Thursday, February 23, 2012

Disposable personal genome sequencers may be available by the end of the year for under $1000

Last week, Nature published a story about portable genome sequencers under development by a UK company called Oxford Nanopore Technologies (US company Ion Torrent Systems is developing its own technology in parallel).  The devices work by electronically reading the "letters" of the genetic code as single molecules of DNA pass through tiny nanometer-sized pores in a membrane.  The company is developing pocket-sized disposable devices to accomplish this for around $900 apiece.  Within a year, you may be able to decode your whole genome for a price cheaper than my family's first computer.

A prototype of the MinION, a personal genome sequencer.   Yes, that's a USB plug.  Oxford Nanopore Technologies.

Its error rate is still high (4%) but the company hopes to reduce this error to less than 1% by the time the device launches.  In addition, thus far they have only reported the sequencing of viral genomes, which are orders of magnitude smaller than the human genome.

Regardless, this is a very promising start.  The technology has been in development for the better part of two decades, but this would be the first practical application of it.  With so many known genetic markers of diseases, this kind of device could help usher in a new era of more personalized medicine (as well as a slew of possible ethical issues).

Tuesday, February 21, 2012

Genesis of a Tyrant: Young Stalin

I am not a history buff.  Frankly, I never really saw the point.  Sure, there is the standard defense that it gives us perspective, that knowing the past gives us insight into the future.  But even a cursory glance at the past several hundred years of history seems to validate the quote attributed to Hegel, that “We learn from history that we do not learn anything from history.”  It’s difficult to derive any inspiration or hope from stories of war upon war, conquest after conquest, and the replacement of one form of oppression with another.

So, I’m branching out a bit with the audiobook Young Stalin by Simon Sebag Montefiore.  I chose Stalin’s particular tale for a few reasons.  First, in contrast to the other great tyrant of the 20th century, I know next to nothing about Stalin.  This is not surprising, since my K-12 curricula gave me a solid foundation in American history but emphasized world history too little (really only in the context of a single class on Western Civilization in 7th grade).  Second, and for the same reasons, I don’t know much about the history of Russia, which seems very alien and exotic to me.  When I hear terms like Bolshevik and Gulag thrown around, a fog of ignorance creeps over me.  Third, as I often hear religious conservatives cite Stalinism as the inevitable endpoint of liberal secularism, I want to understand for myself the relationship between Stalin’s political philosophy, his religious beliefs and upbringing, and the horrid brutality of his regime.

After listening to the prologue and the first couple of chapters, I’m already learning all sorts of interesting tidbits about the future dictator’s early years.  For instance, I never knew that he had grown up in Georgia, the same country that Russia invaded in 2008 – indeed, some of his relatives were from the very South Ossetia region upon which the 2008 conflict centered.  Or that his surname at birth was not Stalin, but the very Georgian name Dzhugashvili. Or that his father was a handsome and successful cobbler-turned-drunkard who savagely beat the young Iosif (Joseph) and his mother in fits of jealous inebriated rage, allegedly desensitizing Iosif to violence and teaching him to hate at a very young age (NOTE: My subsequent reading of Steven Pinker's work, particularly The Blank Slate, calls this heavily nurture-ist perspective into doubt).  Or that his mother dearly cherished him after losing her first two babies to illness, yet exerted a stern disciplinary hand (i.e., she beat him to keep him in line... apparently, it didn't work).  Or that he grew up in a culture rife with gang violence and male bravado, influenced by militant revolutionaries and romantic tales of righteous despoilment of the ruling class.

I'm just scratching the surface, though.  It will be interesting to see how a sensitive, flower-loving little boy was transformed into such a brutally oppressive dictator.

Saturday, February 18, 2012

Talent “ex nihilo”: How brain damage can make people more musical

When you think of brain damage, what effects come to mind?  If you’re like me, probably mental and physical handicaps – aphasia, amnesia, perhaps loss of coordination or personality changes.  As I finish Musicophilia, one of the standout surprises for me was that brain damage can sometimes add function… or so it seems.

Owing to the book’s focus, Dr. Sacks focuses on several cases of brain damage or disease contributing to “hypermusicality,” an enhanced appreciation of and/or talent for music.  The most striking example comes at the beginning of the book, where he describes a patient who became obsessed with music after an encounter with a bolt of lightning (see what I did there?).

Image credit: David Selby
The patient, Tony Cicoria, apparently had no major adverse health effects apart from burns to his face and left foot as well as some temporary sluggishness and memory loss that lasted a few weeks.  However, Circoria had a sudden irrepressible urge to learn piano music, despite having virtually no interest in performing music in his forty or so years.  He bought recordings of Ashkenazy playing Chopin and adored every one.  Around that time, a family babysitter needed somewhere to store her piano, and this was just the ticket he needed to start making music himself.

