Tuesday, February 24, 2009

Introductions aren't for discussions

There are two schools of thought on what should be included in the introduction of a full-length paper (i.e. one with defined sections for intro, methods, etc.) The first is that the introduction should set up the problem that the paper addresses. The second is that the introduction should both set up the problem and summarize the paper's findings.

I see a lot of papers in the second category these days. Many authors seem to prefer the opportunity to state their conclusions early, so the reader can make no mistake about the direction the paper is taking.

But I personally prefer the older-school style in which the introduction functions more like the start of a murder mystery, leaving the reader to consider the problem without having an answer immediately presented. It's a trope, of course, because no one on Earth reads the introduction without having first read the abstract, which has already established that it was Professor Plum in the drawing room with the pipe wrench.

But it's a nice trope, even a civilized one. It's as though the author has said, "If you care enough to read this paper start to finish, then let's lay out the groundwork of intellectual premises together, without knowing the foregone conclusions. I'll tell you how I plan to address the question, but not what I found. You can sit for a moment and think about how you might have chosen to approach the problem, or what you might expect to find, without being told my conclusions at the outset."

Besides, there are already at least two other spots in the paper where the authors have a chance to summarize their findings: in the abstract and in the first paragraph of the discussion. Do you really need another?

I understand, of course, that the goal of a paper is to persuade the readership that you've found what you claim, and that repetition of the findings can aid you in this goal, but still and all--I prefer the classic intro.

Then again, I'm still using Pine in a Unix shell to check my email, so you might just want to file this entry under Cranky Granny Jekyll.

Monday, February 23, 2009

Lazy CRISP question

Let's say that I am looking for a second postdoc. Let us stipulate that as a smart, DrugMonkey-trained bioscientist, I am making sure to check the status of a possible future PI's grants on CRISP.

Let us further suggest that this PI has one R01 that will last a while (but isn't on the stuff that really grabs me), and another R01 (on the stuff I love) that is due to expire in March of 2009.

How do I find out if this R01 is getting renewed? Would it already list an expiry date of 2014 if it had gotten renewed? Presumably by now the PI has heard back on the renewal, but would it be in CRISP already? I have every reason to think that this PI is deserving and has published enough to survive a competitive renewal. If it weren't that our banks are on fire, I would feel confident...but as it is...

(I should mention that I feel sure the PI would have applied to renew this R01. It's not a defunct part of the lab's activity.)

Tuesday, February 10, 2009

Protocol protocol

Everyone who works with animals is supposed to regularly fill out and update Animal Care and Use Protocol forms that detail precisely what is happening to experimental organisms in the lab.

These protocol forms require description of the experiment, a thorough explanation of how the animal will be treated or sacrificed, any analgesic/anesthetic usage, and an estimate of how many animals per year will be treated in this fashion. There is also a section asking you why you can't do your experiments in "lower" animals or with computer modeling.

Filling out these protocols can be a bit tedious, but the second step, in which the animal committee asks you to clarify or fix what you wrote the first time, often takes even longer. Missing dosages, inappropriate anesthesia, etc are the frequent points of concern.

Now, I'm about as animal-rightsy as anyone working on rodents can be. I take seriously even psychological stress to these critters. So I'm happy that the animal committees demand thorough accounting from investigators.

In theory, these protocols must be filed and accepted before any experiments start. However, because PIs have many uses for their time, and because no one is monitoring the lab on a daily basis, and because researchers often want to start different lines of experiments without waiting for approval, in reality every PI I know fills out an animal protocol form only after the technique has already been in use for some time in the lab.

I would go so far as to say that I have never known a PI to fill out an animal protocol form ahead of experiments, except if the animal department requires the protocol before allowing researchers access to a certain room. Or perhaps when a researcher arrives at a new location and simply doesn't have animals to work with until the protocols are approved (though even then I have seen people sneak around this by getting animals from other labs).

