22 Responses to “Systems Biology”

1. hrun Says:
   June 4th, 2008 at 12:17 am

   Why do you call it 'Darwinian reductionism'?

   And do you think reductionism has not been useful in the field of biology?

   And do you think that systems biology would be possible without a healthy dose of reductionism?

Comment by hrun — June 4, 2008 @ 12:17 am

2. johnnyb Says:
   June 4th, 2008 at 12:46 am

   empirical reductionism is in essence methodological; it is simply a mode of analysis, the dissection of a biological entity or system into its constituent parts in order better to understand it. Empirical reductionism makes no assumptions about the fundamental nature, an ultimate understanding, of living things. Fundamentalist reductionism (the reductionism of 19th century classical physics), on the other hand, is in essence metaphysical. It is ipso facto a statement about the nature of the world: living systems (like all else) can be completely understood in terms of the properties of their constituent parts. This is a view that flies in the face of what classically trained biologists tended to take for granted, the notion of emergent properties. Whereas emergence seems to be required to explain numerous biological phenomena, fundamentalist reductionism flatly denies its existence: in all cases the whole is no more than the sum of its parts. Thus, biology of the 20th century was in the strange position of having to contort itself to conform to a world view (fundamentalist reductionism) that 20th century physics was simultaneously in the process of rejecting. In a metaphysical sense, molecular biology was outdated from the onset! What makes this curious period in biology's history doubly bizarre is that a fundamentalist reductionist perspective wasn't even needed in the first place in order to study biology on the molecular level. The simple empirical reductionist outlook would have done just fine, and technology was moving us in that direction anyway! It will be interesting to see what history has to say about the biology of the 20th century.

   …

   I think the 20th century molecular era will come to be seen as a necessary and unavoidable transition stage in the overall course of biology: necessary because only by adopting a heavily reductionist orientation and the technology of classical physics could certain biological problems be brought to fruition and transitional because a biology viewed through the eyes of fundamentalist reductionism is an incomplete biology. Knowing the parts of isolated entities is not enough. A musical metaphor expresses it best: molecular biology could read notes in the score, but it couldn't hear the music.

   The molecular cup is now empty. The time has come to replace the purely reductionist "eyes-down" molecular perspective with a new and genuinely holistic, "eyes-up," view of the living world, one whose primary focus is on evolution, emergence, and biology's innate complexity. (Note that this does not mean that the problems worked on in any new representation of biology will not be addressed by customary molecular methodology; it is just that they will no longer be defined from molecular biology's procrustean reductionist perspective.)

   A New Biology for a New Century

Comment by johnnyb — June 4, 2008 @ 12:46 am

3. Bradford Says:
   June 4th, 2008 at 5:26 am

   hrun:

   Why do you call it 'Darwinian reductionism'?

   And do you think reductionism has not been useful in the field of biology?

   And do you think that systems biology would be possible without a healthy dose of reductionism?

   Neo-Darwinian would have been a more apt description. Darwin was unaware of the individual biochemical elements found in DNA and protein synthesis mechanisms much less aware of the means of inducing genetic changes. Reductionism has been useful and we would not have arrived at our current state of affairs without it. We are forever indebted to those whose work brought us the knowledge we have.

Comment by Bradford — June 4, 2008 @ 5:26 am

4. Bradford Says:
   June 4th, 2008 at 5:26 am

   Thanks for the link johnnyb.

Comment by Bradford — June 4, 2008 @ 5:26 am

5. AdR Says:
   June 4th, 2008 at 6:48 am

   I have just been to a systems biology congress here in Amsterdam. What struck me was that system biology now mainly tries to describe a cellular system as a set of nodes and edges, without paying any notice to function. They plot 100s of protein with 1000s of interactions, but they do not have a clue what the proteins' function are. It's like trying to understand a car's engine by describing the electrical system withoiut functional correlates.

