The Dendritic Arbor

Chasing down particles

2010-10-18T00:54:00.003-04:00

I'm up late writing MATLAB code to analyze a whole load of particle tracking data. It's not exactly a fun process, but I can feel myself getting better at MATLAB. It's like the coding equivalent of eating all my asparagus. There are some great tricks you can do to slice and dice arrays with fancy indexing. But, ugh, the syntax for optional arguments makes me wince (and avoid using optional arguments, unfortunately).

But I'm still not in the habit of putting semicolons after everything. Despite studying Java and Scheme in high school, I never got very good with them or did anything practical. Right now, I'd say my native tongue is Python. Maybe if I get into automation, one of these days I'll ~~clamber up on the big-programmer potty~~ learn C/C++.

Storycest Is Best

2010-10-11T01:53:00.004-04:00

For my folk song class, I'm writing an analysis of the old Scottish ballad Kemp Owyne (specifically the version called Kempion; here are some related ballads*). The most interesting part, I find, is looking at the relationships between the different versions and between Kemp Owyne and other stories.

Discovery number one: no version of Kemp Owyne is 'complete' in the sense of containing all the plot elements found in any version of Kemp Owyne. Furthermore, the different versions ('subspecies'?) seem to differ not randomly but systematically in the elements they omit. The Kempion version leaves out the vast majority of the beginning, so for example, you never find out why the evil stepmother curses the princess (in fact, you don't even find out it was the evil stepmother's fault until the very end), whereas other versions start out with a thread where the stepmother is angry about not being called "the fairest of them all". It's hard for me to even imagine what it's like to only know one version of the story, since I'm in the privileged position of being able to read them all and cross-reference.

Discovery number two: there's a lot more swapping of story elements than I thought -- a lot more random ligation of characters into new situations. I suppose most folktales are fanfiction of other folktales, for some sense of 'fanfiction'. For example, Kemp Owyne is supposed to be identified with Ywain/Yvain from the Arthurian legends, aka the historical Owain mab Urien (and "Kemp" means 'hero' or 'champion'). Why? No reason. He's just a convenient fictional knightly hero type. But interestingly enough, there's an invocation to St. Mungo at the end of Kempion... and yet, Yvain is also supposedly St. Mungo's father! How did that happen?? Either there is massive storycest going on, or someone chose to invoke a saint who wasn't even born yet. (You have to admit that time-traveling Scots heroes and saints would be pretty awesome.)

It really is like evolution, complete with horizontal gene transfer. But also with revival and retelling and all sorts of processes that don't have obvious biological analogues. Fascinating!

[*] Those texts have some typos in them, but I wasn't about to type all of Kemp Owyne again, and I'm really fond of that whole website because it makes up in quantity what little it lacks in quality. (The typos are few enough that I feel like only scholars really ought to care about them.)

Science poetry: Heredity, Thomas Hardy

2010-09-26T19:40:00.002-04:00

I am the family face;
Flesh perishes, I live on,
Projecting trait and trace
Through time to times anon,
And leaping from place to place
Over oblivion.

The years-heired feature that can
In curve and voice and eye
Despise the human span
Of durance -- that is I;
The eternal thing in man,
That heeds no call to die

--Thomas Hardy [source]

I like the alliterations and internal-half-rhymes in the first stanza. They remind me of what little I know about Anglo-Saxon verse. (I read Beowulf once...)

Milk Hero

2010-09-13T02:39:00.002-04:00

That's a cup in the foreground. I wish I could play this every morning.

$18 can buy a lot of fun

2010-09-05T22:41:00.002-04:00

(My living group is doing Rush right now, which means my life is basically eaten for the next two weeks, such that I feel no shame about writing a punt-tastic post like this.)

I will just note that $18 can buy more dry ice than twenty MIT students can play around with for three hours. Try it out some time. Make sure to bring soapy water, interestingly-shaped glass vessels, small white and colored lights/LEDs, coins, spoons, and hot water.

Try putting a little water in a spoon and then resting the spoon on top of a chunk of dry ice. You can see the water freeze right before your eyes. It's pretty cool.

What's wrong with the cartoon eukaryotic cell? [Unusual Cells pt. 1]

2010-08-29T12:39:00.008-04:00

I'm starting a series of posts based on a class I taught about "Unusual Cells" for Splash. Eventually, each post will include links to all the others.

The point of this series is to understand the wild and crazy unusual cells that populate the world (and that populate us!). But we should first understand the usual cell... or, perhaps, we will find that there is no such thing as a usual cell.

Consider the cartoon eukaryotic cell that we all know and, presumably, love:

Figure 1: Typical eukaryotic cell. I'll refrain from listing the organelles, in order to prevent yawning; if you're curious, check Wikipedia, where this image is from.

So... what's wrong with this cell? Here's a sampling of some of the answers my Splash students have given me:

You can't see the DNA

You can't see the proteins

It's cut in half (yes, some of them are smartasses)

There are no membrane proteins

The answer I'm really looking for is this:

It's empty!

(To be fair, Splash students pretty much always get this one too, and it's a general case of the answers I gave above except for #3.)

There's nothing in this cell! Yes, the major organelles are there, but where is the cytoskeleton? It's just that tiny little fiber (#7), which you can barely even see. Real cells are just packed with stuff. Structural proteins, membrane proteins, highways of vesicles wandering to and fro...

Now, of course, this is kind of a necessary evil. We can't include all that stuff in cartoons of the cell that are supposed to show the major organelles, because it would just be a distraction. Visual noise. For example, check out this slice of a more realistic watercolor:

Figure 2: You can see a bit of the Golgi (yellow stacks) in this picture. The geodesic-dome-looking thing is a protein framework that's making a vesicle bud out from the Golgi. [Source]

Seriously, check out the whole thing. It's beautiful. If I could get a quality print of this I would hang it above my bed. But even this is far from showing everything. The empty space between all those blobs is filled with crazy amounts of ions, small molecules, and of course water.

For a different perspective, check out these photos of cells in which the cytoskeleton has been labeled with green fluorescence. Yep, that's just the cytoskeleton... it reaches everywhere, helping the cell maintain its shape and move around (just like the human skeleton), and giving direction to packages of important chemicals as they motor their way hither and thither (something like the human circulatory system).

To do: find out what percentage of the membrane surface area is proteins. I know this is in one of my textbooks somewhere.

Perhaps I should flip a coin?

2010-08-23T00:45:00.003-04:00

I'm working out my class schedule for the upcoming semester, and I've run into a bit of a dilemma. Two classes are at the exact same time. Both clamor for my attention. Both are only offered in the fall, and this is my last year. They are as mutually exclusive as it is possible for two classes to be.

THE CANDIDATES

7.32 Systems Biology: This field is a sister to synthetic biology. I'm interested in to the point of wanting to pursue it in grad school. The Silver lab, where I'm working, is a systems biology lab in more than just name (although it's certainly not typical, being focused on engineering). Networks! Switches! Stochastic behavior! Dynamics! Oscillators! Pattern formation!

21A.212 Myth, Religion, and Symbolism: This class looks like it's going to hit one of my biggest avocational buttons. Despite being atheist/agnostic/nonreligious (damn labels), I've always had a fascination with the power of ritual and storytelling -- the roles they play in our lives and how they adapt to non-religious contexts. How did I manage to not notice this class existed before?

THE ARGUMENT

I want to study systems biology in grad school. Therefore, I should get started. Taking this class may help me with my continuing work in the Silver lab, and might even help me get into a good grad program.

THE COUNTERARGUMENT

I will have plenty of time to study systems biology in grad school. (And if I really get an itch, I can always pick up Uri Alon's book.) I should take this chance to explore a humanities topic that I'm really interested in, while I'm still an undergrad, because time is short.

------------------------------------------

So, what do I do? Both of these arguments are fairly convincing to me. Which one wins? Or, are there other arguments I've missed?

Open thread: ask me questions!

2010-08-22T04:45:00.004-04:00

Dear all the CS people who I know glance at this blog: I would love to hear from you! (And, y'know, from anyone else who happens not to study CS.)

I've recently come up short on blog topics, but also had a hankering to explain basic biology items in a way that makes them exciting to people who "hate biology", or are at best indifferent to it.

What would you like to hear about? Is there some old question left over from your intro biology course, to which you've never heard a satisfactory answer? Want quick summaries of recent developments in synthetic biology, or the ways in which biology imitates EE/CS? How about Anthropomorphized Enzyme Comics? Or, perhaps, White Lies Your High School Bio Teacher Told You?

Reply now and you might even get the post before Monday morning! :D

Science Poetry: The Perfume, A. D. Hope

2010-08-15T22:55:00.004-04:00

I ran across this gem while trolling randomly through the archives of The Wondering Minstrels. It's the newest incarnation of the archives of an old mailing list, long gone out of service, but at least all the poems and commentary are still there. I'm in the process of going through all the poems, starting from no. 1. It's a wonderful archive, and I highly recommend spending some time there.

"... marked males of the silkworm moth have been known to fly upwind seven miles to a fragrant female of their kind ... the chemical compound with which a female silkworm moth attracts mates is highly specific; no other species seem aware of it. In 1959, the Nobel Laureate Adolph Butenandt of the Max Planck Institute for Biochemistry in Munich succeeded in analysing it. He found it to be an alcohol with sixteen carbon atoms per molecule...."

L. and M. Milne: The Senses of Animals and Men.

0 Chloë, have you heard it,
This news I sing to you?
It's true, my lovely bird, it
Is absolutely true!
A biochemist probing
Has caught without a doubt
The Queen of Love disrobing
And found her secret out.

What drives the Bombyx mori
To fly, intrepid male,
Lured by the old, old story
Six miles against the gale?
The formula, my Honey,
Is now in print to prove
What is, and no baloney,
The very stuff of love.

At Munich on the Isar
Those molecules were found
Which everyone agrees are
What makes the world go round;
What draws the male creation
To love, my darling doll,
Turns out, on trituration,
To be an alcohol.

A Nobel Laureatus
Called Adolph Butenandt
Contrived to isolate us
This strong intoxicant.
The boys are celebrating
And singing at the club:
Here's Bottoms up! to mating,
Since Venus keeps a pub!

My angel, 0, my angel,
What is it you suffuse,
What redolent evangel,
What nosegay of good news?
What draws me like a dragnet
And holds and keeps me tight?
What odds! my fragrant magnet,
I shall be drunk tonight!

-- A. D. Hope [source]

Figure 1: Bombykol, from Wikipedia. "Doesn't that structure make you simply wild with desire?"

I remember hearing stories about this compound, or one very like it, in my organic chemistry class. Apparently, whenever someone wanted to deliver a vial of it across campus, they would be pursued by a gradually accumulating swarm of moths. I like to play that scene in my head. "I'm a synthetic chemist -- I did not sign up for entomological fieldwork!! *panicked fleeing across campus*"

Even supervillains have work-life balance problems

2010-08-09T00:26:00.004-04:00

I just got back from seeing Despicable Me with my brother. Although this is not a Pixar movie, it follows Pixar's pattern by being about far, far more than the trailer lets on. (I remember being distinctly unimpressed by the WALL-E trailer, and then I cried my eyes out through the whole thing.) The plot is really fun, and the 3-D is unobtrusive enough to be mostly inconsequential.*

I thought it was pretty cool to see a supervillain (and an older, male supervillain at that) deal with the sort of struggles and discrimination normally associated with working mothers. I haven't experienced these struggles first-hand, of course, but a number of scenes reminded me very strongly of things I'd read -- especially Dr. Isis' blog posts and Allison Pearson's book I Don't Know How She Does It. Seeing parent-discrimination divorced from sexism was quite strange; but then again, I don't doubt that there are fathers in the world who have suffered career setbacks and discrimination because of family demands.

The end of the movie leaves open whether the main character continues the same level of career activity (in the same or a different field), or scales back in order to spend more time with the children. I would have liked to see something indicating that he achieved a productive balance; maybe a montage of newspaper headlines showing him up to something resembling his old tricks, perhaps with the children's collaboration.

Also, as a side note, whoever was writing Margo (the oldest girl) has done their homework on sibling-order effects on personality. I'm an oldest daughter, and though of course I'm not exactly like Margo I found myself identifying with her much more strongly than I was expecting to. (The girls in the movie are not biological siblings. Anyone know if sibling-order effects also happen in families brought together by adoption? It seems plausible -- these effects ought to be mediated in large part by environment... but I'm rambling now, because it's late.)

Go see Despicable Me if you're up for some funny, frivolous action, and so much cuteness that all your teeth will dissolve.

* I'm still cheesed at being made to pay an extra $4 for an effect that, IMO, adds very little to a movie animated in Pixar's style. But there's a cute bit in the credits where some minor characters play around with it, so stick around.

Gunnerkrigg Court takes on animal research ethics

2010-08-04T09:41:00.007-04:00

I think I chose a particularly fortuitous time to highlight Gunnerkrigg Court, because it's just started taking on one of my favorite themes, and I think it's being handled very well so far.

First, read the last two pages of the comic: one, two. You don't need much context to see what I'm talking about.

Figure 1: Rock on, Paz.

Now, if I remember correctly, Paz is a character we haven't seen much of yet (her first appearance is basically as an extra), and I'm looking forward to seeing her developed in more detail. I'm very glad to see she's taking (or at least professing) a sensitive, ethical attitude toward animal research. Realistic, too -- I'd swear that Tom Siddell has read the NIH Guidelines. I admire the fact that Paz aspires to reduce or even eliminate the use of animals in her research. Per fantasy conventions, all of these girls are stunningly mature and knowledgeable compared to the average high schooler, but I'm still very impressed by her attitudes and opinions.

(Plus, I'm pleased that she's apparently not white and not a native English speaker. I'm not terribly well informed about racial/identity politics, but nothing about the way she's portrayed jumps out at me as being problematic.)

I will be very interested to see how this plays out. In particular:

How will the teachers and other students at the Court react to the presence of animal research at their school? Will they even find out, or do they maybe know already? Will we see a range of attitudes, from "Animal welfare is not that important" to "All animal research is morally reprehensible"?

How will the supernatural entities in the forest react? Will their reaction be shaped more by opposition to the Court in general, or by the fact that many of them are (at least in some sense) animals themselves?

What is Paz doing, and who is she working with? How did she come by her research assistantship? Is she doing largely self-directed work or is she being used as a pawn by some unscrupulous adults? Is she aware of the broader implications of her work, whatever those turn out to be?

Is this research actually justifiable/ethical or not? Right now all we have is Paz's word, and we have very little idea what they're actually studying.

I have faith that all of these questions will be answered, if not in as much detail as I would like. Gunnerkrigg Court wouldn't just introduce a subplot like this without exploring it in quite a bit of detail.

Watch out for the mad biologist!

2010-07-30T07:40:00.003-04:00

One of my favorite webcomics is Gunnerkrigg Court. It's a mixed fantasy, SF, and school story with some characters who are pretty badass for their apparent age (middle/high school). Antimony and Kat, the two main characters, play a crucial, growing role in trying to preserve peace and increase cooperation between their school (the Court) and the adjacent forest -- but they're also just two girls capering in a world that's often a lot bigger than they realize. It's framed as technology versus magic/divinity, but I have a feeling it runs a lot deeper than that.

I highly recommend reading it, even though it starts out just a little slow -- the 'real' threads start soon enough.

But why am I highlighting it now? I'm super excited, because in among all the magicians and mad roboticists, I think we may have our first mad biologist character.

Should I say that again? Mad. Biologist. Character.

Squee!

Err, I would totally include a small click-to-embiggen preview image of the comic, but I can't figure out how to make Blogger do that. I have been thinking of migrating to Wordpress...

But why is the sky blue?

2010-07-19T01:09:00.005-04:00

Here's a sampling of the random questions I've encountered in the past week that have piqued my interest. I feel like these should be answerable with a little effort (by someone other than me, since my brain is stuck in corners), but they're also fun to just speculate about.

It's a commonplace that Benadryl makes you drowsy. kcr noted that it only seems to make him drowsy when it isn't busy fighting off an actual allergic reaction. Are the antihistamine and sleep-inducing activities of Benadryl different? Does one compete with the other?

Why do martial arts seem to be optimized for fighting other practitioners of that same martial art? I don't know anything about how martial arts develop, but my intuition says something like this: it's dangerous and impractical to always practice by getting in real fights, and if you're going to make a new variant on an existing style, then practicing against others of that style is a decent proxy for being in real fights. Of course, this runs into the bootstrapping problem of where did the first formalized martial art come from... but humans have been punching each other for so many years that I feel like basic instinct can serve as a starting point. (How do you go about designing a martial art for "real combat"? I know these exist -- mumble military mumble something.)

What's the most cost-effective way to make ice cream using a dry ice and ethanol bath?

A sure sign of a healthy lab

2010-07-12T00:14:00.002-04:00

Whiteboard, day 1:

THURS 3:30
GROUP MEETING
DANNY

Whiteboard, day 2:

THURS 3:30
GROUP MEETING
Oh DANNY boy

Paper attached to whiteboard, day 3:

Oh Danny boy, pipets, pipets are calling,
From bench to bench, and in the TC hood.
The gels are gone, and all the yields are falling;
'Tis you, 'tis you must make the data good.

So come ye back, where we cells are abiding,
Or when the lab is lonely as the grave.
'Tis here we'll be, in log-phase swift dividing...
...if you will please not put us in the autoclave!

Bacteria break symmetry too

2010-07-02T22:39:00.006-04:00

It's amazing what you can learn on the internet, especially when looking for something totally unrelated! :)

Caulobacter crescentus is a really cool little bacterial species with a funky two-phase lifestyle. The "stalked cells" attach themselves to rocks or whatever in the freshwater environments where these guys live. When a stalked cell divides, part of it remains a stalked cell and part splits off into a "swarmer cell". The swarmer cells swim around like more 'normal' bacteria.

Check out some images of these dudes. (Blogger's image uploader is misbehaving so you guys get a link to Google Images. Sigh.)

They're a fascinating organism to study because their cell division is asymmetrical. If you think back to the high-school-biology version of mitosis... well, it seems like a totally symmetrical process, right? There would seem to be no reason for a particular set of molecules to end up in one daughter cell and not the other, because everything's floating freely around in a droplet of water anyway. But in an asymmetric division like this, the two daughter cells have to develop in different ways. The stalked cell has to keep maintaining its stalk, but the swarmer cell has to grow a flagellum and start making the necessary sensory proteins to swim toward yummy-smelling food molecules. And not only that, but there's a correct orientation for this difference and an incorrect one. It would be kind of awkward if the new stalked cell started trying to swim away, and the swarmer cell floated around trying vainly to anchor to something.

So there must be some sophisticated mechanisms at play here. Notably, it's not that the two daughter cells end up with different genes -- after all, the swarmer cell will later settle and put down roots as a stalked cell. What matters is the presence (or absence) of proteins and other molecules that regulate those genes, so the stalked cell can keep making stalk proteins while the swimmer turns those genes off and turns on the ones for making a flagellum.

This asymmetric division isn't just some strange bacterial phenomenon. Every multicellular creature goes through this kind of process as it grows from a single cell (a fertilized egg) to whatever elaborate body it has as an adult. Figuring out the origins of symmetry-breaking in cell division is one of the major problems of developmental biology.

It also has to do with stem cells, by definition. The vast majority of cells in your body are "terminally differentiated" -- that is, they've gone from nondescript round blobs to fully elaborated cells with sophisticated morphology, heavily optimized for doing whatever job it is they need to do. But the 'terminally' part means they stop dividing once they reach maturity. So if you lose some mature cells, you need to get new ones from a renewable pool of immature cells. These are stem cells. The key defining feature of a stem cell is that it can divide asymmetrically. One of its progeny will be a precursor cell, traveling inexorably down the path to neuron-hood or white-blood-cell-hood or whatever. The other will be a new stem cell, all set to keep hanging in the lazy infinite loop of waiting until it's needed again.

Life lessons for synthetic biologists

2010-06-24T16:37:00.007-04:00

1. A serious lesson

"Biology may or may not care about the physicist's insatiable desire for elegance." -- Jeff Hasty

Figure 1: In other words, sometimes this happens. From Hasty et al, Physical Review Letters 2002 | doi:10.1103/PhysRevLett.88.148101

2. Another lesson that is just as serious

Humor in lab is essential, of course. However, if you just heard the great story about the giant biohazard bag full of innocuous things in your PI's car... finish laughing before you load your gel.

The idea, of course, is to prevent this from happening. [Original photo source]

MOSS!

2010-06-13T23:23:00.004-04:00

I'm back from a 2.5-week family jaunt to Oregon and Washington. We bummed around a lot of national parks and did a wide variety of Wilderness Things. Here are some of the highlights:

Moss! We did go whale-watching, but for some reason I just don't get that excited about the large wildlife. I like to look at little things. And it turns out, the temperate rain forest is basically an ideal environment for dozens of moss species to thrive, reaching epic heights of lushness that I never dreamed of, growing up with miles of chaparral on all sides. There's lichens and liverworts too, but for some reason the mosses appeal to me the most. I discovered the macro setting on my camera (!) and took loads of pictures, trying to document as many different species as I could... but then I sat down too quickly on a rock and destroyed the screen. Argh! So I had to stop taking pictures. I don't even have the memory card with me, because my dad took it out when we got home and forgot to give it back to me before I flew back to Boston. So rest assured, I'll post my photos eventually. For now, here's a teaser photo taken by Derrick Ditchburn, who is a far better photographer than I. (More lovely moss photos at Dereila Images (do click on "More Moss" at the bottom).)

Stair-step moss, the most elaborate moss I've ever seen. The main fronds get up to 3-4cm long, and grow in long dangling chains. Picture this carpeting an area of several meters square.

Human-powered transport! I fell in love with biking and kayaking. I think the common thread is that they are both human-powered modes of transport that require a lot more thought than walking/running. I find them spectacularly engaging because I can pay attention to either the scenery or the vehicle, as I like. Plus, there's something satisfying about going twice or three times as fast as I could go unaided, but still without using a motor. I intend to continue both biking and kayaking in Boston -- I've borrowed a bike from a friend who's summering out of town, and apparently you can rent kayaks and go out on the Charles River.

Signing ghost! Yes, that said signing, not singing. We stopped in Ashland and caught a performance of Hamlet by the Oregon Shakespeare Festival, which was of course excellent. But one thing in particular struck me -- the ghost of Hamlet's father spoke in sign language! I looked through a couple of brochures and found out the ghost was played by Howie Seago, "the first deaf actor to play on OSF stages". I don't know any sign, so I couldn't tell whether he was using ASL or SEE or something else, but I thought it was a neat artistic choice to have him play the ghost, as opposed to a living character. (Hamlet spoke the ghost's lines, as if he only half-understood sign and was trying to keep up.) I bet translating Shakespeare into ASL is an interesting problem, too.

Wonder?

2010-06-07T02:01:00.004-04:00

Christina Agapakis of Oscillator recently wrote a thought-provoking post about biosafety and synthetic biology. I was particularly struck by this passage:

Why is biology scary to so many people? We've done a very good job of sterilizing our lives, separating ourselves from biology to the extant that when we think of the word bacteria we immediately think of infection that needs to be wiped out, not something that is part of our bodies, part of our everyday ecosystem that keeps us alive.

I've often wondered myself why biology is so scary to so many people, and I think this is a particularly insightful way of putting it. If only more people would play around with sourdough starter or homemade yogurt, or manipulate soil pH to change the color of their hydrangeas, or hell just think harder about the fact that bacterial cells vastly outnumber human cells in a typical human body...

But of course, it's not that simple. Biology is hugely amazing or terrifying to a lot of people -- is there perhaps a good reason this is so? I feel like bio lab work has a really jading, mundanifying tendency: "I have the godlike power to manipulate the very genomes of bacteria!... and the result is that some of these spots are blue where none were blue before." The vast majority of the experiments I've personally done have ended either with a resounding "meh" or with a facepalm and a starting-over. Has this blinded me to the fact that, given sufficient equipment and time, I can engineer freaking life? How wondrous might genetic engineering seem to someone like Leeuwenhoek or Mendel?

What do y'all think? Especially you nonbiologists in the crowd? How weird does it seem to you that biologists collectively have these abilities? (And who's planning on seeing Splice?)

Reading the Histories of Middle-Earth

2010-05-30T23:08:00.002-04:00

With characteristic good timing, I found myself suddenly interested in delving deeper into Tolkien's mythology... right around finals week. (Naturally, this led me to lie awake at night thinking about biological transport phenomena in the Two Trees of Valinor and so on.) But now I have a lot of free time and very little internet access, so I'm working my way through the first volume, The Book of Lost Tales I.

It takes a lot of getting used to. Everything's name is different, and the tales are interspersed with commentary from Christopher Tolkien, which is very insightful but detailed to the point of neuroticism. There are a number of subtle differences between this old material and the published Silmarillion, and very often I'm not sure which version I like better. (For example, in the Lost Tales, Ossë is a much more ambiguous character. He plays an important part in the story of the Lonely Isle, rather than just being "the Maia in charge of waves and storms".)

However, the big difference is that the whole history is framed as a series of tales told to a human mariner, Eriol, who comes to the Lonely Isle and hangs out with the Elves. And, well, it really doesn't work. Neither Eriol nor any of the tale-tellers is developed at all, although we are promised that actual plot events will happen later -- but they really need to happen closer to the beginning. The effect is basically "heroic adventurer arrives in distant mystical land and gets the Bible read to him for several weeks". It doesn't stand well on its own, but only in relation to LOTR, Hobbit, Silmarillion, etc. Let's just say I'm glad the stories were extensively revised before being published.

However, I'm only about halfway through the first history, and there are twelve, if I remember right. So I bet it gets interesting later. And after that, there's the Letters, where Tolkien gives a bunch more explicit commentary on the more philosophical ideas of his mythos -- mortality as Gift of Ilúvatar in particular. I'm looking forward to it!

Project idea: improving my attention span

2010-05-20T20:45:00.002-04:00

By now it's a commonplace that the internet whittles your attention span down to the sort of tiny nub that only lets you focus on one thing for about thirty seconds before popping away to check email or RSS or Twitter or what have you. Word among my older MIT friends is that burnout and curricular exasperation can have similar effects. I'm inclined to believe them, having lost all patience with, say, biomechanics. *growl* *ahem* Where was I?

