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.
PatrickHenry’s types of “knowledge” and valuation of certainties:
1. Theological knowledge, direct revelation: I have Spiritual understanding directly from God concerning this issue, it didn't come from me.
2. Theological knowledge, indirect revelation: I believe in a revelation experienced by another, i.e. Scripture, etc.
3. Theological knowledge, Imaginings: I have personally surmised my own understanding of this spiritual issue.
The separate theology list still needs work. Originally I had only two items (1 = direct revelation, and 2 = faith in someone else's revelation). In 1,022, when we were both working on one list, your #7 was added, and the wording was changed to "spiritual understanding" in 1,037.
In 1,045 I revised the list, using "your" item, which I had been thinking of as knowledge obtained by direct revelation, and adding as a second item having faith in another's revelation. Afterwards you asked why I was separating theological knowledge from the rest, and we decided to keep our own lists. If this list is mine, I'd have only two theological items as follows:
a. Revelation: Spiritual understanding divinely communicated.The casual observer might ask why I don't combine "faith" with number 5 in the non-theological part of the list (Acceptance of another's opinion: I provisionally accept the opinion of X ...) The reason is -- at least to me -- the nature of the track record that inspires the acceptance. In accepting the consensus of, say, physicists on the structure of the atom, there is an objectively verifiable body of evidence that could be reviewed. In the area of faith (in purely theological matters), by definition there is no such track record.
b. Faith: Belief in a revelation experienced by another.
There's probably a fuzzy middle area, like where a clergyman gives advice about matters of this world, but in such cases I'd say his judgment is open to review like anyone else's. Similarly there are situations where a scientist pontificates about spiritual matters. When he does so, his track record in the lab is of no use to him in inspiring confidence, and because he's out of his area of expertise, he's likely to make a fool of himself (as is a clergyman when giving his untrained opinions about some complicated scientific issue).
Below is your compilation followed by mine. I’ve gathered some ideas from your posts and made a few changes to mine as well! Please let me know if the order of certainty is correct for you.
I welcome any contributions for other lists!
PatrickHenry’s types of “knowledge” and valuation of certainties:
1. Revelation: Spiritual understanding divinely communicated.
2. Faith: Belief in a revelation experienced by another.
7. Internal emotional state: I feel I'm happy, or I have empathy, compassion or sympathy for you.Some clarification is probably in order here. I'm entirely certain that I have a feeling, so there is no doubt at all regarding knowledge of the feeling's existence. But as for what it is that the feeling may be telling me -- that is, the quality of the "knowledge" involved -- there's not much to recommend this as a great source of information. Example: I very often feel that I'm going to win the lottery. Because I'm so often being misled by my feelings, I've listed them dead last on my certainty index.
1. Internal emotional state: I feel I'm happy, or I have empathy, compassion or sympathy for you. This is pretty nearly the only thing I am certain of. It's certain even if I am deranged or on drugs, or both. In this category I would place my knowledge of morality, which for AG seems to be expressed as revealed knowledge.
2. Sensory perception of something external to me: I see my dog is lying at my feet. I am aware that this has limitations, but what choices do I have? I learn the limitations and live with them.
3. Personal memory: I recall I had breakfast this morning. Same limitations apply, except that they are more frequent and serious.
4. Logical conclusion: I can prove the Pythagorean theorem is valid and true. The trueness may be unassailable, but the conclusions of axiomatic reasoning are only as true as the axioms, which may be arbitrary. Outside of pure logic and pure mathematics, axiomatic reasoning drops quickly in my estimation of usefulness. People who argue politics and religion from a "rational" perspective are low on my list of useful sources.
5. Prediction from scientific theory: I calculate there will be a partial solar eclipse this week. I am not aware of any scientific theory that I understand which has failed in a major way. Some theories, of course, make sharper predictions than others. Eclipses are pretty certain.
6. Conclusion from evidence: I conclude from the verifiable evidence that ... Oddly enough, "facts" are less certain in my view than theories.
7. Acceptance of another's opinion: I provisionally accept the opinion of X (an individual or group) as knowledge because (a) I haven't worked it out for myself; and (b) I have what I regard as good reason for confidence in X.
This whole subject of "knowledge" is probably worth a vanity thread of its own. If more attention were paid to it, perhaps a lot of confusion in many areas could at least be understood better. Many disagreements are probably the result of different "knowledge priorities" rather than pure stubbornness, as often seems the case. Alas, all this work is somewhat lost here at the end of a thread with an unrelated article.
... nothing physical which sense experience sets before our eyes, or which necessary demonstrations prove to us, ought to be called in question (much less condemned) upon the testimony of biblical passages which may have some different meaning beneath their words.His position didn't prevail at the time. Since then the Church has quite literally modified it's certainty index, as can be inferred from this Papal document:
I had the opportunity, with regard to Galileo, to draw attention to the need of a rigorous hermeneutic for the correct interpretation of the inspired word. It is necessary to determine the proper sense of Scripture, while avoiding any unwarranted interpretations that make it say what it does not intend to say. In order to delineate the field of their own study, the exegete and the theologian must keep informed about the results achieved by the natural sciences.I'm rather confident that you accept the solar system. Nevertheless, to routinely rank the interpretations of others regarding revelation ahead of what we actually observe can generate conflicts of this nature. Or so it seems to me. Anyway, that's why I put theological issues in a separate ranking.
This is very, very helpful in understanding your posts!!!
If y'all would like, I can prepare an article for Freeper investigation on this very subject. But I'll likely be working again this afternoon - so it would have to be this evening at the earliest. If you'd rather do it, then please go right ahead.
Your last post indicates that I too need to make a clarification. I've given a very high priority of 2 to belief in revelations experienced by others. My entry should be clarified as follows:
I think this is the kind of thread that you'd be much better at posting than I could be. I'm content to wait until you have the time for it.
Hey, don't forget to ping me when you post the thing!
I'd like to be pinged to the new thread when you post it. the topic is fascinating. I probably won't contribute much (don't want to embarrass myself in front of the credible thinkers here), but I'll avidly read.
What kinds of "Knowledge" exist, and how "certain" are the various types?
I will ping you as soon as it is posted!
I understand your unspoken oblivion to my posts, but I think the point that should be stressed again: since all knowledge is finite, all that we deem certain is hampered by what is uncertain. That is not to suggest that we must all be sophistic skeptics. It is to understand that there is more to human life than certainty. Freedom of will, human agency, and the interaction of love, is not, as a one-time-poster Jolly Rogers had it, a pure function of reason.
So far, my initial ping list will be: PatrickHenry; atlaw; js1138; betty boop; cornelis; marron; LogicWings; r9etb; Ronzo; RightWhale; OhioAttorney; ckilmer; xzins; Hank Kerchief
These are correspondents who have recently posted on or near the subject of the investigation (as best I can recall off the top of my head).
I also added Hank Kerchief who has a philosophy ping list, but I don't know if he'll be interested in this subject. I added xzins because he also has a "list" albeit perhaps informal of correspondents interested in the theological ramifications of such things.
Hank and xzins, to get an idea what the fuss is all about you might want to read forward from post 1085.
The science ping list for which you are now famous surely includes people who are exhausted from years of contention and may find some relief in seeing perhaps why it has been this way.
Who? Me? I embarrass myself every day when I put my thoughts out there for others to critique. How else can I learn?
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