The Futile Cycle

Via Ars Technica, there’s apparently a new database online called Deja Vu, which catalogues duplicate (or near duplicate) entries in MEDLINE, using an algorithm very similar to BLAST.

The majority of the entries retained in the database seem to be cases of outright plagiarism. Going through a few of the entries is like dredging the bottoms of the academic pool; most of the journals are pretty obscure or quite poor in quality, and I bet most of the authors are pretty unknown, too. It’s a strange world down in the pits…

As I was studying like mad for my prokaryotic molecular genetics final exam, I found an (alas) engrossing anecdotal essay from Seymour Benzer, called Adventures in the rII Region, which contains the following rather amusing story.

Seymour Benzer, who died just one and a half months ago, was one of the giants of early molecular biology. He was one of the first geneticists to show that genes weren’t indivisible subunits on DNA (like beads on a string), but rather linear “regions” of DNA, which he called cistrons. Many consider his mapping of mutations within individual genes to be one of the most elegant and amazing achievements of early molecular biology.

When he first showed Delbruck (his mentor and another giant back in the day) his manuscript, apparently Delbruck commented, “Delusions of grandeur.” Benzer follows:

Delbruck knocked the paper so badly that not until a visit to Caltech the following spring did I dare to approach him with another version. He submitted it to the Proceedings of the National Academy of Sciences, and it contained an appropriate acknowledgement of his “moderating influence.”

Tough love, indeed!

There are all sorts of anecdotes in that essay that a pleasure to read, about the entire molecular biology revolution of the mid-20th century, and the close relationships of the biggest players of the time. Some of those scientists were probably more than a little crazy! Check it out!

There’s an interesting article in Genetics on the luckiness of biology’s initial choice of bacteria to study. One of the most common bacterial types that molecular biologists studied back in the mid-20th century was E. coli K12. K12 was used a lot because it harbored a dormant λ virus (allowing the discovery of one of the most elegant genetic switches ever found), an F⁺ plasmid, and many suppressors of amber mutants (which I mentioned before).

All three of these features of K12 were extraordinarily important to the development of modern molecular biology, including the nature of the genetic code, tools for understanding gene regulation, fundamental mechanisms of transcription and translation, the circular nature of the bacterial chromosome, the mechanisms of transposition, the nature of recombination, and so on.

The paper talks in particular about amber mutation suppressors. Apparently strain K12, back when Edward Tatum first established it, had somehow acquired an amber nonsense mutation in rpoS, which codes for the RNA polymerase σ^S sigma factor needed for survival in stationary phase (i.e. semi-starvation and crowding phase). Lab strains often hit stationary phase when grown on plates, which would lead to a positive selection for amber suppressors. Thus, K12 acquired a large number of amber suppressors, leading to the discovery and utilization of a large number of conditional and conditionally lethal mutations!

Amazing how much biology has been discovered due to sheer chance…

I’ll be writing on microRNAs soon, but here’s yet another example of the extraordinary speed at which some hot fields (like microRNAs) move.

There’s a review paper on microRNAs that was published in advance (i.e. online before its print publication) in Nature Reviews Genetics this past Wednesday. It summarizes the latest and cutting edge of our current understanding of microRNAs, how they’re made, and how they work.

And it might already be (slightly) obsolete, even before it is published!

The review paper almost didn’t get to mention the new upregulatory mechanism of microRNAs paper that I wrote about one month ago, but they managed to squeeze it in at the last moment (there’s an addendum at the end of the paper mentioning this new result). The review certainly didn’t mention last month’s Cell paper on Ago2’s possible role in microRNA maturation and the PNAS paper on the current understanding of the RISC-loading complex composition that was published just over a week ago.

Certainly, the review paper isn’t useless; far from it, as it summarizes much research that is still relevant to our understanding of microRNA mechanisms, and it’s a useful resource for reference and for those who want to learn about the field for the first time. But it is still the slightest bit obsolete even before the ink has hit the page.

Alas, the curse and thrill to live in exciting times.

Alas, I (as a poor, time-crunched graduate student) will not be able to make it to the North Carolina Science Blogging Conference, but they have a nice website that’s going to be aggregating a lot of the content surrounding the conference.

(Beware of that aggregating website; it seems to break on Safari, so use Firefox. Alas, Mac users do not seem to command respect and deference quite yet.)

Over at CoyoteBlog, I’ve made a few comments on this blog post in response to a quip that the author was skeptical about global warming. I’d like to repost my arguments here, since I think it’s a general reflection of my thoughts on science:

I think that trusting scientists on their views in their fields of expertise is generally a good idea, and if the IPCC says that global warming is starting to accelerate, I’m inclined to accept it; it’s really the only intelligent thing to do. Policy and normative notions, one can debate, even if you aren’t an expert, but for facts and other positive notions, I’ll stick to the experts, and they seem to say that global warming is real.

