lab notebooks

So here's something I've been thinking a lot about lately: lab notebooks.

Lab notebooks are something that I have a bit of a love/hate relationship with. I understand the value of a good lab notebook, and I try to write down everything that I do in it. I also find updating my lab notebook to be a rather tedious and annoying process. For the most part, my lab notebooks are reasonable, but the more complicated a project is and the more techniques I use, the more difficult I find keeping an accurate record to be, and my last lab notebook from this summer, while it contains everything that I did in it could be...uh...slightly better organized. When I was working on a project that was just organic synthesis, it was much easier to keep a good lab notebook.

But I guess, the strangest thing to me about lab notebooks is the fact that when you're done with a project, it stays in the lab with your boss. Of course it does; it's not your property. The record needs to be kept in case someone else needs to follow it. But it is a little strange to have something that's recorded in your handwriting, in your style, in a way that is comprehensible to you just gone, in someone else's hands forever. It's like parting with my diary, my record of my life for the past two months. It's strange.

Fuckity fuck fuck fuck

So I'm doing this experiment where I'm trying to get a bioengineered polyketide pathway to incorporate weird starter units. I did a small scale feeding experiment and got a promising looking result in terms of retention time, MS-2, and UV spectra. So then I did a 20L fermentation with hopes of eventually isolating it and getting an NMR.

First I did a huge ass silica column to get a crude seperation of the ethyl acetate extract. Then I did a huge ass sephedex column to get a better seperation. Then I did preparative HPLC to get 2.6 mg of something. I took a proton NMR. It was garbage. There were just too many compounds with similar retention times in there to seperate it, and the proton NMR was entirely too dirty to be at all informative. Basically, I couldn't see a lot of the diagnostic peaks at all, and a bit disheartening. BUT! It could have been that it was just too dirty. So on to further purification!

So then I purified my 2.6 mg on the analytical scale HPLC that has a really intensely good column with really great seperation. I fussed with the method with my supervisor for several runs and eventually got 2 peaks that had UV spectras consistent with my compound of interest (with this really fancy-pants analytical column, there were about nine peaks that showed up as one peak on the LC-MS spectra and maybe 4-5 peaks on the prep HPLC column, it was intense). I collected both peaks and started to evaporate them down on the rotovap using a vial adaptor that you can attach to the bump trap. One of my fractions was fine--I can put it on the vaccuum pump overnight, see if there's enough compound for an NMR (for the 500 MHz, you can get away with a little under a mg and still get spectra, so maybe if I isolate 0.7-0.8 mg of it I have a hope of doing the whole proton, 13C, COSY, HMBC, HMQC, etc. thing to really confirm the structure) and if not at least LC-MS it to see if it is there. There are more fractions from the spephedex column that one could purify--ones that actually had better seperation than the one I did attempt to purify (long story involving leaving in less than a week and the time it takes to get LC-MS samples and access to the prep HPLC in a large lab where a lot of people need the equipment)--but I simply don't have time to do it.

But the other fraction...well, what happened was a disaster. The vial adaptor LEAKED AND THE WHOLE VIAL AND BUMP TRAP FILLED WITH WATER FROM THE ROTOVAP BATH! FML!

So now I rinsed the vial and bump trap with MeOH, and am re-evaporating it and putting it on the freeze dryer overnight, hoping to god that a) something comes out, goddamn it, and b) it's not my compound of interest anyway (it was the less promising of the two peaks..but who really knows).

Seriously, though. FML.

Meticulous vs. Messy chemists

I have come to the conclusion that there are two archetypal "types" of organic chemists.

The first describes my labmate last year and one of my current labmates. This is the anal retentive, obsessive compulsive, neat, constantly tinkering, "hood is spotless" chemist. These chemists have a hugely obessive attention to detail, love excel sheets (one has an excel sheet with the CAS number, boiling point, density, and molecular weight of every compound he has dealt with ever, organized by type--solvent, catalyst, etc.), cannot stand if someone gets a drop of anything on the vacuum pump, never have sodium sulfate or silica crust on the surface of their hood, and are crazy-intense. Some people need this to be productive.

