Recently John has embarked on a new series of studies, collecting DNA samples from all of his patients and sending them out for genetic analysis. He has been very excited by preliminary results indicating the presence of a genetic marker in several cases of bodig – a marker which seems to be absent in lytico and normal controls. His immediate reaction has been one of exuberance: ‘I feel the excitement coming again, and it’s a feeling I have not had since ‘86, when I was captivated by Spencer’s hypothesis.’ But it is an exuberance tempered by considerable caution (‘I don’t quite know what it means’). The search for genetic markers is extraordinarily laborious and difficult – it took more than a decade of incessant work to find a marker for Huntington’s chorea – and John is not sure whether these preliminary results will be borne out. (And even if a clear genetic basis is established for lytico and for bodig, John feels, this will indicate no more than a vulnerability or disposition; he has never doubted that some external agent is also necessary.)
It is now a third of a century since he and his colleagues delineated progressive supranuclear palsy in the early 1960s and perceived it as a unique yet exemplary disease which might shed some light on neurodegenerative disease in general. The similarity of the clinical picture of lytico-bodig and postencephalitic parkinsonism to PSP continues to intrigue him. He had been struck from the start by the fact that supranuclear palsies could also be observed in some patients with lytico-bodig, and on occasion in those with post-encephalitic syndromes too (on a recent trip to New York, he was intrigued to meet one of my post-encephalitic patients who has had a supranuclear palsy for more than thirty years). But he is not yet sure how to interpret these affinities.
He has been fascinated, as well, by the similarities of the neurofibrillary tangles which are so characteristic of lytico-bodig, post-encephalitic parkinsonism, and PSP with those of classic Alzheimer’s disease and has been investigating this with Patrick McGeer, a neuropathologist in Vancouver. The tangles themselves are virtually identical, as are the areas of inflammatory reaction about them (though there are other features of Alzheimer’s, most notably the presence of so-called ‘plaques,’ which one does not see at all in the other three diseases). At an immediate and practical level, the presence of these inflammatory reactions around the tangles makes him wonder whether anti-inflammatory agents can be helpful in lytico-bodig. Their use in Alzheimer’s disease is under study, and John is eager to see if they can help his own patients, if only to retard the course of a fatal disease. This is one of the few thoughts which gives him a brief sense of therapeutic optimism or hope, as he does his daily rounds among chronically ill and ever-deteriorating patients. And he is concerned by the steadily rising incidence of classic Alzheimer’s and Parkinson’s disease – which rarely if ever occurred on Guam before the Second World War – even as the native disease, the lytico-bodig, declines.
After forty years of research, then, we have four (or more) seemingly divergent lines of thought and research – genetic, cycadic, mineral, viral (Alma’s money is on prions) – each with some support, but with no overwhelming evidence for any of them. The answer will not be a simple one, John now feels, but a complex interaction of a variety of genetic and environmental factors, as seems to be the case in many diseases.[73]
Or perhaps it is something else, as Ulla Craig, one of John’s research colleagues, muses. ‘I’m not sure what we are looking for – though, like John, I have the feeling of some sort of virus that came and went. Some mutant virus, perhaps, with no immediate effect, but affecting people later, as their immune systems responded. But I am not sure. I am afraid we are missing something – this is the value of a fresh mind, seeing things in a new way, someone who may ask the question we have not asked. We are looking now for something complex, but it could be something we have overlooked, something very simple.’
‘Back in the 1940s and ‘50s,’ John mused, ‘there was a sense that we would find the cause of lytico-bodig in a matter of months. When Donald Mulder came here in ‘53, he thought he might have the problem solved by the time Kurland arrived six weeks later – but after forty-five years, it remains a complete enigma. Sometimes I wonder if we will ever decipher it. But time is running out: the disease may vanish before we can understand it… This disease has become my passion, Oliver, and my identity.’ If it is John’s passion and identity, it is Kurland’s, and Spencer’s, and many others’ as well. A colleague of mine, who knows and respects them all, says, ‘Guam has been a tar baby for all of them – once they get stuck, they can never let go.’
The disease is indeed dying out at last, and the researchers who seek its cause grow more pressured, more vexed, by the day: Will the quarry, hotly pursued for forty years now, with all the resources that science can bring, elude them finally, tantalizingly, by disappearing at the moment they are about to grasp it?
‘We’re on our way to see Felipe,’ John said as we climbed into his car once more. ‘You’ll like him, he’s a very sweet man. And he’s been touched by at least four different forms of lytico-bodig.’ He shook his head slowly.
Felipe was sitting on the patio at the back of his house, as he does most days, staring out, with a faint fixed smile, at his garden. It was a lovely garden, full of native plants, and the patio itself was shaded by banana trees. He has spent most of his life in Umatac, fishing and farming. He raises cockerels, and has a dozen of them, gorgeously colored, and all very tame. My neurological examination of Felipe was punctuated by the crowings of cockerels, a sound which he imitated, very loudly, to perfection (this was in striking contrast to his poor vocal volume when talking), by their perching on both of us during the exam, and by the affectionate nuzzling and occasional barking of his black dog. This was all delightful, I thought – rustic neurology, rural neurology, in the backwoods of Guam.
Felipe spoke movingly of his life and the past. He enjoyed fadang occasionally (‘we all did’), but he was not, like many other Chamorros, forced to subsist on it during the war. On the contrary, he spent the war as a sailor with the U.S. Navy, stationed part of the time in Portsmouth, Virginia (hence his excellent English), and he was part of the Navy force which retook Guam. He himself had to take part in the bombardment of Agana, a heartbreaking business, for it was the destruction of his native town. He spoke movingly of friends and family with lytico-bodig. ‘And now,’ he said, ‘I have it too.’ He said this quietly, simply, without a hint of self-pity or drama. He is sixty-nine.
His memory, intact for the past, has become severely eroded for recent events. We had in fact passed his house and stopped to say hello the previous day – but he had no memory of this, showed no recognition now we had come to visit again. When John told him the Chamorran version of his name (John Steele translates as ‘Juan Lulac’), he would laugh, repeat it, and forget it within a minute.
Though Felipe had an inability to register current events, to transfer them from short-term to permanent memory, he had no other cognitive deficits – his use of language, his perceptual powers, his powers of judgment, were all fine. His memory problem had worsened, very slowly, for about ten years. Then he had developed some muscular wasting – the thinning of his once thick and powerful farmer’s hands was striking when we examined him. Finally, a couple of years ago, he had developed parkinsonism. It was this, in the end, which had so slowed him down, taken him out of active life, made him a retiree in his garden. When John had examined him last, a few months before, the parkinsonism was entirely confined to one side, but it had progressed apace, and now affected both sides. There was very little tremor, just an overall immobility, a lack of motor initiative. And now, John showed me, there were the beginnings of a gaze palsy too, an indication of yet a fourth form of lytico-bodig. Felipe’s civility, his character, was perfectly preserved despite his disease, along with a sense of rueful insight and humor. When I turned to wave goodbye, Felipe had a cockerel perched on each arm. ‘Come again soon,’ he said, cheerfully. ‘I won’t remember you, so I’ll have the pleasure of meeting you all over again.’