2019 Top 10 Book Review – Ajit Singh, Managing Director and General Partner, Artiman

I have been writing these reviews since 1993. With two gap years, 2001 and 2014, this is Serial Number 25. My stated criteria for a book making to the Top-10 has been the same each year: am I likely to read this book again. Earlier this year, I was tempted to make good on that promise (to myself). But I didn’t. The tug of new books was stronger.

Instead, I went back and re-read the reviews of the past 25 years – nearly 200 pages in all – and some of the blogs that keep me up to date with new books. During this cathartic reading binge, the piece that I most (re)connected with was from Maria Popova’s 2015 Brain Pickings: “Paradoxically enough, the fragment of the universe we seem least equipped to grasp is the truth of who we ourselves are. Who are we, really, when we silence the ego’s shrill commands about who we should be, and simply listen to the song of life as it sings itself through us? That’s what French-born, Baltimore-based artist Jean-Pierre Weill explores in The Well of Being, an extraordinary ‘children’s book for adults,’ that peers into the depths of the human experience and the meaning of our existence, tracing how the stories we tell ourselves to construct our personae obscure the truth of our personhood, and how we can untell them in order to just be.” [More about The Well of Being later in this review]

Our thoughts, and more generally our lives are often inadvertent chains of causal linkages. Maria Popova’s passage made me think about two things – what the passage meant, and what the passage meant to me. Why was I was drawn to it? This reflection led me back through some specific moments of the past several years: when I felt most deflated. As infrequent as these incidents were, they had a common theme. In each of them, I either felt misunderstood, or felt that someone was viewing me through an incorrect or a reductionist lens. In other words, their (stated) version of me severely clashed with my version of myself.

In October this year, I attended Adam Gazzaley’s workshop on brain health at UCSF. This introduced me to several new works in neuroscience – if only to reinforce how little we understand the brain. While the field has made tremendous progress in the recent years, our ability to truly help people with afflictions of the brain has a long way to go, as does our definition of what it means to be normal. Perhaps we all on the spectrum.

Other influencers of what I read this year were some notable students and mentees. Mid-year, on a flight to Delhi, I read the Honor’s thesis of Gil Kornberg. First off, it was beautifully written – mature thinking and mature writing. Second, it gave me many new reading recommendations. Of these, the one that struck a chord with me the most was the 2015 MIT Report, “The future postponed: Why Declining Investment in Basic Research Threatens a US Innovation Deficit.” While the report had a US focus, the issue is quite universal. It also triggered me (caused me?) to start thinking about what I want to do professionally a few years from now. [https://dc.mit.edu/sites/default/files/Future%20Postponed.pdf]

In summary, in a stark contrast to last year when the books I read had an outward focus – politics and societal changes with a dystopian bend – this year was marked with looking inwards and reading books that catalyze introspection. Categories remain the same as those in the past: Fiction, Memoir, Philosophy, Management/Economics, History/Politics, Science, and Mathematics.


1.      Sally Rooney, Normal People, Faber and Faber, 2018

I am not much of a TV person, but I occasionally flip through channels while on airplanes – especially when the meal on the tray table gets in the way of the laptop or a book. This past October I caught a preview of the upcoming BBC TV series based on Normal People.

I believe I have discovered a new favorite author whose works I am going to follow closely. I can also say that epithets like “Salinger for the Snapchat generation” do not do justice to Sally Rooney’s caliber, even though the Salinger bit is probably correct. The book was long-listed for the Man Booker Prize.

In the words of the NPR reviewer, “Marianne and Connell fall into an intense, complicated relationship that’s repeatedly muddled by secrecy, miscommunications, and anxiety about their place in the social hierarchy…. Rooney demonstrates that she is gender blind when it comes to insecurities. Normal People’s third person narrative, which alternates convincingly between Marianne’s and Connell’s points of view, wryly underscores the gap between their perspectives, even at the best of times…. Among Rooney’s abiding concerns are the fluctuating power dynamics in relationships. Issues of class, privilege, passivity, submission, emotional and physical pain, kindness, and depression all come into play. Her focus is on young adults as they struggle to navigate the minefields of intimacy against the backdrop of an economically uncertain, post-recession world threatened by climate change, political upheaval, and questions about the morality and viability of capitalism. Rooney’s characters may be academically gifted, but they aren’t sure how they want to live or what they want to do with their lives. In response to emotional injury, they sometimes seek physical pain. When overwhelmed, they detach. A crippling sense of unworthiness chafes against feelings of intellectual superiority.”

