Friday, April 29, 2005

Shoulda gone with rock, Sotheby's

For some reason, I find this story about a "rock, paper, scissors" game that was worth several million dollars very funny/interesting/nifty. Seems like it's an example par excellence of the theme of "Blink", which, as I understand it, is all about making snap decisions. [Honesty compels me to admit that I've said bad things about this idea, as a general approach to decision-making, before.]

Friday, April 22, 2005

My first scientific abstract

Christina has been working on a story about the Goose Ghetto near MIT; the overall "plot line" is that the pictures were taken as part of a scientific investigation of these geese. I served as the scientist studying them and supplied an abstract for the research. The final series of pictures [alas, without my voiceover explanations of the pictures in my best German accent] can be seen here.

Wednesday, April 20, 2005

Demonic comedy

In one of the stories in "Season of Mists" [Vol 4 of The Sandman series], Lucifer decides he's tired of running hell, summarily kicks everyone/everything out and locks up the place. [Hey, it's a comic book, I mean, graphic novel. Suspend your disbelief.] Now, some of the demons are pretty upset about getting kicked out and hatch schemes to take back Hell. Here's part of the speech the demon ringleader gives, which had me chuckling:

"This will be a new hell. A forward-looking hell, that recognizes individual worth; in which a daemon can raise its head -- or any other important member -- high"

The speech itself, with its "I have a dream" overtones, is absurd enough, but it was the "or any other important member" bit that really made me laugh.

I gotta get me some of that

A few weeks ago, when the TA in one of my classes was returning graded midterm exams [for the exam that served as a Grim Reaper of egos], I saw that the TA had written "Nice job !" on one student's exam, so I presume that she must have done pretty well. I think I've discovered that student's secret: while sitting in class today, I noticed that she was drinking Smart Water. I think I'm going to order myself a case of Smart Water and enjoy feeling my intelligence increase with sip after refreshing sip.

Tuesday, April 19, 2005

The slow loss of blood continues ...

... at Microsoft, accompanied by the occasional spurt from a major artery, like their Director of Platform Evangelism, ie one of their head cheerleaders, leaving the company because, as he says, "I just couldn't go on being an evangelist for a gospel that I don't believe I can sing". Ouch.

I wonder when [or if] they're going to find a tourniquet. The usual cure prescibed, namely getting back to "building exciting products", is way too simplistic: where do you find enough products that are "exciting", can be shipped quickly, keep the tens of thousands of engineers at Microsoft busy and bring in enough profit to show up as anything other than a blip compared to the billions of dollars brought in by Office, Windows etc ? Some of those requirements are mutually exclusive -- if it keeps thousands of engineers busy, it by definition has to be a huge product. And if it's a huge product, it can't be shipped quickly. If it's "exciting", then it's probably meant for consumers, not businesses, and [as far as I know] most of Microsoft's money comes from licensing software to businesses, so it's not going to make the same amount of money as Office, Windows, SQL Server etc licenses. And you can't just parallelize the problem by trying to produce lots of exciting, small products -- [IMO] there aren't enough cool ideas around to create enough "exciting" products to move the earnings dial, expressed in billions of dollars, more than a blip. In many ways, these problems are a reflection of Microsoft's size. In retrospect, it might have been better for Microsoft if the antitrust trial had resulted in it getting split up. The resulting companies would have had more headroom to grow without having to deal with all the "diseconomies" of scale that MS now has to contend with.

Note that I'm not saying "Microsoft is doomed, flee while you can !". I think MS will continue to be a good company to work for for a long time -- they still have oodles of cash, their overall compensation package is pretty damn good, they are working on lots of stuff and, most importantly, they still have lots of smart, creative people working there. But it's now a mature, big company; there's nothing wrong with that, everybody has to grow up sometime. It's just not the special "Neverland"-like place [the Peter Pan-type Neverland, not the Michael Jackson-type Neverland] it used to be. [And not just in terms of shipping products, but also in terms of overall culture and atmosphere.]

