Here’s Autumn again, carrying upon its still breeze a very special flavor of stagnation. With an ineffectiveness that has become emblematic, the US government has shut down. The world stands perplexed. Although large political events can often go unnoticed in daily life, the government shutdown does not seem to fall in that category. It has caused quite a few very visible ripple effects.
Aside from the fact that government-employed friends of mine are furloughed, my brother Andrew was kicked out of Yosemite this month. Rangers announced the government shutdown and gave everyone 2 days to vacate the park, which led to a scramble of many rock climbers to get final routes in before the park closed (or, for the more anarchistic ones, to make sure they were up on a wall and thus unable to be kicked out when the shutdown commenced). The always-booked-to-the-brim famous climber campsite, Camp 4, became eerily empty. Andrew told me a few bummer stories, like about a New Zealander he met who was just in the beginning of a month long US national parks tour. Not a great way for our country to treat guests.
On a more peripheral but personally upsetting note, the shutdown has prevented my all-time favorite rockclimber, Chris Sharma, from joining an all-star team of climbers on a ridiculously hard new route in Yosemite called the Dawn Wall. Since the Yosemite climbing season is short, this will likely throw off attempts at the Dawn Wall for an entire year.
Come on, US government!
To be fair, these issues are mere inconveniences compared to cancer patients put on hold for clinical trials, scientists waiting for grants to come through, and federal employees unable to pay bills or legally seek other work while their paychecks are withheld. The shutdown has been a major inconvenience and burden for a great number of people.
With all this in the news, I became curious about what kind of measurable effect a government shutdown might have on the economy. There seems to be a lot of supposition and back-of-the-envelope calculations about this in blogs and the news, but little data. My question was simple: did past government shutdowns affect any indicators of US economic health in a length-of-shutdown dependent way? While I’m not an economist, I did a naïve set of calculations and found quite a surprising signal -- in short, I found that yes, the economy does seem to suffer after government shutdowns, in the form of inflation. The longer the shutdown, the more inflation is seen.
The data I analyzed is the consumer price index (CPI), which gives the cost of a battery of goods across the US at a given moment in time. The CPI is available on a monthly basis since at least 1914, which easily covers the period from 1976 to 1995, during which there have been 17 government shutdowns. (That's right, I said Seventeen! I could barely believe it when I first read it.) I lumped together two shutdowns that occurred back-to-back in September-October 1984. The dates of the shutdowns can be found here.
I first looked at whether there is a correlation between the number of days of a government shutdown, and the % change in the CPI afterwards. I found that in fact yes, there is such a correlation. Below I've plotted % change in CPI from the day before each shutdown to a day 4-months after each shutdown (y-axis), versus the number of days of each shutdown (x-axis). For the statistically inclined, the Spearman's correlation is: rho=0.77, p=4e-4. For the non-statistically inclined, this is considered a strong and non-random correlation.
A few outliers are marked by the dates of the shutdowns, and each point is labeled R(epublican) or D(emocrat) depending on the party of the president during that shutdown. The correlation here means that the longer a government shutdown, the bigger the increase in CPI afterwards, i.e., the bigger the increase in inflation.
Also, curiously, shutdowns during democratic presidencies have generally been longer than those during Republican presidencies. Hmm...
It is possible that the correlation between length of shutdown and % increase in CPI is simply there because the CPI nearly always rises over time, and thus will rise more during the period of a long shutdown than the period of a short one. To eliminate this confounding factor (or other, potentially more hidden ones), I scrambled the dates of the shutdowns, keeping them the exact same lengths, to see if scrambled dates would show the same correlations as the real ones. In short, the answer is no -- the actual shutdown dates showed a much more significant correlation than scrambled ones. The results of this test are plotted here:
What you see above on the y-axis is the Spearman correlation coefficient, which represents how well the length of each government shutdown correlates with the % change in CPI (i.e., what i just showed in the first plot), for the actual dates of shutdowns (blue bars) and for the dates scrambled in various ways (lines with errorbars, which represent means & standard deviations for multiple random trials). I kept the scrambled dates within the period of 1976 to 1995, i.e., between the first and the last of the shutdowns being analyzed. The x-axis here represents the number of months after the shutdown that we're checking.
The important thing is that for the first few months, the blue bars (correlations for actual shutdown dates) are higher than any of the errorbars for randomized shutdown dates. I circled the datapoints of most interest in red. This eliminates a lot of the chance that the shutdown-length dependency of CPI increase is merely an artifact.
You can also see on this plot that the correlation between shutdown length and % change in CPI is the highest when checked 4 months after the end of the shutdowns. This implies that it takes about 4 months for the inflationary effects of a shutdown to become most apparent. If anybody reading this blog is an economist, I would be curious if it is common to see a 4-month lag in changes to CPI (or other economic indicators) after a causative economic event.
Aside from looking at the % change in CPI, I was also curious if the CPI increases following long shutdowns were more likely than after short shutdowns to exceed extrapolations based on pre-shutdown data. Suffice to say, this is another test that the CPI tends to rise faster after long shutdowns than after short ones.
To check this, I looked at the % difference after each shutdown between the actual CPI and the CPI expected based on a linear fit of data from before the shutdown. I checked this various numbers of months after each shutdown (using an equal amount of pre-shutdown time for the projection), and found that indeed, the CPI increase exceeds projections by more after long shutdowns than after short ones. You can see it in the below plot, as, again, the blue bars (correlations for actual shutdown dates) are higher than any of the errorbars for random shuffles (with the effect being most dominant 4 months out). Again, I circled the most interesting datapoints:
What all this means is that yes, government shutdowns do appear to affect the economy, and they do it more the longer they are. My analysis indicates that the effects will likely peak around 4 months after the end of the shutdown.
