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.
On a related note (with practical applications), one can ask if there is a "Platonic" e-flat (or any other tone.) Also, is the a "Platonic" major third or tritone?
A fair question. If you read my post about the painter who lost his color vision due to brain injury, you might predict what I am going to say.
First, let us concede that light has the property of wavelength, and that this property is independent of human perception. But radio waves share this spectrum and this property, and we do not identify broadcast stations by color.
There are two kinds of people who do not have the concept of color. One person in 33,000 is born without color receptors in their retinas. And a few people have lost the concept of color due to brain injury.
Considering that we do not give color names to radio waves, can you honestly believe that we would give color names to bands of the visible spectrum if no human had ever been born with retinal receptors that are differentially receptive to the spectrum, or a brain that processes spectral input?
I might make another analogy with sound. We do not give color names to sound frequencies.
AH HA! you might say. We do give names to musical notes, and there are people with perfect pitch.
But musical notes are the height of arbitrary labeling. the oldest musical scales are based on the natural overtones of plucked strings. The original scales have an integer relationship among notes. Seconds, thirds, fifths, etc.
The modern, or tempered scale, is kludge designed to allow transposing songs from one key to another while still matching the pitches of keyboard instruments. the scale is based on the 12th root of 2, and has only an approximate resemblence to natural overtones. People with perfect pitch had trouble accepting this scale when it was invented.
I am unaware of any color concept that isn't tied to physiology.
subjectively green placemarker
See #402
So we seem to be singing the same tune.
Hello StJacques! You stated that Biological Information "reflects" an objective reality. I would put it a bit differently: Biological Information "constitutes" an objective reality.
You seemed to suggest that DNA/RNA sequences are the sole source of Biological Information. But how can this be? You give the impression that if we could just tally up the total number of DNA/RNA communications at any given moment in time (and that number verges on the astronomical), we would have a complete physical description of the organism -- at least at that given instant of time. (You see what a totally unmanageable problem this shapes up to be.) Yet your suggestion seems to overlook the fact that biological organization is based on the complete non-separability of the constituents of living organisms: there is the macroscopic organization of a single, dynamic system which is more than just the sum of its parts (e.g., particles, atoms, molecules, cells, organelles, tissues, organs, organic systems [e.g., digestive, circulatory]).
Organization, by definition, means that the system’s parts are highly correlated. In a living organism, all the constituents are interwoven into a uniquely behaving system. The biological organization is present exactly in the interactions between subsystems. As Lehninger noted, “If biology is chemistry, it must be a kind of ‘superchemistry’, which includes but at the same time transcends classical chemistry. This is because the molecules found in living organisms not only conform to all familiar physical and chemical principles governing the behavior of all molecules but, in addition, interact with each other in accordance with another set of principles...."
That "other set of principles" is what correlates all the system's parts into an integrated whole. Do you think that DNA is responsible for this? I would argue that this set of principles is not governed by DNA. One speculates that DNA itself is "governed" by this principle. Our name for this principle (A-G's and mine, as seen on many recent threads) is not terribly "scientific": It is the life principle, or fecundity principle, or "will to live." It is fundamentally an informative principle.
At which point you usually conclude that we've wandered off into Cloud-Coo-Coo Land yet again, getting all "metaphysical" on you. Well, that's fine. Still, the macroscopic organization of a system composed of zillions of constantly active parts organized into sub-systems within the global system have to have an information source that facilitates globally-coordinated, sensitively-responsive behavior. It has been observed that DNA is simply too "information poor" to be the source of this dynamic information flow all by itself.
Who got zotted?
Seems to be "mkll."
What was that about? I thought this was a civilized thread with actual content.
Perhaps someone sneaking back in after the bans were announced? (I don't know anything about the bannee.)
We do not. We believe that the certainty of explanations posited to explain certain phenomena is weak and is not being defended on scientific grounds but on emotional ones.
In other words laws of nature have not been discovered but invented and we are just objecting.
My faith is not threatened by science
Neither is mine.
And what medium did these 'sounds' propagate through that we would still consider them to be sounds?
Here's something else to consider: purpose. Purposefullnes.
I'll state as a theorem that "no green exists without a purpose".
Space itself, radiating out in every direction and uniformly. We are speaking of the cosmic microwave background radiation, which is a radiation bath that permeates the entire Universe. It was discovered in 1965 by Arno Penzias and Robert Wilson, using a small horn antenna. More recently it has been confirmed by recordings made aboard the COBE satellite. The CMBR is often referred to as the "echo of the Big Bang." It's still echoing.
"So unless you are going to say color, the concept, is equivalent to wavelength, you have no basis for saying it exists outside the perception. If color equals wavelength, then the concept of color is superfluous, except in common speech. It adds nothing but confusion to a technical discussion."
Since both the word 'colour' and the concept of a specific 'colour' are arbitrary sounds we make with our mouths to describe something our brain interprets from input to our nerves, it really has no bearing on whether or not it can be said that colour exists outside of our perception. Light has measurable wavelengths that we can document and reliably duplicate. Since there is no guarantee that any two of us actually sees that wavelength identically but we still agree to call that wavelength green, then it is 'green'. The perception of something need not be the same between observers for us to assign it a name.
There is a large difference between the objective existence of a specific waveform and the label we assign to our perception of it.
Of course I have probably babbled on about something so far from the course of the conversation that it is immaterial but I did say it was worth only .02C.
You're saying essentially what I've been saying, so I'd bump that up to three cents.
Unless of course DNA is algorithmic in nature, using multiple iterations to produce as much information as necessary.
Well DNA is useless by itself. Put pure DNA in a test tube and see what it does.
The presence of DNA in the cells of a corpse cannot reanimate it, bring it back to life. But it's still the same old DNA as it was when the corpse was still living....
Thanks. I'm familiar with the CMBR, but that doesn't address the concept of 'sound'. I may just be being picky, but we have defined sound very specifically such that it has to propagate through a medium capable of vibrating in a physical sense, whether it be air, water, or a chunk of wood. The CMBR is electromagnetic,( and yes I am aware of piezo materials,) and as such would not normally be defined as 'sound'.
I'm not disagreeing that sound exists outside of our perception, I'm just saying that the analogy AG used isn't perfect.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.