The Futile Cycle

Though I’ve worked in labs as an undergraduate, picking one for graduate school will be very different, if only because it won’t just be an extra-curricular anymore, but pretty much my life for the next 5 years or so.

Some of the post docs that hang around the internet have compiled some helpful lists of how to choose labs and deal with lab politics. These lists are more than just lab advice, however, as it seems like they would apply to any sort of job or life situation.

Jenny F. Scientist recently put up a series of three articles on choosing a lab, and what kind of questions and topics one should pay particular attention to. The advice all sounds very sensible, and I will definitely be using the list as a way to focus when I’m juggling lab choices:

• Part 1: Introduction
• Part 2: Professional Factors
• Part 3: Personal Factors

Post doc ergo propter doc has a “Lab Survival Guide” pair of articles up. She’s a chemist (probably organic), and the first part of the guide is more about the tools valuable for doing chemistry (e.g. different colored septa, a metal TLC spotter). Her second part is about dealing with people, and that’s something that translates quite well to biology:

• Lab Survival Guide Part I: Essential Lab Kit
• Lab Survival Guide Part II: Dealing with Difficult Lab Folk

Dr. Mom explains how to write the first paper, a great series that she eventually hopes to give her students as she starts her assistant professorship.

• Step 1: Am I Ready?
• Step 2: Where should I submit my paper?
• Step 3: Title, Affiliations, Abstract
• Step 4: Introduction
• Step 5: Materials and Methods
• Step 6: Results — Figures
• Step 7: Results — General Comments and Tables
• Step 8: Discussion

From the BBC, real “Kryptonite” is found in a mine in Serbia, with the chemical name “sodium lithium boron silicate hydroxide”. Apparently, in “Superman Returns,” that was the name of the rock with kryptonite that Lex Luthor stole.

Too bad it can’t officially be named “Kryptonite”, considering it has no krypton (the noble gas) in it.

I’ve decided that there are a few standard rules for making good titles for talks at small symposia:

1. The title must be short. No more than six or seven words. These can be exceedingly long, compound words, but please keep it to six or seven.
2. Use a colon.
3. It must not communicate anything concrete about the actual contents of the talk.
4. Don’t let the title pin you down; talk about whatever you feel like. Change the title/topic without prior notice, if you wish.
5. The title can be either grandiose and far-reaching or short and quirky, but keep in mind rule number 3.
6. Puns are optional.
7. Include some form of “new”, “novel”, “super-fantastically cool”, etc. This goes after the colon.

Any other rules that you all can think of?

For those who are interested, Papers has reached version 1.0. I’ve written before about this Pubmed-integrated literature organizer and viewer.

In addition to a whole slew of bug fixes, my favorite new feature in this version is that Papers has gained built-in integration with proxy servers and authentication pages, which most of us need to use in order to access institutional subscriptions to journals. I, for example, have to append “ezp1.harvard.edu” to all website domain names (so, something like www.sciencemag.org.ezp1.harvard.edu). Up until recently, I’d been using some Perl scripts and a patchwork of programs to let me switch over to the institutional subscription with keyboard shortcuts whenever I needed (yes, it’s only 16 characters, but it was maddening); now Papers will do it for me!

Papers won’t be taking over my entire workflow (Pubmed still doesn’t update as frequently as, say, my email news alerts and RSS feeds), but it’s definitely taken over every aspect of actually reading papers.

UPDATE: Ok, so Papers’ authentication and proxy-server support is actually broken right now (at least, it doesn’t work for me). Not so great, especially for a supposedly 1.0 release, but I still appreciate the other bug fixes.

UPDATE 2: With the new bugfixes, Papers now works with the Harvard authentication server (at least). I can’t verify it for other servers, but it works swell for me!

