This is dumb

I was reading a paper today, and it indicated in its figure legend that it used CS ChemOffice to draw some organic structures. And I begin to wonder, why the fuck is this information necessary to include in a figure heading?

I mean, I get with proteins and shit that it's important to say what program you used for your refinements and such when presenting a structure because...uh...that's part of your method. But this a) was not presenting novel results--just giving background in the intro and b) is there really any substantial difference between a line drawing made in ChemDraw versus a line drawing made in IsisDraw/BKDraw/ChemSketch/whatever? Why don't we say "I did my word processing in Microsoft Word." Or "I analyzed my data in Microsoft Excel." "I did my lit searches in PubMed." Or "I looked up this reaction on SciFinder". Or "I edited my gel images in Adobe Photoshop". Yeah, I guess you get the picture. I just don't understand why this is in a JBC article.

Step I in applying to graduate school

Took the general GRE today and took the subject GRE a week ago. The general didn't go as well as I hoped, but at least they show that I'm not totally retarded.

This means I'm done with standardized tests forever?

Switching gears...

I spent time today scanning NCBI for start and stop codons and got an email from my advisor about how we would discuss whether I should put my protein in a GFP or SUMO plasmid and what restriction sites would work tomorrow. I really am going into biochem land.

thesis

So I've got a thesis topic for my undergrad thesis. And a thesis meeting early tomorrow morning with my two advisors. I'm pretty psyched about it. I'm going to be co-advised by one of my favorite profs at Reed and someone who works in the area of natural product biosynthesis at Portland State University.

The project is going to be to clone and express two enzymes responsible for an interesting transformation in an antibiotic biosynthetic pathway. If I manage to get them pure I'm going to assay them with the appropriate analogs of the natural product and attempt to characterize them. One of them is interesting because it shows no sequence homology to the class of enzymes you would expect it to be in. It's required for the biosynthesis in knockout studies at the genetic level, though so it will be interesting to see what the deal is there (if I get that far).

So basically messing around with cloning and expression for nine months. Protein biochemistry is my one big gap right now in my lab training. I've got basic molecular DNA & RNA techniques down, I've done some cell bio stuff like ELISAs and Westerns and histology and various biochemical assays and shit, and I know how to do synthetic organic chemistry. But I haven't worked with cloning and expression and protein purification and all that stuff that makes you a real biochemist.

I hear protein work is boring as shit and frustrating as hell. But running silica columns is also boring as shit and can be frustrating as hell. So I guess I will finally have a true opinion of which is more boring: cloning or silica columns. And I can tell my chemist and biologist friends to STFU because I know all of boring, thank you very much, in all of its flavors.

Anyway, my general philosophy on this matter is that all fields of science has its boring and you just choose your boring and go with it. I can get through boring--the project just needs to be interesting. To quote the aforementioned Reed professor "Experiments suck. Until they don't."

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.

I am going to have an honest appraisal of my scientific strengths and weaknesses. Let’s start with the negative:

• I have trouble with school. I’m not an abysmal student, but I’m not an exceptional one either. I have trouble with exams, and you’ve probably seen this whine before. For whatever reason, I have difficulty presenting information on a page that is demonstrative of my conceptual understanding of material—and all of my professors have commented on this. My current boss, actually, who is a brilliant PI, claims to have had similar problems as a student. He is extremely creative, has an encyclopedic knowledge of his field, is able to pull the right people together to manage a productive lab dynamic, is able to follow over 30 people’s projects (many of whom have multiple projects), and is able to publish in great journals in part due to his great sense of presentation and his ability to spin results into narrative stories. He tells us that he wanted to study biochemistry in university but his grades were too bad so he had to study chemistry instead (he’s German, so there you have to choose your field of study before you start), and that for whatever reason he just didn’t fit in the mold that school expects from you. My professors keep telling me that this will really only be a problem that will persist through my first two years of graduate school, and that it’s unfortunate, but wouldn’t it be worse if it were the opposite—I flew through my coursework and then I crashed and burned in a research project? I suppose that’s true, but it also makes getting into a decent program more of a crapshoot.
• I’m a little bit messy and spacey and I have difficulty with attention to detail. I’m just not a meticulous person by nature, and I tend to do spacey shit like letting something go on the rotovap for ten minutes before I realize that I forgot to shut the vacuum every now and then. In written work, I have difficulty with catching typos and small but stupid chemical errors like dropped carbons. Usually, at least in lab, when it’s really important I can focus, but sometimes…sometimes shit happens.
• I have a really shitty math background. Math has never been my strong suite, and I’m in a program that let me get away with taking very little math due to the way math is taught at our school (i.e. for mathematics students, we don’t have applied math classes for science students since it’s not the liberal arts “way”). Of course, I needed to get through physics and physical chemistry, which means I have some basic competence with algebra and calculus, but I imagine that if I ever need to take stat mech or biophysics or biophysical chemistry or anything like that in grad school, it’s going to be a fight. I just tend to look at scientific concepts in more pictorial terms.
• Adding to the "messy and inattentive to details" bit, at times I will cut corners that I maybe shouldn't cut when I'm under a time crunch. My lab notebook, for example, gets progressively worse the more I work on a project. Again, I think this is normal.
• I really can't handle extremely aggressive people. A lot of the cutthroat competitive behavior I find pretty distasteful and I'm generally pretty intolerant of that kind of BS. It strikes me that there are a lot of these type of people in science--especially science at a high level--and I need to learn how to deal with them.
  

Okay, the positive:

• I’m always praised on my creativity and the degree of sophistication that I have in putting together scientific concepts, and this has come from professors, my current boss, and the PhD students that I work with currently.
• I’m always praised on my ability to process the concepts and link them up to what I am physically doing in lab. One of my supervisors told me that I have such a high understanding of the theory that it’s often difficult for her to remember how much help I need with the little lab things that only come with experience, one example being how much trouble I had figuring out the right way to set up my first sephedex column. I had done many silica columns, but there are a few tricks that you need to do with sephedex columns that I just didn’t know. But she says that there are many undergraduates who come in and they don’t really have the big picture of what they are doing and why they are doing it.
• I’m very good at processing the literature. I know how to find papers and how to mine them for information. I also can competently read organic chemistry (synthetic, mechanistic, and natural products), biochemistry, and molecular biology papers. I’ve also been told that I know how to write about/talk about/communicate science in a story after reading papers/seeing talks/working on a project. At least profs tell me positive things when I turn in term papers.
• Sort of combining all of the above points together, I noticed that people tend to give me more autonomy in lab after I chat with them about science a bit. This is kind of strange, because just because I have the conceptual framework in my head doesn’t mean I need any less help getting the wet work to work. But I think there’s a psychological component with people where they are more likely to treat you like a colleague when your ideas are in place. That comment isn’t meant to under-value good lab skills, though.
• I have the obsessive sort of personality that once I get started on a project, I get completely and totally into it and don’t want to stop. I can be a bit of an obsessive work-a-holic from time to time. It’s difficult for me to disengage and I’m either completely into it or not into it at all. I suppose this is a good quality to have as a research scientist.
• I really like working with my hands in lab. Doing office work all the time is boring, and I think physically doing things with ones hands is sort of relaxing (sometimes; unless it's annoying).
• I have a good intuition for organic chemistry and bioorganic chemistry in terms of structure and reactivity. I just sort of know what reactions are reasonable, what structures are unstable, and have a solid sense of this in my head.
• I’m pretty good at spectroscopy, especially NMR. I’ve got a lot of chemical shifts, j-values, and solvent peaks for proton and carbon (well not j-values, but whatevs) in my head from doing a lot of synthetic organic chemistry, and correlations make sense to me. It’s the sort of visual puzzle that I’m good at, and I have a fair bit of experience with it. I’m also decent with MS, UV, and IR.
• I’ve got a decent knowledge base in a variety of fields. Along with knowing organic chemistry, I also know a fair amount of biochemistry and molecular biology, both the theory and the lab techniques. I’m kind of one of those hybrid interdisciplinary scientists, and this is just because I really do like it all.
• I'm pretty used to the idea that shit doesn't work most of the time in science. I guess I've spent enough time in labs to figure that out. Having shit not work doesn't really bother me that much--you just need to keep trying and hope that with hard work and a bit of luck it will all work out.
• It's pretty drilled into me to write everything in my lab notebook and label everything. One of my profs said that it was very easy to repeat reactions that I did and to keep up the good work. But my synthetic organic lab notebooks are a lot better than, say, the project I'm doing now where I'm never sure how much to include and there's a lot of "continued on page XXX" and MS spectra after MS spectra. My molecular biology lab notebooks are the worst, especially when I'm using a lot of kits.
  

AA structures

I recall last year a senior biochem major told me that she had forgotten the structure of the amino acids over the summer DESPITE THE FACT THAT SHE WAS DOING A THESIS ON PROTEIN BIOCHEMISTRY*. This horrified me. She was a great student, a hard worker, got good grades, etc. I guess people give memorizing structures a bad rep, but I think if you get a degree in biochemistry, you should fucking have the amino acid structures in your head, IMHO.

So today, I decided to test myself to see if I was being too judgmental. I needed to memorize the structures of the amino acids and the one letter codes last fall for structural biochem as well as the nitrogenous bases, so it's been several months since someone demanded that I have this knowledge at my fingertips. I guess took another biochemistry course after that, and I look at a lot of nat. product structures, so it's not like I just shut my brain off to biochem and peptides since I took that course. So I drew them all out from memory today just to test myself.

And I knew all of them still. All 20 of them right, suckers! Well, the one letter code for aspartate slipped my mind briefly, which is D, by the way. And I stupidly dropped a hydrogen drawing a couple of the bases. But I still knew which places had carbonyls and which had amine functionalities.

So phew. I guess I still feel justified in calling myself a biochemist, and in holding people to this standard. Is this an unreasonable standard? I dunno. I don't think so.

*okay, it was enzyme kinetics, so she wasn't exactly looking at her protein structures all the time--just dealing with bi-bi ping pong shit, but still. Still. Degree in biochemistry.

angst

I'm starting my last year of college in the fall, and this is causing me more mental angst that it probably should. It stems from feeling unprepared for dealing with What Comes Next.

Senior year at Reed is a pretty hyped process. Everyone needs to write a senior thesis and the science seniors lock themselves in the lab and look haggard and depressed by shit not working and start prematurely behaving like grad students. They keep odd hours and are totally devoted to their thesis at the exclusion of everything else and thus whine-a-thon culture is encouraged by the culture of the school. At the end you need to give an oral defense and (in the chemistry department) an oral presentation to your classmates during one of the seminar days.

I have a lot of plans for next year, perhaps too many. I got in contact with a professor at a neighboring institution who works on polyketide biosynthesis so I can continue work in the area that I'm doing this summer because it fascinates me. I'm excited, but I have no idea what to expect and whether I've cut out more work than is strictly necessary in facilitating this project that involves a Reed advisor and an advisor from this neighboring institution. Hopefully I'll manage to arrange a project where I can have a Reed lab setup for instead of having to commute to the neighboring instution to do my labwork (I don't have a car) so that I don't loose time constantly, although I'm worried that our instrumentation is not adequate.

I'm also tentatively trying to organize a journal club starting in the fall, and trying to organize an independent study project in the spring on biomimetic synthesis. My rationale for the independent study (not a lab independent study, but a reading papers and writing a review-style document at the end sort of independent study) is that it's more interesting to me than taking a structured course and probably just as much work. I don't really like taking exams much, and I read papers all the time anyway, and it's in a subject that's not really related to what I'm probably going to do my thesis in (thus a bit of a mental break from that), but in a subject that I have a lot of interest in. But I suppose I might feel differently about it at the end of next year.

And I'm trying to figure out this whole grad school shit, while angsting about it and paging through professors' webpages and sending emails instead of hammering through GRE problems. I mean, I've little bit of GRE prep, but not a sufficient amount, and as the days crawl closer and closer to the academic school year, this is starting to stress me out more and more. The problem being, I guess, that I'm pretty caught up in my labwork here. Studying for standardized tests is boring, whereas labwork and paper reading is engaging. I fear this problem will be the exact same one I'll face in the fall. I also have to take a stupid analytical chemistry course that I know I'm going to abhor that will probably get pushed to the last priority.

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.

Boring talks

So, the lab's summer retreat is coming up. I'm going to be back in the good ol' US of A at the time, but I get to hear about it, and one thing is that everyone needs to give a talk.

These talks can be about whatever anyone wants to talk about, whether it's related to their research or just some random topic they find interesting. For example, last year someone decided to talk about whether science and religion were at odds with one another (this topic is dull, sry, I just am sick of hearing about it), which apparently started a lot of discussion.