   The other thing is that they are somehow convinced that evolution is irrelevant for the current function and that complex sets of interacting and interdependent protein functions have no evolutionary constraints, but evolved to the 'best' (antropomorph!) solution. A long way to go, I guess. So far, we also have seen no progress in the evo-devo field which has similar problems: a fundamental lack of understanding of evolution.

Comment by AdR — June 4, 2008 @ 6:48 am

6. hrun Says:
   June 4th, 2008 at 7:56 am

   Neo-Darwinian would have been a more apt description. Darwin was unaware of the individual biochemical elements found in DNA and protein synthesis mechanisms much less aware of the means of inducing genetic changes. Reductionism has been useful and we would not have arrived at our current state of affairs without it. We are forever indebted to those whose work brought us the knowledge we have.

   Why would you call it Neo-Darwinian reductionism? Reductionism was, is and will remain a useful paradigm in biology. This has nothing to do with Darwin or Neo-Darwinism.

   And, more specifically, Systems Biology at its heart relies on reductionism. Only because we know a lot about the function of individual parts of a system can we set up models that recapitulate the interactions of such parts to see what their function as a larger complex would be.

Comment by hrun — June 4, 2008 @ 7:56 am

7. Zachriel Says:
   June 4th, 2008 at 7:57 am

   Leroy Hood, Founder of Institute for Systems Biology: Evolution has had four billion years to figure out really clever solutions for new materials, new chemistries, new types of molecular machines, even new approaches to computing. I think by studying living organisms and deducing the mechanisms that underlie these evolutionarily sculpted solutions to complexity, those solutions can be applied to other fields. A classic example is materials science. The spectrum of different materials that organisms have evolved to make is enormous.

Comment by Zachriel — June 4, 2008 @ 7:57 am

8. hrun Says:
   June 4th, 2008 at 8:00 am

   I have just been to a systems biology congress here in Amsterdam. What struck me was that system biology now mainly tries to describe a cellular system as a set of nodes and edges, without paying any notice to function.

   Albert, I just browsed through the publications of the members of the HMS Systems Biology Department. I did not find anybody there who describes a cellular system as a set of nodes and edges without paying any notice to function.

   Could you maybe link to a few papers as examples. Since this is what Systems Biology mainly does, there should be numerous examples.

Comment by hrun — June 4, 2008 @ 8:00 am

9. AdR Says:
   June 4th, 2008 at 11:15 am

   hrun, the meeting was about networks and the figures I've seen were mainly interaction graphs. I was disappointed that the systems were not analyzed in a way we analyze other complex systems such as software. Basically, they tried to analyze the system at the wrong level.

Comment by AdR — June 4, 2008 @ 11:15 am

10. hrun Says:
    June 4th, 2008 at 11:23 am

    hrun, the meeting was about networks and the figures I've seen were mainly interaction graphs. I was disappointed that the systems were not analyzed in a way we analyze other complex systems such as software. Basically, they tried to analyze the system at the wrong level.

    I gathered that you were disappointed.

    I just wanted to point out your gross misrepresentation of systems biology. In fact, as you must be well aware, Systems Biology DOES NOT "mainly [try] to describe a cellular system as a set of nodes and edges, without paying any notice to function."

    And, just as a side note, what do you think do these 'interaction graphs' mean? Could they possibly be functional interactions between two components? If they describe signaling networks, then they would indeed describe more than just mere interaction. They would describe specific functional interactions between components like activation or deactivation.

    And finally, if you think they are trying to analyze the system at the wrong level, then go ahead and either do a better job yourself (you are a biologist after all) or just explain to them the appropriate level to analyze the systems. Biologists (system or not) are always on the lookout for better ways to analyze their data. If you actually have a better way, they'd jump on it in a second.

    EDIT: You know, coming to think of it, you were probably just disappointed that they were not studying the systems using your 'design by contract' framework. If that is the 'better' way of doing it, it shouldn't be hard to convince some systems biologists thereof.