The second type of chemist--which I fall into--is the messy chemist. These chemists know when it's important to be meticulous (like when a reaction really needs to be totally anhydrous to work and will be very careful to work dry in those situations), but are okay with being sloppy from time to time when it really doesn't matter. Their hoods might have some dirty glassware awaiting cleaning, probably because they started another reaction before getting a chance to clean up. The surface of the hood might have a bit of silica gel crust from hastily pouring a column (but when it comes to actually running the column, they are very precise). Their organizational system makes total sense to them, but perhaps from the outside might seem bit in dissarray. They realize that it really doesn't matter whether you work something up with 30 mL of the aqueus layer or 50 mL. It just simply doesn't. The messy chemist, while inattentive to some details, is probably obessive about others, like, say, labelling so that they can keep track of everything they are doing at once. And they probably have some bizarre OCD system, like the way they have their reagents arranged on the bench and when it's disrupted they're like WTF DID YOU FUCKING DO TO MY FUCKING CHEMICAL SHELF? And people are like "dude, you're shit is everywhere, and you are about something little like someone putting one bottle in the wrong order? you are a MASSIVE hypocrite."

I think both chemists types of chemists have their merits and drawbacks. For example, while being meticulous is generally praised in science, a lot of the meticulous chemists really can't multitask at all because they are so busy tinkering and making everything just so which can lead to them being less productive overall. On the other hand, some of the messy chemists tend every now and then make a wrong call on whether meticulousness really matters or not. All in all, there's a place for both types and both types can be very good chemists, but it can make lab dynamics a little rough if messy chemists and meticulous chemists need to share common space.

lab safety

There is one PhD student in my lab whose job is to be safety hardass. This means she's constantly yelling at me to wear goggles--something I can never remember to do unless I'm working with something that will light on fire if it's exposed to air or if the pressurized air is being really strange and popping the top off my column and it's freaking me out. The thing is, most days I wear very large-framed hipster nerd glasses anyway and as far as I can tell, they protect my eyes just as well as any of the lab glasses--perhaps better than the ones that don't look freakishly nerdy. In order to find goggles that actually fit over my hipster nerd glasses I need to get the huge ass glasses that fall off my face and are a huge nuisance because I'm always pushing them back up and I really don't like having my gloves that near my face when I'm, uh, working with shit that might be toxic. Furthermore, for 90% of the things I do, I really can't understand what could possibly go wrong. Okay, so maybe I'll get some ethyl acetate in my eye one day. Big fucking deal.

I understand that I'm much more lax about saftey much of the time than is entirely wise, and I'm trying to get better about it. I mean, I'm not hella old school like this one very old PhD chemist research assistant at my school who says "gloves are for pussies" and refuses to run columns containing chloroform under the hood and turns off the hoods when he feels like that lab is getting too cold. That type of shit freaks me the fuck out, and I rather like fume hoods because I dislike feeling woozy. When I TA sophomore organic lab I'm always yelling at people to keep chemicals under the hood because when 20 people are keeping beakers of ether on the bench it makes me feel quite ill. But occasionally I'll forget to wear gloves when I really shouldn't and I've spilled far more chlorinated solvents on my hands than is probably ideal. I also work with natural products quite a bit, and while my streptomyces aren't pathogenic and the compounds I'm trying to isolate are not accutely toxic as far as we know, you never know for sure, I really should always do those extractions with gloves. OOPS. It's all pretty dilute, but still. There are some people in the lab who work with very very toxic natural products and they need to be hella careful. But I'm also 21 and in that phase where I don't really understand the long-term consequences of my actions at all and feel like death is far and I am immortal. And as far as I can tell, a little bit of methylene chloride stinging my hands every now and then, while unpleasant, is not going to kill me. The other thing is, I've gotten into the biologist mode of thinking that being careful is not to protect my health, but rather it's to protect my experiments from getting fucked up, like working sterilely and shit.

But anyway, I digress. Today I was cleaning up after a prep HPLC I did on Tuesday of a synthetic compound I made recently. After finishing evaporating down fractions and making up an NMR spectra and such I needed to dispose of the rest of my fractions. I came in, asking where the waste for re-distilling acetonitrile went. I touched the top of my test tubes from my fractions (not, did not get liquid on myself, just touched the upper rim, where anything that was ever there would have evaporated off anyway). Immediately, this PhD student yells at me "DON'T TOUCH THAT IT MIGHT BE TOXIC!!!!"

