in singulo: A blog that used to be about Single Molecule Biophysics

Surprise! Grad School Sucks! Now STFU and Get Back To Work!

2013-04-14T21:26:00.002-07:00

Point: Rebecca Shuman

Getting a literature Ph.D. will turn you into an emotional trainwreck, not a professor.

By the time you finish—if you even do—your academic self will be the culmination of your entire self, and thus you will believe, incomprehensibly, that not having a tenure-track job makes you worthless. You will believe this so strongly that when you do not land a job, it will destroy you, and nobody outside of academia will understand why. (Bright side: You will no longer have any friends outside academia.)

Counterpoint: Karen Gregory
You’re Fucked, and You’re Probably to Blame.

Yes, things suck. I make no bones about that, but these screeds overlook the work that students are doing to organize, agitate, and resist the restructuring of higher education. And this oversight raises the question...did you then get involved in your union, in an activist group, in an education alternative (like the Free University), or in a conversation with your students? When did you start realizing that a career in academics also means addressing the very conditions of our labor? What have you done besides comparing the kind of tenacity it takes to be a graduate student today to being a willful smoker who smokes “four packs a day” and hopes to not get cancer?

My contribution to this insipid debate: I think they're both right, and they're both full of horse shit. Rebecca Shuman is right that graduate school sucks and you will hate yourself for failing to get a tenure track professorship even though it's statistically almost a certainty that you will fail. Karen Gregory is likewise correct that Rebecca Shuman is wallowing in her own steaming pile of self-pity, and she should STFU and deal with the fact that it is, in fact, a meritocracy, if a flawed one, and she failed on her own merits, not because the system is rigged. But, more importantly, Karen Gregory is blaming the victim, and is completely full of shit if she thinks that activism and organizing by grad students is going to have even the slightest effect on the commoditization of higher education and the resulting decline in quality and jobs in academia. I was a union organizer in graduate school. I organized the SHIT out of grad students. Guess what? It still sucked. And in the end, we may have gotten cheaper healthcare, but we didn't change The Academy™ at all. We weren't in it for that, we were in it to make our lives suck just a teeny bit less. No amount of singing protest songs is going to change the fact that our society is evolving, that engineering and data are on the rise, and erudition and the storing and reproduction of factoids in a mushy mass of cells is no longer the sine qua non of human achievement. The Academy is gone. It's never coming back. It's being replaced by Year of Code and Open Courseware and all sorts of amazing open self-directed self-didactics. Hard sciences will always be a mainstay, and will continue to require enormous amounts of cheap graduate student labor powered by coffee and hope. But college as a Place of Learning, as opposed to a Place of Credentialing while Drinking, is not coming back. Give it up.

Rectal epistemology

2012-11-11T11:19:00.003-08:00

A selection of results obtained from Googling "you wouldn't know if it crawled up your ass", presented without any further commentary (except to note that an exceptional number of these came from YouTube comments):

You wouldn't know [heavy metal] if it crawled up your ass wearing snowshoes in a blizzard.
You wouldn't know a first rate interviewer if it crawled up your ass and spit out Glen Beck[sic].
You wouldn't know a truth if it crawled up your ass and tickled your tonsils.
YOU WOULDN'T KNOW A STORY IF IT CRAWLED UP YOUR ASS, CAME OUT YOUR NOSE, LAY ITSELF IN YOUR ARMS AND CALL YOU MOMMY!
You wouldn't know a fact if it crawled up your ass and gave you bad breath.
You wouldn't know cool if it crawled up your ass and fucked you.
You dipshits wouldn't know good commentary if it crawled up your ass and blew your fucking fartbox apart.
You wouldn't know what butthurt looks like if it crawled up your leg and sodomised you with a rusty cheese grater.
You wouldn't know what a fact was if it crawled up your trashy ass and died.
You wouldn't know a good idea if it crawled up your ass and chewed off your balls.

Okay, I take it back, I will provide one piece of commentary, in the form of my contribution to this genre: "You wouldn't know [insert topic about which the subject knows nothing here] if it crawled up your ass wearing a tutu and danced the Nutcracker."

It's all in the swagger

2011-08-01T00:01:00.001-07:00

If I need to explain what this is to you, you shouldn't be reading this blog.

Happy Passover!

