Friday, December 4, 2009

The Seductiveness of Crystals



That's one DnaC protein sticking to another DnaC protein . The dotted lines detail the interactions down to .01 Angstroms (1/1000000000000 meters). Never mind the fact that the actual data on which the image was based has a "resolution" of 2.6 Angstroms.

Your typical protein contains several thousand atoms. To generate these images, the coordinates of all these atoms must be known. That information is normally painstakingly acquired by crystallizing the protein in question, followed by X-ray analysis. There's an element of karma/luck/art involved in generating a crystal; crystallographers can regale you with tales of how they worked fruitlessly for years to coax proteins into a repeating structure, with a drop of spilt coffee proving to be the catalyst that finally gets the job done. A recent Nobel prize in chemistry was awarded to an individual, Ada Yonath, who stubbornly devoted more than 20 years to obtaining her crystal.

More than 60,000 protein structures can be found at the Protein Data Bank. Human DNA only codes for a tad more than 20,000 proteins, but a crystallographer need not fear for his career. You can crystallize proteins interacting with other proteins or ligands. You can crystallize various "isoforms" of proteins. You can mutate your protein strand and recrystallize it. Once you've got the atom-by-atom coordinates in hand, your software can zoom, rotate, label, and color the image. You're an artist. And an explorer, flying over and through the ridges and chasms that might be essential to catalysis.

The work can be important. If you've got a high resolution image of a disease-related protein, it's possible to design drugs that clog it up. It's arguable, however, whether "rational drug design" has come anywhere close to living up to its early promise.

But does this sort of work deserve a Nobel? Does it push boundaries and alter paradigms? Are we talking about extraordinary acts of intellect and creativity? Or just perspicacity?

The questions above are personal, believe it or not. It was flattering to have a professor pursue my services, offering financial inducements, and even pointing out my future lab bench, currently unoccupied. I practically begged for reasons to get excited about the work. I was told of the beauty of meticulousness, the wonders of knowing a subject from the bottom up.

But what about "top down?" Synthesis, integration, binding principles, systems, dynamics, interactions?

The research in question involves a bacterial protein, Cry4a, that is presumed to form a channel in mosquito guts, causing deionization (i.e. death); "presumed" because 20 years of research in labs around the world has failed to prove the point. It would be nice, of course, to benefit humanity by wiping out disease-carrying critters, but...

*Assuming we can engineer a deadlier protein, who's to say it won't get rejected by the bacteria after, say, 1000 generations? The assumption seems to be that a deadlier protein confers greater fitness on the bacteria. Quite naive.

*Assuming a competitive population of bacteria, who's to say the mosquito won't develop resistance to our protein?

*Assuming that resistance doesn't evolve, are we clear about the environmental impact of wiping out a species of mosquitos?

These are "top down" questions. Their answers inform us of the odds that the research might actually be of benefit to humanity. I didn't like the odds. It's possible that some world-beating toxinologists could change my mind. It's surprising, however, that a number of highly respected authorities at my own institute couldn't. There are no vendettas or personal gripes being aired here. I simply wonder a bit about the real state of science in institutes around the world.

Monday, October 12, 2009

Flora and Fauna in Salaya



You can see some more images of my environs here. It's a "photobucket.com" slideshow. I strongly advise against saving pics on photobucket's incredibly counterintuitive, ad-laden website. I do it simply because that's where I've already uploaded a fair number of other pics. It's reasonable to assume flickr.com would be a better choice.

More pics to come...

Tuesday, September 22, 2009

Alternative Dwellings in Bangkok

Here's a strange dwelling just off Phaholyothin Road, near the Mor Chit Skytrain Station:

Passing by at night, the lights are on. Somehow, just a sliver of a former apartment was preserved in the process of demolition. A parking lot surrounds the structure.

I wouldn't mind living there. Deck it out with vines, potted plants, and eerie lighting.