Oh, yes. I've been thinking that, among the other soul-restorative measures I plan to take this summer, I should work on reconstructing my attention span. According to my parents, when I was young I had a wonderful attention span, and could admire a pebble for ten minutes together. I'm not sure how much I believe them, but I do feel like my attention span has decreased dramatically over the past couple of years as I've started to read more and more things on the internet.

So I gave myself a test. I had to read something all the way through without looking at anything else on my computer. I picked the first interesting-looking article out of Give Me Something To Read, which turned out to be an NYTimes article about arranged remarriages in China following the 2008 Sichuan earthquake. (Incidentally, the article is very good -- thought-provoking and emotional without being overwrought.) Even though it was interesting, it was surprisingly difficult to get through. My mind kept wandering. Indeed, my mind is still wandering. I've pulled up my chat client once already while writing this blog post, and I keep having the urge to do it again. I'm like Randall Munroe at the typewriter here.

But with summer comes the opportunity to read books again! Do you have any idea how long it's been since I just sat down with a book and plowed more or less straight through the whole thing? I feel like I haven't done that since high school... So, as I pick up books again for the summer, I'll consciously practice keeping my attention on one thing for an extended period of time, and try to avoid get up every five minutes to get food or check my mail. We'll see how well I do, and whether this will translate to an improved studying efficiency in the fall.

Silliness: Legos and BioBricks

2010-05-17T01:12:00.007-04:00

It's finals week around here, which means you get a brief post while my brain tries to figure out electroosmosis and Van der Waals forces.

The similarities between Legos and BioBricks are legion -- in fact, if I'm explaining synthetic biology to someone and I've got more than ten minutes of their time, I'll break out my favorite Lego Analogies for the desirable properties that we want biological parts to have.

But they're similar in another way. Everyone refers to BioBricks as BioBricks, but you're supposed to call them BioBrick Standard Biological Parts.

Trumpet fanfare optional. [Source]

Likewise... hope I'm not ruining all your childhoods here... The LEGO(tm) corporation will be very, very sad if you refer to their product as "legos" instead of "LEGO bricks" or "LEGO toys". They might even cry.

Apparently if you went to legos.com, you used to see this before being redirected, according to Mental Floss.

This sort of prescriptivism amuses me a little. I don't know enough about the relevant laws to comment on the legal necessity of being anal about plurals. But I was in a class co-taught by Drew Endy once, so I know he can say "BioBrick Standard Biological Parts" until he's blue in the face. Better him than me, I suppose.

Times when biology knowledge comes in useful

2010-05-09T23:36:00.003-04:00

I love pineapple. Really, really love pineapple. Unfortunately, it irritates my mouth. I recently found out that this is not only due to the acidity -- pineapple contains a protease, bromelain. Bromelain will eat your face pretty effectively -- in fact, apparently there's a lot of interest in using it for wound debridement. [visceral shudder]

Unfortunately, the last time I ate a ton of pineapple all at once, I forgot about the protease until it was too late. But then I thought, "aha! I can saturate the protease with another type of protein and my mouth will remain unaffected!" Then I drank some milk.

Bio labs use milk as a generic solution of "loads and loads of proteins" in a lot of techniques. The one that springs to mind is Western blots. Basically, you run proteins through a gel that separates them by size and/or charge, to help identify what proteins you've got in the sample. Then you put your gel onto a nitrocellulose membrane that adsorbs proteins, so the spots from the gel transfer onto the membrane. Next, you want to probe the membrane with antibodies that should bind to your protein of interest, if it's on the membrane, and light up. But what's the problem? Antibodies are proteins, and the nitrocellulose membrane grabs onto all the proteins it touches, so unless you do something the antibody will just bind to the entire blot. What to do? Enter the milk! If you soak the membrane in milk before adding antibodies, then the milk proteins will bind all over the place and saturate the membrane, so then you can add antibodies without fear.

I told Zek about this and she mentioned another method for taking the bite out of pineapple: soak it in salt water. Apparently this is traditional in some places. We speculated that the high salt denatures the bromelain. I have yet to test whether this works or not, and whether it affects the taste.

Meal planning: harder than it looks

2010-05-03T00:54:00.004-04:00

Today was ET's Brunch in the Park, an event we throw every year for the current actives and alumni. A bunch of us made various breakfasty dishes. Watching the meal planning and preparation process was quite interesting. Most people went with something very simple, such as "pancakes" or "bacon", where the planning reduces to "Step 1: Buy a lot of whatever. Step 2: Cook all of it." I volunteered to make eggs, but I unwisely decided to get all fancy and make oven scrambled eggs with lots of mix-ins on the side.

My crucial mistake was not bothering to figure out the proper ratios -- I just went to the supermarket and bought "one" of everything: one head of broccoli, one 3-pack of bell peppers, etc. It turns out that one head of broccoli has significantly less mass than three bell peppers. It also turns out that it's hard to pan-fry things when all the stove space is continuously occupied by the pancake makers.

The worst part, though, was that the eggs were far too little and far too late. I cracked 25 eggs, but I should have done two or three times as many (or used an equivalent amount of that egg stuff that comes in cartons). We had around 30 people and only about 10 of them could have gotten an adequate amount of eggs. (As consolation, I can offer the fact that eggs + sauteed mushrooms + fresh basil = awesomeness!)

This episode gives me a whole new appreciation for the work our cook Karen does in planning meals and specifying what needs to be bought. She specifies the week's shopping list very neatly -- 4 pounds of broccoli, 3 cans of butter beans, foo units of bar, baz units of quux. Of course, she's had at least 20 years of practice, so I shouldn't be surprised that she's expert. After all, 2h/meal * 7 meals/wk * 20 full academic years works out to ~ 10,000 hours.

I just hope I can devote that kind of time and energy to some kind of lifetime pursuit or career...

Invasion of the possibly useful jargon

2010-04-26T03:33:00.004-04:00

Every time I take a class, I semi-consciously pick up its jargon and use it for all kinds of unrelated things. I'm aware that this is very common among nerds/hackers -- after all, I hang out with lots of them. I, too, speak of "pinging" people in real life, and of the "failure modes" of couches and suchlike. But because I'm a biologist hanging out with mostly non-biologists, it stands out a lot more because everyone else isn't using jargon from their biochemistry classes. I don't know many other people who use words like "inhibit" and "saturation" and "depletion" and "steady state" and "modularity" on a daily-to-hourly basis. (OK, maybe the last two are more widespread than I think, and I just need to hang out with more MechE or EE people.)

The most recent one is "timescale", or "on the timescale of". I picked this one up from my biomechanics class, which analyzes bio-materials of all different sizes from single molecules to whole organs. In order to keep ourselves sane, we have to take into account the size of the object in question when choosing an analysis method. Should we speak of the stresses and strains in a rod made of continuous material, or of the entropy-driven behavior of a randomly meandering chain? Can we ignore thermal motion of molecules, or the transient behavior when you begin applying force? It all depends on the length scale.

I find the word "timescale" very useful in my daily life. It's much easier to say exactly what I mean if I say "on the timescale of weeks" rather than "in the medium-term". I would love to say that it helps other people understand, as well, but unfortunately no one else seems to have picked up on it yet, so I will have to wait and see.

Strangely enough, the jargon-adapting habit seems to be largely involuntary. However, the success or failure of a given word is definitely related to its usefulness, to the usefulness of the metaphor. There's not that much difference between a feedback system in a cafeteria and a piece of complex software, so it makes sense to speak of both of them as having "failure modes". I guess this is what the "seeing-as" theory of intelligence is all about. (Something I read in one of Hofstadter's books... I don't remember which it was, and I don't know what this is all about.)

Addendum: jargon-adapting is also not particularly widespread among people who aren't part of hacker or twinkie social circles. Or, at least, I don't encounter it very much, and I often get laughed at (in a kind way) when I'm hanging out with my friends from Bioengineering and I speak of rainwater "saturating" a drain, thus forming a puddle.

Exhaustion

2010-04-19T02:52:00.003-04:00

This semester, I've been mentoring a team of two freshmen working on designing a cooperative system of biofuel-producing algae and nutrient-recycling bacteria. It's a really neat project -- in fact all three of this year's 20.20 projects are really interesting. They have more of a focus on system dynamics / population engineering, where my year we focused on devices. I think this may be due to having Ron Weiss instead of Drew Endy. (Another indication of Weissitude is that we're all modeling our systems in MATLAB... sigh. I am not fond of MATLAB.)

I don't actually know much about biofuels, synthetic cooperation, or complex metabolism. I also don't know much about mentoring a team in the sort of hands-on, hands-off style that's appropriate when the point is for everyone to learn and stretch themselves. So it's a challenge, but an extremely satisfying one. I have watched my team drink the synthetic biology Kool-aid in the most remarkable way. There was a palpable transition from naivete to relative understanding;

Mentorship is important, but providing it at this level is also exhausting. Every day after class I feel physically tired (actually, that may have more to do with my sleep schedule than my mentoring schedule).

Gaze Direction, or How Your RSI Prevention Software Can Distract Other People Too

2010-04-05T02:27:00.001-04:00

The other day I noticed something funny happening. To set the scene, recall that humans are wired to detect other humans' gaze direction as a method of figuring out where the important stuff is happening at the moment. Robots are working on this too.

For the last several months I've been having problems with eye strain after using my computer for too long at a time, so I've been using RSI prevention software to remind me to look away from the screen every so often. (I use TimeOut (review here) because it doesn't reset its timer if you leave the mouse alone for 10 seconds while you're reading something.)

When anyone else is in the room and I look up from my laptop to stare fixedly at the opposite wall, about half the time they will look up too, wondering just what is so interesting about that light fixture or Periodic Table poster. It usually takes them several seconds to figure out that I'm not actually looking at anything in particular... we're just so used to thinking of gaze direction changes as highly meaningful.

Of course, this indicates to me that almost everyone I know needs to look away from their screens more often. Do it right now (seriously, I don't mind waiting) ...................................................................
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you'll be surprised how your eyes feel when they refocus.

Overdue Ada Lovelace Day brief post

2010-03-29T01:11:00.003-04:00

Typical. I don't get an idea for an Ada Lovelace Day post until well after the day itself has passed. "But I just don't know any women scientists other than the obvious ones!" Not an excuse. How many women scientists was I taught by in elementary and middle school, completely oblivious to their prior lives? Of course, I was taught by men scientists too, and they have equally interesting stories. I'm just going to focus on one particular woman for the moment.

Molly was the science specialist at my elementary school. She gave the impression of a powerful but friendly science warlock, introducing us grade-school apprentices to a world of wonderful things. Yes, it sounds cheesy, but there you are. I don't have any data, but I think I must credit Molly with giving me that initial (strong) inclination toward science that tipped and boiled over when I ran into a copy of The Cartoon Guide to Genetics (Gonick & Wheelis). It's been more than a decade since then, and I've never looked back.

I can only remember a few fragments of specific things that Molly taught us, but I distinctly remember some of the things that we did. My school had a lot of forested property around the buildings, some of which had been invaded by the vinca that someone decided to plant around the parking lots. We spent many an hour tramping around the woods, of course, and not only identifying trees and noticing erosion, but waging war on the vinca. We marked out test plots and poured mulch over some, staked black plastic over others, and wielded picks, shovels, and good ol' pulling on the rest. I lost track of the project once I was in middle school, so I don't know how successful the ongoing efforts were, but it was pretty awesome at the time.

We also -- this is kind of surprising, in retrospect -- had a strong focus on communication. At some level, every third grader is going to remember "communicating" (writing the occasional couple of paragraphs). But we wrote full-length letters to lawmakers about environmental issues (not skimping on either the science or the rhetoric), and drew a cartoon illustrating a forest fire. The final exhibition of everyone's cartoons was a sight to see.

The other day, I happened to idly wonder what Molly was up to now, and so I googled her. I found out little about what she's up to since her teaching career, but there was quite a bit about what she had been up to before taking up the overhead projector. She published several papers in the sixties about Blepharisma and the recovery of cells from X-ray irradiation. She was at Stanford! Doing real science! Back in the day, before sequencing and so on were invented! Why was I not informed?

She also had an active life outside school, running marathons and working with the San Francisco Sidewalk Astronomers to build DIY Dobsonian telescopes. Man, how cool is that?

Molly Lusignan, scientist, scholar, teacher, and all-around awesome woman, I salute you. The moral of the story for the rest of us is to find out what our teachers (and our children's teachers) do outside of the classroom, about their history, their hobbies, and their dreams. These days, it's of course made easy to stalk people via Google (and Google Scholar! <3), but there's a lot more to be said for connecting in person. I wish I could have found her current contact information...

Journal Club Followup: The amber-suppressing AND gate

2010-03-21T21:44:00.000-04:00

We went over the AND gate paper in class, and generated a lot of constructive criticism that I hadn't thought of by just reading it on my own. I guess this is what class is for, huh.

In particular, we addressed the question of whether the AND gate is truly modular. As I discussed in the previous post, in principle this AND gate is modular in the sense that it can be plugged into different inputs and outputs. However, this isn't the whole story. "Plugging it in" to a different input is not so simple as just putting a new promoter in front of Input Gene 1. The whole promoter/RBS/coding-region assembly has to be tuned to have an appropriate strength. If you swap in a stronger promoter, you might have to weaken the RBS (ribosome binding site) in order to get just the right amount of protein expression to feed in to the rest of the AND gate.

In fact, that's exactly what the authors had to do when they first put their AND gate together, which I kind of glossed over. Recall that the system works by expressing an mRNA with amber stop codons in, and the amber-suppressor tRNA that can read those stop codons; the mRNA codes for a protein that transcribes the output promoter. Now, in principle this should Just Work. But in practice, if there's enough mRNA around, you can get spontaneous read-through even if the amber-suppressor tRNA is supposedly turned "off", for two reasons. One, even if the tRNA is "off", it might still be produced at a low basal level. Two, the amber stop codon is relatively "weak", and sometimes just gets read through anyway. (That is, it's not very good at recruiting the translation-stopping machinery, which is supposed to disassemble the ribosome and cut loose the newly translated protein.) So the authors had to adjust the RBS that governed translation of the mRNA, so there wouldn't be too much of it floating around and you wouldn't get this spurious effect.

Apparently this sort of adjustment is called "impedance matching", for those of you who are more familiar with electronics than cells. I don't know enough about electronics to explain exactly what impedance matching is or why it's a suitable analogy here, but it boils down to "make sure all the wires are carrying appropriate amounts of current, and if you connect something new to a wire you might have to add a resistor or something to fix the current back to how it used to be."

So, no, it's not plug-and-play quite yet. More like plug, mutagenize the RBS, and play... but maybe we'll get there eventually.

The other main criticism of this AND gate, from a modularity point of view, is that you can't have two copies of the gate in the same cell and expect them to operate independently. mRNAs and tRNAs float around, and if one AND gate is expressing mRNA and the other is expressing tRNA, then both of them will output ON, even though both of them ought to be OFF. This is a more serious problem, because you can't just tune an RBS and expect it to go away -- this design for an AND gate is in principle not modular with respect to other AND gates placed in the same cell. (Possible workarounds include hiding different AND gates in different cells and mixing several populations together, but then you have to work with cell-to-cell cooperation, which is a whole different ballgame.)

Where I'm going to be this summer

2010-03-09T19:37:00.002-05:00

I hope you can forgive me for prematurely tooting my own horn, as there are many logistical details still to be worked out, but... I'm going to be working in Pam Silver's lab this summer! Squee!

Figure 1: Yeast cell cycle counters! Hmm, those sound awfully familiar....

The answer to my question about scaffolds

2010-03-06T12:29:00.000-05:00

I passed my scaffold question on to my 20.20 professors, and got a very thoughtful response. (To their credit, it was also a very timely response; I've just been slow in posting it.)

Recall my question: there seemed to be a conflict between the role of kinase cascades as signal amplifiers, and the role of scaffolds as giving specificity. Turns out, naturally, that there isn't really a conflict at all. Rather, I didn't fully understand what scaffolds do. The crux of what I wasn't understanding is that proteins go on and off their scaffold all the time -- they don't stay bound (semi)permanently.

One of the main benefits of scaffolds is to make signaling pathways more efficient: they help bring proteins close together so they can interact. If you have only a few molecules of Protein A and Protein B, then they may not encounter each other very often if they're just freely diffusing around the cell. A scaffold can grab one Protein A and one Protein B, hold them close together long enough to interact, and the release them and go look for two new proteins. Or if A is a kinase for B, then A can stay on the scaffold and multiple copies of B can take turns.

Scaffolds also act like little switchboards, dictating where signaling pathways are allowed to cross and merge or where they must stay separate. Suppose a scaffold has one binding site for the kinase A, and a second binding site that can fit either Protein B or C, but not D. In this case you get activation of both B and C, and the signal from A propagates in two different directions, provoking two separate responses (but not provoking a third response). This is really helpful because a lot of kinases are promiscuous -- they'll phosphorylate anything they can get their hands on -- so if they're confined to scaffolds, then they'll do whatever the scaffold says they can do, and no more.

To see the beauty of a paper towel, and the world in an empty dewar

2010-03-06T11:44:00.006-05:00

If you ever work in a bio lab, you'll find that often the closest piece of paper to hand is a paper towel, and the closest pen to hand is a sharpie or lab marker. Predictably, a lot of scientific note-taking happens on paper towels. I know I've done my share of calculations on paper towels, and I've heard of some students keeping their notebook as a stack of scribbled-on paper towels. (Shame!)

And then I walk down the infinite corridor and see something like this:

Figure 1: Yes, Anonymous Lab Worker, someone appreciates your calligraphy. I love it when people do a little to make the world a weirder and more beautiful place. (Click to embiggen; the handwriting actually looks a lot better in high resolution.)

Ideas dump

2010-03-01T17:25:00.006-05:00

I'm looking over some old brainstorms, because of course I'm not busy at all, no sir, ahahaha... Anyway. I keep getting neat ideas, and I'm going to put some of them here so that (1) I don't forget them before I find time to investigate and (2) maybe someone will actually look at them and think about them. Also, I apologize for not explaining these ideas for the benefit of biology neophytes.

Enzymes that bind DNA and perform actions including cutting/pasting DNA or recruiting other enzymes. Can you inhibit their action by adding short pieces of RNA (or similar) with the same sequence as their binding site?

RNAi seems to exist in bacteria, kind of (not as much as in C.elegans). Is it useful for creating synthbiological devices? I don't recall seeing any; what's the roadblock?

In particular, RNAi could be a neat way of getting around the crosstalk/specificity problem, since it's very sequence-specific and designing RNA sequences is easier than designing proteins.

What would it take to drive localization to a synthetic organelle?

Need to learn more about riboswitches. All the riboswitches I've seen so far are the kind that respond to a small molecule. Hmm: can you make a riboswitch that responds to a short ssRNA??

What are the primitives of biological circuits? In a regime where it's easier to build monolithic black boxes than to reuse parts, how do things like two-component signaling evolve, that almost look intelligently designed with modularity etc?

I think I'm on an RNA kick. Is this justified?

Whoa, DNA scaffolds? Clever! read this at some point

Which tissues are anisotropic?

2010-03-01T14:39:00.006-05:00

Today in my biomechanics class we moved out of molecular mechanics and into tissue mechanics. This will involve a lot of stereotypical mech-E stuff like stress and strain and elasticity that all us biologists have never heard of before -- deterministic, bulk properties of continuous solids (or gooey things), rather than stochastic models of single molecules or long chains of molecules being buffeted around by thermal motion.

In this field, as in every other, you have to make simplifying assumptions. Two of the key assumptions we often make about bulk materials are that they are homogeneous and isotropic. That is, they're uniform throughout, and they're the same in every direction. Tissue like muscle (with fibers) or substances like string cheese (also with fibers) are anisotropic (there's your five dollar word for the day). If you're stretching them and you want to find out how they deform, it matters which direction you're pulling. After we learned what all these fancy words meant, we categorized a few tissues:

Isotropic:

Liver

Blood

Cartilage

Anisotropic:

Muscle

Bone

Skin

Ligaments

As I was writing these down, I noticed a pattern. All the isotropic tissues are what I'd call "biochemical tissues". Their main role is to store chemicals or make reactions happen. In contrast, all the isotropic tissues are "mechanical tissues", that make stuff move or stick together. Huh! Insight! But then it occurred to me that this makes total sense. After all, if you're doing a chemical reaction in a test tube, and you pour it into a bowl, the reaction will still happen. Whereas if you suddenly make all the fibers in a muscle run in a different direction, the muscle will do something completely different. If a tissue's job is to apply a force, it needs to apply that force in the right direction. Biochemical tissues are OK being isotropic, because their job is isotropic, and it seems like it ought to be harder for a developing organism to grow an anisotropic tissue, so why bother.

(Cartilage goes under "isotropic tissues", not because it does much in the way of chemical reactions, but because it's basically just a cushiony substance.)

Neat, huh?

Addendum: what about neurons and nerve tissue?

Well, we can throw out "neurons" straight out, because neurons are single cells, and tissues can only be treated as bulk materials if you've got a lot more than single cells. Trying to treat tissues on the tens-of-micrometers scale as bulk materials is like trying to calculate the viscosity of minestrone. It just doesn't apply. The viscosity of chicken broth is way different from the viscosity of beans. It only works if you zoom way, way out so that the effects of all the little bits and bobs become uniform over the entire blob of whatever you're looking at.

But we can totally look at nerve tissue this way. Your spinal cord, I would imagine, is a little bit like string cheese or rope. It's a whole bunch of long cellular fibers in parallel. If you pulled on it lengthwise, I would expect it to stretch; if you pulled on it widthwise, I would expect it to fray apart. It's anisotropic.

Gray matter in your cortex, on the other hand, I would call isotropic, or at least closer to isotropic (the cortex does have layers after all). Gray matter is mostly made up of cell bodies arranged more or less randomly, not a bunch of fibers all aligned with each other. Having dissected the odd brain or two, I think the best comparison for gray matter might be a firm jelly. (Exactly how firm it is depends on whether it's been preserved and how.)

So, does nerve tissue fit into the "biochemical" vs. "mechanical" tissue dichotomy? Not very cleanly. Then again, it's an atypical tissue. Its job is to send signals from point A to point B. For spinal cords and nerve bundles, point A and point B are far enough apart that it becomes important, on a macro scale, for the cells to go in the right direction. Gray matter contains mostly cell bodies rather than axons, so it's like a pile of Point As (or Points A, for the Captains Pedantic), whose job is to turn chemical signals into electrical activity.

Where do you learn?

2010-02-25T00:42:00.003-05:00

Since gaining actual friends at college (I know, I know), I've been repeatedly surprised by how often people skip lecture. I must have noticed this earlier -- after all, I did observe that lecture halls tended to get less full as the semester went on -- but somehow I thought that all good students always went to lecture or some such. Apparently this is not the case.

Also, it seems like people are supposed to know by this time whether they're "visual learners" or "audio learners" or some such. I have never been able to figure this out. But apparently I learn pretty well by going to lectures (as opposed to doing the reading), although this is probably a motivation problem rather than anything else.

For 2.5 years this strategy served me well, but now that I run into courses with mediocre-to-poor lecturers who are always unclear and often omit large quantities of important material, it's becoming problematic.

Learning to read all over again: Addendum

2010-02-18T20:50:00.000-05:00

The project of learning to critically read the primary literature is going pretty well so far. I'd like to add another stage to the four stages I mentioned:

5. Selectivity. At this point you become able to read "the literature" as a whole, not just individual papers. You can make a good guess about what's important without having to read everything in excruciating detail.

I'll also note that the stages overlap quite a bit. I'm still mostly in Credulity, but there are some papers I can actually criticize, and some I still fail to understand.

Impressions

2010-02-17T20:45:00.001-05:00

The water dispenser outside my lab has a cold spigot and a hot spigot. The hot spigot dispenses water which is actually quite hot. However, I couldn't figure out how to use it at first... until I realized that you have to put the handle in a certain position, which is not its natural low-energy gravity-ordained position, and then press it. It's a safety interlock! Good thinking! *makes tea*

I drove in snow for the first time recently. Well, not snow, but there was some kind of sleet-like substance on the roads and falling (slowly) from the sky. It was also the first time I ever skidded (a small amount). I've been on a skid mat, but it was a while ago and I remember it very poorly. I think the problem with the skit mat was either that I was unable to actually skid, or that it made no sense out of the context of a street and the slight hazard of hitting parked cars. There's no spatial reference on an infinite frictionless plane, after all.

Plates of fermenting bacteria on a phenol-red containing medium have this wonderful tendency to grow into miniature sunrises (although they do develop a rather off-putting smell).

Figure 1: Like viewing the sunrise from a mountaintop outhouse.

I just reread Terry Pratchett's Going Postal, and I really liked it. He gives the sort of lovely far-off impressions of the world of the clacks towers that I want to go there but that might destroy the mystique -- you know, the same thing people always say about why the Silmarillion is written in such a dreamy mythic tone. And if Thief of Time is the Discworld's The Matrix, then Going Postal is its Jargon File.

Ruuuuuuuuuuuuuun!

2010-02-16T10:47:00.000-05:00

I was reading my perfectly innocent-looking homework assignment, when all of a sudden I saw this:

Figure 1: Augh!

You know, I figured a biomechanics class (which is, after all, all about the realistic physicality of biology as opposed to magic cartoon enzymes that always work) would feature more realistic estimates of a bacterium's size.

Figure 2: I also figured it would feature less fleeing and primal terror. [Source]

Of course, the answer is that E. coli are measured in μm (micrometers), not meters, and that the micro sign simply failed to render due to some strange failure of MS Word. The lesson is clear: Mistakes in character encodings will kill us all. Go forth boldly, my friends, and godspeed.

Journal Club: The enzyme bucket brigade

2010-02-15T19:59:00.000-05:00

JE Dueber, GC Wu, GR Malmirchegini, TS Moon, CJ Petzold, AV Ullal, KLJ Prather, & JD Keasling. Synthetic protein scaffolds provide modular control over metabolic flux. Nature Biotechnology 27, 753–759 (1 August 2009) | doi:10.1038/nbt.1557

I read and presented this paper in my lab class this past fall -- and I thought it was just one of the coolest papers I'd ever read. Cool concept, rational design, elegant solution to a Hard Problem, multiple benefits, modularity/composability, real-world results... this paper has it all.

