Saturday, May 28, 2005

The [Amish] house always wins

Last night, Christina and I watched "Devil's Playground", a documentary about a portion of Amish life called "rumspringa" [which means "running around" in Pennsylvania Dutch; funnily enough, that's exactly what it means in Swabian too]. When Amish teens turn 16, they're allowed to go out into the rest of the world [ie the devil's playground], to go and try whatever it is they want, for however long they want, and then decide whether to join the Amish church or not. Sounds like an enlightened way of doing things, right ? Don't force anybody into the religion but let them choose for themselves, that sort of thing. And it seems like a pretty good strategy: according to the documentary, 90% of Amish teens choose to return to the Amish church.

Turns out the deck is totally stacked. The most obvious hurdle is that if you're used to being part of a close-knit family and community, have never driven a car, gone to the mall, watched TV etc and are then suddenly thrust into modern American culture, you're going to experience serious culture shock; that alone may be enough to send you scuttling back into the safe culture and environment you grew up in. The far more insidious thing, though, is that Amish kids [of the Old Order Amish] have to leave school after 8th grade, because the Amish believe that education leads to pride.

The upshot of this is that, at 16, Amish kids are let loose and they spend a bunch of time livin' hard and fast -- partying, trying out drugs etc, trying to cram in as many new experiences as possible. Then, after a few months/years of the rockstar lifestyle, they start asking the "what next ?" question, which is where I think harsh reality sets in. And that harsh reality is that with an 8th grade education, you're not going anywhere fast nowadays; you're pretty much condemned to a lifetime of menial, low-wage jobs. The two choices they have are thus either permanently being on the lower rungs of the socioeconomic ladder in the uncertain outside world, or going back to a culture that emphasizes community, in which there are no/much fewer class distinctions, with a strong safety net built in. Faced with those options, and the pressure they get from parents, relatives & friends who have chosen the Amish lifestyle, it's not surprising that so many of them choose to "join church" ie become Amish permanently.

What irritates me so much about this is that it seems like a very hypocritical way of going about things. The kids are only given the illusion of choice -- they're [intentionally, one suspects] woefully underprepared for one of the supposed choices they have, making it much more likely that they'll choose the option the Amish community wants. Almost makes you wish for a proper authoritarian cult that doesn't beat about the bush -- "You leave us, you die. Any questions ?"

[This is, of course, a totally off-the-cuff, knee-jerk reaction from me -- some Amish/Mennonite orders do allow their kids to go to high school & college. That doesn't make the ostensible choice offered to teens belonging to the other orders any less hypocritical.]

And to those 10% who choose not to go back: good for you. You're brave. Or you really, really like inventions of the devil like electricity and cars ;-)


Thursday, May 26, 2005

31 and counting

I turned 31 today. In a city that has ads for a hopped-up version of beer + ginseng [or something like that] which say "You can sleep when you're 30", I guess that means I'm now definitely on the downhill slope and picking up speed. Watch out, people below me, 'coz I ain't got brakes !

I got some very cool gifts:

- Christina's parents gave me comics, vintage-y ones, from as far back as 1972: "Mighty Mouse", "Sergeant Rock", "Mickey Mouse & Goofy" and "US 1". I've only had the chance to read "US 1", but it's one of the [possibly unintentionally] funniest comics I've ever read. It's about the adventures of one Ulysses Spencer [aka "U.S."], a long-distance trucker, who happens to have a "CB skull" ie a bunch of metal implants in his head that allow him to pick up CB radio. He also has a super tricked-out "rig", with flamethrowers, a recoil-less cannon and all other kinds of good stuff. In the course of this story, he happens to come across an alien who speaks in CB lingo ["good buddy", "breaker", "what's your handle ?", that sort of thing] who needs frozen chicken parts [which U.S. happens to be hauling] to repair the "organic-integrated technology" that powers his spaceship. This thing had me howling with laughter. Somebody at Marvel must have been smoking some good weed when they approved this. [There's a synopsis of the whole storyline arc of this comic here, if you're interested].

- Explanatory digression: as a wee lad, I used to enjoy two things: jumping off stuff and water. The former meant that I used to give my gym teacher fits because I kept jumping off stuff when she wasn't looking and the latter meant that I spent lots of time at the public pool. Then I discovered the joys of putting these two activities together: jumping off stuff, into water. In other words, jumping off a diving board. This, in turn, freaked out many a lifeguard; once, I had to swim a couple of laps of a pool to convince a lifeguard that it was ok to let me, a 6 year-old at the time, jump off the 5m platform.