Here's another joint I've long eyeballed as a possible dwelling:

Cinderella's Castle at the old "Din neramit" Amusement Park. Several generations of Thais have fond memories of this place, as elementary schools would bus their students here for a day of enjoyment. It was hardly world-class and became redundant following the opening of "Dream World."

The park closed about a decade ago, with virtually all the attractions being shuttled off to wherever antiqued attractions get shuttled. Only the castle remains. In the background, you see unfinished condos, victims of the 1997 Southeast Asian currency crisis:

My solution to this double boondoggle:


Wednesday, July 15, 2009

In the course of a day of studying...

...I stumbled across a couple of oddities.

First, there's a web page devoted to documenting instances of left-handed DNA in the media and technical publications. "Handedness" is not a difficult concept. Every nut and bolt and spiral staircase is either left-handed or right-handed. Viewing a spiraling structure from an end (either the top or the bottom), you'll see that the rails spiral away from you in either a clockwise (right-handed) or counter-clockwise direction (left-handed). If a spiral is left-handed when viewed from the top, it will also be left-handed when viewed from the bottom. You can verify that in 20 seconds by twisting up a piece of paper.

The DNA in your cells is right-handed, so any depictions otherwise are in error. The aforementioned website lists almost 700 instances of left-handed imagery, some of which appear in technical papers. The first instance, dating to 1964, was a minor national embarrassment:



(from http://www.ccrnp.ncifcrf.gov/~toms/icons/stamp.israeli.1964.jpg )

If you want to be finicky, you can point to the rare left-handed form of DNA known as "Z-DNA." In that case, however, half of the "bases" (say, all of the orange and pink strips) would have to be depicted outside the black and white rails, not inside.

The second oddity was this video:



This is farrrrrr from the level of detail I desired. What's more, the video is quite lame from any number of perspectives. But something about the speaker's accent, cadence, focus, and who knows what else, set my brain a-buzzing.

The buzz. Does that ever happen to you? For myself, it occurs when I watch or listen to a person who is intensely wrapped up in whatever he or she is doing. I can recall a couple of instances where the feeling was particularly strong. The first was in watching a cook prepare a hamburger...grilling the buns, treating them with mayo and sauce, gently squishing the oil out of the patties, etc. All accomplished with the utmost TLC. My new-age friends would probably expect such a burger to be especially tasty, with the normally unwholesome, fatty, and carcinogenic properties of various ingredients being negated by the purity of the chef's consciousness.

Another instance was in listening to a speech on the part of a vice-presidential candidate perhaps 20 years ago. Searching the net for third-party candidates at that time, I'm thinking it was Sonia Johnson of the Peace and Freedom Party. Whoever it was, she spoke with strange urgency. If she felt that the audience hadn't fully grokked her message, she'd pause, shift her feet around in little increments, and try to find a new angle of expression. Her gestures were odd, too. Again, a new-age type might see her as a channel for the Truth, with the Truth feeling a tad uncomfortable in that particular body and those particular garments. I wondered if she wasn't a tad nutty. It didn't matter, though, as most of my mental energy was focused on enjoying the buzz.

Anyway, you might want to view the video and see if it produces any odd feelings.

Wednesday, July 8, 2009

Gratawn, Santol

Here's an amazingly delicious fruit that's difficult to find outside Southeast Asia.



The closest thing to an English name for the fruit would be "Santol", from Tagalog. The Thais call them "gra-tawn". You gotta say the first syllable staccato-like.

How does it taste? That's a difficult question. No other fruits come to mind as a reference. Looking at its lineage, you can see why:

Species: Santol Tree (Sandoricum Koetjape)
Genus: Sandoricum
Family: Meliaceae
Order: Sapindales

The Meliaceae family contains about 575 different shrubs and trees, but the Santol is one of the few that produces a fruit of distinction. So, unless genomics proves otherwise in the future, it seems that the Santol is somewhat evolutionarily removed from run-of-the-mill fruits in your supermarket. Moving to the broader category of "order", you do find that Sapindales include ordinary citrus fruits, lychees, and more.