If you are looking for a plot, there isn’t one. Rather, it is narrative of real life – of a generation to which my (now grown up) children belong. Here is an extract, illustrative of the meter and style of prose, as well as the nuances of its content.

The silence becomes very intense after that. For a few seconds he lies still. Of course, he pretends not to know Marianne in school, but he didn’t mean to bring that up. That’s just the way it has to be. If people found out what he has been doing with Marianne, in secret, while ignoring her every day in school, his life would be over. He would walk down the hallway and people’s eyes would follow him, like he was a serial killer, or worse…. With his friends, he acts normal. He and Marianne have their own private life in his room where no one can bother them, so there’s no reason to mix up these separate worlds. Still, he can tell he has lost his footing in their discussion and left an opening for this subject to arise, though he didn’t want to, and now he has to say something…. For a moment it seems possible to keep both worlds, both versions of his life, and to move between them just like moving through a door. He can have respect of someone like Marianne, and also be well liked in school, he can form secret opinions and preferences, no conflict has to arise, he never has to choose one thing over another. With only a little subterfuge he can live two entirely separate existences, never confronting the ultimate question: what to do with himself, or what kind of person he is. This thought is so consoling that for a few seconds he avoids meeting Marianne’s eye, wanting to sustain the belief for just a little longer. He knows that when he looks at her, he won’t be able to believe it anymore.

If you want a flavor of Rooney’s writing in short fiction format, try Color and Light (The New Yorker, March 2019). Her interview https://www.youtube.com/watch?v=pqWEiiELzfoat the Louisiana Literature festival is also worth watching if you can spare a half hour.

Her 2017 debut novel Conversations With Friends is in my stack of books to read.


2.      William Finnegan, Barbarian Days: A Surfing Life, Penguin, 2016.

The scaffold that holds this rich memoir together is surfing.

I am afraid of water. I never learnt to swim.

Why did I end up reading this book? It was because of a conversation with my friend André Brink during a visit to Cape Town in 2007.

André and I had first met in Berlin in 1989. The Berlin Wall was still there. Mass media was replete with rhetoric about the upcoming economic upheaval in Europe. In one of our discussions, I said, “Someday I would like to study economics, formally, in order to make sense of all this.” He looked at me, quizzically. Almost being defensive, I responded, “I believe that someone trained in physics and engineering can easily study economics later in life. The reverse would be very difficult.” Brink was silent for a while, then he said very thoughtfully, “I supposed you are right. Someone trained as a journalist could become a novelist later in life. The reverse would be very difficult.”

In our meeting in 2007, I reminded André of that conversation. I asked him if he still believed in the statement, “…the reverse would be very difficult.” He said, “yes,” almost instinctively, then paused, and added, “unless you are a William Finnegan.”

Finnegan studied English Literature at UC Santa Cruz in the early 1970’s. Working as a school teacher in Cape Town nearly a decade later brought him face to face with apartheid. This experience led him to write his first book, Crossing the Line: A Year in the Land of Apartheid, and marked his transition from a novelist to a political journalist.

