Wetware: a computer in every living cell

Joseph Jebelli reviews ‘Wetware: a computer in every living cell’, by Dennis Bray.

Sir Paul Nurse, Nobel prize-winning biologist and President of the Royal Society, gave a fascinating lecture at the Royal Institution earlier this year on one of biology’s ‘great ideas’ – the Cell. Taking over 200 years to fully develop, the idea of all life being composed of cells is still not fully appreciated. “This was a major milestone in biology; we don’t recognise nor celebrate it enough,” explained Sir Nurse. But Dennis Bray, Professor of computational biology at Cambridge University, does exactly that in his beautifully crafted book, ‘Wetware: a computer in every living cell’.

Drawing on analogies from simple computer games, such as Pacman, Bray begins by discussing the peculiar feeding behaviours of single-celled organisms. Whilst the scholarly tone of his writing soon becomes apparent, Bray does well to ease the reader into to a complex subject by describing cells at their most basic level of organisation. He argues that humans are usually reluctant to ascribe subjective states, such as hunger, pain, or fear, to single-celled organisms. But does, for instance, an Amoeba’s rudimentary anatomy really lead to functional simplicity? As we learn more about these microscopic creatures, it is clear that even at this level, cells are nevertheless complex, organised systems that must have a high degree of knowledge about themselves and their surroundings.

Bray quickly descends into the molecular realm of the cell, wherein he likens chemical diffusion and enzyme biochemistry to the conditional connections inside a computer. Proteins, he argues, represent the ‘wires’ between different processes of a cell, akin in many respects to the circuitry of the human brain. The digital nature of DNA, exemplified by its reduction to a two-digit binary code, is also employed to bolster Brays overarching idea that biological systems use ‘computational elements’ to carry out logical operations. His point is that the cell is not just a haphazard ragbag of chemistry; there is something deeper, more intuitive, and highly non-random about how cells operate that we still cannot explain.

Developing the analogy of nerve cell circuitry, Bray goes on to explain how molecules can function in a similar fashion to neural networks, and thus be modelled computationally to understand how systems of proteins convey information about their environment. Over billions of years of evolution these networks have been refined, trained, and modified by experience to give rise to the higher human faculties, including memory, self-awareness, and consciousness. The prose inevitably becomes more philosophical towards the end, drawing on the thoughts of other complexity scientists such as Stuart Kauffman, who suggests that Darwinism is not enough to explain the kinds of spontaneous order we see in the natural world.

This book has been criticised by some for being too vague, and for not delving deep enough into the regulatory systems and mechanics underlying cellular intelligence. But they have clearly missed the point entirely. If you want detail, seek out a cell biology or biochemistry textbook. As the author puts it, ‘Fortunately, I do not need to know every detail of every last molecule for my argument’. Indeed, wetware is about the bigger picture, and by broadly discussing different aspects of cell function, Bray brings some long overdue theory back into biology.

As Sir Nurse declared, “Until this date, biological explanations have tended to be in a common sense world, but the complexity I think we’re going to see in biology may move us into a stranger world.” Strange, subtle, and exquisitely sophisticated, life at the molecular level is fast becoming an impenetrable chaos of complexity. In Wetware, Bray steps back to take stock of what two hundred years of research, and a few billion years of evolution has done for life as we know it today.

Joseph Jebelli is a Neuroscience PhD Candidate at University College London (UCL) studying the cellular and molecular mechanisms of neurodegenerative disease.

The Other Brain: The Scientific and Medical Breakthroughs That Will Heal Our Brains and Revolutionize Our Health’

Joseph Jebelli reviews ‘The Other Brain: The Scientific and Medical Breakthroughs That Will Heal Our Brains and Revolutionize Our Health’ by R. Douglas Fields.

Ask any academic studying the brain what the fundamentals of basic brain function are and you will almost certainly receive a lengthy monologue on neurons, synapses, and the electrical properties underlying learning and memory. But as Douglas Fields explains in this informative book, only 15% of the brain is comprised of neurons – what about the other 85%!? This ‘Other Brain’ represents another wholly different cell type, collectively known as glia.

