Wordless poems

I remember I wrote a post on a swimming forum sometime ago, something about long-distance swimming. Someone was wondering how long-distance swimmers can endure the lap repetition and stuff like that. I wrote something to this effect: I don't get bored because I got to think, pondering about the problems in school, about unrequited feelings, and incubate wordless poems. The phrase wordless poems occurred to me right then and there and has stuck ever since. Wordless poems. Subconscious jumble. Primordial soup of thought. Aren't we all carrying wordless poems in our heads? That which sometimes has never found its home until we die. Those homeless hermit crabs crawling on the beach bordering the sea of knowledge. Wordless does not mean voiceless. Give it volume, construct meanings out of it, give it a home, give it wings, and let loose.

The flag of ignorance

I heard this somewhere, I think, in a Christian apologist's podcast, arguing about absolute truth:

If everything is relative, then this statement is relative, too.

That stuck with me for the longest time because it is a solid shelter in the wake of Postmodernism.

But no, it's not about Postmodernism. I found that people I talk with (or others in a certain social media) are simply using Relativism because they don't bother to find out, really. 

A friend expressed his astonishment when I was reading a book related to Zen Buddhism:

"But, aren't you a Christian?"
"Yes, but what's wrong with finding out more about other beliefs?"
(Shakes head) "My other Christian friends simply wouldn't do that."

That, I don't understand. How can you defend your own belief if you don't know about others'? Now, I can only attribute that to laziness. Postmodernism is indeed one of those terms that is bloated beyond recognition and no one can offer a succinct definition of it anymore. It's a hand-waving, sweeping-under-the-rug thing. I don't bother to find out, so to cut the conversation short, I shove it to that trashbin of meanings, Postmodernism.

On the other end of the spectrum, there is a striking parallel with God of the Gaps thinking -- I don't understand and God is the totality of what's mysterious, what I don't understand. The danger of this, of course, your God would become smaller and smaller as you understand more, like Santa Claus is becoming less and less real when you are growing up.

Seekers of Truth, don't rally under the flag of ignorance.

A Structural Biologist's Manifesto

"So, what are you studying?" Depending on who is asking, the length of my answer would vary. See, since I go to grad school, quite a number of people are asking me that; and answering 'Biomolecular NMR' would draw some blank stares.

So, go back a little: Chemistry. Ah, my undergrad major, and since my lab uses analytical chemistry technique (i.e. Nuclear Magnetic Resonance) to probe biomolecular structures, this answer is not too far off the mark.

"So why are you in the School of Biology?" Ahem. Here we go again.

So, the slightly longer and my supposed official areas of study: Structural and Computational Biology. I think I shall reintroduce my clockwork analogy here. Imagine a clockwork with all its gears running inside. If one would want to know how exactly the clockwork mechanism work, one would want to take it apart and see the gears; how they are connected together, what are their shapes that fit each other so that the concerted mechanism is running. Now, every living thing is also a machine, a biochemical machinery, that, like a clockwork, consists of tiny, tiny parts that are grinding away and give rise to life as we know it. Ideally we want to map how these biomolecular gears interact with each other (i.e. the interactome). Prior to that we would want to know how these tiny gears look like. The structures of these tiny gears are then what the structural biologist would like to know.

'To know' here, as in all areas of science (or anything, really), should be interpreted philosophically. The usual limit of what a structural biologist want to know goes beyond 'having a visual representation'. Sure, it's nice to know what these biomolecules look like since we normally can't see them with naked eyes. But blobby blobs at crappy resolution (say, 15 Å) doesn't tell much. Like a blurry text on a document for example; it's unreadable. What we would like to know, ideally, is the visual representation at the resolution of individual atoms (i.e. atomistic resolution). The blurry text on your document now gains some sharpness; now you can distinguish individual letters; it's now legible. Often, this is sufficient to establish how it behaves, how it interacts with, say, water molecules, metal ions, drug molecules, or other biomolecules.