You can look at cells as little factories, taking in raw materials and churning out interesting molecules. A cell's naturally occurring assembly lines are optimized by evolution in various ways, to increase efficiency and decrease interference ("cross-talk") with other processes in the cell. In particular, natural metabolic pathways are regulated so that they don't go wildly out of control and start overproducing whatever chemical, because that would be wasteful and expensive (not to mention potentially harmful).

But when you're putting an artificial assembly line into a cell, you have to undo some of these constraints and not others. You have to maximize efficiency, minimize cross-talk, and avoid making toxic products in the middle of the pathway as much as possible. These goals all line up with the goals of the cell. However, your main goal is different from the cell's goal of "produce just enough": you want to produce as much product as possible. More medicine. More biofuel. More super-protein-material-thing. More whatever. So this should be easy, right? The metabolic pathway is made up of enzymes that convert Chemical A to Chemical B to Chemical C, and you're inserting the genes for those enzymes into a bacterium. Why can't you just put very strong promoters in front of those genes, so you get massive quantities of each enzyme, and massive output?

This simple maxing-out approach causes several problems. First of all, it does nothing about the intermediate chemicals along the pathway -- they could still be toxic, or even just float away and go to waste. Second of all, this approach doesn't bother to optimize the ratio of the two enzymes. (If Enzyme 1 is half as efficient as Enzyme 2, then you ought to have twice as much of Enzyme 1.) Third of all, this doesn't do anything to stop the pathway cross-talking with other pathways. Fourth, and possibly most important, there's no guarantee that forcing each individual cell to make as much product as it possibly, possibly can is the most efficient way to convert cell food into useful chemicals. It's probably more efficient to let the cell divert plenty of energy into maintaining its own health and into spawning more cells, so you end up with more product overall.

To solve this dilemma, Dueber et al borrowed a trick that cells often use to regulate their own pathways. A scaffold is a structural protein that grabs on to all the enzymes in a given pathway, and holds them together into something like an assembly line or a bucket brigade.

This neatly solves several of our difficulties. Intermediate chemicals proceed right down the pathway instead of floating off to get lost or wreak havoc. If the system needs more copies of Enzyme 1 and fewer of Enzyme 2, the scaffold can simply include an extra binding site for Enzyme 1. Neither the enzymes nor the intermediate chemicals can run off and cross-talk with other processes -- isolating things on a scaffold is easy, although rather leaky. And because of all these gains in efficiency, it's no longer necessary to max out production of every enzyme in order to make the cells produce a lot of product. So the cells are happier and probably end up producing more total product anyway.

(Side note: scaffolds are a particular instance of a a more general strategy called substrate channeling. There are a lot of synthesis pathways that literally take place in a tunnel, forcing the molecules to stick around and undergo reactions. Tryptophan synthesis is one such pathway.)

But how do you make a scaffold? A scaffold has to hold on to its enzymes as tightly as a lock holds a key. We simply don't know how to design proteins that well. (Predicting protein folding is more or less The Famous Unsolved Problem of biology today.)

Dueber et al's really elegant, clever idea was this: borrow naturally occurring lock-and-key pairs (thoroughly massaged by evolution), and hang the keys as tags on the enzymes we want. It's brilliant, and so simple that I'm frankly astounded it worked, never mind worked as well as it did.

Figure 1: Dueber's artificial scaffold.

The 'keys' are short protein chains, less than 20 amino acids long. The DNA that encodes the 'key' can be easily added to the end of the gene for each metabolic enzyme, so you end up with an enzyme with a little key-tag hanging off one end. The 'locks' are chunks of other proteins, that recognize and bind the keys for their own inscrutable (read: irrelevant) purposes. You can slap the 'lock' genes together into a giant fusion protein, and you have an artificial scaffold!

This is just fabulously elegant. It provides all the advantages of scaffolds, and what's more, it is entirely modular. You can swap the locks around, put them in a different order, add more of them, delete a few, etc, without messing up the rest of the scaffold. This makes it really easy to optimize things like the ratio of Enzyme 1 to Enzyme 2: if you don't know exactly what it should be, you can just try a bunch of different ratios and see what works. The reason it's so easy to change things around is that the scaffold is nothing more than a chain of protein chunks strung together. In particular, the folding of any given protein chunk doesn't depend on the adjacent chunks, as it would if the scaffold was built as a single large unit instead of a composition of smaller units.

Figure 2: Recruiting different numbers of proteins to a scaffold is like adding beads to a chain.

So now we get to the literal million-dollar question: does it work? The authors chose to test their scaffold by synthesizing mevanolate, a precursor to artemisinin (the antimalarial). Using this scaffold, they got 77 times as much product as they did from cells with no scaffold.

Figure 3: Each bar is a slightly different scaffold configuration. The best one rocked all the others into the ground.

What a cool piece of work. A really simple, elegant idea that solves so many complicated and subtle problems in one neat package, and produces real-world-usable results.

A question about scaffolds

2010-02-15T04:51:00.005-05:00

There are two bits of signal transduction dogma that have started to bother me. I don't know why I didn't spot this before.

Kinases are proteins that activate other proteins by attaching phosphate groups to them. Kinase cascades (several kinases in a row) are fairly common in all kinds of signaling pathways. Their main benefits are amplifying and diversifying the signal. Since a kinase is after all an enzyme, it can catalyze the same reaction over and over; it can activate many copies of the next kinase in the cascade, each of which can activate many copies of... and so on into exponential growth. That's how you get amplification, turning a tiny-but-important input into a massive cell-wide response. Diversification comes in when a kinase has more than one target. This comes in handy when the cell needs to respond to one signal by doing several different things all at once.

Scaffolds are large structural proteins that grab several other proteins from a signaling (or metabolic) pathway and hold them together. This helps them get their job done more efficiently. They help make pathways specific. If Enzyme 2 is stuck on a scaffold between Enzyme 1 and Enzyme 3, it can't very well run off to some other part of the cell and mess something up.

So, I perceive a slight conflict here. On one hand, it's helpful to diversify a signal; on the other hand, signals ought to be specific. On one hand, enzyme cascades amplify signals by working catalytically instead of stoichiometrically; on the other hand, when kinases are bound to a scaffold, their stoichiometric ratio is locked at one-to-one. What's going on here?

The obvious answer is that each type of signal processing is used where it's appropriate, and all types are appropriate in different contexts. If this is the explanation, then you would never expect to find a kinase cascade associated with a scaffold. But that's exactly what the MAP kinase cascade does! What gives? I thought the whole point of having a kinase cascade was to amplify and diversify the signal, which is exactly what the scaffold seems to be preventing.

Figure 1: MAP kinase cascade shamelessly associating with scaffold protein. Have they no shame? What has the yeast ~~mating pathway~~ courting ritual come to these days? [Source]

Journal Club: The amber-suppressing AND gate

2010-02-15T03:32:00.005-05:00

Anderson JC, Voigt CA, Arkin AP. Environmental signal integration by a modular AND gate. Molecular Systems Biology 3:133 (2007) | doi:10.1038/msb4100173

Logic gates (AND, OR, NOT, etc.) are the basis of electronic computation. If we'd like to implement biological computation, one of our first steps has to be implementing similar logic gates using proteins and DNA. That is, we need to make devices that accept a few inputs, perform a logical operation on them, and then spit out the result. In the case of an AND gate, we want the output to be ON whenever both of the inputs are ON, and OFF when either input is OFF. It seems easy, but of course, this turns out to be a lot harder in biology (hence, people writing papers about it).

Figure 1: The result of this paper, if you abstract away all the interesting stuff. [Source]

What makes it hard to make an AND gate out of biochemical parts?

Lack of standard connectors. In electronics, every signal is carried by a current, and every connector is a wire. That isn't the case in biology. Biological signals are typically carried by the presence or absence of some protein that carries out some particular chemical reaction that affects other proteins. This is wildly nonstandardized, and it means if Protein A interacts with Receptor A, you can't just plug in Receptor B and expect things to work.

Fuzzy, non-discrete behavior. It's nearly impossible for a biological system to have a perfect ON or OFF state. Even if a signal is mostly off, there'll be a few molecules of it floating around somewhere. And when you go to turn it on, it'll take time. Basically, biological things tend to vary continuously and not discretely (in large jumps).

Crosstalk. If a biological device relies on some particular molecule, then that molecule is going to be everywhere in the cell. So, you can't put two copies of the same device into a cell and expect them to operate independently. They'll interfere or "crosstalk" with each other in ways you don't expect. In contrast, you can throw down dozens of electronic circuit elements onto a breadboard and they won't interfere with each other because they're separated by physical space. In biology, everything's in the same soup.

Anderson et al's AND gate goes a long way toward solving the first problem, standardizing connectors. Both its inputs and outputs consist of the connection between a promoter and the gene it controls. This is one of the most modular, most plug-and-playable connections known in biology today. You can stick basically any promoter in front of basically any gene, and it will work just fine.

Quick aside: A promoter is a short sequence of DNA that sits upstream of a gene and attracts RNA polymerase to read that gene. Some promoters are constitutive (always on), and some are inducible -- they turn on in response to some molecule or other condition. (Usually, the key molecule binds an activator protein and alters its shape, such that the activator can bind to the promoter and help recruit RNA polymerase.)

Figure 2: In the noble artistic tradition of molecular biologists (who draw all proteins as blobs), promoters are usually drawn as these bent-arrow things.

So that's how the authors of this paper gave their AND gate its modular connectors, which can be plugged in to a wide variety of inputs and outputs. You can choose any two promoters (which respond to any two molecules or environmental conditions you want), and hook them up to the input genes. Then once the signal travels from the input genes through the device and to the output promoter, you can hook up any output gene after that. The output gene drives the cell's response when both of its inputs are on.

Figure 3: Biological wires.

Now, let's dive into the guts of the AND gate to see just how it works.

Recall that three bases of an mRNA (messenger RNA) code for a single amino acid. There are three stop codons (UAG, UGA, and UAA) that code for no amino acid at all, but tell the ribosome when to stop translating the protein. Stop codons work because there is no tRNA (transfer RNA) to match them.... usually. There are mutant tRNAs that will do the job. They feel a little dirty, running stop signs, and they can mess up the rest of the cell's workings, but they do exist. One of the AND gate's input promoters is hooked up to the gene that creates the mutant tRNA that reads through the UAG stop codon. UAG is called the "amber" stop codon, and its corresponding tRNA is called the amber suppressor. Hence the title of this post.

(The reason it feels dirty is, of course, that stop codons are there for a reason. Proteins have to end at the right place, after all. But it turns out that running through UAG is less harmful than running through either of the other two, as UAG stop codons are less than 10% of the cell's total stops. And the investigators did check; this system barely affects the cell's health at all.)

But a mutant tRNA won't do anything without an mRNA to match. Now here's the real logic of the AND gate! The other input promoter is hooked up to a gene with UAG stop codons sprinkled throughout. If this mRNA gets transcribed without the mutant tRNA around, it can't get translated into protein because a UAG stop codon will call the whole thing to a halt.

So you need both the gene with stop codons, and the mutant tRNA in order to get a functional protein.

This protein is an Ultra Special RNA polymerase called T7 (it comes from the T7 phage). T7 polymerase recognizes a different kind of promoter than regular polymerase, so it won't work on the rest of the promoters in the cell. It will only work on its partner Ultra Special T7 Promoter, which just so happens to be the output promoter of the AND gate! Man, that's so clever. I never would have thought of that. It's pretty elegant.

Figure 4: The whole shebang in all its glory. The mRNA is the gray line with red TAG (=UAG) stop codons in it, and the mutant tRNA is the yellow splat. Published as Figure 1 in the original paper.

To sum up: when we have both an mRNA with stop codons, and a mutant tRNA that can read through those stop codons, then we get a protein that's capable of transcribing the output gene. Cool!

Figure 5: It works, too. That's Inputs 1 and 2 on the X and Y axes, and fluorescent protein output on the Z axis. Published as Figure 2A in the original paper.

Now, at the very end of the paper, the authors did something that rather endeared them to me. Throughout the design, building, and testing stages, they used green fluorescent protein as an output, because it's easy to read and easy to quantify. This is exactly as it should be. But ultimately what we're trying to produce is behaviors. These are much harder to read and quantify. In most cases, it ultimately comes down to some poor student looking at cells (or worms, or whatever) under the microscope and saying "OK, these ones are behaving in X way, and these ones aren't". So, although behavior is not the most suitable output when you're trying to build a circuit, it's the acid test for when you've got something you're pretty confident in and you want to know, Does It Actually Work?

Accordingly, these investigators took their fancy AND gate and hooked it up to a completely different set of inputs and outputs (incidentally, demonstrating that that was even possible!). The new output was not fluorescence, but invasion -- invasion of eukaryotic cells (using a protein from a close relative of the Black Plague, creepily enough). Sure enough, the bacteria stayed quiet when they received no inputs, or only one of the two inputs; and they leapt into action when they detected both.

Even if we don't want to make a Turing-complete cell just yet, AND gates turn out to be particularly useful for all kinds of biology-specific applications. If you're a cell and you have to tell the difference between Environment A and Environment B (and respond accordingly), often you can't tell by only sensing one thing. You might have to sense the local pH AND the local salinity AND the presence of Random Molecule #32493 AND whether there are more of you in the vicinity... do you see where this is going? Cells in the wild have to do this kind of simple computation all the time, and we'd like our engineered bacteria to do the same. It'll enable them to make sophisticated decisions like "Hmm, this patch of cells is expressing Cancer Marker A, and Cancer Marker B, and Cancer Marker Q... I'll secrete poison and destroy it!" Et voila, cancer-killing bacteria! (In principle. You've still got to get around the immune system and so on and so forth...)

Learning to read all over again

2010-02-09T12:48:00.000-05:00

In my RNAi seminar, one of the instructors (they're both postdocs) noted that reading primary literature is a legitimately difficult thing. He expects us all to progress through several stages:

Incomprehension. At first, it's difficult to even figure out what the authors are talking about, or trace the flow of experimental logic. Sometimes it just doesn't flow quite right; other times you get distracted by all the technical details you don't understand at all or don't understand the need for.

Credulity. Once you learn how a few procedures work and start to understand why people do experiments in the order they do, you can finally pull out a paper's main substantive point from all the noise. At this point you'll believe whatever the paper says, because the graphs look pretty compelling, right?

Savage nitpicking. Next you learn to ask methodological questions: why did the authors omit that control, or choose this particular method of statistical analysis? Why do the experiments in this order and not that order? Suddenly every paper looks like complete crap.

Understanding. You begin to understand what is good and what is bad about a paper, and how it fits into the context of the field. This does require some familiarity with that context, but it's also a matter of general experience.

I think I'm more or less at the Credulity stage. I can figure out what a paper is about, though it takes me a while, and I get super excited about the key results. I've gotten to the point where I can read papers by myself, but I've never seen a paper picked apart, analyzed, and criticized in any detail where I could actually follow the conversation (this is hard in high school). So I think I'll be needing professional help, as it were, to move beyond Credulity.

(I might have gone a little bit overboard with the paper-reading classes for this semester, though. I added it up and I think I'm going to be reading 6-8 papers a week, or about one per day. Wow.)

Courses for this semester

2010-02-08T00:28:00.000-05:00

This semester's coursework has two themes: "Let's Read And Discuss Primary Literature", and "Time To Stop Abstracting Away The Physical Nature Of Biology". Both of my required bioengineering core classes are about cells, molecules, and tissues from a mechanical engineer's perspective. All three of my electives are literature-discussion classes on various topics.

20.310 Molecular, Cellular, and Tissue Biomechanics - think introductory mechanics, only all the examples are biological things instead of, you know, steel beams or something. Up till now, I've been accustomed to thinking of DNA as a string of digital (AGCT) information, or maybe as a helical molecule; now it's time to think of DNA as a charged elastic rod, or a randomly-walking polymer. How much force can a motor protein exert to pull a vesicle where it's going? What happens when you push and pull on the cytoskeleton? What's the effect of pressure on cells? How do bones reshape themselves in response to forces?

20.330 Fields, Forces, and Flows in Biological Systems - fluids and E&M, only again all the examples are biological things. How do things like diffusion and electrophoresis work? How can you model the cell membrane as an RC circuit? What's the best shape / flow pattern for this sample chamber so that the most protein binds to the sensor on one side?

20.385 Advanced Topics in Synthetic Biology - this is paired with a freshman design/seminar course, 20.20, which I took two years ago and which rocked my world so hard. It's a great introduction to synthetic biology. The frosh get to do design projects, and because it's surprisingly hard to do this when you've only had introductory biology, the upperclassmen mentor the frosh teams. And when we're not busy mentoring, we have synthetic biology journal club. I'll be presenting a couple of papers and I'm super pumped.

7.25 Biological Regulatory Mechanisms - this just sounds fascinating. All the different ways gene expression or protein action can be controlled. Apart from being cool, this is also highly relevant for synthetic biology. Even apart from that, I'm excited about the lectures. This class involves picking apart the experimental logic of papers in a more rigorous way than I've ever had before, which I'm sure will be good for me as well as being fun. We're focusing on demonstrating results and excluding alternative explanations to an extent that seems to be missing in the modern age of "let's generate a zillion data points and then sift through them". Plus, it's a chance to pick the brains of some aged, sage professors. All in all, it really reminds me of ((my interpretation of) what Raffi said about) learning Talmud.

7.346 RNAi: A Revolution in Biology and Therapeutics - yet another paper reading class. I know nothing at all about RNA interference, but it's extremely important both theoretically and (potentially) medically. I'm also interested in using it to make synthetic-biological parts that don't crosstalk as much as protein-based parts do; we'll see if that's feasible.

I plan to blog a lot more about the papers I read in these classes. It probably won't be a full Journal Club post for every paper because I'll be reading about 6-8 papers a week, but I'll at least try to summarize them. (This is partly for your benefit and partly for mine -- I expect that writing paper summaries for the blog will help me read and understand the papers better.) But I will do full Journal Club posts for the papers that I find most interesting, and definitely for the ones I present. I might also write about interesting things that happen in the other two classes.

Academic identity crisis

2010-02-01T01:33:00.003-05:00

My dad and I happened to be talking about construction failures earlier today -- a raised highway section that collapsed in the Loma Prieta earthquake; the tiles that fell off the Big Dig ceiling. He spoke about them in terms of redundancy and single points of failure, using the engineer lingo that he's picked up from reading books about civil engineering. When I'm being cynical about synthetic biology, I think biologists like to use these terms to make themselves sound sophisticated.

It does bother me, though, that I will graduate from this place with the word "Engineering" on my degree but possibly without the ability to analyze a design, find its flaws, and fix them. I will be able to design an experiment to determine whether Protein X affects Process Y in the cells of Species Z, which covers the word "Biological" on my degree... but will I be a real engineer?

A lot of synthetic biologists come into the field from computer science or electrical or civil engineering, and the whole point of synthetic biology is to turn biology into a Real Engineering Discipline that systematically uses ideas like redundancy in design. If you count up the most prominent synthetic biologists and their origins, it's easy to get the idea that "foreigners" from Real Engineering Disciplines are coming into biology, understanding the science within a week or two, and then dragging it kicking and screaming out of laboratories into design studios and factories. This, too, bothers me.

I do believe that this endeavor will be a truly collaborative one, and will require people with a thorough grounding in biology-the-science as well as people with classical engineering training. I even have a couple of professors' opinions to back this up, although I won't get actual data to confirm or deny this belief until I'm at least in grad school. Certainly biological training helps with designing and conducting experiments; you have to know what a Western blot does in order to know when it's appropriate to do one, and to do it properly. But this makes the biologists sound like the servant underclass in the making of synthetic biology.

Even apart from all this, I worry that synthetic biology, as the newest addition to the family of bioengineering subfields, is not yet ready for its practitioners to be trained in bioengineering instead of in biology or in engineering. I worry that, with an interdisciplinary education, the only thing I'm becoming good at is dabbling, and that I won't develop a true expertise in any particular subfield. -- Then again, isn't undergrad for exploring, and grad school for developing a focus?

You can talk to me! Can I talk to you?

2010-01-23T02:12:00.006-05:00

Hi everyone! This is Paul from Colorado. He's a masters student in Course 16 (Aero-Astro), and he's in the Air Force. He's currently taking this really awesome sounding class called System Architecture (ESD.34), and his project is to analyze this really neat-sounding military helicopter. The idea of the class, and of the project, is that you take a sort of half-reversed approach to analyzing complex engineered systems. What is this part for? How does it relate to the other parts around it, and how does it fit into the system as a whole? How did this system evolve? What was the designer thinking at this step? How can I take this big monolithic-looking complicated thing and break it up into meaningful parts? The helicopter he's looking at is an 80s model which was based on an architecture originally built in the 60s for search and rescue, then adapted for some of the surprisingly similar circumstances of special ops (flying at night in horrible weather, for example), but with the greatly expanded capabilities necessary to deal with things like hostile airspace.

Most other people in his class are also analyzing large mechanical devices (one girl is doing the ISS), but one or two are doing more abstract things. Someone is studying air traffic control, and oh there was another neat project topic that I unfortunately forgot.

We thought it would be amusing to analyze the Saferide shuttle system from this perspective. If it hadn't inexplicably held up for ten minutes at the student center, we would never have started talking.

Figure 1: No, really.

Why don't I do this more often? Just strike up a conversation with random people? You do have to exercise care in choosing the right opening question ("What are you doing this glorious IAP?") and refrain from talking too much about yourself... but it really, really isn't hard. There's not even any risk. The worst that happens is that the conversation fizzles and you go back to your book or iPod or whatever. But despite what people tend to think when locked up inside their own heads, everyone else is a thinking human being with interests and passions and opinions and experiences, and these can differ from your own in fascinating ways.

I'm not saying that everyone should be engaged in conversation all the time. I enjoy reading on the bus too, and I certainly enjoy solitary time, being somewhat introverted. But there's no reason to fear or avoid the nontrivial stranger conversation.

Tomorrow I think I'll strike up a conversation with the bus driver.

[The only problem I have with the "Just Shy" shirt is that it automatically puts the onus on the other party to initiate conversation. I think that, in wearing it, one must also resolve to initiate more conversations oneself. If that is done, there can be no harm in advertising that your ears are open for business.]

Focusing on the high order bits

2010-01-21T01:00:00.004-05:00

I was flipping through some bookmarks just now and ran across Scott Aaronson's post on Umeshisms, a particular type of exhortation to think about important things and not about trivia. Now, I usually find it difficult, if not impossible, to keep my focus on the high order bits in life, including both the Important Science Questions bits and the Stop And Smell The Roses type of bits. This puts me into a bit of an existential quandary, as it seems to be particularly important for scientists (and scientific engineers) to think Big Important Thoughts and not get distracted by minutiae.

Partly, perhaps, this is because I'm still an undergrad and lack the context to ask the Big Important Questions. (I'm taking a seminar-type course next semester, which I hope will help. But really, at what academic age are you supposed to learn how to ask Big Questions?) Partly also, perhaps, I have been trained all my life to turn every assignment in on time, get every point, answer every question, take every note, and it's proving difficult for me to evolve into something other than a student. I've certainly come a long way since freshman year, but naturally I begin to recognize how very far I have to go. And, anyway, I've been this way all my life. Call me "conscientious" if you wish to be kind, and "neurotic" if you don't.

Today in lab, I was tired and made a conscious decision to stop working on Science and start working on chores like pouring petri plates and unpacking boxes of pipette tips. I'm unsure how much this was due to my being tired and having a mediocre-to-poor week in general, versus being due to my intrinsic inclination toward the more brainless side of technical work. My brain seems to be at its happiest when I'm doing mildly repetitive, not particularly demanding work that is nonetheless not entirely stupid and requires concentration. Despite how tired I became the other week when I was doing the growth curve, I actually really enjoyed it because by the fifth or sixth hour I had the whole process down to an entirely mechanical, meditative series of pipettings and platings. For a further example, in high school I made a lot of chainmaille (both armor and jewelry) -- and it doesn't get much more repetitive than concatenating hundreds or thousands of little metal rings.

For this reason, I'm thinking hard about where I actually want to end up when I graduate. Reportedly, there exist jobs where one is primarily a lab technician but can also do a small research project on the side, and I'm extremely tempted by such a job. But I feel like if I did that, I'd be wasting my education or something. What to think?

I, for one, welcome my new bacterial overlords

2010-01-15T09:45:00.001-05:00

Over the past 24 hours, and yes, I really do mean the past 24 hours, I've been constructing a growth curve in my lab. The idea is this: there's an easy way and a hard way to tell how many bacteria there are in a culture. The hard way is to take a sample of that culture, spread it out on a plate, and count the colonies by hand (assuming each colony arose from a single bacterium of the original culture). The easy way is basically a more sciency version of "just look what color it is".

Figure 1: Shall I compare thee to a summer's day? Thy color is more lovely and more linearly related to the pH of the solution. [Source]

The bug I'm working with ferments sugars for a living, so as it grows it makes its environment more acidic. This is really handy, because we have wonderful molecules like phenol red that change color according to pH. In this particular case, yellow means acidic and red/pink means basic, so as the bacteria grow, the ratio of yellowness to redness should tell us something about how long the cells have been growing and how many there are. Here's a paper by another group that used this method, although they did so much other (amazing!) stuff that you'd have a hard time finding the details (look at figure S4 on page 41). So it really does boil down to "just look at what color it is", except that if you need to be precise, you use a spectrophotometer instead of your eyes.

The trouble is that the yellow/red ratio doesn't actually tell you anything about the number of cells in your culture, unless you take the trouble to do it the hard way and the easy way at the same time and figure out how they correlate. This is called doing a growth curve, and it's something that has to be done for every different bug if you want to measure it by any method that's easier than counting spots in a dish the day after you wanted to know.

So... while I can't say I have been in lab for the past 24 hours (I took a couple hours off last night to go get food and a nap), I have been running this same experiment for the past 24 hours and taking samples more or less every hour. It's tiring in multiple ways. I could barely make myself come back from my dinner-and-nap break because I was in physical pain from being tired. Also, having to go do something for 15 minutes out of every hour is hell on your ability to get anything else done.

When I said I had blocked out the entirety of my IAP for this research position... I guess I really meant the entirety of my IAP. All hail science!

Obligatory navel-gazing

2010-01-12T20:15:00.000-05:00

...or gazing at whatever counts as a blog's navel. I don't think blogs are placental mammals, after all.

Figure 1: Also not a placental mammal.