Monday, April 18, 2005

Isolating the @$$-kicking gene variant

Despite the fact that I no longer compete, I continue to follow what's going on in the world of Olympic-style competitive Taekwondo. Over the last week, the Taekwondo World Championships unfolded, in Madrid. And something pretty damn unbelievable happened: 3 siblings, 2 brothers and their sister, managed to win 3 gold medals. The siblings in question happen to be members of the Lopez family, which the Taekwondo equivalent of the Williams sisters in tennis, except that there are four of them and they actually get to hit their opponents [I think if the Williams sisters were allowed to do that, they'd still be dominant -- those women look scary strong]. One of them, Steven, has so far managed to win 2 Olympic gold medals and 3 World Championship medals, hasn't lost a match in 5 years and shows no signs of slowing down.

You may [or may not] ask yourself "How much of this is due to genetics [ie nature] versus their training environment [nurture] ?". While part of their phenomenal success is undoubtedly due to the fact that they train together [starting out from humble beginnings in a garage (insert Rocky theme music)], I think a very large part of it is due to genetics. Having competed [and lost, badly :-)] at that level before, I can attest to the fact that if you ain't got the "nature", no amount of "nurture" is going to get you there. The only nurturing you're going to be doing is nurturing your bruises ...

I think the Lopez family should submit their DNA for testing to the HapMap consortium, which is trying to characterize the little differences in DNA that make some people more susceptible to certain diseases, respond to drugs etc while others remain unaffected. Seems like they'd be the perfect sample population from which to isolate the gene[s] positively correlated with the ability to literally kick some @$$, relative to the general population.


Wednesday, April 13, 2005

We hateses the nasty, smelly Systems Biologies

Here's a quote from a paper that we're reading for my cell biology class

"In an age when a great deal of cant has been written about the coming of age of systems biology, the experiment from Musacchio's lab reveal the variety of experiments that are essential to understand complex biological control mechanisms in this day and age. Structural biology, genetics, hardcore biochemistry and sophisticated imaging of tagged proteins in vivo are all required simply to begin to think clearly about sophisticated biological processes, and highly sophisticated experiments are required before one can begin to contemplate the utility of mathematical modeling. Future departments of systems biology might take note."

I found this particularly interesting because I'm in the brand-spanking-new [just started this year] Computational and Systems Biology PhD program, so it's educational to hear what people think of "systems biology", a term that has come into vogue relatively recently. I've also wondered what "traditional" wet lab biologists think of the general push to introduce lots of computation and mathematics into biology and all the noise being made about the future of biology being in computation. Even if you apply an appropriate discount factor to take into account the usual overly optimistic predictions that "the future of X is Y", all that talk has to be somewhat disconcerting if computation is something you have little/no background in, especially given the need to constantly be on the cutting edge of science.

Based on the quote above, Kim Nasmyth's opinion of systems biology and computational modeling seems to be rather low. On one hand, I agree with him that, in the end, you're going to have to confirm your mathematical models with experimental support [and have said so, towards the end of this post] and so you shouldn't be too gung-ho about these models. On the other hand, I do think that making the blanket statement that [all] mathematical models are currently useless is throwing the baby out with the bathwater.

I think the utility of a model depends on what you want to do with it. His take on mathematical models seems to be that they're all intended to either be based on or give deep insight into what's happening at a mechanical, molecular level, and that if they can't do that, they're useless. That seems to miss the point of many models, which is to give you an idea of the sorts of things you should observe at a high level if the system works the way you think, allow you to easily experiment with different possible system organizations and just try to get a feel for what might be happening in the system. For example,
if all you want to do is built a model that will tell you what will happen if you press on a car's accelerator, you don't need to know things like the volume of the cylinders, what metal they're made of, what the length of the crankshaft is etc., which is what Nasmyth appears to be arguing for. What's kind of ironic is that in this paper he makes arguments about what could/should be happening in a cell based on notions like relative amounts of certain proteins and the rates of some reactions. That's a computational model, even if it's not explicitly expressed as a set of equations.

All that said, my personal goal is to end up with expertise in both computational and wet lab experimental work so I can alternate between doing biochemistry, genetics etc and computer modeling on my own [ie without relying totally on collaborators]. Now I just have to figure out what advisor/co-advisor combination is going to allow me to do that ...

[I wonder what Kim Nasmyth thinks of the branch of synthetic biology that doesn't even pretend to be interested in how cells "really" work but rather is intent on just building biological systems entirely from scratch.]