To even arrive at this point is an accomplishment (to illustrate, resolving a previously unresolved structure of a big protein and analysing its structure-function relationship may occupy the whole PhD thesis, to give you a sense of scale). Could we do better, you ask? Erm, there's actually some problems -- hitting the philosophical wall, so to speak. Let me explain.

*WARNING: TECHNICAL TERMS AHEAD*

So, there are two common techniques used to probe biomolecular structures. (Oh, when we are talking about biomolecules, we mostly talk about proteins -- the biomachinery mostly comprises them).

The first is X-ray diffraction. It works by interpreting the diffraction pattern of X-ray by electron density of the atoms that make up the biomolecule. Since the atoms are arranged in a particular way for a biomolecule, the diffraction patterns are unique to each biomolecule; and long story short, the X-ray crystallographer would be able to construct back the electron densities of the biomolecule, thus she would able build a model of the biomolecule.

Now, problem #1, for a nice diffraction pattern, you would need repeating units, so you would need crystal of your protein, and crystallising a protein is honestly a PITA. Arising from that, problem #2, you would try a lot of different conditions until you find one that is suitable for crystallisation -- who is to say that that particular condition doesn't affect the structure of your biomolecule? Still arising from problem #1, the protein in say, your body, is in aqueous environment, but in your crystal it is obviously in solid -- problem #3, who is to say that your protein structure is not altered by crystal packing, and problem #4, your final structure would be a static snapshot of the structure frozen in the crystal, while the structure in solution must be a lot more wiggly-diggly -- do you now claim you 'know' the structure? (There, your epistemological wall). Problem #5, most of the atoms comprising a biomolecule -- C, O, N, S, Se, and some metals -- have nice, fat electron densities, but that ubiquitous Hydrogen, the most abundant element in the Universe of things living and non-living, does not. As such, H atoms are not visible in the crystal structure. Problem #6, so are regions of the biomolecule that does not form regular repeating units (most likely because they are floppy).  Problem #7, when you are matching atoms to your electron density map, some are ambiguous (e.g. you can point sidechain A at this orientation, it fits ok, flip sidechain A 180° and it still fit ok, even though on one orientation it's N but the other is O -- since N and O have similar electron densities).

So your typical X-ray structure file would miss its H's and its flexible regions (the termini are usually susceptible); some sidechains may not be at their correct orientation; and there's only one frigging, static frame. Would you now consider you 'know' the structure?

Oh, then there's NMR. The laypeople would be more familiar with MRI (Magnetic Resonance Imaging). Indeed the underlying principle is the same: both exploit the same phenomenon, i.e. nuclear magnetic resonance which arises from nuclear spin (which belongs to the wonderful, you-will-understand-better-if-you-don't-try-to-understand-it world of quantum mechanics (for instance, there's no way to visualise quantum spin)). Long story short, NMR yields a set of restraints. If in X-ray crystallography one needs to fit the biomolecule to the little pockets of electron density, in NMR one needs to fit the molecule to satisfy these restraints. So you would have to know the amino acid sequence of your protein. So then you have a totally linear peptide -- make the peptide explore different conformations to satisfy the restraints, a game of Twister if you will. What you end with would be a set of conformers, which would be ranked according to their energy. Usually the first 20 low-energy conformers are deposited in public domain. The fact that there is a set of conformers, called an ensemble, is important. By aligning the conformers in an ensemble, it's usually clear which region is flexible -- the deviation for that particular region would be more pronounced across the conformers. So an NMR structure would have its H's, all amino acids visible and it's not a static snapshot (cf. X-ray structure). Also, if you do solution NMR, it's may be possible to as close to physiological condition as possible (may not be totally tractable because of limitation in NMR setup itself, e.g. NMR signal at high pH condition decays too fast).

