Reporting the story

Presumably most of you have read Gina Kolata's take, in the Times, on why cancer research hasn't cured cancer yet. It's the super-conservative grant review process that rewards only incremental research and variations on well-established themes, it turns out.

Well, yes, that's something that all of us, cancer researchers or not, complain about fairly regularly: the requirement for in-depth preliminary data that signals "The first aim is all but complete" before funding shows up.

But I think she buried the real story. Anyone else catch the graph?


Let's take a couple of years here for illustrative purposes.

In 1996, we spent about $3 bn on NCI total, of which $0.6 bn went to "Other expenditures--non research." That's 20%.

In 2005, we spent about $5 bn on NCI total, of which $1.5 bn went to "Other expenditures--non research." That's 30%. Aka, a 50% increase in proportion of non-research expenditures.

Now, there are plenty of other remarks to be made about the article, including "Biology is really complex and simplistic formulations like 'The War on Cancer' are downright silly;" and "You see how funding flatlined and then actually sank? That might have something to do with reviewers becoming conservative." Neither of which was ever addressed in Kolata's article.

But looking at that graph, all I can ask is: where is this non-research money going? Is this due to an increase in overhead/indirect costs? And if so, why? Did it really get that much more expensive to administer and run science buildings starting around the year 2000?

For 2005 alone, if these non-research costs could have been kept at their original 20%, there would be an extra half-billion dollars freed up for cancer research funding. At, say, $250,000 per project/year, that's an extra 2000 projects that didn't happen. In 2005 alone.

This article felt like one of those talks where the speaker doesn't address some really fundamental issue up front, and I can't even process the rest of the talk because I'm so focused on this problem raised by the graph on the third slide.

Leave the epic similes to Virgil, sir

A PI to a classroom of students and postdocs, regarding a scientific issue of signal propagation:

“Here’s an analogy. It’s like when you’re on the same floor as the secretaries, and there’s only one thermostat, and the secretaries, who are always young women with very little body fat and they’re wearing kind of skimpy clothing, are always turning the thermostat way up, and it affects you even though you’re at the other end of the hall, but your feedback doesn’t change the thermostat.”

Cruel to be kind

Good old Blog Fodder the Tech, who astounded me with his many iniquities before shaping up as a reasonable lab member, has announced his plans to attend graduate school.

BF had previously mentioned grad school as a possible future, but had acknowledged that he was just as interested in business school (poll: which requires a better grasp of basic arithmetic?). Now, however, he is actually studying for the general and biology GREs (and taking a Princeton Review course). Last week he came into lab on Saturday to do a couple of small lab tasks and grind away at a practice exam.

The problem is, of course, that BF lacks the fundamental curiosity, let alone the determination, to make it through grad school. He asks questions....about the tasks he is given. Perhaps once a month, he asks a question about the research presented in lab meeting, but these questions are not typically experimental in nature--they are more likely to run along the lines of, "Does this relate to phenomenon X that I read about in Science/the Times/the Economist?" Sometimes it's an interesting question, but it's pretty much never what I would expect from a first-year grad student--i.e., a question about experimental details, or whether one could follow up with Experiment Z, or even just what the heck the significance of an observation is.

(And no, this is not because he fears me; he doesn't ask these questions of anyone.)

When he told me recently that he was studying up for the GREs in preparation for grad school applications this fall, I asked him more about his research interests. In the past he has mentioned labs that do fairly similar work to our lab, but this time he mentioned some labs that are further afield. It's fine for your subject affinity to shift over time, but I think in this instance he's probably just hoping that the work of Other Labs is more interesting to him than the work of This Lab.

In any case, I tried, gently, to dissuade him from Ph.D. programs. I pointed out that if he's still thinking about going into business in some capacity (the business end of a pharma company, for example), then an M.S. would likely give him the training he needs for much less hassle.

"I just figure that if I'm going to grad school, I might as well go the whole hog," he replied. "Besides, I'd be happy to spend six years in [City With His Dream Grad Program]."

Blink. Blink.

Despite BF's many failings as a scientist, I have developed a certain fondness for him, the way one does with household items. So I should probably try again to steer him in the direction of the M.S., or even an entire life re-evaluation. (Note to readers, BF is loaded, so the cost of doing an M.S. should not be a hurdle.)

