The Futile Cycle

There’s been a lot of media hullaballoo about the whole creation of human stem cells from skin cells, which is really just a confirmation of the research from last year on mice.

For some reason, some people, like this Washington Post editorialist, seems to think that this research side-steps the whole embryonic stem cell morality debate, that it “vindicates” George Bush’s decision to fight embryonic stem cell research.

It doesn’t.

The stem cell research from mice showed that these “created” stem cells can grow to become a whole embryo and organism. Let’s assume for a moment that in this respect, human biology is similar to mouse biology (it’s not far-fetched). If the newly created stem cell can grow to be a new person, doesn’t that mean it has a “soul”? So, then is it bad to do research on such a cell?

If, theoretically, this technology is perfect and can actually transform a skin cell to a good stem cell, then that stem cell would be no different from an embryonic stem cell, and all the same morality rules apply here (regardless of whether you are for or against it). This isn’t some sort of magic morality bullet. No ethical dilemmas are resolved here. You can’t support this sort of research and be against embryonic stem cell research, because this is embryonic stem cell research.

When I was little, I thought it was awfully boring how grown-ups would sit around and just talk. I mean, not play games, watch movies, they’d just talk! How could they spend hours doing that?

I realized today, though, that’s what I do now. I like talking to people for hours and hours. Am I grown-up now? This made me sad, and so I indulged my inner child a bit as I waited for my experiments to finish.

Dry-ice filled plastic vials that make loud bangs in people’s trash cans to startle them? Check. Water with bubbling dry ice and heavy vapors to make me feel like a mad scientist? Definitely. Squirting ethanol solution on the little crawly bugs that appear in our lab? Of course! Looking at random puddle water on a slide under the light microscope? Awesome.

Little things that keep me from growing old too quickly.

Alex Palazzo has a picture that is well familiar to anyone doing molecular biology. Alas, that is my life right now. Cloning, or rather, troubleshooting cloning, saps the spirit of all that enter biology.

One of the topics that came up at a “town hall” meeting between graduate students and the department faculty recently was how to increase attendance of the department seminars. There were some good insights, like “attendance at each seminar is inversely proportional to the frequency of seminars”, but really, was it that hard to miss the most compelling incentive to attend seminars? It seemed like 50 scientists just could not figure out!

Today’s Ph.D. comic summarizes:

One person spoke up and mentioned, in passing, “It always seems like more people come if you put out snacks.” The comment was mostly ignored, in favor of other speculation, like “what if you send out abstracts of the relevant papers beforehand?”

Hellooo! Feed them, they will come!

I don’t normally delve into ethics that much, because I don’t think most people share my eclectic set of reasonings, but when I saw the comments on this Crooked Timber post on the economics of the death penalty, I decided I’ve got to say something. I am not an economist, but I am a scientist, and science is as science does, so I’m going to comment on this from the point of view of a scientist.

One thing I saw quite often was people saying, “Economists always assume that people are rational, but that’s obviously not realistic!”

This is misleading! Economists define “rational” differently from the normal word, just like how every other field has its own jargon (”text” in literary studies, for example, doesn’t mean “written words”, but any human-produced work that can be analyzed; “energy” in physics doesn’t mean the same thing that normal people mean, but rather the capacity to accelerate a mass (or counteract an opposing force) over a distance).

In any case, when economists say “rational”, they mean someone who has some sort of internal set of goals and attains them. A “rational” person responds to incentives in ways that maximize how much they get what they want. So, if a person wants to not die, they’ll avoid things that might kill them. The goals can change over time (an old man has different goals from a toddler), and from person to person (Bill Gates obviously has different goals from Brittany Spears, which led to their different decisions in life). Economists tend to muddy the jargon more and talk about “utility”, but that has nothing to do with money, in general. “Utility” is just “how much the person has reached their personal goals.” So, in a sense, a person’s ultimate goal is to get what they want, which is kind of logically redundant.

This hypothesis is pretty good! People want things, and they do things to get them. Simple! They want to be happy, or maybe they’re hugely emo and want to be sad. Maybe they’re masochists and want to feel pain. Maybe they’re ultra-patriots and so want to die for their country. Maybe they want fame, or maybe they want money. These are all perfectly rational reasons; the key is just finding out the underlying “want.” Everyone is motivated by something; it’s hard to think of someone who isn’t. And people respond to incentives based on their wants.