If everyone trusted the experts more, the world would be a better place. None of the pseudo-science homeopathy/complementary medicine nonsense, none of the liberalized ignorance of basic economic facts, and none of the nonsense of evolution denial.

Here, someone replied to me:

Your response would make sense if you didn’t take into account the idea that scientists get way more money to do research about catastrophic global warming versus natural equilibrium.

In addition, I don’t agree with the “trusting experts” argument because I have yet to see an approach to global warming based on the emerging field of complex adaptive systems. As one who studies this field, am I not an “expert”, shouldn’t you trust me? Because I’ve found that complex systems move towards different equilibriums, not tipping points. By classifying the global climate as a complex adaptive system, I have to disagree with the current so-called “experts” who claim there is a tipping point.

Personally, I think this whole argument of “trusting experts” is flawed because one is only an expert until somebody with a new theory comes along that is better. Let’s not forget the “experts” told us that the Earth was at the center of the universe, and they had the majority consensus. It used to be mind boggling to think otherwise.

“Trusting experts” is probably one of those things which will lead to the loss of individual liberty and further reinforces the point of this blog article

Thus, I replied,

Well, notice that I used the plural here. The views of an individual scientist are, for better or worse, his/her own views. The scientific consensus, on the other hand, represents the views of a large swath of scientists, and the competition between scientists for funding and publication generally means that, on the whole, the “most correct” interpretation tends to win. I don’t know how much I can trust an individual scientist’s views, but if a vast majority of scientists support a view, then I’ll stick with that one. I’m not addressing here the whole “tipping point” phrasing or alarmism that the particular journalist used in the above blog post. I’m talking about general skepticism about global warming. Unless I have specific, methodological problems with the general field’s reasoning, and have experience in in that field, I’d say that I will always accept the field’s scientific consensus on a subject.

There’s a word for people who, with absolutely no expertise, think that they have the answers in the face of tons of experts: crackpot. Lay people (i.e. non-scientists) who go against scientific consensus are the same as people who think that they can prove Einstein’s Theory of Relativity wrong, or who think they’ve proved Fermat’s Last Theorem in two short sentences. They’re not brilliant critics; they’re raving madmen. Just because Rob is an expert in complex adaptive systems doesn’t mean he’s an expert in climate science. That’s like saying a mathematician is an expert in cryptography; yes, cryptography uses mathematics, but unless that mathematician has a focus on cryptography, they won’t know all the algorithms, all the details, all the issues involved. If a mathematician were to persist in making sweeping non-consensus claims about cryptography without reading about cryptography, he or she’d be a crackpot, regardless of how smart they are.

So if Rob is going to make some claim about climate science because he’s in a field he thinks is related, he’d better have much better reasons than “adaptive systems converge upon fixed points”, cause climate phase trajectories lie in a large-dimensional manifold, and in such situations, fixed points often abound; in addition, we don’t know the rate of convergence to the various fixed points, and presumably the ever-changing flux of the sun, geothermal activity, and rotation of the earth would prevent such steady-state convergence. Perhaps anthropogenic climate change is driven by the evolution of fixed points in certain directions; perhaps our introduction of greenhouse gases has led to some sort of bifurcation, and that’s leading to the increase in temperatures. Hey look, I can make vague generalities about climate science as a complex system, too! Do you believe me? I would hope you go to the experts instead.

Sure, some “experts” in the past have claimed that the Earth was in the center of the universe, perhaps, but they were not scientists; they didn’t follow the scientific method, they used state-mandated religious views to arrive at their conclusions; religion obviously is not a source of facts, and isn’t a way to find scientific truths.

The IPCC (a coalition of most climate scientists) thinks that currently, mankind’s contribute to the environment has caused a significant change in the climate, leading to a significant change in the world’s temperature compared to the past. The main objections to this that I’ve seen come from 1) people with no expertise, and 2) a few (very few) climate scientists. The people with no expertise include members of the press, politicians, random scientists from other fields, and so on. I don’t think they have valid points to make unless they really read the literature first. That the vast majority of climate scientists agree with the IPCCs statements nullifies my second concern.

And an expert in climate science is still an expert in climate science once new theories come about. Did physicists stop becoming physicists with the quantum mechanics revolution? No, they instead all became expert quantum physicists. Did they leave the theory up to the public to decide? No, they evaluated it themselves, because people intimately familiar with the experimental details and the underlying facts and methodologies are the best ones to evaluate new theories and evidence. Let the scientists in the field determine what theory is sound and what isn’t; I don’t think the uninformed public should.

I’ve always had a strong dislike about certain biology naming conventions, but one thing that I always found rather strange was some of the whimsical and utterly meaningless names given to some genes and mutants. Take hedgehog, for example, or Bicoid. Meaningless names, really; they vaguely correspond to some sort of phenotype, but other than that, have very little to do with the actual biological function.

