I hate it when you're right

Paramed  and I got into a not-so-little tiff last night. We were supposed to be enjoying a relaxing dinner. He was stressed from several insanely busy weeks, at both school and work. I was frustrated because of a number of things going on at work. During the course of conversation, I commented that I realized I needed to start thinking about a backup plan to the tenure track. Things went downhill from there.

That statement surprised Paramed because he'd never heard me express any doubt about where I would end up in my career. It was also not an easy thing for me to say aloud because, as irrational as it may seem, it felt like I was giving up a little bit--though when Paramed voiced that same sentiment, I denied it. He asked what I would do, if not what I've been working toward for years. I responded, "I don't know. There are a lot of options. But I do know that I don't want to stay at the bench if I'm just going to be treated like a set of hands the rest of my life."

"Do you feel that you're treated that way here?" he asked.

"Yes," I replied. "Guru has told me exactly what experiments to do. Before I can even finish a set of experiments and think about where to go from there, he's telling me the next set of experiments that I should do. I don't even know what the big picture is; I've asked and all I got was a bullshit answer." I should note here that as a grad student, I was expected to design my own experiments, to take ownership of my project. Bear still had a hand in guiding the project, but he did this largely by asking questions to get me thinking about it, recommending priority order for experiments that I designed, and sometimes suggesting experiments but in a more abstract manner, leaving the design and interpretation to me for the most part. Perhaps I am idealizing my past experiences, but I have always been more committed to and excited about projects that requires critical thinking (outside of technical troubleshooting) and interpretation. I thought that's similar to what I would get here, but it turns out Guru is a micromanager--and I don't respond well to micromanagement. Anyway, back to the story at hand...

The ensuing argument revolved around the following main points:

• Paramed was pissed that Guru was making me doubt myself.
• Paramed was pissed that I was not being assertive and implied that I should stand up for myself and call Guru out when he's spouting bullshit.
• I was pissed that Paramed was telling me that I was doubting myself and that he was telling me what I should do.
• I was pissed also pissed that he was not accepting my excuses for me not being assertive.
• There was back and forth about the correlation coefficient between amount of listening vs. amount of ranting on both sides.
  

Now only if said argument had taken as little time to fizzle as it did to write out those points. Eventually we called a truce and we got over it.

Of course, after I had calmed down and started thinking about what was said, I realized what had really pissed me off so much: the fact that Paramed was right. Or rather that what he said was true. It kills me that I've fallen back into being so polite and diminutive that I don't take a stand, that I've allowed that monstrous self-doubt to creep back in. I felt that I left grad school as a confident scientist, but I no longer feel that. And it was tough to be forced to admit it. Paramed can be brutally honest--which is a great trait and yet often painful at the same time. I am reminded of an insightful post and am now at the point where I "sack the fuck up and feele extremely grateful for his penetrating insights". Next to decide what to do about it.

The epic battle of Pitar and Belle

As you may have gathered from my midweek post, the past few weeks in science have been pretty crappy for me. The first half of this week was particularly rough and was not helped by the fact that I started the week sleep-deprived from working furiously to finish revisions on a manuscript from Bear's lab, required by PITA reviewer (who we shall refer to as Pitar, henceforth). Moreover, this wasn't just any manuscript, but one of the major projects I worked on in Bear's lab, the one for which I was awarded an NRSA in grad school, the one that I carried out almost singlehandedly and thus carried the name of only one other author aside from myself and Bear.

Pitar basically wanted to see every piece of data we mentioned in the manuscript. This included controls, negative data, and data that looked almost exactly like other data that was already in the manuscript. Yes, I understand, there's a whole heap of lying, data-manipulating bastards in science these days, so Pitar cannot be expected to take my word that when I say data for thing 2 looks like data for thing 1. Still this made my life miserable. Pitar has no concept of what went into making the figures in the paper presentable, clear, and quite frankly beautiful. Nor does Pitar care.

