Friday, April 29, 2005

Science is all crap.

Well, it has been a few days and I have no new data. I forgot what this was like: as a postdoc, stuff has generally worked for me. I've had some dry spells, but I usually always have something cooking. A few days of solid failure brings me back to grad school... ahh, grad school. What a miserable time that was!

What I can report is that I can't clone this mystery protein, now that I know what it supposedly is. I can detect the transcript, no problem, using a commercial quantitative PCR kit (of course the sequences of their probes are proprietary). But when I go to amplify it to clone it, nada. Nothing. So I don't know if the Q-PCR is crap (probably) or if it's all my fault (quite possibly). Probably both!

Meanwhile, I have been trying to do sequence alignments. Now mind you, I'm familiar with proteins that are not well-conserved, and I have done quite a few alignments using CLUSTALW, and by hand. So my mystery protein is supposedly related to a well-conserved family of proteins, and it comes up in BLAST with this similarity. But when I do alignments with various family members, it is not at all obvious that this protein actually belongs to this family. Depending on which member I choose, I get a totally different alignment. I mean, TOTALLY. If there are really 20 conserved residues, as the literature says, in this family, shouldn't those at least come up every time? Noooooo....

Anyway I guess I am off to prep more RNA, because I'm worried my cells might not last until tomorrow if I blow it off, and possibly stain some coverslips, mostly because I'm worried I will be too lazy to come in and do it tomorrow.

Hard to want to come in for more punishment on the weekend.

Tuesday, April 26, 2005

chaos, databases, and minor victories

You would not believe the week I've had. Middle of last week, I was designing some oligos and discovered a major error in the Entrez database. As in, the people working on the Human Genome Project messed up royally, and named a protein wrong. The name they used already belongs to another protein (the rightful owner).

I contacted the guy who originally discovered this mystery gene, since I know him personally. I tried to convince him to correct the databases himself, since he's the expert, and he didn't seem like he really cared. He acted like the database people are idiots and it's their fault and not his problem, or something. More amazingly, he said the original name was wrong anyway, because the gene does not code for an enzymatic activity of the type it was named for.

At all. This thing is not an enzyme. And they never published the correction.

Anyway, long story short, I filed a complaint, and they are going to fix the database, so I feel like maybe that was my big contribution to The Progress of Science. Who knows, maybe my whole purpose in life was to find this mistake, nevermind if I ever publish another paper again! And I got a discount from a company that uses these databases to sell their products, since I ordered the wrong product and realized why on the day it was shipping out.


Meanwhile, I may have lost 6 months of work here on the wrong protein. I'm torn because I think I should have known better, but in a way it's not my fault if the databases everyone trusts and relies upon have mistakes in them. And, there were other issues, like my wonderful collaborators who refuse to give me their detailed protocols, and insist that it is too 'tricky' for me to set up here. And, because of issues with mailing things overseas, it has been hard to send the samples and have them do the assays that would have made it more obvious that something was wrong.

Actually I got the results of the assays last week, and it was obvious something was wrong, so now it all makes sense. Really should have done that sooner...

Meanwhile, my project has now fragmented into two parts. My amazingly supportive boyfriend says he's sure I'll sort them both out and turn it all into a cool story, but I'm feeling stressed beyond belief because I can't make this go fast enough to satisfy my fear. I'm worried it's all crap. There are no reagents to study this mystery protein that I wasn't meaning to work on. So I am ordering oligos (what got me into this mess in the first place!) and planning to clone the gene from my own cDNA preps, tag it, and go from there. I am definitely seeing an effect in my assay, so it makes sense to go ahead and pursue it. But, this is way up there on the 'most embarrassing things' that ever happened to me list. I still think the dance recital when I was about 9 years old was worse: the stereo system broke, so I was dancing to music only I could hear.

Kind of metaphorical, really....

Anyway, my undergrad is doing great, she actually seems to like research despite my warnings about how messed up the system is. And today when I went to get something signed, I ran into the Dean and he asked me how I'm doing and what are my plans, etc. Of course I said everything is terrific.

I keep trying to picture how my seminar is going to go, am I just going to present one half or the other of this story, or am I going to link it all up and explain point-blank what happened? I'm supposed to present a poster at a meeting soon, and I don't know if I will have this 'sorted out' by then. It is embarrassing to even think about it.

Wednesday, April 06, 2005

Reputation, the end of papers, and databases anonymous?

I recently brought up the idea that we should not have names on papers on grants, that everything should be anonymous.

Last week, I went to a panel on the ubiquitous "leaky pipeline". Of course the panel devolved into the usual disorganized bitching session, and I sat there and listened to senior women professors who said they had witnessed first-hand on study sections that men support each other to such a degree that when someone submits a crappy grant, and everyone on the section knows it is crappy, his buddy will get up there and vouch for him.