Comment by hrun — June 4, 2008 @ 11:23 am

11. Salvador T. Cordova Says:
    June 4th, 2008 at 2:58 pm

    How do we characterize functionality in terms of selection? Do we assign the degree of functionality to the degree of selective advantage? Do we say something is more functional based on the degree of immediate selective advantage it confers? This makes little sense in general, and especially when we are dealing with deeply redundant systems.

    Indentifying a system implies perceiving the appropriate analogy, and sometimes this means seeing an analogy that might be distributed throughout the organism rather than localized to a cell or organ. For example, we have the immune system, the nervous system, the digestive system, etc. etc. etc….there are numerous subsystems associated with each system. Since we can't measure selective advantage effectively, what point is there is even invoking selection as anything meaningful in the characterization of systems? We're identifying things just fine without a selectionist paradigm (except to say if we break something bad enough, the thing dies)…..

    Furthermore, as Wagner pointed, we can't even measure selective advantage most of the time. Hence functionality is in practice identified by means independent of the selectionist paradigm. It was Wagner who said:

    fitness is hard to define rigorously and even more difficult to measure"¦..

    An examination of fitness and its robustness alone would thus not yield much insight into the opening questions. Instead, it is necessary to analyze, on all levels of organization, the systems that constitute an organism, and that sustain its life. I define such systems loosely as assemblies of parts that carry out well-defined biological function.

    It should be noted that the inclination to liken biology to engineered systems is inspiring a degree of distress among evolutionary biologists:

    His most recent, "Stand up for evolution" (Evolution and Development 7 [July 2005]:273-275), advises biologists to police their own language when describing biological systems. As Raff writes:

    "¦let us not play into the hands of ID propagandists. For instance, be careful about using teleological words to describe biological entities in our teaching and writing. Calling cells "machines that do X," or describing biological structures as "well designed to do Y" will be duly cited in ID propaganda as one more biologist-supporting design.

    Send us your trash

    What does it mean to make analogies? We can say we have computer system, the specific details are abstracted away. It matters less that the memory implementation may be made of transistors versus capacitors (Mircron Technology) versus DNA or proteins, but that we have identified the fundamental analogy or organizational principle that the system abides by.

    In similar fashion, we have numerous things in biology that are appropriately classified as analogous systems. For example, we may have feed-back control systems, error correction systems. These systems trancend the parts that compose them just like an image has some independence from the material substrates and chemistry which compose that image….

    The notion of computer, error correction, feedback control, interfaces, digital-to-analog, coding-decoding, modularity, inter-operability, are engineering concepts readily imported into biology. An nice article exemplifying biology as an engineered information processing system was symbolized by this article: Two Operative Concepts

    We present an analogy between living systems and informatics systems by considering: 1) the cell cytoplasm as a memory device accessible as read/write; 2) the mechanisms of regulation as a programming language defined by a grammar, a molecular algebra; 3) biological processes as volatile programs which are executed without being written; 4) DNA as a database in read only mode. We also present applications to two biological algorithms: the immune response and glycogen metabolism.

Comment by Salvador T. Cordova — June 4, 2008 @ 2:58 pm

12. Bradford Says:
    June 4th, 2008 at 5:22 pm

    Salvador Cordova:

    Furthermore, as Wagner pointed, we can't even measure selective advantage most of the time. Hence functionality is in practice identified by means independent of the selectionist paradigm

    It's revealing how those who would argue that terms like teleology and intelligence are ill defined have no trouble with the definitions of terms used frequently to support their own views. For example, it is far from clear what the selective advantage of the individual parts of some irreducibly complex systems would have been en route to the evolution of a particular IC system. Arriving at a hypothesis as to what the pathway would have been frequently entails the cognitive use of a top down analysis of an IC system even as the methodology employed might not be thought of as stemming from downward causation.

Comment by Bradford — June 4, 2008 @ 5:22 pm

13. Bradford Says:
    June 4th, 2008 at 5:42 pm

    hrun:

    And, more specifically, Systems Biology at its heart relies on reductionism. Only because we know a lot about the function of individual parts of a system can we set up models that recapitulate the interactions of such parts to see what their function as a larger complex would be.

