BMC Research Notes – a place to publish the results languishing in my drawer?

July 1, 2009

I have previously addressed the unfortunate bias in the scientific literature that arises from the tendency not to publish results that are negative, or that simply show that a certain direction of scientific exploration is not very promising.

The other day, I learned about the relatively new journal BMC Research Notes. This is an open access online journal with the mission to publish:

scientifically sound research across all fields of biology and medicine, enabling authors to publish updates to previous research, software tools and databases, data sets, small-scale clinical studies, and reports of confirmatory or ‘negative’ results. Additionally the journal welcomes descriptions of incremental improvements to methods as well as short correspondence items and hypotheses.

Here is, at last, a scientific journal that will not shy away from making accessible data that will only be valuable to a small set of researchers. There have been several times when I have run across scientific questions that I know must have been addressed many times before, but the results of which haven’t been published. I also know that if my new question were known to the other scientists, they would probably have published. From this I have learned that it is difficult to predict which findings might become important in the future, and that the best course is to simply make data available.

The key question is not whether BMC Research Notes will come to be regarded as a ”dump journal”. It will, by arrogant investigators who would rather drop a project than publish it in a less prestigious publication. But their attitude is doing the scientific endeavour a great disservice by contributing to the already heavy bias of what gets published.

When you see another researcher’s publication list and it includes only top journals with the occasional Nature or Science paper like icing on the cake, the relevant response is not just “excellent!”, but also “what is this person hiding?”. Where are the great heaps of data that this scientist has generated, but that never made it into one of the top articles? Have they been forever discarded? Is that in anybody’s interest?

Self-referentiality in cell signalling

June 20, 2009

”This title is false”

Thus begins a reflection in the April 23 issue of Nature, by Mark Isalan and Matthew Morrison. They are alluding to Epimenides’ paradox, the famous philosophical concept where a statement, if true, must be false, and if false, must be true. (The paradox is usually related in the form: All Cretans are liars, as Epimenides himself was from Crete.) As Douglas Hofstadter so brilliantly exposed in his canonical book “Gödel, Escher, Bach”, this same phenomenon underlies Gödel’s incompleteness theorem. In effect, if a mathematical system is “complete” and able to incorporate such phrases as “this theorem is false”, it will therefore contain self-contradictions. 

Statements referring back to themselves occur very frequently in biology, if you take a broad view of information transfer. For example, many cell signalling molecules induce an inhibitor of their own activity, in a negative feedback loop. What Isalan and Morrison highlight is the need to envision such systems not in the familiar two dimensions, but over space and time.

Consider the following ostensibly simple system:

p53 MDM2It looks quite straightforward: p53 induces MDM2, which in turn inhibits p53. But can you predict how this system will behave?

A number of possibilities present themselves. Is there a steady state, where the two molecules are at equilibrium? Is there, perhaps, a constant slow decline of p53 until there is no activity left? It’s even imaginable that p53 could be completely uninducible in a system corresponding to the picture above.

In fact, p53 oscillates very dynamically when it is induced. It is thought that the number of peaks, rather than their amplitude, determine signalling intensity. This was only discovered fairly recently in Galit Lahav’s laboratory at Harvard.

The former president of the Karolinska Institutet, Hans Wigzell, often likens reaction pathways like the one above to “Donald Duck biology”. They present a tremendously oversimplified view of the system in question, by omitting time, space, and weighting of the processes involved.

With the rapidly increasing possibilities of resolving molecular interactions in time and space, we will have to get used to abandoning simplified models in favour of more complicated representations. I wonder how long it will take before differential equations are required knowledge for biology undergraduates?

The Scientia Pro Publica blog carnival is up

June 15, 2009

Scientia Pro Publica

The sixth edition of the Scientia Pro Publica blog carnival is hosted by Kelsey Abbott at the Mauka to Makai blog. Among the rousing stories of sex, drugs, cannibalism, phylogenetic classification, and sheer madness, you will also find my recent post on Open Access publishing.

Head over there and have a look!

Who is the woman in your relationship?

June 14, 2009

For some, it’s a bitter fight. Check out this video of two flatworms mating!

The first one who gets stabbed by the other’s penis will become the mother, and both are struggling with gusto and determination for the fatherhood.

Hat tip: Deep Sea News.

My research is published with Open Access!

June 8, 2009

My latest paper has just been accepted for publication in the Journal of Experimental and Clinical Cancer Research. This is an open-access, online-only scientific journal. When the paper comes out I will cover it in another post. Meanwhile, let me exhort my fervent commitment to open access scientific publishing.