On the other hand, it's not as though he's coming to me asking for advice or help, and often it is easy to irritate people by profferring unasked-for advice, or so I am told. Since I've already suggested the M.S. to no effect, I could just wash my hands of the situation.

Still, though, I dread the moment that BF asks Advisor for a recommendation. The problem is that BF likely won't ask until it's actually grad school application time, i.e. November, by which time it will be harder for him to change his plans in response to Advisor's anticipated reaction ("You are applying to what?")

So I feel as though the Right Thing To Do would be to sit BF down and try again to persuade him to think this all through. It might be a waste of my breath, because he has a certain unshakeable confidence, but I think it's worth a try, on the theory that a little effort now might save some misguided university the cost of his tuition and stipend for 2-3 squandered years. Have any readers ever successfully talked someone out of applying to Ph.D. programs? Particularly someone who is a bit stubborn and ignorant, and perhaps also very bad at math?

Why do you write a training grant?

I've been funded off an NIH training grant (T32) at two different points previously, and I'm applying to be put on another training grant in the future.

My participation level in these training grants has been, at maximum, to write a paragraph of application explaining why I should be on one, and another page or so each year I'm on the grant to update NIH on my progress. Ridiculously easy.

But the person administering the training grant seems to do an awful lot of work. They write the grant, pick trainees, and generally deal with the flow of funds. My question is, what's in it for them? It seems like a giant hassle for very little professional benefit--perhaps you can stick one of your own trainees on the grant, but beyond that it just looks like scut work. Yet the two training grants I've been on have been administered by high-ranking PIs (and sniffing around T32s at other institutions on CRISP, this doesn't appear to be uncommon).

Do you just get departmental brownie points for writing/running a T32? Is it the sort of service activity that gets you out of jail for some other service activity, like being on a search committee? Is it just out of the greatness of your heart? (And if so, how to explain the presence of some T32 administrators who are well known not to have hearts at all?)

I'm grateful to have this funding, but can't imagine that "postdoc gratitude" inspires a lot of would-be grant-writers. So I have to assume there is something I don't understand about the apparently selfless action of these folks. Internet, please explain.

Your personal eigenvalue

This just cracked me up:

http://www.pnas.org/content/106/17/6883.full

PNAS publishes a letter on the "Eigenfactor" version of citation ranking, some attempt to come up with yet another version of impact factor. The fawning conclusion? That you can "publish in PNAS with the full knowledge that you are contributing to one of the most influential drivers of scientific progress."

Also, apparently, in JBC, which way outranks Cell.




Who amongst you doesn't want to know what those tantalizing unlabeled dots near Cell and Phys Rev B are? J Nobody Reads This?

A very small snippet that says oh so much

From this week's NY Times Week in Review:

But Justice Ginsburg said her own influence in all sorts of cases at the justices’ conferences was uncertain. “I will say something — and I don’t think I’m a confused speaker — and it isn’t until somebody else says it that everyone will focus on the point,” Justice Ginsburg said.

That is, she is one of the nine highest-ranking judges in the nation, with the power to define and defend constitutional law, and she sometimes kinda feels like people ignore the points she makes...until a guy says the same thing ten minutes later.

Staying awake, staying (scientifically) alive

I can't imagine I'm the only person with this problem: I sit down at a seminar by a visiting scientist, or at a conference talk, and my mind drifts.

Who's that sitting in the third row? What's the name of that grad student I just met? How should I persuade my PI that my proposed Experiment X is higher priority than his proposed Experiment Y? What is Experiment X, anyhow? Also, dinner.

It isn't necessarily because of fatigue, though some days that plays a role; and it isn't only for boring speakers--it's just easier to retreat into Headworld than to stay focused on whatever's going on in Realworld. But I always feel ashamed fifteen minutes later when I turn my attention back to the seminar and find myself hopelessly lost. Back to musing on dinner.

Sure, it'd be nice if all speakers were so dynamic that they engaged us from the first slide, but the horrid truth is that there are some very smart scientists doing interesting research who speak in monotones, or use tiny fonts, or work outside your immediate area so they're just plain harder to follow. The challenge is, how to maintain attention even if they're not making it easy for you.