*Update: After thinking about this a bit more, I think Nasmyth misunderstands what's probably the most fundamental aspect of what's being called "systems biology". He seems to equate systems biology with mathematical models, whereas what systems bio is really about is looking at entire systems and trying to figure out how they function as a whole, instead of just characterizing the parts in isolation. Mathematical models are a tool that can help because it's hard to reason in a principled, consistent way about interactions between multiple components without math, but they're just a tool, not [necessarily] an end in and of themselves. I don't think any reasonable "systems biologist" would argue that experiments aren't incredibly important in understanding whole systems, much more so than computational models are at the moment.

As I mentioned above, I think it's ironic that Nasmyth rails against computational models when he's using one himself, albeit not explicitly. I think it's even more ironic that most "systems biologists" would probably look at the argument he lays out in his paper and say "That's systems biology !", because he's reasoning about various aspects of cellular mechanism that come together to make sure that chromosomes separate at just the right time during cell replication ie he's looking at how the system functions as a whole. He's doing the very thing he seems to despise so much.

Ok, enough about that now ;-) I think the biggest reason I felt compelled to write about this is because Nasmyth is a well-known and respected cell biologist, so it's a bit disconcerting to see him so [apparently] virulently opposed to the field I'm going into.

Tuesday, April 12, 2005

Strangely disturbing protein pictures

Computer simulations to predict protein structure/folding can be used to produce pictures simulating proteins moving from one state to another. I find some of these pictures a little creepy -- check out this picture, that one or the one I personally find the creepiest, a virus protein. [There's a gallery with a few more pictures].

Monday, April 11, 2005

Vatican Biotech

[No, the Vatican hasn't cloned the Pope. At least, not as far as I know.]

Slate's William Saletan provides a [relatively] quick tour through various bioethics conferences, starting off with a reaction to a recent proposal from the President's Council on Bioethics [which I mentioned earlier], moving on to the Vatican and ending up at Penn, twice.

The short version, if you believe Saletan: Catholic priests are dealing with the challenges posed by advantages in biotechnology at a much more nuanced, scientific and thoughtful level than [liberal] advocates of all the possibilities offered by the technology. In other words, they're investing in actually understanding the science, and trying to delineate what is acceptable to the Catholic church based on the current state of scientific understanding.

I find the "Vatican approach" an interesting contrast to the approach taken by the Intelligent Design [ID] movement in the US [the folks who are agitating against evolution] -- their whole approach is premised not on trying to convince scientists of anything, but rather convincing the public at large that "evolution is just a theory". Of course, they were forced into that approach because they don't have a scientific leg to stand on, and were dismissed as wingnuts by scientists a while ago. When you can't win the game, you have to change the rules ...

Maybe the more subtle Vatican approach also reflects the fact that it's been around for centuries and had time to refine its approach to problems [no more of that heavy-handed Inquisition stuff], whereas the religious right in the US [which is behind the ID movement, however much the people pushing ID may dispute it] is relatively new and not quite as suave yet. That said, shifting the debate about ID into the public domain may prove to have been a strategic masterpiece after all, given the scary fact that some insane percentage of Americans already don't believe in evolution.

I hope that what Saletan saw at the Penn bioethics conference isn't a trend ie that biotech advocates don't take the "Look, biotech is good for you, and if you don't understand that you're just an idiot, a religious zealot or somebody stuck in the previous century" approach. Trying to convince people of something by telling them they're stupid if they disagree is seldom a winning strategy.

Friday, April 08, 2005

N.S.F

As I said a while ago, I applied for a Graduate Fellowship from the NSF, the National Science Foundation. I finally heard back from them today and I was awarded an N.S.F -- No. Such. Fellowship. Apparently, the winning arguments I described earlier weren't so winning. Instead, I got an "Honorable Mention".

That Honorable Mention bit is actually mostly what chaps my hide about the outcome of this. Last year, about 2000 people were awarded Honorable Mentions, which makes me have my doubts about the veracity of the NSF's claim that the Honorable Mention is awarded to "meritorious applicants who do not receive fellowship awards. Honorable Mention is considered a significant academic achievement nationwide". Granted, I don't know how many people applied, but, still, being one of 2000 isn't something that makes me feel particularly special. I feel it's kind of like being slapped on the ass and being told "Nice try, tiger, you'll get 'em next time. Now run along and play". And while I can review my "ratings sheets" [ie what the various reviewers thought of my application], they won't be available until May 2nd, so I'm left to steam for another month until I get an idea about which bits of my application didn't make the cut.