Anyway, the PhD student I'm working with is trying to come up with her talk. The other talks that people are giving seem pretty dull so far. This one guy is talking about lab safety and security (snore), this other guy who is one of those obsessively meticulous tinkering organic chemists is talking about how to use lab equipment properly. He basically is going to go on for ten minutes about how no one really knows how to use the high vacuum pump correctly and you actually do it like this and blah blah blah blah blah (the PhD student I'm working with said she hoped she would be drunk by that point). Someone else is talking about the antibacterial problem, bugs versus people, which, while in principle is interesting, it's a topic I've heard so many times that it's become pretty dull. I guess last year there was a talk about how to troubleshoot PCR (change the Tm, change the cycles, change the magnesium chloride concentration, etc. etc. ad nauseum), time management, and teamwork in science.

I suggested that she give a talk on how to multitask in lab. I mean, if someone can talk about how to use lab equipment, then why not? She's famous for being "a scientist on speed" and always running 90 million things in parallel. The other thing I suggested was that she give a talk on the chemistry and health benifits of coffee. She's a huge coffee drinker, so it would be pretty amusing. Then I suggested that the other PhD student I work with should give a talk about how smoking cigarettes lowers your risk for Parkinson's (since he's know for being a chain-smoker). That might cause a few laughs, at least. And the dopamine axis is pretty fascinating.

But anyway, I think I'm going to make a list of boring talk topics that I've had to sit through:
1) How to use Web of Science. Really, seriously, it's a frickin' search engine.
2) How to use Sci-Finder. This was useless to me, because things like Sci-Finder (and Web of Science) are things that I just need to tinker with to really learn how to use.
3) Lab safety in all its iterations.
4) How to properly tutor someone, how to deal with personality clashes, how you weren't supposed to have whine and commiseration sessions about particular professors during tutoring, etc. etc. During that seminar I wanted to ask, just to be obnoxious by the end "what do you do when if you sleep with your tutor/tutee and they won't respond to your emails because shit got awkward?"

So yeah. I think horrendiously dull talks should be outlawed.

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.

Biomimetic synthesis

Lately I've been getting really into biomimetic synthesis.

It's interesting to me because one criticism I hear a lot of total synthesis is that it doesn't ask questions. Or rather, the question is, "can we make this huge-ass natural product with eight bajillion stereocenters?" and the answer seems to always be "with enough depressed, overworked graduate students, yes?" It's been described to me as the "climbing the mountain" metaphor by a professor, whatever that means. Actually, it's mostly molecular biologists, I've noticed who go on this Theory of Science rant about the scientific method (observation, question, hypothesis, experiment, knowledge or some variant of that) and how synthetic organic chemistry doesn't follow it. It's a favorite rant of a physiology professor of mine's.

Then, as far as I can tell a lot of mechanistic organic papers are like "so dude, we noticed this stereochemistry forming and thought that was cool so we invoked a Hatree-Fock 31-G transition state model and then examined some MO secondary orbital effects and tried to rationalize the stereochemistry and found out that this other cool reaction also occurs so we examined that too and it occured in an x:x dr because of blah (probably)". I had a physical organic chemistry class where the professor was really into asking us questions like "is this paper hypothesis-driven or a data-driven?" and then he and I would get into long discussions in his office/email exchanges afterwards about it because I nearly always would claim that the paper read like a fishing expedition. But I digress.

Biomimetic synthesis is definitely hypothesis-driven, because it asks the question, "is this putative biosynthetic pathway plausible?". Furthermore, the stereoselectivity lends evidence as to whether the reaction is enzyme-mediated or spontaneous. If the natural product is racemic, it's probably spontaneous, but if it's enantioselective, it's probably not (but, as one person pointed out in a paper I read recently, the cell is a chiral environment, so perhaps that is leading to some stereoselective effects that are difficult to predict) . I read of this one example of a biosynthetic Diels-Alder reaction that only resulted in the exo product, despite the endo product being highly favored in the RBF. Or, if you can only get stereoselectivity with a Lewis acid, that indicates that there is probably an enzyme there performing the role of the Lewis acid. And this is really cool, because you can think like a synthetic chemist, but you can also ask questions about how the world works. And not just at an abstract theoretical MO level, but at something that's a little more discrete to me--a biosynthetic pathway leading to a metabolite structure.

I guess it's also appealing to me because I finally have enough of a background in pericyclic reactions (due to the aformentioned professor and the aformentioned physical organic class, which was called "Advanced Mechanistic Organic Chemistry") to make sense of all these 8π-6π electrocyclization cascades and Diels-Alder reaction selectivity nuances and Cope rearrangements and [1.7] hydride shifts. And some of the structural rearrangements are wicked. They are generally basically just pericyclic refoldings of polyenes derived from fatty acids or polyketides. It blows my mind that something so simple can re-arrange into such a vast structural diversity.

The other thing that occurred to me while reading these papers, is I recall (sorry, I'm too lazy for refs at the moment, although I really should link most of these papers) that in the past few years there have been several papers on "On Water" Diels-Alder reactions. Sharpless has done a bunch of work on this, and the principle is the same principle that drives most of structural biochemistry in terms of lipid structure and protein folding: the hydrophobic effect and solvent entropy. There have been some pretty impressive rate and stereoselectivity enhancements from doing Diels-Alder reactions on water, since the reagents are forced to be in close proximity, minimizing the entropy of finding one another in a reactive conformation relative to being dispersed in solution. Since many Diels-Alder (and other pericyclic) reactions require thermal conditions that are far from physiological (beyond weird thermophilic archea and such), it's interesting that there is such a rate enhancement from these on-water reactions, and I imagine that there's a lot of work in the future that needs to be done to elucidate exactly how the role of the cellular aqueus environment impacts the kinetics of these biosynthetic reactions.

On Review-Writing

About a month ago, my PI asked me if I'd like to write a minireview with him. This was like "whoa seriously?", and I dove into a huge pile of papers on primarily pretty obscure natural products research. This is really only an opportunity afforded to me because a) my PI is a really nice guy and b) I'm an American abroad, so being a native English speaker is considered a huge advantage and c) I have no idea, it just sort of happened when I was in his office one day. I've been slogging through a ton random plant pathways in old articles from the '70s and '80s in Phytochemistry and huge exhaustive Angewantde reviews on polyketide biosynthesis and biosynthetic Diels-Alder reactions and Natural Products Reports reviews on biomimetic synthesis and so on and so forth.

I'm kind of known in my lab for being strangely obsessed with reading papers for a 21 year old student who isn't done with her bachelors yet. I don't know when I got into this habit, I guess over the past year or so I realized that reading papers on my Google Reader RSS feeds was a great way to procrastinate memorizing point groups and doing arduously long problems on the Boltzman Speed distribution when I just wasn't in the mood for it. It's also a habit, I guess, that people encourage in me, like attending seminars, so it tends to get reinforced. I am lucky enough to attend an undergraduate institution that puts a lot of emphasis on processing the primiary literature, so in a sense doing a minireview is just a step up from writing a review-style term paper, which I have written several of. It needs to be more polished and incorperate more references, but in essence the task is the same: read a shitfuckton of papers, summarize them, re-draw a bunch of schemes in ChemDraw the way you want them drawn to illustrate your point, and keep reworking the document until you're like "when the fuck will this goddamn thing be written?" while somehow perversely enjoying the process.