    Or you might first observe function and then discern the component parts that enable it. If you are going to trace a pathway backwards in time consideration of a trail of modified functions as well as an analysis of the individual components forming such functions is useful.

Comment by Bradford — June 4, 2008 @ 5:42 pm

14. Salvador T. Cordova Says:
    June 4th, 2008 at 5:56 pm

    Let me try to hit the point home further about why I think defining function in terms of selective advantage is clumsy. Lets say we are dealing with the functions in a female when she is past child bearing….Are we going to try to characterize her digestive system, her immune system in terms of reproductive advantage, even though at this point it makes little sense?

    Selective advantage is being inappropriately applied to everything. There are domains it may be valid , but Occams razor would suggest that if an explanation is superflous, it is best to discard it.

    If the search for analogies and designed patterns is more effective in elucidating the details of a system, then there is no need to try to fit most of biology into an adapation/selection story….and in the practice of systems identification, invocation of selection is rarely done in any formal way any way, as evidenced by Wagner's comments…

Comment by Salvador T. Cordova — June 4, 2008 @ 5:56 pm

15. hrun Says:
    June 4th, 2008 at 6:46 pm

    Let me try to hit the point home further [...]

    And that's why you can find literally hundreds of thousands of papers in biological research that talk about the workings of specific aspects of biology without talking about 'selective advantage'.

    I just don't understand what the point is you (and Bradford) are trying to make. Take quantum mechanics for example. Not everything in chemistry will be related to quantum mechanics. In fact, quantum mechanics is only rarely considered in chemistry publications. Would you likewise argue that because in many cases quantum mechanics is a rather clumsy tool to do chemistry, it should thus be discarded?

Comment by hrun — June 4, 2008 @ 6:46 pm

16. Salvador T. Cordova Says:
    June 4th, 2008 at 8:31 pm

    I just don't understand what the point is you (and Bradford) are trying to make.

    I can't speak for Bradford, but my point is that the search for analogies is the heart of systems biology. Phylogenetic relationships and selective advantage (which are the main aspects of Darwinism) are excess baggage….

    But consider the implications, if structural relationships and the search for convergences between two biological structures, or the search for convergence between a human design concept (like a turing machine) and a biological system become the norm, then these developments would be highly ID friendly whether your side wishes to acknowledge it or not.

    I pointed out Rudy Raff is not comfortable with importation of teleological language into biology, but teleological language is the most natural and effective way to understand these organisms, namely as collections of machines and systems….selection and phylogeny are excess baggage — and frankly if the creationists are right, it would be inappropriate baggage….but the general lack of utility of Darwinism makes the creation/evolution question somewhat a moot point. The search for design (as in the search for analogies), oddly enough, trancends the creation/evolution issue to some extent…

    Whether one feels the existence of systems in biology implies an intelligence was behind the system is another issue, but it seems that systems biologists will treat these systems as designs and be less concerned whether selection or phylogeny were involved in the origin of these systems. I would argue structural relationships which trancend phylogeny (like the 40 or so architectures of the eye) might be an important consideration some day. Sternberg was very fascinated with structural relationships that defied phylogenetic explanations. These might be fruitful areas of exploration for identification, characterization, and elucidation of systems….

    We know of some basic systems like the digestive system, the respiration system, the immune system…but there will be many many more systems and subsystems to discover and understand….

Comment by Salvador T. Cordova — June 4, 2008 @ 8:31 pm

17. hrun Says:
    June 5th, 2008 at 12:36 am

    I can't speak for Bradford, but my point is that the search for analogies is the heart of systems biology.

    So now 'the search for analogies' is the heart of systems biology. And again, I bet that you would find nary a systems biologist who would agree with your assessment.

    Phylogenetic relationships and selective advantage (which are the main aspects of Darwinism) are excess baggage"¦.