Whilst neuroscientists have known about glia for over a century, they have been largely ignored, being regarded as mere passive support cells. It is on this note that Fields begins. Part 1 of the book outlines the history behind the so-called ‘neuronal doctrine’ and recounts the very first glimpses of the brains microscopic structure by the pioneers of modern neuroscience, including Ramon y Cajal, Camillo Golgi and Theodore Schwann. Grounded in the peculiar post-mortem observations of Einstein’s brain, this part of the book offers the reader a good lay overview of the basic cellular components of the brain, and the historical settings in which they were discovered.

Fields goes on to discuss how the technique employed by neuroscientists to study brain cells, namely electrophysiology, restricted their focus to the electrical properties of neurons. As electrically passive cells, glia communicate in other ways (e.g calcium signalling), and it is only now that we are beginning to appreciate just how widespread and crucial this method of communication is for basic neurobiology. His referencing is sound, citing a plethora of cutting-edge research, which does a great deal to put the reader at ease over the veracity of his claims.

The second part of the book is a thought-provoking and comprehensive discussion on the significance of glial cells to nearly all maladies of the brain, from Alzheimer’s and Parkinson’s to cancer, pain, and addiction. Fields manages to deliver a succinct report of recent discoveries on the role of glia in each disorder, whilst also putting forward many unanswered issues left to resolve. Particularly gripping is his chapter on scientist’s first encounter with the infectious prion protein, discovered by Dr Carleton Gajdusek in the 1950s, whilst living with and treating a cannibalistic forest tribe in eastern New Guinea afflicted by a disease known locally as ‘Kuru’. The letter excerpts from communications between Gajdusek and research colleagues back in the states vividly brings to life a powerful tale of adventure, endurance and a discovery that started a new field and is shaping others to this day.

Nonetheless, whilst I thoroughly enjoyed the second parts sweeping account on the role of glia in different brain disorders, there are occasions where the author overstates the implications of particular findings – a habit most likely picked up from years of writing research grants! What’s more, the lay style of writing that was evident at the beginning starts to fade as the book progresses, leaving me inclined to suggest that, on the whole, this may be more a popular science book for scientists than the lay public.

The final part of the book is more theory than fact, describing the overarching implications of glial cell biology to higher human faculties such as memory and consciousness. As a neuroscientist myself, I know that many in the field do not believe the binary electrical signalling between neurons is sophisticated enough to give rise to the higher human faculties, and that neuronal-glial cell communication may represent the true cellular substrate of such phenomena. As Fields points out, recent findings have shown glia can actually control neuronal excitability; a fact that certainly bestows these cells more prominence than the archaic notion of a passive support cell!

Although glial biology is still very much in its infancy, this book is an excellent guide to an exciting paradigm-shift occurring in neuroscience. I highly recommend it for anyone interested in our current understanding of the brain, and deem it mandatory reading for anyone who, like myself, spent too much time learning about neurons during their undergraduate studies.

Joseph Jebelli is a Neuroscience PhD Candidate at University College London (UCL) studying the cellular and molecular mechanisms of neurodegenerative disease.

The Tiger That Isn’t: Seeing through a world of numbers

Joshua Prettyman reviews ‘The Tiger That Isn’t: Seeing through a world of numbers’, by Michael Blastland and Andrew Dilnot.

This is one of the very best books I have read about the importance of being careful around numbers, written by the creators of radio 4’s More Or Less it is a fact-packed gold mine of interesting statistical nuggets that really make the reader pause to think. The book makes the analogy that the human instinct which tells us to run every time we see stripes just in case there’s a tiger applies just as strongly in the modern number-filled world. Who wouldn’t cheer the previous government for spending £300million to create new childcare places? The authors put that number into context and explain that it means roughly £1.15 per week per child; could you find childcare for £1.15 per week? The human brain is not set up for dealing with massive numbers and yet the papers are full of them, each week a story about the economy tells us that £70billion is spent here, £12trillion is owed there; slapping zeros in the headline sells papers but it is misleading. Saying, as papers in 2007 did, that the NHS had a deficit of £800million makes the institution appear to be in dire straits, saying that the NHS hit its targets to within a 1% margin makes it sound well managed, so which is correct? Both are in fact; £800million is only 1% of the NHS budget, it equates to less than the cost of one visit to our GP each! The press are looking to stir up trouble and if they want to make any government, or organisation, look bad it’s very easy to do so simply by confusing the public with large numbers. Similarly, if they wish to make someone look good, such as themselves or the political party they support, with clever reporting they can do just that and they depend on the public’s ignorance of statistics to bend our opinions.