Another Meliaceae that produces edible fruit would be the Lansium Domesticum. The Thais call these fruits "longkang" and the Philipinos "langsat". This is a source for eternal confusion, since "langsat" in Thai refers to a particular variety of longkang. What's more, there's another fruit that we call "longan", but Thais call "lomyai". Not to be confused with loganberries. Longkang and longan look similar, but belong to different botanical families. Longkang are tasty. Somewhat woody. On occasions when I have the will to peel and de-seed the little fruits, I mix lime, longkang, sugar, and gin in a blender. I don't see the appeal of longan, though...they're kind of radishy.

You can see a few similarities between longkang and gratawn. They both have yellow, leathery skin, and a handful of seeds inside. In Thailand, the two fruits come into season in the same brief period...usually June and July. But gratawn are much bigger and taste different. Longkang resin will stick to your hands even after you soap them off, and the pulp will occasionally squirt in your eye. If you let a gratawn ripen fully, however, the flesh is custardy. The seeds are big and tough, so you cut a circle around them, twist the two hemispheres apart, and dig into the flesh with a spoon. The sweetest pulp surrounds the seeds, so you suck on the seeds.

The flavor is...still difficult to describe. Bear in mind that Meliaceae includes frankincense and myrhh and mahogany. There's something spicy going on. I'm guessing that the pulp is loaded with interesting terpenes like linalool, the distinctive fragrance of Froot Loops. When I worked as a chemist at a winery, we had bottle of linalool in the refrigerator. I'm not sure why, actually. Perhaps because the winemaker desired to make illegal midnight flavor adjustments, dripping a few drops into the tanks. Opening a bottle of pure linalool was something like finding yourself in the midst of an exploding Froot Loops factory.

A couple papers suggest the presence of catechins and proanthocyanidins in gratawn...these are more typically found in teas, fruit skins, cinnamon, cocoa, and tree bark.

I just cut a gratawn open...there's something banana-ish in there too.

Unfortunately, I haven't been able to dig up a full profile of the flavor components of gratawn in the academic literature. There are plenty of papers focusing on possible medicinal qualities of the bark and leaves, but no in-depth analysis of the qualities that make the fruit distinctive from an olfactory/gustatory perspective. Sounds like a decent Masters or Ph.D. thesis for someone interested in natural products chemistry.



Tuesday, June 30, 2009

Transformers and Michael Jackson

Normally I refrain from commenting on pop phenomena. This week, however, my brain has reached a state of pop hypersaturation, so I'll blog in the name of self-help.

In college, a friend of a friend (and a distant friend at that...let's get this straight!) was a big Jackson fan and bought tickets for a number of his concerts on the West Coast. Los Angeles, San Francisco, etc. She reported that the show included a segment where Jackson began a song and then ordered the band to stop playing after maybe 30 seconds. You see, his emotions were bubbling over, and he absolutely needed to express them via a different tune. That's nice, but it turns out that Jackson went through this routine at every concert. Offhand, I can't think of a more extreme example of feigned spontaneity.

Some call this sort of behavior "showmanship." Mick Jagger is supposed to be a great showman. When the 40-up crowd (of which I'm a member) ventures out to see a Rolling Stones mega-concert, they inevitably return with high praise - Jagger still has "got it." Then, of course, there are the obligatory comments about Keith Richard's appearance and longevity. To me, it feels like the concert-going fogeys are simply rationalizing their existences; see, us old farts can also prance around a stage. We might just still "have it." Hell, in high school, my circle of friends felt that the Rolling Stones began a downward spiral in 1967, when Brian Jones died. In the early 90's, I was pleased to hear that a decent chunk of the younger portion of the audience walked out on the Stones after a couple tunes. Pearl Jam, it seems, was the opening act, and the contrast between Eddie Vedder's genuine spontaneity and Jagger's rehearsed "professionalism" was too much to bear.

