Metamorphosis of a brain

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The Dying of Enoch Wallace: Life, Death, and the Changing Brain

McGraw-Hill: 2000. 256 pp. $24.95

Like Kafka's Gregor Samsa, Enoch Wallace woke up one morning to discover that he had changed. But whereas Samsa's metamorphosis was instantaneous, the metamorphosis of Wallach was slow, sometimes insidious, yet in no way less frightening. This book is about the transformation of a healthy human brain into a demented one. Ira Black, a clinical neurologist and prominent neuroscientist, invites us to accompany Wallace on his ordeal. Black uses a proven literary device: one story as a frame around another. The frame-story tells us how a powerful, self-confident, 62-year-old New York investment banker turns within a few years into a helpless resident of an old people's care home. The core story is about the biological processes that might have been contributing to the dying of Wallace's brain.

The Dying of Enoch Wallace should be considered in the context of recent developments in the neurosciences. They all relate to the question of how the brain generates and sustains our humanity and individuality. Consider, for example, the following issue: we change dramatically throughout life, yet normally maintain a sense of persistence of self over time. This leads to the intuition that, in our unstable world, at least our brain of today is the same as our brain of yesterday and of tomorrow. Alas, science has deprived us even of this meagre consolation: in recent years it has become evident that Heraclitus' maxim panta rei — “everything flows” — applies to the brain as well. Not only do nerve cells and synapses change their shape and function, some of them are born or die even while you are reading this passage.

The classical problem of 'the ship of Theseus' becomes inevitable: the mythical Greek hero's ship was placed on display in Athens, and over time parts of it were replaced, one by one, until none of the original remained. Is this still the same ship? Connections in our brain are continuously replaced — is this still the same brain? Well, it appears the same to us; science is challenged to demonstrate how this happens.

Even if we push metaphysics aside, the everlasting flux of brain tissue still leaves us with more tangible questions. How are our experiences encoded over time in an unstable substrate? How is an appropriate balance kept between birth, maintenance and death of connections in the brain? One of the conclusions of modern neuroscience is that development, response to stress, and learning and memory all share molecular and cellular universals. We thus become familiar with the molecular building blocks of the brain. We even get a notion of the algorithms executed by the neurons, and the circuits that are based on these building blocks.

But in most cases, we still miss the computational theories beyond it all. They should explain how stability is maintained in spite of the biological flux. In the meantime, the changing brain appears frail and ephemeral to us. And fragility is not merely a metaphor. We now believe that brains become demented when the balance between renewal, maintenance and death of brain tissue is disrupted. We certainly wish to know how this malfunction starts, and how we can stop it once it has been triggered.

The tragedy of dementia is the theme of the frame-story in this book. This will surely attract readers, because dementia is the terror of ageing societies. Only a century ago, less than 1% of the world's population was over 65 years of age. Now, it is already about 7%, and the prediction for 2050 is 15–20%. Therefore, ailments of old age such as dementias are becoming an epidemic.

The main concern is Alzheimer's disease. Named after the physician who first described it in 1906, it typically starts with recurrent lapses of memory, progressing to severe global memory deficits accompanied by other cognitive and emotional disturbances, and culminating in dissolution of personality and inability to perform even elementary bodily functions. This is what happens to the probably fictitious Enoch Wallace.

Black's account of this human misfortune is stereotypic and dry. We are left, hence, with the core story, which focuses on the discovery of growth factors in the nervous system, and their role in the development, maintenance and death of the brain. The description of how nerve growth factor and other neurotrophins were identified is interesting. The journey leads us to laboratories all around the globe, where we get to meet some leading investigators.

The factual depiction of the history of this field is clear and straightforward. Black does attempt to colour the facts with information about the people involved, but unfortunately the fate of these accounts is similar to that of Wallace and his family in the frame-story. The attributes of the heroes include physical appearance, sometimes their hobbies, rarely conceptual incentives. For example, we are told (twice) that a certain leader in the field is a “lean, sinewy 6 feet 5 inches”; his colleague is a “willowy 6 feet, 2 inches”; another is “short and spare of build”. Is neuroscience in the National Basketball Association? Some researchers are “wizards”, “stars” and “geniuses”, yet others are identified only by name; is this the evaluation sheet of the discipline?

The jury is still out on the causes of Alzheimer's. Possibilities include defective growth factors; faulty cholinergic neurons (nerve cells that secrete the neurotransmitter acetylcholine); and lesions in inter- and intracellular cascades, involving molecules such as amyloid precursor proteins and their so-called β-amyloid fragments, and resulting in the senile plaques and intracellular tangles that are the hallmark of Alzheimer's pathology.

Some important findings in the neurogenetics of dementia are missing from the book. This might be attributed to the rapid tempo of the field. It does, however, raise the question of when one should attempt to write the history of a discipline. It might also be due to the author's intention of focusing mainly on growth factors. However, the frame-story primes us to expect a broader account of what the dementias might be.

The seam between the frame and the core story is sewn in coarse, loose stitches. The text of the core story contains many technical terms and acronyms (all explained), and is accompanied by ample references, but this may not necessarily be attractive to the general reader. In spite of queries such as “Who are we? Where did we come from?”, it is not a philosophical book. Despite the potential Kafkaesque connotation at the introduction, literary fiction it is not. The glimpses of inside information about the scientific scene and the scientists who did the work do not suffice to ensure Enoch Wallace a prominent place on the shelf of scientific reportage: it lacks the thematic flow and captivating style of some other books in this expanding literary genre.

It is also not a personal account of how science is done; we miss an opportunity to really learn about the scientific culture at work from the point of view of a seasoned practitioner. The epilogue, expected to encapsulate the author's world view, occasionally reads too much like a proposal to a prospective donor: “how do we image a thought, an emotion, attention?” And the answer follows immediately: “Absurd religious questions [sic]. But neuroscience is providing the answer.” Still, The Dying of Enoch Wallace is a story about what is going on in a prominent subdiscipline of brain research in which matters of development, learning, ageing, life and death intermingle. As such, it might provide an incentive to read more about these matters.

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