The Future of Biology: Reverse Engineering

Creation-Evolution Headlines ^ | 3/14/05 | Staff

[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.
    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.

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.
    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.

[betty boop]

Sounds like something that I would have said, considering a literal translation of Grandpierre...

LOL Junior! I remember it well!!! :^)

Well, it's true that Grandpierre has been a "performer" in the past. But not in the sense that you and r9etb have suggested (i.e., "French porn star")....

At least, not as far as I know. :^)

[xzins]

it probably wouldn't hurt anything plainly to point out the polemical or propagandist aspects of the work you're posting.

Yes. I would agree with that. Hardly any perspective is without its own spin, rationalizations, extended explanation, propaganda...

It would be nice to point them out. Sometimes if you're a part of the group, you don't even recognize it as propaganda. And, if you're outside the group, it takes a while to get to know them well enough to recognize how exactly they're spinning things.

Amway is a case study. :>)

[Tribune7]

Darwinistas, your revolution has failed.

I liked it. :-)

[AndrewC]

I would like to see some research that clearly demonstrates non-random variation.

Your wish is my command.

A Biochemical Mechanism for Nonrandom Mutations and Evolution

A multitude of random mechanisms result in hypermutation under conditions of environmental stress and clearly contribute to the variability essential to evolution. However, since most mutations are deleterious, random mechanisms that increase mutation rates also result in genomewide DNA damage. Among microorganisms, from phage to fungi, the overall mutation rate per genome is remarkably constant (within 2.5-fold), presumably reflecting an obligatory, delicate balance between the need for variation and the need to avoid general genetic damage (24, 45, 57). Thus, mutator strains are not selected in nature but remain at 1 to 2% of the population (35, 52); under certain adverse conditions, they flourish for short periods but are then selected against, apparently because of widespread deleterious effects intrinsic to genomewide hypermutation. In contrast, hypermutation that is the consequence of starvation-induced derepression and transcriptional activation represents a very rapid and specific response to each adverse circumstance. The extent to which normal background mutations in nature are due to derepression mechanisms is difficult to estimate, but the location of most C-to-T transitions on the nontranscribed strand suggest that it may be significant. Regardless, a mechanism that limits an increase in mutation rates to genes that must mutate in order to overcome prevailing conditions of stress would surely be beneficial and therefore selected during evolution.

[Alamo-Girl]

Thank you so much for your great posts!

Believe it or not, I lurk more than I post. And that's probably because there is a certain type of post around here that is so totally "out of control" that one does not dare to put one's foot in. And those are precisely the most hilarious, laugh-out-loud, cry-till-it-hurts threads at FR, bar none.

I know just what you mean! LOLOL!

[StJacques]

I cannot believe this is happening. This has got to be one of the funniest events in the history of the Crevo threads at FreeRepublic because the Intelligent Design supporters have posted an analysis of a scholarly article, which they apparently hold in high repute, by a group of authors who will argue if asked, that the inherent design of a biological system is a product of evolution, a position which, if correct, will completely negate the hypothesis of Intelligent Design!

Somebody pinch me! I must be dreaming!

Please examine, if you will, the Position Description for a Post-Doctoral Fellowship at Kyushu University in the Department of Biochemical Sciences and Engineering, the search for which is managed by Hiroyuki Kurata, one of the authors of the Proceedings of the National Academy of Sciences article which is referenced by the original article posted at the beginning of this thread (underline emphasis is mine):

". . . 1-2. Comparative genome analysis for elucidating the evolution of a biological system.

In order to elucidate the design principle of a biological system, research is undertaken not only to determine molecular networks of existing living systems, but also to learn how they evolve, since evolution is a key trigger for the emergence of living systems. In this project, we are very interested in how the initiation factors in the translation system evolved from an ancestral stage. We develop the information technologies necessary for comparative genome analysis of initiation factors in bacteria, archaea, and eukaryotes, and elucidate how they evolved using the developed information technology. . . ."

As you can see, this position's interests are very closely related to the subject matter of the article mentioned at the beginning of this thread. There is no way Kurata would be chairing a search committee to fill the position that is described as quoted above if he did not support the parameters outlined therein. And those parameters are that evolution is the key trigger for the emergence of biological systems and one must understand how those systems evolve in order to elucidate their design principles, not vice-versa or otherwise.

There is an additional reference you view for the work of another one of the authors, J.C. Doyle, who, along with Marie E. Csete, published Reverse Engineering of Biological Complexity, a work referenced in the article at the beginning of this thread, which was reviewed in Science Magazine in the fall of 2002. That review was introduced with an abstract of the book's contents that follows (underline emphasis mine):

"Advanced technologies and biology have extremely different physical implementations, but they are far more alike in systems-level organization than is widely appreciated. Convergent evolution in both domains produces modular architectures that are composed of elaborate hierarchies of protocols and layers of feedback regulation, are driven by demand for robustness to uncertain environments, and use often imprecise components. This complexity may be largely hidden in idealized laboratory settings and in normal operation, becoming conspicuous only when con-tributing to rare cascading failures. These puzzling and paradoxical features are neither accidental nor artificial, but derive from a deep and necessary interplay between complexity and robustness, modularity, feed-back, and fragility. This review describes insights from engineering theoryand practice that can shed some light on biological complexity."