About Barbarian Days: A Surfing Life, Thad Ziolkowski writes in the New York Times book review, “Most canonical accounts of surfing, from Captain Cook to Tom Wolfe, are written by non-surfers who tend to wax gooey about the sport’s joys while getting its mechanics and ethos laughably wrong. Yet when surfers themselves began to write about it, in the 1960s, what they produced was usually bad in other ways — pretentious, semiliterate, purple or merely slight. It came to seem that surfing, like some pagan mystery cult, might simply defy literary representation, remaining properly understood only by initiates who were too busy surfing to learn to write. Then, in the summer of 1992, there appeared in The New Yorker a long, two-part article by William Finnegan titled Playing Doc’s Games that was instantly recognized as a masterpiece. A wise, richly atmospheric account of riding the gelid, powerful gray waves of San Francisco while negotiating the demands of a fanatical surfer-oncologist Dr. Mark Renneker, Playing Doc’s Games combined the deep knowledge of a widely traveled hard-core surfer, the observations of a born ethnographer and the wry aplomb of a New Yorker staff writer… With Barbarian Days, we finally have that extraordinary book in full, including, largely unchanged, Playing Doc’s Games. It is in many ways, and for the first time, a surfer in full. And it is cause for throwing your wet-suit hoods in the air.”

Here is a sampling of Finnegan’s prose – lucid, stably poised on the fulcrum of precision and detail.

“Ignorant of all of this, my parents sent me to the nearest junior high, up in the working-class Kaimuki, on the back side of Diamond Head crater, where they assumed I was getting on with the business of the eighth grade, where in fact I was occupied almost entirely by rigors of bullies, loneliness, fights, and finding my way, after a lifetime of unconscious whiteness of segregated suburbs of California, in a racialized world. Even my classes felt racially constructed. For academic subjects, at least, students were assigned, on the basis of test scores, to a group that moved together from teacher to teacher. I was put in a high-end group, where nearly all my classmates were Japanese girls. There were no Hawaiians, no Samoans, no Filipinos, and the classes themselves, which were prim and undemanding, bored me in a way that school never had before. Matters weren’t helped by the fact that, to my classmates, I seemed not to exist socially. And so I passed class-hours slouched in the back rows, keeping an eye on the trees outside for the signs of wind direction and strength, drawing page after page of surfboards and waves.”

As if in a telling metaphor of life, he writes, “But surfing always had this horizon, this fear line, that made it different from other things, certainly from other sports I know. You could do it with friends, but when the waves got big, or you got into trouble, there never seemed to be anyone around.”

The book is as much a chronological portrait of every wave that Finnegan encountered across the world, rich in texture and detail, as it a reflection on the core of his life-drivers – impulse, courage and strength – whether the arena be the ocean, or the many war zones in El Salvador and Sudan from where he reported for the New Yorker. 

In one word: Masterpiece.

If you are inclined to read the book, I suggest that you also consider some of his unrelated pieces in the New Yorker, https://www.newyorker.com/magazine/2013/04/29/the-deportation-machine, or https://www.newyorker.com/magazine/2017/09/18/is-ending-daca-the-worst-decision-trump-has-made. Also, the first 10-15 minutes of https://www.youtube.com/watch?v=5tibiTwayjU are very telling: why he decided not to use the word ‘anarchy’ in his 12,000 word story on Somalia.


3.      Jim Holt, When Einstein Walked with Gödel: Excursions to the Edge of Thought, Farrar, Straus and Giroux, 2019

Institute for Advanced Study was a short walk from the Electrical Engineering department at Princeton where I used to teach in the early 1990’s. My friend George Chaikin and I used to frequently go to the Institute for the afternoon lecture. George, a true renaissance man – an architect, a computer scientist, and a student of science history – helped me regain my literacy in physics while teaching me about the events from the early days of the Institute.

In 2004 when I covered John Casti’s The One True Platonic Heaven in my Top-10, it was as much out of nostalgia of Princeton days as out of fascination with the Einstein-Gödel dialog. Fifteen years later, when I came across When Einstein Walked with Gödel, it evoked the same tuple of conjoined feelings – with nostalgia being the more dominant one this time around. The richness and diversity of the table of contents was enough to draw me in:

When Einstein walked with Gödel

Time – the grand illusion?

