Skip to comments.The Future of Biology: Reverse Engineering
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 cells 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. Its 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 dont 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.
Its 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.
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.
It is comments like this that display the true intelligence behind the design of cell division, respiration, and even photosynthesis. Why the non-believers persist in ignorance is beyond understanding.
Wow, I'm a control system engineer and my last name is Esch...
"God saw all that he had made, and it was very good." Gen 1:31a
Get your asbestos underwear on!
I have seen such comments launch a flame-fest in the past. :)
It takes a lot of faith to be an evolutionist. (my fuel to the fire)
I have to repeat Craig Venter's comment on this term. There is no such thing as the post-genomic era. The post-genomic era is when one is dead.
It is simply the genomic era.
Amen. The religious Darwinists will come out of the woodwork with their tinfoil hats on any second now...
"Note for the analytically challenged... you can't reverse engineer something that was not engineered to begin with. "
I'm taking part of that as my tagline :) Thanks :p
At a gross level the idea of a designer is inherently plausible -- we as humans can understand how a designer might have come up with the things we can observe. At finer levels one can also see how randomness could play a role in the process. We can also understand ways in which randomness and design could both play roles in what we see. The "reverse engineering" aspects of this article are addressing that basic point.
Why the non-believers persist in ignorance is beyond understanding.
That's a pretty sticky statement, though. There are plenty of processes that really are explainable as random and/or non-directed events.
One can hypothesize that the "problem of life" belongs within that group, and that's what the theory of evolution basically does. The question is whether it should be so included.
The underlying issue is a philosophical one: is it scientifically plausible to a priori assume that life is wholly explainable in strictly naturalistic terms? Put another way, is it scientifically plausible to simply rule out the possibility of "intervention" from some external source? This is the current "scientific standard" for the problem of life.
It appears that some folks have an almost ideological devotion to the "current standard," in the sense that their opposition to the idea of "intervention" seems to have roots that are not so much scientific, as an unwillingness to confront a different possibility. For some, I'd go so far as to say they're emotionally opposed to suggestions that God might actually play a role in something.
At any rate, it seems that there are a number of folks who will not admit even the inherent plausibility of a design approach. The interesting thing there is, those who deny the inherent plausibility of design, often argue against the idea by asserting that their design choices would have been much different -- which essentially validates the claim that "design" is inherently plausible.
That is not to say that those who hold to the current scientific standard are entirely wrong to ignore the idea that intervention might have occurred: some of those who argue against evolution do so very poorly indeed, which lends a bad odor to those whose objections are more respectable.
Nor am I going to claim that, because design is inherently plausible, it must be the correct explanation -- that is not a logically sound conclusion. In order to arrive at proof of design, one must find some method by which to discriminate between design and random circumstance.
You gotta be careful, though, to distinguish between the words "reverse engineer," which were chosen by the author; and the actual phenomena that are being investigated. It may be that the phenomena were in fact the result of a design effort, or it may not. The words used to describe their work have no bearing on what they're actually doing.
"There are plenty of processes that really are explainable as random and/or non-directed events."
Only disagreement I have with your post is right here, even then it may seem a small (yet could be vital) piece.
I must correct that statement by editing in that "There are plenty of processes that could be explainable as random and/or non-directed events, or simply we have not observed the director scientifically yet"
You address this later in your post (by stating In order to arrive at proof of design, one must find some method by which to discriminate between design and random circumstance.), so I'm sure you don't disagree entirely, but I just felt like adding the qualifier.
If we can't discern random events from design, how can we claim that there are indeed inherently random or designed events?
Looks like another opportunity to plug Dr. Shapiro.
As I see it, a 21st Century view of evolution has to include the following features:
Major alterations in the content and distribution of repetitive DNA elements results in a reformatting of the genome to function in novel ways --without major alterations of protein coding sequences. These reformattings would be particularly important in adaptive radiations within taxonomic groups that use the same basic materials to make a wide variety of morphologically distinct species (e.g. birds and mammals).