By the way, I did not see similar trends in the S&P500, the NASDAQ composite, or the GDP. I’m guessing that the stock indicators equilibrate to the expected slump after a shutdown, and the GDP is simply too rough of an economic estimate to be useful since it’s posted only once per year. It's also possible I just didn't look hard enough.
One note -- even with my paltry knowledge of economics, I'm aware that an increase in inflation is often a sign of economic growth. Despite this, I would wager that the post-shutdown inflation is not a sign of economic health, but rather a sign of economic illness. I'm sure there's a way to tell between helpful and harmful inflation. Maybe a nice follow-up study for an enterprising economist?
It's a shame to me that our government can't do such an elementary task as passing a budget. This hurts Americans on many levels, including, I would argue, broad economic ones. It also makes us look like damn fools. I only hope that in future shutdowns, congress will be so kind as to consider my family, my friends, and the entire US economy. Not to mention, I would like them to also consider the Dawn Wall.
Past cafes and restaurants and sandwich shops, dodging couples and bikestands, skipping over the piles of sewage at the rear of the shuk, and onto the beachside tayellet, I ran. Green and red and orange fluorescent lights flickered across women with strollers, bike riders, and slick torsos. Before long, the rainbow-colored hotel loomed before me. It’s where I usually turn around. But today, for some reason, I kept running.
Israeli folk dancers and peddlers of cheap perfume slipped past me. Intermittent crowds became clusters of dining families and teenagers out shopping. I was entering the port. A street angel held a child, and delighted parents took pictures. Kids played on scooters. I skipped down to a low dock to avoid a mass of people congesting the slim walkway bordering the marina, and, jogging on past all the crowds, came to where the waves boom like cannons against the walls of the dock and then erupt into saltwater sprays, a place beyond the pedestrians. Just past that is the bridge that marks the end of the port. For the first time I hesitated, for I’d never run past here before. But, feeling spry enough, I took but an instant to decide, and went on.
Somehow I lost sight of the beach. I passed alongside a factory guarded by serious-faced men with machine guns, followed the road inland, and then continued along a highway while cars swam languidly by. My attempts to get back to the beach were continually stymied. Beyond a small airport, I found myself on a dark dirt road, unsure if it would lead anywhere, but hoping it would provide a shortcut between highways and building complexes to the beach. Kitchy Israeli pop music trickled in on the breeze. It became louder around this bend and softer as I went behind a high mound of dirt, but progressively closer until I realized that my meandering path was leading me towards it. Then I burst out of the darkness into a set of young and middle aged revelers dancing under too-bright lights, too bright for a party but fit for an exhibition, as if their festival had been planned on a stage for my benefit. To what I owed this, I don’t know. I was tired, my knees ached, and I didn’t belong there, so I ran past them, and as I climbed the dune of shoveled dirt beyond the party, I slowed to a walk. What was on my mind now? Not that which had set me to run. Peace had swept in, with only disconnected thought snippets interpolating between the sounds of the night. A bird chose that moment to fly over me and squawk shrilly.
I had arrived at a vista from which I could see the staged party behind me, a smokestack from the factory jutting up from the south, and what I thought was the rim of the sea straight ahead. Fields and low enclaves inhabited the darkness, followed by a wide trench cutting off two long archipelagos of office buildings and apartment complexes, and beyond that, an even, grassy hillock atop the dunes lining the ocean. I glanced once more at the party and, with dirt cascading into my running shoes, slid down the far side of the dune. The night filled with crickets. I wondered, then, if I could see the stars, and was surprised to find that the night was half shrouded in clouds, a rarity for summer in Israel. I kept on. The way was straightforward, and in not too long I was back on another beachside tayellet, passing quiet conversers on park benches, nodding to an old couple planted down by the entrance to the beachfront, and then, rounding a tall dune, making it back where I was aiming -- to the beach.
The beach was dark, quiet, and empty. Only occasionally did I pass solitary walkers, mostly lost in their own reveries, faces featureless in the shadows. Hot plumes of ocean air rolled over me and swept up the dunes, which were as tall as houses, and the stir of the waves over the low natural jetty obscured all other noises. I passed a couple having wine by the light of a headlamp and a fisherman whose head swiveled the whole way around to keep tabs on me, as if he were suspicious I might contaminate the night’s stillness. I looked backward and forward. Cities stood on both horizons, equidistant: the smokestack, high-rises, and lights of Tel Aviv to the south, and a mirrored collection of lights and buildings to the North, which I suppose were Natanya. Once more, I hesitated. My mind was now tuned into the night’s sensual offerings, with my initial thoughts dissolved into the ocean’s roll and the natural solitude of the duned, darkened landscape. I hadn’t thought about getting back, and now I started to wonder -- how would I? But the thought washed away, and my body said “forward,” and I obeyed.
Fireworks suddenly rose one after the other like phosphorescent palm trees across the northern skyline, their low thuds blowing in softly, long moments after the palm trees themselves had evaporated. I kept on, not able to move faster than a walk for the last hour probably, thirst beginning to harden my throat, yet determined. After a long while, high dunes and low jetties finally fell away, and I emerged at the other end of the beach into a Disneyland tayellet, with manicured grass on multiple clean terraces broken neatly apart by curvilinear rock walls. There was a water fountain. I drank and then sat, watching the waves break apart over the jetties.
