Review: "Letters", by Oliver Sacks

During his 82 years on earth, Oliver Sacks produced such a virtual torrent of writings that he continues to speak to us from beyond the grave nine years after he died. This collection of his letters is the fourth book of his writings that has been published after his death, and I would not be surprised if more trickle out in the upcoming years. The man’s passions and intellectual curiosity were so multifarious and deep and his sheer urgent need to express them was so constant and acute, that thoughts and words rushed out of him like a never-abating volcano. Nothing might be so indicative of his prodigious powers of expression as these letters, lovingly edited and presented by his longtime associate and friend, Kate Edgar.

As Edgar tells us in the preface, it was hard to keep up with Sacks. His writing, while joyously readable and interesting, was vivid and complex, and he poured out words at a tremendous clip, often caring little about trifles like punctuation and capitalization because of the sheer speed. His method of getting Edgar to fix typos and punctuation was to have her sit next to him as he furiously typed on his typewriter, asking her to instantly edit every page as it came out of the machine. When an exhausted Edgar would make it back to her apartment late in the evening, there would be Oliver calling her, asking her to take a look at a few more pages that had somehow been produced even after that avalanche. It would surely have been the experience of a lifetime for her.

As anyone who has read Sacks’s oeuvre would know, Sacks was passionate about a remarkable number of things - medicine and neurology, chemistry, history of science, earthworms, plants, motorcycles, bodybuilding, narcotic drugs, travel, and of course, writing and people. There was nothing in his life that he did not commit to with extreme passion, sometimes gambling with his life while doing this as in the case of extreme bodybuilding and extreme drug use. His body of knowledge was tremendously diverse, ranging across science, literature, poetry, history and philosophy. In the tradition of the Great Books, he had digested classic works by Darwin, Hume, Shakespeare and other great writers and thinkers in their entirety, along with assimilating great works by neurologists and doctors. A remarkable memory seemed to enable him to summon references from these disparate sources on demand.

All these qualities are on incandescent display in this collection of letters, which start with his arrival in the New World in the 1960s and end two weeks before his own death in 2015. Every single one of them is full of vivid, gushing, empathetic, bracingly honest writing. They span so many different topics, emotions, people and thoughts that it would be impossible to do their contents justice. So a brief overview would have to suffice.

The first third of the collection is perhaps the most fascinating. It deals with the self-discovery of his coming of age in a new country, his explorations of his sexuality (he had several amorous encounters which he kept from his family), travels around the country on his motorcycle and the people he met as a doctor. For me one letter, written to his brother Marcus in 1966, stands out. It is almost phantasmagoric, and was likely written when he was on an amphetamine high. In it he performs an excruciatingly painful, vivid analysis of his family and especially his mother, that would make a psychoanalyst (especially a Jewish one) salivate. He presents his mother as a kind of loving Gorgon, crushing everyone who stood in her way and reducing his father to a whimpering non-entity. Undoubtedly the dominant personality in their family of six (which included his schizophrenic brother Michael), she was alternately a font of wisdom and love and a terrifying presence. When his father indiscreetly broke Sacks’s trust and told her he was gay, she flew into a violent rage and told him she regretted him ever being born. The subject was never brought up again, but it is obvious that Sacks’s passionate early relationships with men , followed by his complete withdrawal from those relationships until he was in his 70s were influenced by the trauma inflicted by his mother. And yet the letters back home are warm, loving and full of interesting observations on people and places. Sacks is often fighting battles with hospital personnel depicted in his book and the movie “Awakenings”. In one, he pleads with the administrators to let patients on L-DOPA outdoors, pointing out the rejuvenation that he has witnessed in them.