Instead, most of the problems with economics come from economists trying to get from looking at individuals to groups of individuals, because it’s very hard to analyze even one person; more than one is almost impossible to do in any detail. (Studying just one individual in really great detail is called a “biography”, and economists generally want to study how most people work in general). Often, for the sake of simplicity, economists assume that individuals are more or less similar, or that they vary only along very specific characteristics. This is obviously not true, but the assumptions can be useful and good enough for the particular thing they’re studying. The assumptions can break down, but it’s not because economists assumed that people were “rational”; it’s because a particular economist assumes that individuals are motivated by the same things.

So, saying “people aren’t rational” isn’t a good criticism of economics. People are pretty rational. It’s the other assumptions on top, the “useful approximations”, that make the theories sometimes a little shaky.

Science has a reputation for really esoteric jargon, but sometimes science writing is refreshingly casual (Liu, XS (2007) PLoS Comput Biol 3(10): e183):

“If users encounter array images with blob defects, they are advised to use a ‘microarray blob remover’ to detect and remove affected probes before running MAT.”

Ah yes, the hi-tech “blob remover” algorithm.

When I was in college, my biology friends would all mutter “ethidium bromide” in hushed tones, as if discussing the devil incarnate. It was the evil-but-necessary chemical, the mutagen that would cause dozens of cancerous masses all over your body with the slightest bit of contact. Meanwhile, I happily worked my hours away in a chemistry lab using pyrimidine, benzene, toluene, and plenty of more mutagenic stuff than that. Pansies.

But when I started working in biology, again, safety training indoctrination told me: Ethidium Bromide is hazardous stuff. Use a fume hood. Any spill must be cleaned immediately, and so on. It’s dangerous.

Well, apparently not. (via Life of a Lab Rat) Eh. Guess I shouldn’t worry so much that we heat our running buffers with EtBr already it in. I probably do worse things to my body by being lazy about sunscreen in the summer.

For my current lab research, I spend a substantial portion of my time filming and photographing sex — baker’s yeast mating, or pheromone-y, cytoplasm swapping, petri dish action, if you will. Take a look at this classic shot:

They’re finicky, shy little things. I have to go to a lot of work to make them comfortable. Not too hot, not too cold, just the right humidity, not too crowded, not hungry or too full. I hope they appreciate my efforts!

Malaria is a very weird parasite with biology that we still really don’t understand.

For example, since it lives in the red blood cells, everything it makes has to come from, essentially, hemoglobin. Scientists think that’s partly why the parasite has a lot of As and Ts in its DNA, but not too many Gs and Cs. In fact, about 80% of its genome is made of As and Ts!

Now, this is a problem for the malaria. If it has to use mostly two letters to write out everything, then it can’t say as much in the same length of DNA. For example, why are words and names in Hawaiian often so (stereotypically) long? It’s because they don’t have as many different syllables as other languages, so it takes Hawaiian speakers longer to make the same amount of information into their words. Binary numbers are also longer than decimal numbers: 1573 is much shorter than the equivalent 11000100101. We say that the decimal system is more information rich; computer scientists like to say that it has more “entropy.”

Biology has a similar problem. If you have only two letters, it’ll take longer for you to say something unique. Unfortunately, biology often needs to use stretches of DNA that are very specific and unique, which act like unique signposts or ID tags that proteins recognize when they’re looking for specific parts of DNA.¹ With only two letters, though, malaria’s signposts will be double the length! It costs energy to make DNA with longer “names”, and it takes another large dollop of energy to make the double-sized proteins that would recognize the double-length names.

So, malaria evolved to survive well in humans; maybe it’s found a way to avoid paying such a huge cost?

The Trick!

Yes, I think malaria has just such a trick! You see, it seems to save the Gs and Cs for the signpost parts of DNA, which turn genes on or off!

You can kind of see that in a new paper published in Molecular Cell² by Olivier Elemento, Noam Slonim, and Saeed Tavazoie. They basically crunched computers to find pieces of DNA that seem to control how genes are turned on and off, which are these signposts (since the proteins that control genes just find and follow the signposts in the DNA). What Elemento and the rest of ‘em found in malaria was that the proportion of Gs and Cs in the DNA rise in these signposts to be a more reasonable 43%!

Cool, no? The authors don’t come outright and say that that’s the reason behind the GC-rich nature of the signposts they find. This is pure speculation on my part, and there are other reasons that the elements might be GC rich, but I think my speculation isn’t pure crap.

Let’s take a look at how much better 43% is than 20%. This will have a little bit of math in it, but settle down, I’ll skip over the unnecessary stuff. It’ll help see if my speculation is warranted.

