Posted on 03/15/2005 2:41:19 PM PST by Michael_Michaelangelo
The Future of Biology: Reverse Engineering 03/14/2005 Just as an engineer can model the feedback controls required in an autopilot system for an aircraft, the biologist can construct models of cellular networks to try to understand how they work. “The hallmark of a good feedback control design is a resulting closed loop system that is stable and robust to modeling errors and parameter variation in the plant”, [i.e., the system], “and achieves a desired output value quickly without unduly large actuation signals at the plant input,” explain Claire J. Tomlin and Jeffrey D. Axelrod of Stanford in a Commentary in PNAS.1 (Emphasis added in all quotes.) But are the analytical principles of reverse engineering relevant to biological systems? Yes, they continue: “Some insightful recent papers advocate a similar modular decomposition of biological systems according to the well defined functional parts used in engineering and, specifically, engineering control theory.”
One example they focus on is the bacterial heat shock response recently modeled by El-Samad et al.2 (see 01/26/2005 entry). These commentators seem quite amazed at the technology of this biological system: In a recent issue of PNAS, El-Samad et al. showed that the mechanism used in Escherichia coli to combat heat shock is just what a well trained control engineer would design, given the signals and the functions available.
This is no simple trick. “The challenge to the cell is that the task is gargantuan,” they exclaim. Thousands of protein parts – up to a quarter of the cell’s protein inventory – must be generated rapidly in times of heat stress. But like an army with nothing to do, a large heat-shock response force is too expensive to maintain all the time. Instead, the rescuers are drafted into action when needed by an elaborate system of sensors, feedback and feed-forward loops, and protein networks.
Living cells defend themselves from a vast array of environmental insults. One such environmental stress is exposure to temperatures significantly above the range in which an organism normally lives. Heat unfolds proteins by introducing thermal energy that is sufficient to overcome the noncovalent molecular interactions that maintain their tertiary structures. Evidently, this threat has been ubiquitous throughout the evolution [sic] of most life forms. Organisms respond with a highly conserved response that involves the induced expression of heat shock proteins. These proteins include molecular chaperones that ordinarily help to fold newly synthesized proteins and in this context help to refold denatured proteins. They also include proteases [enzymes that disassemble damaged proteins] and, in eukaryotes, a proteolytic multiprotein complex called the proteasome, which serve to degrade denatured proteins that are otherwise harmful or even lethal to the cell. Sufficient production of chaperones and proteases can rescue the cell from death by repairing or ridding the cell of damaged proteins.
The interesting thing about this Commentary, however, is not just the bacterial system, amazing as it is. It’s the way the scientists approached the system to understand it. “Viewing the heat shock response as a control engineer would,” they continue, El-Samad et al. treated it like a robust system and reverse-engineered it into a mathematical model, then ran simulations to see if it reacted like the biological system. They found that two feedback loops were finely tuned to each other to provide robustness against single-parameter fluctuations. By altering the parameters in their model, they could detect influences on the response time and the number of proteins generated. This approach gave them a handle on what was going on in the cell. The analysis in El-Samad et al. is important not just because it captures the behavior of the system, but because it decomposes the mechanism into intuitively comprehensible parts. If the heat shock mechanism can be described and understood in terms of engineering control principles, it will surely be informative to apply these principles to a broad array of cellular regulatory mechanisms and thereby reveal the control architecture under which they operate.
With the flood of data hitting molecular biologists in the post-genomic era, they explain, this reverse-engineering approach is much more promising than identifying the function of each protein part, because: ...the physiologically relevant functions of the majority of proteins encoded in most genomes are either poorly understood or not understood at all. One can imagine that, by combining these data with measurements of response profiles, it may be possible to deduce the presence of modular control features, such as feedforward or feedback paths, and the kind of control function that the system uses. It may even be possible to examine the response characteristics of a given system, for example, a rapid and sustained output, as seen here, or an oscillation, and to draw inferences about the conditions under which a mechanism is built to function. This, in turn, could help in deducing what other signals are participating in the system behavior.
The commentators clearly see this example as a positive step forward toward the ultimate goal, “to predict, from the response characteristics, the overall function of the biological network.” They hope other biologists will follow the lead of El-Samad et al. Such reverse engineering may be “the most effective means” of modeling unknown cellular systems, they end: “Certainly, these kinds of analyses promise to raise the bar for understanding biological processes.”
1Tomlin and Axelrod, “Understanding biology by reverse engineering the control,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0500276102, published online before print March 14, 2005.
2El-Samad, Kurata, Doyle, Gross and Khammash, “Surviving heat shock: Control strategies for robustness and performance,” Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0403510102, published online before print January 24, 2005. Reader, please understand the significance of this commentary. Not only did El-Samad et al. demonstrate that the design approach works, but these commentators praised it as the best way to understand biology (notice their title). That implies all of biology, not just the heat shock response in bacteria, would be better served with the design approach. This is a powerful affirmation of intelligent design theory from scientists outside the I.D. camp.
Sure, they referred to evolution a couple of times, but the statements were incidental and worthless. Reverse engineering needs Darwinism like teenagers need a pack of cigarettes. Evolutionary theory contributes nothing to this approach; it is just a habit, full of poison and hot air. Design theory breaks out of the habit and provides a fresh new beginning. These commentators started their piece with a long paragraph about how engineers design models of aircraft autopilot systems; then they drew clear, unambiguous parallels to biological systems. If we need to become design engineers to understand biology, then attributing the origin of the systems to chance, undirected processes is foolish. Darwinistas, your revolution has failed. Get out of the way, or get with the program. We don’t need your tall tales and unworkable utopian dreams any more. The future of biology belongs to the engineers who appreciate good design when they see it.