The cycle of scientific endeavour typically goes like this (substitute your favourite researcher if you want):

  1. Somebody gives me money
  2. I do research
  3. I write up the tattered remnants of my grand designs into a decent manuscript and send it to a journal
  4. The journal sends the paper off to other scientists who review it for free, while I review papers from other scientists in other journals in my spare time because of loyalty to the Scientific Endeavour or something
  5. The journal decides, hopefully, to print it and then charges me at least 1000 USD for the luxury. It also charges subscribers and university libraries fo the right to read the article in print or online, making it impossible for anyone outside the system to access the knowledge I have painstakingly assembled.
  6. The Cancer Fund or the NIH (substitute your favourite funding body) counts my journal articles and then, hopefully, gives me more money.

While both I and the funding bodies (which are often backed by public tax-money) want the results to be as accessible as possible, the lock-in behind paywalls becomes an unfortunate consequence of the fact that journal article are nearly the only metric of achievement by which I can be measured.

Furthermore, I need access to all the journals in my field. It’s not the case that one could simply be substituted for another. This means that my university is almost completely price-insensitive, a situation upon which the scientific publishers have been quick to capitalise. Elsevier, one of the “Big 3” together with Springer and Wiley, has had an operating profit margin above 35% in recent years in the science and medicine section of its business.

A recent industry report (not online) from Deutsche Bank on scientific publishing states that “We believe the publisher adds relatively little value to the publishing process.” This is true. The value added lies, besides the typesetting, mainly in that the credibility of the research can be boosted by the strong brand of a prestigious journal. And I don’t have to add that that sort of bias in the scientific community is a problem even though some may benefit from it.

A bunch of corporate behemoths are making obscene amounts of money by keeping (mainly) tax-funded research results out of the public domain. Outrage is warranted.

The solution? Open access publishing, of course!

There are a few different models for open access, including self-archiving of manuscripts and data on public servers. But the simplest and best-functioning solution, in my humble opinion, is the open access journal. It’s just like an ordinary journal but with free online access for everyone. The costs of publication are covered by a fee (again, around 1000 USD) payed by the scientists themselves (us).

The health worker whose hands are in the foreground will be able to read my latest article online without a subscription, should he/she want to.

The health worker whose hands are in the foreground will be able to read my latest article online without a subscription, should he/she want to.

The cost is not greater than for many traditional journals, and is offset by the greater availability of the article. Some studies suggest that open-access articles are cited at least twice as often, at least in certain fields. But most of all, there is an imperative stemming from our purpose as scientists to generate knowledge and actively share it around the world. We have no reason to keep supporting the self-serving oligopolies of knowledge that still publish most scholarly articles, when we can instead make them freely available to the entire world.

Alan Sokal of the Social Text hoax visits Stockholm

May 28, 2009

Many of the readers of this blog will be familiar with the 1996 hoax perpetrated against the journal Social Text. The physicist Alan Sokal, in an attempt to expose the low standards of intellectual rigour in contemporary post-modernist scientific debate, wrote a parody of an article of scientific theory, and got it accepted.

The article begins by asserting that many scientists continue to “cling to the dogma […] that there exists an external world, whose properties are independent of any individual human being […].” It continues by weaving a strange cloth of disparate concepts from physics and philosophy, without any real justification, increasing in preposterousness to a magnificent climax, where Sokal claims that Lacan (the notorious psychoanalyst) has derived a mathematical justification for the phychoanalysis of AIDS from differential topology theory. It ends by saying that mathematics must be revised to be able to participate in the struggle against capitalism, patriarchy, and militarism.

Afterwards, he published another article, revealing that the first one was a hoax. This caused considerable debate, most of which is found on Sokal’s website. Richard Dawkins has summarized the arguments from the side of the stringent scientists with his usual humour and brilliant ire in a review of Sokal’s subsequent book.

Alan Sokal and your humble blogger outside the Royal Academy of Sciences
Alan Sokal and your humble blogger outside the Royal Academy of Sciences

In his speech yesterday at the Royal Academy of Sciences, Sokal set out in more general terms to discuss the importance of the scientific world view.

In essence, his main argument was that the scientific method is simply an effort to find out facts with rational methods, and furthermore, that most of us are completely able to do so in most aspects of our lives. Yet we often keep double standards and cease to question some aspects of our world view. For example, religious people are perfectly able to examine the factual basis of any religion besides their own – i.e. when were the sacred texts written, by whom, on what basis, and why should we believe them. But when it comes to their own religion they revert to the circular logic that the doctrine of the faith is true because the doctrine says it is.

In his talk, Sokal pointed out four main enemies of scientific reasoning:

  1. Potsmodernist theorists and extreme social constructivists. Sokal noted with pleasure that this group appears to have retreated somewhat over the past ten years.
  2. Advocates of pseudoscience. Here, Sokal went to some length to explain the impossibility of homeopathy, mainly by showing that it is entirely inconsistent with our current knowledge of chemistry.
  3. Advocates of religion.
  4. Lobbyists and spin doctors. And here, Sokal went into a rather long critique of the Iraq war and the loose factual premises on which the war was founded.