A paper I’m reading for a class, however, gleefully points out that meaningless names have their purpose: they don’t go obsolete with new information:

Epstein was struck by the similarity of the amber mutants and the so-called hd, or host-defective mutants….Who first had the idea that amber mutations are a general class of “suppressor-sensitive” mutations, I don’t recall….That year, Campbell did further experiments to show that the hd mutants (then renamed sus, for suppressor-sensitive) were in fact responding to a bacterial suppressor gene…

(It is amusing to note that Campbell found it necessary to rename his mutants after learning more about them, whereas the name amber is just as meaningless, and thus just as useful, now, as when the mutants were first discovered and named for Mrs. Bernstein.)

Edgar, R.S. 1966. In: Phage and the Origins of Molecular Biology, Cold Spring Harbor Laboratory, NY. p. 166-170.

hd and amber mutants are the same type of mutant, and “amber” is the English version of the German name “Bernstein.”

So, perhaps those Drosophila geneticists are doing a service to the rest of us after all.

The simplest answer isn’t always right, but it’s often one of the most convincing answers. John Timmer over at Ars Technica talks about the rise of a very simple answer to a whole swath of questions that include

1. How do transcription factors, splicing factors, and other such DNA and RNA interacting proteins operate accurately when they’re so promiscuous in what they choose to bind to?
2. Why is so much of the DNA transcribed to RNA?

The simple answer that John gives is simply, transcription and splicing factors don’t operate that accurately, and most of the DNA is transcribed to RNA because of this inaccuracy. Simple! And quite a compelling theory, actually, something I like very much.

The question this line of reasoning raises, then, is whether the RNA editing and selective degradation pathways are sufficient to prevent something bad from happening to the cell. There’s nonsense-mediated decay, signal-sequence localization, non-stop mediated decay, and complicated RNA localization and export control. That’s in addition to RNAi, the evolution of which may have been driven in large part in order to weed out bad RNA.

This would, perhaps, explain why RNA editing features are so much more complicated in mammalian cells than in Saccharomyces cerevisiae, as S. cerevisiae (baker’s yeast) tends to have very highly conserved, high-consensus splice sequences (i.e. low error, but also low complexity), as well as more well-defined and static chromatin and no RNAi.

The story vindicates that complicated gene regulation and patches and makeshift fixes for errors are two sides of the same coin.

Annoyed that if you see a song in an iTunes playlist and you hit “delete”, it’ll only disappear from the playlist and not the library? Dislike having to go and hunt for the file in your actual library to delete it?

My expanding iTunes library has made me write this Applescript (oh, the horror!) that’ll delete the original songs from the iTunes library if you select a song in a playlist. Installation and usage instructions are in the Readme file, and I’ve zipped the whole thing.

Note, of course, that this script only works on Macs…

UPDATE: Apparently, there’s a not-well-documented keyboard shortcut for deleting songs from the library straight from the playlist. Instead of hitting “delete”, the keystroke is Opt-delete. Thanks to manduca for the tip!

In my current rotation, I’ve been doing a little self-experiment; the lab has a group wiki where everyone can post things that would be relevant to everyone else, such as protocols, lab reagent lists, etc., and I figure that my lab notebook is of interest to other people. After all, it’s not just for my own records.

Thus, I’ve been keeping my lab notebook on our lab’s wiki. I know that OpenWetWare and other groups have been doing the whole “keep a lab notebook online” for a while, but I’ve been skeptical up until now about the value of an online notebook. I’m a wet lab scientist, not a dry lab scientist, and so I thought that I might run into some trouble with data and such that I wouldn’t be able to put online (or that would be too cumbersome to do so). In this day and age, though, everything is electronic. The microscope takes digital pictures, I scan in pictures of my gels, and the 96-well plate reader exports plaintext files that I can process with Python and R. Everything basically has to be able to get onto a computer anyway in order to be written into a paper.

So far, it’s been going great! It’s nice to be able to access the notebook from home or from any computer in the lab, for example, and I don’t misplace it. If I have a contact on a particular project, his contact information is always online at my fingertips. I can even search my lab notebook, or cross-reference easily! I’m a convert!

Unfortunately, I am not an open lab notebook convert, for two reasons. First, I’ve signed a non-disclosure agreement with a company to use one of their proprietary discoveries, and though we’re allowed to publish results, I figure blabbing about it all over the internet is something I’m clearly not allowed to do. Second, I work in a very competitive, fast moving, popular field, and it’s very possible that we would get scooped. We’ve already had that happen once. Even if the likelihood that someone will swoop by our lab wiki and scoop us that way is low, any little bit can be quite detrimental. And because I’m collaborating heavily, and not all of my collaborators may feel the same way about open science that I do, I am unable, alas, to endanger their own careers by putting my lab notebook on the open.

I also think that open notebooks work best in small communities, such as fields with very few people that are all friendly, or a small group of collaborators. Or even a field that moves slowly enough that it wouldn’t be possible to scoop someone based on their lab notebook. I do think that small communities make it much less likely that you’ll get scooped, as people tend not to mistreat people they’ve met and put a face to.

But in any case, as god is my witness, I’ll never keep a physical lab notebook again!