It’s amazing to ponder that a cell is programmed to deal with heat shock better than a well-trained civil defense system can deal with a regional heat wave. How does a cell, without eyes and brains, manage to recruit thousands of highly-specialized workers to help their brethren in need? (Did you notice some of the rescuers are called chaperones? Evidently, the same nurses who bring newborn proteins into the world also know how to treat heat stroke.) And to think this is just one of many such systems working simultaneously in the cell to respond to a host of contingencies is truly staggering.
Notice also how the commentators described the heat shock response system as “just what a well trained control engineer would design.” Wonder Who that could be? Tinkerbell? Not with her method of designing (see 03/11/2005 commentary). No matter; leaders in the I.D. movement emphasize that it is not necessary to identify the Designer to detect design. But they also teach that good science requires following the evidence wherever it leads.
Read the follow up. I posted it once I realized there would be confusion.
I don't want to side-track the discussion over this, but your post is a good one and deserves a reponse. My interpretation of what you've just described is that the vibrations existed when no one was around. Just like the case of the lonely tree falling in the forest. That's not "sound." (I think this is a meaningful distinction, and not just a freepish quibble.) Hearing is an independent event, and it's the hearing that gives us "sound." So -- stubbornly, as befits my grouchy nature -- I repeat: no listener, no sound; no viewer, no green.
So now that we have reached agreement that green means a band in the spectrum, can you say what its upper and lower bounds are? Or is it a single frequency? And what are we to make of physical objects that neither emit nor reflect light in this spectral band, but are nevertheless perceived as green?
539 and 541nm would be called "shades" if 540nm was to be "true" or "platonic" green.
There is a true "hunter green."
In regards to shifting completely other wavelengths into the green wavelength: If it walks like a duck and quacks like a duck...
Though I will go and bite on this-
If one can alter other wavelengths into being percieved as another, though the wavelength is not NOT itself, it is different. This would mean that -perception- of colors is indeed a thing of the brain.
This could also suggest that as the univers is expanding, the older radiation is becoming a different type the slower it goes. But it does not stop being radiation (unless of course... it stops entirely) and if the Universe were to be contracting, we would see forms of radiation "revert" to higher-energy lengths.
It does seem to me that people are starting to talk past each other. I don't know whether I'll decrease or increase the confusion by adding my two shekels, but here goes.
Where color is concerned, the candidate for 'universalhood' is a specific shade of subjectively experienced color. I, right now, am experiencing a specific shade at a specific location in my visual field. I don't care what wavelengths or frequencies or intensities gave rise to that experience; I'm talking about a quality that, strictly speaking, can't occur in the absence of subjective, conscious experience.
If I could experience that same shade at two different times (or at two different locations in my present visual field), or if two different people could experience the same shade (even if it's not possible to verify that they do so), then that shade is a 'universal'. Otherwise it's not. It doesn't matter whether it's possible to give an objective definition of it. (And js1138, in #323 I posted a brief reply along these lines to your example.)
Do those colors still 'exist' when they're not being experienced? In a sense, they exist as causal potentialities (in whatever sense causal potentialities exist), but I suspect a discussion of this question will turn into word-chopping very quickly.
The earlier 'sound' example introduces another confusing turn. Here, too, there's some confusion between the physical events (pressure waves, basically) that give rise to subjective sound-experiences when they whap into our eardrums, and the subjective experiences themselves. The pure tone 'middle C' is a feature of conscious experience and therefore exists only 'as heard'. If it's an in-principle-repeatable experience, then the tone is a universal; otherwise not. At any rate, this subjective experience is different from the pressure waves themselves; those may also be called 'sound' but the fact that they can occur unexperienced doesn't mean that the subjective experience of tone and pitch can occur unexperienced.
Of course the physical phenomena themselves presumably include universals as well. But that's another matter.
Have a good weekend, everyone.
Love the book. Read the series?
My favorites (or at least most readily recountable) were when we were introduced to a hyper-intellegent shade of blue.
That and the missles that turned into a whale and a flower pot... "not again"
No. Non-deterministic natural processes are common.
I think this is a meaningful distinction, and not just a freepish quibble.
So do I. See my post #368, which I'd have pinged you on if I'd seen this comment first.
It's not a very good example of a universal.
Gotcha. I tend to think of the "billiard ball materialists" myself. 8-)
You sure got a lot to think about in the little time you come and go! Lol, well put. I would have to agree (even on my original, un-discussed standpoint) with your assertions.
Safe trip!
I am very hard of hearing and oftentimes see lips moving but do not hear anything. If I were arrested for failure to stop when a peace officer verbally demanded me to do so - if the jury was full of PatrickHenrys - would it be a viable argument that the officer never told me to stop because I didn't hear him?
"Green" in and of itself is a wavelength. It has always existed.
The perception of "green" is a thing of the mind.
I hope thats what you were getting at as well, because that's my undiluted and intended statement.
Look at the problem. Goedel demonstrated that there is no time, that it is an illusion, an idea. For all the praise we give to Kantianism, we don't follow Kant very well.
Goedel and Einstein were both Kantian Idealists in good standing.
To return to PatrickHenry's sound being in the hearing - the point of my posting the technical definition is that there is no hearing where there is not prior existence of sound (wave function).
Likewise there is no perception of green without the prior existence of that wave function, no pi without prior circles, etc.
A "universal" exists independent of (and prior to) any observer.
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