My new solution is this: Pretend I am the host (if at seminar series) or session leader (if at a conference). What's that person's job? To be ready to ask a question, any question, at the end of the talk if no one else in the audience has a hand up, to avoid the dreaded awkward no-questions silence.

The criteria aren't very stringent for my ready-to-ask question. I try to stay away from just "Have you tried that experiment under Condition Q?" unless there's a valid scientific reason to think that Condition Q might be relevant for the topic.

Ok questions, even if a bit anodyne, include things like:

"What's the behavioral outcome in that transgenic fly/mouse/worm?"

"Would your new technique be applicable to Issue Z?"

Better questions of course are more analytical, even if still pretty open-ended:

"Could that result be due to some developmental compensation?"

"Are there any other consequences to that manipulation?"

Obviously if I can manage to come up with a really good question, hey presto, I'll just ask it. But the point of this exercise is that if you are the person responsible for starting a discussion in the face of a quiescent audience, you just need to have something coherent ready to go. It needn't be fancy, but the speaker shouldn't have already answered it during the talk, either.

Simply setting this goal is usually enough to keep me focused and engaged with the talk, even in the face of poorly-designed slides or, heaven forbid, Comic Sans.

The downside being, I don't manage to figure out dinner.

What I've learned in the last 24 hours

1) If a reviewer appears batshit crazy on the first round of review, you should not assume that you can reason with or placate him/her. Madmen are only enraged by appeals to logic. Get the reviewer rejected before resubmission or you will regret it, forever.

2) Chocolate chip cookies, standard recipe: after substituting in 1/2 whole wheat flour in response to the Mom-voice in your head, also add 1/4 tsp ground cardamom. NOM.

3) Synecdoche, New York is not, as its title might suggest, a charming pastoral about the vagaries of upstate.

Dr Jekyll's Guide for Reviewers

Thanks for agreeing to review a paper for Glamour Biology! Forthwith, some suggestions you may find helpful for your reviews.

1) There sure are a lot of techniques out there these days, aren't there? We don't want you to be deterred by the prospect of reviewing a paper whose central technique is unfamiliar to you. So we'd like to encourage you to apply the standards of your technique to other techniques in the field, whether or not you have any experience with them.

For example, if you request an experiment from the authors of a manuscript, and they decline to do it on the grounds that it is technically impossible, you have every right to insist. Pushing authors to accomplish the impossible is the only way science progresses!

2) Similarly, different biologists study different organisms. Again, don't let this get you down! If you review a manuscript in which the model organism is different than your model organism, you are encouraged to suggest that the authors expand their study to include your model organism. This is a great way to foster communication among biologists.

3) Our special checkbox review portion asks you whether you think this manuscript would be equally appropriate at a more specialized journal, i.e. Unglamorous Biology. Some reviewers have mentioned concern that they think Unglamorous Biology and Glamour Biology are actually equally respectable. Um, ha ha! If this is your concern, please contact the editorial office straightaway so that we can put you on an internal list. This list isn't for any purpose, just that we like to keep track.

4) Think that the authors didn't read your first review carefully enough? Here's a handy tip: during re-review, write the critical point in ALL CAPS. That way, the authors won't miss it.

5) Sometimes, a manuscript lacks a certain je ne sais quoi. What can you say? Perhaps it's just not feasible to explain your underlying dissatisfaction with a manuscript. Your best bet in these circumstances is to be vague. Don't try to detail experiments that should have been done, or questions that need to be resolved; this will only clutter up your review. Just say that the manuscript is "unsatisfying" or "needs work" or "lacks a certain something." Most authors don't like being told to do additional experiments, so avoiding any detail on this point will help them feel better about your rejection.

6) Do the authors have a Nobel Prize? If so, we will EZPass(tm) their submission so that it goes right out for review, and you as a reviewer are encouraged to overlook any inconsistencies in the interests of expedience.

7) We're regularly asked by prospective reviewers whether the fact that they've been declared non compos mentis disqualifies them from reviewing. Not at all! The pool of possible reviewers is so very small; also, we do not like to exclude people on the basis of intellectual discrimination. That would be wrong.