The middle third of the book details letters to new friends, including the writer W. H. Auden and the poet Thom Gunn whose poem, “On the Move”, inspired the title of Sacks’s memoirs. He is constantly receiving copies of books written by others and sending them his own work. A full chapter is devoted to letters to Sacks’s lover Jeno Vincze, a Hungarian theater director who Sacks met in Europe. The early letters display an intensity and a passion rivaling anything in D. H. Lawrence or Anais Nin; there is the usual ardor for physical and mental connection and impatient waiting for replies, followed by grumblings about the delay. But soon it’s over. He breaks up in a letter alternately filled with sorrow and vicious, almost cruel rejection. Sacks would not have a romantic relationship for another 40 years.

If the personal is on full display in the first half of the book, the professional is equally so in the second half. The letters here include his correspondence with scientific and literary luminaries like Susan Sontag, Stephen Jay Gould, Roald Hofmann, Francis Crick, Robert Silvers (the famed editor of the New Yorker, where Sacks published several essays) and Gerald Edelman. He calls Crick an “intellectual nuclear reactor” after meeting him and strikes up a particularly close friendship with Gould. I was especially pleased to see some dear friends make an appearance here: John Horgan to whom he writes a letter discussing stage fright, Richard Rhodes whose fascinating book on prion diseases he refers to, and Freeman Dyson to whom he writes praising Dyson’s essay on teaching. He seems particularly taken by Edelman and Crick, and by Crick’s protege Christof Koch.

Sacks was diagnosed with metastatic melanoma in early 2015. The cancer had been detected earlier and had been removed. But nine years later it came roaring back. Sacks responded in the best way he could - by writing about it in the New York Times and in letters to friends and family. He is frank and matter-of-fact about it (“I don’t think I will outlast the month”) and even in the last few weeks his letters are full of discussions about science, literature and essays that he would urgently like to publish - there’s not a trace of self-pity or long-winded philosophical reflection. The publication of his memoir, “On the Move”” was fast-tracked after his diagnosis.

The essays that he wrote in the months before his death include one in which he expresses gratitude for the opportunity he had been given to have discourse with a global community of writers and readers; and one in which he seems to reconnect, in a way, with his Jewish roots. These were published as part of a slim book after his death. Sacks’s last letter was written on August 15, 2015. In it he described the writings he would like published after he was gone, and ended with an exhortation: “Let us begin - soon!”. He died two weeks later, on August 30.

There are few writers and thinkers I have come across who wrote so vividly and honestly about so many different things, and perhaps none who lived life so fully, compulsively, passionately, enjoying its every offering. Along with his memoir, this letter collection showcases Sacks at his most genuine and most inspiring. It should be an enduring monument to his legacy.

On their birthday: The wisdom of John Wheeler and Oliver Sacks.

A rare and happy coincidence today: The birthdays of both John Archibald Wheeler and Oliver Sacks. Wheeler was one of the most prominent physicists of the twentieth century. Sacks was one of the most prominent medical writers of his time. Both of them were great explorers, the first of the universe beyond and the second of the universe within.

What made both men special, however, was that they transcended mere accomplishment in the traditional genres that they worked in, and in that process they stand as role models for an age that seems so fractured. Wheeler the physicist was also Wheeler the poet and Wheeler the philosopher. Throughout his life he transmitted startling new ideas through eloquent prose that was too radical for academic journals. Most of his important writings made their way to us through talks and books. Sacks the neurologist was far more than a neurologist, and Sacks the writer was much more than a writer. Both Wheeler and Sacks had a transcendent view of humanity and the universe, a view that is well worth taking to heart in our own self-centered times.

Their backgrounds shaped their views and their destiny. John Wheeler grew up in an age when physics was transforming our view of the universe. While he was too young to participate in the genesis of the twin revolutions of relativity and quantum mechanics, he came on stage at the right time to fully implement the revolution in the burgeoning fields of particle and nuclear physics.

