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.
Yes, I am an agent of Satan, but my duties are largely ceremonial.
I see what you're getting at, but I think the illustration leaves open the possibility that each of the specific subjectively-experienced shades could be identically repeated.
Indeed, there's a sense in which each shade has to be 'repeated' even to be experienced at all: an instantaneous shade of color at a dimensionless point is no color at all, so the experience has to be 'spread out' over both space and time in order to happen in the first place. In that case, I can mentally subdivide either the space or the time and get two (or more) identical color-experiences.
Now I really have to go. Thanks to all of you for an interesting chat, and I expect I'll be around again on Monday or thereabouts.
I normally dont do this,but I'm going to play devil's advocate here.
I think Pat's arguement was that "yes, we can hear it" but before it's percieved, is it sound? The mechanism that triggers "sound" in our brain is activated on the outside. We percieve "sound" only when we can record it.
Stop me if I got you wrong Pat.
This is a specific arguement I don't claim to have full knowledge of either, but I do like to play it out as much as I can, reardless of who I'm speaing with/for.
LOL
speaing=speaking
LOL!
Great observation, A-G!!!
If color exists independently of the eye and brain, why will some people say that two color chips match exactly, and other people say they don't?
And to play out what I just stated about liking to argue either side:
If the reactive element existed until now, that would prove, still, that "sound" (as a vibration- as we percieve it) did in fact function in the same manner before us as it does now, and will likely continue to do so.
Moving from one sore point to another, is there a Platonic role for "whale"?
No link.
Color does exist seperately. The problem is that "perception" is still playing it's hand.
A machine would identify them as different colors. But they still, in fact, exhibit color.
IMHO, the "does the tree falling the forest make a sound" argument can be boiled down to a dispute of definitions:
sound
2. A sensation evoked by the oscillation described above in the human ear.
In case of possible confusion, the term sound wave or elastic wave may be used for concept 1 and the term sound sensation for concept 2. Not all sound wave can evoke an auditory sensation, e.g., ultrasound. The medium in which the sound exists is often indicated by an appropriate adjective, e.g., airborne, water borne, structure borne.
bump
Can you concieve of a whale but not give any details defining it's exact species?
Large, aquative mammal with a horizontal tail fin that eat. Can you give me an exact species that that whale is?
It swims, we know this by "aquatic"
It consumes, has a spine, breathes air. We know this because it is an animal, as evident from the fact that it is mammal.
The roll is filled, but I am yet to tell you if it is a Blue Whale or a Sperm Whale, or even a toothed Orca.
Indeed, you may present the same color chip multiple times to a single observer and get mixed responses - when you as the investigator have prior knowledge that it is in fact the same color chip.
Actually, something like this can happen. The best way to demonstrate this is to get out some black and white film and take some pictures with a red filter over the lens. That would simulate blue-blindness (although human blue-blindness is not exactly equivalent).I had a college professor with a blue deficiency. He said he could see blue in sunlight, but in dimmer light, blue objects looked black. Since he could see and understand blue, he could describe the perceived difference.
All objects in the real world have complex spectral distributions. Nothing in real life emits or reflects a single wavelength. There are an infinite number of possible mixtures of spectral colors that can give the subject impression of green (or any specified shade).
"And as to my religious beliefs, I state without reservation that I do believe in God most fervently. I consider my faith to be quite strong in fact. But I reject the notion that the Theory of Evolution undermines that belief in any way. My faith is not threatened by science and never will be."
Then we are of one accord, brother. :)
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