I was here, I was -- where? Somewhere.
The city lights to the North were still a ways off, but not nearly as distant as the Tel Aviv lights, which shimmered like a tiny bundle of lightning bugs. I had gone far past the halfway point, far past the point from which my body could carry me comfortably back. I hadn’t budgeted for the return; I had only blazed forward, carried first by my legs and then by my spirit, and now I had gotten to this somewhere, and I felt lost. Thirst abated, I felt a deep strain in my leg ligaments, long unaccustomed as they were to running. I looked back and forth and then out to the ocean. The waves rolled in endlessly. For a while I stayed, soaked in sweat, sand carpeting my insoles, the tayellet's floodlights overpowering the dark night I had journeyed through to get there. Wherever I was going, no matter how weary I felt, I couldn’t stay here. I would have to keep moving. Somehow, I would have to get home.
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Categorizing people is only natural. We decide that this one could be a friend and that one could be a lover, and the one over there should be avoided, because he’s toxic. We list in our heads the attributes that we like, and then tick items off the list when we meet someone. But it’s the ones who don’t fold neatly into our boxes who intrigue us. We can’t keep our minds off of them. Those are the ones we become obsessed with, or fall in love with, become elated and then crushed by.
We also categorize things, situations, life events, and indeed even reality itself. On a bad day, the world can appear filled up with demons, and on a good day, with angels. We frame the way it should all be interpreted. But these frames are illusions. Any frame misses something real, and the deeper we fall into a frame, the more inflated and distorted become its edges, until they are ready to devour us. This is our shadow world -- the world that lies outside of our frames -- and if we are too rigid, the shadow will eat us. Look no further than Ted Haggard.
Our frames go way beyond where we think they do. We see, we feel, we hear and touch and smell and intuit things, but are those things actually real? Usually not. We experience a physical presence to objects like wooden tables, but it turns out that at the atomic level, tables are mostly empty space, and it’s electrical force fields that make them seem solid. Quantum mechanics makes us wonder if any of the components of the table have independent existences at all. Human consciousness seems to be actually a grand experiment in framing, because the reality we experience is certainly not much like the reality which actually exists. Our animal past has forced us to categorize. We are evolutionarily tuned for survival, and we must understand our surroundings in a way that allows us to wield it, whether or not that understanding is accurate.
If our frames are too feeble, we’ll wash about in the frames of others, like plankton. If our frames are too strong, they’ll force the world to our image, and we’ll be blind to the world’s actual shape. What we do not think a person capable of, if our frame is strong enough, he actually won’t do, and what we decide a person ought to do, he or she will. The stronger our frames the less we are ever surprised, because our world is so tightly controlled.
But ever so occasionally, an encounter can slap the frames away from our eyes. For that split second, we can see the world naked. These are the events that have the power to change us. We are left shocked, lost, and with edges of frames jutting everywhere, exposing all of the monsters that were hidden. We are suddenly aware of our frames, and of the fact that they’re frames, and of all the truths that, by operating within them, we’ve been missing. We see our old world as a dance of illusions. And we experience a choice -- to fit the frames back upon ourselves ever tighter, or to transcend them.
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She was a dignified beast. Stuffed full of coils of wire and disk drives and mysterious metal-laced innards, she occasionally emitted whirring sounds or high pitched beeps from within her thick plastic carapace. Her husk was beige and somewhat rough, because those were the textures of that day, kind of like black and white photographs. We had to feed her a floppy disk to get her to boot. She only had about a thousandth of the storage space of a modern thumb drive, and the same computing power as a modern throwaway flip-phone, but we didn’t care -- she crunched our numbers for us and had a word processor. What else could we ask of one? My brother was one of the few, the elite, who understood how to even use her. He was fluent in DOS. He even taught himself back then a few of the mystical languages of programming. Yes, my family’s first computer was a Brontosaur. But she was a Brontosaur with some megs, and it made all the difference.
All that wasn’t so long ago. Who would have thought we would have smartphones and tablets with apps for every bit of our lives in our hands by the year 2013? Computers have exploded in speed, functionality, and ubiquity since those early days. While this explosion involved billions of programmer-hours, its most convenient metric is Moore’s law, which states that computers tend to double in computing power approximately every two years. The trend has held since the mid 1960’s. Bootstrapping off of those advances, we have reached an era of computerization that a generation ago, few could have possibly predicted.
But this blog post isn’t about computers. You see, there’s another technological explosion happening right in front of our faces, an explosion every bit as far reaching and powerful as the computer one, but one about which tremendously fewer people are aware. I mentioned it in my last blog, but I didn’t get too deeply into it. What I’m talking about is the explosion in Genomics.
What is most striking is that over the last decade, genomics has been advancing at a rate even faster than Moore’s law. How much faster? Well, if we measure the progress of genomics by the cost at which we can determine the sequence of DNA in an organism, then nearly four times faster. This means that while sequencing the length of DNA in a bacterium in 2001 would have cost around $20,000, today it would cost something less than a dollar. The cost to sequence is not the whole story -- to actually assemble the genome of a whole bacterium you need to do quite a bit more sequencing and other processing, and interpreting genomes is one of the biggest challenges we face in science today -- but you can imagine what this reduction in cost has enabled. What this all means is that what took ~3 billion dollars, 13 years, and millions of man-hours to achieve in 2001 at the pinnacle of the Human Genome Project -- sequencing a human’s genome -- is now possible in a few weeks for several thousand dollars, and will be possible for less than a $1000 price-tag within only a few years.