While seemingly answering to all X-ray crystallography's woes, the NMR spectroscopist faces a totally different set of problems. First off #1, NMR is an indirect technique, unlike X-ray diffraction which directly constructs a map of electron densities. So NMR structure doesn't really have a concept of 'resolution', which makes it kind of hard to assess the quality of a structure. So, you have made your protein play a game of Twister to satisfy your restraints, now #2, the quality of restraints -- if I see a flexible region in the ensemble, is it really flexible region, or I didn't apply enough restraints, that's why it's fuzzy? #3, the game of Twister is called restrained molecular dynamics, basically a computer simulation. Of course, it's only possible to incorporate approximations and assumptions, not the whole physical law shebang, into the software. Some of those may not be appropriate and may affect the resulting structure in a significant way. There are some technical obstacles as well, like how the protein of interest needs to be isotopically labelled with NMR-active nuclei (15N, 13C). The final step of reconstructing the structure is tedious both for X-ray crystallography and NMR spectroscopy -- so that adds to the time needed to produce a good 3D representation of a protein. 

So, for the umpteenth time, after successfully determining a structure, the structural biologist should ask, metaphysically, Do I 'know' the structure?

Science, people. 

That's it. Next time I will just reply, "I do Science."  

Delightfully Lost and Human

Onsen, yukata, tatami, futon.

Those are some of the things I knew about Japan. Most of my knowledge about the Japanese language and culture came from my extensive manga reading. You may have friends who faithfully follow scanlations the Shounen Jump Big Three — One Piece, Naruto, Bleach — but the amount I read is much more. For example, to my own astonishment, I have to spend one whole day catching up on my manga reading after a two-week trip to Japan, during which I didn't read manga that much due to the limited screen estate of my puny laptop.

My manga obsession aside, I've learned that I have nuanced knowledge of the Japanese culture that my travel companion, an advanced-level student of Japanese language, does not know. I recalled telling him that in several mangas I read, people enjoy a drink of cold milk after soaking in onsen — I was telling him this when we have just finished our own share of hot spring soaking. So I wandered to the vending machine to verify my own trivia, only to discover other bath-related stuff in the vending machine: shaver, soap, shampoo, a pair of boxers — the latter an interesting finding notwithstanding, there was, to my dismay, no cold milk. However, imagine my delight when I paced to the other hand of the changing room and found, you guess it, a cold-milk vending machine. Needless to say, we teetered gleefully to it and fed it some coins. 

There were other moments like this, when my knowledge of some obscure aspect of the Japanese culture showed. On the other hand, there were also moments when my companion has to rescue me from drowning in the verbal torrent that is Japanese speech. And there we go, two people who have some knowledge in the Japanese culture and language, and somewhat lacking in travelling experience.

--

Where one goes on a journey, is quite inevitable really, that one will sooner or later get lost. In my native language, there is an aphorism that says he who is too shy to ask directions will get lost. My companion, who was keen to apply his Japanese language and finding our own way, was averse to asking. Myself, following wisdom of the ancients and being emboldened by the fact that we were in a land of strangers, would go up to policemen or other young-looking people in businesswear (more likely to speak English), said sumimasen (excuse me) and went straight to a mixture of dumbed-down English and animated, flailing, Tarzan-and-Jane sign language. Fear of getting lost triumphs over introversion.

Towards the end of the trip, we visited the Ghibli museum. There was one sentence in the pamphlet that is decidedly stuck in my mind, namely, I paraphrase: The visitor is encouraged to get themselves lost in this museum. Indeed, if you have seen even one or two Ghibli animations, the brand of the fantastical will soon be impressed upon you; what seems like a normal scene gradations into the magical, the preternatural. True enough, for an establishment that encourages one to get lost inside, the interior of the museum is delightfully confusing so that one would be delightfully lost. Upon entering reception, one would choose to view a short animation à la Ghibli, that would jumpstart a fantastical journey; or, one can choose to view various zoetropes of familiar Ghibli characters. Real time animations are hypnotic; it sucks you in, it transcends to your plane of reality: like Hey, this is not the animations you see on your silver screen, these characters come to life; right here, right now. Only after visiting Ghibli museum, I understood that getting lost is okay; that one should wonder and wander in lostness; bringing out that childlike quality of marvelling in everything, worrying not a farthing about how to get home, because one would be home eventually, for now be hypnotised by the present and seize it, the present and the day.