Oh, and as part of that Honorable Mention I get to request computer time at an NSF supported Supercomputer Center. Yippee-kayee, computer time, just what I wanted for Christmas !

Grrr. Mongo no happy.

Protein folding and the benefits of ignorance

First, a bit of background: there are lots of different types of proteins and they [mostly] do different things. Some make chemical reactions go faster, some serve as little machines to help make other proteins, some degrade proteins, some form a cell's "skeleton" etc. The bottom line is that proteins make the biological world go round -- without them, we wouldn't be around, at least not in our present form.

What a protein actually does is, to a good first approximation, determined by it's three-dimensional shape. If you know what shape a protein is, you can start to make some guesses about what it does, even if you've never seen the protein before; this is useful in cases like when you've isolated some proteins from a pathogen and are trying to figure out what they do that causes disease. It would also be nice to be able to "custom-design" proteins that have a particular shape so that you can, for example, have them stick to the proteins produced by a pathogen and prevent them from doing bad things.

So -- protein structure matters, for lots of reasons. Unfortunately, it's pretty difficult to determine what a protein's structure really is, involving stuff like X-ray crystallography where you shine X-rays on a crystal of the protein, get a bunch of dots as a picture and then do lots of complicated math to try to figure out what structure could have produced those dots. And the hardest thing isn't even the math, it's trying to get the protein to form nice, regular crystals -- that part alone can easily take a couple of years [of a graduate student's life ...].

Given that it's so hard to get the "real" structure of the protein, lots of effort has been [and is being] expended on trying to predict protein shape using computer models.
One way that this is tackled is by trying to simulate a protein going from it's initial extended, "cooked noodle"-like shape right after it's been made into the eventual complicated shape it assumes -- this process is called "protein folding". And trying to simulate protein folding is pretty hard. For example, it took 512 months of supercomputer time to simulate one-millionth of a second of actual protein folding a few years ago, for a pretty simple protein. Granted, that was in 1998, so it'd probably take a lot less computer time now, but, c'mon, one-millionth of a second ? The fastest-folding protein takes one-thousandth of a second to fully fold, so they basically managed to only simulate one-thousandth of that time. What about proteins that take several seconds to fold ? Makes the X-ray crystallography method not look so bad ... unless you're the poor sucker who has to try to get the protein to crystallize nicely.

In any case, I've now sat through three lectures that deal with how to predict the 3-d structure of proteins and I think my reaction is best summed up by what my niece Chloe said to the pastor when he asked her what she thought of the service: "Booooring". It's not that the professor is bad, it's that I find the material rather uninteresting. I think there are a couple of reasons for this. The most important one is probably that trying to figure out exactly what shape a protein is is a bit too far down in the details for me. Returning to my favorite "living things as machines" analogy, it's kind of like trying to figure out whether a bolt in the machine is 2.5cm or 2.51cm long and which direction its thread runs ... I'm much more interested in understanding what big piece that bolt is a part of, and how that piece interacts with the other big pieces. The other part of it is that a lot of these algorithms involve a level of physics and chemistry that's just way beyond me [and the other people in the class], so a lot of the lecture slides have basically consisted of complicated-looking equations that are explained in a hand-waving way by the professor because we're not really supposed to understand them anyway. Not something that inspires me to be very engaged.

So, in summary, computational structural biology is an important thing for somebody to do, as long as that somebody isn't me.

The ironic thing about this is that one of the things that first got me interested in the intersection of computer science and biology is IBM's Blue Gene supercomputer, built expressly to help model protein folding. It's a good thing I didn't know then what I know now [ie that I find computational structural biology boring], or I might have been turned off by the whole idea and never gone down the computational biology grad school path. Sometimes, ignorance is bliss.

[One question that occured to me today as I thought about this was -- why is it called Blue Gene if it's concerned with protein folding ? Shouldn't it be Blue Protein ? I guess that wouldn't be quite as catchy a name ...]

