on knowing when to quit

Parts of science are extremely frustrating in that almost nothing works the way you want on the first try. Many assays and techniques need optimizing and multiple confirmation steps before they can yield decent data. But how do you know when to abandon something? Or is it ok to simply keep beating your head against a wall?

A good example would be in 2009, when I was trying to clone an antagonist to receptor X; I spent July to November cloning, and when I finally got a clone, I found I couldn't make cells produce mass quantities of this antagonist. Which meant I had to either reclone it, or optimize production methods. It turns out altering production methods didn't work, so I had to reclone it into a different plasmid and test for production again. By the time all this was done, it was March 2010, and I didn't actually get the antagonist tested in cell culture until June 2010.

My adventures in cloning this antagonist isn't the only one in our lab. My predecessor had done the original mutagenesis and cloning of this protein and found that he couldn't get the cells to produce it. When I took over the project, I cut off some stuff from his original sequence and cloned it into a different plasmid, but it didn't seem to make a difference, so I had to keep cloning until I got one that worked.

There are different ways to block cell signaling, but I can tell that my advisor thought it would be useful to have a receptor antagonist as a possible tool for future studies. But is the time spend on cloning and testing (in this case, more than two years) worth it? How much money and time needs to be spent in order to get this one tool?

A second example involves my time working as an undergrad in the plant lab downstairs. My job was to optimize primers that came in; since we were working with plant DNA, PCR could be a bit tricky since plant cells have all this glop (resins, tannins) that interferes with the yield of good, clean, DNA. The problem here was that I was even more clueless back then, so I just did what I was told, and couldn't explain the strange bands I kept getting on my DNA gel. So I had to try different temperature and time settings to get the primers to amplify the sequence of interest. Someone later asked me "why don't you just get new primers? They're pretty cheap."

After I left, the lab did get new (redesigned) primers. I talked to the lab manager after I started grad school, and she told me that someone else designed the old primers, and that their design had a lot of mistakes. But why couldn't we have checked them for mistakes earlier?

It sounds like many of the reasons for stopping or not stopping with a given project are financially motivated, but it can't be the only reason. Clearly the benefit of having a functional receptor antagonist was worth the time and funds spent to clone and test it. But what if the tests showed spotty results, as in sometimes it worked well and other times it didn't? Would we have abandoned that project?

Might be another thing that comes with more time in school...

The Quarter-Life Crisis

Fourth year is starting in two days, and the progress meter is at a standstill. While there are day-to-day frustrations with experiments and strange results, the sudden (or not-so-sudden) realization that we're a little closer to graduation (hopefully) and finding a real job can be jarring. I heard more stories of people leaving their PhD programs in the past year; they decided the pressures experienced in academic research weren't worth the end product of having the degree. Even amongst the people who stay, I find that more are struggling to figure out what the next step is going to be.

For instance, one of my friends is experiencing a few funding issues in his lab. We were talking about the pros and cons of a career in academia, and came to the conclusion that we might not be as well-prepared for such a career as we once thought. Nobody enjoys the grant-writing process, and I have limited patience when it comes to teaching. At the end of it, he said "industry doesn't look so bad now, does it?" He might as well have said it to himself as to me, since when we started grad school, he was vehemently anti-industry and didn't like the idea of science for profit's sake. Now that we've spent a bit more time here, we're both wondering what we might and might not be cut out for.

Being in industry has its own problems, and even people in that field may be rethinking what they want to do. Someone I know who is currently an industry postdoc is considering a career switch. It seems to be that there are more freedoms in academia than in industry; there's no well-defined end result in academia, whereas in industry all the time and resources are poured into drug development or disease therapy. That's not to say that all of academic research is purely for knowledge, but from my own basic science perspective, the line between academics and industry is much more pronounced.

Looking back at the past few years, I feel like I just stumbled into grad school. The story begins much earlier that college, however. In high school, my counselor highly suggested taking AP biology as prep for the college premed track; taking this class was enough for me to major in biology in college, and even though I started out premed (like everyone else), the further I went along in my college career, the more I realized that I didn't want to pursue medicine. A series of dev bio classes, a certain GSI, and a string of lab rotations helped me carve out what I wanted to do in grad school...and here I am, working on a project I enjoy that borders development and evolution.

My biggest problem now is that I can't "stumble into" the next step. I'm having some doubts about staying academia after graduation (when that happens), but so far I know that I want to remain close to the science.

Bubble

One thing I've noticed about school is that it tends to shield people from the "real world." This was especially apparent during my freshman year of college, and gradually got better when I left the dorms. However, the shield is still there; sometimes it's a good thing, but other times it means an somewhat isolated existence.

A lot of people have said that the past couple years has been a good time to be in school. The number of people pursuing post-college education has increased as the economy tanked, and in many ways, grad school is a shield from having to search for a "real" job or worrying about the consequences of not having such a job.