The writing of Augustine of Hippo was described to be 'digressive'. Although undoubtedly this gives headaches to his translators, the commentator mentions this in the tone not of derision, but of delight, because eventually everything would tie in together and the reader is brought to the home of the argument. Augustine would take his reader to a journey with a lot of detours, just like life, that grand scheme of things, is itself a journey with a lot of detours. (If this is not obvious to  the reader by now, I'm using this digression to justify digressions. Feeling delightfully lost yet?)

--

I read travelling accounts sometimes, and now I understand why there is a whole genre dedicated to travellogues: travels expose you, force you to rethink your assumptions and prejudices, shove a new paradigm down your throat. And if that doesn't wring creative juice out of you, I don't know what will.

I foolishly only recently made the connections between manga and cartoon. During my travel in Japan, I was confronted several times with a nagging feeling. The nagging feeling that the real thing does not hold up to my expectations. We were lucky enough to witness summer festivals, where stalls of food and other amusements were set up in the neighbourhood of nearby temples and shrines. In my mind, it was a magical place — you would go to one wearing yukata, treating yourself to takoyaki, candied apples and a game of goldfish-scooping; you would pray at the shrine and give offering, buying charms and draw fortunes; you would wait until late at night when fireworks like a spontaneous field of blossoms would burst, colouring the night sky. Yes, I did witness some of this, but somehow something was lacking. The first fantasy-shattering thing: the price of takoyaki (and other treats) was exorbitant. Secondly, and this is the major source of that nagging feeling: Real people actually do this? The moment this thought surfaced, I realised that I have been treating the Japanese culture as precisely that: a fantasy. In my own imaginations, it has become glossed over, raised to the ideal. In my mind, the Japanese have become 2-dimensional, cartoon figures of themselves.  Kierkegaard would call it a repetition.

And this brings me to the second big thing I learned from this travel, besides getting delightfully lost; that we are not that different after all. Strip that shiny veneer of culture and language and fancy clothes and we are not that different after all. And of all places, I learn this at onsens.

I had an inkling of this already when I first joined the lifesaving team. We strip down to our swimsuits, which are all Lycra, which are all of similar thinness. Understandably, this would make anyone anxious: your fashionable clothes are not there, your fake mannerism is not there; everyone speaks the same language and passion of swimming while laid bare in the bodies you carry with since birth with all its imperfections and what separates you from other human beings is just a thin layer of Lycra. 

And this is also the onsen philosophy: that every man and woman is forced to shed the onion layers of labels that society and oneself have plastered upon. The onsen etiquette prescribes that, firstly, one takes off all one's clothes in the changing room before entering the bath area. Needless to say, what one should take off is not only his regalia, but also his own social status that is implied by that set of regalia, for in the onsen everyone is his own naked self. Secondly, one should wash oneself clean before soaking in the public bath. What one previously has taken off is not enough, one should go a step further and take off the dust and the grimes; and the implication is quite clear: that wickedness and prejudice should be washed off, too. Only then, one is allowed to soak in the public bath. When one has traded his regalia with a cloth of vulnerability; when one has traded his prejudices and wear a robe of humility and open-mindedness. In From A Distance, Bette Midler sang, "From a distance, you look like my friend", but the onsen philosophy asserts that we should transcend that distance and stand nakedly side-by-side and the verse would go "From up close, we are actually the same, you and I".

--  

I would close with another aphorism from my mother tongue that came to mind: "Where the earth is trodden on, that's where the sky is supported", which is roughly equivalent to "In Rome, do as Romans do". And I think most travellers would come to this same conclusion: That deep down, we are all the same. That deep down, we are all humans. That yes, we tread on different earths and burden different skies, but we stand on the same Earth and hold up the same Heaven.

