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.
A Dunkin Donuts is an arrangement of inanimate matter coordinated and put together by a group of intelligent agents (humans).
A (living being) is an arrangement of inanimate matter coordinated and put together by an intelligent agent (God).
It's remarkable how much that fits into Creationist thinking. We don't know the true reason of the organization so how can one assert that indeed ID or self-organization is the culpret?
If the researchers argue that "convergent evolution" leads to biological complexity, they do present a theoretical model to explain the origins of complexity. And I submit that this approach is fundamentally sound since it interprets whatever evidence is presented within a framework that is scientifically-justifiable since it does not ask that we retreat to mathematical probability, but rather to actually use the observed dynamics of biological systems as a guide when interpreting the evidence of observed phenomena.
Good point. In that case, even if they did have to present a theoretical basis on which all that nifty complexity could have emerged, they have in fact done so to the degree reasonably required by their own work.
For "hard evidence" evolution turns to molecular biology - the mutation of bacteria, viruses, etc. A comparable level of success has not been achieved with the more complex organisms, e.g. the fruit fly.
The authors showed how a naturally occuring temperature regulator differed from that of a designed regulator. The showed that the system they examined regulated temperature, not that it was "intended" to do so. If anything, they showed that the system did not appear to be designed.
I read (and described on FR) the paper some time ago. There is no evidence of design. Just evidence of accretion (and deletion) of parts.
No, they are asserting causation . . .
I agree with this statement entirely, as regards the quote under discussion in StJacques's post. My remark above (that the researchers don't say anything one way or the other about causation) applies to the article posted at the top of this thread, which is not the source of this quote.
So what do we call it when electric power grid engineers use genetic programming (evolutionary algorithms) to converge on the best solutions for power distribution? The key requirement of these programs is that they have to solve very complex problems quickly.
"a perfectly good analogy"
sidenote: no such thing.
What exactly do you expect from research on fruit flies?
"Just evidence of accretion (and deletion) of parts."
Kind of to be funny, but mostly to make you think:
You mean like an eraser?
So what do we call it when electric power grid engineers use genetic programming (evolutionary algorithms) to converge on the best solutions for power distribution? The key requirement of these programs is that they have to solve very complex problems quickly.
I don't mean to be obtuse here but I'm not sure what you're asking.
By making a correlation to advanced technologies and declaring that "convergent evolution" is applicable to both domains - advanced technologies and biology - they named a causation for both, i.e. evolution.
That holds no water at all unless they also establish strong determinism which renders a space shuttle the effect of the cause, evolution.
Storks, babies...
I love verbs!
Yes, verbs me very happy.
A rhetorical question. Some folks think that having engineers copy natural designs is proof that natural designs are engineered. Industrial espionage, so to speak. No talk of paying royalities to the Patent Owner.
But the niftiest thing in nature is the concept of evolution itself, which is increasingly being put to use in hard-nosed computer programs being used to solve real life problems.
By making a correlation to advanced technologies and declaring that "convergent evolution" is applicable to both domains - advanced technologies and biology - they named a causation for both, i.e. evolution.
All right, if you're speaking in the wider context of their research generally rather than just this article about 'reverse engineering', then I agree that they do cite evolution as a cause of complexity. Why do you say this is based solely on a 'correlation'?
The test of a scientific argument -- falsifiability -- depends on observations of phenomena that reside within the 4D block of "ordinary" space-time. However, neither mathematics nor information appears to be the product of the 4D block, although we readily recognize that both are in evidence within the 4D block. Similarly, we can readily observe evidence of design in nature. But design presumably is also "extra" to the 4D block, similarly as mathematics and information. So how can we directly test it? How does science test a universal that does not have its origin in ordinary space-time?
And yet the evidence or by-products of design are there in nature, and can be observed.
Evolutionary theory likewise is not a phenomenal object in the sense that it is not a direct production of nature. It is a conceptualization; that is, it is an immaterial entity that purports to be a universal rule of nature. In this regard, I do not perceive any real difference in its status as compared with design theory: Both are non-phenomenal, immaterial objects that arise in human consciousness -- another non-phenomenal reality that appears to be irreducible to "matter in its motions."
That is, consciousness is something that is "extra" to the 4D block of directly observable phenomena. Because it is intangible, ought we to ignore it? If we must ignore it in order to satisfy the scientific method, then what would be the status of either evolutionary theory or design theory? Falsify their source, and what have you got left?
Good point, I should have said ANY analogy.
A rhetorical question. Some folks think that having engineers copy natural designs is proof that natural designs are engineered. Industrial espionage, so to speak. No talk of paying royalities to the Patent Owner.
But the niftiest thing in nature is the concept of evolution itself, which is increasingly being put to use in hard-nosed computer programs being used to solve real life problems.
Ah, I see your point now. Thanks.
Agreed on all points, and your example makes clear that -- now that we've got a clear concept of how natural selection works at the algorithmic level -- we're actually 'designing' software using natural selection itself as a model.
In the end, they establish two things in biological systems: design and purpose.
They should have left it there. Causation cannot be addressed without the mathematics and physics - and intent is in the domain of philosophy.
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