This took me aback for a second because, well, it was said in an exceedingly aggressive tone. And even thought I'm just a baby undergrad, I really dislike when people condescend to me. It's one thing if you're like "hey dude, it would be a really good idea to wear gloves while you're working with that, because, you know, DCC is pretty toxic or whatever," but this was different. The thing that seemed really illogical to me was that the fractions I had were almost entirely acetonitrile and water. My compound was not in those fractions, and the only toxic things that may have been there was trace amounts of DCC (which was primarily removed in the workup anyway) and other side product junk that might have been present in very trace amounts. And my compound was not exceptionally toxic either. I mean, I certainly wouldn't eat it, but it's not something that would make me pass out if I spilled less than a miligram of it on my hand. Ironically enough, the student who was yelling at me was a smoker, which is far more carcinogenic than trace amounts of standard synthetic materials getting on your hands as far as I know.

And so, yeah, the explanation I get for such aggressive lab-saftey seriousness is that the lab is liable for anything that occurs there. But the lab is not responsible for a stochaistic effect that may happen 30 years from now for reasons that are entirely untraceable to one day of carelessness in discarding some prep HPLC samples. So I wish people would chill the fuck out about shit like that. It's my body to abuse as I choose.

I guess I just don't understand. For example, in the chemistry lab I handle carbiimides all the time on the normal scale weighing them out, which are pretty frickin' toxic. Yet when I'm visualizing a gel, there is a lot of paranoia about getting ethidium bromide anywhere. Like, special hoods and you can't bring plastic epi-holders from the EtBr hood to the rest of the lab. It just seems to me that the way lab safety is handled generally is completely absurd, and while it is definitely important, it's also not worth flipping out about to the degree that most people do.

Unless you're working with something that is seriously accutely toxic. Then it's well deserved. But if you treat everything like you're going to die if you touch it, it kind of undermines how careful you need to be with some things, I think.

Everyone in my lab thinks that I'm a chemist by training. My degree is going to be in "biochemistry & molecular biology," but they all think I'm a chemist because, beyond a little bit of microbiology, I mostly do extractions, a little bit of synthesis, and a lot of staring at MS and NMR spectra. This is strange to me, because the synthesis I'm doing is basically a simple coupling reaction. It's a one-step synthesis to make substrates for my bacteria. Although purifying the shit on a column is always a bit of a pain (I fucking hate silica gel columns even though I do them basically every other day now), it's pretty much chemistry that anyone with a little bit of lab experience and someone to show them how to use the argon-line should be able to do. I mean I know how to set up organic reactions, work them up, purify them, and analyze them. I can follow a lit prep, but that doesn't seem so special to me. I'll be the first to admit that I'm more of a chemical biochemist than a biological biochemist, but I'm also pretty early in my training.

I guess in a sense I'm a bit of a weird biochemist in that I'm exceptionally interested in organic chemistry. I've done some organic synthesis research, and I guess I know about as much organic chemistry as any undergraduate interested in organic chemistry could be expected to know, but much much less than anyone who really calls themselves an organic chemist. I can make it through total synthesis, methodology, and mechanistic papers as long as I do a little bit of wikipedia-ing, I have a basic set of background knowledge of useful synthetic reactions, and I'm pretty decent at interpreting proton and carbon NMR spectra. But this doesn't mean anything. My undergraduate synthetic projects were trivial relative to what real synthetic chemists do. Christ, my synthetic target on my last project didn't even have any non-trivial stereocenters. And anyway, I also know how to do enzyme assays and Western blots and PCR and reverse-transcription and all that shit. It just doesn't happen to be what I'm doing for this particular project.

To me the borders of biology and chemistry are entirely trivial and artificial anyway, and being expected to regurgitate the derivation of the Boltzman distribution on an exam (which was required of me for my biochemistry degree) is far more "different" to me from protein biochemistry and molecular biology than being able to run a fucking silica gel column. I'm just not sure why it's so strange to everyone that I'm a biochemist by training who is also has decent organic chemistry lab hands. Yeah, okay, you transfer small volumes in molecular biology and large volumes in chemistry, but in a sense it's all the same. Transferring liquid, following preps, troubleshooting.

