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Raymond Chandler wrote that a detective story is “a tragedy with a happy ending”. Medical research is often compared to detective work, with each disease a tragedy, and a cure the happy ending, I suppose. But how apt is this comparison really?

That’s a question I ended up addressing in my first piece for Mosaic. I’d started out wanting to do something that people would find useful – explain exactly what goes wrong in Alzheimer’s disease. I pitched it as a molecular whodunnit, complete with the human brain as crime scene, various proteins as suspects, trails of genetic and pathological clues, a plethora of scientific Sherlock Holmeses, and me as a kind of Dr Watson guiding the reader through the mystery. A new genre, perhaps: ‘neuroscience noir’.

I was, perhaps, naïve. We still don’t really know very much for certain about Alzheimer’s disease at a molecular level. For patients and their loved ones, ‘what goes wrong’ is all too clear: it may start with lapses of memory but the disease progresses inexorably towards the loss of the capacity to function intellectually and then physically in the world. But while there are stark clues in the brains of people who die of it – lost brain cells, deposits of proteins called amyloid beta and tau, and so on – researchers haven’t been able to reconstruct all the events that lead to dementia. When proposed mechanisms of the disease have been put forward, treatments based on these theories have been disappointing in their effectiveness.

So Alzheimer’s remains an unsolved mystery worthy of the greatest fictional detectives. I couldn’t hope to represent it in all its complexity (there are enough twists and turns to fill a book, such as Margaret Lock’s recent The Alzheimer Conundrum). Instead, I tried to do what researchers do when they want to get a handle on the disease: construct something simpler.

Threading the labyrinth

‘On Exactitude in Science’, by Jorge Luis Borges, is a short short story in which a group of imperial cartographers have made a 1:1 scale map of the Empire that “coincided point for point with it”. Such a map is, of course, useless. Science works not by trying to replicate 1:1 every aspect of every thing in the universe – we have the universe for that – but by constructing models. Inevitably more simple than the real thing, models nevertheless allow for insight, comprehension and intervention.

This tension between complexity and simplicity seems to me to be fundamental to the philosophy of science – and also the biggest stumbling block when it comes to communicating it. How do you talk about something so complex in ways that other people will find informative rather than overwhelming?

Mosaic’s answer is to tell a great story that, through the telling, conveys some essence of the science behind it. I like that, but I also wanted to play with the forms of storytelling we can use. In choosing a frame of detective fiction, I felt I could afford to put less emphasis on characters and instead plot a century’s worth of research and the clues, deductions and theories that have tried to pick apart the tangle of Alzheimer’s disease. In a way, science itself became my detective, complete with ‘internal’ struggles, particularly the rift between two theories centred on the amyloid beta and tau proteins.

The clues are there

I’d started reading Mystery to a Solution, by John T Irwin. This book delves into the mesh of connections between three short stories written by Edgar Allan Poe – the first modern analytic detective stories – and three stories written exactly 100 years later by Borges. Poe and Borges are two of my favourite authors, hence choosing this book as my guide to the genre of detective fiction. But as I read Irwin’s comprehensive dissection of the links between them, I found myself adding the story of Alzheimer’s disease to the mix. In many regards, the story I was hearing in my interviews and research on this disease fitted with the points Irwin was making about Poe’s and Borges’s stories.

In particular, I was drawn to the recurrent image of the labyrinth. This features in many stories by Borges, who was once described as “the architect and prisoner of labyrinths”, and Irwin made the point that Poe’s first detective story, The Murders in the Rue Morgue, has elements that refer to the Greek myth of Theseus and the Minotaur, in which the hero has to find the monster at the centre of a labyrinth. The brain is often described as a maze, but I felt that I could build on this slightly jaded imagery in the context of Alzheimer’s disease, and perhaps come up with something that would be useful after all – a way of understanding what Alzheimer’s is, not in a scientific or clinical sense, but in a more poetic sense – and hopefully no less real for that.

One early temptation was to twist the features of the Alzheimer’s story into a convoluted knot of symbology such as you might find in a Dan Brown novel. The names of the two main proteins, amyloid beta and tau, with their Greek characters could easily suggest a path back to mythological stories. Tau of course can be found in Taurus and in the name of the Minotaur, the half-bull at the centre of the Cretan Labyrinth. But amyloid beta is often written in scientific literature as Aβ, and A was also associated with bulls in ancient Greece (an upside-down A looks like a bull’s head). Consider, too, that Poe’s detective hero was called Auguste Dupin and the first patient described by Dr Alzheimer was Auguste Deter (both with the initials AD, therefore, the same as Alzheimer’s disease itself); Deter was anonymised in Alzheimer’s report as Auguste D– while Dupin’s arch-rival was anonymised by Poe as Minister D–. The letter D itself has scientific associations, being the Latin equivalent of the Greek letter delta (Δ), the symbol of change, and I was asking what changes in Alzheimer’s disease… Trivial coincidences, but such stuff as (some) fictional detectives’ dreams are made on.

This would have felt rather forced if I’d put it in the final piece, though, not to mention potentially disrespectful to people who are dealing with the reality of Alzheimer’s disease. Even now, I’m hesitant about one image that might occur to the reader as a result: the Minotaur as a metaphor for Alzheimer’s disease – a condition in which the head becomes less human, intellectually degenerates; a brain at odds with the body, which is left to fend for itself. I hope that is not an offensive image (Borges might have defended me because he apparently identified himself with the Minotaur, as in his story ‘The House of Asterion’).

This idea of intellectual degeneration does, however, set up a tension between Alzheimer’s disease, which attacks the intellect, and both science and detective work, which prioritise the rational intellect as the most effective way of understanding the world. For me, this made Alzheimer’s disease an appropriate and specific ‘case study’ through which to examine the trope of comparing medical research to detective mystery-solving.

Finding the end

Right from the off I was worried about how to end this piece – after all, we are far from achieving a “happy ending” to the tragedy of Alzheimer’s disease. Given that there would be no denouement in the dining room, no revelation of exactly what had happened, no culprit arrested, what conclusion could I provide?

Poe begins ‘The Mystery of Marie Rogêt’ with a quote that starts: “There are ideal series of events which run parallel with the real ones. They rarely coincide.” It is a warning about the relationship between our perceptions, the truths we construct about the world, and real life. As one of the researchers quoted in the feature says, much of real life, including medicine, is ‘constructed’: specifically, we do not know whether what we call Alzheimer’s disease is one disease or many, or even just one subtype of neurodegeneration caused by dysfunctional protein folding.

The labyrinth is equally applicable, therefore, as a metaphor for the challenge of doing research into Alzheimer’s. Theseus had a simple ball of thread to lead him out of the labyrinth after defeating the Minotaur; researchers are trying to construct a similarly ‘simple’ solution (i.e. a single drug) to this convoluted, constructed disease. My editor, Mun-Keat Looi, and I talked about what note we should end on. I wanted to find some glimmer of hope for our readers in this labyrinth, while Mun-Keat was adamant that we should not sugar the pill if the situation was as confused as I was implying.

Well, the point about a labyrinth is that you never quite know how close you are to the way out until you actually get out. So, as I say in the piece, the solution may be just around the corner, but I’m afraid there may be a long way to go to get there all the same. And that’s where I leave the reader: in the labyrinth with the scientists and the patients, all looking for an exit.

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