So, How Much More?

We want some measurement that’ll tell us how long a word we need for a certain amount of information. For example, if I have just one letter (let’s say ‘X’), then I’ll never be able to tell you anything! Turn left, turn right, meeting’s canceled, even if I have an infinite amount of space, I can’t tell you anything! (Note that not sending something counts as a letter; ’space’ is equivalent to a letter here. In my hypothetical ‘one letter’ alphabet, spaces don’t exist, and so I can’t even stop!) If I have two letters, say ‘0′ and ‘1′, then I can uniquely identify 8 things with 3 letter-long words (000, 001, 010, etc.). Let’s say I have 4 letters, A, G, T, and C. Then with a 3-letter long word, I can uniquely identify 64 different things with the same length word! Much nicer, eh?

Now, things get complicated when you have to follow percentages for how often you use certain letters. For example, if your words have to have a certain average percentage of As and Ts, such as 80%, then you can’t quite say as much, right? In a way, you can think of this situation as being partly in between the 4-letter alphabet and the 2-letter alphabet. If the required percentage for 2 of your 4 letters is 50%, then you have a perfectly 4 letter alphabet. If you have to use those 2 letters 100% of the time, then basically you can’t use the other two letters anyway, so you’re reduced down to a 2-letter alphabet.

Using a formula³ that generalizes the above concept, we can calculate that without adding Gs and Cs back into the signposts, malaria would have to have DNA addresses that are almost 40% longer in order to identify the same number of items uniquely! That’s a pretty big cost! Imagine if you needed to spend 40% more energy to do everything. Your 25 miles per gallon car would become a painful 18 mpg gas guzzler. Your $70 / month electricity bill would go up to almost $100! I mean, that’s a ton of energy wasted. And evolution seems to have come up with a simple solution to the problem!

It’s simultaneously marvelous and terrifying how efficient and systematic malaria is, but in a way, we can use that to our advantage, because we can assume that malaria has rapidly evolved to reproduce well in humans, and then we can explore its biology with hypotheses generated from that. I didn’t know, for example, that malaria’s DNA signposts had more Gs and Cs than the rest of the genome, but I figured it might, since natural selection would push malaria that way. (Intelligent design, now your turn for hypotheses. No? No hypotheses? No no, don’t cry, it’s not your fault you aren’t a real science.)

I’m really curious if looking for particularly G and C rich pieces of DNA on malaria would make for finding new signposts faster, as right now, we don’t know of too many. Malaria is forced to use Gs and Cs in the DNA for its genes, so it balances out the AT/GC ratio by draining its in-between regions of Gs and Cs (so there, the proportions are actually 90% As and Ts). That sounds like a possible science project somewhere…

1. The pieces of DNA are called ‘cis-acting elements’ for historical reasons that date back to the early days of genetics.

2. Elemento et al. (2007) “A Universal Framework for Regulatory Element Discovery across All Genomes and Data Types,” Mol Cell, 28: 337-350.

3. It’s called Shannon’s Entropy

Since right now it’s both fellowship-writing and graduate school application season, I figured this was as good a time as any to post about this.

For those undergrads out there considering whether to enroll in a four-year combined Baccalaureate/Masters program, a word of advice: if you’re planning to try for a Ph.D. in the sciences later, the Masters may not be worth the hidden cost: you may lose a year of eligibility for applying to graduate fellowships during your Ph.D. program.

If you’re planning to do a Masters in, say, philosophy, and then you want to do chemistry for your Ph.D., then fine, no worries, get your M.A. and be joyful. On the other hand, if you plan to go do your Ph.D. in the same field as your Masters, it’s probably not worth it.

First of all, you’ll get a Masters in most Ph.D. programs after a year or so, regardless of whether or not you pass the qualifying exams. Secondly, your Masters work is sufficiently related to your Ph.D. work such that you may not be eligible to apply for many graduate fellowships—such as the NSF, DoD, or DoE fellowships—as a second-year Ph.D. student. Since getting the fellowships is a bit of a crapshoot, the extra year of eligibility in graduate school is quite helpful.

The main reason to get that Masters in chemistry (or whatever science) would probably be if you want to take time off before graduate school and get a job, in which case the Masters might come in handy (I’m assuming), and that advantage might outweigh your possible fellowships eligibility loss later on.

In any case, the choice ultimately comes down to personal factors, of course, but this is an often-overlooked factor when people consider the four-year Masters program in college.