An article published recently in Science Express focuses on the growing trend of team-based research in science and engineering research, and the decline of the individual. This has all been known for quite some time, especially with the rise of massive collaborations a la the Human Genome Project and large particle accelerators, and also because of increasing interdisciplinary research that requires teams of specialists. The trend, however, is apparently also increasing in the social sciences and mathematics, where lab-work isn’t always as critical to the success of the project and where one might think that having too many people might even hinder good work.

The most interesting aspect of the paper was their analysis of the quality of team-based research. They showed was that team-authored papers in science are being cited almost twice as much as solo-authored papers are, even with self-citations removed.

One could also consider that, although solo-authored papers would be cited less on average, they might make the greater portion of the hugely influential papers. In the past, apparently solo-authored papers were more likely than team-authored papers to gain the highest numbers of citations, but now, team-authored papers are more likely to gain a high number of citations.

It’s clear from the paper that in all disciplines, from science and engineering to mathematics and the social sciences and even to the arts and humanities, team-based research is coming to dominate the solo researcher. The image of the lone-genius is slowly dying, I think. Maybe in the future students will learn about the Grubbs-Evans-MacMillon-Sharpless (GEMS) catalyst, or the Schreiber-Lander-Maniatis-Weissman-Walsh-Eggan-Melton (SLM-WWEM) embryonic stem cell protein complex!

I went to part of a recent conference, “New Directions in Quantitative Biology“, this past weekend, which was pretty neat. The talks I enjoyed the most (of the ones I attended) were Celeste Nelson’s talk on investigating branching growth in 3D cell cultures, Claire Tomlin’s talk on using control theory to decode the hair patterning on Drosophila wings, and Ron Weiss’ talk on synthetic biology.

The overall theme of the conference was on research that integrates mathematical and physical methods and understanding into traditional biological concepts. One of the problems with this mesh of topics is that both traditional biologists and traditional physicists and engineers populate the audience, which means that some of the mathematics will inevitably be over the heads of some of the audience, while some of the biology will be cryptic and inexplicable to much of the audience as well. I think the speaker who balanced the two the best was Claire Tomlin, who managed to present her engineering modeling work without filling slides with equations; she chose to focus on the assumptions, the process of choosing the appropriate implementation of the model, and the results of her modeling, and how the simulations both explained and contributed to the fundamental biological research on fly development. Not only were they able to show that Jeff Axelrod’s autoregulation model was sufficient to explain the hair patterning in Drosophila, but they also showed that the biological behavior “disproving” the model actually supported it, as they were predicted and (nonintuitively) consistent with the simulations. Finally, the model predicted new phenomena that was then later independently confirmed by other labs. The talk was really beautiful work, and is summarized in this paper:
Amonlirdviman et al. (2005) Science 307, 423-426 (PDF)

Another problem with these interdisciplinary talks (or a benefit, to see it from another direction), is that it’s very possible that one side of the “cultural divide” will ignore or overlook something that’s very obvious to the other side, which makes for much awkwardness. When one physicist gave a talk about how certain cell movement dynamics indicated that microtubules are buckling, a biologist raised the question, “Well, what if this behavior is because of de-polymerization of the microtubule?” The physicist sort of stammered, “Well…well, ah, I guess it could be de-polymerization.” The silence in the audience was very awkward for a few moments, before another audience member helped the physicist rationalize mechanical buckling as the explanation instead of de-polymerization. It reminded me of another anecdote from around here: there was one physicist who worked hard for a year on the dynamics of DNA unzipping, and after analyzing many computer simulations and mathematical models, finally concluded that AT base pairs unzip faster than GC base pairs. A biologist quipped, “My four-year-old granddaughter could have told you that, and it wouldn’t have taken you a post-doc and one year.”

