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22 April 2020

The mysteries of the brain

Despite 2,000 years of study, there is still so much we don’t know about how the brain works.

By Henry Marsh

Although some early authorities including Aristotle dismissed the brain as no more than a radiator for cooling the blood, it was already clear to many – such as Hippocrates and, later, Galen – that the brain plays a central role in our bodies and lives. Galen, rather horribly, contradicted Aristotle and demonstrated the primacy of the brain over the heart by showing that squeezing the heart of a vivisected animal did not stop it from squealing, but squeezing its brain did. It is hard for us now, looking back to the pre-scientific era, when there was no knowledge of electricity or chemistry, to appreciate just how difficult, indeed impossible, it was then to reach any kind of understanding of how our brains might work. How could one and a half kilograms of jelly generate thought and feeling? And yet, how does electricity and chemistry do it?

Matthew Cobb is a zoologist with a research interest in the neuroscience of smell (and also, inter alia, a historian of the French Resistance during the Second World War). In The Idea of the Brain he recounts the story of how philosophers and latterly scientists have tried to understand the brain.

Philosophers have spilt much ink on the so-called mind-brain problem, with their talk of qualia (individual instances of subjective, conscious experience) and arguments as to whether consciousness exists. Cobb eschews these pitfalls and verbal games. He quotes Francis Crick (who had moved into neuroscience after his work on DNA): “Listen to the questions that philosophers ask, but not to their answers.” Instead, Cobb takes a historical approach, although he is at pains to point out that he is trying to write not just a history of neuroscience, but also a cultural history of how we have tried to understand our brains.

He succeeds magnificently – the book is an intellectual tour de force, and a brilliant demonstration of how a historical approach is often the best way of explaining difficult scientific problems. Science is, after all, a long series of questions. You open a door into a room, only to find many more doors, with yet more rooms beyond them. You are less likely to get lost in the resulting maze if you start from the beginning.

Nonetheless, as Cobb tells us, the questions the early thinkers raised about the brain still resonate today, 2,000 years later. Perhaps to the surprise of many, our understanding of our brains remains remarkably limited despite the vast and detailed scientific knowledge that has accumulated since Hippocrates. We are little closer than he was to understanding how the activity of nerve cells gives rise to conscious experience. And then there is the “binding problem”. The activity of our brain is spread out in both space and time – there are probably at least 37 separate areas for vision – and yet we experience a unitary, integrated vision of the external world, and the illusion of the smooth passage of time. We cannot even begin to explain how our brains achieve this.

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Cobb combines scholarship with clarity to a remarkable degree, in the process resurrecting many forgotten names who made important and often prescient contributions to understanding the brain. The Danish anatomist Nicholas Steno, for instance, who in the 17th century was one of the first to describe the brain explicitly as a machine, which could only be understood by being taken apart. Or Julian Offray La Mettrie in the next century, who anticipated Charles Darwin by stating that from “animals to man there is no abrupt transition” (his book L’Homme machine was burned by the public hangman in Amsterdam, probably because of which it became a bestseller).

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There are also many famous names, such as René Descartes, who was inspired by the fashionable hydraulic automata seen in ornamental gardens, to use a hydraulic metaphor to explain how nerves functioned, but who invoked an immaterial soul that somehow communicated with the physical brain via the pineal gland. Gottfried Leibniz, on the other hand, was completely opposed to the concept of thinking matter. If the brain is a machine with moving parts, he argued, and you greatly magnified it so that you could enter it, it would be like entering a mill and seeing the moving cogs and wheels, but nowhere “would we find anything that would explain a perception”.

We are condemned to understand things in terms of ideas with which we are already familiar, and the history of neuroscience is essentially a history of analogy, driven by new scientific technologies. The 17th-century mechanical comparisons with hydraulics and mills came to be replaced in the 19th century by telegraphs and then telephone exchanges and in the 20th century by computers. But, as Cobb points out, these are all metaphors. The computer comparison is superficially compelling, but the brain does not work on digital principles – nerve cells are not simple on/off devices like transistors – and the idea that the brain represents the outside world in some form of neural code is far from certain.

In the 19th and 20th centuries it  was established that the human brain consists of nerve cells (86 billion at the most recent count) connected by electric action potentials and chemical transmission at synapses. The first attempts by Warren McCulloch and William Pitts in the 1940s to show how theoretical neural circuits could encode information in fact had more influence on John von Neumann’s development of computers than on neuroscience. 

The story becomes increasingly complicated in the past 100 years, and starts to involve artifical intelligence (AI) as well as electrophysiology, pharmacology, functional MRI scanning, optico-genetics, gene editing and abstract modelling, but Cobb makes it all entirely comprehensible without any recourse to obscuring jargon. (I was very reassured to find that I am not the only one who fails to understand Giulio Tononi’s integrated information theory of consciousness.) There is also now fascinating research into unconscious mental processes that is properly scientific, as opposed to Freud’s mythologising.

In the last two decades “Big Science” neuroscience projects have been set up, to the tune of billions of dollars. In Europe, the Human Brain Project – infamous for promising much that has yet to be delivered – plans to reverse engineer the brain from the bottom up using computer simulation. In the US, the “connectome” project aims to produce a complete wiring diagram of the 75-million-nerve-cell mouse brain (with a view to producing one of the human brain in the distant future). 

It is worth noting, however, that the recently published connectome of the hemibrain of the fruit fly drosophila, beloved of geneticists, with a mere 25,000 neurones, cost $40m and took 12 years. And then there is the “brutal fact” as Cobb calls it, that establishing the connectome of the ganglion that controls the lobster stomach – consisting of a few dozen nerve cells – does not fully explain its function. And the human brain, with 86 billion nerve cells? Structure is not everything, only a beginning. Brains are dynamic networks, not static maps. 

Cobb is suitably cautious about the future of brain research. We are drowning, he says, in a tsunami of data produced by thousands of laboratories. It is time for new metaphors. “Breakthroughs” are needed. In the parallel field of AI, we need breakthroughs to produce general AI (leading, perhaps to the “geek rapture” of the Singularity, when machine intelligence outstrips our own). In physics we need breakthroughs to marry quantum mechanics and general relativity, and now it seems that there is a similar impasse in neuroscience. 

You may recall the geneticist JBS Haldane’s remark that, “It is not only that the universe is queerer than we suppose. It might be queerer than we can suppose.” But it would be wrong to conclude that just because a problem is very difficult to solve it is impossible to solve. Cobb remains an optimist about the future of neuroscience. 

He doubts if Big Science will achieve much. He is, of course, a zoologist and hopes that further research on small brains –  even the brain of an insect, which Darwin described as marvellous and which the Astronomer Royal Martin Rees has said is so much more complicated than a star – will bring progress. What he does not explicitly mention is that we are very limited, for obvious ethical reasons, in the extent to which we can explore and experiment on human brains. This may yet prove a seriously inhibiting factor. Mice, after all, are not people, but they do have brains, and we have to start somewhere. 

For anybody who wants to understand the depths of our understanding of our brains, and our even deeper ignorance, I cannot recommend this book strongly enough. 

Henry Marsh’s books include  “Admissions: A Life in Brain Surgery” (Weidenfeld & Nicolson)

The Idea of the Brain: A History 
Matthew Cobb
Profile Books, 480pp, £30

This article appears in the 22 Apr 2020 issue of the New Statesman, The coronavirus timebomb