So, I have a first draft written, and thus I've stepped into the process of starting to seriously write it instead of it just being some abstract Thing. It's just I talked to my PI last week and he was like "oh yeah, well I think we should re-order the examples like this and this and this and by the way this random metabolite pathway actually incorperates this intermediate not the one you have drawn and here's 8 million more references because I think you should talk about xyz pathways as well. But I don't want it to be exhaustive! Oh, also, you should download the paper template to the journal I want to submit it to, even though we are far from done writing it." I'm a little bit overwhelmed by the prospect of re-ordering all the ideas and putting them in a cohensive whole because, well, god, I don't know, it just really is a lot of work that still needs to be done. Also, I fucking hate when you track down eight references from some obscure research done in the '80s only to find that there was a relatively recent review article that incorporates much more recent findings on the topic that for whatever reason just wouldn't show up in your original Web of Science search. You find out in review writing that there's a lot of trash published in the literature, like structures that are just plain wrong or have ambiguous stereochemistry when they really shouldn't (endo or exo isomers in Diels-Alder reactions are, uh, kind of important, and you'd think something that one could elucidate via NMR) and a lot of citations that are just wrong (like papers that were published in 1982 cited as being published in 1992? and when you can't track down the reference you're like...wtf is wrong with me? oh wait. no, it's not me, it's them). I guess I also have my fair share of problems with making stupid chemical errors in my schemes and reference list, though, so I shouldn't be so harsh.

Also, I seem to have some paper that for the life of me I can't figure out what it has to do with the topic I'm writing about. I'm pretty sure it's a paper he handed me and not one I found on my own. It's like "blah blah blah his tag blah blah blah PCR blah blah blah protein expression blah blah blah enzyme blah blah blah iron center blah blah blah".

But yeah, it's a process. An interesting one, at the very least.

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.

Among the many things I admire about my boss includes his sense of scientific presentation and his creativity in communicating science. His papers read like narrative stories, and he has a great sense for the right sort of catchphrases to use. I want to be able to write that like.

Combinatorial peptide synthesis

Yesterday we talked about a paper in journal club from Nature Chemical Biology. It was one of those combinatorial peptide synthesis papers--in this case to find a inhibitor of a protein in the clotting cascade (a serine protease that activated a precurser of a signalling cascade, I guess). It struck me that all these papers are the same. Do some combinatorial peptide (or peptide analog, or chemical altered peptide with some functional group sidechain), create a library of compounds, screen them, and try to find some compound that is an inhibitor or probe or whatever of some protein of pharmacological or biotechnological relevance. The targets change, the screening methods change, sometimes the synthetic methods change (although it's usually some variant of solid phase peptide synthesis). But the general idea stays the same: boring. There wasn't even any interesting structural biology about how the compounds worked as an inhibitor (my PI suggested that perhaps one of the moeities on a segment of the peptide blocked the catalytic triad--now that sort of hypothesis is something I can actually get into).

I guess I wouldn't be so judgmental about this research if it didn't seem like every issue of Nature Chemical Biology (or ACS Chemical Biology or Chemistry & Biology or ChemBioChem or what have you) had at least one article like this. In the introduction they always introduce their methodology as a novel (novel!?!) modular combinatorial method that is very promising as a way to find compounds of medicinal interest blah blah blah.

There's nothing that is really all that intellectually satisfying about this area of chemical biology to me. It's all the same. There's no narritive story to it--just hammering.

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.

When can we start calling ourselves an "ist"?

I was talking to my friend, and I made the mistake of saying "I think I am more of a chemical biologist than a biochemist in the traditional sense."

He said "You're a fricking undergrad. You're neither. What do you mean by that, that you took a few organic chemistry classes and liked them? That's absurd."

Then I said, "You're absolutely right. Right now I am just a student. But what I mean is how I think about science."

He said, "What do you mean, how you think about science, that is ridiculous. I just don't understand what you're talking about when you say shit like that."

But what I mean, I guess, is that in the biology-chemistry interface-land, what is biology and what is chemistry and what is biochemistry and what is chemical biology is totally artificial. But they are words that we use to describe an approach to solving problems, the way experiments are designed, and a school of thought of training.

I mean, one could say "I just don't think like a cell biologist, I think like a geneticist." This means something to me, even though there is a large degree of overlap between what a cell biologist is and what a geneticist is, and a cell biologist better know genetics and a geneticist better know some cell biology. The way papers in Cell are laid out are just different from the papers in Nature Genetics. And not just visually, in the intellectual approach.

Biochemistry is neither biology nor chemistry (although it's both) in a lot of ways. It's kind of its own thing. It's got it's own kinetics. It's got it's own brand of tedious separation chemistry. It's got it's own sort of sensibility. The mindset that I am in when I read a paper from Organic Letters is totally different from the mindset I am in when I read a paper from ACS Biochemistry.

I feel like by junior year, as a student you have a pretty good sense of what sub-specialty of your science training you are good at and interested in pursuing further and what area you are most "minded" like. And as far as I can tell, I'm most "minded" in this relatively new biology-chemistry hybrid business people refer to as chemical biology. Is that so absurd?

Enzyme Kinetics

I've taken two biochemistry courses now, structural biochem and metabolic biochem. I guess this is a pretty standard undergrad curriculum. Both dealt with enzyme kinetics fairly extensively, and I realized today, sitting in class and going over bi bi multi-substrate mechanisms--ping pong and ordered sequential--that both classes took a totally different approach in allowing us to think about enzyme kinetics.

In structural biochem took an approach where we did Michaelis-Menton, inhibition, etc. but it was always in a "how can we change this interaction in the active site with the substrate to affect catalysis". It was pretty concrete to me, because you can mess with concrete, chemical interactions, like a hydrogen bonding interaction between residues, or some residue that kinks the protein out of alignment conformationally. Km and kcat had a directly linked cause--and that cause was intermolecular interactions.