After acquiring his PhD, Wheeler went on a fellowship to what was undoubtedly the mecca of physical thought – Niels Bohr’s Institute of Theoretical Physics in Copenhagen. By then Bohr had already become the grand old man of physics. While Einstein was retreating from the forefront of quantum mechanics, not believing that God would play such an inscrutable game of dice, Bohr and his pioneering disciples – Werner Heisenberg, Wolfgang Pauli and Paul Dirac, in particular – were taking the strange results of quantum mechanics at face value and interpreting them for the next generation. Particles that were waves, that superposed with themselves and that could be described only probabilistically, all found a place in Bohr’s agenda.

Bohr was famous for trying to describe physical reality as accurately as possible. This led to his maddening, Delphic utterances where he would go back and forth with a colleague to rework the fine points of his thinking, relentlessly questioning everyone’s reasoning including his own. But the process also illuminated both his passion to understand the world as well as his absolute insistence on precision and honesty. His talks and writings are often covered in a fine mist of interpretive haze, but once you ponder them enough they are wholly illuminating and novel. Bohr’s disciples did their best to spread his Copenhagen gospel throughout the world, and for the large part they succeeded spectacularly. When Wheeler joined Bohr in the mid 1930s, the grand old philosopher of physics was in the middle of his famous arguments with Einstein concerning the nature of reality. The so-called Einstein-Podolsky-Rosen paradox, published in back-to-back papers by Bohr, Einstein and their eponymous colleagues in 1935, was to set the stage for all quantum mechanical quarrels related to meaning and reality for the next half century.

For Wheeler, doing physics with Bohr was like playing ping-pong with an opponent possessing infinite patience. Back and forth the two went; arguing, refining, correcting, Wheeler doing most of the calculating and Bohr doing most of the talking. Wheeler came from the pragmatic American tradition of physics, later called the “shut up and calculate” tradition. While not particularly attuned back then to philosophical disputes, Wheeler rapidly absorbed Bohr’s avuncular, Socratic method of argument and teaching, later using it to create probably the finest school of theoretical physics in the United States during the postwar years. His opinion of Bohr stayed superlative till the end: “You can talk about people like Buddha, Jesus, Moses, Confucius, but the thing that convinced me that such people existed were the conversations with Bohr.”

In 1939, with Bohr as a sure guide, Wheeler made what was practically speaking probably the most important contribution of his career – an explanation of the mechanism of nuclear fission. The paper is a masterful application of both classical and quantum physics, treating the nucleus as an entity poised on the cusp between the quantum and the classical worlds. In the same issue of the Physical Review that published the Wheeler-Bohr paper, another paper appeared, a paper by Robert Oppenheimer and his student Hartland Snyder. In their paper, Oppenheimer and Snyder laid out the details of what we now call black holes. The seminal Oppenheimer-Snyder paper went practically unnoticed; the seminal Wheeler-Bohr paper spread like wildfire. The reason was simple. Both papers were published on the day Germany attacked Poland and started the Second World War. Just eight months before, German scientists had discovered a potentially awesome and explosive source of energy in the nuclear fission of uranium. The discovery and the Wheeler-Bohr paper made it clear to interested observers that weapons of immensely destructive power could now be made. The race was on. As a professor at Princeton University, Wheeler was in the thick of things.

He became an important part of the Manhattan Project, contributing crucial ideas especially to the design of the nuclear reactors that produced plutonium. He had a vested interest in seeing the bomb come to fruition as soon as possible: his brother, Joe, was fighting on the front in Europe. Joe did not know the details of the secret work John was doing, but the two words in his letter to John made his general understanding of Wheeler’s work clear – “Hurry up”, the letter said. Sadly, Joe was killed in Italy before the bomb could be fully developed. His inability to potentially save his brother’s life massively shaped Wheeler’s political views. From then on, while he did not quite embrace weapons of mass destruction with the same enthusiasm as his friend Edward Teller, his opinion was clear: if there was a bigger weapon, the United States should have it first. One of the hallmarks of Wheeler’s life and career was that in spite of his political leanings – his conservatism was in marked contrast to most of his colleagues’ liberal politics – he seems to have remained friends with everyone. Wheeler’s life is a good illustration, especially in these fraught times, of how someone can keep their politics from interfering with their fundamental decency and appreciation of decency in others.

