A Shot Against Forgetting
Some of medicine’s most important answers arrive by accident. Israel is sitting on the next one.
Some of the most consequential discoveries in medicine arrive not from laboratories but from administrative accidents. A few years ago researchers at Stanford noticed that Wales had rolled out its shingles vaccine using a blunt rule: anyone born on or after a particular date was eligible, anyone born a day earlier was not. Two groups of people, near identical in everything that mattered, divided only by the side of a line they happened to fall on. When the scientists followed them, those offered the vaccine proved measurably less likely to develop dementia in the years that followed. Because the dividing line was arbitrary, the comparison came close to the gold standard of medicine, the randomised trial, without anyone having designed one.
That Welsh accident is one reason a once eccentric idea is now taken seriously. The shingles vaccine, accepted by most people only to avoid a painful rash, may also protect the ageing brain.
The evidence has been arriving from several directions at once. The Welsh result has not stood alone: the same natural experiment, repeated in Australia, returned the same answer, in a country whose dementia research ranks among the world’s most respected, anchored at the Prince of Wales Hospital and the University of New South Wales in Sydney. An Oxford team, sifting through medical records, found that people given the newer recombinant vaccine lived longer without a dementia diagnosis than those given the older formulation. This spring, in the journal Alzheimer’s and Dementia, a study of one and a half million American Medicare recipients reported that those who completed the two dose course carried roughly a third lower risk of dementia, with comparable reductions for Alzheimer’s disease and for vascular dementia. The protective signal, oddly and consistently, looks stronger in women. The earliest natural experiments, in Wales and Australia, tested the original live vaccine, now largely discontinued; the recombinant version that replaced it, the one now in Israeli arms, appears to protect at least as well.
The biology has caught up with the statistics. Shingles is the varicella zoster virus stirring back to life after decades of dormancy, and that reactivation is increasingly understood to inflame the nervous system and perhaps to rouse a second sleeping virus, herpes simplex, long suspected in the formation of the amyloid deposits that scar the Alzheimer’s brain. Calm the reactivation and you may, almost as a side effect, be defending the mind.
And yet none of it is settled, and every careful scientist says so. These remain associations, not proof. People who present for vaccination tend to be healthier, better educated and more watchful of their bodies than those who do not, and that difference alone could manufacture the appearance of protection where none exists. To convert a tantalising pattern into a finding a doctor can act on, you need one of two things: a vast randomised trial, which would take many years and a great deal of money before it spoke, or a population whose records are so complete, so linked and so clean that the confounding can be stripped out with confidence.
The world is now drifting towards the first option, slowly and expensively. Israel could supply the second.
Few countries are as well equipped to answer the question, and arguably none is better. Every Israeli resident belongs by law to one of four health funds, Clalit, Maccabi, Meuhedet and Leumit, each holding decades of linked electronic records under a single national framework rather than scattered across rival insurers and incompatible systems. Two of those funds have built research arms that now rank among the most productive in the world: the Clalit Research Institute, which covers more than half the population, and Maccabi’s Kahn Sagol Maccabi Research and Innovation Center, with its biobank of a million samples. Above them sits TIMNA, the health ministry’s national platform of deidentified records drawn from across the system. When the world needed to know, in real time, whether the coronavirus vaccines actually worked beyond the artificial conditions of a trial, it was Clalit’s records that produced the landmark study the rest of the world leaned on. Those analyses became the global benchmark precisely because the data were good enough to trust.
Better still, Israel has its own version of the Welsh accident, and it is dated with unusual precision. The recombinant vaccine entered the national health basket on the first of July 2023, recommended for those over fifty and subsidised for the over sixty fives and for younger people with weakened immune systems. A sharp threshold of introduction, set against a long and granular record of who was vaccinated and who was not, is exactly the instrument that lets researchers separate the effect of the vaccine from the character of the people who seek it out. The raw material for testing one of the most hopeful ideas in modern medicine is already sitting in Israeli databases, waiting to be read by anyone who thinks to look.
The stakes more than justify the effort. Dementia is the disease our lengthening lives have handed us. The global total is forecast to climb from around fifty seven million people in 2019 to some hundred and fifty three million by 2050, and there is still no cure and nothing yet that reverses the descent once it begins. Against that arithmetic, even a modest delay, multiplied across a population, would rank among the most valuable public health gains of the century. If a vaccine already on the shelf and already paid for can buy years of clarity, the case for finding out without delay is overwhelming.
There is something fitting in the prospect. The trail begins with a line drawn by accident in Wales and runs to a line drawn on purpose in Israel on a summer day in 2023. One was noticed by chance. The other is waiting to be examined. The difference between a curiosity and a discovery, in this instance, is simply whether someone with access to the right records decides the question is worth answering. In Israel, the records exist, the line is drawn, and the only thing still missing is the will to read them before another generation begins to forget.