On Reading the Lit

I don't read journal articles for fun the way I do for class--where I sit down and try to understand as much as I can, devoting hours to reading a single article. I read them just to be swept in awe by the overwhelming amount of fantastic science being done right now, browsing through, clicking around, mostly skimming abstracts and figures. Mostly I find myself reading biological chemistry and organic chemistry. And lately biophysics (mostly just the abstract and introduction because I really don't understand the math behind it). Some of the biophysical techniques that are going on...I can't even imagine how fantastic the scientific world is going to be in 10 or 20 years. For example, they can do NMR imaging of a virus now.

I read a review of total synthesis in the last hundred years and how far it has advanced. And docking carbohydrate synthesis on DNA as a way to functionalize microchips. And each leads to references to wander to, letting my mind wander and skim and wander and skim.

I'm realizing that it's now getting to be time to start actually keeping up with the lit--even if it is just skimming every few weeks, or even if it's just reading C&E News and/or review journals. Since there's so much out there and no one can read everything, my professors are reading the same journals, they've just been doing it for longer and with more specialized interests.

I finally have the background to get a vague sense of what articles in the current lit (at least in organic chemistry, biological chemistry, some of the more qualitative aspects of biophysics, biochemistry, and cellular & molecular biology) are about, even if I don't fully understand them, and learning about science isn't going to be spoon-fed to me through assignments for the rest of my life. It's time to start getting into the habit of reading journals like it's time to get in the habit of reading the newspaper. Not cover to cover, not necessarily every day (or even every week--after all, I still am a student), but as something I do periodically.

On Stupidity

My roommate's thesis advisor sent her a link to the following article The Importance of Stupidity in Scientific Research. It was interesting to read, because I think it is absolutely true.

Second, we don't do a good enough job of teaching our students how to be productively stupid – that is, if we don't feel stupid it means we're not really trying. I'm not talking about `relative stupidity', in which the other students in the class actually read the material, think about it and ace the exam, whereas you don't. I'm also not talking about bright people who might be working in areas that don't match their talents. Science involves confronting our `absolute stupidity'. That kind of stupidity is an existential fact, inherent in our efforts to push our way into the unknown. Preliminary and thesis exams have the right idea when the faculty committee pushes until the student starts getting the answers wrong or gives up and says, `I don't know'. The point of the exam isn't to see if the student gets all the answers right. If they do, it's the faculty who failed the exam. The point is to identify the student's weaknesses, partly to see where they need to invest some effort and partly to see whether the student's knowledge fails at a sufficiently high level that they are ready to take on a research project.

Productive stupidity means being ignorant by choice. Focusing on important questions puts us in the awkward position of being ignorant. One of the beautiful things about science is that it allows us to bumble along, getting it wrong time after time, and feel perfectly fine as long as we learn something each time. No doubt, this can be difficult for students who are accustomed to getting the answers right. No doubt, reasonable levels of confidence and emotional resilience help, but I think scientific education might do more to ease what is a very big transition: from learning what other people once discovered to making your own discoveries. The more comfortable we become with being stupid, the deeper we will wade into the unknown and the more likely we are to make big discoveries.


I think Reed is actually abnormally good at making you feel very small and very stupid. Even if it's not quite the same as research, the classes are geared towards giving you problems in the current literature and making you think about them in novel ways. My organic chemistry tests and biochemistry tests were not dependent on just knowing the information, but also knowing the information and learning how to apply it to a new setting. We also spend a lot of time sifting through the literature in upper level classes, and you get a sense that you are very small and there is a whole unknown, unsolved world out there. On top of which, we have an unusual grading policy where we are not shown letter grades for the work we do; we are assigned letter grades for our classes, but to see them we have to ask our advisor, and we are only informed if we performed above a C which is "satisfactory" when we receive reports at the end of the semester. You see numbers, you see correct or incorrect answers on exams, you get comments on written assignments, but you never know exactly how well or poorly you did, just an overall sense, which is often skewed anyway. I also struggled with my intros, and didn't really start to do well until I hit my upper level classes, so I dealt with a lot of academic failure and feeling stupid in my time. And even so; it didn't end there. In advanced synth a class I did very well in, Pat assigned us problems that he didn't even expect us to get correct. I mean, sometimes I did but mostly I didn't. The point was learning a process of solving problems and to demonstrate that you have picked up that process. The point was just to grapple through some really tricky questions that are a little bit above your current level.