If we'd stayed in Germany, I probably would have taken up competitive diving. As it is, we moved to Ghana, where the opportunities for that are ... limited, shall we say. A more blunt way of saying it is that there are no such opportunities; at the moment, I don't actually know of any pools in Ghana that have diving boards. That said, when I was in high school, my friend Bernard and I used to skip physics class [the teacher sucked], go to the one pool that did have 1m and 3m boards [which has since been closed], and try out whatever dives we could muster up the courage to do. I got as far as being able to do a double forward somersault off the 3m board by dint of sheer pig-headedness ie trying it until it worked, sort-of, in that I didn't land on my back or my stomach. I'm sure from a style perspective, it would have made a diving judge fall out of his/her seat laughing, kind of like the really bad auditions you see on "American Idol".

Anyhow, after high school I pretty much forgot about it; never took any lessons in college, or even really thought about it, for the last twelve years. When we came to Boston, I noticed that the MIT pools had open diving sessions a couple of times a week and talked about maybe checking them out, but never actually got around to doing so. Until today.

[Whew, that was a long digression]

Christina got me a set of private diving lessons, with the assistant coach of MIT's diving team, as a birthday present. Today was my first session. And, as usual, that stuff is harder than it looks. And I'm not even talking about all that fancy, twirly stuff in the air -- I'm talking about just the proper takeoff, which was pretty much all we worked on for an hour. Turns out my brute-force approach of jumping onto the end of the board with all my weight and then pushing off as hard as I could isn't quite the way to do it; instead, you're supposed to let the board do the work, with only a gentle assist from your legs. And there's a whole set of proper arm movements that goes with it, too, as well as torso positioning, to make sure you have proper positioning once you take off. Trying to get all that right -before- even taking off meant that by the time I was finally in the air and thinking about what dive I was trying to do, it was almost too late, which made for some pretty comical "dives".

In any case, it was an awful lot of fun, and I'm looking forward to my next few lessons. Maybe I can finally learn to do a double forward somersault with decent form.

- "Highlife" music from Ghana, from my parents [which hasn't actually arrived yet, but I already know what they're getting me =)]. Very few things remind me of Ghana as much as that kind of music does, and I only have one highlife CD, which my brother happened to forget when he was visiting. And there are only so many times you can listen to one CD. It'll be nice to have some new stuff to listen to.

Besides the gifts, the rest of the day was pretty cool too. Christina and I went to dinner at a good Italian restaurant in the North End and then came home and had some of Christina's kick-ass cheesecake, after which we sat back, held our bellies and groaned about how full we were, but how very good it all was.

All in all, modulo some rough patches, it's been a pretty damn good year. Here's hoping the next year is even better !

Wednesday, May 25, 2005

No, no, actually it's not reading

The NYT has a story about the increasing trend towards audiobooks, and the question of whether that can be considered "reading" a book. I have nothing against audiobooks -- they make perfect sense in some situations [eg on the bus, on car trips], whereas in other situations, they don't [for example, when the subject is somewhat technical -- having to rewind because I didn't quite understand something would drive me insane]. But I do take issue with the claim that "it is too reading" because

a
) reading involves taking in written or printed characters, per dictionary.com:
  1. To examine and grasp the meaning of (written or printed characters, words, or sentences).
  2. To utter or render aloud (written or printed material): read poems to the students.
  3. To have the ability to examine and grasp the meaning of (written or printed material in a given language or notation)
  4. ... etc ...
b) you don't actually have to know how to read to take in an audiobook

So, no, sorry, you're not reading the book, any more I would say that I was "listening" to a song if I wrote down its lyrics and then read them. That's not a judgement about listening somehow being "inferior", it's just inherent in the definition of the verb "to read".

Tuesday, May 24, 2005

First-year recap: was it all worth it ?

Consider situation A:
- a well-compensated career that's going well
- toys
- hobbies [no, that's not me, and, no, I'm not even close to that good]
- an established network of friends and family
- beautiful scenery [in all directions]

and situation B:
- living on a student stipend
- an insanely expensive city
- pretty damn crappy weather [now experiencing a "spring" that's breaking records for cold and rain]
- no social network
- starting at the bottom again

which situation would you rather be in ? If you said 'B', you're a liar, or a masochist. Forget all the "fuzzy" stuff about hobbies, friends etc and just look at the economics of it. Just doing a rough back-of-the-envelope calculation puts the opportunity cost into almost seven figures. In other words, this move was non-optimal in so many ways, it's hard to even count them, which brings me to the question:
was it worth it ?

Short answer: yes.