The potential “benefit” from these interactions, of course, is that if the biologists and physicists didn’t get together and talk at conferences like these, both sides would have gone about their merry way, ignorant of spuriousness of some of their efforts and results. Still, it probably would have been better that the biologists and physicists had interacted earlier in order to stave off too much wasted effort. One graduate student who was a teaching fellow (a.k.a. TA) for one of my classes does interdisciplinary work in both theory and wetlab biology, but he is a part of both a computational biology lab as well as a traditional biology lab, because only the theorists who really work and live on theory can really do a good critique of theory work, and only the biologists who do lab-work full-time can tell what are good and bad experiments. Each side knows the nuances of their own field that the other side wouldn’t know, and the grad student gets the benefit of both sides by having one foot in each lab.

I’ve heard that graduate students with more than one advisor are a rare bunch, but I wonder if it will become more and more common, now that interdisciplinary research is really starting to take off in a huge way. Maybe even I will consider it as an option in the next year or two.

I find it really hilarious that an outage of the Blackberry email network for a dozen hours or so at night warrants widespread coverage in the media.

I understand that Blackberries are really addictive; I myself can get addicted to information sometimes (what with my 100+ news feeds that I follow), but this is a little ridiculous. Most of it didn’t even happen during normal North American business hours. I can step away from the computer (though it does take some coaxing, occasionally). Can’t they?

There’s a discussion on In the Pipeline about the value of going to get a Ph.D., and one of the big questions being raised is why people want one in the first place.

For me, I don’t know what I’m going to do in the future (i.e. after graduate school). That’s several years down the line; I might do a post-doc, go into academia, maybe go for industry, go into business, I don’t know.

What I do know, right now, is that I want to do research in biology. When I look into a microscope and see a nemotode slithering around, munching on bacteria, that’s fascinating. Finding a visible colony that’s replicated overnight from a single, invisible bacterium is really amazing. And transforming bacteria with new genes that make them do things is completely awesome!

The theory side of things is really amazing, too. I love how enzyme cascades make switches possible. I like that feedback can create oscillations. I wonder why organisms evolved to be the way they are. It’s really neat that mathematics actually works to describe biological systems and find new things out, even if we don’t exactly have the universal laws to do so.

There are some really cool questions to be answered from all sorts of angles, mathematically and experimentally. I want to get a Ph.D. because I want to spend my time (getting paid!) to study this stuff. It sure isn’t about the money or future job prospects right now. It’s all about the science!

There is a really great post and discussion on Marginal Revolution on a book, Money Driven Medicine (by Maggie Mahar) about the source of the spiraling costs in American health care that don’t seem to improve patient health at all. The best part is the comments, I think. There are some good commenters, and then the author comes to respond to some of their questions.

I really like this part of a comment from Yancey Ward:

Our problem is that we treat medical advances differently than we treat other technological advances…

In the early 80’s, the first personal computers cost over $10,000 a piece. Such computers were only purchased by people with the means to do so, and no one really questioned this inequality- for almost all new goods and services, it is only the upper income cohort that can afford to purchase them. This was true for personal computers in 1981 as it was true for automobiles in the early 20th century….In addition, one will surely find examples of luxury goods and services that never really spread down through the lower income cohorts because they were ultimately found to have no benefit or use-in other words, they were found to have no larger potential market.

However, when it comes to medical goods and services, especially goods and services that claim to be life-saving/prolonging, the inevitable inequality I wrote of above assaults our sense of fairness. We demand that such goods and services be available to all regardless of the cost and the efficacy. All other new goods and services first prove their worth to the small cohort that can afford the luxury of trying them out, but this is not the case with medical care- we consider it unfair that the wealthy can afford new cancer treatments of questionable worth- thus the process of real-world testing of efficacy is short-circuited. (Emphasis mine)

We seem to have the perverted thought that good health should have no price, and that all patients deserve the latest and greatest, when simply prescribing last year’s remedies (or even the old soap and water) would be significantly cheaper and create real improvement in the patient’s life, with only a tiny extra benefit from using the newest drug instead.

There’s also a good comment from “happyjuggler0″:

When Pharma comes out with a new drug treating something that was previously untreatable, it is meaningless to say that costs for that treatment have shot up, since there was no treatment for it before. Eventually, rather quickly I might add all things considered, this drug will go off patent and become dirt cheap. each year more and more drugs go off patent, and thus in reality drug costs are going down radically, not increasing.