Oliver Sacks relates an anecdote from the aphasic ward of a mental hospital. Aphasics have a difficult time formulating and understanding concepts, so Sacks initially found it odd to see a group of them laughing hysterically at President Reagan's televised speech. As Sacks says, though, "It was the grimaces, the histrionics, the false gestures and, above all, the false tones and cadences of the voice which rang false for these wordless but immensely sensitive patients." Perhaps I lean a tad toward the aphasic end of the spectrum, as Michael Jackson always seemed too cartoony to take seriously. For those who perceive him a master showman, you're entitled to your own personal mix of neurotransmitters.

Regarding pedophilia, I'll give him the benefit of the doubt. Did he fantasize about becoming white?...no, it seems like he really did have a hangup with vitiligo. I know because I've been dowsed with spam e-mails that prove the point with attached photos. What bothers me, however, is the praise he has received as some sort of music pioneer. Sly Stone and Hendrix were crushing racial boundaries when the Jackson 5 was a generic (but good) Motown act. One might argue that Jackson's transformation into whiteness, like Emperor Leto's transformation into wormness, was an act of sacrifice, designed to carry all sentient beings to a new degree of awakening. But the vitiligo spam disproves that theory.

Then there's the idea that Jackson was responsible for MTV. There may be some truth in that. In which case, the need for a successful musician to have a pretty face, dancing and acting skills, and to be on the cutting edge of fashion and personality - a 30 year trend away from actual musicianship - is Jackson's doing.

*********************

Now, let it be known that "Transformers II" is dreck. I just have few observations. In the spirit of the film, they're disjointed.

Following release of the excellent, "Elephant", Gus Van Zant predicted the demise of the "narrative format." No more linear story-telling. That's what you got in "Transformers II", which willfully discards plot and continuity. I say "willfully" because it's impossible to believe that these myriad discontinuities (a robot busts through the wall of the Smithsonian...into a remote jet airstrip) went unnoticed in production. Van Zant's vision, of course, is one intended to challenge the audience. "Transformers II" is the ugly, cynical side of the "non-narrative" format.

In fact, it feels as if recent films like "Star Trek" and "Transformers" operate on the principle that there's no limit to the degree of "suspension of disbelief" that the human brain can tolerate. "Suspension of disbelief" has now been expanded to include much more than run-of-the-mill violations of the laws of physics. We're talking about slashing through a coherent plot and timeline.

I found the first Transformers film notable for its ability to invoke a sense of wonder. That's a rare quality in a film. Somehow, you've got to mix nature, the right music, a sense of connection to the deep past, the grandness of the cosmos, paradox, and death and suffering, in just the right proportions to pull it off. This sense was totally lacking in the second film, a testament to the slipperiness of awe and wonder.

We poke fun at Bollywood productions. Singing, dancing, and fighting. There's something for every audience sector...slapstick for the kids, sex and violence for the teenage boys, true love for the chicks, and family values for mom and dad. But films like "Transformers II" run the risk of falling into the same "variety show" trap. You've got robots speaking with ghetto accents, plenty of slapstick, militarism, and the family pulling through in the end. Unnecessary skits. When Megan Fox's foxiness is the focus, the music changes suddenly, the film slows, and the camera zooms...very Bollywood!

On the positive side, I hope that this piece of garbage forces a number of critics to reassess Star Wars Episodes I-III. Lack of humanity?

Undoubtedly, the execs are rolling in the dough and lighting Gran Coronas with critics' reviews. Prediction: they'll be puzzled when "Transformers III" fails to meet box-office expectations. Hmmmmm.

Friday, June 26, 2009

Pigasus



Google "Pigasus" and you'll find it's a well-used pun. It's unlikely that the Thais at "Satapon Plastic" company were aware of that when they created their logo, however. One wonders what inspired them.