Bear and I decided that most data requested would appear as supplementary figures, which meant they didn't have to be as beautiful as figures in the main paper. But me being me, and my name being associated with this work, I could not bring myself to just put the standard analysis program output into the supplemental. The 1/2-pt lines and 6 pt font just looks amateurish. So I spent hours resizing, ungrouping, deleting, adding, copying, pasting, regrouping to make the figures at least look decent. After working into the wee hours of the morning Monday, my shoulder, elbow, wrist, and thumb hurt from all the clicking and typing, and my ass and back ached from hours of sitting in a hard chair. I was so exhausted that I couldn't think straight enough to write comprehensible figure legends, so that had to wait until after I had gotten a few hours sleep--and when I should have been doing ELISAs or Westerns or something in Guru's lab. I will admit that insanity of trying to get so much done in such a short period was really my own damn fault--due to procrastination.

Either way, I got it done and addressed all but one main bullet and one sub-bullet Pitar fired through modification of a main figure or addition of supplemental data. I truly hated the fact that Pitar made it one of 'those' papers, where there were supplemental figures than figures in the main text. Bear sent in the revisions early in the week.

The long wait began.

And ended. I received word from Bear yesterday that the manuscript had been...

ACCEPTED!

It was so nice to end the week on a high note, even if it was a note from my past.

Hopefully it is an omen for the week(s) to come.

What the hell did I do to you?!?!

I think I have expressed previously that I am one of those strange people that absolutely loves science. The process, the work, the discoveries... Science is an integral part of my life. I often speak of science in anthropomorphic terms.

And now I'm trying to figure out what the hell I did to her. Why does she hate me now? Why is there so much general suckitude when it comes to research and science these days?

When I started my postdoc, I took on two somewhat related projects. The person who previously worked on one of them (we'll call project A) had been gone for over 6 months. The other project (B) didn't even have preliminary data.

I came to realize as I tried to get project A off the ground, that the supporting data for it was almost nonexistent for the in vitro system. And that data from the in vivo system was notoriously difficult with regard to quantification and reproducibility--this from the people who actually did the work. So I tried a different approach, which kind of worked the first time, worked beautifully the second time (early this summer), utterly failed the third time (a few weeks ago), and provided a negative result in a different cell line (sometime last week).

Project B had to basically be started from scratch. It took a couple of months to get the in vitro model system up and going, thanks to one crucial detail left out of the methods section of one group's papers. After that problem was solved, I had to get the Western blots to work, dealing with trying to get efficient transfer of proteins of interest and the fact that the commercially available antibodies are crap (one band my ass, Santa Cruz). This finally started to show some promising results this summer as well. But I again ran into the problem of reproducibility, trying to figure out whether it's the crap antibodies, differences in experimental conditions, or just something that I screwed up. And then there was writing and revising a protocol for the in vivo work, which I was looking forward to.

Other things I've worked on have either just not worked or have given wonky results that require additional troubleshooting/control experiments. The real-time PCR was screwing up intermittently, which in the end, required setting up every experiment twice to get usable results. Regarding one completely unrelated idea (which I felt was a good idea and a nice reflection/application of my previous training), the guy heading the core facility that I need to use is a butt munch--ignored me once, blew me off the second time, was curt the third time, and is ignoring me again.

So basically the past couple of months have sucked (even if you don't count the shit I've been dealing with outside of science).

Yesterday I'm perusing the RSS feeds for new PubMed entries on topics of research interest. And I find an 'early edition' PNAS paper that is basically describing my project B, with in vitro and in vivo data (using different but closely related model systems). I thought I might actually cry (when it comes to my life, it takes a lot to make cry). I still have to read the paper in detail. I might be able to salvage something of my work, but it definitely steals my thunder.

I realize that all of this is 'part of science'. But that doesn't really make me feel better. I've been having a very tough time this year, scientifically speaking. I keep telling myself that it's important to encounter adversity at this stage of my career, so I can (hopefully) deal with it better in my independent career. That it's "character building". But that doesn't make it any easier.

In recent weeks, I had decided that it was time to start considering alternative projects, for a myriad of reasons. In a way, this most recent development may just be another cutting of ties to current projects to push me into another one. It still doesn't entirely remove that feeling of science kicking me when I'm down.

