Repost: The ancestor of the hairball

October 8, 2010 § 2 Comments

While we were playing “cite the oldest paper“, Pam Silver suggested this paper (Srb, AM and Horowitz, NH, 1944. The ornithine cycle in Neurospora and its genetic control.  J. Biol. Chem 154 129-139), as a distant antecedent of the field we now call systems biology. Published only three years after Beadle and Tatum used Neurospora to demonstrate the connection between genes and enzymes, and at a time when the nature of genes was uncertain — it was suspected that they consisted of nucleoprotein complexes, or at least contained such complexes as essential elements — this paper describes the existence of a network of genes whose products perform a complex set of biochemical reactions, producing arginine.

Now one of the less fashionable model organisms, but once a supremely important one, Neurospora first came to scientific notice as a major pest in bakeries, growing as large salmon-colored clouds on the bread loaves. The menace was later reduced somewhat by the routine use of mold inhibitors, but by that time scientists were hooked.  In the ’20s it was discovered that what makes Neurospora so good at thriving in bakeries is that the spores survive high heat (indeed, require heat to germinate).  It also turns out to be the first organism that colonizes areas that have been semi-sterilized by volcanic eruptions — “producing great masses of brilliant conidia of bizarre appearance”.  [Google Images has failed me on this one, if anyone can find some “brilliant conidia” please send me a picture or a link]. Early scientists who collected Neurospora species in the tropics ran in to some difficulty: it had a tendency to grow straight through the cotton wool they were using to close the tops of their tubes. But once they got it into a cool, dry climate, it became more manageable.

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… and the case for physics in biology

August 6, 2010 § 1 Comment

John Higgins pointed me to this superb discussion of the challenges for physicists posed by biological systems (Phillips, R., & Quake, S. (2006). The Biological Frontier of Physics Physics Today 59 38-43).  In this paper Rob Phillips and Stephen Quake offer — as a public service — three examples of big fascinating problems in biology that physicists could get their teeth into.

The first is the operation of molecular machines: “[t]hey are incredibly sophisticated, and they, not their manmade counterparts, represent the pinnacle of nanotechnology.”  The authors choose ATP synthase as an example of a machine to marvel at.  Run in the forwards direction — transforming the energy in a proton gradient into chemical energy — ATP synthase delivers approximately your body weight in ATP molecules per day. Run backwards, ATP synthase is a rotary motor, delivering 120 degrees of rotation for every ATP hydrolyzed;  the absolute thermodynamic efficiency of this reaction has been estimated as up to 90%.   That’s going to be hard to beat.

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The case against interdisciplinarity

August 5, 2010 § 2 Comments

One of the minor joys of writing this blog is that people send me interesting opinion or ideas pieces — pieces that they found inspirational or important — that I haven’t previously read.  If I don’t have time to write about them at that moment, I print them out, put them in a file, and promise myself I’ll get back to them later.  From now on, I plan to note who sent them before filing them, because I can’t currently recall who sent me this particular suggestion.  (Whoever you are*, if you’re reading this, thank you!)  It’s an opinion piece from Sean Eddy (Eddy SR (2005) “Antedisciplinary” Science. PLoS Comput Biol 1(1): e6. doi:10.1371/journal.pcbi.0010006), reacting to a statement in the NIH “Roadmap” that the complexity of biomedical problems now requires “new organizational models for team science” — teams of people drawn from different disciplines, that is.

I remember reading that section of the Roadmap when it came out and wincing.  Having been to one of the meetings NIH organized to get advice about how to encourage interdisciplinary science, I had seen some of the discussion leading up to this publication.  It all reminded me of a comment in a short story by one of my favorite humorists: “The cook was a great believer in the influence of environment, and nourished an obstinate conviction that if you brought rabbit and curry-powder together in one dish a rabbit curry would be the result.”

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Guest post – What Protoplasm can tell us about systems biology

July 12, 2010 § Leave a comment

Jagesh Shah writes: In a recent perspective piece, Rick Welch and James Clegg re-visit the timeline of modern theories of cellular function.  Their central thesis is that the theory of the protoplasm (e.g. as proposed by Edward Curtis), which was displaced nearly one hundred years ago by the cell theory (e.g. as laid out by Schwann), is the antecedent to modern-day holistic cellular systems biology approaches.  The piece highlights a remarkable struggle between a view of the basis of life that focuses on cellular forms and constituents, versus a focus on the dynamical behaviour of cells in their environment.  Modern systems biology is undergoing a similar struggle.

The conception of the protoplasm was an attempt to describe the living dynamical nature of the cellular constituents.  It derived from observations of cellular behavior that were shared between the smallest unicellular organisms and the cells of much larger multi-cellular creatures.  Competing with this view was that of the cell.  This view again aimed to describe the commonality between living organisms, that they were all composed of cells (a la van Leeuwenhoek), but it emphasized structure and composition over cellular behavior.  In both views we see the tension between the long-standing epistemological distinction between form and function.