Numbers guy: the neuroscience of math

The Riemann Zeta conjecture and the laughter of the primes

Sir Francis Galton, the father of statistics…and Eugenics

A mathematical romance

The avatars of higher mathematics

Benoit Mandelbrot and the discovery of fractals

Geometrical creatures

A comedy of colors

Infinity, large and small. Infinite visions: Georg Cantor v. David Foster Wallace

Worshipping infinity: why the Russians do and the French don’t

The dangerous idea of the infinitesimal

The Ada perplex: was Byron’s daughter the first coder

Alan Turing in life, logic, and death

Dr. Strangelove makes a thinking machine

Smarter, happier, more productive

The string theory wars: is beauty truth?

Einstein, “Spooky action,” and the reality of space

How will the Universe end?

Quick studies: a selection of shorter essays

Dawkins and the deity

On moral sainthood

Truth and reference: a philosophical feud

Say anything

The book is a collection of essays previously published by Jim Holt. One of the finer testimonies to Holt’s brilliance is John Horgan commentary in Scientific American, “When I’m in a provocative mood, I argue that it’s tougher to make it in science writing than in science, hence science writers are, on average, smarter than scientists. As an (admittedly single) data point, I might cite Jim Holt. As he demonstrates in his 2012 bestseller Why Does the World Exist? and new essay collection When Einstein Walked with Gödel Holt writes with pizzazz about scientific, mathematical and philosophical concepts that cow lesser minds. No mere explicator, he is intellectual aesthete, a connoisseur of concepts. He holds ideas and their inventors up to the light for our delectation, pointing out features that we might have missed. In the preface of his new book he says his goal is to enlighten the newcomer while providing a novel twist that will please the expert. And never to bore.”

Jim Holt’s 2014 TED talk https://www.ted.com/talks/jim_holt_why_does_the_universe_exist is a treat – if only for its punchline at minute 16:40. Also, if you simply want to try out a few of his essays before committing to the book, https://www.newyorker.com/contributors/jim-holt is a good place to start.

4.      Giulio Tononi, Phi: A Voyage from the Brain to the Soul, Pantheon, 2012

This is an older book. I missed it when it originally arrived in the bookstores in 2012. I learnt of it only during a conversation with David Eagleman in 2017. We were talking about the musical adaptation of Eagleman’s book Sum when the conversation turned to the topic of consciousness and the work of Giulio Tononi.

In the manner and spirit of Dante’s Divine Comedy, Tononi relies on eminent scientists of different eras – Francis Crick, Alan Turing, Charles Darwin – to serve as guides to Galileo and to teach him the many attributes of consciousness. Crick relies on the corticothalamic system of the brain to illustrate a biological view of consciousness. Turing, on the other hand speaks of the possibility of consciousness in a simple computing machine. In the dialog that ensues between him and Galileo, the latter takes a contrarian view – asserting that consciousness must stem from integration of concepts. The machine could store and compute, but not integrate. This anti-reductionist view is what Galileo labels as “phi.” Darwin, the third guide, illustrates the dynamic nature of phi to Galileo – how imagination expands consciousness. Throughout the narrative, other characters are brought into the mix – be it Copernicus in a comatose state as the result of stroke, or the poet Borges in his library, or the painter Lomazzo, who can’t see because of blindness, but can visualize the canvas.

Tononi experiments with literary constructs and metaphors with aplomb. For instance, one of his narrators is a bat – visually blind but able to navigate with sound. Its conscious experience, while relatable to a human, is perfectly relevant to the bat. In another scene, a paranoid king puts each person of his kingdom into an individual cubicle. The kingdom, lacking any communication between its people, loses its soul.

In the words of David Eagleman, “… the writing is often gorgeous, a lyrical flight that tells an enchanting scientific story without jargon. It is the love child of Oliver Sacks and Italo Calvino, carrying the best genes of both genres…. the book is a masterwork. Mr. Tononi could have turned his science into a sequence of monographs that only a handful of academic colleagues would read—but he chose an unusual, courageous approach… Phi is an almost unique poetical work about science. I say “almost” because there was another like it, two millennia ago: Lucretius’s poem On the Nature of Things. But as Mr. Tononi points out in an endnote, that the genre ‘has not had much success since.’ Phi may represent our best hope for this genre’s change of fortune.”