In metabolic, it's sort of at this gross scale of when the substrate binds and when the substrate comes off. It's taking a step back from structure, and thinking about timing and mechanism at a larger scale. It's no longer this glutamate residue--it's just substrate A binds before substrate B. The mathematics feels so abstract, because I feel like I can't really picture in my head the fact that the blobular enzyme is undergoing small scale intermolecular interactions with the blobular substrate. It's just line drawings; it's schematics. I like it ok, and it's certainly a powerful approach. But what draws me to chemistry is structure, reactivity, and function. It's this viceral visual way of thinking about molecules coming together in space. And that's kind of lacking for me in Lineweaver-Burke plot after Lineweaver-Burke plot.

Incidentally, in reading the enzyme kinetics page on Wikipedia, I found it ammusing that "bi bi ping pong" was a totally technical term, and not a Ron-ism. Ron throws in conventional technical terms (which are, to be fair, often goofy sounding) with his own enzyme kinetics lingo, so sometimes hard to tell what is a general term that the biochemical community uses, and what terms are unique to him and his research. For example, he studies an enzyme that never lets go of its substrate, and so he likes to call those enzymes "Promethian enzymes". If you recall, Promethius in Greek mythology stole fire from Zeus, and to be punished, he had to be chained to a rock for the rest of his eternity while eagles ate out his liver. Then he would re-grow a liver and the cycle would repeat. So I guess that is an apt analogy.

How I'm spending my weekend:

Pictures tell this story better than words

pKas

One thing I am apparently good at:

I am a pKa machine. I basically can tell you the pKa of just about any organic molecule off the top of my head. If I don't know it, I can usually extrapolate what it is from related structures and by how well you can stabilize the conjugate base. I continually impress people by this ability and by how rarely I need a pKa table.

Usually I have a shoddy memory for rote memorization, so I have no idea how this stuck so well.

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.

Last year of college?

My course schedule for next year (my last year of college, eek) looks tentatively like this:

First semester:
--Thesis
--Analytical chemistry; graduation requirement. Enough said. I don't think anyone enjoys propagating error and if they do they are a freak of nature.
--Imperial Christianity; religion class, gotta get those liberal arts requirements done, plus it's with a badass prof
--Topics in Biochemistry; a mellow seminar that meets once a week for an hour and a half to discuss papers, next year the topic is the role of metals in biochemistry

Second semester:
--Thesis
--Cellular biology; only going to take the lecture portion of this, though. I've had experience culturing cells and doing Westerns. The only thing I feel like I'm really missing is learning how to use the qPCR machine. In any case I don't want to be in cell bio lab when doing a thesis, but I really would like an introduction to the field beyond what I've picked up over the past few years (i.e. run away from the MAP kinase pathway).
--Advanced inorganic chemistry; it's a half-unit lecture only course. I-chem is just starting to pick up for me since we are doing transition metals and you get to go into the really cool stuff in there; it also derives group theory.
--Intro drama; an English class, I feel like I could use some more literature classes in my life

I have enough credits that I could drop either cell or advanced i-chem second semester and still be good to graduate and may very well do that so I can spend more time on my thesis. More importantly, my classes are clumped together well so that I have a lot of time to spend in the lab.

Yesterday my boyfriend was sitting in the chemistry lounge, listening to a podcast of an NPR interview with David Foster Wallace. One of my chemistry professors walks by and starts chatting about how David Foster Wallace taught at Pomona at the same time he taught at Pomona.

Alan (my professor): So apparently he wasn't a very happy guy.
My boyfriend: Well, you know, that's what writing about the postmodern condition will do to you.
Me: Or thinking about molecular orbital theory too much.
Alan: Oh that was sharp. Is this a disgruntled chem 324 student I hear? [i.e. advanced mechanistic organic chemistry]

Yes, Alan. Yes it is. I have such a love hate relationship with MO theory. On the one hand it explains...just about everything more or less and is really fundamentally important for understanding chemistry. I switch between thinking the quantum mechanical explanations behind it are fascinating at a conceptual level and not particularly interesting in its details. Bond models feel like bullshit to me; with all the different iterations of orbital theory, I don't know how someone can graduate with a degree in chemistry thinking that it's any more than an amalgam of useful models that sort of kind of approximate reality and happen to explain shit well.

Usually I'm ok with this fact. If I felt that science was free of "woo woo" (as one of my bio profs liked to call things like lit theory and epistimology) then I would really be a headcase. At the same time I'm sick of hearing soc majors after taking a sociology of science class tell me that science is just socially constructed and no more legitimate than any other dicipline of study because, yeah, bonding models do--at some level--contain some "bullshit" but people have still used them to, like, make an LED out of a fucking semiconductor. And band theory is hella useful for explaining that behavior.

Stat therm

Last night my boyfriend asked me (he's a chemistry major, although a sophomore taking organic right now) what the reagent NBS did. I could answer him immediately and even describe the structure of the molecule and that NBS stood for "n-bromo succinamide".

Organic reagents, pKas, structures of the amino acids, NMR shifts and typical J-values, IR shifts, even some boiling points, this is all at the tip of my fingers. It's just stored in my head--anything organic or bioorganic is just there. I haven't forgotten it.

There's an incredible amount of information pertaining to organic chemistry and biochemistry that is just completely accessible in my head. I do not understand then, why it is so difficult to download thermodynamics equations in there. It's not like I enjoy memorizing pKas anymore than I enjoy memorizing thermodynamic definitions.

I realized earlier today that I have been approaching physical chemistry all wrong. I have a really shitty memory for information without context and so while some people can just cram equations into their head for tests that tends to not work for me. Organic rarely required memorization beyond a few weirdo reagents whose mechanisms were beyond the scope of the class; it was just mastering a few trends and then applying problem solving. Math is like this too, and physical chemistry is math. I need to learn the definitions and work from there and apply problem solving to derive everything I need.

Since I am uncomfortable with math as a language given my poor schooling in calculus, I have generally considered myself not mathematically facile enough to apply this approach to stat therm. I realized today, though, that the memorize special situations equations approach and memorizing derivations approach isn't going to work either, because there is just too much goddamn material for that. And I am facile enough with algebra and calculus...I just need to be confident that is the case. I need to work with the language and do the problem solving.

Why won't the algebra work out?

Fugacity is currently the bane of my existence.

Electron spin existential crisis

Last night while studying for an inorganic chemistry exam I have tomorrow, I suddenly had a huge existential crisis about not understanding magnetism.

It went something like this: how does MO theory tell us that oxygen should be paramagnetic and carbon should be diamagnetc?

Well, oxygen has unpaired electrons in its HOMO. Carbon has paired electrons in its HOMO. One or more unpaired electron leads to paramagnetism.