Large-scale genome-wide reorganizations occur rapidly (potentially within a single generation) following activation of natural genetic engineering systems in response to a major evolutionary challenge. The cellular regulation of natural genetic engineering automatically imposes a punctuated tempo on the process of evolutionary change.
Targeting of natural genetic engineering processes by cellular control networks to particular regions of the genome enhances the probability of generating useful new multi-locus systems. (Exactly how far the computational capacity of cells can influence complex genome rearrangements needs to be investigated. This area also holds promise for powerful new biotechnologies.)
Natural selection following genome reorganization eliminates the misfits whose new genetic structures are non-functional. In this sense, natural selection plays an essentially negative role, as postulated by many early thinkers about evolution (e.g. 53). Once organisms with functional new genomes appear, however, natural selection may play a positive role in fine-tuning novel genetic systems by the kind of micro-evolutionary processes currently studied in the laboratory.
Is half an hour since the last post without a darwinian in here trying to butt heads generally a sign of concession from them?
Or are they all in church?
Darwinism is a recent appendage to science that adorns itself with the name. Scientific progress takes place in spite of Darwinism, not because of it.
"Darwinism is a recent appendage to science that adorns itself with the name. Scientific progress takes place in spite of Darwinism, not because of it."
In other words... the a$$ thinks it's the brains of the operation....
Indeed, sometimes the butt bone really is connected to the head bone.
Thanks for the ping!
So I guess the control systems observed in cells arose by chance, just as the control systems in plants (i.e., engineered systems).
Good question. I think the answer is that we probably can tell the difference, at least some of the time.
We can easily recognize human-manufactured things, for instance ... even if you find them off in the middle of nowhere, and even if you don't know what they are for. Perhaps we have enough experience with such things that we can recognize the hallmarks of human handiwork.... And perhaps as we become more able to manipulate things at the cellular level and below, we can begin to recognize design (or not) there, too. I think the fundamental requirement would be to gain an understanding of the processes required for a particular design.
Perhaps the same question could be posed to the SETI folks: how would they infer that a signal came from an intelligent source? Seems to me that the problems are have a lot of similarities.
It's amazing the parts of the Bible people don't read.
And the LORD God said, Behold, the man is become as one of us, to know good and evil:...
And the Unitarians miss the US part!
As long as you realize it's just a CLAIM....
Gee. I think we could have done very well without that "editorial." What does it have to do with science?
Thanks for the interesting post, Michael!
Seems more plausible to me than to believe that life came from lifelessness all by itself.
IMHO, the general public is always "turned off" by bickering - thus, the first side to master the diplomacy always has the upper hand.
I can't fault this reasoning.
Good luck with the evidence search.....
Very well stated and appropriate.
BTW Thanks for the ping.
Great insight, r9etb. I certainly agree with you that randomness has a role to play in the Universe. Were that not the case, then the Universe would be utterly determined, frozen; and free will (and individual atomic and biological collective degrees of freedom) would have no meaning and no role.
There is some very interesting work being done in Hungary right now (and elsewhere) on a reconceptualization of the role of thermodynamic entropy in living systems. As I understand it, in physical objects (i.e., non-living systems) it is entropy that characterizes the number of possible states the physical object could be in at any particular time. In other words, entropy represents a probability distribution (i.e., a random set) from which all real-world processes are realized or become possible at any given time. Prof. Kaitalin Martinas and Dr. Attila Grandpierre have suggested that living systems require very high rates of entropy continuously. In the case of living organisms, Grandpierre introduces an entropic measure of Gibbs free energy and points out that it may contribute to the generation of biologically possible states. In short, he argues the relatively high value of entropy in living systems enhances the ability of living matter to represent information.
And of course, information is not a "random" thing in itself; but according to Grandpierre's concept, informative transactions in living systems require randomness -- an astronomically large set of possibilities -- in order for "successful communication" that "reduces uncertainty in the receiver moving from a before-state to an after-state," in Shannon information terms.
With a name like that, he oughta be a French porn star... ;-)
This is the false dichotomy that the ID movement is trying to transcend. Evolutionary theory may correspond with factual evidence or not. ID theory may correspond with factual evidence or not. All IDers are asking is for a judgment regarding which theory best explains the available data.
