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.
But computers can be designed and programmed to solve problems stochastically, in which case they can arrive at solutions without the designer/programmer being able to explain how.
The information for constructing the solution comes from input data rather than from the programmer. This is, in a simple way, equivalent to being able to know that something is true without being able to prove it.
Analog computers are somewhat out of fashion. Too quirky and in need of constant watching. Organic processes are taken to be stochastic, but that would be us. Would stochastic computers be taken as machines if they get to the level of complexity of life itself, or is it even possible that they could be made so complex?
I can't believe I am doing this but I can't resist. Your post cries out for it.
I saw a cross at a Church last Sunday and got an epiphany. I plan on writing a detailed explanation of where it came from and it's impact on me but is is as follows:
We live in not four, but five dimensions. The first three, height, width and depth, are shaped by the last two. The fourth is time, in which the first three exist.
The fifth dimension: Consciousness.
The explanation is going to take more than a few pages, so I'll leave it at that right now.
They don't have to be analog, although I believe they would have to emulate analog processes. I'm told this is no sweat, although I believe it has a lot of hardware cost.
I saw a TV show about walking robots. It's quite difficult to get a robot to walk.
One guy had a successfully walking four legged robot using six transistors for the computer. An analog computer.
That's my suspicion too, RobRoy! I'm truly looking forward to reading your essay in due course! Thanks so much for writing.
A mathematician of repute suggested to Einstein that his theory would be better with five dimensions. One temporal, four spatial. Then Goedel showed that time is an illusion. So, are we back to four?
You think you did. Some of your customers might dispute that and if any of them have a grasp of Goedel's reasoning there could be some neuronal overheating.
Everybody stay calm. No need to panic. There is an unspoken agreement to continue to ignore the illusion, and to ignore Goedel. Even if he is right.
How world a spiritualst world allow you to know that your senses are working? How do you distinguish the validity of voices telling to kill a few people (Andrea Yeats) or many people (Joan of Arc)?
Propel, propel thy craft, down a liquid solution.
Ecstatically, ecstatically, ecstatically, ecstatically.
Existence is but an illusion.
Then do rocks have conciousness?
Gurdjieff said so, or intelligence. He may have been speaking allegorically, or he may have understood intelligence in a more subtle way.
His comment would appear to be self-evident.
I do know people with the conciousness of a rock.
Yes, StJacques. But it appears that you are assuming that DNA is the sole source of biological information. The obvious reason that this is not the case is DNA is exactly the same whether the organism it "specifies" is living or dead.
No matter how much the proponents of Intelligent Design may argue to the contrary, the basis of its argument is that because science has not yet developed a satisfactory answer that explains the origins of biological complexity, no such explanation can be developed from an examination of the uniform and naturally-occurring processes of nature and we therefore must postulate the intervention of an outside designer to produce that satisfactory explanation.
You seem to argue that the IDers suggest that, because "science has not yet developed a satisfactory answer that explains the origins of biological complexity," therefore they postulate a deus ex machina to explain it. Perhaps you are right to suspect that they believe "no such explanation can be developed from an examination of the uniform and naturally-occurring processes of nature," if by nature you effectively mean the evolution of matter as described by the physico-chemical laws. But I have not encountered anyone of the ID perspective who says that matter, the physico-chemical processes, and/or the physical laws are illusions. What they do suggest is that these taken altogether do not provide a complete, exhaustive explanation for what we observe in living systems.
It seems the naturally-occurring processes of nature themselves including matter may be specified from outside the 4D block of "ordinary space-time." Consider what we mean by "naturally-occurring." If some things are "natural," that implies there are "unnatural" things. What is the standard that allows us to make distinctions between the two in the first place? Is the criterion a material object, or is it a deeper principle, and one which is not going about on all fours in 4D space-time, so to speak?
The basic issue between the metaphysical naturalist and the IDer is that the former wants to explain everything in terms of matter/material causation. You object to smuggling in a so-called "designer," for (apparently) you fear it might be God. But then you turn around and make matter the "god" that rules all of universal nature. For the metaphysical naturalist, matter alone must explain everything we observe in nature, including its designed quality. And as Richard Lewontin has stated, this [materialist] position is [quote] "absolute"; i.e., non-negotiable in principle.
Yet it seems possible that the seemingly designed qualities/properties of the world could simply be the result or outcome of an underlying universal geometry playing out in physical reality, for instance. Are we supposed to NOT investigate any possibility that does not pass muster with dogmatic materialism first?
NOPE. I strongly doubt it.
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