However, grad school comes with its own bubbles; depending on the day, labwork can be stimulating, tedious, meditative, or just plain robotic. While the schedule is relatively flexible (I go to lab when I want, but I leave when the work is done), the flip side of having such fluidity is that everyone else is on a different schedule, and sometimes I'm there by myself with just my iPod and the frogs for company. It's gotten much better, since there are more people in the lab now and the chances that I'll have human company during work hours has increased. But since people have different projects, sometimes it can still feel a little isolating, especially when the people you interact with the most aren't present.

I don't mind the lab bubble as much as I do the bubble that extends outside of work into "normal life." I've noticed lately that people are less willing to go out and do semi-organized activities. My friend, who's in a different program at another school, has noticed it too and pointed it out to me. She had tried to get people together for a wine-and-games night at her house, but out of the 30-some people she invited, only half replied. And out of the half that replied, 8-10 actually showed up, which is a pretty good sized group, but considering the number of people she asked, it's quite a low turnout. I've started to notice that as well; people are increasingly wrapped up in their own lives and not extremely willing to go out and do something social (myself included).

One of my other friends (in med school) thought that we're all in a particularly antisocial period, since we're trying to get enough done to graduate, but also trying to figure out what we want to do in the long run...a "quarter-life crisis" of sorts. As a result, many other things, including attempts to have some semblance of a social life, is seen as a distraction. An alternative is that we're all reaching the end of our third year, and "what have I (not) accomplished these couple years" syndrome is starting to sink in. That being said, I wonder if this is going to get worse as fourth year approaches in a few months...

Unfounded Anxiety

People who know me at least a little bit know that patience is definitely not one of my virtues, which doesn't bode too well for a career in science. When I started grad school, I noticed that I had more patience waiting for my experiments to stop running than I did for certain situations outside of work. Lately though... I haven't had much patience for ANYTHING, including bad experiment results.

I don't even have a good reason to feel rushed; I'm nowhere close to graduating, and the only person who's complaining about how little data I've gathered is myself. I have a problem accepting that are some lab days where the only "benchwork" there is to do is wait for cells/animals to grow, and I feel pretty guilty when I'm in lab and not doing benchwork. One of my friends pointed out that benchwork isn't the only way to be productive, but that's also something I have difficulty realizing.

I think the anxiety might rub off on others, namely my advisor. He was working on a paper that I contributed some data to, and I got a draft of it about two weeks ago. It's not complete at all, but I was visibly anxious about getting a draft to look at. I think I asked him every (other) day about it until he sent it. Hopefully he's just thinking I was super excited to get my name printed on something... which I am, but for some reason I still feel I need to push harder to get another paper out.

By now it sounds like my only interest is in boosting my resume. While more publications is always a good thing, there's obviously a limit to how much I can do within a certain period of time. My biggest problem right now is that I feel rushed to produce something, and get really upset/jump to conclusions when things don't work the first time around, regardless of me making some stupid mistake that caused it not to work. I'm hoping it's just a phase I'm going through, but in the meantime, I should probably find something to calm my nerves...

The Love-Hate Relationship

Several weeks ago I was talking to a group of third-year medical students, and one of them asked me how I liked my work as a grad student. I think they have the impression that I work weird hours and live to serve whatever samples I have running or animals I've isolated. Then again, what they consider as "weird hours" is seemingly normal for me and for several other grad students I've talked to. My friends in med school have more of a set schedule; they're required to be at a certain place by a certain time, rather than coming in whenever they want and leaving when the work gets done.

That doesn't mean that I walk into lab at 1pm every day and work until 9 or 10 at night. There's still an expectation that I'll be in the lab enough to get the appropriate amount of face time with my advisor, but there's not much of an endpoint to when I'll be done for that particular day, which may be irritating for some people. The good part is that I can at least estimate the amount of time I need and plan accordingly, which is often what I tell people who think I'm overworking (namely my parents).

I have this ongoing love-hate relationship with grad school. Good results and published papers aside (which everyone loves anyway), I'd have to say I like the steep learning curve which can't be picked up in any class and the fact that I get paid to do something I enjoy (i.e., biology). It's also nice to have labmates I get along with.

That being said, I haven't met anyone yet that enjoys every minute of grad school; there's always bound to be something unsatisfying about it. When I first started, there were only three grad students (including me) and two undergrads. One of the grad students was MIA due to prelims, and the other came in at sporadic times. The undergrads had set schedules, but since I didn't know what they were, it seemed like they came into lab pretty sporadically as well. I had just started in the lab, and aside from not knowing where any reagents were kept, I also was unfamiliar with the project. So I got to sit in the office and read papers all week... or week and a half... which was an utterly isolating experience. The lab has since then gotten more members; there are now five PhD students, including me, a Master's student, an assortment of undergrads, and a lab tech, which livens things up a little. Plus I'm not completely lost as to what I'm supposed to be doing, so I can spend lab time actually doing benchwork instead of reading.