Is there a better way for this to work? Pragmatically speaking, I just don't see any way that full protocol approval prior to experimental modifications is feasible. Labs just won't operate on administrative timescales. What if there were a way to file a sort of Notice of Intent, the way that eateries have to post their applications for liquor licenses before they're actually approved? The Notice of Intent form could be quite short--brief methods description with a comment like "We're piloting this method to see if it will be useful."

The animal committee could take the Notice as an invitation to visit the lab and make sure the investigators knew what the hell they were doing. Then there would be a time window--say two weeks--from the Notice after which investigators were required to file a real protocol amendment or to cease these experiments.

Advantages:
1) Less unregulated work. We all know it happens; we like to imagine that people are respectful of animals even in absence of real protocols; but it's never a safe assumption.

2) Not filing a Notice of Intent could become a serious offense, whereas I've never heard of anyone getting busted for starting their experiments without a protocol in place--because inspections are so rare. But since there would be no excuse for not doing it (ie no time delay between filing and starting experiments), it would be hard to defend if you were caught working without one.

3) Prompt visits from vets/other relevant people following a Notice of Intent filing could help investigators refine their protocols from the beginning, rather than following a back-and-forth with the IACUC several months after the lab has already decided how to do its experiments.

I don't think it could ever happen. It's convenient for everyone to live under the fiction that experimenters only function with approved protocols--neither the PI nor the animal committee need rush to get protocols in place, and meanwhile science goes on its merry way.

But it's sort of sad to me that everyone does operate under this fiction, because I think it engenders routine disrespect for the "meddling busybodies" over at animal care who make you change around your protocol to meet the established standards. Because of this disrespect, some trainees learn implicitly that their goal is to shield the lab from careful scrutiny, and to evade the animal care folks when they visit.

I can't think of any better solutions though.

----

Headed on a week's vacation to home town and environs--happy Presidents' Day to you all.

Sunday, February 8, 2009

Trainees training trainees

Today a tech asked me to look at one of her experiments and give my opinion. It became clear that there was a significant artifact contaminating and obscuring whatever real results might have been present. I explained to the tech how she could recognize that this was an artifact, not an acceptable result.

(For those who are wondering, this is not BlogFodder Tech. He is shambling along in mediocrity and exhibiting zero interest in the intellectual life of the lab.)

I then tried to figure out how this artifact could have occurred. It was quickly apparent that the tech was preparing the samples incorrectly, and that this error likely produced the artifact. However, I only noticed that she was making an error in this step of sample preparation because she was mid-task; due to the nature of the mistake, if I had only looked at the final product, I would not have thought to ask her about the possibility of this error.

The error that she was making was quite egregious and when I was trained in this same technique, I was explicitly warned against committing it. There are two possibilities:

1) The person who trained her warned her about this error, but she forgot or thought it wasn't important.
2) The person who trained her didn't warn her.

If scenario 1 is true, this tech is careless, but her carelessness would not be apparent until a lot of time and effort was spent troubleshooting her problem (there are several other steps that could have caused this particular artifact, and they would be considered more likely sources of error). Eventually, if this sort of thing happened enough, I would conclude that the tech should leave the lab. This would be regrettable, but it happens.

What if it's scenario 2? Though most people who could have trained this tech would have warned her not to make this mistake, it's possible that she was trained by the lab's undergrad, who might not have mentioned it.

This is the sort of thing that worries me about lab management. As a PI, you obviously want to trust your lab members to train each other on basic tasks. At the same time, you need to keep up the quality control, which can be difficult if you see the end result and not the process.

In the best situation, I think, the PI trusts other lab members to train new lab members, but still invests significant time, especially at the beginning, in working one-on-one with new trainees. In fact, this is more or less how my current Advisor operates: he was constantly checking in (up?) on me in my first six months in the lab, but has left me more to my own devices of late, now that he is confident I am performing well. (At least, I hope that's the reason.)