Longer answer: The first 5-6 months here were pretty damn tough emotionally. Having lived in Boston for a year after graduation and having liked it, I figured I'd still like it. Well, turns out that it's all relative: I initially moved to Boston from Philadelphia, so it was definitely a step up. However, after spending 7 years in Seattle, coming back was a rude shock and made me realize
how attached I'd become to Seattle. And it was even tougher for poor Christina, born and raised in Seattle -- talk about getting dumped into an alien environment. The transition was made tougher by not having a network of friends and family, although once again Christina got the short end of the stick -- I at least met people through school, but until she found a job she was pretty much totally cut off from contact with anybody except me [and her job hasn't really helped either]. Not that meeting people through school helped all that much, because I'm 6-8 years older than the vast majority of people in my classes; add the fact that I'm married and you end up with relatively little common ground between my classmates and me in terms of how we like to spend our free time. That's probably why most of the friends I've made are also married =)

There was also the lifestyle adjustment, having to cut down on the non-essentials; we never really realized how much money we were spending on non-essential stuff until we moved here, and that took a bit of getting used to. The toughest bit, though, was the feeling that, for the next 4-5 years, our lives were going to stand still in terms of taking the next step towards "adulthood" -- having kids. This was compounded by the fact that just about all of our friends have been insanely fruitful in the last couple of years, having kids like they're going out of style, which made us feel rather left out.

All this made me seriously consider whether all this was really worth it ie how badly I wanted to switch careers. At one point, it got bad enough that I got in touch with Werner Vogels, who was
recruiting people to come work at Amazon on building real-world distributed systems, since I had experience with just about all the stuff he was looking for and it sounded like an interesting gig. It was indeed an interesting gig, and I was sorely tempted to take him up on his offer to come back out to Seattle for interviews. In the end, I didn't, for a couple of reasons. First, I felt like 6 months wasn't really long enough to make an informed decision about whether I really wanted to do this and, more importantly, it came down to the realization that I could always go back to being a software engineer, but in order to go into biotech I really need that PhD. In other words, sticking with the PhD expands my universe of "adjacent possibles", whereas bailing on it is a one-way street.

That still left open the "life standing still" issue, which was a biggie and appeared insoluble. However, most "insoluble" problems are only insoluble given a particular set of constraints, so it was a question of figuring out what constraints we were willing to relax. It took a bit of hard thinking, but in the end we came up with a solution that we like. With that, I think we turned the corner in terms of not having overwhelmingly strong reasons to leave.

From a more positive perspective, being here is also doing good things for both of us: Christina's photography school is
going well -- she's getting a chance to do something she loves, she's making like-minded friends and totally geeking out with Photoshop. I've found a lab I like and research areas that I'm looking forward to diving into for my PhD. And if I ever lose interest in those research areas, there's a whole slew of other things I find really cool, and I'm sure more interesting areas will continue to crop up. I feel a bit like a kid in a candy store -- too many good things to try at once. When I contrast that with the fact that I don't feel even remotely as excited about anything in the software industry as I am about biology, I'm convinced that I/we made the right long-term choice. We're both getting to do something we're excited about, and expect to be excited about for [a good chunk of] the rest of our lives, so dealing with some short-term pain is worth it.

I couldn't have done this without Christina encouraging me from the get-go, being supportive when things got tough and generally just being the best partner I could wish for. Big ups to my elder wife ;-) !

Monday, May 23, 2005

First-year recap: school choice addendum

One area I wanted to write about a bit in my earlier post but forgot about was some more on the issue of school choice. Those of you unfortunate enough to have been subjected to it will remember that I had a really hard time deciding between Berkeley's Bioengineering program and MIT. As somebody put it, I was flip-flopping before flip-flopping was fashionable.

I originally didn't think I'd really be interested in the Berkeley program, but my visit really changed my mind, not least because the program seemed be much more laid back than the MIT computer science [EECS] program, another program I was considering. The Berkeley faculty presentation was laced with lots of jokes and slide transitions that showed people doing outdoorsy stuff in the area around SF [ie skiing, biking etc], whereas the MIT EECS presentation started off with one professor telling us what the academic requirements were, and all the ways to flunk out of the program; this cheery intro was then followed by about 30-40 professors each telling us, in staccato machine gun-style delivery, what their area of research was, in 2 minutes or less. Welcome to MIT !

In the end, I decided to go with MIT [obviously]. Part of that was familiarity: I visited MIT a bunch of times as an undergrad because one of my best friends was there and
I also lived in Boston for a year after college and liked it. Part of it was the faculty: I thought there were [marginally] more faculty doing interesting things at MIT than at Berkeley and thus more people I could see myself working with/for. What really swung the pendulum, though, much as I hate to admit it, was the "MIT mystique", the often-heard notion that MIT is -the- place to go for a scientific/engineering education. That, and the fact that I'd made two previous attempts to go to MIT -- once when applying to undergraduate schools and once when applying for grad school during my senior year in college. Both of those attempts could reasonably be called half-assed, for various reasons, and neither of them worked out. Even though, in retrospect, it's a good thing that those attempts failed, it did leave me with a bit of a complex about MIT. So, given that bit of personal history, I figured if I turned down the chance to go to MIT, I'd always wonder whether I really could have made it here and I didn't want to be in that situation. Hence, MIT.