Oliver Sacks, shortly before his death in 2015, said in his praise of Phi, “Giulio Tononi is a man of bold and original mind who has developed a fundamental new theory of consciousness. In Phi, he calls on all the resources of drama, metaphor, and the visual arts to present his scientific insights, in the form of imaginary dialogues in which Galileo meets Francis Crick, Alan Turing, and other major thinkers of the twentieth century. This is an astonishing (and risky) literary device, but Tononi pulls it off triumphantly. He makes the deepest neuroscientific insights come alive.”

If the general topic of consciousness is of interest to you, I have covered several classics in the past. V. S. Ramachandran’s A Brief Tour of Human Consciousness, Gerard Edelman’s A Universe of Consciousness: How Matter Becomes Imagination, and Oliver Sacks’ The River of Consciousness will make great companions to Phi

In video form, Gerald Edelman’s https://www.youtube.com/watch?v=2RMXujk5AhM, is one of my favorites. [A sincere thank you to Dan Goldin for pointing it out to me last year]

Also, John Casti’s Cambridge Quintet has the same basic model for conveying the narrative as Phi. Casti imagines a dinner hosted by C. P. Snow where the guests are Ludwig Wittgenstein, Erwin Schrödinger, J. B. S. Haldane and Alan Turing. The dinner conversation is on intelligence.

5.      Jean-Pierre Weill, The Well of Being: A Children’s Book for Adults, Flatiron Books, 2016

“As the train is late, let me take you on an excursion to the place we long for… and value this listening as if it were a mysterious gift, yours for the taking.” These opening lines of the book had the same impact on me as M. Scott Peck’s Road Less Traveled, which began with “Life is Difficult.”

In my role as a coach, I have been practicing listening. I am constantly reminded that listening is a difficult skill to master. Just when I think that I have made progress, the goal-post moves farther. I also notice that only about half of the people I meet seem to listen thoughtfully about half of the time (the number is less than 10% when I am in India). It is perhaps not their fault. Perhaps their parents were not good listeners. Perhaps their parents’ parents were not good listeners. Perhaps their teachers were not good listeners. Perhaps their teachers’ teachers or may be their teachers’ parents – they all had the same pathologies.

What if listening was taught, didactically, in schools at a young age. What if we had workshops in all grades K through 12 that help us practice listening. What if our teachers were especially trained in that skill? The Well of Being got me to think about these questions, and many more about our well-being – in our relationships and in our social configurations.

Weill’s protagonist character is a man in a suit. The vignettes that he runs through in the book are accompanied by visuals that span from the very abstract to very grounded. The stories (rather, aphorisms) all focus on the power of reflection. “When we lose touch with well-being, joy seems to depend on circumstances, on what happens outside of us.”

Borrowing the words from William Arthur Ward, “Happiness is an inside job.” 200 pages of pithy insights. You can read them in an hour. Or take a week.

Management / Economics:

6.      Paul Collier, Future of Capitalism, Harper Collins, 2018

I had covered Collier’s The Bottom Billion in my 2007 Book Review. He is a Professor of Economics and Public Policy at St Antony’s College in Oxford.

The Table of Contents of Future of Capitalism is as follows:

Part One: Crisis – The New Anxieties

Part Two: Restoring Ethics

The Foundations of Morality: From the Selfish Gene to the Ethical Group

The Ethical State

The Ethical Firm

The Ethical Family

The Ethical World

Part Three: Restoring the Inclusive Society

The Geographic Divide: Booming Metropolis, Broken Cities

The Class Divide: Having It All, Falling Apart

The Global Divide: Winners, and the Left Behind

Part Four: Restoring Inclusive Politics – Breaking the Extremes

I will borrow an excerpt from Steven Pearlstein’s review of the book in The Washington Post. “With its ruthless focus on profits and its increasingly unequal distribution of income and opportunity, he argues, Anglo-American capitalism has forfeited much of its economic, political and moral legitimacy. Collier puts much of the blame on ideologues of the left, with their excessive faith in government, and those of the right, with their excessive faith in unregulated markets. His pitch is for a return to the kind of pragmatic, centrist communitarianism that characterized the years immediately after World War II, when the focus was on shared prosperity and reciprocal obligations that enhanced trust and cooperation… The Future of Capitalism has the discursive charm of a lecture delivered by a well-read and slightly acerbic Oxford don. An American reader might find it a bit academic at times, or Anglo-centric. And readers everywhere will be rightfully skeptical of his proposal to make corporate directors legally liable when they ignore the public interest in their private-sector decision-making. Much better is his idea to raise taxes on those who benefit undeservedly from modern capitalism… All that extra revenue he would recycle to the Youngstowns and Sheffields of the world, not for higher welfare payments but to jump-start the creation of new industrial clusters that could create fulfilling jobs for those being left behind. There is nothing socialist about Collier’s critique or his prescriptions — like Adam Smith, the oft-misunderstood father of modern economics, he’s about restoring a moral sensibility to a market system that is falling short of its potential.”

Collier’s central thesis of ‘Reciprocal Obligations’ as the repair tool is compelling, even though it appears impractical at the first glance. I believe that a well-designed model of incentives can safely translate Collier’s ideas to their viable, pragmatic versions.

A 20-minute video interview of Collier https://www.youtube.com/watch?v=Jh141TCqgas is a good place to start – especially if the description above sounds too idealistic. A more detailed alternative is his one-hour lecture https://www.youtube.com/watch?v=hyrZXNInfD4 at the launch of his book in October last year.

[I had covered Lester Thurow’s book by the same title, Future of Capitalism in my 1997 review. Thurow was the dean of the MIT Sloan School of Management, and one of the founders of Economic Policy Institute.]


7.      Daron Acemoglu and James A. Robinson, The Narrow Corridor: States, Societies and the Fate of Liberty, Penguin, 2019

I had included Acemoglu and Robinson’s Why Nations Fail in my 2012 Top-10. Prior to that I was unfamiliar with their work, but Jared Diamond’s commentary in the New York Review of Books was very compelling and it motivated me to read the book.

I started following the authors more closely after a dinner conversation with Jean Tirole and Nick Rawlins at the Toulouse School of Economics during my visit there in Fall of 2018.

Tirole writes in praise of The Narrow Corridor, “Liberty does not come easily. Many populations suffer from ineffective governments and are stuck in a cage of norms and traditions. Others are subdued by a despotic Leviathan. In this highly original and gratifying fresco, Daron Acemoglu and Jim Robinson take us on a journey through civilizations across time and space. A remarkable achievement that only they could pull off and that seems destined to repeat the stellar performance of Why Nations Fail.”

In The Narrow Corridor, Acemoglu and Robinson argue that political liberty cannot naturally emerge from a state of enlightenment and cannot simply stay that way. Rather, it requires a very delicate balance between the state and the society to make liberty robust and sustainable; there is a very ‘narrow corridor’ between the power of the state and the strength of society. 

Drawing upon the Hobbesian construct of Leviathan – the all-powerful state, the authors provide the following taxonomy:

Despotic Leviathan, where there is too much state and too little society. The state forces political conformity and controls the economy.

Absent Leviathan, where there is too little state, too much society. In extreme cases, this leads to a stateless society where persistent tribal warfare replaces the basic law and order.

Paper Leviathan, which is a blend of the two. It is bureaucratic and it favors the elite and the privileged. It is unable to serve the majority – either politically, or economically – and it is unable to contend with economic or class inequality.

Shackled Leviathan, where the power or the state and the power of the society are in balance. At least in principle, the more the society trusts the state, the more it demands of the state, which in turn makes the state more effective. [I can’t help but relate it to my simple-minded ‘Dialog leads to Trust which leads to Performance’ principle of leadership that I wrote in the mid 1990’s and have been using ever since https://www.linkedin.com/pulse/principles-life-leadership-ajit-singh].

The authors use a vast range of historical and current examples from across the globe to illustrate these principles. From the city-states of medieval Italy to the caste system of India, from tribal warfare of Albania and Montenegro authoritarianism in China, the emergence of democracy in Costa Rica and the end of Apartheid, and with scores of other events of history, the book weaves a rich tapestry of insights leading up to the thesis of The Narrow Corridor.