Okay, hold up. So why does oxygen want to have its electrons have the same spin when one goes into each degenerate orbital? Why, well, electrons repulse each other since they are negatively charged, thus if they can, they will go into separate degenerate orbitals (following Hund's rule). Due to the Pauli exclusion principle that means that electrons cannot have the same spin and position. If they have the same spin, they necessarily have different positions, which leads to less electrostatic repulsion. This is my qualitative understanding of the issue, and it is also--to my understanding--responsible for the phenomenon of exchange energy in half filled shells.

(Filling out orbital diagrams in this order has become intuitive to me after three years of undergraduate chemistry, but I guess I rarely step back and re-rationalize why it's the case).

So coming back to paramagnetism. This means that if those two electrons have the same spin, there is a permanent magnetic moment in the molecule (right? but what what is a magnetic moment anyway?!?! crap.) which means that it creates its own magnetic field. I recall the Lorentz Force law from physics (is this even exactly related?) although much of what I remember from electricity and magnetism involves a lot of fussing around with the right hand rule and being confused by which direction my thumb went. Anyway, if there is a permanent magnetic moment when put in an external magnetic field, the magnetic field can be parallel and thus be attracted. Whereas when a diamagnetic species is put in a magnetic field, since there are two electrons going in opposite directions, one of the vectors must necessarily oppose the magnetic field.

Okay, this makes sense, although I'm sure I butchered a few of the details. Then there's something something angular momentum vector something something spin momentum vector something something more quantum mechanics something something. But then I ask myself what is spin really? Why does it run parallel to the magnetic field. Why are parallel magnetic fields attracted to one another? Does it just have to do with the orientation of the electrons compared to the nucleus? WTF? Wait, wait, this was all beginning to make sense, and now it's all falling apart again.

So I waste hours of time on Wikipedia physics pages being confused.

It's funny that we use the same language as people who actually have a deeper level of understanding of these phenomena, but don't actually understand it at a deep level at all. It's all about shorthands to understand the parts we need to understand--in this case--for chemical reactivity and understanding MO theory.

The more chemistry I learn, the more of a head-case I become.

Junior Qualifying Examinations

So at Reed you have to pass a junior qualifying examination before you can register for your senior thesis. As an interdisciplinary major, I had to take both biology and chemistry. Biology was an open note/book/internet exam basically based on my coursework. I wrote an essay about haploinsufficiency in Marfan's syndrome fibrillin-1 gene and the elastin gene in Williams' syndrome and another essay where I wrote about the growth hormone axis and how nutrition (both being malnourished and obese) affected this axis. I also did some quantitative questions like calculating Tms of DNA strands and making buffers. I should hear back about it soon, although I'm afraid I might have gotten a conditional pass from messing up calculating TRIS on that buffer question, eeek. It's not a big deal if that happens, I just need to fix what I got wrong.

The chemistry qual was an oral exam where I was given this paper and had to learn as much as I could about it in 48 hours. Then they asked me questions, specifically about the paper, but really probing my organic chemistry knowledge as a whole. I had two options, an organic option and a biochem option, and I decided to go with the organic option. The biochem option was interesting too, it was on nicotine binding in the brain and how it is different from its inhibitory effects on your muscles (if it did hit the receptor in your muscles you'd be dead). But ultimately I felt more comfortable with the sort of questions they would ask in an organic qual, especially since my advanced synthetic final last semester was in the exact same format. Luckily, my organic paper was a synthetic paper and not a mechanistic paper--because for some reason the long lists of data tables with numbered compounds in mechanistic organic papers followed by colums of de's and ee's result in my eyes glazing over a lot of the time.

I think it overall went well. A lot of the questions were definitional--what is the kinetic enolate vs. thermodynamic enolate, what is an allene functional group, what is "latent stereochemistry". The main places I got tripped up on were mechanisms. I had this divinyl oxy-anion cyclopropyl Cope rearrangement mediated by a Brook rearrangement, and I started off drawing the reaction in a different perspective than I had in my notes which kind of threw me. The paper went to great pains to discuss why this enolate attacked from the more sterically hindered side (because it was reversible and resulted in the more stable transition state for the subsequent Cope) but to demonstrate it only showed what didn't happen due to steric repulsions--so there was no picture to look at what did happen. Which I knew, but it's just sort of difficult to pull all of that together visually on the board with weird bicyclic systems and the boat transition state and so forth. It went ok, I just had a moment where I was like "wait Connie..."

The other place I got tripped up due to nerves was the mechanism for oxidizing an enolate with a Davis oxaziridine. Again, it was ultimately ok, just a little bit of nerves. Also drawing 7 and 8 membered rings on the whiteboard was tricky!

The spectroscopy portion was easy since they had already assigned the peaks in my paper and my profs didn't ask me anything too difficult. Just like, why methyl groups attached to silyl groups were more upfield than methyls attached to carbons and whether this one set of diastereotopic methylnes were chemically equivalent or not, and why they had different J-values coupling to a neighboring proton that sort of thing.

It also struck me last night that wow, college has crammed a lot of chemistry into my head in the past 2 years.

So I should be hearing back about whether I passed, conditionally passed, or failed those shortly.

Nature Chemistry and Twitter

This month is the first issue of Nature Chemistry, and as far as I can tell they appear to have some sort of free preview for the first issue because I'm positive that Reed doesn't have access to this journal, but I've been able to access the full text PDFs. It seems like a good read, although I haven't had a chance to look at it all that thoroughly.

In addition, I have learned that all the major journals AND sigma aldrich have twitter feeds. As if I really needed to know about the latest advance in chiral chramotography in a two line twitter blurb, heh. It's sort of an interesting form of information flow, because I've noticed that this sort of abstract of an abstract catches my attention occasionally in ways that my RSS feeder doesn't.

I also learned that Nature Protocols gives out the occasional free featured protocol. This week it is how to produce silk-like spider proteins recombinantly. Which I'm sure has a lot of relevance to my life, but anyway, it's kind of cool that you can get random protocols without paying $500 a month. So if you were ever curious about how to make and purify spider silk-like proteins, you're in luck, I guess. I learned this from twitter as well.

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.

Molecular computing: logic gate

This is pretty neat: it's a molecular logic gate. It senses pH, sodium concentration, and zinc concentration, and if all three are present, it fluoresces. I just found the concept to be pretty clever. The molecule looks like this:

J. Am. Chem. Soc., 2006, 128 (15), pp 4950–4951

DOI: 10.1021/ja058295+

I am so fucking tired. My god. I don't know how I managed to get this sleep deprived.

The semester goes ok. Physical chemistry is giving me some demons because I suck at math. That last stat therm test was pretty brutal. I hear Dan's tests are always brutal though. Anyway, it's just going to be something to get through.