In the past year, I've discovered that people here, just like everywhere else, put their pants on one leg at a time, so to speak. Sure, there are some people here in comparison to whom I'm basically a lab rat [like a 17-year old computer science PhD student, and a math professor in his early 20's], but they're a minority. Having erased that particular doubt, my main goal now is to get out of here as quickly as I can ;-)

From a science/research side, if I had to choose again, knowing what I know now, it'd actually be a much harder call. Berkeley's Bioengineering program has rotations, and is run in conjunction with UC San Francisco, which has a medical school, so it fits both my previous lessons about school choice. In addition, there are people working on synthetic biology [like Jay Keasling and Wendell Lim], on malaria genomics, on developmental genetic regulatory networks etc. Basically, because it's run in conjunction with UCSF, which has a great biology department, there are twice as many biology professors to choose from as you'd get in a normal program. So, given my [more informed] interests, Berkeley actually has an edge over MIT.

All that said, I'm happy with my lab choice and projected area of research; it's not like I'm now dying to go to Berkeley. Which, I guess, leads me to my

Third lesson learned: at a certain level of quality, you can't really go wrong, science-wise, with any school you go to.

... something lots of people told me, but I didn't fully understand until now.

Saturday, May 21, 2005

Getting high, McDonalds-style

McDonald's is going all-out with the TV advertising for the "latest addition to their salad portfolio", a fruit and walnut salad. Salad portfolio ? Did somebody really write that with a straight face ? Quite apart from this, what I find funniest about the ads are the fact that all the people in them talk about the "fruit buzz" they get from eating this salad. From their ad PR: A “Fruit Buzz” is a change in attitude and an overall happy feeling you get after tasting the new Fruit & Walnut Premium Salad. Is it just me, or does that sound like Engrish ? I guess if you regularly eat at McDonalds, eating fruit will give you a buzz, since it's like eating food from another planet, food that won't cause your body to shut down in a month.

[I gotta admit, though, McDonald's fries are pretty damn good.]

First-year recap: research interests, lab choice

I started out the year interested in a few rather different areas: immunology, malaria and synthetic biology, and a vaguely-defined notion of working on problems involving interacting "networks" of biological entities. Unfortunately, I ended up having to give up on two of these: the professor I talked to about immunology just ... disappeared, under circumstances nobody wants to talk about. And I couldn't find anybody at MIT interested in collaborating with Dyann Wirth, the Harvard professor heading up the malaria effort.

First lesson: if you're really interested in working on disease-related research, go somewhere that has a medical school.


As part of the CSBi PhD program, I was also required to do several rotations. The rotations were o
riginally supposed to be three month-long rotations, but the program was restructured to give us four two month-long rotations, and then I snuck in one more short rotation. The people I rotated with were:

- Drew Endy, synthetic biology's most visible proponent. Got a bit of wet-work experience, and actually got something to work.
- Doug Lauffenburger, one of the first people to start building mathematical models of signaling pathways. Learned a bit about the challenges of systems biology.
- Tom Knight, the other pillar of synthetic biology work at MIT. Got the chance to spend some time noodling about an idea I had to engineer cell-to-cell communication, as well as getting a good view at what it looks like when a good computer scientist becomes a good biologist.
- David Gifford, whose group works on machine learning algorithms that help shed light on genetic regulatory networks. Learned what large amounts of genomic data look like, and various ways to look at and try to interpret the data.
- David Bartel, one of the top folks in the currently hot field of microRNAs. More experience with evaluating large amounts of genomic data.

Originally, I was upset when the rotation program was expanded because I just wanted to select a lab and get going. With the benefit of hindsight, doing more, longer rotations and waiting an extra semester to pick a lab was a Good Thing. I got the chance to see more labs, and work in a few different areas. That said, one area I didn't really explore at all was cell biology, which deals with phenomena like how cells grow, move, divide etc -- basically, the next level up from the genome.

Second lesson: All other things being equal, pick a school/program that has a rotation system over one that doesn't.