    And again. Certainly no agreement there by systems biologists. Just because 'selective advantage' is not explicitly studied in every systems bio approach does that make it 'excess baggage'.

    I pointed out to you before there are hundreds of thousands of biology papers that don't concern themselves with 'selective advantage'. Why do you think this is particularly relevant for systems bio, but not for the many, many other studies where 'selective advantage' was not an issue?

    But consider the implications, if structural relationships and the search for convergences between two biological structures, or the search for convergence between a human design concept (like a turing machine) and a biological system become the norm, then these developments would be highly ID friendly whether your side wishes to acknowledge it or not.

    And again, I don't think you have a proper understanding of systems biology as a discipline. Systems biology does not specifically look for the convergence between 'a human design concept' and a biological system. Maybe a subset of systems biologists might do so on occasion, but it is not the thrust of systems biology. You might call it ID friendly, yet, if you were to ask the actual systems biologists you might be surprised by their answers.

Comment by hrun — June 5, 2008 @ 12:36 am

18. hrun Says:
    June 5th, 2008 at 12:39 am

    Or you might first observe function and then discern the component parts that enable it.

    Yes, exactly. That's the first step of reductionism. You observe a function and break it down into it's individual parts and see what every individual part does. Then, you slowly start to put those parts back together and see how they work as a whole.

    In previous times, without technology advances, this was generally done just a couple of proteins or genes at a time. Now, using lots of experimental and computational parallelization it can be done with many components at a time.

    Yet, in the end, the approach is at it's heart still reductionist. Observe function, break it down into it's parts, see what these parts do, bring it all back together and see if the function of all these little parts can explain the original observation.

Comment by hrun — June 5, 2008 @ 12:39 am

19. Salvador T. Cordova Says:
    June 5th, 2008 at 11:47 am

    So now 'the search for analogies' is the heart of systems biology. And again, I bet that you would find nary a systems biologist who would agree with your assessment.

    But the construction of models is the search for an analogy. Here is an article that I think is balanced Cover Story

    "BEING A NEW field, a definition is going to evolve and get settled on," says Douglas A. Lauffenburger, professor of biological engineering and a member of the Computational & Systems Biology Initiative at Massachusetts Institute of Technology. "It's going to be defined by what people actually do that's productive and effective."

    and

    All biologists should really think in terms of two subjects," Hood says. "If you're a biologist, you should also think about computer science or applied mathematics or engineering. I think everybody ought to learn biology, plus either a quantitative computational skill or a physical skill. I'm very much attracted to a dual mentorship idea."

    This is a development I'm personally pleased about. Many years ago, engineers and computer scientists were publicly dis-enfranchised from biology by the NCSE types. Look at the complaints about the dissent from Darwin list: "most of them aren't biologists". Well it seems, because of systems biology, these disciplines are essential to understanding biology….

    Schneider advocates borrowing methods from engineers, particularly from electrical and chemical engineering. "The key is the unit-operation approach. You have to define the physiological unit operations," he says. "On a fundamental basis, there's really nothing different between unit operations for resistors, capacitors, and induction coils than for Michaelis-Menten kinetics, membrane transport, and chemical equilibria. They're just equations that apply."

    One challenge of modeling biological systems is that most biological data are "differential display" data, dealing with changes between states. "It's not measuring an absolute level," Schneider says. "This is where we went back into chemical engineering and process control theory and figured out you can do some really nifty linear algebra. Then you don't have to worry about absolute numbers anymore. This linear algebra trick took us out of having to do numerical integration into doing algebra problems."

    An engineered system follows at least 2 major constraints:

    1. physics (lots of reductionism)
    2. requirements or goals for the system (lots of holism)

    Re-verse engineering means identifying the goals and requirements of the system, or the meaning of the system. Re-engineering involves changing the design to different requirements….

    Selection and phyologeny (the bread and butter of Darwinsim) are almost completely irrelevant. Understanding the physics of the system (reductionism) and identification of requirements and goals of the system (holism) are far more important.