But this book is not at all patronising, it never makes fun of the public for their shortcomings but treats the subject very maturely. The only time the authors resort to a more childish style is when it isn’t the general public but the professionals in charge who are so easily swayed by dodgy stats. There is an amusing (and rather worrying) account of a survey conducted at a conference of senior civil servants; when asked how much a family would have to earn to be placed in the top 10% of UK households some of those asked overestimated the figure by as much as five times! None got near to the true figure of £35,000 and these are the people who are in charge of taxes and benefits. Another case study involves asking 24 physicians what the chances are of a woman having breast cancer given that a test for it came back positive. The test is 90% accurate for a positive result and 93% accurate for a negative. Only 2 of the 24 got the correct answer (11%), 20 of them guessed around 90%, if you are a woman with an 11% chance of having cancer and some professional tells you that you have a 90% chance of having cancer there could clearly be a lot of unnecessary grief caused.

Like myself, I suspect that the authors wish to see a greater level of mathematical competency across all professions and in general, but this isn’t the message given by their book. Instead they merely call for us all to be more wary of big numbers and baffling percentages in the media, they constantly praise the good work of statisticians throughout and blame bad reporters and journalists for twisting the figures to fit their ideals. I was surprised how much I learned (as a mathematician I presumed I would encounter nothing new here) but the day after I finished the book I was told by the BBC news that drinking can increase a woman’s risk of cancer by as much as 20%! Oh my god, my own mother is on death row, 20% is a huge number, the women in my life are doomed (except my wife; she doesn’t drink). Or at least that’s what I might once have thought, but having read the tiger that isn’t I know better than that; the BBC will always tell you how much the risk is raised by but they never tell you what the risk actually is. Say the risk of any given woman getting cancer is 0.5%, a 20% increase means that this is raised from 0.5% to 0.6%; not so scary now, eh? But a number like 0.6% won’t grab the headlines, 20% will. This kind of alarmist reporting is everywhere, from the Daily Mail and the BBC to the Guardian and the Independent, journalists are shocking and caution is required at all times; a big number such as £800billion might look like a scary tiger but it’s often just grass waving in the wind and whenever this happens there is a reporter waiting to convince us that it really is a tiger and maybe make some money out of our panic.

I promise that you will look at the world differently after this book, if everybody reads it we might finally stop running from imaginary tigers and start dealing with numbers sensibly.

Joshua Prettyman is studying Maths at the University of Edinburgh but he has a massive passion for natural history and wildlife as well as all things scientific.

The First Circle

Toby Stead reviews The First Circle by Alexander Solzhenitzyn.

Slaving away in a dingy post-doc lab? Underappreciated? Underpaid? You’ve never had it so good!

The First Circle, by Nobel Laureate Alexander Solzhenitsyn, is a (thankfully) fictional account of science under Stalin. Thanks to Article 58 of the Soviet criminal code (under which the author himself was imprisoned during Stalin’s Great Purge), post-war Soviet Russia is blessed with thousands upon thousands of political prisoners. A large proportion are sent to forced labour camps, but the scientists and engineers among them represent a resource that ‘the Leader’ is loathe to waste.

Which is why Mavrino, the ‘special prison’ and principal location of the story, was established outside Moscow. A cross between a detention centre and a government research facility, Mavrino is the scene of an intensive programme of top-secret R&D commissioned by ‘the Boss’ himself. The irony of assigning ‘traitors’ to this kind of work is not lost on the inmates, yet for the most part they approach their work with all the dedication of free men.