Over the course of the year, a couple of new interests came up:

- RNA: As I've mentioned before, RNA used to be thought of as mostly just an intermediate messenger between DNA and proteins, but it's becoming clear that it's a lot more than that. What I think is neat about RNA is that it can act in both "digital" and "analog" ways: in its digital form, as messenger RNA, it can be viewed as a message that specifies how to make a particular protein ie it contains "pure" information that can be read by a "machine" and used to make a protein. However, it can also act in an analog fashion, by folding up into three-dimensional shapes that then serve to catalyze reactions. In this case, what's important about it is not the information it contains, but the actual shape it adopts ie it acts like a machine itself. It's kind of like the difference between the instructions on how to make a shovel versus the shovel itself -- RNA can act as the instructions, or as the shovel. [Sometimes even at the same time, like in self-splicing RNA.]

- Development: I find the notion that a single cell can give rise to an animal with 50 million million cells [in humans], of hundreds of different types, arranged in a precisely-defined three-dimensional pattern [to give you 2 legs, 2 arms etc] mindboggling. Talk about the ultimate algorithm.

I also went from the fuzzy "networks are cool" notion to being interested in genetic regulatory networks specifically. I think of genetic networks, determining when genes are turned on and off, in what order etc as being the source code for life -- when you run it, you get living things. And that, of course, appeals to my computer science side. You could certainly make the argument that the networks of interacting proteins, the end result of these genetic networks, are as important, if not more so, but I'm just more drawn to the "lower-level" genetic networks. I guess I'll always remain a systems-level [in computer science terms] geek at heart :-)

So, in terms of biology, I'm interested in synthetic biology, RNA, development and genetic regulatory networks. On the computational side, I'm still interested in pretty much all ways of modeling biological systems, whether it's via differential equations, Bayesian networks or stochastic approaches etc. That list of topics is, of course, non-exhaustive -- I can think of a bunch of other areas I'd like to work in [like malaria, immunology, protein motors, digital oscillations in cells etc] but it represents the subset that I plan to explore in my thesis.

I spent a lot of time thinking about lab choice, and broke it down into

- Science: can I work on stuff I'm interested in ?

- What I want to learn the most, computational or experimental methods:
whether I want to become a computer scientist who works on biological problems or a biologist who uses computational methods to work on biological problems, as well as where I need the most help/education ie the stuff I'm less likely to be able to pick up on my own.

In terms of science, think I could have satisfied my interests in several labs, whether by joining Drew or Tom's lab and building synthetic networks that mimic some aspect of development, by joining Dave Gifford's lab and working on embryonic stem cell differentiation or in Dave Bartel's lab, working on the impact of microRNAs on development. What really ended up being the deciding factor was the second question, the expertise I most want to gain -- I came down on the "biologist who uses computational methods" side, in the sense that, right now, I think it's more useful for me to be in a lab that has a lot of experimental expertise that I pick up, than in a lab focused on computation.

With that in mind, I ended up choosing to join Dave Bartel's lab, at the Whitehead Institute [which conveniently has a picture of Dave right on its homepage at the moment :-)]. From what I've seen, Dave is a hands-on guy who is very much up-to-date on the experimental work being done by his students and can give concrete advice when experiments are going wrong, and there are lots of folks in his lab who have oodles of benchwork experience. Both of these are good pre-conditions for somebody like me who has no clue about labwork, especially when coupled to the fact that the Whitehead is one of the best-known biological research institutions in the country and so hopefully I'll pick up more knowledge about biology just by osmosis.

That said, my plan is actually to end up being a joint student between Dave Bartel and somebody with a computational focus, but we haven't yet figured out who that second person is. The idea is for me to spend the summer thinking about a thesis project and then use that to decide whose computational expertise to tap into.

So, the first academic year is over and I've picked an advisor. Now all I have to do is the hard part of getting a PhD, the actual research ;-)

Thursday, May 19, 2005

First year recap: classes

Booyakasha ! My first year of grad school, at least the "taking classes" part, is over. This is, of course, cause for both celebration as well as some reflection [ie long, rambly posts that only family members will read, more out of obligation than anything else ;-)]. As I try to mentally summarize the past 9 months, stuff falls into 3 big buckets:

1) Classroom education -- what I learned from the classes I took
2) What I want to get out of my PhD overall, in terms of specific training and the area[s] of research I'm deeply interested in
3) The overall question of whether making this move was a Good Thing or not

We'll start with #1, because it's the easiest, most concrete topic, because #2 [my lab choice] isn't settled yet and because #3 depends on the first two.

As I described earlier, fall semester was devoted to building lots of detailed models of biological systems ie lots of computational stuff. This semester was evenly split between "straight" biology and computational biology. My molecular biology and cell biology classes, for all my complaining about them, were actually my favorite classes because I feel like they were the ones in which I started to learn how biologists think ie the classes taught me more than just facts. The other two [computational] classes were certainly not short on material covered, but they mostly expanded my repertoire of computational tools I can use, they didn't really show me a totally new way of looking at a problem.