8) We know that we just rejected a paper from your lab. Still, no hard feelings, right? Could you please review this paper? From a competitor? That looks suspiciously like your rejected paper?

9) Any questions, just hold onto the manuscript you're reviewing until an answer comes to you! We don't want you rushing into any rash decisions.

10) Please don't question our authority to make decisions. All of the editors here have rigorous scientific training, and the fact that none of us was ever able to publish our own scientific work in a journal like Glamour Biology gives us the proper respect for the high standards to which these submissions must be held. We are unbending in our defense of this journal's scientific rigor mortis.


All the best,

The Editors

Life's little mysteries

What genius thought it would be a good idea if two major microscope brands (Olympus and Zeiss) used opposite conventions for which direction you turn the knob for "focus down" vs "focus up"? So that after you are accustomed to one and have to use another, you end up wasting half your time focusing the wrong direction, or if you are very lucky, crashing the expensive 63x objective into the specimen?

Anyone who wants to clear this up for me, go right ahead.

When the PI's away....

What happens in your lab when your PI goes to a conference or vacation for a week or longer? (Or if you're a PI, what do you imagine happens in your absence?)

For the most part, of course, people just keep working. We're not there to please a boss, we're there to get our science done, and the boss's presence or absence makes little difference.

But on the basis of very little evidence, let me offer this hypothesis: in labs with involved, ever-looming PIs, lab members are more likely to skeeve off work when the PI is gone for significant periods; whereas in labs with fly-by PIs, lab members keep up their pace when said PI is gone.

(There could be two explanations for this hypothesis, if true: first, that the trainees with omnipresent PIs work harder when the PI is in town, necessitating a break when s/he's gone; second, that the trainees with absentee PIs sometimes don't even notice that their PI has vanished for a week or two, because it makes so little difference in lab life.)

I hasten to add that I, of course, work virtuously and steadily, unaffected by my PI's absence, much less by absurdly warm and sunny days that occur during said absence.

Blog Fodder update

Some of you may have been wondering how Blog Fodder, our haplessly ignorant tech, has been doing. Last I spoke of him, this Ivy graduate was learning how to use a pipetman, revealing remarkable deficits in conversion factors and even arithmetic of the simplest sort, unwieldy with his hands, and dismissive of animal welfare.

I am happy to report that he has cleaned up his act a great deal. His fine-motor skills are somewhat improved, but more importantly he has figured out how to compensate for his shakiness. I still wring my hands when I watch him do anything delicate, and he's slower than I would like (on some tasks where speed is important), but he doesn't biff everything he touches any longer.

I haven't dared to watch him do conversions again, so I don't know how well he's learned the necessary arithmetic. The jobs I give him either don't entail making calculations, or rely on protocols with the calculations pre-done, and if he's screwing up other people's experiments, I don't know about it.

He appears to have figured out pipetting.

He has become the go-to tech for the animal colony, and it became clear that his initial stupid comments were due more to awkwardness, or mild idiocy, than actual disregard for animal welfare. Recently he wrote an email to the animal facility director pointing out some problems with the animal care in our room, and requesting specific improvements.

He is still slow to understand what I consider straightforward instructions, but those of us who supervise him have taken to making sure he writes down what is said--and then reads it back to us--so that we know we are on the same page.

What has caused his improvement? I would like to think he was afraid of my wrath, but in reality I think there are several causes.

1) He became more at home in the lab. We all know the experience of joining a new lab and feeling ignorant and out of place. Some of us perhaps learn sooner than BF did, but he did eventually adapt.

2) As we got to know him better, we made more use of some of his previously unappreciated skills. He is extremely neat, and he keeps various benches and cabinets about 1000% cleaner and better organized than they had been before. Once we saw this, we started asking him to do more organizational tasks.

3) He has many friends who went to work in the financial industry. I suspect that in the last six months, he has come to value having a steady job more than he did at first.

4) This is his first serious job, as far as I can tell. He may have simply needed to learn what having a job is all about.

He still shows little to no interest in the intellectual life of the lab, but while it is nice to have techs who care about the science, they can be time-consuming in their own way (since they always have questions about what's going on), so this is only moderately disappointing. I wouldn't recommend him to another lab, particularly, but I no longer dread dealing with him. I'm hopeful that he will someday figure out what he is truly excited about, because science is not for him, but at least he's reached a sufficient competence level for us.