2011-04-19T20:15:00.000-07:00

Since we had our seder last night, some friends requested Diana's superb chicken recipe (nobody requested my brisket recipe, though. Sniff.) Reproduced here:

I used Rub with Love Chicken Rub http://store.tomdouglas.com/products/rub-with-love-chicken-rub. If you don't want to order it, you can make a reasonable substitute with 1/4 cup brown sugar, 4 tsp smoked paprika, 4 tsp coriander, 4 tsp garlic powder, and 2 tbsp chinese five spice powder.

Clean and rinse the chicken. Coat liberally with olive oil, then season with spice rub and salt and pepper. Place the chicken breast side down in the roasting pan. Roast for 15 minutes at 350 per pound of chicken. 2/3 of the way through the cooking time, flip the chicken breast side up and coat again with olive oil. Use a meat thermometer to test for doneness- the chicken can be removed from the oven when the temperature reaches 145 in the thickest part of the chicken (between the drumstick and the thigh). Allow the chicken to rest, tented with foil, for 15 minutes before cutt

On This Day In History

2011-04-01T14:18:00.000-07:00

For a few years at Princeton and U of I, I was in the habit of making posters for fake talks and hanging them around the physics department on April Fool's Day. Some of my favorites included:

Applications of Non-Linear, Non-Homogeneous, Non-Solvable Partial Differential Equations

and

Theoretical Biophysics Colloquium

Insane in the Membrane:

Insane in the Brain?

Prof. B. Real

Cypress Hill University

The Journal of Universal Rejection

2011-03-20T19:53:00.001-07:00

http://www.universalrejection.org/

This is so brilliant that I'm actually sad I didn't think of it myself.

"The founding principle of the Journal of Universal Rejection (JofUR) is rejection. Universal rejection. That is to say, all submissions, regardless of quality, will be rejected."

I may dig up "Quantify vs Quantitate" and submit it, but right now the Intarwebs have forgotten it, and I'd need to go back through my old archives to find it.

This Shit Just Got Real

2011-01-19T10:44:00.000-08:00

Because I know you've missed me.

A Discovery with Many Potentially Useful Applications

2010-12-03T07:26:00.000-08:00

Via regs to my inbox (it's not new, but still funny): Medical researcher discovers integration, gets 75 citations

For Hire: LabView coders and optics jocks

2010-11-19T10:00:00.000-08:00

I've been doing some work for a local biotech, and they're currently in need of somebody to do some short-term LabView coding and optics work, like in the next few weeks. It pays well, I just have absolutely no time for it right now. If you do, let me know! This could become a longer-term situation if it works out. The location is in silicon valley not far from Stanford. Struggling grad students welcome!

Graphene? Really?

2010-10-05T12:32:00.000-07:00

Can somebody with more condensed matter background explain to me why the 2004 discovery of graphene is worth the Nobel? It was less than 10 years ago, and although everybody is predicting lots of practical applications, so far there have been none. I presume that it's being used by a lot of people to test lots of theories about 2D electron transport and quantum behavior, but to me that makes it more of a tool for testing interesting theories than an interesting discovery in its own right. Of course, people do win Nobel prizes for tools (laser cooling, for example) but I don't see graphene as being in the same category of importance. Anybody want to tell me what I'm missing?

You call this programming?

2010-09-23T11:52:00.000-07:00

In the past couple of months that I've been learning Java on-the-job (i.e., incorrectly, with no formal guidance), I think I've spent the majority of my time doing the following, in order of how much time I've actually spent doing it:

1) Trying to convert properly between several roughly equivalent types in order to feed data from package X into a method from package Y.

2) Figuring out which package contains what I’m looking for.

3) Figuring out why eclipse is F’ed up.

God Man versus Science Hero!*

2010-09-16T16:58:00.000-07:00

Via BoingBoing

*Note: My views on theology, religion, deism, and atheism are actually complicated to enunciate**, and reference Gödel's Incompleteness Theorem, the problem of induction, and the semiotic fallacy, and are still evolving. I don't really endorse the view of SCIENCE!(tm) being in direct opposition to RELIGION!(tm). I just thought this was a funny cartoon.

**Maybe if you ask nicely I'll write about it someday.

Churn

2010-08-31T08:31:00.000-07:00

PacBio going public in order to raise...$200M? That's kind of a pittance compared to the $300M they already have from VC. Is that a bad sign? I guess I don't really understand the finance side of things.