Crick's central dogma: Information flows in molecular biology and scientific discourse

Following the discovery of DNA structure by Watson and Crick (as well as Franklin, the crystallographer—I'm very partial to crystallographers!) in 1953, Crick went on to construct the central dogma, stating it in 1958 and restating it in 1970.

Why the restatement? Because during the period in-between, other people have come up with responses to it; evidently, Crick is dissatisfied with those articles that 'misunderstood' (Crick's own wording) the idea of central dogma.

To be fair, when I hear the term 'central dogma' in a Biology class, I was perplexed, too. The term 'dogma' belongs to philosophy, specifically epistemology, what is it doing here in a Biology class? If the Wikipedia page is to be believed, basically, Crick couldn't find a more awesome word. Hypothesis was taken by sequence hypothesis; framework probably sounds too ordinary; axiom probably sounds too mathematics-y; truth probably sounds too epistemological. Though considering that the central dogma describes universally almost every genetic system, it may be just a little exaggeration to call it universal genetic truth or something like that.  
Your Biology teacher probably explains the central dogma like this: In genetics, there are three important macromolecular carriers of information — DNA, RNA and proteins. DNA is inherited from your parents and sit in your cell nucleus (and mitochondria); DNA is replicated in cell division; DNA is transcribed to RNA. RNA (specifically, mRNA) is translated to proteins by the ribosomes. Central dogma is thus that framework in which the genetic information encoded in the DNA is finally expressed as proteins; it's a schematic of (genetic) information flow. Understand, class? And at this point, Crick would shake his head, raise his hand, and say, "If I may elaborate?"

And that is exactly what Crick wrote in the 1970 Nature paper. He would like to "explain why the term was originally introduced, its true meaning, and state why [he] think[s] that, properly understood, it is still an idea of fundamental importance."

The abstract:

The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid.

Crick would like to point out that the central dogma is a negative statement, while the earlier sequence hypothesis is a positive statement. Thus it is intentionally limiting: the genetic information ends in protein and stays there—it's a cul-de-sac.

There are 3 other misunderstandings that Crick addressed, but I will leave it to you to read for yourself.

—

This whole chronicle of central dogma—besides teaching us about information flow in molecular genetics—also says something about information flow in scientific discourse.

First, the way Crick formulated the central dogma is exemplary. Early molecular geneticists knew about DNA, RNA, and proteins; but how the genetic information flows among them was less elucidated. Crick and and his collaborators first assume that all possible information transfers exist (Figure 1, as reproduced below). 

From there, they took away the arrows. They realised that two-way arrows are improbable because forward transfers already involve complex machinery, so "it seemed unlikely that that this machinery could easily work backwards". Protein-to-protein was out, too, because of  "stereochemical reasons"; in other words, proteins that so depend on their 3D structure to function cannot simply transfer its sequential information, like the nucleic acids which possess base-pairing that make replication possible for the nucleic acid since it serves as its own template.
And if this whole process sounds like detective work, well, that's the other way round; reasoning is the basis for both science and detective work, in this case deduction in particular. I particularly like the way they dismantle the arrows that did not stand up to scrutiny, it's kind of Holmesian.
Second, the precise way Crick formulates the central dogma. Crick formulated that abstract with extraordinary precision that stood up to scrutiny. He said:

In looking back, I am struck not only by the brashness which alowed us to venture powerful statements of a very general nature, but also by the rather delicate discrimination used in selecting what statements to make. Time has shown that not everybody appreciated our restraint.

As explained in this paper, he intentionally focus on the protein and how information cannot get out from there. He remained "discreetly silent" about DNA and RNA, which he was not sure of. The astute reader may also point out about prions, aren't they protein-to-protein information transfer? Yes, but it's not "residue-by-residue transfer of sequential information", but transfer of 3D shape — Crick got that covered. And that is why scientists need to be unambiguous in their language: you may think that we of the ivory tower spoke in something akin to medieval Latin (a.k.a. academic writing), but we do need to transfer our information precisely, or else we will face... 