His scientific gifts and political views led Wheeler to work on the hydrogen bomb amidst an environment of Communist hysteria, witch hunts and stripped security clearances. But after he had done his job perfecting thermonuclear weapons, Wheeler returned to his first love – pure physics. During the war, he had teamed up with an immensely promising young man with fire in his mind and a young wife dying in a hospital in Albuquerque. Richard Feynman and John Wheeler couldn’t have been different from each other; one the fast-talking, irreverent kid from New York City, the other a courtly, conservative, Southern-looking gentleman who wore pinstriped suits. And yet their essential honesty and drive to understand physics from the bottom up made them kindred souls. Feynman got his PhD under Wheeler and for the rest of his life loved and admired his mentor; his work with Wheeler also inspired Feynman’s own Nobel Prize winning work in quantum electrodynamics – the strange theory of the interaction between light and matter. Wheeler’s love for teaching and the art of argument he acquired from Bohr crystallized in his interactions with Feynman. It set the stage for the latter half of his life.

Wheeler is one of the very few scientists in history who did breakthrough work in two completely different branches of science. Before the war he had been an explorer of the infinitesimal, but now he made himself an intrepid Marco Polo of the infinitely large. In the 1950s Wheeler plunged headlong into the physics of gravitational collapse, starting out from where Oppenheimer and others had left off. Memorably, he became the man who christened Oppenheimer’s startling brainchildren: in a conference in New York, Wheeler called objects whose gravitational fields were so strong that they could not let even light escape ‘black holes’. Black holes and curved spacetime became the foci of Wheeler’s career. While pursuing this interest he contributed something even more significant: he essentially created the most important school of relativistic investigations in the United States. And combining this new love with his old love, he also created entire subfields of physics that are today engaging the best minds of our time – quantum gravity, quantum information and quantum computing, quantum entanglement and the philosophy of quantum theory.

As a teacher, Wheeler could give Niels Bohr a run for his mentorship. Not just content with supervising the usual flock of graduate students and postdocs, Wheeler took it upon himself to train promising undergraduates in the art of thinking about the physical world. Story after story flourishes of some young mind venturing with trepidation into Wheeler’s office for the first time, only to emerge dazed two or three hours later, staggering under the weight of papers and books and bursting with research ideas. In fact Wheeler supervised more senior research theses at Princeton than any other professor in the department’s history, and for the longest time he taught the freshman physics class: what better way to ignite a passion for physics than by taking a class as a freshman from one of the century’s most brilliant scientific minds? To top it all, he used to sometimes take his students to see a neighborhood resident at the famous address 112 Mercer Street – Albert Einstein. Sitting in Einstein’s room in a circle, the awestruck young minds would watch Wheeler trying to gently convince a perpetually resistant Einstein of the correctness of quantum ideas.

Out of Wheeler’s fertile school emerged some of the most interesting minds of postwar physics research: a very short list includes Jacob Bekenstein who forged startling links between black hole thermodynamics and relativity; Hugh Everett who came up with the many-worlds interpretation of quantum mechanics, an interpretation which flew in the face of Niels Bohr’s Copenhagen Interpretation; Bryce Dewitt with whom Wheeler made the first inroads into the deep realm of quantum gravity; Kip Thorne, gravitational wave pioneer whose dogged efforts finally won him the Nobel Prize last year. With some of these students Wheeler also wrote pioneering textbooks, including a doorstop of a book that has been gracing the shelves of students and professors of relativity like a patron saint since its publication. Very few teachers of theoretical physics equaled Wheeler in his influence and mentorship; certainly in the twentieth century, only Bohr, Arnold Sommerfeld and Max Born come to mind, and among American physicists, only Robert Oppenheimer and his school at Berkeley.