Paley's watchmaker was never more than an allegory. The string theory is also allegorical. We call these things theory in the sense of being a best guess, not because they contain a god.
Sorry you were offended by his comments, BB. Next time I go to post something from that site, I'll be sure to not include the Editor's commentary if it contains potentially flammable material. (truth be told - I find his commentary refreshing, informative, and funny)
So it caused itself? Or did it arise by a mechanism inferior to itself, thus contradicting the principle of causality, that the effect cannot be superior to, or exceed, the cause?
Well, that's the rub though. In many cases, IDers are coming to the table with nothing except demands that they be listened to. By that standard, pretty much anybody should be able to demand a hearing from "science."
Those on the "science" side have a variety of reasons for not wanting to discuss "design" in the first place. The lack of some objective basis on which to discuss ID simply makes it easier for them to dismiss the concept out of hand. (We cannot dismiss, btw, the fact that some on the "science" side are ideological, rather than scientific, in their rejection of the idea.)
The second step in gaining "respectability" would be for the ID contingent to develop a set of "design markers" -- properties that can (to some extent) distinguish between "designed things" and naturalistic phenomena. The SETI folks face a very similar problem -- it might be helpful to the ID community to see how they're approaching it.
The first step, though, is I think still not well-defined: what is it that ID proponents hope to gain from this debate? I think there are all kinds of competing goals, and some of them have nothing at all to do with science. It seems to me that if the ID proponents are going to challenge science on the matter of life, then those goals first need to be identified and understood.
The first, and most important, question is this: why do IDers feel it necessary to conduct a debate with scientists?
It'd be interesting to see how some of the folks on this thread will answer the question.
Also gets to what "irreducible complexity" means -- a system so complex, it can not arise through mere random dynamics; it's probability of having happened without a designer is so exceedingly low, as to be in all effect zero.
Probability is ignored by hard-line orthodox
marxists evolutionists, yet actual physics and chemisty can't ignore it.
There is a confusion between what is possible and what is probable. There is a confusion between what chemical process we know by pure scientific method is occuring and how it could have happened, that is to say -- many evolutionists seem to think that because we have identified and know to some detail a process, therefore that process and its component parts could have arisen through random dynamics in the absense of a designer. That second confusion seems like a specific instance of the first, but I take it to be unique. Unique because it can be held by people who well know the difference between probable and exceedingly improbable.
Three grand confusions. The third is that if we NOW don't know what a system of thing -- the male nipple -- does, it is a mistake if assuming a designer or just another random circumstance if designer-free.
It was a mind-croak to them.
Because evolutionary theory looks like bad science. I don't see much of a connection between the evolutionary theories that I'm aware of and the factual evidence. Either evolution happened gradually or in great leaps. The lack of fossil evidence contradicts the former, and the lack of a plausible mechanism contradicts the latter.
IDers simply postulate design as an explanation for apparent design. For example, what would be a more "scientific" explanation for the discovery of a spaceship on Jupiter, the existence of extra-terrestrial intelligence or random chance? Similarly, it seems to me that design is a better explanation of "irreducible complexity" and order in nature than random chance, particularly since we know through reason the existence of God. (The notion of "spontaneous order" seems nonsensical to me, as it seems to violate either the principle of sufficient reason or the principle of causality).
In essence, then, you're proposing ID as a strictly scientific approach to the problem, which is certainly a valid thing (though not a universal goal among those who get collected under the "ID" banner).
But if you're going to approach ID from a strictly scientific standpoint, then you've signed yourself up for providing more than just an inability to "see much of a connection." Rather, you've got to show the specifics of where the current theory is incorrect; and after that, you've got to provide the scientific basis for why design is a better explanation.
IDers simply postulate design as an explanation for apparent design.
Well yes -- but on what basis would you objectively demonstrate that? What criteria could separate between "designed" and "naturalistic" phenomena? It would be hard enough to overcome "science's" existing animosity to ID, even with those criteria. Without them, ID doesn't stand a chance.
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