The school also pushes you to your limit emotionally; I feel intellectually accountable for my work, and like when I'm not doing it well I'm actually disappointing my professors. Basically, Reed College makes me feel very stupid, even when I'm doing well. I feel like there's always more I could be doing, more I could be learning, more about every topic I should know. This is not quite the same as addressing new, unknown problems (hell, the known ones are intimidating enough), but the feeling that I'm stupid is something I am very used to, and embrace. I've even heard the phrase "if you don't feel stupid all the time at Reed, you're not doing it right".

The world is a big place with a lot of smart people in it. No, I'm not a super genius, and in some ways I'm not even that conventionally intelligent (I have trouble with things like standardized exams). I don't mind the idea of failure in lab, because so many things are out of your control. Isn't that the exciting part, muddling through until you figure it out? Tweaking this and that? Few things are as simple as they look on paper. Lab is different from school, which is awesome in my book. It's a whole different set of puzzles. But I like chance games and gambling. Things that involve a lot of skill and a lot of luck. Keeps things exciting.

So what is the big deal about feeling stupid all the time anyway?

Life plans

I've been thinking more and more about graduate school lately, and I'm pretty into the idea of going. I've spent a lot of time not marrying myself to the idea due to a lot of reasons (mostly including self-doubt, a low GPA, a keen awareness of how competitive the world is, and a certain resistance to the idea of doing something just because it's what you are "supposed" to do) and trying to convince myself it's not what I necessarily want, or that I shouldn't close myself off to other options in life or to the idea of not doing it. But when it comes down to it, I want to do science at that level eventually and I know that, and have basically been becoming more and more sure that I love science, I can handle being pushed to my limits with work emotionally, and that I have the drive to work on the sort of project a PhD would be. And while I'm not the best test taker, I have strong skills in other areas. I'm good in the lab, I'm good at communicating ideas face-to-face, I know how to retrieve I don't know quickly on the internet, I can talk about science cogently, I know how to digest the primary lit. I know professors who can attest to these skills.

But then I try to take things in perspective. I'm studying the hard sciences at a hard school. I know several profs who could write me good recommendations. I have a lot of research experience. And a really broad scientific background with a solid academic program. These things all matter too, right? Perhaps matter more than my GPA?

I don't know. It's hard not to worry, but I spend so much time consoling other people that I'm starting to believe my consolations. It is scary. We have this giant recession and everything worth doing, or so it seems, is incredibly competitive. Medicine and law and grad school in most other fields are more competitive, it seems, so maybe I should count my blessings.

But off of this "woe is me, can I hack it?" shit, I think I've finally figured out what I want to study, broadly. Basically, synthetic organic heavy-yet-still-interdisciplinary chemical biology. I want to do something more at the interface of chemistry and biology. The ideal program would be something like (ha! ha! ha! after talking about all this GPA woe) UCSF's Chemistry & Chemical Biology program. As far as I can tell, a lot of this interdisciplinary stuff is under all different labels, so my actual PhD could be in any number of things (including biophysics), it all depends on the individual labs I am interested in. I should start keeping lists of labs that are publishing projects I'm interested in that I come across in the lit.

So this is the plan right now: finish off this year (my junior year) strong, get a another summer of research this next summer (and prep for the GREs), take the GREs next year, then take a year off and apply to grad school during that year, and tech. I've also seriously thought about moving to the Bay Area after Reed, although possibly staying around Portland and trying to get a job at OHSU.

Okay, this moving to the Bay area thing is a recent idea, related to this whole actually I kind of want to go to grad school thing. I visited some friends there who were in biophysics programs at UCSF and Berkeley. Which basically was what made me come to believe that these were the sort of people I wanted to be around and the sort of environment I wanted to be in. We talked about science! Even when we were in the bar! And more science! Some people think this is sad and indicative of an utter lack of ability to fit in socially. Perhaps, but I want to be able to talk about science with my buddies when drunk. The facilities at UCSF blew me away, and the projects they were doing where just so spectacular. The sort of stuff you read about in Nature, but at a small liberal arts school, we just don't even have close to the facilities to do.

But oh yes, I was talking about why I want to move to the Bay after Reed. It's a bigger city than Portland, but one I have ties to. A lot of people I go to school with grew up there, but there are also a lot of Reed alumni who move there for work or grad school, and so there's the sort of safety net of being around Reedies, but the novelty of being in a new city. In addition, I was born there and lived there until I was 2 and a half, and my parents have a lot of family friends who live there, some of their oldest friends from before they were married. There are even a couple friends from high school who went to school out there who might be around. It's not totally restablishing myself in a new city as much as moving other places would be.