The point made clear in the abstract is essentially the same one made clear in the description of the Post-Doctoral Fellowship position described earlier. According to Doyle and Csete "convergent evolution" in the domains of "advanced technologies and biology" produces "complexity" or "modular architectures." So in Biology, evolution leads to design.

Therefore, it is the clear opinion of the authors of the PNAS article that evolution produces both "design" and "complexity," two terms that are almost interchangeable.

Now; at the beginning of this thread we read the following quote put up by Michael_Michaelangelo:

". . . But they [the leaders in the I.D. movement] also teach that good science requires following the evidence wherever it leads."

Well, in the opinion of the experts you have brought to our attention Michael, the evidence leads to the conclusion that design and complexity were the result of evolution. That is indeed good science and I thank you for your post.

[MacDorcha]

"The point made clear in the abstract is essentially the same one made clear in the description of the Post-Doctoral Fellowship position described earlier. According to Doyle and Csete "convergent evolution" in the domains of "advanced technologies and biology" produces "complexity" or "modular architectures." So in Biology, evolution leads to design."


I can sum up most of what you have to say in this statement above.

Now, for the operation of removing your foot from your mouth...

If, biology (and evolution) lead to design, as you put it... Where did the necessity of this evolution come from?

From your analogy, technology is changed to fit the new requirements of newer products, and this is technological "evolution" and where we design new things.

However, the NEED for these things was created in the first place. Humans specifically made both the machine and the need to change (and thereby design) the machine. The initial design was not an evolution, but a simple creation that got changed by will of the initial creators (humans)

The subsequent "evolutions" that "prove creation" are really orderly updates from the need that arose from their creation in the first place.

In the simplest terms I can offer: If creation is the result of evolution, why do we have evolution? A need is obvious if creation is present, regardless of the side in which creation arises.

Or more simply (now that I think about it): Quit trying to use double-speak, you'll put your eye out.

[bondserv]

The commentary is most often hilariously ironic. In our age of Political Correctness, we don't need more of the same.

Some of the best mud slinging comments are by Balrog. He ain't running for a position in the State Department, and neither should we. Nothing is more boring than passion free arguments. It's like no ones eternity is on the line or something.

If something someone says is stupid, it should be called stupid. They can take Dodgeball out of school, but they can't take straight talk out of a free exchange of ideas. I never call someone a Troll, because often it is the one who barks loudest that was hit by the rock that was thrown, and that might shake them out of their groupthink that has been conditioned into them by the world system.

Carry on posting the whole flaming mess. It does us all some good. But then I am a guy who was smacked around by my Dad at appropriate times. I can always tell when someone wasn't.

[Ichneumon]

In the simplest terms I can offer: If creation is the result of evolution, why do we have evolution?

We have evolution because evolution is simply the result of the interplay between reproduction, variation, and selection. When those three things are present, you can't *not* have evolution occur unless you take steps to prevent it. It's just the way things work out when imperfect reproduction interacts with selective processes.

In technical terms, evolution is the name we give to the directed stochastic walk of variably reproducing entities.

[Ichneumon]

Why the non-believers persist in ignorance is beyond understanding.

I don't know, but there are always folks who, through ignorance, remain non-believers of what has been repeatedly demonstrated, both in practice and through theoretical analysis -- the fact that evolutionary processes can produce vast amounts of complexity and results that are so elegant that they look as if they were the work of a clever engineer, even though they're not.

Even so, many people remain ignorant of this fact and continue to naively believe that only intelligent planning can produce complexity and intricate processes.

[MacDorcha]

Read the post I was responding to to get the full background on that statement.

I was playing with his words as he played with his own silly thoughts. He was backwards (though due to the superficial understanding he exhibited in his post, I guess it couldn't be helped) And I was pointing it out to him.

My bigger question to the likes of you would be something I have been toying with recently (and even earlier in this thread I believe)

Until we can discern random events from inherent design, how can we suppose either creation or evolution? If it LOOKS like it could be created, but we can think of a way it COULD happen (however slim the probability) by chance, how can we support one over the other? Or in fact, either?

[MacDorcha]

"Even so, many people remain ignorant of this fact and continue to naively believe that only intelligent planning can produce complexity and intricate processes"

Can only chance occurance and natural selection produce complexity and intricate processes?

It's a two-way street. Why should one be supported over the other if both are POSSIBLE? (We can ignore probability for the sake of this particular discussion due to the lack of a statistic provided for creationism)

[StJacques]

". . . If, biology (and evolution) lead to design, as you put it... Where did the necessity of this evolution come from? . . ."

Well I do believe the best evidence yet produced indicates that evolution leads to design, but I was not the one who put it that way first, as you reference in my post. That specific hypothesis comes from the authors of the article published in the Proceedings of the National Academy of Sciences which was discussed in the opening post of this thread.