The $1000-genome milestone matters, because around that price, genome sequencing starts to become relevant on an individualized basis in medicine. To put this more clearly, this means that when you go to the doctor not too long from now, she will be able to send off a drop of your blood or skin and have your genome sequenced as a routine procedure. In fact, even now, companies like 23andme will sequence parts of your DNA that indicate susceptibility to a plethora of diseases for just a few hundred bucks.
Just as with the computer revolution, by the time that the genomics revolution is done, we may barely even recognize the world that we live in.
If you were to ask a person on the street what genomics will do for them in their lifetime, they probably wouldn’t even know what you’re talking about. They might respond like a 1950’s housewife may have responded to a question about computers, or a pre-industrial farmer to a question about gasoline. Or perhaps they’ll think about embryonic stem cell research or human cloning and have a gut negative reaction. Most wouldn’t think of designer bacteria that emit wonderful perfumes, genetically modified algae that may solve the majority of our energy needs, cures for pretty much any genetic disorder, or totally personalized medicine (like a more advanced version of this). But these things are precisely what scientists think, talk, and dream about. The field is so rife with potential and is expanding so rapidly that how it will reshape us in the future is extremely hard to predict. But just as computers have changed our lives in ways we couldn’t have fathomed, so may genomics. And just as with computers, although there are certainly negative consequences, the potential of genomics for our lives is one of vast improvement in quality of life and happiness.
Genomics is the study of genomes. A genome is the collection of all DNA in a person or organism. DNA is a long, stringy molecule that dictates all of your genes, i.e., the traits passed on to you by your parents. The most amazing thing about DNA is that it dictates our genes using a digital code with only four basic letters -- A, T, C, and G -- which act sort of like binary code in a computer. This makes it extremely amenable to computerized analysis, an aspect that scientists have taken tremendous advantage of.
Every person on earth has a unique genome, and to sequence a genome means to use a combination of automated physical platforms and sophisticated computational methods (often run on a huge number of computer servers) to figure out the exact series of the A’s, T’s, C’s, and G’s that make a particular person genetically unique. Although the genome doesn’t explain a person’s every trait, it explains a great majority of them. In 2001 when researchers published the first draft human genome, it was actually an averaged genome of several people. Now, our technology enables us to sequence individual genomes to near completion, which may be the key to truly personalized medicine.
Each one of your cells has a couple copies of your own personal genome (except for a few weird cell types, like red blood cells, which contain no DNA). The fact that there’s a copy in every cell is how, for example, scientists were able to create embryonic-like stem cells out of skin cells, a technology that may both bypass many ethical issues and allow for some amazing new therapies. Imagine regrowing a damaged organ, and having a transplant from yourself. As we get better at understanding and manipulating genomes, we will shine guidelights into many more areas than just that.
This was amply demonstrated in 2010 when a team led by Craig Venter created the first ever synthetic lifeform. To do this, they synthesized from scratch the entire genome of an organism based on a string of DNA code that had been planned on a computer (mostly following the DNA plan of a natural organism, Mycoplasma mycoides), and then implanted the synthesized genome into a cell whose DNA had been removed. The “synthetic” cell proved to be viable, replicating billions of times. While this synthetic cell was not so different from its natural parent, the process could be repeated for much more outlandish designed genomes.
I saw Craig Venter speak about this in Tel Aviv last year when he accepted a science award called the Dan David Prize. During a student Q&A session, he spoke about automated evolution: creating synthetic lifeforms and then mutating, evolving, re-sequencing, analyzing, and re-designing them, and thus closing the loop between computers and biology, enabling us to build and understand bugs that do anything. He spoke about cells in a way I had never heard before from a biologist -- as computers running DNA software that is now, with Venter’s technology, easily exchangeable between silicon machines and biological hardware. I asked him about Ray Kurzweil’s singularity, and whether he feels his technology is driving towards it. He smiled like a man in the know.
Of course, such power is not without dangers. Who should be able to wield this technology, especially if synthesizing new genomes becomes cheap enough to be commoditized? Because of the potential damage, it is almost inconceivable to release synthetic cell technology into lay hands. Think atomic energy. Good bioethicists and regulators must play a role, but even there we will face difficult dilemmas.
And the dilemmas don’t just begin with synthetic lifeforms. There are also basic ethical questions surrounding the mere sequencing, and not even getting into the manipulating, of genomes. Sergey Brin, the co-founder of Google, knows this well. When his wife founded the sequencing company 23andMe, Sergey Brin was one of the first to have parts of his genome sequenced. It turns out he has a rare mutation putting him at high risk for Parkinson’s disease. Brin has taken a pragmatic approach, and is now doing everything he knows of that will decrease his risk. But the lesson is obvious. Even if you can know about all the diseases you’re at risk for, do you really want to? Do you want potential employers to? Your insurance provider?
That being said, to forsake such technology because of fear of its dangers seems foolhardy. Last century saw the atomic age and the space age and the computer age, and I believe that when we look back, we may call nowadays the genomics age. We should proceed with caution… but we should proceed.