Third, misunderstandings. I don't know how it looked like in the 1960s, but nowadays information flow in scientific discourse seems to hit the cul-de-sac in bad journalism. Admittedly, there are a lot of papers in which the language is unnecessarily complex and only a few shine in clarity while maintaining precision. That may be one factor, but still, journalists need to put aside the sensationalism, explain our jargons, use a lot of proper analogies; in other words, transferring the information with high fidelity.

Bad journalism, like bad protein, generates more of itself. Both are not good for the brain.

Crick F (1970). Central dogma of molecular biology. Nature, 227 (5258), 561-3 PMID: 4913914

Punctilious

I've been wondering why I've never learned this stuff at school proper: the more exotic members of punctuation marks, such as en and em dashes, semicolon, colon, etc. I suspect the philosophy here is like the lion cub being pushed off the cliff: we the fledgling young writers are to fend off  in the real word of writing and out of the jungle of words we would have gained the arcane secret that a cub on a rite of passage has to find out for itself.

And indeed it is best to let soak in the ocean of words to let the subtleties percolate into the deepest of your subconscious, rather than superficially reading the rules from the guidebooks (don't get me started with Strunk and White's Elements of Style, that some linguists love to hate). That said, I will attempt to write a guide of sorts, the purpose being: 1) to crystallise and organise my own knowledge, and 2) to soften the landing for a cub I'm about to push off. Here goes.

Laughter

[I rewrote this composition from my student's 'O' Level EL Section 1 practice composition, keeping roughly the same plot]

The falling water droplets drummed a monotonous, reverberating rhythm in his mind. He absent-mindedly stared at the plates, endlessly scrubbing every inch of each plate and bowl, cleaning the spot over and over again. There was a curtain of somnolence veiling the muffled chuckle in the next room and his own wandering mind in the labyrinth of memories. Inevitably, his mind returned to her, as it had been, again, and again, and again.

He first met her in high school, when she transferred to his class. He didn’t talk much to her, since he was unnerved by her beauty and especially those lips that can launch a thousand ships: when she laughed, it came as a deep rumble in her throat, smoothly rolling out her tongue, quivering her lips a little, like deep-red blossoms in morning dew rattled by the gentle breeze. Her laughter; the pitch, the timbre, the accompanying dimples, the joy, the happiness of being that defined her so much, all these were etched in his heart. Still, his own laughter and happiness were absent. Oh, how he longed to imbue his own laughter on top of hers, making a resonant melody that would echo deep to the very fibre of existence; interweaving laughters, interlocking lips, interbraiding passions!

That was why when he coincidentally met her again in the university, taking the same class even, he was elated beyond measure. He was determined be close to her this time. He mustered the courage to utter her name after class, and she turned, her long hair making gentle waves, spiralling in the gentle springtime gust of wind. Her lips moved and out came his name, tenderly clear and resonant. He said he was surprised she still remembered him—instead of replying with words, she let out that laughter of childlike innocence and amusement and joy, that same dew-soaked field of blossoms as he knew before.

His quest of love afterwards was punctuated with ups and downs but gradually he was able to reach that harmonious chord—her happiness was his happiness and his was hers; her laughters that bewitched him so now was his, too. And to the duet choral of laughters was soon added a more harmonious depth, the ringing of the wedding bells, and thereafter, the healthy cry of a baby daughter.

Unfortunately, the sound of dissonance came. A malignant tissue was found in her breast and it already spread to her trachea. No one said the C-word but it thumped in everyone’s mind, unceasingly, ruthlessly. Her battery of chemotherapy left her weak; it robbed her of her luxuriant hair and cheerful voice and laughters, it drained her lips of colour, it sapped her will of living. It ultimately snatched her away from him. Now those etched impressions in his heart were raw wounds instead, gushing blood, seething immeasurable pain.