With his students Wheeler worked on some of the most preposterous extensions of nature’s theories that we can imagine: wormholes, quantum gravity, time travel, measurement in quantum theory. He constantly asked his pupils to think of crazy ideas, to extend our most hallowed theories to their breaking point, to think of the whole universe as a child’s playground. His colleagues often thought he was going crazy, but Feynman once corrected them: “Wheeler’s always been crazy”, he reminded everyone. Like his mentor Bohr, Wheeler became a master of the Delphic utterance, the deep philosophical speculation that could result in leaps and bounds in humanity’s understanding of the universe. Here’s one of those utterances: “Individual events. Events beyond law. Events so numerous and so uncoordinated that, flaunting their freedom from formula, they yet fabricate firm form”. The statement is vintage Wheeler; disarming in its ambiguity, deep in its implications, in equal parts physics, philosophy and poetry.

Many of Wheeler’s ideas were collected together in an essay collection titled “At Home in the Universe” which I strongly recommend. These essays showcase his wide-ranging interests and his gift for philosophy and uncommon prose and are full of paradoxes and puzzles. They also illustrate his warm friendship with many of the most famous names in physics including Bohr, Einstein, Fermi and Feynman. Along with “black hole”, he coined many other memorable phrases and statements: “It from Bit”, “Geometrodynamics”, “Mass without Mass”, and “Time is what prevents everything from happening at once”. He always believed that the universe is simpler than stranger, convinced that what is today’s strangeness and paradox will be tomorrow’s simple accepted wisdom.

John Wheeler died at the ripe old age of ninety-six, a legend among scientists. In affectionate tribute to his own way with words, a sixtieth birthday commemoration for him had called his work “Magic without Magic”, an that’s as good a way as any to remember this giant of science. A fitting epitaph? Many to choose from, but his sentiment about it being impossible to understand science without understanding people stands as a testament to his scientific brilliance and fundamental humanity: “No theory of physics that deals only with physics will ever explain physics. I believe that as we go on trying to understand the universe, we are at the same time trying to understand man.”

We come now to Oliver Sacks. Strangely enough, it took me some time to warm up to Sacks’s writing. I read about the man who mistook his wife for a hat, of course, and the patients with anosmia and colorblindness and the famous patients of ‘Awakenings’ who had been trapped in their bodies and then miraculously – albeit temporarily – resurrected. But I always found Sacks’s descriptions a bit too detached and clinical. It was when I read the charming “Uncle Tungsten” that I came to appreciate the man’s wide-ranging interests. But it was his autobiography “On the Move” that really drove home the unquenchable curiosity, intense desire for connecting to life and human beings and sheer love for living in all its guises that permeated Sacks’s being. I was so moved and satiated by the book that I read it again right after reading the last page, and read it a third time a few days later. After this I went back to almost the entirety of Sacks’s oeuvre and enjoyed it. So mea culpa, Dr. Sacks, and thanks for the reeducation.

Like Wheeler Sacks was born to educated parents in London, both of whom were doctors. He clearly acquired his interest in patients, both as medical curiosities and as human beings from his parents. A voracious reader, he had many interests while growing up – Darwin and chemistry were two which he retained throughout his life – and like other Renaissance men found it hard to settle on one. But family background and natural inclination led him to study medicine at Oxford and, finding England too provincial, he shipped to the New World, first to San Francisco and then to New York.

Throughout his life, Sacks’s most distinguishing quality was the sheer passion with which he clung to various activities. These ranged from the admirable to the foolhardy. For instance, Sacks didn’t just “do bodybuilding”, he became obsessed with it to the point of winning a California state championship and risking permanent damage in his muscles. He didn’t just “ride motorcycles”, he would take his charger on eight hundred mile rides to Utah and Arizona over a single weekend. He didn’t just “do drugs”, he flooded his body with amphetamines to the point of almost killing himself. And he didn’t just “practice medicine” or writing, he turned them into an observational art form without precedent. It is this intense desire for a remarkable diversity of people and things that defined Oliver Sacks’s life. And yet Sacks was lonely; as a gay man who repressed his sexuality after a devastating reception from his mother and a series of failed encounters during his bodybuilding days, he refrained from romantic relationships for four decades before finally finding love in his seventies. It was perhaps his own struggle with his identity, combined with recurring maladies like depression and migraines, that made Sacks sympathize so deeply with his patients.