It's especially strange because it's a very interdisciplinary lab where everyone needs to do a little bit of everything. I mean, even if you're a biologist, you've probably seen an NMR spectra and even if you're a chemist you've probably done some bacterial culture in my current lab. Yeah, everyone is a specialist in something or another, but everyone also needs to be reasonably literate in fields outside of their own because the nature of the projects are so interdisciplinary and collaborative.

When it comes down to it, I think what's most telling about the fact that I'm not really a synthetic organic chemist is the fact that I consider synthesis to be one more lab tool to use investigate interesting questions rather than the intrinsic puzzle of making a complicated structure. To me, methods are methods. They are important, and it's important to learn how to do them well and how they work. But at this point in my training, there is always someone (a professor, PhD student, or post-doc) to teach me the methods. So whether the methods are chemical or biological makes no difference, really since I'm just at a stage where I'm learning how to think and troubleshoot anyway.

But damn, do people like their catagories. This is something I'm going to have to learn to deal with if I want to stay in interdisciplinary science.

On Being an Undergrad...

The annoying thing about being a wee-little undergraduate student is that at my current lab, for safety regulation reasons, I’m not allowed to do labwork “unsupervised”. This means that someone has to be in the wing I’m working in while I’m working. This is understandable because I don’t have a degree and I might fuck shit up I guess, but on the other hand it’s really annoying. When I’m in lab, I’m rarely “supervised” in that it’s very unusual that someone is sitting with me looking over my shoulder telling me what to do. Usually a PhD student teaches me how to do a technique once and then expects me to do it on my own the next time, which is exactly how I like to work. If I’m doing something new or tricky, I might be supervised, but generally I’m off doing my thing and my supervising PhD student is off doing their thing and if something goes wrong or I need help or whatever I might find them but otherwise we’re both on our own, doing our things.

The project I’m working on now involves feeding bioengineered bacteria shit and hoping that they make interesting secondary metabolites with it. Feeding bacteria cultures 5 mg of some strange chemical is not difficult and takes about 15 minutes to do, but since bacteria are living things, the experiment is time sensitive and not always on my schedule. This means that I often have to go in on the weekend. This means that I need to coordinate my schedule with my supervising PhD student on the weekend while she has her life shit going on and I have mine. Which is ANNOYING.

I’m also used to going to a small liberal arts school that is undergrad only, so I’m used to having an exceptional amount of autonomy in lab. When I’m doing lab work I either have a key or swipe card access to the lab, and unless I’m doing something really dangerous or using expensive, tricky equipment that is easy to fuck up, no one gives a fuck whether I’m doing it during the day or at 2 am. I’ve come in hungover on Saturday morning to work up a reaction. I’ve come in at midnight on Saturday to run a PCR. I’ve wandered in at one in the morning to follow a reaction by TLC. In fact, I can think of two things that I’m not allowed to do by myself in lab: use the catalytic hydrogenator (in case it explodes) or use n-butyl lithium (in case I light shit on fire). A couple of my friends procrastinated their lab work so much that they pulled an all-nighter to run a bunch of Western blots and one of their girlfriends called them up panicked because it was six in the morning and they still hadn’t gone home.

So, sigh. I suppose soon enough I’ll have my degree and my own lab space and it will be the time when no one gives a fuck when I’m in lab. But for now I’m a young’un hopelessly reliant on everyone else.

Various musings

The lab I’m in currently is very interdisciplinary. The department is “biomolecular chemistry”, and the PI is originally a chemist by training, but now works with polyketide biosynthesis. His group has biologists, chemists, and biochemists working together. It’s great because there are people with all sorts of specialties, and the biologists have some proficiency in reading NMR spectra, the chemists might do a bit of molecular biology, and everyone works together. When you read his papers, you can tell that he thinks like an organic chemist, and even though he has projects that use molecular biology techniques, the goal of the lab is to understand the chemistry behind biosynthesis.

I’m happy because the project I’ve been working on uses everything I’m interested in: microbiology, molecular biology, synthetic chemistry, and spectroscopy. I’ve done a lot of bacterial culture, a conjugation, a proplast preparation, prepared spore suspensions, extractions, some DNA extraction and a restriction digest, looked at LC-MS spectra, and looked at NMR spectra. I get to hear talks about all these different projects—some chemistry, some biology, some biochemistry. It’s really stimulating because it’s all my interests coming together in one institute.

