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.
Whatever scientists call "matter" isn't what Aristotle called "matter." Aristotle's "matter" can't be further reduced.
Agreed. My point is precisely that someone who is not a 'materialist' with respect to one definition may nevertheless be one with respect to another.
The perception of color is completely beside the point. The point of a universal is that it exists, even if it cannot be perceived at all.
Would you care to shift universals with RWP and try pi or threeness?
"Our perception of color is entirely subjective."
You are recognizing this... but missing the point that "perception" is not the focus!
Did green exist before we did? Well, lets ask our good friend Photosynthesis.
Did spheres exist before man? Lets ask the planets. Just because you can't percieve a rock in the desert, doesn't mean it isn't there.
What you are trying to argue is that "We do not know what way the coin in the closed box is facing"
What we are arguing is that indeed "the coin is facing some way"
Was getting there myself, but thank you:)
The point I was first trying to drive home was that "perception" does not quanitfy existance. I have a bed behind me right now. I can't see it while I'm typing, but it's there.
And you wouldn't count the correlation between that location, and a specific range of wavelengths of light, to be objective? Sure you would -- and if you can map that location, then it would be duck soup to show that it really does respond to certain wavelengths of light.
As for the perception experiments you mentioned ... well, your description of the phenomenon shows that you've already identified how the aliasing works.
I'm pinging my favorite Freeper philosophers to the discussion as well in case y'all would care to get into the details of that discipline.
Not arguing evolution here.
Arguing perceptions.
I don't dispute that some mechanism made life on this planet more complex.
Doesn't this whole "green" problem boil down to the classic "if a tree falls in the forest and no one's around to hear it" question? In the case of the lonely tree, it certainly falls, and the air vibrates, but "sound" is a reaction in a human brain. No listener, no "sound." Or, to tie this in to the "green" question: no viewer, no green. However, I'm probably missing a bunch of subtleties, as I often do in such discussions.
If color is a behaviour of the brain, then why are people who are color blind still able to see the sky? If it is indeed simply the reaction of our brains to moving electrons, why don't coloblind people have a blank space where things with those colors are?
Our receptors are divided into spatial and light sensitive receptors. If color is objective, then shapes are as well. A blunt object would cut one person, but bounce of another. Balls only roll because we percieve them to roll.
Now does that make sense?
No, I say God created life. But of course, if God is left out of the 'equation', then one is left with life coming from lifelessness all by itself.
- Kettle Belly Baldwin in "Gulf" from Assignment in Eternity by Robert Heinlein
Not a useful test. People can identify cows, but there is no Platonic cow.
And so a fictional character represents your ideas.
Loud and clear.
Excellent post, Aquinasfan!
No, but there is an idea of "cow"
The roll of "cow" existed before you woke up this morning. You don't have to percieve it for it to be.
In general . . .
I hope you'll continue to contribute to this discussion of universals!
. . . I'll participate when I can but I probably won't be back online until at least Monday (my Internet connection on my other machine has recently become, um, suboptimal).
Here are the bare bones, for the benefit of anyone who could use a little background.
According to the standard philosophical definition, a universal is any characteristic, property, quality, or what have you, or a complex of such properties, that can occur identically in more than one context. (You may encounter the definition 'repeatable predicable', meaning a property that can be repeatedly predicated of more than one object.) If there is an identical 'man-ness' among men, then 'man-ness' is a universal; otherwise not. (I think not.) If a specific shade of green can occur identically in two different conscious experiences, it's a universal; otherwise not. (I think it is.) If the number pi can occur identically in more than one context, it's a universal; otherwise not. (I think it is.)
The problem of universals, in a nutshell, is whether there are any real universals at all, and if not, why we 'think' as though there are.
The two logical possibilites are realism (the view that there is at least one real universal) and nominalism (the view that there aren't any real universals at all).
'Nominalism' gets its name from medieval disputes over the problem, in which one view (most famously propounded by William of Ockham) was that 'universal concepts' were really just names for ranges of nonidentical objects. Today most philosophers probably wouldn't use it quite that restrictively, so we'd regard conceptualism (the view that apparent universals are really just concepts, not really-out-there objects) as a form of nominalism, not as an alternative to it.
Please note that a 'realist' is not committed to the view that anything we think is a universal really is one. For example, there may be lots of proposed universals -- I'd list 'man-ness' here -- that turn out on inspection to represent not a single identical property but a (possibly ill-defined) range of distinct properties or complexes thereof. Denying that these are universals doesn't make you a 'nominalist'; as long as you acknowledge at least one real universal, you're a 'realist'.
There are several varieties of 'realism' that I'm not going to try to sort out here. There are 'realists' who (like Aristotle) tend to think that universals don't exist 'on their own' but only 'in' particulars; these realists might also deny that universals exist in any 'eternal' or 'timeless' way. The more Platonistic ones will claim that at least some (not necessarily all) universals are self-existent and timeless. But those are subsidiary issues.
Perhaps I can give a concrete example.
It is possible to construct a set of color patches using different pigments, so that people with "normal" vision will say that two patches are identical, but people with color deficiencies will see them as different. Color blind people have been used to detect military camouflage, because they match colors differently.
Aside from monochromatic light, which can be described objectively as a wavelength, color is constructed in the eye and brain.
We can also identify herrings, red or otherwise... ;-)
Unlike the cow, you've provided an objective definition of "Platonic Green," as a specific wavelength of light. You could create and measure that wavelength without ever having to "perceive" the color of it.
There was no physical organism to hear that sound yet there you have it - proof that sound exists even if noone hears it.
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