Learning to read all over again

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:

1. 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.


2. 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?


3. 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.


4. 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

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

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?

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

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

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

...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.)