Two things made Sacks wholly unique as a neurological explorer. The writer Andrew Solomon once frankly remarked in a review of one of Sacks’s books that as purely a writer or purely a neurologist, while Sacks was very good, he probably wasn’t in the first rank. But nobody else could straddle the two realms with as much ease, warmth and informed narrative as he could. It was the intersection that made him one of a kind. That and his absolutely transparent, artless style, amply demonstrated in “On the Move”. He was always the first one to admit to follies, mistakes and missed opportunities.

For Sacks his patients were patients second and human beings first. He was one of the first believers in what is today called “neurodiversity”, long before the idea became fashionable. Neurodiversity means the realization that even people with rather extreme neurological conditions show manifestations of characteristics that are present in “normal” human beings. Even when Sacks told us about the most bizarre kind of patients, he saw them as lying on a continuum of human abilities and powers. He saw the basic humanity among patients frozen in space and time when the rest of the world simply saw them as “cases”. And he displayed all this warmth and understanding toward his patients without ever wallowing in the kind of sweet sentimentality that can mark so much medical writing trying to be literature.

Sacks persisted in exploring an astonishing landscape of aspects of the human mind until his last days. Whether it was music or art, mathematics or natural history, he always had something interesting to say. The one exception – and this was certainly a refreshing part of his writing – was politics; as far as I can tell, Sacks was almost wholly apolitical, preferring to focus on the constants of nature and the human mind than the ephemeral foibles of mankind. His columns in the New York Times were always a pleasure, and in his last few – written after he had announced his impending death in a moving piece – he explored topics dear to his heart; Darwin, the periodic table, his intense love of music, his satisfying and strange connection to Judaism as an atheist, and his gratitude for science, friends and the opportunity to be born, thrive and learn in a world full of chaos. In the column announcing the inevitable end he said, “I cannot pretend I am without fear. But my predominant feeling is one of gratitude. I have loved and been loved”.

Why remember John Wheeler and Oliver Sacks today? Because one taught us to look at the universe beyond ourselves, and the other taught us to look within ourselves. Both appealed to the better angels of our nature and to what we have in common rather than what separates us, asking us to constantly stay curious. These lessons seem to be quite relevant to our day and age. Wheeler told us that the laws of physics and the deep mysteries of the universe, even if they may not care about our fragile, bickering world of politics and social strife, beckon each one of us to explore their limits and essence irrespective of our race, nationality or gender. Sacks appealed to our common humanity and told us that deep within the human brain runs a thread that connects all of us on a continuum, independent again of our race, gender, nationality and political preferences. Two messages should stay with us:

Sacks: “Above all, I have been a sentient being, a thinking animal, on this beautiful planet, and that in itself has been an enormous privilege and adventure.”

Wheeler: “Behind it all is surely an idea so simple, so beautiful, that when we grasp it – in a decade, a century, or a millennium – we will all say to each other, how could it have been otherwise? How could we have been so stupid?”

This is my latest column for 3 Quarks Daily. Image credits: Wheeler, Sacks

What Oliver Sacks could teach us about the value of anecdotal information in drug discovery research

Oliver Sacks was a writer who elevated the art of anecdote to an art form. He did not write authoritative medical books filled with numbers, graphs and statistics. Instead he focused on individual cases and the human element in medicine. A 2015 Wired magazine profile of Sacks highlighted his signature achievement in resurrecting the value of anecdote in medical research.

