The blackouts can happen two or three times a day, and so everyone is prepared for them – we call them snakeouts. Of course, the actual times are quite unpredictable.
‘How have you been sleeping?’ he added, inconsequentially.
‘Rather well,’ I said. ‘Better than usual. At home, I tend to be woken by the birds at dawn.’
‘And here?’ John prompted.
‘Well, now you mention it, I haven’t heard any birds at dawn. Or any other time, It’s strange; I hadn’t realized it until you asked.’
‘There is no birdsong on Guam – the island is silent,’ John said. ‘We used to have many birds, but all of them are gone – there is not a single one left. All of them have been eaten by the tree-climbing snakes.’ John had a prankish sense of humor, and I was not quite sure whether to believe this story. But when I got back to my hotel that evening, and pulled out my trusty Micronesia Handbook, I found confirmation of all that he had said. The tree-climbing snake had made its way to Guam in the hold of a navy ship toward the end of the Second World War and, finding little competition among the native fauna, had rapidly multiplied. The snakes were nocturnal, I read, and could reach six feet in length, ‘but are no danger to adults as their fangs are far back in their jaws.’ They did, however, feed on all manner of small mammals, birds, and eggs; it was this which had led to the extinction of all the birds on Guam, including a number of species unique to the island. The remaining Guam fruit bats are now in danger of vanishing. The electrical outages, I read, cost millions of dollars in damages each year.66
The next morning I had arranged to spend some time hunting for ferns in the Guamanian jungle. I had heard of Lynn Raulerson, a botanist, from my friends at the American Fern Society in New York. She and another colleague, Agnes Rine-hart, both work at the herbarium at the University of Guam and had published, among other things, a delightful book on Ferns and Orchids of the Mariana Islands (its frontispiece, a representation of the life cycle of a fern, was drawn by Alma). I met Lynn at the university, and we set off for the jungle, accompanied by one of her students, Alex, who was equipped with a machete. Alex remarked on the denseness of the forest in places. ‘You can still get completely lost, even with a good sense of direction,’ he said. ‘You go five yards in, and it’s so thick, you’re already dislocated.’
The road itself was soon surrounded by an ocean of very large, bright-green sword ferns. Hundreds, thousands, of them pointed straight up into the air, almost as far as we could see. Nephrolepis biserrata, at lea
st the variety we saw, is not your ordinary, humble sword-fern, but a species indigenous to the Marianas, with huge fronds sometimes as much as ten feet long. Once we had waded through these, we were into the jungle, with its great pandanus and ficus trees, and a canopy so dense it closed over our heads. It was a jungle as rich, as green, as any I had ever seen, the trunks of every tree blanketed with a dozen epiphytes, every available inch crowded with plants. Alex walked a few yards ahead of us, clearing a path with his machete. We saw huge bird’s-nest ferns – the Chamorros, Alex told us, call them galak – and a smaller ‘bird’s-nest’ fern which looked like a close relative, but was actually, Lynn told me, a different genus, a Polypodium indigenous to the Marianas.
I was delighted to see ferns of all shapes and sizes, from the lacy, triangular fronds of Davallia, and bristly Pyrrosia sheathing the trunks of the pandanus, to the gleaming shoestring fern, Vittaria, which seemed to hang everywhere. In moist, protected areas we saw a filmy fern, Trichomanes, which excited me, not just because of its delicacy and beauty, but because Safford, in an uncharacteristic error, had written that there were no filmy ferns on Guam (there are actually three species, said Lynn). We came upon the rare Ophioglossum pendulum, an immense ribbon fern with great succulent fronds, rippling and forking as they descended from the crotch of a tree.67 I had never seen this species before, and even Lynn was excited to find it. We took pictures of it, with ourselves standing by – as one might photograph oneself with a marlin one had caught, or a tiger. But we were careful not to disturb the plant – and glad to think that our path to it would close itself up within days.