From Maggie Mahar:

In the mid-ninties insurers were fairly successful at containing costs (if not improving care) for a few years–but the backlash was so great that they began losing customers. As a result, at the end of the nineties insurers decided to just cover whatever consumers asked for–and pass the cost along in the form of higher premiums. This explains why premiums have risen 87% in the past six years.
….
Why can’t consumers themselves push back–and demand lower prices and higher quality (as they do when shopping for other goods and services)? It’s not because they are, as Nathan puts it “you know, too lazy to actually talk to their doctor.” It’s because, first of all, they are sick….Secondly, even if they are not elderly, in pain or frigthened, the subject that they need to master is dauntingly complicated.
….
Moreover, the consumer is not in a position to push down prices because when you are dying of cancer (or congestive heart failure, etc.) you are not bargain-hunting. You become a “price-taker”–you will pay whatever price is necessary to end the pain, prolong life, be able to get up out of bed and function, etc.

Even if you are paying out of your own pocket you will do whatever is necessary to come up with the money–which is why medical bills are the leading cause of personal bankruptcy in this country.

One thing I don’t see, though, is why Maggie Mahar is lenient on insurance companies for being profit-driven, while blaming pharma companies on being profit-driven (in her comment, at least; I plan to read the book soon). She says, “After all, a for-profit corporation’s first reponsibility, by law, is to its shareholders–not to its customers,” but is far more reticent to give that excuse to drug companies: “Arguably, a for-profit manufactuer that promotes its product as widely as possible is only doing its job. (Though one would like to think “caveat emptor” shouldn’t have to apply when it comes to products that could mean the difference between life and death for the customer.)” Partly, it’s because it’s easy in this society to demonize pharmaceutical companies. It’s even possibly the fashion, right now. They do sometimes do unscrupulous things. But they don’t always, and there are plenty of people in their ranks that work hard at a very difficult task.

She also says,

For years, drug-makers and device-makers have fought tooth and nail against “head to head” comparisons that would test the effectiveness and safety of a new product against the older, less expensive product that it hopes to replace. And what’s amazing is that drug-makers and device-makers have won this battle: In order to earn FDA approval for a new product, the manufacturer only has to show that the benefits of his product outweighs the risks WHEN COMPARED TO A PLACEBO.

I really don’t see what’s wrong with comparing to placebos. The FDA is just supposed to be a gatekeeper screening for safety and efficacy. Why does everything have to be an improvement over what exists already? Knock-offs are good for consumers, too, because they increase competition and lower prices. How cheap would painkillers be if there was only one kind? Maybe cheap, maybe not, but because of competition, I can walk to a CVS and buy a 200 tablet bottle of ibuprofen (”Advil”) for $7.

Now, just because pharma makes the knock-off doesn’t mean doctors have to prescribe it. Of course, they need to know the data in order to decide what to prescribe. What is needed is an organization of researchers and doctors to do more head-to-head comparisons that would actually determine the efficacy of new drugs and determine standards of care, because doctors are really the gatekeepers of health care. I’m sure this already happens, to a certain extent, but it needs to happen more. Patients can’t negotiate the system, insurers are unwilling to, and do you really want pharma to stop producing drugs? Doctors are the ones prescribing and advising; that’s part of their job, so something should exist to help them. Now, if pharma and drug companies have been preventing head-to-head comparisons from happening at all, then fine, hound them for it. But I don’t think they are, since I’ve seen plenty of them appear in the wild.

Read the whole thread, if you have time; it’s very good, and Maggie Mahar makes some very good points, not all of which I agree with.

I thought my days of discovering new holidays was over in elementary school, but I learned that Monday was “Patriots’ Day”, at least in Massachusetts, Maine, and Wisconsin. Very strange. I still had class, though…