And, on the heels of that announcement...

Helicos sues PacBio. The last refuge of scoundrels.

In Silico

2010-08-19T13:47:00.000-07:00

In case you've been coming here day after day, wondering why I have stopped posting, and where in the world is Carmen Sandiego, I thought I would update my (rapidly shrinking) fan base with my whereabouts: for almost a year, with the prospect of my funding drying up, and no publication in easy sight, I spent some time taking stock of my options, and deciding what I wanted to do with the rest of my life. And, the fact of the matter is: I was bored. I was unhappy. I really think single molecule biophysics is awesome, and fun, and there's great stuff happening. But I had discarded enough plastic pipette tips to last a lifetime, and was finding it increasingly difficult to care about the rate constant for phosphate release of E. Coli RNA polymerase in the presence of XYZ. Additionally, I had grown to really love the bay area, and didn't want to leave my friends, my girlfriend, and my hang glider behind.

My options, as I saw it, were:

Keep on keepin' on, and try to find a professorship at the University of Wallamaloo, or wherever I could, and hope that things would be more fun and interesting as a mid-grade intellectual at a mid-grade university.
Back out, and try to find another postdoctoral appointment doing something completely different, and hope that, four years down the line, at 38, I wasn't totally burnt out on that as well. I considered computational evolution, or even getting a masters in EE or CS, and seeing where that took me.
Get a real job.

I talked to a lot of people, and received some encouragement from some corners, most notably from Ben Ovryn at AECOM who strongly encouraged me to not give up on academic science. Just as conspicuously, I received no such encouragement from my research advisor, who, when I discussed my options with him, basically shrugged.

I applied for biotech jobs, software jobs, and a professorship at City College of New York, because I thought it would be fun to live there and teach there. I considered taking a year off to write a book, or become a professional hang glider pilot, or both. I thought of opening an artisanal sandwich cart in San Francisco with a friend of mine, because, let's face it, you can't get a decent deli style sandwich in the bay area. In the end, I had a job offer from a high flying biotech startup that would have required me to move to the east coast, and a job offer to work at a friend's software company, and I chose the latter.

So, this is where I am. I'm currently employed as a Forward Deployed Engineer at Palantir Technologies in Palo Alto. The software is incredible, the people are amazingly smart and fun, and my group is mostly comprised of Ph.D.s who left science to try something else, and wound up here. I do a bit of everything: I project manage, I code, I do some outreach, I integrate data, and I sometimes look for new and interesting ways to use our product. I've been here for four months, and it's been pretty much non-stop excitement.

I've learned a lot. First, that there are a lot of really smart people out in the private sector, if you look in the right places. Scary smart people, the kind that academics will tell you don't work in the private sector. Second, I've realized that many of the dysfunctional relationships I had in the academic world were not actually due to my personality flaws, but were largely due to the peculiar culture that tolerates (and in some cases rewards) dysfunctional interpersonal relationships in academia. It's refreshing to work with people who are smart, engaged, enthusiastic, and who genuinely want to work together to create something worthwhile and powerful. I think, to some extent, the archetypal academic interaction is the pissing contest, where people jockey for status, because status is the only currency in the academic world. All other forms of interaction are subordinate to the pissing contest. It's refreshing to step away from that world. And, third, it took me two or three months out of academia to realize how really bored I was with what I was doing. It's not that I think it's intrinsically boring; it's just that it wasn't really driving me to do more and accomplish more, but I had had myself convinced that this was the way to go, that this was interesting because everybody else said it was. With some hindsight, I can see that if I had found it really that fascinating, I would have been eager to get up and get in there to do more. And there just wasn't that drive, and it was making me miserable.

So, I'm here, I'm finally liking what I'm doing, and I'm liking the people I'm doing it with. I'm getting up in the morning excited to come over here and face the challenges of the day. I'm still advising the grad student who's following up on my work a little bit, and I'm even doing some consulting for a biotech startup in Silicon Valley, just to stay in the game for fun. And, if I ever start to get bored with what I'm doing, I'll remember what it feels like, and I'll do something else. I don't know if I'll keep updating this blog again. Now that I've come back and gotten the long-overdue explanation out of the way, I may just post little sciencey tidbits here and there to amuse myself. We'll see.