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Why a black swan named Brooke Greenberg might make you immortal -- or not
Back in the old days, black swans used to take their tea with purple zebras, play hopscotch with orange kangaroos, and ride the unicorn skiff down the Cadbury-cream river with yellow porcupines. That is to say, black swans didn’t exist. At least Europeans were certain that they didn’t until a seventeenth century Dutch explorer actually discovered one on a trip to Australia. It turns out that in the land down under, black swans are not only possible, they’re common. So if you happen to see an inverted swan waddling by outside of your window, don’t panic. First off, you're probably in Australia; and secondly, you've just seen a reminder of how a single unexpected observation can topple hundreds of years worth of dogma.
I first heard the story of black swans in a talk by the Chief Scientific Officer at TEVA Pharmaceuticals, Michael Hayden, a few months ago in Jerusalem. Hayden’s topic was not actually swans, though, but rather drug discovery. He summed up his philosophy on finding new drugs by saying that people who display rare physiological attributes, either beneficial or harmful, may be the key to our next blockbuster medicines. He was referring to people who experience pain excessively and also people who don’t experience pain at all, who are extremely tall, who are resistant to deadly diseases like AIDS, or people who don’t age. Hayden called these types of people black swans because, like their namesake, they exhibit traits that we never would have expected to exist. That is, until the day we actually encountered people who have them.
Perhaps the idea of developing drugs by studying black swans seems like no big deal to you. Of course we discover new drugs by studying people with rare conditions, there’s nothing new about it, right? The answer is somewhere between “sort of” and “no.” Actually, new drugs are typically developed either by searching for molecules that can cause a beneficial-seeming effect in cells growing in a petri dish, or by testing large collections of drug-like molecules for their ability to target a protein that is thought to be important to a disease. These approaches are problematic because they often lead to new drugs that are dangerous in humans, have major unintended effects, or simply don’t work. Even a drug that perfectly targets a protein we think is important can be a failure, because targeting that protein in a human may lead to effects not encountered in the cells assayed. It is because of such an unintended effect, for example, that the hypertension drug Sildenafil became the erection drug, Viagra.
A black swan approach would be different. The key to Hayden’s philosophy is that if we are able to identify the cause of a black swan trait and to perfectly target it with a new drug, then we already know what the side effects of the drug will be from the get-go. The side effects, if there are any, should be readily apparent from observing the black swans after whom the drug was fashioned. This idea isn’t just science fiction. I mentioned before that there are certain otherwise healthy people who simply do not experience pain. A black swan approach to developing a new pain medicine would involve identifying the mutated protein that causes this rare trait (if such can be found), and then developing a drug that makes this protein in normal people act like the mutated one. A well-targeted drug would have a very low chance of being harmful, because we already have examples of people who have this condition permanently, yet who display no seemingly adverse side effects. In fact this example is real. Drug makers are now developing a new class of highly effective, non-addictive painkillers based on this no-pain trait, which may soon be changing the lives of sufferers of chronic pain.
There is another black swan named Brooke Greenberg, who may hold the secret to aging.
Brooke enjoys being swung around in the air, playing with her sisters, crawling on the floor, giggling, and getting attention. Do these activities seem strange for a twenty year old? That’s because despite being twenty, Brooke stopped developing around the age of five, and still has the mentality and physical appearance of a toddler. Her case has baffled doctor after doctor, and has led to stupefying interviews and media appearances by her family. It’s too early to tell if Brooke Greenberg actually holds any keys to immortality, but it certainly appears that in some aspects of aging she has either stalled or has almost done so, which provides hope. Taking a forever-young pill may be possible in the not-so-far future.
The key then lies in being able to figure out what’s causing Brook’s condition. If we can determine its cause, maybe we can develop drugs that can mimic it. But the thing about black swan traits is that up until recently, we haven’t had a reliable way to figure out what was causing them. We could do a battery of physiological tests, take blood samples, search for abnormal proteins or tissue functions, and write case studies, but these often just led to more head scratching or a long process of biological discovery, rather than a straightforward path to a cure.
This whole process may be on the verge of an overhaul.
In January, 2013, in an interview alongside Brooke’s family on the prime time show “Katie,” a geneticist at Mount Sinai Hospital named Eric Schadt explained that his group has sequenced Brooke’s genome, and is in the process of analyzing it for clues about aging.
Until very recently, sequencing an individual’s genome would have been either impossible or prohibitively expensive. Not so anymore. A full human genome now can be sequenced with reasonable accuracy for something around 5 thousand dollars, down from 50 thousand dollars just in 2009, and hundreds of thousands or more just a few years before that. This opens enormous new avenues for understanding black swans like Brooke Greenberg. Many of the differences between her genome and a “normal” one will be readily apparent, and as more people’s genomes are sequenced as references, the differences will stand out more and more clearly. Knowing these differences is the key to then developing cures.
Of course, knowing what’s in the genome is only a part of the whole picture. But, as Michael Hayden pointed out in his talk, there is a hidden advantage to the black swan approach over other drug discovery methods. This is that when dealing with a black swan trait, we have a very good hunch before we even start drug development what a well-targeted drug would have as its side effects.
The importance of knowing the side effects of a drug from the get-go cannot be overstated. Developing drugs is almost inconceivably expensive -- in the neighborhood of four to eleven billion dollars per drug. The majority of this cost is from the huge number of drugs that fail during clinical trials because they’re not safe, which in turn pump up the cost of the drugs that do make it. Although it may not seem to matter how much drug companies pay to develop drugs, it matters hugely -- lowered cost could be a game changer, making drugs cheaper for consumers, and enabling drug companies to focus on many diseases that are not now on their radars because they simply aren’t cost effective.