*ahem*

When I signed up for the Iron Blogger challenge (blog >=once a week or contribute $5 to a communal beverage pool), I could have started an entirely new blog, as many participants did, even if they had old fossilized never-updated blogs. I was really tempted to do so, because I named this blog The Dendritic Arbor back when I thought I was going to study neuroscience or cognitive science. Dendritic arbors are cool, but they really don't have much to do with synthetic biology.

Figure 2: Santiago Ramón y Cajal's drawing of this blog under a microscope using Golgi's silver nitrate stain.

But then I got lazy and I realized that if I attempted to set up an entirely new blog, I would be trapped in the same yak shaving that was trapping my friends. Yak shaving, while fun, is not very productive. I already shaved yaks to produce this blog. Besides, what would you call a synthetic biology blog? Genetic Memory? On The Scaffold?

Of course, that means I have to come up with a retroactive justification for naming my blog after a Neuroscience Thing. Dendritic arbors are some of the most gorgeous, elaborate cellular structures anyone has ever seen. More abstractly, they allow a single neuron to take thousands of individual inputs from dozens or hundreds of other neurons, and they integrate the total incoming signal to allow the cell to make its perpetual decision: fire, or don't fire?

I like to think that I can source interesting information from all over the place and integrate it all together here for your viewing pleasure.

(ScienceBlogs fans will note that I'm imitating the picture usage style of the fabulous Dr. Isis, which always makes me laugh, but I'm not sure how well it works for other people. It's an experiment; I'm sure I can never live up to the science goddess' hilariosity and fabulosity.)

Lab Resolutions

2010-01-11T10:49:00.005-05:00

Last summer I had an undergrad research position (UROP) in the lab of Tom Knight, one of the founders of synthetic biology. It was pretty good, but I really didn't make as much of it as I could have.

Then I went incommunicado for an entire semester. I just dropped off the face of the planet, as far as TK was concerned. Taking a break from research for a semester is not in itself terrible -- if you have a difficult course load, you have a difficult course load. However, just dropping off the face of the planet is highly unprofessional and not recommended.

In about half an hour I'll be in a meeting with TK, beginning my re-entry into the lab. There'll be random technical detail updates to go over... but privately, there are a lot of things I want to improve about the way I approach lab work. Thus, this list of resolutions, which I'll be periodically updating.

Scheduling / Productivity

- I will filter my internet access while at work, both WWW and zephyr. (I already have filtering mechanisms; it's just a matter of applying them strictly.)

- During IAP: I will go in to lab every weekday, and if I miss a lot, try to make up a bit on the weekend. Once term starts: I will schedule blocks of lab time among my classes, going in at least 3x a week... I'm undecided about the weekend. I will adhere to this lab schedule as if it were a class schedule, i.e. no skipping.

- If I didn't pipet something or run a gel or look at my cells or do any other Real Lab Thing, it didn't count as being in lab. (I'm not sure about this one... probably needs some caveats about "what if I'm waiting for my primers to come in the mail" or something.)

Communication & Stuff

- I will continue working on my M. florum project from the summer, and also discuss with TK what's best to do about the fact that I don't actually find it tremendously interesting. The solution may involve picking up a second project.

- If I'm having difficulty extracting some nugget of information from the literature, I will get help by the next day instead of putting it off. I will strive to ensure that said help actually improves my literature-searching skillz instead of being just "Professor Awesome saves the day again".

- In order to keep myself accountable for time management, and to keep a clear view of overall project goals instead of being bogged down in minutiae, I will have some kind of meeting or status update with TK every day I am in lab unless he's out of town. If he's out of town for several days running, frequent email updates.

- I will figure out a way of explaining my research to my relatives that does not include the word "plasmid" (and probably should not include the words "user interface" either -- last summer I got lazy and made up a computer analogy that wasn't very accurate).

Do I get a Home Improvement merit badge now?

2010-01-09T06:01:00.007-05:00

I didn't grow up tinkering or making things or using tools, and this has always sort of bothered me -- especially since coming to MIT, which is full of tinkerers and makers, even in the more theoretical majors. And, the DIYbio movement notwithstanding, mainstream biological research is not exactly hands-on or building-intensive. I've learned to program a little and taken an excellent hands-on circuits class, but that's about it. So you can imagine my trepidation going into Help Week, in which the pledges of my fraternity kick the initiates out and devote lots of time to home-improvement projects.

My pet project was to install a towel bar in the women's bathroom so that people have someplace to put their washcloths that dirty water won't get all over the shelves. At the beginning, I knew absolutely nothing about how this was done. I spent some time deciphering the pictorial instructions that came with the towel bar, then went to the Internet and learned about using plastic anchors to put screws in drywall.

The trouble started when I realized I didn't know what size hole to drill in the wall. The internet said to use a bit "a little smaller than the diameter of the anchor", but it didn't say how much smaller, and the towel bar package didn't specify a bit size appropriate to the anchors that were included. So I just guessed too small to start with. After enlarging the holes once or twice, I attempted to hammer the anchors into the wall. The first one went in fine, but the other three didn't go in straight. It was here that I discovered I was using craptastic cheap anchors -- when I hammered on the last one, it bent and broke rather than going into the wall.

So now I had to figure out how to get them out. I had an idea, but I wasn't sure it would work, so I went back to the internet. It suggested (a) pulling them out with pliers, (b) pushing them all the way into the wall with a screwdriver, or (c) cutting them away with a drill in the process of enlarging the original hole. I was able to pull out three with no trouble, but the fourth wouldn't come out. So I pushed on it -- no progress. So I drilled on it -- also no progress. (Why? Was my drill bit dull or something?) So I went back to the original idea I had before consulting the internet: screw a screw halfway in, then pull it out using a regular hammer. Thankfully, that worked.

However, I was now without anchors. A quick search of the hardware closet found no extra anchors, and I was just about to start getting upset when I realized they must have been taken upstairs by the person who was working on fixing the banister. Sure enough, there they were -- actual quality plastic anchors with actual mechanical strength, able to withstand hammering, plus matching screws. And get this, the package even specified the appropriate drill bit size! I attacked the wall for the third time...

...and luckily, before I hammered the new anchors in, I thought to test the depth of the screws. Turns out they were too long for the wall. What to do now? I went back to the package and looked at all the mysterious numbers written all over it, and eventually decided that "#10" must refer to the size of the screw shaft. Then I looked through our Big Box O' Screws and found some more #10 screws that were shorter.

It was amazing how much better the new anchors worked. They went smoothly into the wall with no trouble, and I had the towel bar on the wall inside five minutes. Hey! I did a thing with tools and screws and stuff! I performed an act of home improvement by myself! Why isn't there a Science Scouts badge for biologists who step outside their academic bubble like this?

Figure 1: Hells yeah. That towel bar ain't going nowhere.

A women-in-science take on Avatar

2010-01-07T02:44:00.007-05:00

A lot of the critical analysis of Avatar that I've seen so far is, unsurprisingly, from a racial standpoint. You can find that discussion by googling; I have nothing to add to it. I'm somewhat surprised, though, that none of the women-in-science bloggers I follow have said anything about Dr. Grace Augustine. Compared to discussing the plot flaws and the ecology and the racial aspects, I suppose it is a little bit peripheral (or maybe they haven't seen it yet). The only comment I've seen from the science blogosphere is from Sheril Kirshenbaum, about how Dr. Augustine and the rest of the movie scientists are a good portrayal of scientists in general:

1) Dr. Grace Augustine. Sigourney Weaver’s portrayal of a research scientist was uncharacteristically good. Instead of the typical caricature we see in Hollywood, she wasn’t socially inept (i.e. typical Rick Moranis roles) or out to destroy everything (i.e. Dr. Evil). Instead, Grace conveyed the natural curiosity about the world that I observe so often in colleagues. Also noteworthy, she was funded by a program with corporate interests, but really using the opportunity to pursue her own research. Sound familiar to anyone?

Since I've never personally encountered serious sexism, I'm a little new to the game of thinking hard about portrayals of female scientists, but my impressions were generally very positive. As Sheril and others have noted, the scientists were realistic curious-about-the-world types, and they were Good Guys too. The lab population seemed pretty diverse, with female technicians in addition to Dr. Augustine. And clearly they've done a lot before the main character even gets there (written books, learned the Na'vi language, taught the Na'vi English, etc.) There's a scene where Dr. Augustine has been mortally injured and is being carried past some biological wonder, and instinctively murmurs, "I should take a sample!" Awwwww.

(Also, points for bio-lab realism: there was a fridge labeled "Only FOOD in this fridge".)

I'm a little curious about why Cameron et al chose to make the head Avatar scientist a woman. Possibly just because Sigourney Weaver is awesome (and I'm sure I'd have more to say about this if I had seen the Alien movies). Possibly because the Good Guys are fairly diverse in general, including women and ethnic minorities, as part of the overall racial-tolerance message. The one possible motive that bothers me is that perhaps it was felt that a male head scientist couldn't possibly spout all this unity-of-nature Gaia interconnectedness stuff, but that seems like a weak motivation compared to the chance to have Sigourney Weaver. When Dr. Augustine explains to The Evil Corporate Weenie how Pandora is all interconnected and networked, he is naturally incredulous, and I picked up a "you women and your earth-mother crap" vibe from him, but he's a Bad Guy so of course he's allowed to think that way. The film overall implies nothing about Dr. Augustine's femininity affecting the validity of her conclusions about Pandora.

Perhaps best of all, Dr. Augustine struck me as having a decent mix of stereotypically masculine and feminine traits. In her first scene, after she's woken up to meet the main character, she acts like just another unfriendly hard-ass who thinks Jake Sully is incapable (by lacking scientific training, not by being disabled). Her "where's my cigarette? What's wrong with this picture?" line reminded me of Noah Vosen the abrasive CIA team leader from the Bourne movies, which I had just been watching. But as we get to know her better, she reveals quite a bit of depth for a minor character. She's not a dumb blond and she's not socially dysfunctional. She's a good mentor to her research assistants, and takes a nurturing role towards Jake Sully when he starts neglecting his human body in favor of his avatar (making sure he eats and at one point covering him with a blanket when he falls asleep in front of the video log). And she doesn't take any crap from the military-industrial folks who are cramping her style -- she doesn't stop doing science until she's physically restrained in one fight scene.

It took me a while to realize this, because I had to get past the fact that she's a field scientist and I'm not, but Dr. Grace Augustine is something like the kind of scientist I'd like to grow up to be. I'm pleased that she exists as a role model.

ETA:

Grace Augustine is actually the first Sigourney Weaver doll that you can take home to play with. "I didn’t want a Ripley doll. That’s why there’s a Ripley doll with blue eyes. But Grace, I hope she has a few little pieces of plants and things like that. I hope she comes with a little botany kit. It’s good for girls to see a woman scientist who’s so good at what she does." [source]

Awesome! I want a little botany kit!

The sovereign importance of mentorship

2010-01-06T13:02:00.003-05:00

A few days ago I met up with the professor from the lab at Stanford where I worked in high school. I had a pretty rough fall semester, and I felt totally unmotivated and lost, so I wanted to hear what an Actual Successful Scientist had to say on the subject.

We spent nearly two whole hours talking, and his message boiled down to: "Mentorship is the most important thing."

This Ur-message applies, or has applied, or will apply, to my life in many different ways. I'll do my best to summarize here. (Context: I'm currently aiming for grad school and academic research, but considering alternate careers. In particular I have half-formed intentions of taking a gap year after I finish undergrad, and working in industry to see what it's like.)

If you have good grades, lab experience matters more than improving your grades. I have a very good GPA, mostly because I still have the overachieving high school student complex. I'm a perfectionist and I prioritize classwork above everything else. Last semester, I prioritized classwork above continuing my research from the summer, which was a big mistake. I was trapped by the subconscious impression that I absolutely had to maintain my very good GPA or else... what?

Really good lab experience, including good mentorship, is harder to come by than well-taught or interesting classes, and much harder to come by than an A+. It also yields greater benefits later on. I had to take this part on faith a little, because I haven't been to grad school, but it seems very plausible. "Lab hands" are very hard to teach, but a small gap in knowledge is easily corrected.

This is going to be really difficult for me to implement, because I'm so well trained at Being A Student that it's difficult to even imagine doing anything else as a primary occupation. But it has to happen eventually, and it may as well happen now.

The best mentors are those with proven track records in both scholarship and mentorship. It's often said that there's a tradeoff involved in choosing an older or younger advisor for your Ph.D.: the older profs are better mentors, but the younger ones are doing all the exciting new stuff. From what I remember of our conversation, and also a little bit from my own experience, I understand that well-established advisors beat young flashy advisors hands down.

A lot of this apparently comes down to having observed the most common failure modes in one's students. My prof was able to advise me particularly aptly because he's seen many people go through similar struggles to my own. It wasn't that he had seen my exact set of problems before; it was that he had seen parts of my problems in many other people and was able to synthesize them. He had something cogent to say about gap years, about engineering vs science, about depression, about grades, about anything I cared to ask.

A diverse lab environment is better for everyone. This goes hand in hand with the previous point: the greater variety of problems a mentor has seen before, the bigger the library of memories they can draw on when advising someone with the same problem or a new problem. (Not to mention issues of sexism etc, which are also very important.)

Finally, never hesitate to ask for help. People who can give good advice love to do so, because it makes them feel helpful and all warm and fuzzy inside. People who don't wish to give you advice may ignore you or brush you off, so there's basically no harm in asking very widely. It took me years to accept that my parents might occasionally have something wise to say, but it's true. Now that I've reached the point where my parents' academic/career advice is no longer particularly helpful, I have to cast a wider net -- but it's crucially important that I actually do so, and not rely on assumptions or PhD Comics.

My brain just isn't interested in itself.

2010-01-02T06:35:00.005-05:00

Reading through jhamrick's last couple of posts at Artificial Awareness made me think about how I used to be enamored of all this stuff -- AI, philosophy of mind, cognitive linguistics... That was everything I was into, around the last two years of high school and first semester of college. It was who I was. I was Going To Be A Cognitive Scientist, I Was. I read all the right blogs and tried to drag my way through some of the right books (though most of the time I ended up rereading The Language Instinct, which I must have read upwards of a dozen times in its entirety).

Then I changed fields. Long, mostly unrelated story.

But I got to wondering why I'm no longer particularly interested in cognition, AI, or related subfields ('cogsci' for short). I think it's a combination of several factors.

I had lousy teachers for my introductory psychology and neuroscience classes, and a lousy research experience in cognitive linguistics.

This is not cogsci's fault, but it is a plain fact of my experience and a large part of the reason why I chose to change majors.

The field is immature; it hasn't had its Watson and Crick.

I consider biology a mature field because so much of it comes down to simply "DNA makes RNA, RNA makes proteins, proteins build the cell's traits and perform its behaviors (and affect DNA)". This was all elucidated in its basic form many years ago. It provides a framework for understanding new experimental results and generating new questions. It is a Coherent Overarching Theory. Cogsci does not appear to have a Coherent Overarching Theory yet, though it seems to have plenty of contenders. I should note that I would expect the Theory Of Cogsci to be significantly more complex than the Theory Of Biology, and take a much longer time to discover.

(I think this point actually applies to basically all of the brain-related fields, although you could argue that basic neuroscience had its Watson-and-Crick moment when people figured out the structure and function of the neuron. I suppose it's also hard to reconcile my assertion that brain science is immature with the current, legitimately amazing progress in brain-machine interfaces -- but I don't know how well we actually understand how they work, or how well we can distinguish them from magic. Anyone who actually follows the news in that area, care to enlighten?)

I'm too lazy to have philosophical opinions.

Perhaps in a few years I will have the energy and the intellectual horsepower to grapple with the philosophical side of cogsci. But as it is, I can only stomach it in the kind of small doses Douglas Hofstadter likes to sprinkle into his books about poetry. I have always had a hard time motivating myself to think hard about philosophical arguments, figure out their axioms, pick holes in them, etc. etc. -- or, most of the time, to even figure out whether I actually agree with them or if I'm just reading along. I'm much more comfortable playing with cells, or even models of cells where the error is quantifiable.

---------------

There are enough cognitive/AI people amongst my acquaintance that I expect I'll hear some eloquent defenses -- and I'll be glad to hear them, I really will. I'm just happy the field is in such competent hands. If you put me in charge of AI, after all, we'd never discover anything.

For those of you who care

2009-12-31T02:35:00.002-05:00

...I'll note again, as I did at the inception of this blog about 3 years ago, that I also maintain a personal blog over at Livejournal. Also, there is an LJ syndicated feed of this blog.

Exposing oneself to disturbing things

2009-12-31T02:05:00.003-05:00

[If anyone's here from Iron Blogger, welcome!]

Home for the holidays, I've been rewatching a few Firefly episodes with my family. Because everyone gets to pick, said rewatching has not consisted solely of "Heart of Gold" over and over and over :) -- and I end up watching the episodes with disturbing bits that I don't like.

What don't I like? I don't like stabbings or incisions (and I'm not fond of injections either, or at least the needle-entry part, though IVs are OK). I don't like torture scenes. I don't like when characters walk alone through dark creepy hallways where it's implied that Reavers or similar will suddenly jump out at people. I don't like half-rotted or mummified corpses.

I'm not sure what the common thread is between these things -- or between the things I don't mind (blunt trauma, gunshots... or most anything not listed above).

Somehow I keep making myself sit through movies that have this stuff. I managed to freak myself out pretty badly at a free showing of 28 Weeks Later a couple of years ago, when I could have just got up and left. Perhaps I feel it's unseemly for a grown, voting adult to have to not watch things. After all, when I was a kid I didn't have any compunction about leaving the room when it got to the Emperor-electrocutes-Luke scene in Star Wars. My dad's philosophy on scary things is that he leaves the room because "I don't need that stuff in my head, it's not worth it", which strikes me as very sane. What, after all, is the higher purpose served by my watching Mal and Wash get electrocuted repeatedly?

However, I feel that there should be a corresponding policy to not avoid watching (or reading about) the horrific things that go on in the real world, because in that case a horrified reaction can translate into a call to action (charitable giving, political action, whatever). This is actually one of the strongest arguments I've heard in favor of free speech, and in particular freedom of hate speech: let's get it all out there so everyone's at least aware that this sort of badness exists, rather than letting it stew in private gatherings until it becomes hate crimes.

Review papers are your friend!

2009-08-07T14:18:00.003-04:00

I've been attempting to read a lot of papers in the past week, and struggling fairly badly. Reading primary literature is hard for two reasons: you need to have enough background knowledge to understand the experiments, and you need practice at parsing the language and form of papers (a nontrivial skill). I've come a long way since high school, when it took me several days to look at all the words in a paper (and I still came out the other end with little understanding of what actually happened)... but I still have an awfully long way to go.

Which is why I love review papers. The literature search is done, the information is chewed-but-not-digested. It's just the right level for an undergrad. (Book chapters can also be good, but seem to be a bit less up to date because the publication cycle is longer.) A review paper is the best way to start a new literature search, or to get the "state of the union" on an interesting area you're not expert in.

<3 people who write review papers

The strawberries are delicious

2009-08-01T02:57:00.004-04:00

Today I decided to try a DIY DNA extraction. I started with Meredith Patterson's informal instructions, figured out what chemistry was actually happening, looked up some protocols from actual labs, and found what might be the original paper presenting the method of "salting out" DNA. Perhaps more research than I really needed to do, but it was pretty satisfying.

Then I went out and acquired a bunch of things: non-iodized salt, isopropanol, ethanol, papain (aka meat tenderizer), some "test tubes", a "centrifuge"... and strawberries.

For some reason, strawberries seem to be the canonical thing to extract DNA from if you're just demonstrating, so you can show your audience slimy white strands and have them go "ooh, aah". Maybe they have a lot of DNA or something. (What ploidy are generic commercial strawberries?? EDIT: they are apparently octoploid. Impressive!)

Right now, one mashed-up strawberry is sitting in a solution of salt (I should probably be using a real buffer), shampoo (disrupts cell membranes and precipitates proteins), and papain (slices up proteins). All the amounts of things were totally guessed. I put the solution in a double ziploc bag and set it on top of a hot computer case to speed up the reaction. This is the first step, where I break apart the tissue and lyse the cells to get at the DNA. I'll leave the strawberry to digest overnight, and tomorrow I'll centrifuge to try and remove as much protein and random crap as possible, then add concentrated salt and isopropanol to precipitate the DNA. If all goes well, I might even post photos.

Watching the strawberry get slowly digested is interesting by itself. The red juicy parts got digested first, turning the solution a lovely pink, and leaving behind all the white fibrous stuff from the center. Did you know each seed on the outside of a strawberry has a tract of white-fibrous-stuff connecting it to the center of the berry? Since all the red stuff surrounding those tracts has already been digested, it's a little like looking at the skeleton of a strawberry. Kind of creepy. We'll see what happens by tomorrow morning.

...Oh, a word about test tubes and centrifuges. For test tubes, I went to a florist and bought some of the plastic tubes they use to keep single flowers moist. Ten cents each, and with neat little lids. For a centrifuge, I was toying with the idea of modifying a blender or something, but then I found the lid to a salad spinner, which lots of internet people have used as a makeshift centrifuge. Unfortunately, not the whole salad spinner, which would have been brilliant; but I added some zip-ties and it became a centrifuge capable of generating about 32 Gs. This is probably good enough for a proof-of-principle DNA isolation (though of course I want to do more than prove the principle). So far, I haven't spent any money on lab equipment that's sold for the purpose of being lab equipment. I'm going to have to get fancy sometime soon, because you can't do bacterial work with a piddling little 32-G centrifuge; you need something that can get up above 10,000 Gs. (Ebay, here I come!)

Bitesize Bio is shiny!

2009-07-31T11:23:00.003-04:00

I just discovered Bitesize Bio, an awesome site full of discussions of common molecular-bio lab questions and problems. It has an RSS feed but is also set up with categories and menus for non-blog-style browsing. The ~5 posts I've read have all been informative, well-written, and interesting. I got a couple about interesting new techniques, a couple about theoretical questions and their practical consequences, and a couple about being a good grad student or a good mentor. It's really shiny, especially for a new lab member like me who wants to know the reasoning behind the magical incantations we sometimes do. "Wash with 0.75mL Buffer PE"? What does Buffer PE even do? ...OK, that's a cheating example -- Buffer PE is a proprietary mix from a commercial kit (but I'm told that after you add ethanol to it, as you must, it's just an improvement on straight ethanol).

For example, I just read an article about touchdown PCR, a neat hack on traditional PCR.

Sometimes in a PCR reaction you'll have trouble with the primers binding in incorrect places, because there happens to be some random sequence in your sample that's sorta-kinda complementary to your primers. Then you get nonspecific amplification of random crap, which can drown the gene fragment you actually wanted to amplify. What do you do?

You can calculate the optimal annealing/melting temperature (Tm) of your primers, and make sure to do your annealing step at that temperature. But random salts and stuff in your reaction can affect the Tm, so the calculated Tm is only an approximation. And at any temperature reasonably close to the Tm, even if it's not optimum, some annealing will happen. Maybe not much, but some. That's thermodynamics for you.

The idea of touchdown PCR is that there's a sweet-spot temperature where, statistically, it's too hot for nonspecific annealing, but just cool enough that the correct annealing can happen. You can't know exactly where this temperature is -- and you wouldn't want to run your whole reaction at that temperature anyway, because you'd only get a small amount of primer annealing and your yield would be low. So instead, for your first cycles you use an annealing temperature significantly higher than the calculated Tm for your primers (about 10 C higher). Then, in subsequent cycles, you gradually lower the annealing temperature. So in early cycles, only a few primers will anneal, and they'll almost all anneal to your actual sequence of interest, and not to random other sequences that are close-but-a-little-off. By the end of the cycle, you've amplified your correct sequence by a little bit relative to incorrect sequences. Run through several more cycles, and by the time you get to a "standard" annealing temperature where nonspecific annealing can happen, you've hopefully amplified the correct sequence quite a bit already, so nonspecific annealing becomes less of a problem because there are just more copies of the correct sequence available for the primers to bind to.

When I read about that, I was blown over. It's such a clever thermodynamics hack! -- it takes advantage of the fact that chemical reactions (DNA base-pairing or anything else) have fuzzy, stochastic behavior. For a given reaction, there isn't a sharp cutoff temperature where it goes from "too hot to react" suddenly to "OK now reaction proceeds fully". It's fuzzy. If it's too hot, a few molecules will react. Get a bit closer to the optimal temperature, and more molecules go. If you have two competing reactions with slightly different optimal temperatures (like specific and nonspecific annealing!), it's like having two bell curves overlapping, centered at slightly different values. You can find a value where one bell curve is acceptably high and the other is very low -- and then once you've amplified your chosen sequence N-fold, the game changes and you don't have to worry about the incorrect sequences nearly as much. It's like magic!

References (from original post):
1. Roux KH. Genome Research. 1995. 4: S185-194.
2. Mattick JS et al. Nature Protocols. 2008. 3(9). 1452 - 1456

I return

2009-07-30T10:51:00.002-04:00

Hello all,

Yes, I've been away from this blog for a very long time. But I find myself having more science content that I want to talk about, so I figure it's time to revive the Dendritic Arbor.

(Originally, I tied this blog not to my main Gmail account, but a different one. This turned out to be really annoying because every time I signed in to Blogger, I got signed out of my email. This was a major disincentive to post, and since I didn't realize you could transfer blog ownership between accounts, I just posted less and less. But now everything is fixed. Hooray.)

Where am I now? Well, I'm between my sophomore and junior years at MIT, I've radically changed my social circle, and I've pledged a (coed) fraternity, Epsilon Theta. More relevantly, I've finally entered a lab where I'm doing productive work on an interesting project in an environment I like, after a couple of short and ill-fated other lab positions. I'm working in one of the wellsprings of synthetic biology, Tom Knight's lab, studying a very intriguing and not very well-known bacterium.

At the same time, I'm also trying to get more into DIY Bio -- cheap open source lab equipment, electrophoresis gels in drinking straws, that sort of thing. We'll see how this goes. I may or may not be too busy to ever get started on this, what with classes (those random annoying peripheral activities that colleges insist you participate in).

It's good to be back.

Open Courseware is not the be-all and end-all

2008-09-29T23:25:00.005-04:00

MIT's Open Courseware gets a lot of press. And a lot of it is well deserved -- it's fairly comprehensive, and does a good job managing the technical side of throwing vast amounts of material up on the internets (hooray for PDF). But it's not everything.