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The ancestor of the hairball

July 5, 2010 § 1 Comment

The first entry in the “cite the oldest paper” competition is in, a suggestion from Pam Silver.   Ever the student’s friend, Pam also wanted to offer a clue: there is at least one paper written in French, published in 1959, that has a very clear relationship with systems biology.  Can you find it?  [Remember, it is the difference between your age and the age of the publication that matters, not the absolute age of the paper.  Anyone under 38 would spring into the lead with a paper published in 1959.]

Pam’s entry is older (Srb, AM and Horowitz, NH, 1944. The ornithine cycle in Neurospora and its genetic control.  J. Biol. Chem 154 129-139), but also perhaps more controversial. Published only three years after Beadle and Tatum used Neurospora to demonstrate the connection between genes and enzymes, and at a time when the nature of genes was uncertain — it was suspected that they consisted of nucleoprotein complexes, or at least contained such complexes as essential elements — this paper describes the existence of a network of genes whose products perform a complex set of biochemical reactions, producing arginine.

Now one of the less fashionable model organisms, but once a supremely important one, Neurospora first came to scientific notice as a major pest in bakeries, growing as large salmon-colored clouds on the bread loaves. The menace was later reduced somewhat by the routine use of mold inhibitors, but by that time scientists were hooked.  In the ’20s it was discovered that what makes Neurospora so good at thriving in bakeries is that the spores survive high heat (indeed, require heat to germinate).  It also turns out to be the first organism that colonizes areas that have been semi-sterilized by volcanic eruptions — “producing great masses of brilliant conidia of bizarre appearance”.  [Google Images has failed me on this one, if anyone can find some “brilliant conidia” please send me a picture or a link]. Early scientists who collected Neurospora species in the tropics ran in to some difficulty: it had a tendency to grow straight through the cotton wool they were using to close the tops of their tubes. But once they got it into a cool, dry climate, it became more manageable.

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Cite the oldest paper: the competition

June 17, 2010 § 2 Comments

So we have four articles so far that prefigure the development of the field we now call systems biology, ranging in date from 1948 to 1972.  Let’s play this game a little differently.  Instead of focusing on the date when the article was published, let us consider the delta between the age of the person submitting it and the age of the publication.  Walter’s, John’s and Allon’s submissions score somewhere between -6 and -12, while the Bonner piece (sent to us by Elliot Meyerowitz) comes in at +9.  Let’s have a little competition to see who can find the oldest paper, relative to their birth date, that describes an approach to science that looks like systems biology*.  Alert students will realize that they have a considerable advantage in this game.

I’ll offer a small prize (TBD) for the top three submissions.  To ensure that the older generation isn’t put off entirely, I’ll also think of a prize for the chronologically oldest submission. I guess I’d better say that articles written by someone whose work has already been submitted don’t count; I know there’s at least one more article out there by Frenster.

I’ll award the prizes at the end of the summer.  See you all in the library stacks…

*According to whom?  According to me, of course.

Systems biology in wartime

June 15, 2010 § 1 Comment

Walter Fontana has taken a great leap forward (backward?) in the “cite the oldest paper” stakes by offering up this 1948 opinion piece by Warren Weaver.  (Weaver, W. 1948. Science and Complexity.  American Scientist 36, 536.)  One amusing thing about this piece, at least for me, is its lessons in the ways that writing has changed over the last 60 years.  The first sentence, “Science has led to a multitude of results that affect men’s lives” would instantly be edited today to avoid a charge of sexism; and while the last sentence of the first paragraph, “Still other aspects of science are thoroughly awesome” has a modern ring, what he probably meant was awe-provoking, not AW-sum.

Anyway — back to the science.  Weaver starts by describing the physical science of the 17th-19th centuries as being focused on (largely) two-variable problems that he calls “problems of simplicity”.  The life sciences, however, could not make progress in the same way: “The significant problems of living organisms are seldom those in which one can rigidly maintain constant all but two variables. Living things are more likely to present situations in which a half-dozen, or even several dozen quantities are all varying simultaneously, and in subtly interconnected ways. Often they present situations in which the essentially important quantities are either non-quantitative, or have at any rate eluded identification or measurement up to the moment. Thus biological and medical problems often involve the consideration of a most complexly organized whole.”

Yes indeed.  Just look at this heroic recent study on autism disorders, which identifies over 200 rare gene copy number variants (CNVs) that are over-represented in autism disorders; the authors estimate that their findings probably explain about 3% of the autism risk in the population.

Three percent.  Better than nothing, but still. Lots of job security there for disease geneticists. (Or maybe not) « Read the rest of this entry »

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