I find it interesting that these guys are heroes on the cutting edge of true science as they were introduced as supposedly supporting I.D. and, after it has been made clear that they do not, their viewpoints suddenly become heresy. All of the points you raise with me in your post should also be addressed to those same scientists whose work was cited at the beginning of this thread. That is not "double-speak," as you put it. It is simply a presentation of the arguments two of those scientists, Doyle and Kurata, are advancing in their own work.

Or do you think I made those quotes up on my own?

[StJacques]

As a followup to my previous post, here are the relevant snippets of the two quotes in question.

From the description of the Post-Doctoral Fellowship position for which Hiroyuki Kurata chairs the search committee:

"In order to elucidate the design principle of a biological system, research is undertaken not only to determine molecular networks of existing living systems, but also to learn how they evolve, since evolution is a key trigger for the emergence of living systems . . ."

And from the abstract of the review of Doyle and Csete's Reverse Engineering of Biological Complexity:

"Advanced technologies and biology have extremely different physical implementations, but they are far more alike in systems-level organization than is widely appreciated. Convergent evolution in both domains produces modular architectures that are composed of elaborate hierarchies of protocols and layers of feedback regulation, are driven by demand for robustness to uncertain environments, and use often imprecise components. This complexity may be largely hidden . . ."

It is from those two quotes that you can see that the very same scientists whose work was lauded at the beginning of this thread make the argument that evolution leads to design. I didn't make that up on my own.

[MacDorcha]

So do you agree or disagree with the author?

Whether or not we support the article is secondary to your support of this person's assertions that you brought forth.

If you support him, and laugh at us for supporting this article, then you miss the purpose of the article.

If you do not support him, but we do, what do you care about his professions in his field? It may be laughable to you for us to support him, but why use his crude and wrong analogies to denounce us?

Either we tout this article and you laugh that we agree with one of your mentors on something or;

We tout this article and you cite the man's contrary (yet bad) work to convince us that he's wrong.

[MacDorcha]

To put it yet another way:

If this author is supposed to have convictions one way or the other in science, why do you care what he says? A true scientist avoids bias.

Even then, however, isn't it marvelous that people with differing ideas can come to different conclussions than your own on the meanings of these findings? It means the facts were presented without a supposition of what they meant!

But I suppose you may be right. We may have to abandon his works, because he is notably an advocate (politican if you will) in a non-political field: science.

His bias would then betray him as one who could not be a scientist, but a seeker of proof for his own ideals.

[AndrewC]

Not exactly a mathematical proof, but some interesting work nonetheless.

From your link...

So Dusan Misevic, a biologist at Michigan State, has spent the past couple of years introducing sex into Avida.

This just demonstrates the problems with argument from computer program.

[js1138]

Regardless, a mechanism that limits an increase in mutation rates to genes that must mutate in order to overcome prevailing conditions of stress would surely be beneficial and therefore selected during evolution.

That's interesting, but the mechanism sounds like something that evolved via Darwinian selection. At least that's how I read the text.

[Fester Chugabrew]

I find it interesting that these guys are heroes on the cutting edge of true science as they were introduced as supposedly supporting I.D.

Actually their non-support I.D. has been freely acknowledged. "This is a powerful affirmation of intelligent design theory from scientists outside the I.D. camp."

Evolutionary thought subscribes to the notion that designed entities can come into being apart from a designer. As such it is better qualified as a philosophy than as science. The references to evolution in the article above are indeed incidental. I would not be surprised if they were thrown in so that the author(s) could keep a chair at the university.

[OhioAttorney]

Thanks for the pings.

The point of the posted commentary, I take it, is that biologists use concepts from control theory to understand how biological structures work, and the commentator thinks this fact is 'a powerful affirmation of intelligent design theory from scientists outside the I.D. camp'.

My (brief) comments, below, are made on that understanding. If I've gotten it wrong, I'm sure someone will tell me. (Of course, even if I've gotten it right, there's a nontrivial chance someone will tell me I've gotten it wrong anyway. But I feel able to deal with the signal-to-noise problem.)

There is nothing remotely newsworthy about the fact that biologists use mathematical concepts from control theory, cybernetics, and such in order to understand how biological systems and structures work. Such models have to do with function, not origin, and they imply nothing either way about where the system in question 'came from'.

If we need to become design engineers to understand biology, then attributing the origin of the systems to chance, undirected processes is foolish.

Which, of course, is why Darwinists don't do so. The existence of apparent design is where Darwinist theory starts, and its question is precisely: this stuff obviously didn't happen at random, so how did it happen?

Our commentator's conclusion is a remarkable one: a scientific theory is being declared wrong on the grounds that the phenomenon it seeks to explain exists in the first place.

Talk about a straw man chasing a red herring up a blind alley without a paddle after a horse of another color has been stolen in midstream.

Darwinistas, your revolution has failed.

I don't think so. Indeed, the fact that biologists are now using mathematics to understand biological structures is clear evidence that the Darwinist revolution has succeeded even beyond the wildest dreams of Darwin himself.