***
I really don't think the in-lab isolation aspect is nearly as bad as the out-of-lab aspect. There are days when I come home pretty late and the only thing that I want to do is wash up and read a mystery before bed. There are also days when I use going to lab as an escape of sorts from whatever problems I don't want to think about in the "real world." Other days it's equally painful to go into lab as it is to stay away from it, but the good part is that those days are rare.

Mentorship

I'm a horrible mentor. There, I said it.

Back in August, I told my advisor that I was interested in getting an undergrad helper for my research. There's a school-wide program here that helps undergrads (particularly underclassmen) get started on research by getting in touch with different PIs and their projects. I got to interview the students, and chose one to help me out, so he's been here since mid-September.

Unfortunately I've realized that I'm not very good at thinking of spinoff projects for other people. A few weeks ago, my advisor asked me how everything was going with the undergrad helper -- what was his project exactly? What was he doing? My answer was something among the lines of "he does what I tell him to do," which didn't sit very well with my advisor.
I've been teaching the student various molecular biology techniques, along with an overview of how they fit into the bigger picture of my project, but this approach doesn't work very well, especially if I just dictate what he's supposed to do and watch over his shoulder while he does it.

One of the biggest problems is that I don't trust other people to do "my" work, for fear of things getting messed up. I'm pretty sure my advisor had the same problem with me when I first started working in the lab; it got to the point where my advisor asked another grad student (a year above me) to watch my technique... as in look over my shoulder. When the other student said "but I don't think she's doing anything wrong," my advisor said "well, just in case..."

I'm trying to get the student to see the big picture before he goes off to work, but sometimes I glaze/skip over things that seem second nature to me, without realizing that the student is lost. However, there's a limit to how much "big picture" stuff can be covered before the students lose interest, and many subtleties can only be learned through actually DOING the work.

If I continue mentoring throughout the next school year, hopefully the current student stays in the lab...

Conflict of Interest

I'm in grad school at the same place I went to undergrad, and I was telling a recent seminar speaker over lunch that the divide between college and grad school seemed much more pronounced. Then again, I have no other basis for judgement.

However, my first teaching experience was in a class that I had taken my junior year of undergrad, and my GSI was one of my current advisor's former students. He seemed pretty relaxed about class policies, given that we didn't do anything stupid, like take naps or text people. I think one of the best parts about the class was that everyone who was registered actually wanted to be there, and nobody was in that "I need an easy lab course to cruise through my senior year" mindset, which made life easier for both the GSI and the students.

Unfortunately cases like that are pretty much utopia.

I ran into that GSI about a year later, and found out that he was teaching the same class again. When asked how teaching was going, he gave a different response: students had become whiners. Granted, it was a lab class that met for four hours on a stretch, and lab activities aren't always going to be fun and games, especially if grades (and possibility of future schooling) is at stake. The biggest problem is that most of the students WERE in the "I need an easy A to graduate" mindset, and as a result, procured mediocre work and less-than-stellar behavior.

So what changed? The undergraduate biology program here requires all students to have at least 2 lab classes picked from a specific list. This class wasn't on the list when I took it, and suddenly it was, resulting in an influx of students that may or may not (most likely the latter) have wanted to take the class to begin with. The class always counted toward a biology degree, but since it wasn't on that specific list of labs, most people overlooked it.

One of things I struggled with a lot during my year of teaching was a huge conflict of interest between me and the students, or me and the institution. I wanted to students to care about the material they were supposed to be learning, and I expected them to put in the effort to do well in the class because they chose to take it. On the flip side, most students wanted an easy A and do just enough to cruise by. I had one student turn in his Google search list about Compound X as his bibliography about how Compound X affected embryonic development. I emailed him and asked him to redo it, which he never did. Two weeks later, he came into office hours in a panic because he claimed that he was "snowboarding in Canada" that day and didn't get the email. And also, "can I still get credit if I redo it now?"

Seriously? Why even bother asking that question? The answer is obviously no.

***

I was having a discussion with one of my friends about institutions of higher learning; I was angry about our current system and how much grade inflation there was. I think bell curves can be pretty fair, but right now our bell curve has shifted so much to the right; the average, instead of being a B- or B like some of the classes I saw in undergrad, is now an B+ or even an A-. How are you supposed to differentiate between the average students and the outstanding students then?

On the flip side, instructors get in trouble with admin if their class averages are too low. My professor for Orgo II got fired after her term teaching us. Student evaluations aside, she had one test that was so difficult that the class average (for 1000+ students) was a 42%. So part of this huge grade inflation problem stems from instructors wanting a bit of job security... I understand that at least in part. However, things get out of hand when a student who clearly deserves a C- or a C ends up getting a B... just so we can move the class average up a few points and avoid getting in trouble by admin.

No instructor wants to reward mediocrity, but it ends up that way because students are the ones who are paying... and therefore the customers. So what do we do?