I don't have much structured course-time as I am only taking one lab class but a lot of homework all the time. I'm also working on something in one of my profs labs so in between classes I'm usually running reactions and working things up and taking NMRs and so on. Squeezing in time in the lab on top of a full load of classes is a completely different matter than having seven or eight hours during the day to just do chemistry like it has been doing summer research. It's making me really excited for thesis next year, though.

I love being in the lab doing projects. What I don't like are class labs. It honestly just feels like a huge waste of time to spend eight hours taking data that no one gives a fuck about and has been done thousands of times before and will yield crappy results and then spend another ten hours writing some bitchy-ass stupid lab report where you have to anal-retentively propigate all the error and so on. It's just biochem methods and analytical that I have to get through still and then I am relieved from stupid lab classes. I guess I see why they are useful and necessary, but by junior year you just sort of feel done with it. I want to be in lab the doing research and not doing annoying pedigogical exercises. The exposure to lab techniques is good, I guess, but I almost feel like I'm at a point where I can pick up most lab techniques as necessary.

I've also been thinking more and more about applying to grad school next fall. Basically, I just want to be in a situation where I am discussing and learning about science at a high level and being in the lab. I've always thought I would take a break between grad school and undergrad but I'm starting to think that I'm ready to move on to that phase of my life.

quantum mechanics won't solve all your problems

It took three years of chemistry education, but I think I finally understand what a wavefunction is and what quantum chemistry is. While I have very little native interest in the process of integrating over all space and solving differential equations to reach quantum mechanical approximations (I'd rather appreciate the fruits of other people's labors in that area...or get the computer to do it), I think I finally get quantum chemistry is all about conceptually (and why it is very bizarre). I think having calculus, statistics, and physics really solidified all of this for me--even if I can't do the math facilely operationally, I do know what a differential equation is, what the dot product is, why probabilities have to integrate to one, what the complex conjugate is, and what polar coordinates are...and Dan, Maggie, and Alan have given me a pretty solid conceptual idea of what the mathematical gears behind orbitals and energies are.

Depending on what I do later in life, I may or may not need to confront all this at a higher level, and beyond just a conceptual level, but I think I'm content now with the fact that I'm not going to have time to take it before I graduate.

I'm feeling better about my life choices right now. Working on my inorganic chemistry problem set--and I realized that this class is really fucking cool. It gives you just enough quantum mechanics to appreciate what quantum is and what the beauty of it is. I mean, I know that at some level I knew what orbitals were, but it's kind of neat to see a function (even if we're not going into the nitty gritty details of the mathematics) graphed in polar coordinates and suddenly an orbital appears.

I'm also feeling better about the freakout I had on Friday where I wished I had been a straight chemistry major. Because effectively, I've taken pretty nearly the same courses as a chemistry major but I also know about as much biology as a biology major. I'm a little deficient in the math department, but I do know a lot of science.

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.

There's so much to chemistry

Basically what this semester seems to be boiling down to is physical and inorganic chemistry are waaaaayyyy different from organic. Jesus christ.

I've been fussing around trying to calculate the numerical radii for the radial nodes of a 3s and 3p orbital for frickin' ever.

and so it goes

Today I decided to drop my biology seminar in favor of keeping all of my chemistry courses. I'm feeling good about this decision, and I have a tough semester ahead of me but I really like all my courses (well, besides stat therm, but stat therm is a necessary evil), and regardless of whether or not it's more or less work than my other classes, it is one more thing to keep track of. The course is offered every year so I can take it next year, and bio seminars are good courses to take as a senior. I haven't attended it yet, which makes it easier to drop, and I really like my advanced mechanistic organic chemistry class. Advanced mech only has 5 people in it which gives it a nice small feel, and overall it's just a fun course. Which means I'm taking all chemistry courses, and only 3 units (technically). Inorganic (even without the lab) and stat therm in particular are highly time consuming courses and not going to seminar on Wednesday nights gives me more time to hammer through psets and study for them. I have a good feeling about this semester; not taking any biology courses is going to be a little weird, but whatevs, at least I have biochem.

It also gives me more time to play with my little project (although PEOPLE KEEP USING THE COMPUTER LAB SO I CAN'T USE SCI-FINDER! grrrr).

Onto making flashcards to help me memorize the periodic table for inorganic.

I feel like my rather shitty math background has been a constant handicap. Due to the fact that the math department at Reed only teaches theoretical math geared towards math majors, and due to the fact that Rao (the math head) determined my semester of calc I at UIC as equivalent to Reed math 111 (calculus), I have managed to skate through Reed college only taking probability & statistics. Because of this wacky math system, math 112 is more introduction to proof writing than a calc II course, and I was told that unless I was really into theoretical math it wasn't going to be fun and it certainly wasn't going to be useful. I never took calculus in high school and I didn't want to push physics to my junior year (thank god I didn't).

Due to this situation the chemistry and (especially) the physics department pick up some of the slack. Yesterday I learned how to take a second partial derivative with respect to two different variables. Having never taken a multi class, I picked up the concept of a partial derivative and how to do it in intro physics when learning about the wave equation. I had never seen the notation for a double partial derivative before. I'm a little shake on integral tricks too.

I'm usually ok with this fact, and I've kind of accepted that I'm more prone to think about the world in descriptive terms. This doesn't mean that I'm not down for a few computations, but I'd rather plug it into a modelling program or mathematica. I'm good with scooting around arrows, stability rationalizations in the style that organic chemists do it, and basically things that operate in pictures and words with small amounts of algebra and maybe a derivative or two. I love to learn about biophysics and I think the techniques that are out there are quite fantastic, but my understanding of them is all in pictures and words. Same goes with NMR. My feeling for the physical world is one where math is a tool, but I'm not interpreting it through it. I see math is a way to get better pictures in my head. This is at a stark contrast to the way physicists--and for that matter, even physical chemists--seem to view it--as if they interpret physical phenomena through math.

I'm re-learning about the quantum numbers for inorganic (I learned it in intro chem once but forgot) and there's always something in the book like "you can solve the Schrodinger equation for hydrogen and hydrogen-like nuclei, but we're not going to go into it in here" and sometimes it makes me feel bad about not taking quantum. It's like, even though I did quite well in my synth class, I feel like I don't have quite the feeling for what is all behind it as some people. I know that what I learned in intro physics I generally rarely use beyond bits and pieces here and there, but it was good for backing up my general physical intuition and understanding for how things work. Conservation of energy, waves, momentum, acceleration, electric and magnetic fields, these are all fundamental things that I need to understand as any sort of scientist--and are even helpful conceptually for biology. Ploughing through it all, I can't really do those problems anymore but I left with a better conceptual understanding of the physical world. Dan reminded me the other day that physical chemistry does this for other types of chemistry, i.e. the pictorial representations of stability rationalizations are quantifiable (well, sometimes) and that's where the theoretical basis for these qualitative observations come from even if we don't always have the computational power and models to find them quantitatively. It doesn't mean I have to want to be a physical chemist, but I do realize the power in other chemical approaches and understand why I need to learn about them.

