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.