So, what's this big insight I got from my biology classes ? In the end, it's embarrassingly trivial: biology is analog and physical, not digital. "Well, duh, no sh!t, Sherlock", you say. Allow me to expand.

When you're trained as a computer scientist, you're trained to solve problems using layers of abstraction. Suppose you're given a problem that you don't know offhand how to solve. Start out with some "black boxes" that magically do what you want, without necessarily knowing how that black box does its thing. Then, take each black box in turn and subdivide it into another set of smaller black boxes that work together to perform the overall function of the bigger black box, again without worrying exactly about how each smaller black box does what it does. Keep doing this and eventually you get to a list of small things that you -do- know how to do and now, when you combine all of them, they build on each other to solve the overall big problem that you started out with. For a computer scientist, getting to "something you know how to do" basically means that each sub-problem is small enough that you can write some fairly simple code to do it, and be reasonably sure that your code does the right thing.

Here's the point, though, that I never really thought about too much: even when you get to the point where you're writing code, you're still really, really far up in the abstraction hierarchy. Underneath the code you write, there's a boatload of other black boxes that all have to work together to make your code work: your operating system, the microcode controlling your computer's CPU, the transistors the CPU is made of, the logic gates each transistor is made of, etc all the way down to electrons flowing along tiny little wires. In other words, you're still very far removed from the actual physical reality of what needs to happen in order for your code to have the effect you'd like it to have.

What does all this have to do with biology ? It has to do with the way I used to think about biological processes, or rather, the way I didn't. Before this semester, when I read a sentence like "The cell senses DNA damage, activates protein A and protein A in turn activates proteins B and C, which move into the nucleus and cause production of proteins that can repair the DNA damage", I didn't really think much about it beyond what was said -- seemed like a reasonably straightforward process, what else is there to ask ? For most computer scientists, that sentence above is a perfectly good explanation of how the cell handles DNA damage. Biologists, however, start asking all kinds of uncomfortable questions, like: "The DNA [for E.coli] is about 4 million letters long, how exactly does it sense DNA damage ?", "How does protein A, which is just diffusing around in the cell, actually find proteins B and C, which are also just randomly floating around in the cell ?", "How do the repair proteins find the damaged DNA ?" In other words, they start asking about the physical and chemical details of how exactly something happens, which is so far down the abstraction hierarchy that computer scientists get vertigo from looking down.

This is what I mean when I say biology is analog and physical, not digital: when you're digital, you're sitting on top of a pile of abstractions, whereas biology occupies the [unfinished] basement, physical reality. In some ways, this actually makes biology easier to think about because you can construct simple mental models based on your knowledge of how physical objects interact. For example, you can visualize "protein A displaces protein B from being bound to protein C" as "ball A knocks ball B off ball C". And if you can't form a consistent mental picture of a biological process in physical terms, you probably don't really understand it or the proposed model of the process is wrong. There's nothing magical about it -- it has to obey the laws of physics [in contrast to the unfettered nature of computer code].

So, this semester served to refine my mental layer cake, and give me an even greater appreciation for the amazing machine that a cell is.
All it has to work with are totally "dumb" materials and physical concepts: molecules that float around & bump into one another, concentration gradients of chemicals, physical barriers like membranes etc. There's no "master controller" that magically knows what to do eg how to react to a virus invading the cell, or how to duplicate DNA so the cell can divide -- it all has to happen by itself, just by following the laws of physics and chemistry. That's a pretty humbling thought when you consider that for all the expressive power of modern computer programming languages and runtime systems ie lots of "smarts" not constrained by physical reality [to some extent], we're still nowhere near being able to construct a software system nearly as flexible, versatile and fine-tuned as a cell.

More concretely, when I see/read a description of a biological process, I now start thinking about questions like "Where does the energy for it come from ?", "What gives the interaction between protein A and protein B its specificity ie why doesn't protein B also interact with protein C ?", "How do you make sure protein A doesn't interact with protein B all the time, but only during a specific phase of the cell lifecycle ?". In other words, not just "What's the logic flow in this process ie what are the data inputs, what are the key decision points, what happens at each decision point, what are the outputs ?" but also "How is this process actually implemented physically, at the level of dumb molecules ?" That's what I mean when I say that I've started to learn how biologists think -- what questions they ask, why they're important and how they go about answering them.

In summary, at this point I feel like I have a pretty solid array of computational techniques I can work with, as well as a good foundation in basic biology. There are still a few gaps to fill [like taking a probability course so I don't have to try to appear inconspicuous each time the phrase "random variable" is mentioned for fear that somebody will ask me something about random variables], but my areas of ignorance are not the sucking voids they used to be. The next step is picking an actual research problem to work on, so I can start to apply all I've learned in the classroom, and figure out what actually doing science means, as opposed to just learning about it.