The past few days I've been stressing over various topics from my genetics class, mostly yeast tetrad analysis. Going to lecture hardly helps; for this class, it's been generally true that the more confusing topics are very poorly explained. Usually the textbook does a good job of explaining things, but it doesn't cover yeast tetrads hardly at all. And I have a test in two days.

(Yeast tetrad analysis is pretty interesting, by the way. I might write a post about it if I ever actually understand it.)

Turning to OCW didn't help, because more or less the same professors have been teaching the class for N years, so the lecture notes are exactly the same. I can get practice problems (old homeworks and exams), which are very useful once I actually understand something, but not in this case.

So I turned to Google. And lo and behold, googling {yeast tetrad analysis} brings up several universities' intro-genetics webpages about yeast tetrad analysis! With clear, coherent explanations and well-drawn diagrams! UC Berkeley (pdf), Indiana U (pdf), U of Saskatchewan, and U of Rochester, just to name a few.

(Even better, some of those are straight-up webpages. Better than everything being PDF, although not better than everything being .doc, which sometimes happens.)

I often hear, second or third hand, how people from other schools use MIT OCW all the time. And I'm not denying that OCW is awesome. But it's not perfect, and there are other places to go if the OCW explanation of a topic happens to be consistently lousy.

To be intellectually uncomfortable

2008-08-21T12:50:00.005-04:00

From one of Uncertain Principles' link dumps comes this piece from Inside Higher Ed: Tolerant Faculty, Intolerant Students. Apparently, despite the myth of the politically stubborn professor forcing his views on poor openminded students, the truth is more like students haranguing each other and professors doing fairly well at not inappropriately expressing political views. (Well, at least in Georgia. The study might have turned out differently if done on CRAZY CALIFORNIAN COLLEGES!!!!1!11!one.)

(I should note that I have only been in actual political discourse once all year, and it was with a student on my hall who fervently supported Ron Paul. Perfectly friendly, civil discussion; I didn't enjoy it because I don't enjoy political discourse, period. I haven't seen any politics in classes, probably because I haven't taken any classes where it's even marginally relevant. Coulomb's Law? Politicize that, bitches.)

The thing that really struck me about this article, though, was one particular quote: universities are a place to go to feel uncomfortable intellectually. Obviously, the article means this with regard to one's political beliefs -- but it's applicable in a much larger sense.

When I encounter something I can't understand, something really confusing, I get anxious and upset. This happens a lot because I'm at a difficult school, and it's to be expected that I will encounter confusing things. But why should I get upset? This is an artifact of tying understanding to Success and Achievement (TM), rather than understanding for its own sake. Even though I went to one of those hippie elementary schools where there are no grades, I suppose I still have kind of a hang-up about 'succeeding' versus being way outside of my comfort zone.

I really admire people who respond to confusing things by first feeling humble, and then feeling happy that they have another puzzle to solve. People who get suspicious if it looks like they understand everything. It's not that I think such people never get frustrated, but that seems like a highly useful mindset for a scientist or intellectual, much more so than getting upset and frustrated. (Certainly, given the complexity of the real world, if you think you understand everything about X, you're almost certainly wrong.) This mindset should also make for a happier person overall. Apart from that, it feels like the right thing to do -- it appeals to the idealist in me.

Universities are a place to go to feel uncomfortable intellectually.

The world is a place to go to feel uncomfortable intellectually!

I'm going to try and embrace this mindset, embrace this mantra. A form of "intellectual asceticism, perhaps?" Hopefully I can change my knee-jerk reaction to the difficult and the confusing.

New Look & Feel!

2008-08-15T08:45:00.005-04:00

So I changed the blog template.

The main thing that bothered me about the old template was that the main text column, the most important part, was of fixed width. Which is annoying if you have a wide monitor. With this new template, go ahead and change the width of your browser window, and the Dendritic Arbor will change right along with you. We strive to provide a customizable reader experience. We strive to be adaptable, plastic, and dynamic, like actual dendritic arbors.

(It also bothered me that approximately 80,000,000,000 other people are using the old template. Then again, this is Blogger, what was I expecting, hmm?)

I chose this particular theme via the complex and deliberate heuristic of seeing which one looked the most like the one Larry Moran picked for Sandwalk. I've been reading his series on protein structure and admiring Sandwalk's look-and-feel. I guess this is the exact same theme as Sandwalk has, just with different colors.

By the way, the protein structure series is excellent and here are links to all its items. There isn't really a 'best' order to read them in, but I've put them in an order that sort of makes sense.

Evolution and Variation in Folded Proteins
Levels of Protein Structure
The Alpha Helix
Beta Strands and Beta Sheets
Loops and Turns
Examples of Protein Structure

Why I am a hard agnostic

2008-08-12T16:52:00.000-04:00

I believe that the nature of deity is both unknown and unknowable (by humans).

As I understand it, "the nature of deity is unknown (and may or may not be knowable)" equals 'soft' or 'weak' agnosticism, and my position is 'hard' or 'strong' agnosticism. I was a soft agnostic up until relatively recently.

(Quick aside: that terminology bothers me because it's possible to be a strong weak agnostic -- i.e. you believe very strongly in the soft-agnostic position -- or a hard soft agnostic, or also a soft hard agnostic ("I'm pretty sure the nature of deity is unknowable as well as unknown"). Not sure what would be good alternative terms, though. Also, hard agnosticsim != militant atheism.)

I've been fairly sure for many years that the nature of deity is unknown, what with implausible theologies and the power of science, etc etc, blah blah woof woof -- this argument has been made, and people have responded to it, a million times.

There are two possible arguments, I think, for why we cannot know the nature of deity (as opposed to merely "we don't know it, but we might figure it out"). One is the "perverse liar god" argument, and it's sort of tongue-in-cheek. If there's an omnipotent deity, then it could make itself unknowable, never mind why it would want to. It could even put on an understandable mask while leaving its true nature hidden.

The other possible argument is "fundamental limits of human understanding". The human brain may be the most amazingly complex awesome thing in the universe, capable of conceiving arbitrarily complex and abstract ideas... but is it capable of understanding something omnipotent, omnipresent, omni-everything, possibly vaster than the universe? I highly doubt it, given how hard it is to truly grasp (say) the sheer size of a galaxy. (And I do mean truly grasp. Saying "oh, it's so many frillion light years across" does not count.) A galaxy has got to be a lot smaller than an omni-deity.

You'll note I said "fundamental limits of human understanding", not "fundamental limits of any understanding". I don't doubt that an omnipotent deity could understand itself perfectly well. It's perfectly possible that there are forms of understanding out there that are orders of magnitude more powerful than our piddling little thoughts, or maybe even have a completely different basis -- call them "super-understanding". But given that humans are limited to human understanding, can we understand super-understanding? I doubt it.

(For a very readable, math-flavored analogy to the topic of super-understanding, see Scott Aaronson's fabulous essay Who Can Name the Bigger Number?, which you should read anyway. He discusses Turing machines and Super-(Super-Super-...)Turing machines, among many other fascinating topics.)

And by the way, I have high standards for what I'm willing to call understanding deity. I'm not willing to settle for a grammatical string of English words, or a bunch of math, or whatever, that describes deity perfectly. I am perfectly capable of 'understanding' (sneer quotes!) a sentence like "God is a spirit, infinite, eternal and unchangeable, in His being, wisdom, power, holiness, justice, goodness, and truth", in that I know what all its words mean and I can parse the sentence, because that is perfectly fine English. But can I fully appreciate the impact of a spirit, infinite, eternal and unchangeable, in its being, wisdom, power, etc? Can my body generate a sufficiently large visceral/emotional reaction to the import of that idea, or will it run out of neurotransmitters first? Can my humble heart and mind contain the infinite? I think not.

Now, since I'm feeling a bit Hofstadterian, try this one on for size: "God is a spirit, infinite, eternal and unchangeable, in His being, wisdom, power, holiness, justice, goodness, truth, abstraction, recursion, subtlety, and inscrutability." Can this new, improved sentence give us a true, visceral understanding of an omni-deity? It's certainly an improvement.

(God-sentence is from Chapter 7 of Anne of Green Gables. I love that book.)

The Right Way to Respond to Getting Hacked / Cracked

2008-08-11T03:43:00.007-04:00

Wired: Boston Subway Officials Sue to Stop DefCon Talk on Fare Card Hacks

Three MIT students have figured out how to hack the fare card system used on the Boston-area public transit ("the T"), to ride for free, add money to a stored-value card, and other such things. They cracked both the RFID card and the magnetic-stripe card. Here is a PDF of their presentation.

They were planning to give a talk on their discoveries at DefCon, the big annual hacker/cracker convention. The Massachusetts Bay Transit Authority (MBTA), which runs the T, sued them to prevent them from giving the talk. The talk will not be given. The students' faculty advisor, Dr. Ron Rivest, is being given a hard time.

The MBTA are going about this exactly the wrong way! (Although their response is understandable.)

Security systems are only trustable if they are thoroughly tested in actual use -- including normal users, hackers, and crackers. No matter how hard the MBTA try to hush up their security flaw, it will not make their security flaw magically go away. They should fix the flaw. Yes, it will cost money, but my sympathy is limited.

It is basically a given that many people will hear about this security flaw, whether or not there is a DefCon talk about it. Hello, Internet. But if people hear about this flaw only through underground/unofficial channels, what impression does that give them of the MBTA? It gives the impression that they either don't know about the flaw, or know about it and aren't doing anything about it. It gives the impression that the people who run all of Boston's public transit are a bunch of incompetents.

Moreover, by stage-whispering "Shh! Don't tell anyone about this!", they're also saying "Hey, this is significant! And leaves us very vulnerable!"

(By the way, if their goal is to decrease the number of people who hear about their security flaw, they have failed dramatically, because it's getting all over the news now. For example, I don't know anything about the presentations at DefCon, but now I know there's a security flaw in the subway system I use all the time, precisely because they're suing my classmates over it.)

What should the MBTA be doing? Shouting this as loudly as possible: "Yes, we have a security flaw! Thank you guys so much for pointing it out! We're working around the clock to fix it!" This would give the impression that the MBTA is run by intelligent people who can face reality instead of frantically trying to make it magically disappear. People would realize that the MBTA is serious about fare security.

The "Fare Security: SERIOUS BUSINESS" attitude would help decrease all kinds of subway sleaziness, including people who break fare security by the super-advanced hack of jumping over the fare gates. Not to mention things like littering, graffiti, and panhandling (none of which are huge problems on the T, I'm glad to say!). If I see someone fare-jumping, it makes me think the subway system is for shit anyway, so what does it matter if I stick gum to my seat?

And besides, the MBTA's anti-hacker attitude will just annoy crackers and make them more inclined to crack the T fares. Being realistic, and trumpeting increased security, will make crackers less inclined to attack the T.

Come on, MBTA. Have the grace to admit you've been hacked, instead of going into denial. Fix the vulnerability. Show us all you're serious about fare security. In fact, why don't you talk civilly to the people who hacked you? I'm sure they could help you build a better system.

...And, because I need some levity, here's a related episode in the adventures of Domo-kun. Hooray, cute pictures.

Some programming resource reviews

2008-08-10T12:29:00.001-04:00

Since I've been teaching myself, and especially since I've been flirting with several different sources rather than settling into a steady relationship with any particular one, I thought I'd share my impressions.

So you know where I'm coming from: I took AP Computer Science AB (Java) in junior year of high school. Then in senior year we had a semi-experimental Scheme class based on the classic SICP (see below), but nowhere near as hardcore. Because Java and Scheme are so different, and because I forgot a lot of Java over the intervening summer, this amounted to me learning to program two separate times with very little cross-contamination.

After that, I didn't write so much as a line of code for my whole first year at MIT. (Yeah, I know -- how could I?!?, etc.) But somehow a lot of vague programming ideas seem to have stuck in my brain, making it much easier to (1) learn a new language, and (2) re-learn programming in general. So I'm somewhere between 'rank beginner' and 'person who wants to pick up a second language after their first CS class'. This will affect my assessment of resources.

>> Learning Python, Mark Lutz & David Ascher

...Comprehensive, I suppose. It's the O'Reilly book, which gives it lots of reputation points. It goes into a lot of detail about basically everything (I'm reading it online, but the dead-tree edition is quite hefty). Tables of built-in integer and string functions, that sort of thing. Even -- get this -- more than one chapter on getting Python to run on your system, choice of IDE, and how to run programs you write from a variety of situations. This makes it surprisingly useful as a reference, for a book with the word "Learning" in its title.

The thing that bothers me about this book is that it can't seem to decide where it's aiming. It's definitely a programming book, not a computer science book; but it's in between "dense comprehensive tutorial/reference for people who already know what they're doing" and "learn programming from scratch using Python". For example, it explains the ideas of iteration and recursion, gives very basic examples, and discusses the general sort of situation in which you might want to use them -- and then a minute later it hits you with a lot of jargon and dense stuff. Curious approach.

Perhaps some of the confusion is because the authors are trying to take a "quick survey first, then dig into the details" approach on each section, and their definition of "section" is too short, leading to a confusing rapid alternation between the high view and the details.

I'm only up to the section on classes and OOP so far, because I've started to run into stuff I never learned or have forgotten; so I can't comment on the GUI section or anything like that, but I'm sure everything else is quite comprehensive.

>> Structure and Interpretation of Computer Programs, Abelson & Sussman

Ahh, the classics. Especially the classics that are available online, for free, in full, under Creative Commons, and not in a really irritating interface!

This is a hardcore nerdy book. It doesn't teach you computer science, it ties you down and throws computer science at you thick and fast, but in a totally awesome, non-evil way. It's really not a programming book, either -- the authors go out of their way to teach you the absolute bare minimum of Scheme syntax to handle the concepts they're presenting. This is kind of irritating if your goal is to be able to do practical things quickly (ha). But if your goal is to achieve nirvana, you could do a lot worse than this book.

Read the footnotes. They are snarky, and competently so, unlike the lame attempts at humor you see in most textbooks.

>> Teach Yourself Scheme in Fixnum Days, Dorai Sitaram

This is a straight-up no-frills tutorial for people who already know how to program, more or less. Reading this after having taken a SICP class was pretty interesting: I kept going "Hey! That piece of syntax makes it really easy to do X thing we were always beating our heads over in class, because SICP HATES SYNTAX OR SOMETHING." Hooray for actually doing things with Scheme. I'd gotten the (not entirely wrong) impression that Scheme was good for nothing but theoretical interest and formalism with a dash of AI.

I'm not sure whether to recommend reading this along with SICP. On the one hand, I tried it and got really confused. Part of the charm of SICP's syntax starvation is that it actually helps you figure out how to do things; they simply refrain from teaching you the four other ways to do it. On the other hand, Scheme can actually do stuff that's not all abstract and theoretical and weird, and this teaches you how to do that.

>> [pdf] How To Think Like A Computer Scientist: Learning with Python, Downey, Elkner, and Myers.

This, I think, would be a good book for a (dedicated) beginner. It starts right at the beginning with the very fundamentals, and keeps a great balance between new concepts and new syntax. I haven't gotten very far at all in this book, mostly because I've spent so much time on the O'Reilly Learning Python book, but I like it very much so far.

Plus, how can you say no to a book that's written in LaTeX? Seriously, now.

>> Project Euler

Oddly enough, none of the above books have enough exercises in them. Teach Yourself Scheme has none at all. Learning Python only has a few, once every five chapters or so, and they're all about catching tiny nitpicks that trip you up. SICP has plenty but they're geared toward teaching CS principles, not coding practice. How To Think Like A Computer Scientist has good ones but not many of them. I googled around but the only thing I found that wasn't too advanced was FizzBuzz, which wasn't enough.

Enter Project Euler. It's a site full of math puzzles, varying in difficulty from "ludicrously easy" to "frackin' impossible", and set up such that you basically have to solve them by programming. Things like "find the ten-thousandth prime number", too big to be solved by hand. Excellent!

The site is obviously run by people who know what they're doing -- all the problems are very unambiguously stated, with examples, and the site keeps your score for you. Once you've solved a problem, you can look at the discussion thread where other people post their code and discuss alternative methods. The other people, by the way, are brilliant, and come up with all these elegant methods and neat optimizations for you to imitate.

Look Mom, Tags! And a Coding Trance!

2008-08-09T07:00:00.005-04:00

[Before I start, let me admit that I am still very much a programming n00b. Everything that excites me is probably old hat to the majority of the coding population.]

I like tags very much. They are a million times better than folders. 'nuff said.

I've been writing a tagging system. It's nothing special -- just something that pairs up items and tags, and can do some of the same kinds of lookup that the tagging systems on blogs can do. Have been wanting to do this for quite some time, so now I feel all accomplished :D

I haven't finished testing the thing yet, so there are probably a lot more mistakes hiding in there, but most of the ones I've caught so far have been pretty similar. I tend to confuse the actual tag object with the tag's name, and refer to one when I should refer to the other -- kinda like confusing the phrase "scientists are people too" with the tool that lets you do this. Same thing with confusing tagged items and the objects they contain. These are pretty easy to fix.

There are a couple more functions I want to write -- eg, I haven't got a thing that lets you organize the tags in order of frequency of usage (as they are in the sidebar). But I've got the majority of what I wanted. (And no, that doesn't include a GUI. This is strictly text-based, Python-command-line stuff.)

I guess I'm kind of excited because, back when I was thinking about teaching myself to program again, a tagging system seemed like kind of a big challenge -- one I could do relatively quickly, but a challenge nonetheless. And now I'm about 90% of the way there. It's astonishing how fast you can learn to program when you've already learned to program twice before! ^^

This is also the longest block of sitting-and-writing-code time that I've spent in quite a while. I seemed to fall into a sort of trance -- very focused, very losing-track-of-time. This is an interesting mindstate (not to mention a very productive one!), and I'd like to get into it more often. (It helped that some people over on the XKCD forum turned me on to the streaming lyricless music from Blue Mars, which bills itself as "music for space travelers". Despite the word "mars" in their title, I think they really mean "music for headspace travelers". I find it quite relaxing and focusing.)

EVOLVE: Eyes

2008-07-30T02:46:00.007-04:00

I just watched the History Channel's program on the evolution of eyes. Overall it was pretty meh, but there were a couple of interesting parts.
ETA: I didn't liveblog it or take notes, so there are things I forgot. Memory is fallible. I'm human.

My favorite was in the first segment -- the experiments on the jellyfish in the tank. The researchers got a jellyfish with primitive eyespots and shone different colors of light into its tank to see how it reacted. Green light made it "relax", stop swimming, and sink to the bottom of the tank. Purple light made it start swimming really fast, and for some reason it shortened up its tentacles by a factor of 2 or 3. How do they do that? And why do they do that? Is it for speed (shorter tentacles = more drag)?

I was interrupted by a phone call and missed most of the segment on trilobite eyes. My brother, who was watching, informs me that trilobite eyes are made of calcite. Huh.

The segment on the tapetum lucidum (shiny layer in the back of some nocturnal predators' eyes that makes them look all glowy and creepy) was quite good, relative to the other sections. Not so much with the ferocious dinosaur predation or the "T3H STRUGGLE FOR SURVIVAL ZOMGZ", lots of nice creepy glowy-eyed panther shots.

Dragonflies apparently have tens of thousands of lenses in their compound eyes, and have a visual "processing speed" (define please??) ~5x that of humans. Badass.

There was a weirdly long segment of dinosaur obsession. Whenever I see this kind of sensationalism it makes me sad, but I suppose it's only to be expected anymore. The epic, ceaseless struggle for survival! Eat or be eaten! And I imagine, sometime when this episode was being planned, some editor was all "we gotta have dinosaurs in all our nature programs!". Far too much time spent on dinosaurs in a program about eyes. They should have cut this by 90% and spliced in some material on cephalopod eyes, or the design flaws in the human eye, or more than perfunctory detail on intermediate stages between "patch of light-sensitive cells" and "fully evolved eyeball". All of which were either mentioned briefly or omitted altogether.

The other thing that really bothered me about this program was some of the things they felt necessary to explain: Humans are mammals. Vertebrates include reptiles, mammals, and birds. How can kids past kindergarten not know this stuff?

Also -- ok, I would really have liked to see a mention of how wildly different species use a lot of the same genes to control development, and how this interacts with (convergent) (eye) evolution, but this is a ridiculous thing to hope for, given the level of the program. Why are they showing kids-level programming at 10 pm?

Password-fu

2008-07-22T23:00:00.002-04:00

Here's how I make good passwords:

Pick a short keyword that's easy to type -- say, 'left'. Replace some letters with numbers (l3ft) and, for good measure, capitalize some stuff (l3Ft). Now, every time you need to make a password for something, take the name of the thing and stick your keyword on to it somewhere: l3Ftgmail.

This part is fairly well-known (although, still, not enough people use it!!!). What's fun is to make like a linguist and treat your keyword as a real affix. You can affix it anywhere to the name of whatever you need a password for, not just at the beginning or end (prefix or suffix). You can also infix it (gl3Ftmail or gmail3Ftl), or circumfix it (l3gmailFt).

This method doesn't completely specify your password. Sometimes you need to use an acronym for the service instead of the full name (su, or supon, for StumbleUpon), to keep the password from being too long. And sometimes I can't remember whether my YouTube password uses yt, ytube, or youtube. But it doesn't matter, because there are only a few possibilities I need to guess. What's more, this makes it easy to change passwords and still remember them fairly easily -- just move your keyword from prefix to suffix to circumfix to infix...

Forest-path connectivity

2008-07-20T00:21:00.003-04:00

There's a decent-sized blob of public forested space right behind my house. It's crisscrossed with unpaved bike trails -- and a good thing too, because it's difficult to walk through the forest off the trail without getting caught in dense coyote-scrub bushes or masses of poison oak. There's a little pond. From several points you can get a lovely panoramic view of the San Francisco Bay and/or the rest of the forest. All in all, it's quite the concentration of nature for someplace in the middle of a suburb.

One of my mini-projects for the summer is to learn my way around the forest trails. There are maps posted at the trailheads, but I'm challenging myself to use them as little as possible and to figure out the connectivity by myself, for two reasons. One, I'm too lazy to bother making myself a copy. Two, there are a number of "unofficial" trails that are perfectly walkable but aren't on the map. (I suppose the unofficial trails get made when people start riding their bikes down deer tracks or dry creek beds.) So I get to combine physical exercise, nature, and mental exercise. Three for the price of one!

Another point of interest: the forest is in a valley, so it's hard to find a piece of land that isn't steeply sloped (especially once you get away from the surrounding houses). Also, for some reason, the soil is such that trees fall over a lot, but often survive. So the whole place is full of trees with interesting geometries. There are horizontal trees. There are trees that form arches over creek beds -- they don't just sort of bend toward the creek, they actually start growing downward once they get to the other side, so you could almost climb up onto them from either end. Today, I saw a tree that, I kid you not, made four ninety-degree turns, each a foot or two apart.

Timprov, a friend of mine who's a pretty good photographer, is coming over tomorrow and we're going to poke around the woods and take photos of stuff. Should be fun.

It was the Summer of the Library Books. San Mateo County glowed red...

2008-07-17T23:36:00.007-04:00

[The title is an allusion to the pseudo-medieval text on the cover of one of the Redwall books: "It was the Summer of the Late Rose. Mossflower Country shimmered...]

"A red sun rises. Ash has been spilled this night." -- all right, that was worse. I couldn't resist making another allusion, though. All the wildfires in Northern California have been sending so much smoke into the air that, many days, the sky has been silvered over and the sun has turned red long before setting. (I don't remember exactly how long before setting, but the sun's been red while still five or more diameters above the horizon.) It's actually a beautiful sight, for all it's a symptom of fire and destruction elsewhere, and for all the smoke is causing trouble for people with asthma (especially in cities closer to the actual fires).

Other than that, though, mostly the weather has been fantastic. There have only been two days so far that I'd call "uncomfortably hot". Take that, friends back in Boston. It doesn't even matter that my house doesn't have air conditioning! I don't need it!

For the first time in four years, I'm not doing any kind of science research internship thing over the summer. This is mostly because I was too lazy to get myself a lab job, although it's lovely to have all this spare time. And since I have almost nothing but spare time, I've been lavishing attention on my book heap. I've taken an inordinate amount of books out of the library, bought a few from Barnes & Noble, and pulled several out of my family's rather large collection. I even have time to reread books! What a luxury.

(Because I've started to get a little tired of just reading, I'm also teaching myself Scheme in fixnum days.)

Here are some lists of books, with comments. I may write up more details on some of the sciency ones.
(Lists are not in any kind of order, and are not exhaustive (I'll probably remember more and add them later).)

Finished

The Hobbit, JRR Tolkien. This is a lot more fun than I remember it being when I read it as a kid. Tolkien's prose style is maybe a little difficult for kids -- but this time around I kept wanting to grab a bunch of random kids and read aloud the fun parts, really perform them. On a totally unrelated note, it's also fun to reread The Hobbit after knowing Lord of the Rings; Tolkien is constantly hinting at things. For example, it makes so much more sense that the Necromancer could cause Mirkwood to be nasty and gross if you know that the Necromancer is actually Sauron. And, there are the Dwarves charging into battle yelling "Moria!".

This is Your Brain on Music, Daniel J. Levitin. This one had me itching to make funny waveforms to screw around with my auditory perception, and to listen to the pieces of music he mentions with a totally different ear. Unfortunately, I was stuck on an airplane. Quite a ride. I took note of several small things Levitin said about his approach to his area of research, and am planning to write them up.

When You Catch an Adjective, Kill It: The Parts of Speech For Better And/Or Worse. Ben Yagoda. This one's good for dipping into because each of the chapters (Adjective, Adverb, Article, Conjunction, Interjection, Noun, Preposition, Pronoun, Verb) is relatively short and stands alone. Yagoda writes as a serious linguist, but not a dry one: he clearly enjoys language for its own sake, as any geek ought to. This is not a writing-advice or prescriptivist book (although it does contain some tidbits of writing advice).

How To Dunk a Donut: The Science of Everyday Life, Len Fisher. This is an interesting popular-science book. Rather than describing one small area for the public, Fisher describes applying a "scientific" approach to random topics like "Why do cookies crumble when you dunk them in milk?". I'm somewhat wary, because some of his projects seem to have been solicited by companies who want publicity for their cookies or whatever. Similarly, some of the "scientificness" of his approach seems to consist of wrapping things in numbers and graphs. A very laudable goal, but in some places the description is pretty dense for a book with that goal.