Black swan-based drug discovery may be the ticket to reducing drug failures because of side effects, but black swans can sometimes portend some pretty serious side effects, too. Brooke Greenberg is no exception. First off, it may not be so simple to isolate Brooke’s anti-aging trait from fundamental and crippling developmental abnormalities, which have kept her not in the prime of her life, but as a toddler. Secondly, Brooke has had a smorgasbord of medical complications, including stomach ulcers, seizures, a stroke, a brain tumor, and non-uniform tissue aging, which led to her esophagus closing and her needing to eat through a feeding tube. These are discouraging. Yet Brooke has also recovered from many of her complications astoundingly quickly, lest we forget that her body is harboring a great many secrets. To some of these secrets, her genome sequence may yet reveal answers.
Brooke Greenberg was born into an exciting age, in which a confluence of technology and knowledge has given a condition like hers a tremendous potential to help others. It’s yet unclear if her condition will enable us to attack aging, but genome sequencing gives us a leg up on any other time in history, and we have reason for optimism. Sequencing a person’s genome now costs on the order of Lasik eye surgery, and it’ll soon be much cheaper. The possibilities are as numerous as the traits we can see in people around us. We’ve really only just cracked open the doorway revealed by genomics, and the next leaps in medicine, in biology, in our very culture, may be incubating even now, somewhere, in the nest of a black swan.
“To admit you to the “little nucleus,” the “little group,” the “little clan” at the Verdurins’, one condition sufficed, but that one was indispensable: you must give tacit adherence to a Creed one of whose articles was that the young pianist whom Mme Verdurin had taken under her patronage that year and of whom she said “Really, it oughtn’t to be allowed, to play Wagner as well as that!” licked both Planté and Rubinstein hollow, and that Dr. Cottard was a more brilliant diagnostician than Potain.”
So begins part two of Swann’s way, the first one of the seven volumes of Marcel Proust’s masterpiece, In search of lost time. Swann’s way was handed to me by my friend Hagai as he was packing his things several months ago to leave Israel. “Take it,” he said. “It’s a marvelous novel. There are sections about nature, which are generally boring. But the sections about society, relationships, and memory are exquisite. I think you’ll find it worth your while.”
Well it certainly was a while: it took me over two months to read. But in sum, I also feel it was definitely worth it.
Proust is notorious for being difficult, for being pretentious, and also, with his great novel often touted as the definitive masterpiece of modernist literature, for being one of the greatest writers in history. In Search of Lost Time is the choice tome for many literati when asked the ‘what would you take to read if you were stuck on a desert island’ question. But let’s discard these prejudices, because indeed when I approached Proust I didn’t really know what I was getting into. All I had to go on was the recommendations of a close friend.
I finished Swann's way just this weekend, turning the last page with nostalgia almost as if I had relived a childhood. As is true of the events of actual life, the most prominent feature of the earlier parts of the novel was not a collection of sharp instances or details, but rather a haze which is best defined by the emotions it has the power to conjure. The book itself is, not surprisingly, Proustian (by this I refer to the principle of involuntary memory). I couldn’t even recall the individual events of the novel which had conspired to generate this nostalgia in me, for many of them had been submerged into the atmosphere of the thing and were certainly not in themselves relevant. Finishing it gave me the same longing and apprehension that one gets when approaching a life transition, or when saying adieu to a loved one.
But attaining this feeling came at a cost, for getting through the novel was, as it was promised to be… difficult.
There are three sections to Scott Moncrieff’s translation of Swann’s way: Combray, Swann in Love, and Place-Names: The Name.
Combray was the tough one. There were vignettes in it that kept me happily reading, but those were interspersed between long slogs. Comprising sometimes dozens of pages of florid description with no plot, the slogs were equally abstruse as they were slow. The whole book is, in fact, written in long, periodic, convoluted sentences that use a vocabulary of the very highest English, all of which requires rather a lot of attention to follow. (I’m strange in that I actually particularly liked this). Proust is not to be read by the impatient or the attention deficit. Despite all this, and because I glimpsed brilliance in certain segments of Combray, I never seriously considered putting the book down. But I wasn’t sure if I would ever really get into it, or rather if the book would remain as merely a time-consuming curiosity in my life-history of reading.
All of that changed with the sentence that I pasted at the top of this blog post. Within pages of starting part two (Swann in Love), I was mesmerized. A two month journey had gotten me through the 264 pages of Combray, but I swept through the 279 pages of Swann in Love in about 4 days. Consider that the sentence at the start of this blog is neither more nor less complex than the average sentence in the Swann’s Way, and you will understand that I must have been very engaged to have done this.
I thought then that Combray should simply be skipped, because it and Swann in Love don't really need each other. However, I’m not so sure now. The last, short section of the book, with the awful name Place-Names: The Name (which I’m guessing comes from a clunky translation of the French), evokes both Combray and Swann in Love and creates certain images which, without the context of Combray, would lack the lingering depth perhaps best characterized by feeling something just at the tip of your tongue, which you just can't quite put a name on. I was impressed by the crafting of this emotion, and I realized that without Combray, the effect would have been thinner.