But in my experience, PIs are far less likely to invest this time in techs, for understandable reasons (tech duration in lab is often only 2-3 years; techs may be less scientifically engaged; and of course, the main reason one gets a tech is to deal with stuff that you don't want to have to spend time on!) This is where the quality control issue can really fester.

Perhaps the simplest solution is to have a trusted lab member act as direct supervisor to the tech, but this only works in cases where the tech is primarily helping one person, rather than serving as technical support on a few techniques for many people in the lab. I don't know how to keep high standards in that situation, because relying on eagle-eyed lab members to spot problems in someone else's benchwork seems like a recipe for trouble.

Tuesday, February 3, 2009

Telephone

The classic children's game of Telephone, in which one person whispers a sentence into the ear of another, who then whispers it to one more person...and so on until the last person in the chain repeats an incredibly garbled or unrecognizable version of the original sentence, is meant to teach children the danger of repeating rumors.

(I don't think that lesson ever "took" with me, but that's not the point here.)

Here's the grown-up version:

Person 1: "Hey, did you go to that seminar this afternoon?"
Person 2: "Yeah, it was pretty good, I guess."
P1: "I was stuck doing experiments. What'd they talk about?"
P2: "Well, the gist was that they think that walnuts are more bitter than pecans because of their shape."
P1: "Huh, really?"
P2: "Yeah, and they did a couple of experiments to show it. First they ground up walnuts and reformed them into the shape of pecans, and the taste-testers found them less bitter than regular walnuts; and then vice versa."
P1: "Whoa, really? That's a surprise, but what if you're changing the chemical composition by the grinding?"
P2: "Yeah, they had some kind of control for that, but I can't remember what it was."
Person 3 [wandering by]: "Are you guys talking about that seminar? I was confused by the talk because I'm not sure they ever actually proved that walnuts really are more bitter than pecans, and it's not just an artifact of the aroma."
P2: "No no, they addressed that in the experiment in the second half with the plugged noses."
P3: "No, I thought during that experiment the eyes were blindfolded but the noses weren't plugged."
P2: "What?? No, they definitely plugged the noses. I think."
P3: "I was pretty sure they blindfolded people instead."
P2: "Really? I could have sworn they plugged the noses."
P3: "I guess I could have missed it, but I don't think so."
P2: "Was that on the slide with all the blue on it?"
P3: "The second slide with a lot of blue, not the first slide."
P2: "I only remember one slide with a lot of blue."
P1 [bewildered]: "So did you guys believe the data, or not?"
(Simultaneously) P2: "Yes." P3: "No."

What's funny is that these scenarios occur even when both seminar attendees are smart, interested in the talk [read: awake throughout], and well versed in the literature.

It's hard to believe that eyewitness testimony is ever considered reliable.

Sunday, February 1, 2009

Great expectations

An eye-opener from this paper rejection: while I am disappointed and frustrated, the "grown-ups" (PIs) without exception are quite happy.

GradAdvisor: "Once we strengthen the paper with the functional experiment and a few other things, it's really going to become a great paper. It got rejected because the reviewers thought that if we wanted to overturn the textbooks, we had to provide exceptionally good evidence. And we will!"

PostdocAdvisor: "I don't understand why you are sad. They left the door open, right [for de novo submission]? Anytime that happens, I am just ecstatic, because I am expecting the door to be slammed in my face."

CollaboratorPI in another country: "I think this is quite good news."

Although I am a bit chagrined not to receive the commiseration I expected to get from a paper rejection (and bonus nutty reviewer), it sure is educational.

The PIs seem to have one thing in common: they are all taking the long view. It's a small setback, they say, but the interest the reviewers express in the main finding is terrific, and though it may take some time and trouble to strengthen the paper as needed, the end result will be just that: a stronger paper with greater credibility.

It's harder for me to feel any enthusiasm for these reviews, presumably because I'm a trainee and take a shorter-term view of the results ("I'm going to have to sink a helluva lot more time into this project.") But I respect these PIs, and their opinions are starting to help me look ahead, rather than at my plodding feet.

So that's my droplet of education for this week.