Proust Was A Neuroscientist, Jonah Lehrer. This was really well-written and engaging. Lehrer's idea is to show how various artists/musicians/writers (mostly of a certain Paris avant-garde club, it seems) anticipated recent developments in neuro / cognitive science. For example, Walt Whitman's "the body includes and is the soul" lines, and embodied cognition. I thoroughly enjoyed the arts-description parts and the science-description parts. And sometimes the connection between the two was strong and clear, as in the chapter on Proust; not so much in the chapter on, say, Stravinsky (that one felt forced). Still, eminently worth a read.

The Time Machine, H.G. Wells. Oh boy, did I ever get the wrong impression from the movie version of this. The book is a lot more realistic and a lot more... quietly horrifying? I don't think it's at all plausible that class separation will lead to humans splitting into two species, but it's thrillingly creepy to imagine humans evolving into either the Eloi or the Morlocks. I guess this one is halfway between dystopia and SF. (And I'm still a fan of the virtual-encyclopedia guy from the movie.)

Across the Wall, Garth Nix. I'm a big fan of the Abhorsen trilogy, and the first half of Across the Wall is a shorter story that's part of the canon. The rest of the book is a bunch of short stories outside the canon that I didn't find all that interesting. Nix writes young-adult stuff; Abhorsen aged well, IMO.

Autobiography of Benjamin Franklin. Wow! Franklin gets short-shrifted among the Founding Fathers because he didn't do "hero" stuff like command armies or ride at midnight through Massachusetts, because he doesn't look all that dignified and because the things he did do were quietly behind-the-scenes and/or sounded silly (kite, anyone?). But his autobiography is full of all kinds of interesting things, like the brilliant way he basically tricked the people and the legislature into funding a new hospital. And it's packed to the gills with advice that's a little antiquated, but still good. This is a real self-help book, not some lame thing full of whining and words like "self-actualization". I would have liked to hear more about his experiments with electricity.

In Progress

Le Ton beau de Marot: In Praise of the Music of Language, Douglas Hofstadter. What can I say? This is a book about translation -- but it's also a book by Hofstadter, which means it's a book about the idea of translation stretched and twisted and abstracted and applied to all different kinds of things, and at the same time it's also a book about poetry and music and elegance and math and computer science and AI and love. The book describes itself as something of a memory of Hofstadter's wife, Carol, and it's touching to read it as the world's longest, most elaborate love letter.

Gödel, Escher, Bach: An Eternal Golden Braid, Douglas Hofstadter. This one is also about music and elegance and poetry, but with a much larger dose of logic and math and AI and symmetry and abstraction. It's more work to get through, but it's so worth it.

On Food and Cooking: The Science and Lore of the Kitchen, Harold McGee. A really well-written guide to food, "scientific" in that it describes foods using scientific terms, not "scientific" in the sense of nutrition-reductionism. Sort of a Hacker's Guide to Culinary Experimentation.

On Deck

I Am A Strange Loop, Douglas Hofstadter

Diamond Age, or, A Young Lady's Illustrated Primer, Neal Stephenson

Vaccine, Arthur Allen

Jonathan Strange & Mr. Norrell, Susanna Clarke

On Intelligence, Jeff Hawkins

Dante's Inferno (anybody got recommendations about which translator to read?)

Perverse, Ugly, Terrible Beauty

2008-07-16T19:49:00.011-04:00

Neurophilosophy writes about amyloid plaques and Alzheimer's, showcasing this really interesting 3D rendering of the plaque's constituent protein fibrils -- larger picture with the original article at Discover. The article and the post are really informative and you should go read them because I'm not going to address their content. (Gasp!)

My first reaction on seeing the image was, "How strangely beautiful". Even though this is a picture of a prime suspect in an absolutely horrific disease. Even though it's got a rather menacing fire-and-brimstone color scheme. Even though I shudder at the idea of these nasty little fibrils snaking their way through my brain, withering neurons like the Goo of Death from Princess Mononoke.

It's well established that good, hardworking, well-oiled biology is a joy to behold (if you have the right mindset). Listen to PZ Myers rhapsodize about the time he got a close-up look inside his hand. Read Dr. Sidney Schwab's eulogies to the body unmarred, and to the regal liver and warm, welcoming intestine. You've all seen The Inner Life of the Cell; watch it again and marvel.

It's also pretty well established that diseased, shattered, out-of-control biology is ugly, ugly, ugly. Hear Dr. Schwab, again, on how injuries and cancer ravage and ruin the anatomy that was so lovely. And who hasn't shuddered (inwardly) at the sight of scabs and puckered scars?

But somehow, I find there's a genuine (albeit perverse, ugly, terrible) beauty to diseases and such evil things. In the same way that it's interesting to watch flames blacken and consume a sheet of paper, it's interesting to imagine a cancer burning its way through a tissue. There's an elegance to the way viruses hijack and pervert cells to their own nefarious ends. And so on. I'm not saying that I think diseases are a good thing, or anything that causes pain/death is "nice" or "pretty"; far from it. But can't you see the grace, the sweeping lines, the eye-drawing colors, of those evil amyloid fibrils?

(Having thus far skirted the edge of hell, with these paragraphs I commit my soul to the inferno.)

I'm quite the Douglas Hofstadter fan, and I'm right in the middle of rereading his book Le Ton beau de Marot: In Praise of the Music of Language. In the introduction, Hofstadter dedicates the book to his wife, Carol, who was "hit from out of left field by a strange and eerie malady with the disgusting name of glioblastoma multiforme... vanishing from our midst almost as suddenly as if she had in fact been hit by a bus, with so much of life still left in her... all cut short by some cell gone wrong." Le Ton beau de Marot is in large part a commitment of their shared soul to paper. The book is stimulating, beautiful, and moving; I cried when I read of her death and his grief. I don't mean to minimize any of that. But I have to disagree with Hofstadter on one point. I don't think the name glioblastoma multiforme is "disgusting". "Strange and eerie", yes, and awful and dreadful (in the sense of inspiring awe and dread). But not disgusting. There's even some euphony, some beauty in the sound of the term.

Of course, I say this as someone who has never lost a close and treasured friend or family member to cancer (and I'm very grateful for that!); I certainly don't blame Hofstadter for describing as "disgusting" a name associated with so much pain and grief. His reaction is completely natural; in fact there would probably be something wrong with him if he didn't react that way. You could as well say that I am incapable of tasting all the bitterness as that Hofstadter is incapable of seeing any of the beauty. Nothing wrong with that.

The art of linking

2008-07-15T02:17:00.002-04:00

For some reason I find it really irritating when I'm reading a blog post on some interesting topic, and every third word is a link. Especially when some of them are duplicates* or semi-duplicates (e.g. linking to Foo and also to the blog post that brought Foo to your attention, or to several other people's commentaries on Foo and on each other's commentaries!).

I am generally in favor of Wikipedia-style linkage as a means of optionally explaining terms that may need explaining. Nice and inline. They don't interrupt the flow unless the reader needs them to. (This is less generally true of blog links. On Wikipedia, you know any blue link will take you to a factual description of X. A blog link could point to anything, and you can't always tell from the URL.) Surgeonsblog is very good at this, with links to informative pages that explain various jargon terms.

An alternative strategy is to write easier and harder versions of your post, and let the audience choose -- but I've only seen this well implemented once, in Tailsteak's retelling of a poignant D&D story. Since the story is about D&D, the options to offer the audience are fairly clear: "Never heard of it", "Some familiarity", and "Know it like the back of my hand". Whereas people's understanding of some complicated science thing may not divide itself so neatly into levels**. And it only gets worse if you're discussing two or more topics interweavedly. What are you supposed to do then, write a separate blog post for each permutation?
(You'll notice, by the way, that the main difference between the three versions of Tailsteak's story is that the "Never heard of D&D" variant begins with a paragraph describing RPGs in general; the bodies of the three versions are basically identical. A simple link to Wikipedia might have sufficed, but I rather like the three-versions trick.)

* Some kinds of link-duplicating are good. Mind Hacks is in the habit of duplicating all the links in a post into a little pile at the bottom of the post. This can also be a subtle way to suggest reading the links in a certain order, possibly a different order from how they were presented in the post proper.

** I have another post brewing about being stuck between the level of popular-science writing and the level of professional scientists.

======================

I strive to clarify what all my links are, in the text of the post.

Good: I recently read Lewis Thomas' essay Autonomy, which I thought was a really interesting take on the way our bodies operate independently of conscious control.
Bad: Here is a link to a really interesting essay I read, about the way our bodies operate independently of conscious control.

Notice also the use of Google-friendly link text -- helping Google index things properly. Googling things like "here", "this", "this page", etc. is an interesting exercise.

======================

Here's a more coherent listing of the irritating links from the beginning of this post. They're a selection of random interesting things I've run across in the past week or so.

"Human Guinea Pig" feature on Slate magazine: a Slate writer puts herself in interesting situations for fun and profit. I enjoyed the day in the life of a daycare staffer.

A brilliant and creepy New Yorker article about itching, starring a woman who involuntarily scratched right through her skull.

Three lights in the sky for the price of one: fireworks, comet, thunderstorm. Amazing photograpy.

PDF of Chapter 1 of In Defense of Food, Michael Pollan's new book.

A collection of in-jokes in (mostly) computer books, which has inspired me to look up "self-reference" in the index of any sufficiently geeky book I come across for the rest of my life.

Kurt Vonnegut writes on writing style, with advice that certainly gives me a lot to think about.

Sign of the times

2008-05-23T02:23:00.005-04:00

I finished my last final exam today (woo!!!), so now instead of staying up late studying, I get to stay up late sorting through all my junk and packing some of it in boxes with copious amounts of duct tape -- aka 'packing'. I'm moving to a new dorm on the other side of campus next year, and I'm heading back home to California on Saturday, so I have to hurry up and get all my stuff boxed and hauled across campus before then.

Just now, I was making safety sheaths for a set of cooking knives I bought and never used (because they're mediocre quality, and I just used my pocket knife for everything anyway). Take several sheets of paper, wrap around, duct tape, fold the end over, duct tape again, et voila. It works surprisingly well. For day-to-day storage, these sheaths work fine as is; for longer-term storage, duct tape the knife handles to the sheaths so they don't slip out.

Clearly, though, it is a sign of the times, of the era of online publishing, that I used printouts of PNAS papers to do this. It's the rare, rare paper that I'll print out to read, what with PDFs and having an institutional subscription to everything. Anymore, the only papers I print are ones that I need to read and reread in quite a bit of detail -- say, if I've got to write an essay that addresses the content of that paper specifically. (Intro Psych, I'm looking at you!)

Yes, kids, science saves lives! It keeps you safe! Were it not for science, how would I keep myself from being slashed up by kitchen knives??

Gallery of nudibranchs!

2008-05-15T20:24:00.003-04:00

Check this out: National Geographic nudibranch photo gallery. It's absolutely amazing.

I've seen a couple of nudibranchs underwater, scuba diving in Hawaii. It's neat to see them live and in context, but it being underwater, it's kind of dim and the colors are washed out. Seeing them in optimal photography conditions like this is really cool.

[h/t Pharyngula]

Grad students declared "security threats" by govt

2008-05-09T12:38:00.004-04:00

You have got to be kidding me.

This article, Government Declares Some Grad Students Are ‘Security Threats’, appeared in today's issue of The Tech (MIT's student newspaper). A number of international students working with the Woods Hole Oceanographic Institute are being denied easy access to the ports they sail from because the government considers them, for no reason at all, "security threats".

To get in and out of the ports, you need this RFID card, the "Transportation Worker Identification Credential". Without the TWIC, it's very difficult (though not impossible) to get in and out. Difficult-but-not-impossible is a totally unreasonable restriction to impose on these researchers. It's hard enough not having key-card access to the building that contains the lab you're interning in -- *raises hand* -- and even though it's reasonable to expect a bit more difficulty when you're doing fieldwork, it's not Antarctica these students are requesting easy access to, it's a port. And, I might add, these students are only asking for the same access that their labmates and PIs already enjoy.

As the Dept. of Homeland Security wrote to one student (others received similar letters), “I have personally reviewed the Initial Determination of Threat Assessment, your reply, accompanying information, and all other information and materials available to the TSA. Based upon this review, I have determined that you pose a security threat and you do not meet the eligibility requirements to hold a Transportation Worker Identification Credential (TWIC).” This is what we say to students who come here to carry out government-funded research? We give them grant money and then call them "security threats"?

Two of the students being denied access are from Britain and Germany. Britain and Germany. I thought we were supposed to be all buddy-buddy with these countries? If this is what students from friggin' Britain and Germany have to deal with, how much worst must it be for students from, say, Syria?

My friend Raffi, who's from Canada, mentioned how the Office of International Students is always warning them about how "if you do this you'll get deported. If you do that you'll get deported." Apparently the definition of "security threat" bears this out: you're a security threat if you threaten national or transportation security, if you pose a threat of terrorism, if you have "lacking mental capacity"... or if you simply have the wrong kind of visa.

I'm ashamed to live in a country that funds scientists and then treats them this way.

[Crossposted to LiveJournal]

[Buddhism|Hinduism|Catholicism|*ism] is the new black

2008-04-28T21:13:00.002-04:00

Cosmo: "Choosing a religion is like choosing a MySpace wallpaper"

...WTF?

In what sense can religion meaningfully be chosen? Ideally, everyone discovers what they believe when they look at the world around them and come to an incontrovertible conclusion. Of course this is not going to happen. Conclusions change, and it's impossible to be 100% sure of anything, given the fallibility of human minds. And for a lot of people it's going to be too much work to really figure out what they think, rather than just hopping onto the nearest appealing ready-made philosophy.

[...Ok, I'll bite. I am a hard agnostic: I believe that the nature of deity is both unknown and unknowable. (I used to be a soft agnostic -- wasn't sure whether nature of deity was knowable or unknowable). I believe in questioning but remembering the limits of our understanding, and retaining a sense of wonder.]

I'm honestly not sure what to think of this article (other than the obvious "oh, look, more dreck from Cosmo").

I loathe the aspect that promotes religiosity for appearances' sake. If you're going to take "a shot of Catholicism, a sprinkle of Buddhism, a pinch of Hindu teachings — or whatever else you're in the mood for that day", why even bother? All you're doing is quote-mining to justify what you already (want to) believe. Practicing confirmation bias. Enough of that: just believe what you believe, and stop gilding it.

I'm all for the aspect that promotes having your own worldview, instead of blindly accepting whatever some robed old guys with books say, or whatever your parents said. Anything that promotes seeking and questioning is a good idea.

In the same vein, I'm all for anything that diminishes the absolute blind fanaticism with which a lot of people follow their religions. Even if you simply accept a pre-made worldview, there's nothing that says you need to accept it to the extent that you need to go kill people or spread malicious lies and hatred because of it. But I hate to like the Cosmo article simply for this reason. There is something wrong with the world if Cosmo's viewpoint is the lesser of two evils.

Trivia-heap syndrome

2008-04-25T21:52:00.001-04:00

Part of the reason I think a lot of hard scientists look down on biology is that introductory biology is so often poorly taught in a particular way. Intro physics is almost entirely problem-solving, and intro chemistry is similar, with maybe a bit more memorization (Quick! How many valence electrons does aluminum have?). But biology frequently ends up being taught as a large heap of random terms and facts, almost entirely without any unifying themes or methods of thought -- just a disconnected jumble.

I've dubbed this "trivia-heap syndrome".

Any biologist (or, hell, anyone who's gotten past the required intro course) can tell you that biology is not about memorizing terms and facts, any more than physics is about blocks sliding down inclined planes. But as Chad Orzel says in that post: "To some degree, this is inescapable-- those repeated exercises are used to establish a pattern of thought that is a necessary prerequisite for moving on to more interesting material." A similar thing could be said of biology: to some degree, it's necessary to memorize a lot of terms and random facts and unconnected processes and so on, before you can get to the interesting work of studying how they interact and how they can be manipulated.

But this is actually true of every field, not just biology (or other fields prone to trivia-heap syndrome); it's just not as apparent. Consider intro mechanics again: all about things falling, hitting each other, rotating, etc etc. In order to do interesting things, you first have to know what balls, rods, strings, pulleys, blocks, inclined planes, and gravity are. You also have to understand the basic types of things they can do: move, rotate, accelerate, come into contact, break, exert forces on each other. Of course these are trivial things to know, because we've all been exposed to simple objects and their motions since we were born -- and this is why intro mechanics courses don't begin with a couple weeks of definitions and memorization. The only difference between that and biology is that we're not exposed from birth to genes and proteins and cells and their interactions. The world teaches us the trivia-heap for physics, but we have to be taught about biology's trivia-heap.

All right, so the trivia-heap is an unavoidable evil whenever you're starting in a new field. Fine. But never fear, there are still ways to get around trivia-heap syndrome. As soon as you know a very few things, you can start thinking about them in terms of experiments to be done and puzzles to be solved, instead of facts and descriptions. What would happen if this particular thing were mutated in this way? What effect would that have on the cell? How could you (the experimenter) tell that this was in fact the case? What if you got the opposite observation -- what might have gone wrong? Here's a simple system you're interested in; outline an experiment to find out whether this particular part of it works this way or that way. This is both interesting and a lot more like what actual biologists do; certainly much more so than the typical dreck of "Define a gene", "Outline how a gene gets translated to protein" that most high-schoolers get shoved down their throats. That's lazy teaching for you (or the creeping horror of bad standardized curricula for things like AP tests, which reduces to the same thing).

I learned a decent bit of biology just by reading random things. I can practically recite The Cartoon Guide to Genetics, by Gonick & Wheelis (that link is to the updated edition, not the old-school edition I read). I also took an introductory class at one of those academic summer camps. The net result was that I came into my high school biology class already knowing about half the stuff we would cover, which just made the trivia-heap syndrome that much more painful. A lot of my classmates struggled with memorizing things. Very few people did well on the "lab practical", in which we had to plan and carry out experiments to identify a mystery substance -- precisely because we spent so much time on trivia-heaping and so little time on problem solving / sensible experiment design. MIT's intro biology course (7.013), by contrast, is like a breath of fresh air. It's not entirely free of trivia-heap syndrome, but there's a gigantic emphasis on solving puzzles, considering what-ifs, proposing experiments, and interpreting results. (`Gigantic' emphasis relative to other intro biologies, of course.)

Granted, even MIT's intro biology problem-solving is simplistic, and occasionally feels like doing an inclined-plane problem in physics (especially when I know a decent bit about a particular system, and I can tell the problem vastly oversimplifies the situation, even if I don't know exactly how). But now we're back to Chad Orzel, inclined planes, and "establishing patterns of thought". There is a certain intuition of biological ways and means, of how cells/genes/proteins work in broad strokes, that is immensely valuable but hard to obtain. This intuition is something like a toolkit of abstractions over specific examples, but I'd venture to say it's not something that can be taught explicitly in the abstract, the way math can. The analogous thing in physics, again, is something the world teaches us from birth: unsupported objects fall, if you push something its speed changes; that sort of general idea about how things operate. I've developed my biological intuition somewhat, through reading and studying (and sometimes working directly with) boatloads of examples, and I think that's just about the only way it can be developed. But it's something every experimenter (or bioengineer!) needs in spades, and it's something the general public could also really use.

So, to sum up: the trivia-heap is sometimes a necessary evil, but trivia-heap syndrome is eminently avoidable. Emphasize puzzle-solving and experiments, instead of facts and definitions, and it'll do everyone a heap of good.

Ah, greenery

2008-03-16T03:21:00.002-04:00

If you had ten (soon to be eleven) plants to name after scientists, who would you name them after?

[I've counted the twin bamboo shoots as one plant because I've got them tied together like those ones you see in Chinese kitsch stores -- and thinking of naming them Ramón y Cajal.]

But is conlangery useful?? [Linguists and Conlangers, part 2]

2008-02-06T00:16:00.000-05:00

Yes, it's been quite a while since the first installment of this series. I wrote a whole big long draft of this post and then realized it was mostly wrong, and it took a while to get back on track.

First off, I am not saying that conlangers are oppressed or shunned or anything by academic linguists. Far from it. It's often said that conlangers have a "persecution complex" in this arena -- i.e. we're whiny little geeks. If anything, conlangers get more friendship from linguists than from the general public. That said, most linguists don't exactly brim over with warmth and welcome for practitioners of the secret vice. Conlanging is typically regarded as a kind of silly little hobby or diversion: nobody cares that much as long as you don't let it interfere with your work.

I will admit that there is one anti-conlanging argument that stings me and makes me feel guilty: "Why aren't you out in the field, saving dying languages? You're squandering your talent, skills, interest, and time!"

This argument seems a lot more valid than its generalized counterpart, "Why aren't you working against Great World Evil #42373?" Linguistics interest and expertise are relatively thin on the ground, so it's harder for the cause of saving dying languages to get enough resources/people behind it. Conlangers are often so interested in linguistics that they pursue their interest even when it harms other aspects of their life. Not for nothing do people call it addictive.

But seriously? Firstly, most conlangers just don't have as much spare time as people seem to imagine. Secondly, and more important, most conlangers don't have the expertise to do linguistic fieldwork. A goodly number pursue linguistics in college, but you need a lot more than a bachelor's to do fieldwork. I only know of two conlangers who are linguistics grad students (undoubtedly there are more, but not many more). Most of us have day jobs. We're hobbyists. Would you want model-airplane hobbyists fixing fighter jets?

The other main arguments against conlanging are that it's frivolous, pointless, a waste of time, etc. And for this I can't do better than to point you to The Conlanger's Manifesto, by David Peterson, which eloquently defends conlangery as an art form:

...Looking only at the utilitarian end of it, if the creator isn't going to use his/her language for communication, and since language can be viewed only as a means of communication, language creation is pretty useless.
But is this all language is: A method of communication? If so, what is poetry? what is literature? What possible use could James Joyce's Ulysses have? I suppose if you were on a desert island and needed to smash crabs, it would do the trick—it's pretty thick, after all. But beyond that? According to them, it would have no use. And why stop there? What good do paintings do anyone?...Pretty soon what you're left with is a world without art.
At this point, the argument should come to an end. The rigor and usefulness of art is an argument that has been argued many times by many people much more articulate than I, and by now (I certainly hope), the whole world should have figured out that art really does pull its weight on Earth.

Amen, brother. Conlangery is the art of linguistics, and it should need no more defense than that.

Occasionally, you'll run across linguists actually using conlangs. If you're teaching a linguistics course, occasionally you may want to illustrate some particular concept by using a conlang. That way, you can design the conlang to show off the feature to its best advantage, and avoid all the irrelevant noise/irregularities that you'd get if you used a natlang. It's the same principle as medical illustration: realistic, but with all the fat trimmed away. Just try and find an illustration that shows the pancreas without trimming away a whole load of other viscera! It's damn near impossible. Conlang examples serve the same purpose in a linguistics class. The goal is transmission of key information, not pinpoint-accurate naturalism.

Another, less-used, possibility is to have students create a miniature conlang that exemplifies a particular feature. I've seen a worksheet that taught the basics of ergativity very effectively this way. Unfortunately, it wasn't from an actual linguistics class. It was from a presentation at the 2nd Language Creation Conference. Er, I mean, a presentation that never took place (it was sacrificed in favor of another panel discussion due to time constraints): "Applications of Conlanging in Pedagogy". You can see the worksheet on page 13 of the PDF of the program. I can't genuinely speak from the perspective of a student, because I already knew what ergativity was at the time, but I really think it would have been very effective as a homework assignment, because it gets you actually working with an ergative system.

But the most interesting intersection of conlangs and linguistics, in my opinion, is in the domain of research. A lot of studies have come out recently, where people are exposed to a small conlang and then their learning success is tested and studied. This is a really exciting paradigm, because you can engineer your language to have certain traits in the area you're interested in, and to be `normal' or `easy' in all other areas. If you're testing acquisition of (say) verb-subject-object word order (English is subject-verb-object), you can make your language have perfect consistent VSO order and be completely unremarkable in everything else. Good luck finding a natlang that fits that bill. It's the same cutting-out-the-noise principle we saw earlier.

Or, if you want to put in noise and study how people will deal with it, you can manipulate the type and amount of noise to a very high resolution. Likewise with (say) syllable-transition probabilities in a word-segmentation study (if ba is always followed by ka, but ka is followed by a whole lot of different things, you can deduce that fooBAKAbar is the words fooBAKA and bar, not fooBA and KAbar.)

I'm currently involved in a research project using this paradigm, and I think it's an incredible tool. Look out for a lit review in the near future!

There are some conlangers who would like to see descriptive research done on fully-fleshed-out conlangs. And I hate to say this, especially because I'm good friends with this crowd, but I disagree. I don't think that investigating and describing conlangs can tell you much about the range and properties of human natural language. (Most academic linguists, I think, would agree with me.) To find out anything about human natural language, you ought to study human languages that have evolved naturally, instead of ones that were consciously invented. You can make a conlang with any conceivable twisted logical structure; the structure may be possible, but that doesn't mean it would ever evolve naturally, or that it's reflective of anything in natural language.

But since conlangery is the art form associated with linguistics, you could do the same sort of humanistic or aesthetic studies that you do on paintings (the art form associated with vision science). What do people find elegant or appealing? What conlang properties elicit what subjective reactions? What bizarre structures have what bizarre effects on people trying to use the language (the linguistic analogue of optical illusions)? And this could have implications in the study of natlangs.

Next up: the learn-a-conlang paradigm in language acquisition research.

My Erdős number is 5

2008-01-31T13:40:00.000-05:00

Back in high school, when we got around to it (about once a year) the Neighborhood would publish an issue of the Menlo Math Magazine. It was sort of a random collection of real-world-relatedness, whimsy, and interesting problems. Not an academic publication by any standard. But that didn't stop us all from facetiously claiming an Erdős number of 6, when we heard that Mr. T's was 5.

I just found out that mine is actually 5, and this time it's damn near official, not tenuously based on a high school pamphlet. Over the summer of 2005 I worked on the Stanford ALL project. Mostly as unpaid labor, admittedly, but I did sit in on the meetings and I did point us to a couple of valuable data sources. This meant I got to interact with some big names, however briefly.