I read this book with a wry smile throughout, enjoying the dark humour that the science brings, and the hypocrisy that it illuminates; obviously all research carried out outside the Soviet Union is completely false or is already known to it, therefore access to the huge library of overseas journals, without which Mavrino couldn’t function, is classified; despite their working conditions, all the prisoners are driven by the curiosity that led them to become scientists in the first place, and for the most part they comprise a remarkably successful institution; and the passages involving Stalin are perhaps the most entertaining, as it is here that one finds out the true ‘impact’ of Mavrino’s output: to placate the paranoia of the ‘Immortal One’. What a waste!

In conclusion – it’s a hefty tome, but a masterful one. The characters are charming (even the ‘bad guys’), and when you find yourself drawing parallels with the 12-14 hour days, the impossible deadlines and the miserly pay, Solzhenitzyn’s first-hand experience of Soviet oppression brings you rapidly back to earth.

Toby Stead works in public engagement with science in Bristol.

Early David Attenborough Books

 Joshua Prettyman reviews David Attenborough’s early books: The Zoo Quest Expeditions and Journeys to the Past.

These two books are, together, a compendium of Attenborough’s fantastic travel writing from his early expeditions during the 1950’s and early 60’s, long before he was a household name in natural history broadcasting. The first book covers his adventures in Guyana, Indonesia and Paraguay whilst the second book includes accounts of the expeditions to New Guinea, the Pacific islands, Madagascar and the Australian outback. I recently read both books and loved them; it’s so rare and interesting to read good travel tales from that period, before the days of global flight paths, English-speaking foreigners or even -in every single one of the places visited- currency.

The problems faced are enormous by modern standards but are all faced with enthusiasm and acceptance; I felt, as a reader looking back on these now historical events, that should I be forced to carry a camera and tripod the size of a grown man, along with provisions and other equipment, for whole days through dense jungle, that I would almost certainly die just when faced with the prospect of doing such, but they had no comprehension of today’s palm-sized, digital, HD cameras; they were just grateful that they weren’t encumbered with the even larger film cameras of the 1940’s. The future Sir David travels with very few companions, a surprise when compared to modern natural history productions such as ‘Planet Earth’ with team of hundreds; in the quest to Indonesia, only he and Charles Lagus are present, and between the two of them they must negotiate, barter and force their way through not only dense jungle but also uncooperative, bureaucratic customs officers and government officials with no English and little time for white men (they happen to be there just a few years after the natives won independence from the Dutch as a result of a bloody civil war), a miserable three weeks were wasted queuing up and signing forms in the squalid Jakarta.

It is truly inspiring to think how complicated travel must once have been before many countries had roads, rails or flight paths and before technology was as advanced as it is today; the ‘simple’ process of recording simultaneous sound and video is out of the question, a tape recorder is used to immortalise bird calls or native chants and music performed by enthusiastic villagers but the filming of animals is quite a separate matter and only very rarely is the tape recorder used to capture accompanying sound since the sheer number of cables and processes involved renders this all but impractical.

Of course, when a scientist sees an Attenborough book, they want to know about the natural history and the author provides excellent accounts of the animal encounters. It must be said, however, that filming animals was not the primary motive for these expeditions; the true purpose is to capture animals for the London zoo menagerie. It is heartbreaking for me to read dear Sir David’s account of his netting a (now endangered) Manatee in Guyana or of him collecting orang-utans, rare birds and lemurs for the befit of London’s crowds. But one must remember that attitudes were very different then and most of these areas appeared to contain bounteous supplies of exotic creatures. I hardly think, either, that the author’s actions aided the eventual decline of any single species, that prize must go to modernisation and deforestation. It is also reassuring that, although writing more than fifty years ago, Attenborough is still horrified when a companion (a native Dyak of Borneo) takes a shot at an orang-utan that has raided his bananas, even likening it to attempted murder, he is also scornful of the trophy hunter he meets in Australia and it is perhaps due to his collecting of animals, and the consequential films and books that this anti-eco endeavour produced, that the British are now, generally, so conscientious of wildlife and so disgusted by the once commonplace ‘sport’ of shooting beautiful creatures.