[No, I didn't forget the other two areas I said I'd been thinking about. Those will get covered in subsequent posts.]

Tuesday, May 17, 2005

Mugging by SDS-PAGE gel

Had the final for my Molecular Biology class today. In theory, it was just supposed to be like a third midterm, covering only the last third of the material we talked about in class, and doable in about 2 hours [even though 3 hours were alloted for it]. Given these stated goals, the fact that I did reasonably well on the 2nd midterm and got through the problem sets without major problems, I was lulled into what proved to be a false sense of security. Today's exam definitely wasn't doable [by us, at least ...] in 2 hours and even with the 3 hours we got, I still expect the mean score to be lower than the 55% or so it's been for the last 2 midterms. Oh well. One more exam to go.

[An SDS-PAGE gel is a molecular biologist's favorite experimental tool. It's kind of like the Swiss Army knife of molecular biology tools -- if you can't do it with a gel, you probably don't want to do it.]

Monday, May 16, 2005

"My fake plants died because I did not pretend to water them"

Two more days, then the semester and academic year will be over; this will, I'm sure, result in some lengthy "What I have learned over the past year" posts as I try to assemble a bird's-eye view of the last 9 months. In the meantime, laugh a bit, courtesy of the recently deceased Mitch Hedberg [who I'd never heard of until a few days ago ...].

Saturday, May 07, 2005

Postdocs are highly-trained professionals ...

Highly trained at avoiding the real world, that is, at least according to a report on a series of reports about postdocs that I just read. As I've said before, I just don't get why people would be content to spend 5+ extra years in school beyond their undergrad degree to get a PhD, start a postdoc appointment at about $38K/year [on average], stay a postdoc for 5 years [on average] and then have a 15% chance of getting a tenure-track faculty position. And, despite these dismal stats, over a third of postdocs are apparently "pretty set" on their plan of working in a research university.

Are all these people wearing rose-tinted, high-optimism-inducing, reality-distorting glasses ? It seems like they're victims of some form of brainwashing that induced the unshakeable belief that the only pleasant work environment is in academia, or that you can only do good science in academia, or that only second-rate people end up in industry, or a bunch of other similarly nonensical ideas.

Sure seems like a lot of these postdocs are scientists capable of considering alternative hypotheses, except when it comes to important things, like their own lives ...

Thursday, May 05, 2005

NPR funnies

Being the lefty, pinko communist liberals that we are, Christina and I listen to NPR a fair bit. And sometimes you hear some pretty funny stuff. Two recent excerpts:

- A brief blurb today that some branch of the Homeland Security department wants to use South Boston as a practice ground for "urban combat" this summer. Now, how exactly do you practice urban combat in an real city, not some mock-up constructed in the middle of nowhere ? Anyway, given that South Boston is the [most] Irish part of Boston, I think it may actually be a pretty good place to practice that kind of stuff, since the folks in Southie seem to start working on armed resistance at a pretty young age.

- They [the NPR station in Boston] are running a fund-raiser that's based on getting people to buy flowers for Mother's Day from them. Part of this is various "testimonials" from people that connect their mother and NPR. My favorite one is this [paraphrased]: "I started listening to NPR when I was about 14; my mother introduced me to it. My mother taught me to always examine both sides of an issue and NPR provides me that sort of look at both sides of an issue". Uhm, ok, and by "both sides" you mean the liberal and the really liberal side of an issue, right ?

Wednesday, May 04, 2005

Punctuated equilibrium

The theory of Punctuated Equilibrium in biological evolutionary theory proposes [among other things] that new species don't evolve gradually; rather, they arise fairly quickly, from a small sub-population of the ancestral species. Thus, there are short periods of instability [during which new species arise] punctuated by long periods of stability [where nothing much happens].

This is just a fancy way of saying that when it rains, it pours.

And it's certainly pouring school-wise for me right now, after a few weeks of a reasonably pastoral, idyllic existence:

- Final quiz for one class tomorrow
- Two problem sets due on Friday
- Final project presentation for a class due Tuesday next week
- Final exam for another class Wednesday next week
- Paper writeup due Thursday next week
- ... followed by another couple of final exams the week of May 16th-20th.

To say nothing of
- the fact that I'm supposed to choose a lab on May 20th or thereabouts, and really need to think hard about this because I'm really interested in basically all the labs I've done rotations with [I'm currently doing a 5th rotation with David Bartel, one of the top folks studying microRNAs] and will need to choose one [or two, if I can come up with a research project that cuts across what both labs are doing].
- not having spent much time with Christina in the last week or so because we've both had a lot of stuff going on.