Daron Acemoglu’s lecture at Toulouse School of Economics in Fall 2018, introduced by Jean Tirole, https://www.youtube.com/watch?v=MJnxzdG5QwM is a great 90-minute introduction to the book.


8.      Matt Richtel, An Elegant Defense, William Morrow, 2019

I wrote last year how my walking conversations with Matthew Frank became my primers in Immunology. Matthew also introduced me to Mark Davis at Stanford and to Jake Glanville at Distributed Bio. Listening to their talks helped me improve my literacy in the subject.

As I confessed in the 2018 Review, I had started off with textbooks (my young friend Curran had introduced me to Janeway’s Immunobiology) and had left popular books for later. Elegant Defense arrived at the scene in time.

As Karen Tucker writes in the Washington Post, “In between these four personal stories, Richtel weaves in intricate, sometimes obscure details on the origins of and advances in immunology, the science of the human immune system. He also explores a relatively new mode of treatment, immunotherapy, which helps the immune system fight cancer and other debilitating diseases. To lend further color to the medical narrative, Richtel interviews leading scientists and physicians in the spheres of immunology and oncology, drawing out not only their scientific perspectives but also their soulful takes on mortality. In doing all this, Richtel brilliantly blurs the lines between biology primer, medical historical text and the traditional first-person patient story.”

What are these four personal stories?

·      Jason Greenstein, a childhood friend of Richtel who was afflicted with Hodgkin’s lymphoma

·      Bob Hoff, a man with an unusual immune system that allowed him to live with HIV. His Immune system remained healthy, and he never went on anti-viral treatment.

·      Linda Segre with auto-immune disease – rheumatoid arthritis

·      Merredith Branscombe with two auto-immune disorders – lupus and rheumatoid arthritis.

A Pulitzer-winning New York Times reporter, Richtel weaves a compelling narrative – with a poignant and all too human story of four fellow beings, interwoven with the history and science of immunology – replete with false starts, failures, disappointments and successes, day-to-day realities of translating science to clinical practice, political and financial hurdles, and their complex interplay.

Net net, what Siddhartha Mukherjee achieved in Emperor of All Maladies and Oliver Sacks in The Man Who Mistook His Wife for a Hat, Richtel has managed in An Elegant Defense. The feats are similar – in magnitude and in impact.

Immunology remains an active area of learning for me. Next on my reading stack is An Epidemic of absence: A New Way of Understanding Autoimmune Diseases, by Moises Velasquez-Manoff.

If film is your medium of choice, try the documentary Breakthrough, on the life and work of Jim Allison https://www.breakthroughdoc.com/. Allison was awarded the 2018 Nobel Prize in Medicine for his work on cancer immunotherapies. An interesting supplement is the timeline of progress in immunotherapy https://www.cancerresearch.org/immunotherapy/timeline-of-progress published by the Cancer Research Institute.

9.      Edward Bullmore, The Inflamed Mind: A Radical New Approach to Depression,Picador, 2018

The general topic of depression and anxiety has been of interest to me for a long time.

In 2010 at Artiman, we had just begun to formulate our thesis on Clinical Diagnostics. We were faced with the fact that there was no biomarker-based test for depression, yet over 200 million prescriptions for antidepressants were written each year in the United States alone. 

In a quick scan of the industry, we came across a startup in Southern California that had a blood test for MDD – based primarily on markers of inflammatory response. Since then, I have I kept a close on the work at the intersection of immunology and neuroscience.

Edward Bullmore is a Professor of Psychiatry at the University of Cambridge and directs the Imaging Centre in the Department of Clinical Neuroscience.

Bullmore’s basic premise of the interdependence of depression and inflammation is not entirely new, and the claim of ‘a radical new approach to depression’ is hyperbole. That said, The Inflamed Mind has done an impressive job of making this subject accessible to the layperson without compromising on its scientific accuracy or rigor. One of Bullmore’s key arguments is that the inflammation of the body – caused by physical or emotional stress as well as by other metabolic or autoimmune factors – can penetrate the blood brain barrier to inflame brain cells and networks, and thus act as a trigger point for depression.