The rain suddenly stopped and the sunshine penetrated through the lethargic veil that clouded his mind. His young daughter just laughed upon seeing her favourite cartoon character. He saw his wife’s face mirrorred in this young life; her laughter echoes in her daughter’s — her eyes turned towards him, saying wordless “Daddy!” He hugged her young daughter as tightly as his arms would reach, and let out a wailing cry. 

Or perhaps it was laughter; it was indistinguishable.   

Castle in the sand

Today when I sit on that magical borderline
between grains of silicon dioxide and saltwater,
I dig out a little hole,
(kind of like an antlion's sandpit,
though there is a certain perversion that
the sand is the sand, but
the beach is not the desert)
I haven't so much as thought of digging a foundation
for a castle of sand, when
the waves sweep the sand level,
and the castle in the sand only becomes
the castle in the air.
But what struck me most wasn't the extinguished architecture,
but the fact that the waves gently, ferociously slapped everything even.
Castles of sand, houses, cities, happiness, sadness, anger,
well, people.
And the ancient voices doth spake:
Syrus: In the face of death all men are equal;
A Chinese sage: In the face of Truth, all are students.

(Me: In the face of tidal wave, run away.)

Frostian

Thanks to my overzealous notetaking as of late, I've found out that somehow I have inadvertently plagiarised Frost. See, I have had this fragmental verse written, unfinished, tentatively titled Saltsmith (though it really doesn't sit well with me), timestamped on March 15:

You are a salt statue

The undercurrent of the world is constantly eroding you

Step back, step back

Put the sign 'Under Construction'

And regain yourself

The passing sense of familiarity was tugging when I clipped from Robert Frost's Directive on May 7:

And if you’re lost enough to find yourself

By now, pull in your ladder road behind you

And put a sign up CLOSED to all but me.

Then make yourself at home.

Now I would like to think that I have perhaps tapped to that great ocean of Jungian collective knowledge, though I'm sure there are less romantic explanations to it. Lesson #1: Some things are better left romanticised; Lesson #2: I should not leave such crumbs of verses and dilly-dally until they grow stale and nobody wants to eat them anymore.

Clockworks: The Story of Drugs — Part 1

In this installment, I will discuss why it is difficult to discover, design and develop a drug, in view of our current knowledge of physiology.

With numerous, intertwined reactions happening, our body is a complex clockwork of biomachinery gears. What do you do, then, if some gears fail—that is, if you got sick? On one hand, it is a consolation that many gears are what biologists call 'redundant', which means that it's alright that a certain gear fails, because there are other gears that can take over its function. On the other hand, due to the intricacy of the gears, it is hard to pinpoint which gear is the problem, let alone fixing it. And the sheer number of gears: ICD-10 classifies tens of thousands diagnoses — tens of thousands ways the gears can fail — and those are only the ones we know; how about those we don't? Granted, some are not caused by our own gears failing, but by interferences of other, pesky gear systems: viruses, bacteria, misfolded proteins, errant microbiome, etc.; but the sense of magnitude is there.

The Pool is Indifferent to My Mortality:

It occurred to me twice, first when my chest tightened out of nowhere,
second when I was One with the chlorine water,
having waded interminable laps on the way to two hundred,
the Enlightenment.
The pool would utter, if it can think aloud like the lake in Narcissus, with the royal plural pronoun:
You don't have a set of gills, yet you dare treading in our watery realm?
(But then, in retrospect, fishes, or other possessors of gills, would die in chlorinated water)
You could almost hear this voice resonating in the back-and-forth lapping of the surface,
guided by gentle breeze of the rain prelude.
Mind suspended in contemplation, body suspended in this sort of reverse amniotic fluid
(it doesn't give birth; it kills)
I studied my almost still shadow on the pool floor,
tangled in strands of light, enmeshed
with what looks like the very fabric of Nature itself,
Yes, in the beginning was Let there be light, wasn't it?
And I wondered if I was being brought to the beginning or the end,
the amniotic fluid or the formaldehyde,
kindled or extinguished.