Well, time to suck it up and get back to it.

Survival of the...?

Less than a month after closing its merger with Wyeth, Pfizer announced its latest restructuring plan yesterday. This involves establishing five central R&D sites, 4 in the US and 1 in the UK. Details on the restructuring are slim, but it is reminiscent of the current GSK model.

Also not discussed in the press release: How many scientists will be losing their jobs. Given that Pfizer will be reducing R&D ops at 3 sites, consolidating its R&D sites in Connecticut, and completely shutting down R&D ops at several other sites, the news ain't gonna be good. This follows on news last week that Johnson and Johnson could be cutting up to 8000 jobs. No one seems to know what sort of layoff numbers will be emerging from the Merck/Schering-Plough merger.

Unfortunately this is part of the life cycle of big pharma. They assimilate other companies and then the pruning begins. I don't think this is really anything new. Just ask someone working for Monsanto 15 years ago... which became Pharmacia... which was acquired by Pfizer. There are many other examples. I don't know how numbers laid off in recent years compare with mergers of previous decades (yes, I'm a lazy blogger and have not consulted Wikipedia on this), but mergers and layoffs are nothing new (just like the valleys in NIH/NSF funding are nothing new).

Perhaps this is why I was struck by this comment on Derek Lowe's* post on the subject:

I am Synthetic Organic chemist about to graduate from a reputable group. I am so frustrated with these pharma layoffs and thinking to go to academics. So what do you guys think, is academic job is better in present context?

Of course, one has to wonder what he (or she) means by an 'academic job'.

If he means associate professor position, as interpreted by commenter OrgChemRedundant, then my answer would be 'HELL NO!'. You don't, or at least in my mind shouldn't, pursue that career path as a backup plan. Need I really explain why?

If he means working as a bench chemist in someone's lab, then it's worth considering. Some university departments/institutes have been investing heavily in organic chemists, setting up what I can best describe as mini-biotech groups within academia. These entities utilize chemists to synthesize hits from high-throughput screens, compounds for groups without synthetic capacities, problematic syntheses, etc. To some extent, you're still at the mercy of the grant cycles, but you may be more insulated from the economic swings. You might also be making less money than you would in pharma.

This also highlights a previous discussion we've had here: There are options outside of academia and big pharma. There are those companies that we buy all our solvents and chemicals from. There are many smaller companies, like Cayman Chemical and Santa Cruz Biotechnology, that specialize in classes of compounds or targets for bio-related research. There are smaller companies that big pharma is outsources some of their synthesis to.

If you really want to go the pharma route, whatever the reason, here is a piece of advice that I heard during a talk by an 'old' chemist at Merck. He had been at the company for 20 or 30 years and, over those years, had worked on one particular biological target multiple times. The project was tabled, and almost killed completely, multiple times, mainly because drugs against the target did not appropriately treat the indications they were developed for. Ultimately he had the satisfaction of seeing a drug make it to the market that truly changed lives, one case he witnessed personally. By that point, he was a division head, but the pride and satisfaction was clear. He was trained as an organic synthetic chemist, but one message he had for his audience was this: Even in pharma, simply being a synthetic chemist is not enough; you have to learn and understand at least some of the biology and physiology of the system you're working on.

Honestly, we could turn this into a fill-in-the-blank statement. Science--at the very least, chemical and biological sciences--has changed. For most of us, we can no longer pick a small niche and just stay there, speaking only with our niche-mates. There's a reason multi-/inter-disciplinary training has taken off--and it's not just because of NIH investment in such training programs. It's because we can no longer just be a(n): enzymologist, molecular biologist, organic chemist... As grad students, we may train to become one of these things, but that doesn't mean we can't or shouldn't learn other things. We don't have to become experts in every other field, and the truth is, we can't. However, we can pay attention to what's going on in other fields, to understand the big questions that other scientists are studying, to learn what challenges other labs are facing. That's the way we will make progress. And that's the way we will (professionally) survive.

* Derek Lowe's blog In the Pipeline is an excellent read if you're interested in drug discovery or what's going on in the pharma industry.