Combray focused on the narrator’s childhood, and, like childhood itself, was richer in impressions than in happenings. The very fact that it was difficult, that it took a long time to get through, also played a role in its power. The focus, like childhood’s, wasn’t on plot, but rather on an experience that is often characterized by its very lack of occurrences. The book purposely slowed me down, and forced me into its own, drawn out pace. Only because of that was I able to relish the ending, for I felt as if I had been on some sort of a journey by the time that I got there, with its slow and its faster bits, which is ultimately more similar to life than is any pulp or, indeed, the majority of the media of modern consumption.
Proust is not an author who I feel will appeal all too easily to most modern readers, because, like the literature we have demanded and received, we order our emotions in digestible bites. Proust couldn’t have cared less about word counts or succinctness, which sets him at odds with nearly all modern authors. We live in a world now in which attention is one of the greatest currencies, and grabbing the attention of a consumer is so critical that most of the art about us is designed to first draw us in, and then, perhaps, to release its slower and subtler influences. Without the marketing feature at the outset, these works would simply be ignored. Who has the time to read something that doesn’t get right to the point?
But there is a value in not getting to the point, because life itself doesn’t get to the point, either. Proust certainly could have managed to tell the same story in less or in simpler words, but I don’t believe he even would have wanted to. If you are to appreciate this book’s merits, you are to surrender to Proust’s meanderings, and you are to trust him that these meanderings will be worthwhile. If you don’t trust him, don’t start. I believe that Proust wanted to capture the moments he described in his story as if they were emotional photographs, and to a large degree, difficult as it is, I believe he succeeded.
I have enough faith in Proust now that I'm ready to follow him through another 6 volumes. The end of Swann's way leaves me feeling satisfied but as if the ground has been set for something far bigger. Hopefully I can manage to get my hands on the rest of the set before I ever get stranded on some desert island…
Roman [3:50p,12/27/2012]: Yo! What time ur going today?
Me [3:59p,12/27/2012]: Yoyo, maybe 7?
Roman [3:59p,12/27/2012]: Yap
My hand quivered over my mouse. Milky brown coffee residue lined my porcelain cup, and sugar crystals were splayed over the saucer. Too many coffees. I tried to concentrate on my work but my hand kept drifting back to my phone, and my eyes to the clock. Just a couple more tasks...
I raced out of work as soon as I could, ran after the bus and just barely caught it, and, after gathering my climbing gear, rolled my bike out of my flat within minutes. Halfway to the climbing gym, I felt my pants buzzing. Jeremy was calling me.
“Hey, I’m here already,” he said.
“I’ll be there in three minutes,” I replied, huffing.
“Okay--I’m waiting outside.”
I squeezed the phone back into my pocket and pedaled the rest of the way there. And--there was Jeremy, dressed in what could have been breakdancing attire, a baby-sized yellow pack on his back, and his goateed face breaking into a broad grin. We hugged. Electronic music pumped out of the climbing gym in an overwhelming volume.
“Whoa it’s loud!” I yelled.
“Yea, they’ve been playing around with the volume since I got here!” He yelled back.
“Come on!”
Escorting Jeremy into a climbing gym is like bringing a child into a cookie factory. But tonight the gym’s owner was throwing a party, so aside from the live DJ making the place whomp, there were also a gazillion people. We wove through the crowds. Jeremy’s pupils dilated at the first sight of climbing holds. The moment reminded me of a long time ago, back when Jeremy and I used to visit playgrounds and climbing walls and muck about trying to climb everything in sight. We were just kids then. We grew up together in Raleigh, North Carolina, and a big part of our childhood involved sleeping over at friends’ houses and making up breakdance moves or climbing on trees or over fences or trying amateur parkour. I stuck with climbing while Jeremy merely continued to dabble in everything, his natural talents sufficient to keep him happily lazy.
Pretty soon though we were hopping around the climbing gym just like kids again. Jeremy had his smartphone out and was taking photos and videos, in between traversing the wall on big jugs. I was doing some warmup dynos. “Do that move again,” he said to me at one point, breathing hard and holding the camera up. I tried jumping to a blunt grey sloper, slipped off, and rolled onto my back on the mat. Just as I stood up I felt a large hand grasp my shoulder, and when I turned around there was Roman, tall and hunched and wearing a crooked grin and a grey hooded jacket, his hair as disheveled as ever.
“Romansky!” I shouted. “C’mon, I’ve got to introduce you. This is my friend Jeremy I grew up with…”
Everyone showed up over the next hour. There was Dana, red hair knotted tightly to her head and eyebrow ring gleaming as she wrinkled her brows and narrowed her eyes and struck an aggressive pose, and then broke it up with a huge smile and bear hugged me. Iv, insouciant as ever, sauntered in slapping five and saying what’s up to half the people he passed. He saw me and Roman and dropped his head and chuckled. His dark bangs curled down over his eyes. Then he opened his long arms wide and hugged each of us. Marina moseyed in and, seeing us, gave a little body wiggle and laughed. When Moriel and Claire showed up, Claire butted me out of the way and hugged Jeremy. “You must be Jeremy. It’s so nice to finally meet you!” Moriel and I shrugged and went for the beer. Pretty soon Jeremy was cracking jokes with everyone and telling stories about our youth. I felt a little warmth inside. It was rare to be able to share a night like this with such an old friend, and to have it all in such a good spirit. He and my Tel Aviv crew were already getting along swimmingly.
We all climbed for a few hours but beer eventually took precedence, and the mood went from athletic to party. The energy in the place rose along with the music, and the lights dropped. Finally, the inside of the gym evolved into a club scene. By then I was out in the back with most of my friends, licking my fingers clean of hamburger juice and chomping potato chips.