According to Language Log, the lowest Erdős number known for a linguist is 2, and Geoff Pullum's is 3. A quick Google Scholaring shows that Arnold Zwicky and Thomas Wasow, therefore, have Erdős numbers not greater than 4. And they were both involved in the ALL project, as was I, which makes my Erdős number not greater than 5.

...All right, none of us are actually authors of the paper in question. I appear in the acknowledgement footer on the first page, along with the other students involved in the project. But Zwicky and Wasow appear in the same footer, as does John Rickford (who doesn't have any papers coauthored with Pullum, at least on Google Scholar). (Well, OK, all those big names appear in the references, which I don't.) Their contributions to the project were certainly substantive enough to qualify criteria for what counts as `collaboration'. My contributions were far less substantive, but I still think they counted for something, and if I appear in the same acknowledgements (the same parenthesis in the acknowledgements, even), that's got to be worth something.

(Naturally, this all comes with the caveat that we've been counting non-strictly-mathematical publications, but that has plenty of precedent.)

It makes a fella proud to be a scientist

2008-01-23T10:48:00.000-05:00

Pharyngula linked to this amazing video that "compares creationism and science". Really, it's no comparison. [3:54]

You could watch it without the music -- none of the strictly visual beauty would be lost -- but instead, I highly recommend turning your speakers up to eleven, putting the video on fullscreen, and inviting all your officemates to come watch. Better yet, invade a conference room or a lecture hall for five minutes. It'll be worth it.

I found it incredibly affecting. Some parts had me cheering and yelling "SCIENCE: IT WORKS, BITCHES!". And some had me tearing up. I felt like a little kid again, all "when I grow up I wanna be a scientist!" I'm damn proud to be a part of it (or at least to be on track to become part of it).

Math lagging (or leading) physics

2008-01-21T20:38:00.000-05:00

Senior year of high school, I took AP Physics C and AP Calculus BC concurrently: allowable, but not advisable, the admins said. For a good part of the year, I struggled with physics because I hadn't `really' learned the math yet. Reading the textbook, I'd just skip over derivations that I didn't understand, and hope that the end result was something I could memorize, if not comprehend. Mr. T held a session or two of `physics math', which helped a little, but didn't make me feel less intimidated.

Last semester, I was in pretty much the same situation, only with line and surface integrals instead of all integrals. Oh, we never had to evaluate any -- they were always of the simple kind that reduce to multiplication problems -- but it took several tries to be able to recognize those situations, and remember how to reduce them to multiplication problems. Didn't solve the intimidation problem, either. On the final exam, even though I knew what to do and how the problems worked, I still felt like a trespasser for writing down those fancy-schmancy closed-surface double integral signs, knowing I didn't really know how they worked.

At one point Prof. Hudson said something (can't recall the exact words) that gave the impression this math-lagging-physics business was a dreadful intractable plague, oh me oh my, whatever shall we do. And at the time, struggling to understand everything, I was rather inclined to agree with him. But since then I've somewhat reversed position, or at least become neutral.

Back in high school, after I'd learned to fudge my way through integration, I had a much, much easier time with it when we `officially' learned it in math class. This was especially noticeable in the case of integrating (still in a single variable, though!) over 3D objects. We'd been doing this routinely in physics, to find the moments of inertia of various shapes. So while the rest of the calculus class was struggling to put together the relatively new concept of integration with the relatively new concept of bizarre-shaped objects in 3-space, I could relax.

Recently (within the past two weeks), the same thing happened for me in multivariable calculus. I'm in 18.01A/18.02A, which is a blend of two courses: a quick six-week review of single-variable, and then the regular multivariable curriculum, finishing over the January term. Because of the way things are timed, I never saw a line integral in 18.02A until just now, well after the end of my physics class. And the same thing happened: I'd learned to fudge my way through easy line integrals, and that gave me a leg up on people who'd never seen them before. I had a well-developed intuition about what line integrals meant in terms of the real world, which kept me from getting confused. That in turn allowed me to focus on the complicated aspects that we hadn't worked with in physics.

Given these experiences, I don't think it's a very bad thing at all that math education tends to lag physics education. It can often be a good thing: physics is leading math, to frame it positively. When you tackle something complicated and abstract, having `live-fire' experience with simple cases and workarounds can hardly do anything but help.

This comes with some caveats. It's a classic example of delayed gratification: I sure didn't feel happy about math lagging physics when I was actually struggling with the physics, and it was only a month later that I was able to grin to myself in calculus recitation, watching the people around me struggle with a problem I'd found obvious. (Schadenfreude, too, is not necessarily a good thing. In my defense, I do help my peers if I can, and if they're not already being helped.) And naturally, it's a tradeoff; who can say if knowing the math beforehand would have brought my physics grade up a little?

But most importantly, if physics is going to lead math, physics has to be taught right. I approve very strongly of Prof. Hudson's philosophy here: conceptually difficult problems with easy math = win. If you absolutely must be bashing your head against the wall at midnight the night before the problem set is due, it shouldn't be because you can't solve a differential equation. It should be because you can't figure out which way the induced current goes. Physics can be taught adequately without using too much complicated math (though of course the definition of `complicated' will vary with the physics). You learn just as much integrating (read: multiplying) over a sphere as you do integrating (read: flailing) over the surface of some crazy-shaped thing.

You wouldn't expect it, but knowing too much math can be a problem. Last semester's physics class was taught in a rather unusual format, about which more later. The relevant thing is that I spent the whole time in a group of three. There was me, there was S, and there was L. S had excellent intuition, and tended to approach problems by thinking them through qualitatively first, and then seeing if the math bore him out. This was really a very effective strategy -- a lot of the time the math looked right, but his intuition cried foul, and then we found the sign error twenty steps back. L, on the other hand, was advanced in math, and already pretty far beyond what the physics course used. She approached problems very mathematically, instead of with intuition like S. Even when something made complete physical sense, she wasn't satisfied until she justified it mathematically -- even if it was a qualitative problem and didn't have any equations in it to begin with. and because of how every other thing is backwards in E&M, she tied herself into an awful lot of knots. (Not that she wasn't brilliant; I think she outscored both S and me on every test.) L and S complemented each other, and they were a great group to work with. But I have to say that S's intuitive method was the more effective. To the same question, S might answer "because the charge is over here so the potential is higher here, and then this happens"; L might answer "because the potential is [insert equation here] and the electric field is the negative gradient of the potential."

I admit that this is based on my own experience, and what's better for different students will vary. I said that it's easier to learn complicated abstract math if you've first grounded it in physics; you could just as well say that it's easier to learn physics if you're well practiced with the mathematical tools already. But I think the first argument is more valid than the second. It's easier to abstract from the concrete than it is to learn the abstract first and only then get concrete examples. You see the same thing in computer science classes: pick up a copy of the blue wizard book and on every other page you'll find a discussion of how to abstract some instance, not how to instantiate some abstraction. Even though physics was made genuinely more difficult by not knowing the math, I'd still rather have done it this way around.

Briefly on Sitemeter and privacy

2008-01-21T16:55:00.000-05:00

For the sake of full disclosure: yes, I have a Sitemeter on this blog. It's the free version, which means I can't see anyone's full IP address (just the first three numbers). I can, however, see your location, your ISP, a crappy estimate of your latitude & longitude, what page you came from, and what page you exited to (sometimes; this last one seems to be borked).

I have it on the "medium" privacy settings, which means that all those details are not visible to members of the public, but that certain stats may be given out to indexing sites -- the textbook example is giving out the hit count to a service that ranks sites by number of visits.

I'm not all that interested in most of the information that Sitemeter collects. I mostly have it as a hit counter, not anything fancier. I do get a kick out of seeing what random cities people are visiting from, or what random Google search terms bring me up in the results. It's rather annoying that Sitemeter's privacy options are pretty much all-or-nothing: I can't allow members of the public to see, e.g., just the Google search terms or just the geographic locations, without giving them everything, including partial IP addresses. Grr.

But at some point I think I'll compile a list of the more interesting Google search terms that bring this blog up. Might be amusing.

Feeling a teacher's love

2008-01-18T20:45:00.000-05:00

In high school, we had a teacher, Mr. T, who taught computer science and some of the advanced math courses. And he was wonderful. Everybody loved him. I've never encountered so much infectious enthusiasm, even at the ungodly hour of 8am on a Monday morning. He could light us on fire by drawing box-and-pointer diagrams. We had a party the day we learned the Fundamental Theorem of Calculus. Mr. T was a mentor, a friend, a father, a rock; his room was a haven for geeklings. Everybody loved him, and he loved us too.

I understood his love in a rather abstract sense back then, and up until this morning. But this afternoon, I understood it from the inside.

The research I'm doing at the moment involves teaching pairs of people a constructed language by immersion, and then having them take a test. (More details on this (very interesting) paradigm in an upcoming post!) Today was only the second time this experiment has ever been run, so I'm also happy just because it worked. We ran two pairs of people.

I had an awfully hard time teaching the first pair. They just seemed to fundamentally not get a lot of the grammar. It was very difficult to keep myself from grabbing one guy and telling him, loudly and in English, that "the way to turn a sentence into a question is NOT just to say the sentence with a rising intonation at the end!!!". And so on, and so on. Teaching them was frustrating, occasionally painful.

And then the second pair came in, a pair of undergrads, and they more than made up for the first pair. It only took them twenty minutes to get to more than adequate proficiency, where it had taken the first pair almost an hour to get to less than adequate proficiency. They seemed to pick everything up right away. It was like watching a rose bloom in time-lapse. My favorite moment was when I taught the question form, using only one verb in my examples. When I prompted one of the participants, she immediately came up with several correct question-form sentences, and she generalized to all the verbs we'd learned, not just the one I demonstrated with. If we hadn't been in an experiment, I might have proposed to her on the spot.

I graded the four tests just now. The first pair had decidedly mediocre scores, no surprise there. But the second pair did extremely well, and they both did just about perfectly on the part we're most interested in. I was overjoyed to see them using linguistic terminology correctly to explain their answers (even though their knowledge of terms had nothing to do with how well they acquired the language). When I was done grading, I spontaneously picked up the last test and kissed it.

Tonight, I think I experienced a little of what made Mr. T such a good teacher, what made him love his students and his work. It's not an easy feeling to articulate. Pride and joy in students, enthusiasm for the subject, and a little bit of self-satisfaction that, yeah, I taught them that. The feeling was very powerful, even though the teaching I did today wasn't very real. What if I were teaching material that was beautiful and meaningful, instead of an arbitrary constructed language? What if I could teach for an entire semester and witness long-term progress and synthesis, instead of bidding goodbye after an hour? What if I were teaching students who learned for love of the material, not because they were paid to be subjects in a study?

For the record, this is not the first time I've taught, nor the first time I've found it satisfying. For a couple of years I tutored 6th graders in math and Japanese, and it was always great when they'd get a flash of insight after a long hard slog. (They were remedial students, so it wasn't often.) And in the Karate club, it's traditional that you help teach the people who rank below you. I was co- leading brown belt my senior year, so that meant I taught just about everybody. I always enjoyed seeing some yellow-belts perform a technique really well, and thinking "Yay, they remembered X subtle point I taught them about!". But I've never felt a teacher's love as strongly as I did today; certainly not strongly enough to merit using the word `love'.

If I follow the track I'm planning to follow, I'll end up a professor. I understand that teaching is mostly tedious, frustrating, and difficult, not full of brilliant-student-love. But it's the possibility, the hope that springs eternal, and when it's fulfilled it makes up for everything else.

Problems with the LJ feed

2008-01-08T00:10:00.000-05:00

I recently made some minor edits to "my experience with lab mice", and everything seemed normal. But for some reason the LiveJournal feed saw fit to repost the entire post, clogging up people's friends pages. Meep, sorry!

Funny thing is, this didn't happen anywhere else. The native feed is normal, the blog itself is normal. Only on LJ did the post show up again. And apparently there's no way to go into an admin panel and fix this; it's fully automated. Grr.

Black vs. white backgrounds (also, chalk)

2008-01-07T01:06:00.000-05:00

(No, this post is not about race).
The other night, I and my friend 4pq1injbok were discussing the compelling, overarching, enormously important issue of black text on white ground vs. white text on black ground. (Woo, having spare time!)

Of course, each option is appropriate in different contexts. If you're printing something out, you better have a good reason to do it in white on black, because that wastes so much ink/toner. But for viewing on screens (including projection screens), I vastly prefer black on white because it reduces glare and seems to make my eyes less tired. Mostly the former. Glare is a problem especially on very large projection screens: you can dazzle (in a bad way) an entire lecture class with a white-backgrounded Powerpoint, especially if the projector is having an off day. Not fun early in the morning.
What troubles me, then, is that there seems to be some kind of unspoken rule in academia that you can't use black backgrounds, and I'm not entirely sure why. I watched a dry run of a job talk a couple summers ago, and in the midst of everybody commenting on every facet of every slide, my mentor explained to me that there's just a certain way scientific presentations are done, which includes black text on white ground. The Google example is telling, in one sense -- Google is renowned for the "clean" look of its pages, which I'm sure has a lot to do with being white-backgrounded. Perhaps there's a lot of pressure from older academics who are more comfortable with print on paper. Perhaps, also, it makes pictures easier to see, but you can fix that with a relatively narrow white border. I think we should take a hint from the movie industry; when was the last time you saw the end credits in black on white?

(Also, using black backgrounds probably saves energy -- I don't know any numbers, but the savings must be considerable for large screens. There's even Blackle, an almost entirely black version of the Google homepage. Supposedly if everyone used it, we'd save ~750 MWh a year (hat tip for the calculation to ecoIron).)

Chalkboards are the only common medium I could think of where the default is light text on dark ground. (Not to say there aren't others; it's just that I couldn't think of them.) Nothing profound about it; chalkboards are this way because CaCO3 is white, and slate is dark gray. But it does raise an interesting question. Suppose you draw two circles on the board, and fill one in with chalk while leaving the other one empty. Which is black, and which is white? Do most people just seem to naturally agree, or is there some kind of consistent convention, or is there no consistency at all?
In my music theory class, and anywhere I've seen musical notation on a chalkboard, the convention is that quarter notes are filled/white while half and whole notes are empty/black. In print, it's the other way around, at least with regard to absolute colors. But in this case, you can define it in terms of filling, not color, so it's a bad example. I'm rather tempted to crash a game theory class on the day they discuss chess/checkers, or some kind of visual arts/design class on the day they discuss positive vs. negative space, or take a poll of professors, or some such.
Related linguistic issue: on the Improbable Research blog, a prof rants about the suckiness of Crayola's new chalk, complaining that "the new pieces are thinner, shorter, and don't write as dark", using "dark" to denote degree of whiteness. But "don't write as well" lacks specificity, and "don't write as lightly" would be interpreted the wrong way around. Sounds like "heavily" (or perhaps "cleanly") might be the way to go.

And finally (and randomly): hooray for profs who know how to use colored chalk well, to highlight information and obscure noise, without overusing it. More on this subject if I ever get around to reading Tufte's books.

Finals

2007-12-17T11:21:00.000-05:00

I know it's been a while since I last posted. It's finals week, which means I'm basically studying all the time. I have a bunch of posts in the works,

I just took my first final, physics (8.02, intro electricity & magnetism). I felt really good about that one; everything seems to have come together really well and comprehensibly in my head in the past several weeks. I give the credit to the professor's very intuitive style of teaching and understanding everything, and to his fondness for conceptually difficult questions with easy math. That is how to teach physics, IMHO. (I have a lot more to say about the course format, TEAL ("technologically enabled active learning"), but that's a whole nother post.)

I'm not really so worried about tomorrow, when I have my midterm in calculus (18.02A). I'm in a kind of funnily-put-together course, where you spend the first six weeks reviewing single-variable calculus at high speed, and then follow the regular curriculum for multivariable calculus, finishing over the January independent activities period. It's primarily intended for people who took AP Calculus AB. I took AP Calculus BC and passed the AP exam with a high score, which would qualify me to jump straight into 18.02 (straight multivariable calculus), but at the beginning of the year I felt like I needed the review. I could have done without it, but it was nice to have. The only problem was that it put me farther behind in terms of math lagging physics (a perennial problem), but the math in my physics course is not actually that hard (e.g. all the line or surface integrals we ever have to do are simple cases that reduce to multiplication problems).

The one I'm worried about is chemistry (5.112), on Wednesday. Most of the content on the test will be drawn from the last several weeks of the course, and that's the material I understand the least. The course is taught by two different professors -- one does the first half and the other does the second half -- and the second guy is very difficult to understand, for various reasons which I will elaborate in the future. It's a blessing that it comes last, really; I have about twelve hours this afternoon/evening for studying, and I don't intend to devote all of them to calculus.

MIT really treats its students very well during finals week. There are free breakfasts in all the dorms, as well as one in the lobby of the building where the biggest finals are held. (And not cheapo lousy free breakfasts, either -- good ones. This morning, for the first time all semester, I had eggs and pancakes! It was awesome!) There are a few free lunches and dinners scattered around, and all the food vendors in the Student Center are giving discounts. Alpha Phi Omega holds "Finals Coffeehouse", with snacks in a room of the Student Center that used to be a 24-hour coffeehouse but is now just a sort of miscellany room with tables. MIT Medical holds relaxation seminars, even. This is characteristic of MIT, really: they pound you into the ground academically, and then they reach down and lift you back up...so they can pound you again.

More content to come over winter break. I've got a lot of saved-up commentary on various aspects of the teaching here.

What's This `Conlangery' Business? [Linguists and Conlangers, part 1]

2007-12-09T04:15:00.000-05:00

[This will be part of a series of posts about conlanging and its interaction with academic linguistics.]

So, what is conlangery? It's not a popularly known art, so here's a primer for y'all who haven't ever heard of it.

The word conlang is short for "constructed language". Well-known conlangers include Ludwig Zamenhof (Esperanto), Marc Okrand (Klingon), and the revered JRR Tolkien (who once wrote that he invented Middle-Earth largely in order to give his beloved Elvish languages a place to live). We invent languages: spoken languages, signed languages, artificial siblings and alternative scripts for natural languages, artistic languages, logical languages, international auxiliary languages, mind-extending languages, you name it.

(I should warn you that conlangers, being naturally fond of playing with words, habitually `overgeneralize' and apply all kinds of grammatical forms to the word `conlang'. Just for starters, it's both a noun and a verb. A conlanger is someone who conlangs, what they create is a conlang, and the art in general is conlanging or conlangery. On top of that, the con- prefix has become productive, meaning it can apply to all kinds of invented/imagined things: conlangs, conworlds, conscripts (meaning writing systems, not military draftees), conreligions, consolarsystems, conbiology...the list goes on.)

The earliest known conlanger is Hildegard von Bingen, a 12th century German abbess. She's best known for her gorgeous music, but she also invented a language called Lingua Ignota ("unknown language"), which supposedly came to her by divine inspiration.

The best known conlanger...well, it depends who you talk to, but most people will name either Zamenhof or Tolkien, and here we come to a major split in the world of conlangery: that between auxlangers and everybody else. Auxlang is short for "international auxiliary language", and not to make any sweeping generalizations here, but the sort of people who make auxlangs are also the sort of people who have fiery and/or highly unconventional political agendas, and a lot of them are also shamelessly self-promoting. Unfortunately, if you're auxlanging in earnest, this isn't really fixable. You have to want the entire world unified, in some sense, by your language. And you have to think your language is not only `good' enough for everyone in the world to speak, it's `better' than the dozens and dozens of old failed auxlangs. A certain amount of crankery is inherent to the practice of serious auxlanging.

(Quite apart from the above, the vast majority of linguists and conlangers have a horrible visceral reaction to the thought of losing most -- if not all -- of the world's linguistic diversity. Who wants to replace all that culture, knowledge, and sheer beauty with something necessarily bland?)

(Yeah, and, in case you couldn't tell, I'm totally biased, and I freely admit it. Auxlangs are not all bad; any conlangery effort bears some useful fruit.)

So what about the `rest' of the conlangers? People conlang for all sorts of reasons, but the one that really unites us is, trite as it sounds, is love: love of language, its beauties, its intricacies, its elegances; and love of playing around with that in systems of our own creation.

This is not to say that there aren't divisions within the body of non-auxlangers. Probably the biggest group is the artlangers, like Tolkien, who conlang for aesthetics and elegance. (This is not to say that all artlangs end up looking like Tolkien's Elvish languages, all full of L and R and vowels everywhere with nary a `guttural' consonant. Conlangers have as much variation in taste as the general population. Plus, for example, there's a lot to be said for a language in which you can swear effectively. Imagine trying to shit-talk someone in Quenya or Sindarin.) At the very least, many hundreds of artlangs have been made, or at least started. My own language Tlharithad is a young artlang, though I sadly haven't had time to work on it since the beginning of the semester. You can find quite a few well-developed artlangs, associated with the fantastic conworld of Verduria, at Virtual Verduria, made by Zompist. I have to apologize to the many, many, very worthy artlangers that I haven't linked to, but for non-conlangers, Zompist's work makes a good place to start.

On the flip side of the same coin, you have the engelangers -- engelang is short for "engineered language" -- who design their languages to achieve a particular goal. There are logical languages, like Lojban, which are designed to eliminate ambiguity. And there are other engelangs, whose design goals don't really fall naturally into groups. A seminal example is Ithkuil, which has about five times the information content per syllable of natural languages. In the words of its creator, John Quijada, Ithkuil is "systematically designed to blend a high degree of communication of cognitive intent and meaning with a high degree of efficiency, i.e., to allow speakers to say a lot in as few syllables as possible." While I'm not intimately familiar with the language, I know the making of Ithkuil involved a lot of mindbending reorganization of cognitive concepts. For example, if you're indoors, the spatial axes around which you organize your speech are placed with respect to the long axis of the room! (Of course, JohnQ freely admits that Ithkuil is extraordinarily difficult to learn, and has in fact created a somewhat simplified version, called Ilaksh, for those of us without superhuman vocal tracts.)

It can be argued that artlangers are just engelangers whose design goal is that of beauty, rather that something more conventionally associated with the words "design goal". It's a little like the distinction between architects and sculptors: you have people who are clearly one or the other, people who are mostly one with a little of the other, and people like Michelangelo or Maya Lin who straddle the boundary so well that no one ever finishes arguing about which category they fall into. (And, as good linguists, we have no problem with this, knowing that strict definitions are artificial constructions, and everything is better described in terms of generalizations from prototypes.)

Next up: the enmity, such as it is, between conlangs/conlangers and professional linguists / linguistics research.

Another essay on killing lab mice

2007-12-06T20:58:00.000-05:00

Ran across this essay, which aired on NPR's All Things Considered five years ago. I especially liked this bit:

When I started, sometimes I had to go walk around the lab building afterwards to take a breath and gather myself. Now it still upsets me whenever I have to kill mice, but I'm used to it. I think that probably some scientists do get over it completely; the mice become tools. Other scientists hire technicians to handle and kill the mice. The researcher works with the cells of the mouse once it's killed, but never encounters the living mouse.

But that's not how we do things where I work. In fact, the people I get along with best in my lab sometimes even talk to their mice. While we're herding a mouse towards one side of a cage or another we might say, "Come on, sweetie." Maybe if we're injecting a mouse with something and it squirms, we say, "OK, OK. It's going to be just a second." When we put it back in its cage, we might say, "There you go." And while the mouse is sniffing and inspecting its cage mates, we say, "There's your buddies." I was in the mouse room with a colleague of mine and I noticed her doing this. And I said, "You talk to your mice, too." She said, "Doesn't everybody?"

It really captures the tension between mouse-as-tool and mouse-as-animal. And the -- well, I don't want to call it a happy medium, but the medium that most good scientists find. I dare say that working exclusively with cells, and never encountering the organisms they come from, has got to be dissociative. Seems like it'd be a good idea to keep that perspective in the back of your head, that these little spots in a dish came from a living animal, and serve multifarious purposes in that animal, and do things besides sit in culture and express your marker protein or what have you. They grow, they thrive, and above all, they are more complicated than they seem, even when you take that last into account.

A scientist who gets too debilitatingly upset over the death of a mouse will never get anything done, and a scientist who doesn't care about the mice as living creatures will have less perspective and, in all likelihood, get worse results for not being personally involved with their care.

I don't recall ever talking to the mice, but I didn't handle them all that much. Pretty much all I did was scruff and snip, and then they couldn't listen anymore. If I have to do more involved mouse procedures in the future, I probably will get in the habit of talking to the mice, especially given that I already even talk to inanimate objects when I'm working on them.

Stir-fried wikipedia, anyone?

2007-12-06T15:33:00.000-05:00

The highly estimable Language Log points out yet another instance of Chinese menu translator ingenuity. Wikipedia: now with even more uses!

For more on this phenomenon, see Engrish.com (marginally NSFW), which is devoted to collecting this sort of unintentionally hilarious bad English, mostly from Japan. Aside from just giggling at the bad translations, it's interesting to occasionally catch a nugget of linguistic insight. Well, I mean, the fine folks at Language Log can catch them all the time, but I'm an amateur, so I have to take what I can get.

A while ago, Engrish.com featured a shirt (which I unfortunately can't seem to find now), bearing the sentence "We are dumb and haven't intelligence apes." And I jumped out of my seat, because it made perfect sense to me. In English, that sentence means "we are dumb and do not possess apes of intelligence." Presumably the shirt-writers meant "we are apes who are dumb and do not possess intelligence." (Perhaps dumb here means mute rather than unintelligent -- a relatively subtle distinction, but I've seen Japanese<==>English dictionaries that do very well at this. Or, y'know, maybe it's just redundant.)

What English handles as a relative clause, "apes who do not possess intelligence", Japanese handles by effectively turning the verb "not possess intelligence" into an adjective. To say "we are apes who are dumb and do not possess intelligence" in Japanese, you say something along the lines of "we are dumb and non-intelligence-possessing apes", which is clearly the origin of the T-shirt.

Of course, there's also the complete nonsense, e.g. "I smell the smelly smell of something that smells smell", and the grammatically-correct-but-thematically-inappropriate text, a la this classic example.

So, where do animal protocols come from?

2007-12-03T22:56:00.001-05:00

My dad asked, in a comment to "My Experience with Lab Mice", why the accepted protocol is to gas them with CO2 instead of nitrogen. He writes:

Anoxia through O2 starvation is demonstrably painless. Many research pilots go through it, to the point of unconsciousness, and the general comment on recovery is "Did something happen?"
CO2 overdose triggers the breath reflex, which O2 starvation does not, at least in humans.