What have I learned? That pampered undergrads in their first tussle with the workplace can actually learn to be decent citizens, I suppose. That's useful to know, even if I never again wish to watch this process in action.

I am in love (a pregnancy post)

With Zoe Williams, whoever she may be. All I know about her is that she writes for the Guardian, and that I love her.

I have been spending off hours on PubMed, trying to discover the rational basis for the host of rules pregnant women are adjured to obey:

--Don't eat unpasteurized cheese (Brie, Gorgonzola, feta, chevre...all the good stuff)
--Don't eat deli meats unless they've been heated to steaming
--Don't even think about licking the bowl clean of cookie batter
--Sushi? Do you want the baby to die, or what?
--Lying on your back past the fourth month is going to give the critter brain damage
--A sip of wine? Why not just smoke crack and be done with it?

I'm not talking "old wives' tales your grandmother produces." These things are specifically listed as fetal death-traps in publications ranging from the leaflets I was handed at the ob-gyn to "What to Expect When You're Expecting," probably the single most popular pregnancy book available.

But here's the funny thing. When you look for actual studies about these things on PubMed, you keep thinking that you've entered the wrong search terms, because so little comes up.

For example, many a pregnancy site will tell you that sleeping on your back when preggers will cause pressure on the vena cava, decreasing blood return to the heart and causing all kinds of mayhem to The Little One. What does "pregnancy sleep supine" get you in PubMed? A lot of articles on SIDS, and this saying that blood oxygen drops in pregnant women sleeping on their backs. The same group also says that these lower oxygen levels don't cause any more apnea or less REM sleep, leaving one to wonder exactly what the problem is.

A couple of physicians have gotten so bemused by the onslaught of patients asking them about sleep position that they wrote this piece, opining that back sleeping would only be a problem in a small minority of women, and even for them it was unlikely to cause fetal harm.

Ms. Williams, a tart-tongued Brit (aren't they all?) with a strong sense that the world is deranged, makes the argument that a lot of these rules are based on astonishingly modest evidence, and in fact sometimes directly contradicted by other bits of evidence. She's particularly lit up about listeria, the reason so many foods (unpasteurized cheese, deli meats, and sushi) are verboten, and relays this from a professor of fetal medicine:

Jauniaux cites an interesting difference between Google hit rates and those on PubMed, a collected source of peer-reviewed papers in medical journals. "Listeria and pregnancy - Google, 190,000 hits; PubMed, 107 hits. Cheese and listeria - Google, 194,000 hits; PubMed, 169 hits. Sushi and pregnancy - Google, 628,000 hits; PubMed, 0 hits. Raw fish and listeria: Google, 123,000 hits; PubMed, 49 hits. You can see immediately," Jauniaux concludes, "the disproportion between the epidemiological evidence and the general public hysteria about the disease."

Americans in particular are obsessed with the "right" foods, despite our national inability to figure out what those are, and I think this is one reason that pregnant women here readily accept restrictions on their diet: we've been trained since birth that food is dangerous, and eating the wrong thing will surely give you cancer/make you fat/blemish your skin/diminish your virtue. The idea that pregnant women have to be even more careful follows naturally. Meanwhile, if you told a French lady to avoid Brie, or a Japanese one to shun sushi, you might trigger premature labor due to hysterical laughter.

Of course, it's one thing to say that a lot of these prescriptives are junk, and another thing to be comfortable flouting them. I made my decision to ignore these rules after an internal conversation along the lines of:

Self: "If you miscarry or the critter has some serious problems, are you going to spend days berating yourself for the salmon sashimi?"
Self: "Uh, no."
Self: "Okay then, carry on."

Obviously if your pregnant self responds differently, then it seems reasonable to stick with the guidelines.

But my sushi-eating, feta-nomming, back-sleeping, wine-sipping ass is pretty happy here at the half-way mark.

ps) Don't tell Dr Hyde that the toxoplasmosis bit is farfetched too, as I have no intention of terminating this vacation from cat litter duties. There's skepticism, and then there's stupidity.