“I don’t want to push anything, but there’s a whole bunch of ladies in there dancing, and that isn’t going to last forever…” Jeremy said. I nodded at him. The two of us hopped up and joined the mixed hiphop and trance groove, and within minutes, all of our friends had joined in as well. And then, as if some signal had spontaneously struck inside of everyone’s skull, it seemed that the whole party burst at once onto the dancefloor. I thought back over some of the more outrageous moments from our little community, and I guess I shouldn’t have been too surprised to see all of these folks busting a move--
--not, at least, considering our trips down to Timna, which included a whole carnival of colorfully garbed characters descending upon a red desert setting for Purim, spending our days exploring sandstone blocks and our evenings bouldering by headlamp in full costume, and eating the delicious all-Israeli dutch-oven stew called poike. Not to mention the Israeli bouldering competition, and my friends’ devious and wildly successful scheme to get everyone, guys and girls, dressed up in 80’s style spandex--
--I looked about me again, feeling the bass whump. There was Jeremy doing the robot, as pneumatic as a collection of steam pistons; and next to him Iv, doing his best to teach me the shuffle, his big arms and long body flailing about like comedy props; and there was Claire, thrusting and thumping, her look saying “This is my dancefloor,” just before she broke into a sheepish grin; not to mention Ayelet pulling out some of her old Electro-party dance moves; and finally Valerie and Rony and others, faces lit up with laughter, and their bodies a blur.
The dancing eventually died down and then ended, and we all hung out and chattered and played acro yoga games for a while. Finally, Jeremy was off, with a hug and a promise to meet up back in Raleigh. “We haven’t partied like that since… well, ever,” he said. The rest of us dispersed soon after in various directions.
But the weekend was only just started.
Roman [1:47p,12/28/2012]: Shall I get a crate of beer?
Me [1:49p,12/28/2012]: This is IV. Beer!!!
The next evening, I found myself swooshing off with the same crew towards the outdoor climbing area Ein Fara for the annual Israeli climbing festival, Festipus. We arrived just in time to grab dinner. There was a chill in the air that hovered just outside of our down jackets, but the mood was festive, with people all about the campground playing guitars, talking, laughing, and sharing stories and jokes.
Within a few minutes my friends had all frozen in place in a circle, exhaled breaths curling up into mist, the only motion an occasional arm swiping down towards a stray hand. We were playing ninja, a game in which we take turns trying to slap each other’s hands with minimal extraneous movement, with two slapped hands meaning you’re out.
We had played this game with increasing vigor on each climbing trip that we’d taken over the last year, and by now, it had taken on a nearly archetypal significance. Iv was here on the ground crawling between someone’s legs, there sliding back to back with an enemy, and finally was stretched wide in the center of the circle, arms tauntingly close to the other players, posture deliberate and exaggerated. Yonat, sweet looking but with a catlike ferocity, moved in brief spurts which always ended in loud cries from victims and winces from onlookers. Dana kept a low profile but now and again pulled a zinger out of her puffy jacket sleeve. And then there was little Rony, as silent and deadly as a possum. Our fun caught on and a couple of traveling Americans, as well as a bunch of Israelis, joined in with us. At one point we had fifteen people in the circle and a number of onlookers cheering. Ninja shifted to zoo, to charades and to cowboys and princesses, and other pantomime games. We were almost unable to breathe through our laughter.
The next day dawned cold, and after wiping sleep from our eyes, we all got down to the serious business of rockclimbing. Crisp winter air kept the wall just cool enough for good friction. Iv and I climbed a few steep and pumpy routes in between breaks to drink coffee and greet friends from different areas of Israel. The day swept in and then out and, before we knew it, we were stopping in a small Arab village for a hummus on the way back to Tel Aviv.
Because Roman was driving, we had to go into the sweets shop across the street after our hummus to eat Knafeh, an arab treat consisting of sweet goat cheese and a gooey orange rose-flavored syrup-soaked straw-noodle topping, sprinkled with pistachios. “It’s not Yefet street, but it’s really good--you must eat this one,” he said. We tried three varieties, each one of them sweeter and more delectable than the last, and followed them with Turkish coffees. Five minutes later I was dead asleep in the back of the car.
I woke up when we dropped off our first passenger, Ayelet. I waved weakly at her. Next was Iv. I was awake enough then to get out of the car, and we slapped five and both said simultaneously “New years” and grinned. Next was Marina, who was leaving the next morning on a month-long trip in Mexico. Roman and I hugged her goodbye and wished her safe travels. And finally it was just me and Roman in the car, both wearing lazy smiles. We drove in silence for a few minutes.
It was only seven o'clock, but my body was wracked from a weekend of nonstop action and rockclimbing, and from barely sleeping. But I couldn’t have thought of a better way in which to have spent it. There was something special here, now, with this group of people. Kind of a resonance.
Roman nodded, feeling the same mood. And then he said: “Don’t worry man, this isn’t it. There will be more of these.”
I took a deep breath and felt the hum of the engine. I knew it was true, and I knew that it wasn’t. But there’s nothing to do but to grasp on to these moments as they’re happening. After all, they each but occur once.
We slapped five and I got out of the car. I grabbed my pack, shut the door and waved. I watched Roman pull out of the spot and drive off. And I went up to my flat, exhausted and happy. Just in need of a little sleep before the next big adventure.