By restoring narrative to a central place in the practice of medicine, Sacks has regrafted his profession to its roots. Before the science of medicine thought of itself as a science, at the crux of the healing arts was an exchange of stories. The patient related a confusing odyssey of symptoms to the doctor, who interpreted the tale and recast it as a course of treatment. The compiling of detailed case histories was considered an indispensable tool of physicians from the time of Hippocrates. It fell into disrepute in the 20th century, as lab tests replaced time-consuming observation, merely “anecdotal” evidence was dismissed in favor of generalizable data, and the house call was rendered quaintly obsolete. 

...By exiling the clinical anecdote to the margins of medical practice—to stories passed down in hallways from attending physician to resident—the culture of medicine had blinded itself, forgetting things it had once known. Sacks calls these knowledge gaps “scotomas,” the clinical term for blind spots or shadows in the field of vision. 

...Sacks immersed himself in the neglected anecdotal literature of migraine, feeling that every one of his patients “opened out into an entire encyclopedia of neurology.” 

By studying individual patients with unusual or bizarre neurological symptoms or personality changes, not only the infamous sleeping sickness in "Awakenings" but insomnia, migraines and Tourette's syndrome all revealed their intricacies under Sacks's skillful and empathetic dissection.

Sacks's explorations of anecdotal data were on my mind as I contemplated the pros and cons of anecdotal data in drug discovery, and especially in molecular modeling. It's a topic that is the subject of much discussion, and occasional pugnacious debate. One of the smartest people I know in the field often scorns individual stories of successes in modeling chemical and biological data. If you read about or listen to case studies in the field, you will often find scientists attributing success in a particular drug design study to a particular method, software algorithm or physicochemical factors like electrostatic effects or hydrophobic effects. 

My statistically enlightened colleague has a tendency to dismiss these individual stories: Where, he asks, are the comparisons, often with simpler techniques? Where are the controls? How do you know for certain that there is a causal relationship between a particular method or factor and the success of a particular drug design?

My colleague is absolutely right about the difficulty of extrapolating to causal explanations or general rules based on individual studies. Not a day passes when I don't hear the words "Method X worked for us" or "Method X failed abysmally for us". "Method X" could be a particular assay, chemical reagent, cell line or computational algorithm. The problem is when these statements are extrapolated to "Therefore Method X works" or "Method X does not work". The difference between "works for me" and simply "works" can be the difference between storytelling and actual science.

And yet I cannot help but think, partly based on Oliver Sacks's career, that storytelling has a unique place in drug discovery. And this is not just because of the cultural and community-building role of storytelling that sociologists often extol. It's because I see anecdotes not as data but as starting points for gathering data. And this is because of the sheer complexity of biology, and of drug discovery by extension. The problem is that when you are dealing with a very complex and multifactorial system, one in which the variance of success is large, it's often impossible to find general rules even by running well-designed statistical studies. Do you then completely dismiss individual data points? I think that would be a mistake. 

If a colleague tells me that using a method for optimizing electrostatic interactions worked well for his system, I would try to use that method for my system within time and resource constraints, especially if his study is well documented and carefully done. I would certainly try it out if both of us were working on similar systems (say, kinases) but even if the systems were different I would give it a shot. That's because we know for a fact that similar laws of physics and chemistry operate even in very different systems; often it's a matter of teasing apart which laws among them are dominant and which ones are weaker.

Then there's also Sacks's quote about each one of his patients providing openings into entire encyclopedias of discovery. What Sacks is really talking about here are model systems which highlight a particular feature that is present in other systems. For instance, a patient with memory loss may not be representative of the population as a whole, but he can shed some very valuable insights into the workings of the mechanisms of memory (sadly although illuminatingly, it's only by observing certain damaged neurological mechanisms that you can know more about normal, undamaged ones). 