And, finally, if you're a bit bored or frustrated with academia, you have some programming/technical experience, and you want to work for a company that offers three free meals a day, free laundry, free massages, free beer and cookies, and some of the most interesting and clever people you've ever met, hit me up. We're hiring.

Judge Invalidates Human Gene Patent

2010-03-30T11:48:00.000-07:00

According to the Times, the finding casts doubts on pretty much all patents on human genes. Bad for pharma, good for the rest of humanity.

Worse Living Through Chemistry

2010-03-08T11:54:00.000-08:00

As some people have noticed, I'm not much of a chemist. I would go so far as to say that it's one of my weak points. But this list of "Things I Won't Work With" has to be some of the most interesting and funny reading I've seen in a while. People in my lab tend to freak out about things like acrylamide, ethidium bromide, and beryllium fluoride. I tend to think that as long as you don't ingest anything or get it in your eye, you're probably okay, and shouldn't freak out too much. And, this list really gives you a sense of perspective, e.g.:

You start off by making absolutely pure anhydrous hydrogen azide, which is a proposal that you don't hear very often around the lab, and is the sort of thing that leads to thoughts of career changes...The next step is introduction of the fluorine, and when elemental fluorine is the most easily handled reagent in your scheme, let me tell you, you're in pretty deep

Protons in zeptoliters

2010-03-04T08:56:00.000-08:00

Looking at Ion Torrent's new technology, they are detecting base addition by the release of a single proton. This seemed a bit far fetched to me. I mean, water is constantly in flux between the protonated and deprotonated state, so how could you detect a single new proton? So, a rough back-of-the-envelope calculation (just to prove I can still do it):

Assume that their nanofab chamber volume is about 1 zeptoliter (10^-21L). I got this number from one of Pacific Biosciences' papers, but I'm guessing the scale is quite similar. The concentration of one single hydrogen ion in 1 zL is then:

(1/6 x 10²³)/(10^-21) ≈ 2 mM. That is actually quite a bit! Thought about another way, though, pure water is at 55M concentration, so there are 55M x 6 x 10²³ x 10^-21= 33,000 water molecules in a single reaction volume, so you're trying to detect a single proton against a background of 66,000 possible free protons (two per water molecule.) That makes it sound a bit harder. In any case, it's apparent that it works!

Thanks!

2010-02-24T16:27:00.000-08:00

Just wanted to close out the BPS week with the following graph showing my traffic over the past 30 days:

That big jump there is when the BPS put my blog on the front page. Quite impressive! Thanks to everybody for visiting! Now that the BPS is over, I hope you stick around!

BPS Tuesday Reflections

2010-02-23T17:42:00.000-08:00

I had lunch today with a PI whose lab I applied to several years ago when I was looking for postdoctoral positions. I eventually settled on Steve's lab, but he's one of the nicest guys I've met, and we serendipitously got together at the meeting and had an hour or so to chat. It really gave me a lot of perspective on where my career has come from, and where it's going, the latter question being on my mind a lot lately. I think, if I'm coming away from this conference with anything, it's a commitment to do what I want, and what I think is interesting, rather than what other people think I should think is interesting, and damn the consequences. The fun science isn't usually the easy science, and the science that conventional wisdom holds to be "important" or "interesting" isn't always fun. If Gordon's Law of Maximal Uselessness holds true, and science fails 90% of the time, you're better off having fun than trying too hard to impress people, because your attempts to impress people will probably be futile anyway, and this way, at least you had fun!

I wandered around some posters, listened to some talks about chromatin, and am going to head off for dinner, then back again for the superresolution talks. I have some business at Stanford in the middle of the day that can't be moved around tomorrow afternoon, so I might just stay at home tomorrow, rather than come up for two hours and go back. So, keep your pants and your powder dry, science aficionados, and don't miss your flight!

Intarwebs Scarcity

2010-02-23T11:53:00.001-08:00

The lack of wifi in the conference rooms and the relative difficulty of getting on the conference center wifi even in the lobby is making this a bit rough. I'm back to phone blogging.

William Shih's talk on DNA origami was fascinating, but I didn't really get a sense of how likely some of these more complex structures were to form. They're pretty though!

After an excellent dinner with colleagues, much beer, and watching the American curling team get trounced by the Chinese, we came back for the national lecture, but got shunted into an overflow room. It seems like the conference planners just didn't plan for this vig of a conference.

The national lecture was good though. Roger Tsien really is a great speaker, and his work on genetically encoded EM reporters is really great.