He'll say something like, "Well, this might look bad, but I know this guy, and he does good work. And apparently, that is frequently enough to change the score the grant receives, and get it funded.

They said women don't do this for each other. But when I suggested that the idea of reputation makes no sense in science, that it's too subjective, everyone yelled out that reputation is VERY IMPORTANT!

As if what I was suggesting was absolute heresy, and just showed how little I understand about... what? How good science is done? How good science is deemed good?

Granted, these are the same women who said point-blank that they really do believe there are inherent differences between men and women, so I can't say I think any of them are all that bright. I'm sure not a one of them ever studied the effects of culture and socialization on behavior-!

What I take from all this frustrating stupidity is that senior scientists, and most distressingly, senior women scientists, want to sit on their laurels. They don't want to go back in the pack with everyone else. If we removed reputation from the variables of evaluation, they would have to work a lot harder. And nobody in a senior position wants to do that.

I've probably said this before, but I really do think we could get rid of all this crap if we had centralized databases, where every scientist at every level gets their own personal reference number, and every piece of data gets deposited so that everyone can have access to it. Sure, we could still measure productivity by the number of pieces you deposit, and you could still refer to other people's data, so you could still have something like a 'citation index' to rank people. But it seems to me that even the people who claim to want to get rid of the competitive, wasteful system we currently use, are not willing to give up their reputations in order to make a collaborative effort toward advancing science.

I guess this goes in the category of: people are fundamentally selfish, and the reason most scientists are in science is because they think it's fun, not because they want to help serve the 'greater good.'

Advice: give and take?

So, I had a strange experience recently. My advisor is an editor of a journal, and she happened to receive a submission that was right up my alley, so she gave me a paper to review.

This was my first time as an official, stand-alone reviewer. In the past, I have sometimes been asked to give an advisor my opinion on a paper they were reviewing, but they always concocted the actual review that went out to the authors and the editor. But it is becoming more common that postdocs are considered expert enough to review papers and grants. Yes, grants. Apparently it is quite easy to volunteer to be on a study section as a postdoc, so much so that NIH is begging for volunteers at NPA meetings. Amazing! I wonder how many PIs would really want their grants reviewed by postdocs if they knew that was the current system?

So, the day I got this paper I was in the midst of something with my own paper. I think at that point I was pretty sure it would get in, and I was really grateful that the reviewers I had gotten this last time around were actually giving me constructive advice. So I was in a pretty gracious mood, I thought I should give detailed comments that would be helpful, say very clearly what I liked and what I didn't like, and offer concrete suggestions on how to fix things. You know, write the kind of review I would want to get.

As it turned out, the paper needed some work, but I thought it should get in with revisions. Of course that is not an option you can communicate easily, there are some unwritten rules I'm still not clear on in the scientific publishing world. On the one hand, the instructions to reviewers clearly say that you should NOT include your opinion on whether the paper should get in, anywhere in the text of your review. That goes in a different slot. And of course the options are "accept, modify, reject." So I picked modify, knowing full well that I have ethical concerns about communicating anything to the editor that the authors aren't privy to, but hoping she would read my detailed review and see what I was hinting at.

So I was kind of frustrated because this week I got the revised version of the paper, and a copy of the letter that went out with my review. The letter, which was written by the editor, said that the paper was rejected. I was kind of annoyed by this. I'm really very much against this latest trend of rejecting everything the first time around, especially when it's pretty obvious that the people are sincerely going to do their best to use some elbow grease and polish up their paper in the revised version.

And, upon reading the revised paper, I was pretty shocked to discover that these people had taken EVERY SINGLE PIECE of my advice. They fixed EVERYTHING. It was MUCH BETTER. And I felt strangely drunk with power. I had to wonder if they would have taken my advice if they knew the paper was 'accepted with revisions' rather than rejected (which lends the review a certain amount of YOU BETTER DO THIS, OR ELSE .

So here is my thought for the day:

Does it make sense, if most people rarely take my advice in real life, that someone I've never met should be FORCED to take my advice as an anonymous reviewer?

This is a really fucked up system we're using!

So when I re-read my original review, I felt bad because I didn't recall having written such a long and detailed review, and I thought I had worded it carefully so that some things were merely suggestions. You know, things to consider trying, rather than requirements for the paper to get in. But they did every single thing. They had obviously done a lot of work.

Of course, sadly, they had also added an experiment, the results of which had clearly gone over their heads. So I had to say again that it needed to be modified, but I emphasized in my review this time that I thought it only needed revisions to the text. I just hope they get the message that I liked it, whatever the editor says this time around.

Meanwhile, I'm left with yet another piece of evidence that the peer review system MAKES NO SENSE.