The most upsetting thing about every expedition, however, is the belligerence and arrogance of the disgraceful Christians who have set up missions in every corner of the globe and are purely intent on replacing every modicum of tradition, culture and free thought with bible verses. In the deepest part of the Amazon the adventures meet Akawaio Indians named Clarence and John (their Indian names are ‘sinful’) who have ‘had water thrown on them’ and told not to practice their own traditions. It is almost impossible to find Australian aborigines who still know how to paint in the traditional style and the majority of the native population live within a small radius of a mission which has given them tobacco and medicine in exchange for a promise not to live like a heathen in the bush and hunt kangaroo like their ancestors did. Even in the forests of New Guinea missions can be found, spreading their foul gospel to whoever will accept their bribes. The devastating effects of all this are most clearly seen on the small Pacific islands where confused natives worship bizarre cults, erect long bamboo poles (trying to imitate the white man’s radio masts) and talk to themselves all day into non-functional, wooden radios with the misguided belief that by imitating the white man they might live in luxury as he does: I have never been more angry at the folly of religion.

These books provide wonderful accounts of the trials and adventures faced by pioneering broadcasters and animal collectors, they give insights into how the political world has changed during such a short time span (Guyana, New Guinea, Australia are all members of the commonwealth at this time and Madagascar is under French rule whist Indonesia is only very recently free from the Dutch), how technology has changed and how our attitudes towards indigenous people and wildlife have changed too. But most of all, these stories are a delight to read and come highly recommended; read these books!

Joshua Prettyman is studying Maths at the University of Edinburgh but he has a massive passion for natural history and wildlife as well as all things scientific.

Is There Anything Good About Men?: How Cultures Flourish by Exploiting Men

Lili Tcheang reviews Is There Anything Good About Men?: How Cultures Flourish by Exploiting Men, a book about gender relations by Roy Baumeister.

Just finished the pop science book rather misleadingly titled Is There Anything Good About Men, written no less, by a man who is an eminent professor of psychology so I was looking forward to some good scientific reasons for his arguments.

The core proposal of his reasoning is that even though men tend to sit at the top of the social pyramid, actually men also sit at the bottom. Roy Baumeister goes on to explain that by focussing on the top we do not notice the bottom end of the spectrum, where men do the most dangerous jobs at the risk of their lives. Yes more men do make the most money but also more men die in the line of their work. It’s the age old statistical problem where once again we have not looked at the distribution but only at one specific slice.

A lot of the arguments in the book were very thought provoking and persuasive. But for a book from a scientist there really should have been proper referencing for each of his arguments.

For instance he states that men in China carry the responsibility for looking after parents in their old age. In fact Chinese law has stepped in to ensure that sons take care of their aged parents, or else they can be sued. In my very large Chinese family we have never known this tradition, and the responsibility often falls on the women although there are no hard and fast rules on this. I wonder whether there is an alternative explanation for the introduction of this law with the recent social changes in Chinese society as a result of the one child policy? Parents of sons may therefore have to rely on their only son to take care of them in their old age. Coupled with the fact that men tend to move away to find work, parents with an only son may find that they are no longer around and no longer inclined to look after them. Of course, I am also speculating here but without proper numbered referencing in the book itself, it’s rather difficult to trace the source of the responsibility on men, which lets the book down as I am sure a lot of the other arguments come from valid sources.

Second, is the argument of distribution, and at the risk of sounding like an old school teacher, yes we really should have paid more attention to statistics. Even though men also fall at the bottom end of the spectrum, a lot of studies tend to show that on average women fare worse. Whilst examining only the bottom end of the spectrum I can’t help thinking that Baumeister has made the same mistake at the opposite end by not looking at the mean, median or mode of the distribution, what happened to drawing box plots I say! OK I am beginning to sound like my A-level maths teacher now, so I’ll stop there. Nevertheless, I did agree with a lot of the arguments made, but only in the context of the western developed world. Again, I felt Baumeister let us down as scientists by not qualifying how his sample of men was obtained. Perhaps to him, the rather obvious status of many women in undeveloped countries is so apparent that it didn’t need mentioning.

This book is still a good read and provides insights about the roles of men and women in society. As a scientist, I would also recommend the lectures by Robert Wyman on the Global Problems of Population Growth, which goes one level deeper towards how genes and evolution result in society and behaviour. You can find that here.

Lili Tcheang is a cognitive neuroscientist from London currently working at the Institute of Cognitive Neuroscience, University College London. Her UCL website is here.