    Goal oriented descriptions:

    i.e

    the purpose of this is to sense
    the purpose of this is to provide feed-back-control
    the purpose of this is to regulate
    the purpose of this is to provide a blue print
    the purpose of this is to function as a counter
    the purpose of this is to provide redundancy
    the purpose of this is to provide a general material
    the purpose of this is to provide usable energy
    the puprose of this is to filter
    the purpose of this is to decode
    the purpose of this logic gate is to decide

    Emphasis on the phylogeny and selection (the bread and butter of Darwinism) would be a forced emphasis at best. Emphasis on looking at biology as a designed system is operationally more effective. We are not just modelling physical systems, we are reverse engineering! If we weren't fundamentally attempting to reverse engineer, we probably woudn't be recruiting engineers into the discipline.

    Ironically, whether Darwin did it or God did it, becomes a somewhat irrelevant question with respect to operational effectiveness. At least for now. If Dembski's quest for steganography bears fruit, then that's when the "God did it" factor might be important….

    To perhaps refine Bradford's point, reducing biology to selection and phylogeny (Darwinian reduction) makes little sense. Reducing biology to physics and identifying the holism of the systems is more appropriate. Engineers apply both reductionism (using physics and math) and holism. They don't use much Darwian reduction if any at all…

Comment by Salvador T. Cordova — June 5, 2008 @ 11:47 am

20. hrun Says:
    June 5th, 2008 at 12:40 pm

    Ironically, whether Darwin did it or God did it, becomes a somewhat irrelevant question with respect to operational effectiveness.

    That's what I have been trying to tell you the whole time. For hundreds of thousands of studies published in the field of biology the origin of a particular structure is irrelevant. It does not direct the research, nor is it necessarily relevant for any conclusions drawn. Why do you feel this is so important for systems biology, but not for all the other past and current studies?

    It seems to me that you would like to somehow draw the conclusion that because in systems biology the origin of a system is not necessarily relevant to study its function, that it's finally going to be the discipline that is going to divorce biology from Darwinian evolution. I fear that your hopes will be dashed.

    You can keep on believing that systems biology is stealth ID, yet, evolution is alive and well in the systems biology departments around the country. And it can always lead to beautiful and informative studies when the two intersect. For example here.

Comment by hrun — June 5, 2008 @ 12:40 pm

21. Bradford Says:
    June 5th, 2008 at 3:42 pm

    hrun:

    It seems to me that you would like to somehow draw the conclusion that because in systems biology the origin of a system is not necessarily relevant to study its function, that it's finally going to be the discipline that is going to divorce biology from Darwinian evolution. I fear that your hopes will be dashed.

    I see something else coming into play. When Salvador writes:

    Goal oriented descriptions:

    i.e

    the purpose of this is to sense
    the purpose of this is to provide feed-back-control
    the purpose of this is to regulate
    the purpose of this is to provide a blue print
    the purpose of this is to function as a counter
    the purpose of this is to provide redundancy
    the purpose of this is to provide a general material
    the purpose of this is to provide usable energy
    the puprose of this is to filter
    the purpose of this is to decode
    the purpose of this logic gate is to decide

    It looks to me as if he is looking to establish a theoretical connection between biological constructs and evidence of a telic process. This is a valid approach regardless of the methodology used.

Comment by Bradford — June 5, 2008 @ 3:42 pm

22. hrun Says:
    June 5th, 2008 at 6:12 pm

    It looks to me as if he is looking to establish a theoretical connection between biological constructs and evidence of a telic process. This is a valid approach regardless of the methodology used.

    Yes. It is obvious that he is looking to establish such a connection. However, it is far from obvious that systems biology is doing so. He might believe that it is, yet, systems biologists may not agree with him. Just like they may not agree that systems biology is 'stealth ID'.

    And if systems biology really is 'ID research' then it still remains puzzling to me that the best ID research is actually done by reasonably smart but extremely deluded people.

Comment by hrun — June 5, 2008 @ 6:12 pm

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