But what I’ve noticed—even here—is that I get a lot of questions. “Are you a biochemist or a chemist?” Both, I answer—because I really do feel like I’m a little bit of both at the moment. And while there are a couple people that truly are both—one Japanese post-doc for example--most people are one thing or another by training. As I am only an undergrad now, I don’t have expertise-level knowledge in any discipline yet. I’m proficient with basic biology lab techniques and basic (organic) chemistry lab techniques. I know how to read NMR spectra, but I am nowhere near an expert. With an experimental section and someone to show me where things are and how they are done in this lab, I can set up a synthesis and work it up, set up a bacterial culture, or do a DNA extraction. One of my professors described me as “riding the line between biochemistry and organic chemistry” and I guess he’s right.

I’ve spent a lot of time in the past couple years doing organic synthesis, and I consider myself to be proficient in synthetic chemistry (for an undergrad). Yet my degree is in “biochemistry and molecular biology”. I feel like I always have to qualify myself as a chemist by appealing to my prior lab experience and coursework. Yet the biochemists are surprised by how much chemistry I know, and how I talk to chemists. But I’m not just a chemist. I know how to read biology papers. I know how to design primers. I know my amino acids and my DNA binding motifs. I was interested in biology first.

I feel like I’m well on my way to becoming one of those “jack of all trades, master of none” scientists that people seem to disparage so. I read a lot about this on the internet, how these new-fangled chemical biology PhD programs are producing scientists that are neither fish-nor-fowl and know a little bit about everything, but not enough about anything. I hear the “proper” way to go about an interdisciplinary career is to do a classical discipline and diversity from there (i.e. get a PhD in straight up total synthesis, then post-doc in chemical biology/biosynthesis/med chem.) I don’t know why this is seen to be the case. As an undergrad—whether you are a biology major or a chemistry major, you need to learn things that are entirely unrelated to what you will later study. Physical chemistry is entirely different in mindset than organic chemistry; it’s a different language all together. Likewise, a lot of biology programs (such as Reed’s) require you to take evoluntionary biology. While I’m not opposed to this—it’s necessary background—being an undergrad requires you to be very flexible and mutable. You need to learn a lot things that are very different from one another. Why not take advantage of this time—when I’m young and grabbing information, before my mind is set—to really learn about all these things that I’m interested in?

Coming from Reed, which is a very small school, I think so far I have had a rather unconventional biochemistry training. I had the time to take elective chemistry courses, but also there is no distinction between physical chemistry for biochemists and physical chemistry for chemists. My biology classes, likewise, were also biology classes for biologists. The training I have received so far was not so much a biochemistry education (in the classical sense) as both a biology and chemistry education. In fact, it’s probably more chemical than most biochemistry educations, largely due to my interests in chemistry.

The other thing that constantly strikes me as odd is that there seems to be this assumption among biologists and chemists that you can teach a chemist biology, but you can’t teach a biologist chemistry. I think this is absurd, and it’s a notion propagated by lazy biologists and arrogant chemists. I mean, obviously you’re not going to have a PhD-level proficiency in either subject, but I don’t think there’s anything intrinsically more difficult about (especially organic) chemistry than there is about molecular biology. Take two examples: synthetic organic chemistry and cellular biology. Both are incredibly complex, interrelated subjects that require a huge amount of background knowledge. Neither are particularly mathematical, and both are about arranging patterns in your head more than they are about memorization. I really don’t see why a cell biologist couldn’t sit down with an organic chemistry textbook or sci-finder and learn a bit about organic synthesis and more than a synthetic chemist couldn’t sit with a textbook and pub-med and learn about cell biology. It strikes me that there’s a lot of “chemistry-a-phobia” in biologists, and a lot of “my subject is intrinsically harder that your subject” in chemistry that is all a bunch of nonsense.

Summer in Germany; Polyketide Biosynthesis

As I may or may not have posted before, this summer I'm going to do a lab internship in Jena Germany at the Hans Knoll Institute: Leibniz Institute for Natural Products Research and Infection Biology in the department of biomolecular chemistry in Christian Hertweck's group.