In summary, I really have much better things to be doing than writing this blog post ;-)

Monday, May 02, 2005

Sometimes, you pick a wildcard

A few weeks ago, I was whinging about the fact that I didn't get the NSF Fellowship I applied for. Well, I'm about to whinge some more. You've been warned.

I finally had a chance to look at my "ratings sheets" ie what the 3 reviewers who read my application had to say. It looks like they were asked to comment on two aspects of my application: intellectual merit and "broader impacts"; for each aspect, they had to rate my application [Excellent, Very Good, Good, Less Competitive] and provide a couple of lines of written commentary to ground their assessment.

Here is the raw data:
-----------------------
Intellectual Merit Criterion: Demonstrated intellectual ability and other accepted requisites for scholarly scientific study, such as the ability (1) to plan and conduct research (2) to work as a member of a team as well as independently; and (3) to interpret and communicate research findings.

Reviewer 1:
Overall assessment: very good.
Basis for assessment: More information about why research plan is important would be useful. More publications related to research could strengthen application.

Reviewer 2:
Overall assessment: good
Basis for assessment: plans for both research and education should have been presented. This is a dramatic shift in career paths. Where do you plan to end up -- researcher/professor/back in industry ?

Reviewer 3:
Overall assessment: excellent
Basis for assessment: Strong, well-written plan. Background experiences suggest strong potential for success.

Broader Impacts Criterion: Contributions that (1) effectively integrate research and education at all levels, infuse learning with the excitement of discovery, and assure that the findings and methods of research are communicated in a broad context and to a large audience; (2) encourage diversity, broaden opportunities, and enable the participation of all citizens -- women and men, underrepresented minorities and persons with disabilities -- in science and research; (3) enhance scientific and technical understanding; and (4) benefit society

Reviewer 1:
Overall assessment: Excellent
Basis for assessment: Strong committment to mentoring and recruiting students.

Reviewer 2:
Overall assessment: Less competitive
Basis for assessment: The learning aspects of your application need to be expanded. You will need to have a better understanding of basic cell (etc.) physiology ...

Reviewer 3:
Overall assessment: Very good
Basis for assessment: Background & life experiences suggest potential to contribute to these goals.
--------------------

So, two reviewers put me in the top half and one of them puts me in the bottom half. Well, as Jules Winnfield says in "Pulp Fiction", allow me to retort, especially to reviewer 2 [because, of course, I totally agree with reviewers 1 and 3 ;-)]:

"Plans for both research and education should have been presented. This is a dramatic shift in career paths. Where do you plan to end up -- researcher/professor/back in industry ?"

Uhm, did [s]he miss the section titled "Integrating research and education" in my second essay, with the title underlined ? And, yes, it's a dramatic career shift, but what does where I want to end up have to do with anything ?

"
The learning aspects of your application need to be expanded. You will need to have a better understanding of basic cell (etc.) physiology ..."

I don't even know what is meant by "learning aspects", since that phrase doesn't occur anywhere in the application. But, more to the point -- what exactly does [s]he know about what I know about "basic cell physiology" ? Diddly-squat, that's what. The biology aspects of my research plan were pretty damn solid, even if I do say so myself.

Ah well, it's all water under the bridge now. At least I now have a better appreciation for the fact that the application process is pretty random, confirming what a couple of professors that I've talked to told me. Maybe they should discard the outliers, or ask for another opinion.

And I think that reviewer 2 should go boil his/her head.

Sunday, May 01, 2005

A treat of a retreat

Yesterday was the [first ever] annual CSBi "retreat" [who knew we were under attack ?]. Actually, since this is the first year the CSBi PhD program has been in existence, it was a retreat for folks associated with MIT's Biotechnology training program and we, the red-headed stepchildren of CSBi, were lumped in with them. A retreat, in this case, basically means "show and tell" -- it's intended to give people a chance to showcase their research in a pretty informal atmosphere, allow you to get an idea about the kinds of things other grad students are working on, talk to professors etc.

Getting to know a few more grad students was nice, but the most valuable bit for me was the fact that I had a chance to talk to the keynote speaker, Noubar Afeyan, for a while. He's one of the people running Flagship Ventures, a venture capital company that has a lot of investments in genomics and biotech companies, and was involved in creating the infamous Celera Genomics, the company that was in a race with the publicly-funded Human Genome Project to finish sequencing the human genome. He's a very nice guy, very approachable and down to earth. He was even kind enough to offer me the chance to come talk to him some more if I was interested [because I mentioned that getting into biotech venture capital was something I'd thought about], something I'll probably take him up on, once I figure out what else I want to ask him ;-)