After the talk, I and a few others brought up a discussion on whether we should really be so hostile to useful placebos, even when they have absolutely no scientific merit (e.g. homeopathy and acupuncture). After all, these methods are very useful for patients with certain conditions such as chronic pain, where real medicine often has little to offer.

He responded that there is a need for an ethical debate on what sort of deception you can subject a patient to, and that the complementary therapists have to face up to that discussion. An excellent argument.

All in all, an enjoyable evening! My favourite quote was: “I am a scientist, not a politician. I have the luxury of saying what I think is true:”

In the audience, I spotted dr. Martin Rundkvist of the Aardvarchaeology blog. He has also written a post about the event.

Anatomy of the cell’s brain

May 22, 2009

For some time, I have been wanting to write a post on the ”hardware” of information processing in the cell. AK’s Rambling Thoughts has however beat me to it, in a series of four blog posts describing certain core principles. If I try to sum up the most important points, here they are:

  • Enzymatic reactions can function, in principle, as analog computer circuits.
  • The sheer number of interlinked reactions, both enzymatic and involving the regulation of protein transcription, allow us to view the cell as a computer with a huge processing power.
  • Many of the analog circuits are wired with positive and negative feed-back mechanisms that enable them to give a digital, all-or-none response. This entails a loss of processing power, which is in AK’s opinion offset by advantages of speed.
  • The computing is “modularised” in the cell, meaning that some reactions occur only in specialised compartments (a synaptic bouton, for example), and communication within the cell can take the form of chemical gradients occurring as a consequence of reactions taking place only in one location.

AK gives many specific and detailed examples of the mechanisms that are involved in each of these processes. But to me, the real power of the discussion lies in the presuppositions that are not very explicitly stated, but very strongly supported by AK’s examples.

The cell deals in processing information
It is easy enough to see that cells process matter. They take up glucose and other nutrients and transform them into energy and structural components. It is not intuitive for many to think of these processes as manipulation of information, but here’s how I see it:

If the cell is going to be successful at all, it needs very fine-tuned regulation of its diverse activities. Any regulation that takes place in response to external factors can be thought of as an internal representation in the cell of its exterior. A map, if you wish, in many dimensions – oxygen tension, concentrations of nutrients, activities of hormones, and so on. This map will then be the input into the cell’s “decision machinery”, which will output some sort of behaviour.

Historically, the decision system has often been conceptualised as a set of enzymes acting linearly and without a lot of interconnections. With more sophisticated models derived from computer theory, it is far more likely that we will be able to capture some of the complex goings-on and generate accurate predictions of how these systems will behave.

Important principles emerge even from only a very general knowledge of the signalling networks
We do not have to know exactly which enzymes do what in order to make some pretty powerful inferences about the signalling network. Based only on a few known classes of interaction, like positive and negative feedback, it’s possible to envision properties of the whole system. Prime among these is the strong nonlinearity that must be expected when there are so many parameters.

In a way I envy physicists. If I poke my teacup, they will be able to predict exactly where it will move to, and when, and in what position it will stop. But if I poke a member of one of my cell cultures (gently), or Zelda, my mother’s Chinese Crested, there is no telling what will happen.

Zelda. Yes, she is cute.

Zelda. Yes, she is cute.

Suddenly the system might go into one of these digital, all-or-none responses. I do not believe they are motivated by speed, by the way, because I do not see why an analog response could not be as fast. Sometimes they are probably motivated simply by the necessity to decide some things one way or another. In particular, this concerns “cell fate decisions”, when the cell decides whether to replicate, or to commit apoptosis. There can be no half-measures with some things.

The cell is not a unit
Some things appear to us at first to be one and indivisible. For example, it came as a small shock to me when I learned that my brain sleeps in regions – it’s not at all necessary for the whole brain to sleep at once. I have also discovered an interesting subdivision when I am daydreaming. Rather often, I start constructing arguments or writing a speech in my head. No visual imagery attached. That’s left hemisphere activity. And then I find myself having hummed a tune with no lyrics, almost without noticing, perhaps for several minutes. That’s the right hemisphere entertaining itself when I am not watching.

The “I” of the cell can be similarly elusive. Some cells are several decimetres long, making it impossible for diffusion of small molecules to carry information from one part of the cell to another. Besides the specialised long-distance information transfer systems (such as axonal transport mediated by the cytoskeleton), such a cell is a set of functionally semi-independent decision-making centres. It’s a bit like an 18th-century colonial empire with faraway patches of land, only intermittently connected by slow sailing vessels.

There are times when I feel a pang of jealousy over discoveries already made, that other people have lived to experience. But then I remember that the pace of discovery has only increased and keeps increasing, and then I feel the same sense of wonder as one might before the sky on a starry night, when I think of what we will know about these systems in one or two decades.