At least I haven't set up an Auto-Reply function yet

It is sad to learn what managers the world over know, that you will spend far more time managing the incompetent than managing the competent--the competent, of course, not needing you very frequently.

(Unrelated:
The rain it raineth on the just
And also on the unjust fella,
But chiefly on the just, because
The unjust steals the just's umbrella.
--Ogden Nash, or Lord Bowen, depending on your Internet)

I was thinking about this because I am hemi-demi-semi- in charge of an upcoming event, meaning that my email is on a relevant web page. This event's webpage has almost every conceivable type of information on it. It is thoughtfully and professionally organized. It is fairly easy to find information about the event.

And yet I have gotten thirteen emails from one would-be attendee, and at most two from anyone else. Virtually all of Incompetent Correspondent's emails have asked me questions that are answered on the website.

I typically respond to these emails with a link to the relevant portion of the website, only to get a response back that says, "I found Information A there but now I want to know about Question B. Where can I find that information." Gee, whaddaya know, there is a link on that website that provides the answer to question B! It's bafflingly successful, this Internet linky thing.

If my correspondent were particularly old, I would have more sympathy, but in fact IC is a graduate student. The point-and-click business should be straightforward by now.

So I spend 80% of my event-related effort answering emails from this nitwit, and 20% responding to other nice, competent people.

I begin to understand the mindset of PIs who simply stop responding to their trainees' emails, although that is of course a very very bad way to deal with the burdens of management however much I might like to do it.

Working without a net

Prompted by a few comments on the last post--

Of the many difficult things you learn in graduate school, one of the scariest is that you, and you alone, are truly responsible for what you publish. The logic, accuracy, and weight of what you write are yours to furnish--or not.

I do not mean to say that your PI is not also responsible for your work. His/her name is on the paper too, and if it tanks, the blame will if anything fall more strongly on your advisor, as the senior author.

But as first author you are the one with direct interaction with the actual data. You collect it. You make little tweaks to your protocols to improve your data collection. Are any of those important? And did you do what you thought you did--or did you write one thing in your lab book and pipette another into your eppendorf?

You borrow a colleague's reagent, or code. Does it work as promised? And what makes you sure?

As you're collecting data, you make some snap judgments about experimental success or lack thereof. Is the problem that you put in the wrong concentration of a reagent? Or is the data real, but anomalous, unexpected? Should you trust it?

You analyze the data, and you are the first one to make decisions about what data can and should be excluded; your PI will likely weigh in, but you are on the front line. Are you excluding that data point for legitimate reasons, or because it doesn't fit your hypothesis?

You put the data into graphs. Do those graphs show your data as honestly as possible, or are they covering up something that makes you uncomfortable? When you show your data at lab meeting and someone questions your results, who is right? Is their objection valid, or do you have a better counter-argument?

Some of these questions will be resolved by talking it over with your PI, your lab colleagues, your thesis committee, or even by your reviewers. But in your development as a scientist, at some point you cannot rely on others to catch your mistakes. You will get conflicting advice from the people you talk with. You have to weigh up this advice and eventually reach your own conclusions about the best answer.

This is just plain scary. The fear does not arise out of nowhere. You do actually have to take responsibility for results that you may have gotten wrong. It would be strange if that fear did not haunt you from time to time. (I think impostor syndrome, at least in part, arises when the fear becomes continual and uncontrolled.)

When I was an early-stage graduate student, fretting over these concerns, I asked a visiting speaker during a student lunch, "How do you gain confidence in your own data?" Her advice was along the lines of, "Repetition; experience; and talking to all the smart people you can." She was right, but the best part of the interchange was hearing a highly respected scientist acknowledge that she, too, had faced that struggle--and in some ways still did, as she grappled with understanding and shaping her trainees' experiments.

Sending out my first manuscript was transformative in this respect. When we got page proofs from the publisher, it was suddenly clear to me that the assertions and arguments that I had written (and then had heavily re-written by my PI) might be read by someone, some day. Perhaps other people realize this rather obvious fact earlier in the game, but it took the formatted page proofs to stun me into it. My advisor gave lots of feedback and shaped the paper in diverse ways, and the reviewers nudged it as well, but it was now clear to me that in essence, I was working without a net.

I don't think I've been the same since.