Model systems are similarly invaluable in fundamental drug discovery research. A good example is a hydrophobic protein cavity in which a single engineered polar amino acid residue can provide information on the role of electrostatics in small molecule binding. There also "virtual" model systems; for instance a molecular mechanics force field in which the electrostatic interactions are turned off to study only the influence of the Van der Waals interactions. Synthetic chemists can also tell you about scores of model systems that are constructed to demonstrate the feasibility of certain reactions or conformational effects. These model systems are not infallible, and they are certainly not data by themselves. But what they are are invitations to discovery, curious starting points, hints that point the way to interesting phenomena. Whether one uses them depends to some extent on time and resource availability, but we would be naive to simply discard them because they represent isolated or anecdotal cases.

That brings me to the value of outliers. Outliers are interesting in almost any investigation, but they are especially important in a paradigm like biology or medicine where the emergent, non-linear nature of the system leads to significant variance. In fact one could argue that medicine is currently being revolutionized by the study of outliers in clinical trials. Outliers can point the way to selecting subgroups of patient populations, so-called 'extraordinary responders" who elicit an unusual response to certain drugs. A great recent example is the anticancer drug Iressa which was withdrawn from the market because of lack of efficacy. However, a few years later AstraZeneca could introduce the drug back into the market when it found out that patients with EGFR mutations responded much better to it than the general population. It was thus the outliers that could help repurpose a drug, one which is saving lives today. And as the genetic basis of medicine is unraveled more and more, we can be sure that specific outlier patients who are distinguished by unique genetic signatures will be critical not only in targeting specific drugs but also in advancing basic science; a great example along these lines is the aerobics instructor in Texas who had a mutation in a protein called PCSK9, now a lucrative target for heart disease drugs. It would have been a shame if her particular case had simply been dismissed as a statistical anomaly.

That then is the great value of anecdotes, not as markers of scientific laws in themselves but as starting points for experiment and theory, as signposts leading us to intellectual forests and mountaintops. Whether these forests and mountaintops contain anything of value is a separate question, but without the anecdotes we may never know about their existence.

Oliver Sacks's "mad and impudent" idea for winning first prize in an important exam: five pints of hard cider

Oliver Sacks's wonderful, bracingly honest memoir "On the Move" is a must read. If you see Sacks interviewed he would strike you as a shy and diffident if intensely curious man, but one of the things that shines through the book is his occasional tendency to display "violent enthusiasms, and extreme immoderation" in all matters, whether they concerned alcohol, drugs, relationships, bodybuilding or binge eating. Fortunately for Sacks these risky experiences were instructive rather than ruinous, and they contributed to the further enrichment of what was already an immensely interesting life.

One such early experience was his frenzied, alcohol-laden, impulsive attempt to win the first prize in an important college anatomy exam.

"My mother, a surgeon and anatomist, while accepting that I was too clumsy to follow in her footsteps as a surgeon, expected me to at least excel in anatomy at Oxford. We dissected bodies and attended lectures and, a couple of years later, had to sit for a final anatomy exam. When the results were posted, I saw that I was ranked one from bottom in the class. I dreaded my mother’s reaction and decided that, in the circumstances, a few drinks were called for. I made my way to a favorite pub, the White Horse in Broad Street, where I drank four or five pints of hard cider – stronger than most beer and cheaper too. 

Rolling out of the White Horse, liquored up, I was seized by a mad and impudent idea. I would try to compensate for my abysmal performance in the anatomy finals by having a go at a very prestigious university prize – the Theodore Williams Scholarship in Human Anatomy. The exam had already started, but I lurched in, drunkenly bold, sat down at a vacant desk, and looked at the exam paper. 

There were seven questions to be answered; I pounced on one (“Does structural differentiation imply functional differentiation?”) and wrote nonstop for two hours on the subject, bringing in whatever zoological and botanical knowledge I could muster to flesh out the discussion. Then I left, an hour before the exam ended, ignoring the other six questions. 

The results were in The Times that weekend; I, Oliver Wolf Sacks, had won the prize. Everyone was dumbfounded – how could someone who had come one but last in the anatomy finals walk off with the Theodore Williams prize?"

Needless to say, it may not be the best idea to assume a causal relationship between cider and success and try this in an exam venue.