Then, he began hearing music in his head.  “It’s like a frequency,” he said, “a radio band.  If I open myself up, it comes.  I want to say, ‘It comes from heaven,’ as Mozart said.”  After the lightning strike, he also became hyper-religious, believing that he had been saved for some purpose, and that purpose was his music.

This incessant influx of music needed an outlet, and he began composing at every available opportunity.  It totally possessed him during every waking hour, and his wife was none too pleased.  (I can relate: when I go through obsessive piano binges, it can certainly intrude upon time together with my wife!)  In the intervening years, Cicoria has developed a veritable musical career, presenting his compositions first at informal recitals and later at more formal concerts.  All this despite having only a handful of piano lessons as a young boy, about thirty years before.

So, after being assaulted by several thousand amps of electricity, Cicoria’s brain was not only unimpaired, but revealed talents and interests that he never possessed before!

This sort of phenomenon is not restricted to those struck by lightning.  Sacks also describes several patients with frontotemporal dementia (FTD, or Pick’s disease), a neurodegenerative disease that is similar to Alzheimer’s except that it specifically affects the front and side portions of the brain.  Here is an image of a brain from a patient with advanced FTD:

Note the shrinking of the gyri (folds) of the brain towards the front, on the right.
Unlike Alzheimer’s, the first symptoms of FTD do not involve memory loss, but changes in personality and loquacity.  The symptoms of FTD vary a lot, but in general the patients become more outgoing and less inhibited, which is not surprising since the frontal lobe is involved in suppressing socially questionable behaviors.  Sacks discusses some patients that begin to spontaneously burst out into song, and even some that suddenly develop extraordinary gifts of composition out of the blue.  Bruce Miller described one such man who began composing music at the age of 68!  Sack speculates that these probably don’t represent entirely new behaviors of the brain, but result from the de-inhibition of existing thought patterns that are then free to flourish.

This reminds me of a few occasions I've had to speak French with native speakers while mildly intoxicated.  With a few glasses of wine in my system, I was actually more fluent.  It was as if my conscious brain gave way to a more fluent unconscious self.  Unfortunately, sobriety brought the return of my more typical halting, clumsy manner of speaking.  I have never experimented with psychoactive drugs, but I would not be surprised if such de-inhibitions were responsible for the bizarre creative visions of some drug-using artists and religious cults.

Sadly, most patients lose their newfound abilities as the FTD progresses further.  Many remain ebullient and enthusiastic, but their semantic memories usually begin to fail.  One elderly man would gaily sing “We Wish You a Merry Christmas” but could not tell his doctor precisely what Christmas was.  As Sacks put it,
The musical or artistic powers that may be released in fontotemporal dementia or other forms of brain damage do not come out of the blue; they are, one must presume, potentials or propensities that are already present but inhibited – and undeveloped.  Once released by damage to these inhibitory factors, musical or artistic powers can potentially be developed, nurtured, and exploited to produce a work of real artistic value – at least as long as frontal lobe function, with its executive and planning powers, is intact.  In the case of frontotemporal dementia, this may provide a brief, brilliant interlude as the disease advances.  The degenerative process in frontotemporal dementia, unfortunately, does not come to a halt, and sooner or later, all is lost – but for a brief time, for some, there can at least be music or art, with some of the fulfillment, the pleasure, and joy it can so uniquely provide.
One must wonder, finally, about the “Grandma Moses” phenomenon – the unexpected and sometimes sudden appearance of new artistic or mental powers in the absence of any clear pathology.  Perhaps one should speak of “health” rather than “pathology” here, since there may be, even at an advanced age, a relaxing or release of lifelong inhibitions.  Whether this release is primarily psychological, social, or neurological, it can unleash a torrent of creativity as surprising to oneself as it is to others.
What hidden creative potentials lie in each of our brains, ready to burst out but inhibited by the tyranny of rational thought?  Still, I’m not eager to get struck by lightning or stricken with dementia to find out.

Saturday, February 11, 2012

I don't remember you, but I love you: The story of Clive Wearing

The latest tenant in my dashboard CD player is Musicophilia by Oliver Sacks, the distinguished physician best known for Awakenings. In Musicophilia, Sacks explores the myriad modes of interaction between music and the human brain from a neurologists’s perspective. Topics range from the various components of musical awareness to the infinity of ways in which it can go haywire – musical hallucinations, impaired perception of pitch, harmony, melody, or timbre, and even hypermusicality induced by a lightning strike. However, one of the most intriguing and touching stories in the book concerns the tragic amnesia of musician and musicologist Clive Wearing.