Wednesday, April 06, 2005

Bush: Master Economist

I haven't really been paying too much attention to Social Security reform, other than having an initial reaction of "Hmm, subjecting people's retirement money totally to the vagaries of the market, and their ability to invest it themselves, seems like a bad idea". That reaction was reinforced after reading a series run by the LA Times last year about the increasing shift of economic risk from businesses and government to families, and the deleterious effect that has had on many families -- privatizing Social Security seems like another step in that [bad] direction. There's also an article in the Washington Monthly attacking the Republican definition of "freedom", and its lack of honesty about the increased risks associated with the freedom they propose, that has some bearing on this.

In this vein, I heard a story on NPR this morning that just made me howl. President Bush, in an attempt to gain support for his Social Security reform proposal, displayed a cabinet that supposedly contains all the Treasury bonds that back Social Security benefits and said something to the effect of "Look, this is what all the money you've put into Social Security looks like -- it's just Treasury Bonds sitting in a filing cabinet. Shouldn't that be fixed ?" [AP News story, LA Times story]

This is so simple-minded that I don't even know where to begin. It's kind of like saying "Look, wouldn't you feel more comfortable if the government had a big building just filled with piles of cash ? Or if we had a lot of treasure chests filled with gold, diamonds and other precious substances, buried on an island whose location is on a map that only two people in the world have, and which needs to be read under a special kind of light ? Instead, all we have is this newfangled ... paper thing, called a Treasury Bond ... how can you trust that ?"

So, not only does he impugn the guarantees made by the government he's the head of, but following this impeccable line of reasoning, it must make more sense to invest the money in securities that have virtually no guarantees [as opposed to the guarantees made by the US government about Treasury bonds] ... yeah, I get that. Totally. And Chewbacca lives on Endor.

The mind boggles.

Tuesday, April 05, 2005

Now that's what I call a capital-E Explanation

In today's episode of "House", when one of the doctors is trying to explain why antibodies to a breast tumor might attack brain cells: "Well, there are molecular similarities between breast cells and brain cells".

Yeah, that must be it. Extensive similarities, even. That aren't present between breast cells and any other cell types. Maybe you could get a silicone brain implant to make you smarter. Or saline, if you're worried about silicone. For that "more natural" feeling of intelligence.

I wish I could get away with hand-waving non-explanations like that sometimes [like on my biology opportunity sets and exams :-)]. Maybe I shouldn't be an actual grad student, but just play one on TV.

[I actually like the show, but I couldn't let this one pass without comment.]


20 million perfectly useless lines of code

The NYT has an article about MS being forced to make concessions in how it licenses its source code to people interested in looking at it.

The thing I don't understand about source code licensing is that, unless the source code comes with a bunch of people who actually know it, it's pretty much useless. Even if you get documents covering the overall architecture is, what the main modules are and what the high-level call flows are [and those documents don't generally exist in a useful form even inside Microsoft, trust me =)], you're not going to get very far in terms of understanding 100K lines of source [for a smallish MS product], let alone the tens of millions of lines of code in Windows.

So, unless

- you have lots of money to hire lots of smart people willing to devote months/years of their time trying to reverse-engineer the code
- you don't want to do anything to the code other than something simple like adding a couple of menu items that end up calling your code
- you want to reverse-engineer something reasonably straightforward, like a file format

... I just don't see what good the source code does you without access to people who actually understand it. It's a bit of a paradox -- if the code is simple enough that you can really understand it, then it's probably easier to just write it yourself to begin with. And if its functionality is complicated enough that you really don't want to re-write it yourself, then chances are pretty good that you won't ever understand it without lots and lots of hard work.

So, I just don't get why anybody would license source code. I must be missing something.

Saturday, April 02, 2005

100 Faces

Christina recently finished her first big photography assignment -- "100 Faces". I, of course, think they're great, and not just because I'm in them a lot [I'm kind of the default subject ...]. I'm borne out in my opinion by the fact that Christina's instructor, who is apparently somewhat sparing with praise, also thinks so.

But judge for yourself -- the full set is here, or
you can check out the "Top 10" pictures on her blog [start at the "Avoiding Apples and Toast" post].

Another fine contribution to XML ubiquity

Lots of people complain that XML is bloated, takes up too much space on the [network] wire etc. Here's one way of addressing the problem. Of course, alternative XML encodings fly somewhat in the face of this proposed transport-layers-as-XML RFC, which tries to increase the number of XML-based protocols.

[Both documents best read in a ... near-term-history frame of mind.]