I did a fair bit of searching, but all I could find was protocols describing various euthanasia methods. I couldn't find anything that motivated them. Sure, I found some discussion of why toe clipping is discouraged, but that's because toe clipping isn't The Method for identifying mice (anymore). CO2 gassing appears to be one of The Methods, if not The Method, for euthanizing a bunch of mice -- hence, not much debate or discussion.
I don't know how many readers I've got, but I'm throwing the question open: who decides what the `official' animal protocols are? (Does it differ if you're a university vs. a company?) How do new methods get invented, approved, and adopted? What happens when an alternative method gets officially discouraged/banned? Where can one go to find out all this information about a specific protocol? And if it's the case that O2 starvation by N2 surfeit is painless, why isn't it The Method?

Gmail, how I love thee

2007-12-03T17:10:00.000-05:00

Forgive me for taking a moment to extol the virtues of Gmail. I appreciate it a lot more since coming to MIT, because I get about ten times as much email as I did in high school. And no, I'm not getting paid for this. But people here complain a lot about the volume of email, and if more people would use Gmail then the amount of sniping would drop five-fold.

Gmail has tags instead of folders. Tags are so much better than folders! I have two major ways I categorize my email: by where it was sent to (me directly, my MIT email account, certain mailing lists) and by why I should save it (it points to a resource, it contains someone's contact info, it's one of those "please retain this email for your records" messages). So, to a first approximation, pretty much all the messages I save falls somewhere on a two-dimensional grid. A lot of messages fall in more than one place, and there are miscellaneous tags, and all kinds of stuff you just can't do with folders.

(I'm always a little annoyed by blog platforms that say things like "This entry filed in [list of tags]". They're just trying to pretend tags are the same as folders, no idea why. Inertia perhaps? Bah! Embrace the tags for what they are!)

Since Gmail has tags instead of folders, to get things out of your inbox you just hit "Archive". This puts the conversation in a big all-purpose bin, and you can find it later by searching for text, tags, or sender.

There's also a really nice filtering setup. For instance, I have all my email from my MIT address forward to my Gmail, and I have Gmail tag it `MITmail' so I know what was sent to where. I subscribe to a lot of mailing lists, and I have many of those automatically tagged as well. One list in particular, the Reuse list (for recycling / handing off old computers, furniture, unneeded coupons, etc etc etc...), gets a lot of traffic, and I don't generally want to see Reuse messages in my inbox unless I've got free time to go pick something up. So I have Gmail do two things: tag the messages `reuse', and archive them directly, so they don't appear in my inbox and get in the way of more important things.

On top of tags, you can also mark converstions (or individual messages) with a little yellow star that shows up by the subject line. This is really helpful because I keep several types of messages in my inbox (instead of archiving them): reminders for events, reminders for things I need to do, and messages I'll need to refer to within the next two weeks or so. Reminders get starred, so they stick out visually and I actually get reminded of them. References don't get starred because I only need them when I'm looking for them specifically.

Probably the best feature, though, is this: Back-and-forth emails with the same subject line are organized into conversations. This is just fantastic. It keeps everything related to one topic in one place, instead of having individual messages in several threads scattered randomly throughout your inbox. You can read an entire thread on one page. If a new message appears while you're backreading the thread, Gmail pops up a little "Update Conversation" box so you don't reply redundantly. And since the whole thread is on one page, Gmail hides each message's quoted text, all the lines that begin with piles of >>>s. And you can delete an entire flamewar with one click. Can't beat that.

I know a lot of people are concerned about the direction Google is headed, or that they will end up "owning all the information in the world". Yes, there are legitimate concerns, but I think the danger is way overblown, and Gmail seriously saves me a lot of time and aggravation. (Are you listening, stupid Yahoo email account that I keep for signing up for potentially spammy things? Grr.)

Ping!...Pong!...

2007-12-03T16:18:00.000-05:00

Many, many thanks to Coturnix, of A Blog Around The Clock, for linking here!

I realize this happened several days ago. I plead guilty of falling out of the habit of checking my Technorati page because nothing ever happened on it.

And, I may as well take this opportunity to apologize for the recent lack of activity. Homework is no excuse; there are lots of people out there who are busier than MIT undergrads (though you'd have a hard time getting some of my friends to agree to that)

[Links Dump] Braille and lolpostmodernism

2007-11-26T00:53:00.000-05:00

Alpha Phi Omega goes to the Braille Press, sticking transparent braille-letter stickers on children's books so that sighted and blind can read together. What a simple, elegant, and effective method!
(I've harbored dreams of becoming a Braille transcriber, but that takes a lot of practice and training, and the Braille Press volunteer work is something anyone can do right away.)
(Also, yes, I am planning to pledge APO next semester, which is now very soon. It's kind of a stupid story why I didn't pledge this semester.)

Meanwhile, Jeph, author of the fabulous webcomic Questionable Content, offers up a great selection of postmodern cat macros and other-noun macros.

Who Pays For My Food

2007-11-20T18:27:00.000-05:00

One of the great things about being at a major research institution is that you can always find work as a guinea pig. There are flyers all over the place, advertising this or that experiment, usually for $10 an hour, which isn't half bad for one-time easy unskilled work. I've been a subject in a bunch of different neuro/psych experiments, and it actually does a decent job of paying for my food. It's not steady work, but there are benefits to that -- I don't have to commit to anything major, it's not very many hours a week, I can schedule it around my own schedule, I get to look at what lots of different labs are doing.

Don't worry, I'm not imbibing dangerous substances while guys in lab coats watch to see if I break out in a rash or something. Most of what I've done involves looking at a screen and pressing buttons. The most biologically involved thing I've done is get fMRI'd.

I like to think of guinea pigging as "learning about experimental methodology from the inside". Reading the Materials & Methods section of a paper is really boring, and it's often hard to get an idea of what an experiment was actually like. Now that I've been through a bunch of experiments, I'm developing a sense for what a protocol will feel like from the subject's point of view, and I know something about how to design an experiment so it isn't agonizingly boring. I've also learned a bit about recruiting subjects. All of this, I hope, will come in useful when I start doing my own research, if I'm using human subjects. Or maybe even if I'm using monkey subjects -- they deserve a workable interface too, after all.

I have done a negotiation roleplay while thinking I was on caffeine. I have sat and read in a chair for hours while specialized earplugs play sounds in my ears and measure the echoes of my ear canals. I have identified grey shapes on colored backgrounds as quickly as I possibly can. I have described upwards of a hundred superballs. I have lain in an fMRI for two hours watching sentences full of made-up words. I have had my auditory and tactile thresholds tested and retested and re-retested.

(By the way, getting fMRI'd was actually quite nice. You're in the machine for two hours, and they want you to move as little as possible, so they take pains to make you comfortable, with padded head restraints and a foam block under your knees and a blanket. It was so comfortable that, after a while, it felt like my body was disappearing because it wasn't sending my brain any discomfort signals. Which was incredibly relaxing, but also trippy.)

The most exciting thing, though, has been when I'm actually interested in what the experiment was about, and when I can make contacts this way. A couple weeks ago, I spent a Saturday doing loads of different tests in a psycholinguistics lab. One of the experiments had me listening to ten minutes of sentences in a simplistic constructed language, trying to decipher where the word boundaries were. (Sound easy? Listen to ten minutes of sentences in a language you're not familiar with, then come back and tell me with a straight face that it didn't sound like a continuous stream of speech.) I was surprised to find a conlang being used in a serious research context, since I'd been given to understand that most linguists are dismissive of conlangs and conlanging in general. But I asked, and we got into a neat discussion, and then I asked if they were looking for undergrads, and they said yes! Exciting! More on this in a subsequent post.

Followup: Toe clipping and humane treatment

2007-11-18T21:54:00.000-05:00

I was looking for a diagram of the toe clipping code I described in the previous post. Apparently, though, toe clipping is no longer considered an acceptable method of marking animals, except in unusual circumstances that preclude using other methods. The 2004 edition of Current Protocols in Neuroscience says:

"Lifetime identification of rodents has traditionally been accomplished by coded digital amputation (“toe clipping”); however, this procedure is considered by many to be inhumane and ethically unjustifiable except under special circumstances."

And according to Cornell's document on the subject, you need to get the approval of the Institutional Animal Care and Use Committee (IACUC) before you can use toe clipping, and there are all kinds of restrictions -- age of the animal, total number of toes clipped, etc etc.

I don't know why it didn't occur to me, back in 2005, that there must be other methods of identifying animals. Now that I've looked at a bunch of documents, it seems so obvious. Ear tagging, tattooing, metal rings, reusable microchips...there's all kinds of stuff out there. It's kind of nice to see that new methods are being invented and popularized, and (hopefully) driving out the less humane methods that used to be the norm. Especially for something as routine and universally necessary as numbering your animals.

I still wish it were possible to keep mice in less crowded conditions, in cages that actually let them have a life. Would you like to have lived your entire life in a featureless environment the size of a couple of handicapped bathroom stalls, eating one kind of food and scrapping with your siblings? But keeping animals is already expensive, and if there's only so much money to be spent on improving the daily-life conditions of lab animals, I'd rather it were spent on chimpanzees than mice.

[LJ Repost] My experience with lab mice

2007-11-18T19:55:00.001-05:00

Recently, I visited my friend Rachael. We were talking about our respective summer activities, and since I was working in a neurobiology lab at the time, the topic of animal research came up. Rachael is many things, including (1) highly empathetic; (2) hyperenthusiastic about animals and the environment; (3) very protective of, and caring for, the same. The Rachael I knew back in elementary school probably would have had a fit at the thought that her friend could be involved in something as barbaric as animal research. But we're not eight years old anymore, and instead of going on a long animal-rights diatribe, she just asked me how I dealt with it. I couldn't really give a good answer in realtime, without a chance to think through it. I said something along the lines of "I just push it aside. Yes, it's disturbing, but we try to be as humane as possible, and I push it aside."

It is difficult to deal with the suffering and death of research animals.

I've spent two summers under grad students in a certain neurobiology lab at Stanford. Luckily, the only organisms we worked with were mice and bacteria. (And do I ever feel sorry for the people who work with monkeys.) This post will be about mice. Bacteria are not worth discussing.

Actually, the first time I worked with mice was the summer/fall of 2005, when I interned in a different neurobiology lab, under a scientist named Helen. I only went in once a week, and I hadn't taken biology yet so I hardly knew anything about what we were studying, couldn't really make a substantive contribution...blah blah blah. I'd had pet hamsters before, but that was the first time I had to deal with mice in a research setting.

I remember how freaked out I was the first time I watched Helen handling the mice. To pick them up, you pull them up by the tails and then scruff them. To obtain a very small tissue sample for genotyping, you cut off a bit less than a millimeter of their tail, with a razor blade. To give them each a unique identifying number, you use a predefined code that involves cutting off toes (and sometimes punching holes in ears, though we didn't use that). The mice would get frightened, squeak, writhe, urinate, try to escape, try to bite, and eventually, bleed. Each mouse didn't bleed much, but I was quite surprised at the amount left on the workspace when we finished numbering and tailcutting a couple cages' worth of mice.

Thankfully, that was as much as I had to do while working with Helen. I did do some sectioning and staining of brains, but they had already been dissected out, and I was able to think of them as just tissue. Meat. I suppose I knew, academically, that someone had had to kill mice and dissect them to obtain these brains, but I was one step removed from that and it didn't really hit me. They were just excised brains, just grey lumps in a dish; they didn't look at me with cute little button eyes and squeal, demanding to be put back in their cage with all their paws intact.

At one point, Helen and I walked past a guy who was doing a more elaborate procedure. The mouse was on its back on a styrofoam block, pinned by the paws -- essentially crucified flat. Its chest was cut wide open, and I could see its heart beating. There was blood everywhere, and there were lots of tubes going back and forth from the mouse to this little whirring apparatus in a corner. It would have thoroughly blown my mind, but I didn't catch more than a brief glimpse. Anyway, except for that, my mouse involvement was relatively pain-free in that lab.

I got a bit of a shock when I started in the second lab, in summer 2006 (working with a grad student named John). We were doing a project that involved acutely isolating cortical astrocytes. Translation: killing young mice, dissecting out their cerebral cortices, and processing these in various complicated ways to finally end up with an isolate of single cells of a certain type. That procedure (`prep' for short) takes pretty much all day.

Hah, I'd thought tailcutting and toecutting were bad? We were working with very young mice, recently weaned or not yet weaned. I think the age range was roughly from 1 to 10 days. They were still pink and didn't even have their eyes open yet. With adult mice, you gas them first, but to kill a young mouse, you behead it with scissors. (I think the protocols are similar for rats, except sometimes you use this guillotine-looking thing. I never used that, or saw it used.)

You behead the mouse with scissors, with about inch-long blades. The body twitches, and the head falls onto the table, and it twitches too. Blood wells and drips out of the body, reddening about a square inch of the absorbent pad you do dissections on. (You get quite a bit more blood from an adult mouse.) You discard the body in a biohazard bag. Meanwhile, the head is sitting on the table, looking for all the world like a live mouse, except there's empty space behind its neck. The jaw opens and shuts, which makes the head rock back and forth. It takes about ten seconds to go quiescent, and then you unroof the skull and dissect out the cortex.

Sometimes, when you put the scissors up to their neck, they squeal and put their little hands up, and grasp the blade, and you can't behead them without cutting off their fingers.

The first time I watched John do it, and the first time I did it myself.....I'd like to say I felt faint, or nearly threw up, or something overt like that. But I just felt a deep sort of quiet horror that didn't lend itself to being expressed that way. I didn't feel a physiological effect, like faintness or nausea; just quiet horror and mental revulsion. But I wondered, what was wrong with me? Why wasn't I more upset? As unpleasant as the experience was, I wanted it to feel more unpleasant. I didn't want to feel the beginnings of numbness and desensitization.

I did an awful lot of preps that summer, about two per week on the average. And don't get me wrong, I enjoyed most of the tissue culture work, the part where you're working with bits of tissue or cells in a tube, instead of with (mostly-)entire animals. The summer's work as a whole was fun and challenging and rewarding and all sorts of other awesome adjectives. But I was doing two preps a week, often under tight time constraints, so I didn't spend much time hyperventilating over dead mouse pups. I didn't actually become numb, but I grew much better able to put the horror aside quickly and move on to the next thing that needed to be done. And then after five minutes, the disturbing part was over, and there were just tissue bits in a dish. Meat.

One thing that helped was perverse, macabre humor. It made me realize anew what awful things we had to do, while helping me cope and smile. I guess everybody got into the black humor to some extent -- I sure wasn't the one who put up the "Dr. Kevorkian wants YOU to keep the euthanasia area clean" poster. A lot of people were in the habit of referring to older pups as `pupcorn', because they would jump around enthusiastically when you opened the cage, and they could easily jump high enough to escape if you weren't careful. But my favorite was a random thing that happened to me. Immediately after beheading the pup, you cut away the skin on top of its head using small scissors. John's small scissors squeaked. The first time I used them, I jumped about a mile all "OMG OMG OMG it's still alive it squeaked WTF OMG AAAAAAAACCCCKK", until I realized that the mouse head had no vocal tract, so it couldn't possibly be squeaking. After that, I could always laugh at myself during a dissection.

This summer (2007), I was back in the same lab, working with a different grad student (Lynette). I didn't have much trouble re-acclimating to the lab, the preps, and the mice dissection. The deep breathing, the numbing, and the humor -- all that kept working, thankfully.

I watched another student do a perfusion, which involves pumping out all a mouse's blood and replacing it with saline solution, then pumping that out and replacing it with preservative. This turned out to be the same procedure that I saw back when I was with Helen, with the mouse crucified, heart beating, all that. I watched a good part of it. Got a little nauseous, but not really that much. I knew the mouse was unconscious and completely unaware of what was happening to it; everyone takes great care to make sure that the animals are well and completely anaesthetized. Sure, it bothered me, but not overly much; and pretty soon the spinal cord was being extracted, and it was back to the "it's just tissue" stage.

I watched Lynette euthanize four cages of mice. (I participated obliquely, by carrying cages and suchlike; I passed up the offer to participate directly.) We put a cage into a gas chamber and turned on the CO2. The mice gradually slowed down and got quiescent, and eventually they went from asleep to dead. You could tell they were dead when their eyes turned green. After gassing the mice, you had to verify that they were dead. This meant holding the tail with one hand, and pinching the neck with the other, and breaking their necks. I passed up on the offer to try my hand at this, though I had the feeling I probably should have gone for it.

While I watched the euthanasia, I tried not to block it out or push it aside. I wanted to feel horror and revulsion. I wanted to be upset. I made a point of looking at their faces when Lynette said she always tried to avoid it. Things like that. I wanted to make sure I hadn't gone numb.

The next time we had to euthanize mice, we might have had as many as 50, all piled in a cage. Normally, when you're CO2ing them, they just sort of get sleepy, move slower, and then go unconscious. This time, about 3/4 of the way there, a lot of them suddenly moved/twitched at the same time. I don't know if it was coincidental, but it was scary. I participated concretely this time, by breaking the necks of the last six or so. They're so small and soft and fragile, and their necks break so easily. It's easier than breaking a toothpick.

It's not arbitrary. These mice are killed because they are not useful. They don't carry enough copies of the mutation we need. Some of the mothers get in the habit of having litters and then eating them. (By the way, that's a natural mechanism: when the environment is lousy for raising pups, the mother will eat them to conserve protein, protein being not exactly abundant in a mouse's natural diet.) Litters are the wrong age at inconvenient times. One of the females was pregnant, but the pups would be too old by the time anyone could do anything useful with them, just because of everyone's schedules. No one keeps extra mice around for their own sake. It's a hassle to take care of them, and it wastes funding better spent on expensive experimental apparatus and reagents. I accept all of that.

(I would have offered to adopt them, but I'd asked about that at Helen's lab. For one thing, mice with poorly-understood mutations make dangerous pets. For another, it's a bad idea for mouse researchers to keep pet mice of any kind, in case the pet mice get a disease and the researcher carries it into the mouse colonies at the lab. Apart from all of that, the sheer volume of mice involved would be prohibitive.)

Relatively speaking, I felt OK killing mice for a prep, because they were dying for a reason, and their cells were being put to good use. Even part of them lived on; though we killed the mice, we spent every effort coaxing their glial cells to grow and thrive. They were contributing to science, and might one day contribute to human medicine. But the euthanasia was useless and pointless, and that was what got me. These mice were not being used for anything. They were just extra, and there was no room for keeping extra mice.

Fortunately, there isn't any kind of machoness culture around this in the lab. You don't get ridiculed for being upset about the animals suffering and dying. At most, you get a few odd looks, and a suddenly solicitous mentor. We spent half an hour discussing how badly we felt for the people in another lab who had to kill a monkey. They had known this monkey, had worked with it for months, had trained it to do things, had even named it. And now they had to kill it and extract its brain. We were very glad we were not them.

This post is a combination of two LJ posts. Here are the comments to the first and second original posts.

[LJ Repost] War on The Cult of Genius, The Cult of Theory, and The Cult of Not Biology

2007-11-18T18:40:00.001-05:00

I started working on this post a loooooong time ago -- back in February of this year, when dinosaurs roamed the earth. I wrote up about 4/5 of it, was called away, and forgot to ever return to it. So yes, the blog posts I'm linking to are several months out of date, and I'm sure the discussion progressed quite nicely without me. But it's not like this issue will go away anytime soon.

First salvo fired by Julianne Dalcanton of Cosmic Variance. She attacks a misconception in the physics community: if physics is actually difficult for you, if you're not Feynman-Einstein-Hawking smart, you are pretty much worthless as a physicist. You are only fit to do low-energy, experimental, or otherwise `lowly' work. You would be better off spending your time teaching more sections of freshman mechanics.

Wrong.

Apparently this misconception is unfortunately very widespread among physics people at all levels, and leads to talent drainage as people decide they just don't have what it takes, and head off to some easier field. The vast majority of useful physics work is done by people who aren't off-the-charts geniuses (and this is true to a lesser extent even of the revolutions that individual geniuses catalyze; Einstein was nothing like solely responsible for the theory of relativity). Physics is hard, and if it's difficult for you that doesn't mean you're stupid or unworthy. Welcome to scientific inquiry.

Score one for sanity. (Do yourself a service and go read the original entry; my summary doesn't nearly do it justice.)

Second salvo fired by Chad Orzel over at Uncertain Principles. He attacks the misconception that there is a Great Chain of Being in the physics department, and the more theoretical your work, the higher you rank. Low-energy experimentalists are right down there with biologists (gasp!). You're stupid if you have a hard time with algebraic topology, or if you spend a lot of time fine-tuning apparatus instead of grandly theorizing about the universe.

Wrong.

This misconception is also widespread. Supposedly, the farther removed your work is from `reality', the harder it is. As Orzel points out, a lot of the most difficult work is in experiment, where you HAVE to pay attention to reality. None of this "setting inconvenient constants equal to 1". A lot more of the most difficult work is in integrating theory with reality. Level of abstract or mathematical content (which does correlate with incomprehensibility) does not determine value; not even close. Also, what theorist could come up with this clever use of post-it notes?

[I'll add the following to Orzel's points: One of the things that a prof I've worked under likes about biology is that Experience Matters. This is true at all levels. It takes a fine hand, lots of practice, and an acquired intuition for how reagents/cells/tissues/animals behave, to do complicated procedures properly and get good results. And when you get curious results, it takes experience (and a good mental database of papers) to think of good reasons why that result happened, and especially to think of what followup experiments to do. It seems like this should be true of most experimental work, though I only have direct experience in cell-bio and linguistics.]

Score two for sanity. (Again, do yourself a service and go read the original entry.)

I will attempt to fire a third salvo, though (a) I'm not third, more like twentieth, especially if you count comments discussion and (b) I don't have enough experience for my contribution to be worthy of the title "salvo".

*cracks knuckles*

I declare that there is no Great Ladder of Scientists, going biologist <<< chemist <<< physicist <<< mathematician. Further, there is also no Great Ladder of Biologists, going ecology-level <<< organism-level <<< cell-level <<< molecular. Generally, height on these ladders is associated with abstraction, level/volume of math involved, and smallness of what you study. That, too, is plain wrong.

Sure, it's harder to visualize molecules bouncing around and reacting than it is to visualize zebras bouncing around and getting eaten by lions. That's not the point. Molecules may be smaller, but zebras, by virtue of being made of zillions of the most complex molecules in existence, are complicated. The bigger and more biological the entities you study, the more processes are going on at once. Molecular interactions are hard to model because we don't have an intuition for how things behave at that microscopic level (weirdly). Zebra interactions are hard to model because there are so many variables, and the same is true of organs, and tissues, and cells, and etc.

Also, it's often said that microscopic work is difficult because gut instincts are wrong. That's a fair point. Instincts aren't supposed to be 'right', they're supposed to keep you alive and breeding. And yes, it is difficult to imagine quantum particles going around doing their quantum thing, because "their quantum thing" is so at odds with our daily experience. But the same thing is true of molecular biology. If you think about proteins going around in a cell and reacting with each other, it's likely to play out like a stately dance in your mental theater. In reality, there's an awful lot of aimless random wandering, mistakes, and awkwardness between proteins. It's less of a symphony and more of an enthusiastic but unprofessional pub-session. In ecology or meteorology, gut instinct fails just because of the huge surfeit of variables and random factors. In cognitive science, gut instinct fails because we're not optimized to understand ourselves, and especially because everyone's used to computers, which don't work very much like brains. Etc, etc.....gut instinct fails for different reasons in different fields.

It's worth admitting that some sciences are younger than others, and the easy problems get solved first. The difficulty/scale of a field's "big problems" will be proportional to some function of how many scientist-hours have been poured into that field. But that doesn't mean new fields are inherently easier (or harder); it just means they're new. In several years they'll be at about the same level of difficulty as the fields people have been pursuing since they could walk.

The fourth salvo, "humanities people do not rank just below worms", is left as an exercise for the reader.

Here are the comments from the original LJ post.

Let's get down to business

2007-11-17T22:30:00.000-05:00

What can you expect to find here? I intend this blog to be a serious science blog, one that'll challenge me and have me writing at the top of my game, and hopefully one that will interest and inform you as well. Like I said earlier, take a spin through ScienceBlogs to see who I'm emulating.

I plan to mostly talk about science. This includes interesting new papers, random neat things I encounter in class, what I'm doing research-wise. I don't mean that this blog is supposed to be entirely Serious Business (tm), but I'm aiming for `mostly'.

The first several posts will probably just be reposts of the best content from my LiveJournal, the ones I feel deserve to be in a more serious context and not rubbing shoulders with "OMG this homework is so stressful, eek".

F1RST P0ST!!!

2007-11-17T21:46:00.000-05:00

Welcome to the Dendritic Arbor! I'm Kelly, aka Alioth, currently a (relatively) bright-eyed and bushy-tailed freshman at MIT. I'm interested in all sorts of fields, primarily the ones you see in the blog description. I haven't declared a major yet, but I know I want to go on to grad school and then academic research, and I have a fairly good idea of what sort of research I want to do. So at the moment I'm debating whether to officially major in Bioengineering, Brain&Cognitive Sciences, or (most likely) some combination of the two.

And why, you ask, am I blogging? There are several reasons: an excuse to procrastinate, because it's neat to be able to subscribe to my own RSS feed, because I think it's deplorable that there isn't already a blog called "The Dendritic Arbor", because I read so many blogs that I'm starting to think this blogging lark is something I can actually do (ha)...lots of bad reasons.

But what's the good reason? I've been maintaining a LiveJournal since early in high school, so I have some little experience at blogging. It's pretty thorough, but the vast majority of the content is just me blathering about my personal life, which is not at all interesting to people who don't know me. Occasionally, though, I've made a post that I thought was really worth reading. Perhaps this is arrogant, but I've even regretted that those posts get little traffic, and have guilt-by-association with LiveJournal, the forum of stereotypical pretentious emo teenagers. I like to think I grew out of that when I graduated high school, lo these many months ago.

On top of that, my daily readings page is largely populated by the good folk over at ScienceBlogs. I greatly admire their work, and for a while now I've had an urge to emulate them. Of course, I'm just a first-term undergrad and I naturally don't expect to do nearly as well as grad students, full tenured professors, and big shots from PLoS. We'll see what comes of this little venture of mine.