In 1985, after a rare case of viral encephalitis, Clive acquired one of the most severe cases of amnesia ever documented. He lost not only decades of prior memories (retrograde amnesia), but also his ability to form new memories (anterograde amnesia). As a result, he lives entirely in the present, with only about thirty seconds of conscious memory. This transcends mere forgetfulness, impinging on his very sense of continuity from moment to moment. As his wife Deborah wrote:
It was as if every waking moment was the first waking moment. Clive was under the constant impression that he had just emerged from unconsciousness because he had no evidence in his own mind of ever being awake before… “I haven’t heard anything, seen anything, touched anything, smelled anything,” he would say. “It’s like being dead.”

It’s difficult to imagine how utterly terrifying this would be. On some level, Clive seems to be aware that he is an adult with a history, and has even retained some memories of events earlier in his life. Yet, at any given instant he has no conscious memory of having been awake, or even alive, before. At one point, hoping that it would help him to maintain some continuity from moment to moment, his caretakers encouraged him to keep a journal of his thoughts. This only resulted in page after page of entries like the following (taken from Wikipedia):
8:31 AM: Now I am really, completely awake.
9:06 AM: Now I am perfectly, overwhelmingly awake.
9:34 AM: Now I am superlatively, actually awake.

What kind of life can one hope to lead with such an impenetrable fog occluding both past and future? Yet Clive has been able to live with some measure of comfort and happiness. On some deep emotional level, he does remember his wife, and greets her with a shower of hugs and kisses when she comes to visit (or even when she drifts from his awareness for a minute or two and then he realizes, as if for the first time, that she is there). An accomplished pianist, he can still sight-read, improvise, and play many songs from memory with great musicality, even if he is convinced he has never played them before:
In these moments, it is clear that Clive’s amnesia is not complete. Human memory is a multi-dimensional complex of episodic recollections mingled with deeper emotional and procedural memories, and these latter two are still largely intact for him. He has adapted to his condition to some extent, and can hold conversations and enjoy the company of others in his own way. But it must have been an extremely difficult adjustment, not only for Clive, but for Deborah and their family members as well. I truly admire their courage.
In Total Recall, a perennial favorite of teenage boys, the psychic mutant Kuato offers Arnold Schwarzenegger’s character this admonition: “You are what you do! A man is defined by his actions, not his memory.” Clive certainly doesn’t completely remember the man he was before his encephalitis, but when he sees Deborah, or plays the piano, or directs a choir, he is very much alive.

Deborah Wearing’s Forever Today
Oliver Sacks’s Musicophilia

Motivations and purpose

I used to loath commuting, and it hated me. Now we're getting along a little better. Let me explain.

Every day, I have the distinct pleasure of driving 69 miles each way to the university where I am pursuing a higher education. In addition to expelling several more tons of CO2 into the atmosphere each year, this consumes an even more precious personal resource: time. In the past year, I have spent around 500 hours driving to and from my research lab, which amounts to about 20 days of travel time. I do this so that my wife and I can live together despite attending graduate schools in different cities. It's a worthwhile sacrifice, but for most of these last few years I couldn't help but lament the irrevocable loss of precious time.

Then, about a year ago, we subscribed to a local audio book rental store called Hear You Go. It was my wife's initiative, and I have to say I was pretty resistant to the idea. I enjoyed listening to the radio and my iPod day after day, and stubbornly clung to this habit. Fortunately, she persisted, and now I am probably more enthusiastic about audio books than she is!

Stepping back a bit: I've always been a slow reader. I have an insatiable curiosity about the world, but have generally considered reading books to take too much time, particularly when I must keep abreast of work in my own field of research (which, incidentally, lies at the intersection of biochemistry and nanotechnology). Like many of my generation, I procure the majority of my general-purpose information from blog posts, Podcasts, sound bytes, and of course, Wikipedia. I am part of probably the last generation that is still astounded by the amount of information at our fingertips thanks to the internet. But modern media often sacrifice depth in favor of breadth, and I've long felt that my slow reading speed and short attention span for most topics have kept me ignorant of a whole world of thought and discovery.

Thanks to my newfound passion for audiobooks, I currently breeze through about 2-3 books each month. I'm "reading" more widely and quickly than I ever have before. I actually look forward to my commute each day, eagerly anticipating the barrage of novel ideas, information, and stories that will come pulsing from the well-worn speakers of my '06 Impala. I am hooked!

This blog is about the rekindling of my passion for learning outside of my ultra-specialized field of research. It is about my journey, literally and metaphorically, towards my own internal realization of E. O. Wilson's "Consilience" -- the unity of knowledge from disparate fields. It is a candle lit by the fire of my curiosity that I hope to share with other curious and open minds.

I do not intend for this to be an endless series of audio book reviews. It will be much broader (and probably more random), encompassing any ideas my daily dabblings in the thoughts of others may engender. My initial focus will concern my current interests: science, biochemistry, evolution, music, food, language, and religion. If all goes as planned, this list will expand to encompass other topics such as history and economics. In the end, it's all the same: the attempts of one meager brain to make sense of this beautiful, bountiful, and intractably complex universe.

Won't you join me?