The story of how this works is the following: I was writing a paper for my biochemistry seminar which focused on chemical biology and I stumbled upon work he was doing with polyketide biosynthetic enzymes in the aureothin (a Streptomyces thioluteus polyketide) pathway. Specifically, AurH, an enzyme catalyzes the chiral oxidation of a THF ring. This paper caught my attention as a mechanistic paper that dissected how the enzyme worked to act as a catalyst and this paper* used the enzyme in a stereospecific total chemoenzymatic synthesis. I read about how they figured which enzyme did the oxidation using molecular biology methods, along with how they figured out how the enzyme worked with biochemical methods, and then their application synthetically. It intrigued me because it was basically exactly the sort of research I want to be doing. It seamlessly integrates biology and chemistry. It relies on both synthetic organic chemistry and molecular biology. Dissecting mechanistically interesting biosynthetic steps that are difficult to mimic with classical reagents is just a really fascinating area of study to me. So I wrote a review paper for my class about research from his lab.

So one day, kind of on a whim I emailed Christian Hertweck, the PI with my CV. He was impressed with my background and my strong desire to do interdisciplinary science and offered me a summer internship at the HKI. I've been in correspondance all year working out the details. So I will be in Germany this summer doing chemical biology research.

It hasn't really hit me that I will be in Germany this summer doing exactly the sort of science I want to be doing. It seems like such a lucky shot in the dark.

I'm so pumped for this summer and next year. I like learning, so classes are alright, but what I really like is doing research. It reminds me "oh yes, this is why I study science."

Also, this will be my fourth consecutive summer in a lab, along with doing research in my prof's lab during the year for a bit and an undergraduate thesis. Although not my motivation for wanting to be in the lab in the summer, that's gotta look attractive to graduate schools, right?

*As a tangent, I also really like the journal ChemBioChem, which is a European chemical biology journal published by Wiley. ACS Chemical Biology puts out a few interesting articles, but it feels uninspiring a lot of the time (and virtually indistinguishable from what goes into ACS Biochemistry), and Nature Chemical Biology seems differently focused. There is some interesting bioorganic work being done here but the the mentality seems different somehow. It seems like the organic community is more seemlessly integrated in this European journal. More on this later.

On being an o-chem lab TA

It's very funny to me; all of a year ago I was a struggling sophomore messing up the very most basic of things in organic lab. I remember feeling frustrated, feeling like I was bad at lab, feeling like I was one of "those kids" for the prof and the TA.

Now I am a lab TA for organic, and it's all very automatic. I can anticipate the questions before they come; my eye gets drawn to certain very specific mistakes. It's usually things like "no you're sep funnel isn't broken, you just need to uncap it before running it down," or "by the way, your reflux condenser hoses are connected backwards," or "you don't need to heat that--25 degrees is room temperature," or "do more polar things run higher or lower than less polar things on silica gel?" or "is water more or less dense than most organic solvents?" or "you should really put boiling chips in that".

Furthermore, when people ask me for NMR help, it's funny what seems so obvious now. Like common solvent peaks--being able to just identify ethyl acetate or isopropanol or ether. Just knowing what shifts and J-values are characteristic of what.

I guess I can see how some of my professors are the way they are after, you know, 40 years of this.

I'm a lab TA organic chemistry, and tomorrow they are doing Grignards. Hopefully no one will point the heat gun at a flask of ether. It should be exciting times, though.

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?

decarboxyllating on the rotovap?

In the adv. synth. lab, there are dry ice rotovaps. They're pretty efficient and nice, but there are only two of them and there are eight or so of us. So sometimes we set rotovaps up in the regular o-chem lab (which is right next door, and they are conjoined by a weighing/reagents room) which are normal, cold water rotovaps and aren't nearly as efficient. I was trying to some last traces of ethyl acetate and ethanol out by rotovapping out some toluene, and I really had to crank the heat on one of the rotovaps in the regular o-chem lab in order to get such high boiling solvents out (whereas it would have been no problem with one of the dry ice rotovaps). My professor comes by and he says "well, I guess you have to really crank the heat on that thing to get toluene out. Now, normally that would be a problem, but we're just going to decarboxyllate that diacid anyway by refluxing in toluene for 48 hrs, so if some of it reacts in the rotovap, that's fine." ( It's funny--if I had heard a sentence like that a year ago it would have zero meaning to me.)

It's always nice when lab inconviences work in your favor.

I also really miss my old research lab (which is upstairs). Where there were only two of us, and glassware was plentiful and the only person I needed to share the rotovap with was my labmate.