The author also looks at depression from an evolutionary-biology lens, arguing that the social-isolation aspects of depression may have been selected for, in a Darwinian sense, as a form of quarantine for the immuno-compromised. I am unable to relate to the idea, although that might be because of a sociological bias.

The table of content is long, but here is a list of some representative chapters.

Neuro-immunology and immuno-psychiatry

What does an inflamed mind look like?

Inflammation and infection

Location, location, location

The Cartesian blind spot

Farcical serotonin

Bereft of biomarkers

Extraordinary claims demand extraordinary evidence

The Berlin wall in the brain

What could make you inflamed (and depressed)?

Causal chains and cycles

Ultimately, the answer must always be Darwin

Beyond blockbusters: better but not bigger than Prozac

Schizophrenia and auto-intoxication

A word of caution: one of the biggest risks in medicine is that of reductionism. Looking for simple, binary answers almost always backfires. I first truly internalized this in a conversation with Gerd Grenner at Roche nearly a decade ago. In a thread of conversation on ‘unique’ biomarkers, he looked at me, almost accusingly (but with a smile to dull the impact), and said “What makes you think it is even possible? Nature was not solving for uniqueness. It was solving for redundancy – to achieve robustness.” This applies to depression as well. We now understand that there are nearly 50 genes (that we know of) in our genome that are linked to depression. This only shows that like everything else, the disease lies on a spectrum. Research in this highly promising area of inflammatory indicators of depression, as well as the development of diagnostics and therapeutics, must take that this non-binary-ness into account.

If the book appeals to you, also check out the 2018 Elsevier monograph Inflammation and Immunity in Depression, edited by Bernhard Baune, or the article “The concept of depression as a dysfunction of the immune system,” by Brian E. Leonard (Current Immunol Rev. 2010 Aug; 6(3): 205–212).


10.  David Krakauer, Worlds Hidden in Plain Sight: Thirty Years of Complexity Thinking, SFI Press, 2019

David Krakauer is currently the President of the Santa Fe Institute. He also serves as a Professor of Complex Systems there. Earlier, at the University of Wisconsin, Krakauer served as the Co-director of the Center for Complexity. He is also a fellow of the Institute for Advanced Study, and a visiting Professor of Evolution at Princeton. I attended a Santa Fe Workshop led by him last year

Complexity Theory has a been a topic of high interest to me since my early interactions with Erich Reinhardt. I have covered many of the canonical books on the subject – by Stuart Kauffman, Mitchell Waldrop, Ed Regis, Melanie Mitchell, etc. – in my earlier Top-10 book reviews. Worlds Hidden in Plain Sight is a collection of 37 essays spanning the work done in the past several decades. If you have been following the general field, this book is a perfect reference material. Some of my favorite essays in the collection are:

Complex Adaptive Systems: A Primer, by John Holland

Bounded rationality and other departures, by Kenneth Arrow

What can emergence tell us about today’s Eastern Europe, by Cosma Shalizi

Metaphors: Ladders for Innovation, by John Gray and Michele Macready

What biology can teach us about banking, by Lord Robert May

Imagining complex societies, but Scott Ortman

Complexity: A different way to look at the economy, but Brian Arthur

Complexity: Worlds Hidden in Plain Sight, by David Krakauer

Engineered Societies, by Jessica Flack and Manfred Laubichler

Why people become terrorists, by Mirta Galesic

The source code of political power, by Simon DeDeo

Thanksgiving 2050, by Molly Jahn

Emergent Engineering: Reframing the Grand Challenge for the 21st Century, by David Krakauer.

Despite some remarkable work being done across the globe, the field of complexity remains accessible to a very small subsection of the society. As a corollary, reductionist approaches abound – at home, at school, and consequently in almost all walks of life – in political institutions, industry, and individual as well as organizational problem-solving at large. We will be well served if the science and applications of complexity is brought in as a core subject at the high-school level, or at least early undergraduate level.

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