Also, as far as I can tell, The Bay area and Boston are the place to be for the biological sciences. There's just such a neat relationship between the academic powerhouses and the biotech industry in those locations that I don't think exists to the same degree elsewhere. I could probably find a job as a tech, people seem to, at least. So at least I could be connected to the science, because I think I would be really unhappy in a situation where I wouldn't be doing science to some degree. Also, San Francisco rocks! The city is gorgeous, the climate is great, there's plenty of hipster culture and coffee snobbery and all that stuff. It's still the Pacific Northwest, which I love. I love the West Coast, and I don't really want to move back to the Midwest or East Coast. It's just a vibes and personality mesh thing. The only concern is that it's expensive to live there and rent is expensive. On the other hand, it's just for a year, maybe 2; I just need to sustain myself, and I'm not looking to save money. I can live reasonably cheaply, and I don't want to live in someplace boring just because it's cheap to live there.

I love Portland. Portland is a neat place to live, and I only got tastes of what it is like to be a person in Portland and not a student who spends her whole life between the library and lab during the school year, but I spent a summer there and got a feel for it, and I really do like the city a lot. It's been good, but after 4 years it's time to see more of the world. The argument to stay in Portland is that I really do have a lot of friends out there and possible employment prospects. It's sort of a comfort zone thing. Also, it's really cheap to live in Portland, and Portland is far from boring, unlike a lot of other cheap places to live. Portland is a great place to be a 20something.

So anyway, that's my current life plan. Finish undergrad, take a year off in the Bay Area, go for the PhD. Narrowing down what exactly I mean by "synthetic organic heavy chemical biology" might be good too. Figuring out if those projects are in Chemistry & Chemical Biology programs, Chemistry programs, Biochemistry programs, Pharmacology programs...

What comes after the PhD? Academia, I think, although industry and a number of other paths aren't out of the picture either. This is a little more hazy. But seriously, I think academia is more my style. My friend and I have a running joke that if we decide in ~10 years and/or during our post-docs that if we're not feeling the academic route, then we're starting up a biotech company together; he thinks there's a 10% chance of that happening. So maybe it's making the big bucks in biotech. In any case, it's something, although I'm not quite sure what.

PLoS journals

Constance Bailey: http://www.nature.com/nature/journal/v441/n7096/full/441914a.html
Constance Bailey: (sorry, I've been really intregued by the PLoS journals lately)
gvtennis55: hahaha
gvtennis55: i like the title of this article
gvtennis55: 14.7 is legit, dude (14.7 is the impact factor of PLoS biology)
Constance Bailey: http://www.nature.com/nature/journal/v425/n6958/full/425554a.html
Constance Bailey: yeah
Constance Bailey: i mean, it seems to have legit science
Constance Bailey: and so forth
Constance Bailey: just it's running itself bankrupt
gvtennis55: dude that would suck if you published in this journal
gvtennis55: and then they were no more
gvtennis55: IF of zero motherfuckers!
gvtennis55: also, what's up with this nature article about how it's competitor will ultimately fail with their competing business model?
gvtennis55: because if nature can convince enough authors that this PloS won't be around, nobody will submit and the prophecy will come true
Constance Bailey: it's like the NPR/PBS of science journals
Constance Bailey: i like it
gvtennis55: i know yo udo
gvtennis55: (you also like NPR)
Constance Bailey: they should do pledge drives
Constance Bailey: take the NPR business model
gvtennis55: hahahahaha
gvtennis55: you mean embrace what this article says they should run from - a permanent reliance on philanthropy?
Constance Bailey: "donate 100 dollars to PLoS and we will give you this limited time PLoS logo 1,000 mL micropipette"

AHHHHHHHH. The end of the semester. It's hectic. Writing a bunch of papers, final lab reports, have my final exams coming around the corner. So much work left to do for my synth final--I need to write a paper and then be prepared for an oral grilling.

I'm midway through a paper on inducible nitric oxide synthase's role in type 1 diabetes, got a decent chunk of that done, and but have worrisomely little done on my synth paper on the total synthesis of pyranicin. Oh, and there's labwork to be done and so on and so forth...rawr. it'll be tough for the next few weeks.

But in more exciting news:
--there's a good chance that I'm going to Germany this summer to do biological chemistry work on a polyketide biosynthetic pathway.
--I may get to do a not-for-credit hang out in the lab and work on a project type independent study thing with my favorite prof (the one I worked for last summer who does the synthesis of OncoTools, or carboxyllic acids with pH switches to give them a pKa ~6.5 to target the acidic regions of small tumors that can be tagged with radioactive halogens...at least in concept...we haven't made enough of one to put it into practice, but yeah organic synthesis how I love thee).