I think a lot of my issue with math is a lack of confidence from being "bad" at it for so long. I mean, calculus is a tool like algebra and not like WHOA COMPLICATED OMG MAGIC!

On the up side, speaking of nice, fuzzy picture-based synthetic organic chemistry, Pat gave me a little project to mess around in the lab with. He gave me a couple compounds he'd like to make and test the pKas. I need to go play with Sci-Finder to see if they have been made before. This is good; they're small molecules and models for the types of compounds the lab as a whole works with, but in the past the research I did with him was more guided like "here's this idea I got, I'd like you to try it out" instead of asking me to find preps that I might be able to run. I also know more chemistry and know how to use Sci-Finder better than I did when I worked for him last summer, though.

First day back

As predicted, my chemistry courses are pushing me out of my comfort zone. Inorganic and stat therm are totally different types of chemistry from what I'm used to dealing with. Even adv. mech is pushing me out of my comfort zone with some tough Diels-Alder structures. I'm ok at seeing them retrosynthetically (I think probably from reading Totally Synthetic)--but for some reason the product picking and remembering the endo rule is harder for me to put together since I don't have much experience with dealing with pericyclic reactions. I also realized that I don't know where anything is on the periodic table besides...uh..most of the first two rows. I don't know what Maggie is going to think on my pre-quiz. If only I could take solely organic chemistry classes...

I had a minor flip out about not being mathematically prepared enough for stat therm after working through some calculus review Dan gave us. Also not knowing how to do double partial dervitives with respect to different variables. He sat me down and showed me how to do it and assured me that the calculus would not be my problem--it would be the algebra and the concepts and that I had a decent grasp, even of partial derivitives. I also had an involved conversation with Alan about various things, including things posted the other day, and about how he and his wife coordinated their careers.

I feel so much more at home in the chemistry department than in the biology department like 99% of the time.

Musings about being a woman in science

Again, the fact that I have so much time and intellectual energy to spend writing my thoughts in this blog indicates that it's definitely time for classes to start again (they start again tomorrow...9 am statistical thermodynamics).

One thing I've been thinking about lately is the idea of how difficult it is going to be to have children if I pursue a career in science. Clearly women do it. My roommate's PI at Oregon Health Science University has a daughter. At my school--which is a liberal arts school and not a hardcore research university to be fair--there is one woman chemistry prof who has two children and three women biology biology profs. Only one of the three women biology profs had a son, although one of the three is in her early 30s and just got on tenure track a couple years ago. (Tangentially, it's remarkable how few women faculty members there are in the sciences that is now that I write that out).

People write about how academia is notoriously difficult for women if they want to have a family because there is no good time to get pregnant. By the time you finish your PhD and post-doc, you're already in your early 30s and not in a position of job security. I've heard of people having kids while they are in graduate school, but usually men. My friend and his brother grew up as little kids on graduate stipends (he said his parents always felt guilty about being unable to provide for them well, but they felt like having macaroni and cheese for dinner every night was awesome--you don't notice when you're a little kid). But the thing is there's no way in hell it would be responsible to carry a fetus while doing lab work, especially in synthetic organic chemistry. I mean, I'm just thinking about the amount of chloroform I inhale while running a column, even when using the hood correctly. That means that you have to take, essentially, a whole year off of working if you want to have children. I'm not sure how other careers--like industry careers--are affected.

My mother was an environmental scientists and worked for the EPA when she had me and she basically worked throughout her pregnancy. She at one point did toxicology stuff and would go to the dump to take samples, but she did other office-based work as well that allowed her to do work that one can safely do while pregnant when she had me. After my brother was born she took time off and returned briefly when we got older, but stopped working again when we moved when my dad got another job. She's now an artist and works on Go Green Wilmette, the local environmental effort in the town we live in, a suburb of Chicago. She said that she sometimes feels guilty for not providing a better model for a working mother, and that we don't understand that the field she was working in was highly male-dominated and that she was one of very few women to work in environmental science in the '80s.

She said on the other hand, though, she didn't want us to be raised by nannies. If she was going to have children, she was going to do it right. I grew up in DC until we moved when I was ten, and there are plenty of families with two parents that had high powered jobs and I knew plenty of kids who saw more of and were more attached to their babysitters than their parents. I have a lot of respect for my mother, and I don't think her choice was a bad one or a weak one. I think that I was raised well, that my parents are intellectually curious people who instilled some of that curiosity in me, and that, although I don't agree with 100% of their parenting choices, they are a pretty good model for how I want to raise my children someday.

I'm at a stage in my life right now, unlike some of my friends, where I don't have a serious long-term relationship yet. A few of my friends are trying to coordinate post-graduation plans (whether it is grad school, Teach for America, or employment) and while enough of them manage to work it out, it seems to be a huge headache--especially for graduate school. One or the other person usually has to compromise or else they're doing long distance for 5 years, and I imagine it doesn't get any easier after that. One of my chemistry profs and his wife worked it out nicely where he works at Reed and she works at Portland State University and they have children and each have tenure. Two of my friends worked it out for REU programs last summer, but it was stressful and one of them had to compromise by going to a (very good but) less competitive program than the best one she got into. It gave them a serious taste of how it would be when they both applied for PhD programs...

More of the girls I know--even as an undergrads--are paranoid about planning their lives and their careers. We think about these consequences way more than our male peers, and we wonder about how taking a path that takes a lot of training--like getting a PhD--affects having a family. This is the main argument I see for jumping into grad school directly out of undergrad.

Edited to add: this New York Times article has some interesting statistics. Excerpt:

Surveying outcomes for 160,000 Ph.D. recipients across the United States, the researchers determined that 70 percent of male tenured professors were married with children, compared with only 44 percent of their tenured female colleagues. Twelve years or more after receiving their doctorates, tenured women were more than twice as likely as tenured men to be single and significantly more likely to be divorced. And lest all of this look like “personal choice,” when the researchers asked 8,700 faculty members in the University of California system about family and work issues, nearly 40 percent of the women agreed with the statement, “I had fewer children than I wanted,” compared with less than 20 percent of the men. The take-home message, Dr. Mason said in a telephone interview, is, “Men can have it all, but women can’t.”

Also, this article addresses the issue with some interesting data on it as well.