Tonight there are three simultaneous sessions from 4 to 6 all of which I wan to attend: Biotechnology, Genome Organization, and Force Spectroscopy. Argh.

At The Chieftan with Block Lab!

2010-02-22T18:30:00.000-08:00

Thermo Fisher Makes $6B bid for Millipore

2010-02-22T14:09:00.000-08:00

Via my father, oddly enough (he's a transactional attorney, not a scientist, so I guess this is the closest our lives come to overlapping):

Feb. 22 (Bloomberg) -- Thermo Fisher Scientific Inc., the world’s largest maker of lab instruments, made an unsolicited takeover offer of about $6 billion for Millipore Corp., according to a person close to the situation.

More here.

On a more positive note

2010-02-22T10:45:00.001-08:00

I'm a bit of a curmudgeon (actually, I'm a lot of a curmudgeon) so it's easy for me to complain, and as a postscript, I thought I'd say some nice things:

The talk at imaging and spectroscopy on mNeptune looks like it will be incredibly useful. It's a new fluorescent protein that just sneaks into the water window. You can excite it with 633 nm, and detect it at 650, allowing you to do intravital imaging while avoiding hemoglobin absoprtion. I suspect many people will find that very useful.
Two different talks on superresolution imaging of neurons are starting to show the real promise of superresolution imaging. The attempt to use it to trace all the neurons in a brain sample looks very ambitious, and I appreciate ambitious. Of course, the problem is it's sloooowwwww. If you have to fix the cell, why can't you use EM? That's a genuine question, by the way. Why can't you just do EM on brain slices and trace neurons that way, with way more resolution than you can get with any fluorescence technique? There must be a reason this doesn't work. Are they hard to stain with EM probes? Do they degrade rapidly under EM? Inquiring minds want to know.

BPS Day 3: Monday, must be Paris

2010-02-22T10:16:00.000-08:00

Finally found 1) a seat, 2) an outlet, and 3) an IP address (the Moscone center wifi seems to be pretty overloaded. You'd think a famous important science blogger would be able to get an IP address, but I guess the hardware doesn't distinguish.)

Some thoughts on last night's single molecule workshop:

The workshop was chaired by Steve Quake, and the first talk went to one of his colleagues who basically used the time to demonstrate the commercially available sequencing machine that Steve's company, Helicos, has on the market. He talked about the science behind it, but it wasn't really a "workshop" insofar as he didn't demonstrate single molecule techniques that you could do in your lab. It was a promotional session for a self-contained commercial product for sequencing. I think this was in pretty poor taste. Aside from that, he spoke very highly of their read lengths, topping all of 35 bases. Steve Block very pointedly asked what he thought the upper limit on their read lenghts were, and the speaker started waxing about the biochemical limitations. When Steve pressed him for a number, he said, I think, 100 base pairs (though I might have misheard, and he may have said 500. But if he said 500, I don't believe him anyway.) The reason that Steve pressed him, of course, is the fact that Pacific Biosciences is now boasting an instrument with several hundred base pair read length, which suggests that the Helicos instrument has a very limited future. Of course, Pac Bio doesn't have an instrument on the market yet, and Helicos does, and there are a lot of advantages to being first to market. So who knows.
Zev Bryant's talk was interesting. He described double headed mutants of myosin that could be made to switch directions at will, and described processive motors made out of myosin heads that had basically protein logs between them. I'm surprised that you get processivitiy out of such things, but I guess if the ATP is low enough, the heads spend most of their time bound to the actin, so they're naturally processive. I'd like to see optically switchable myosins, and I'm sure he's working on it. Genetically encodable optical switches seem to be a growing theme, I'm seeing a lot of it all over the place here.
Adam Cohen's talk was a bit silly, I think. He used glass lenses on top of coverslips to create highly confined spaces, 1 nm up, between the glass and the lens, and looked at proteins diffusing. Things undergo confined quasi-2D diffusion, so they stay in the field of view longer without being tethered. But most people are trying to develop assays that get molecules further from the surface, to minimize surface effects. Here, the surface effects are huge, and this is sold as a benefit. The technique didn't solve any particular problem, it didn't present any new science, and it presents a host of new problems. On the other hand, at least it was fun, and fun is good.

At Hotel Utah with Assorted Weirdos

2010-02-21T19:00:00.001-08:00