I'm having a big dilemma over what courses I should take next semester. We are on a unit system (as opposed to a credit hours system), and a normal load is 4 units, although you can take 3.0-4.5 units without underloading or overloading.

Next semester I was originally signed up for:
--intro inorganic chemistry (1.0 units)
--statistical thermodynamics 1.0 units)
--metabolic biochemistry (0.5 units)
--biochemical methods (0.5 units)
--Johannes Sebastian Bach (1.0 units)

Bach is a musicology class to fulfill a distribution requirement with a professor I rather like, so it should be fun. This adds up to 4 units; a pretty normal schedule.

Well then I decided I didn't feel like taking i-chem lab. As a biochem major, it's not required. (I majoring in biochemistry & molecular biology, but at another school that had minors, I would probably be close to doing a minor in chemistry). In any case, I'm a little burnt out on lab classes. I love being in the lab doing research, but class labs are different. Everything isn't where you need it to be, they're short and hectic, and you can't do extended experiments because science doesn't work in once a week four block chunks. It's nice to be exposed to some lab techniques, but in reality I pick those up faster by doing research in a given field, and I'm kind of at a point where I understand generally how labs go and I'm not getting that much out of taking them anymore. Beyond biochem methods and analytical chemistry, both of which I need to graduate, I really don't intend on taking any more lab classes. Also next semester, then, will be the first time in college that I will only be taking one lab class (I'll probably still TA for organic, but whatever).

So the ramification of dropping inorganic lab is that I am taking 3.5 units. Still not technically an underload, but I started fishing around for half unit classes. This is dangerous, because in the sciences half units are classes that don't have lab components (it is pointed out frequently that all humanities classes meet with only a lecture component and you receive a full unit).

My first thought was a membrane-membrane interactions seminar. It's a 4oo level bio class where you meet for two hours a week to talk about molecular neuroscience papers. Seminars are pretty low key, generally, besides that one day when you have to stand up in front of ten or however many people are in the class and talk about a subject for an hour with our professor grilling you (and boy, does that prof know how to grill, he's a toughie). Otherwise, pretty mellow.

My second thought was advanced mechanistic organic chemistry. This might be a bit more work, but maybe not. It meets for three hours a week, and it's lecture only, so problem sets, articles to read. It's about MO theory in organic chemistry and it goes over the theory behind all those weird-ass concerted ring closings which would be nice to know about, even if my interests are ultimately more synthetically oriented (Woodward Hoffman rules, etc.) There's a lot of computer modelling. Also a small class, probably also mellow. With a number of my study buddies. It also may not be offered next year, whereas the biology seminar most definitely will.

My main fear is that if I take inorganic, advanced mechanistic organic, stat therm, metabolic, biochem methods, and a humanities class, I'm going to be drowning in work all the time even if it isn't technically an overload (I also might just maybe hate chemistry after taking all that at once...and will be taking no biology classes that semester). Especially since I am far from a p-chem-minded type and stat therm is going to be fucking hard for me. On the other hand I can always drop something (most likely advanced mechanistic or my humanities class) and I really shouldn't be afraid to do that. So, should I go for it, or is that crazy?

In other news, I am most likely going to doing labwork in Germany this summer in a chemical biology/biomolecular chemistry lab. More on that later.

I'm taking a topics in biochemistry seminar course where we read two papers a week. The topic the course covers this year is chemical biology.

Now, I'm someone who loves organic synthesis, who loves biochemistry, and who loves molecular biology. I think my mind is set up for the type of conceptual trouble shooting of organic chemistry on terms of diagrammatic reasoning as opposed to mathematical reasoning (like in a lot of computational and biophysical approaches). At the same time I'm an arrow pusher, and I think of this very much at a structural/chemical intuition level as opposed to a gross biological scale. But as much as I love organic chemistry I like applied organic chemistry. The entire complexity of biochemical systems is both fascinating and overwhelming. So where this rant is all going, is basically I thought chemical biology would be exactly my cup of tea.

Turns out that there are a lot of chemical biology projects that seem just sort of...pointless to me. Like they are doing an interdisciplinary project for the sake of being interdisciplinary? I'm skeptical, because a lot of these projects don't seem to be tackling interesting questions, really. I mean, there is some chemistry in there that appeals to me, some biology, but rarely do I find a paper where I think "yes, this is a good mix of concepts."

But I think, actually, I'm probably going to end up in a chemical biology program, it'll just be a matter of finding one of them that does something really cool, or the intellectual challenge of working on a piece of a collaborative project knowing the big picture but being an expert in a small area. Or somesuch.