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.
No, there's life of humility between the universe of pure theory and the five senses of the infant.
Either you "know" or you "don't know" what Socrates said about those "natural philosophers."
I'm glad you decided to throw in "or its unmistakeable effects," PH. Like you, I do expect that as technological advances permit, science will be able to "see more." Notwithstanding, the possibility occurs to me that certain real things may only be observable indirectly; that is, in their effects. No matter how finely calibrated our observation tools may become, such phenomena may not ever be directly observable in principle because of the fact that, as creatures whose minds seem to be organized in terms of 4D frameworks, we may not be capable of directly "seeing outside" of 4D; and the point is hypothetically such objects may never be capable of isolation within 4D space-time, because they are not the result of causes within 4D space-time.
Meanwhile, we humans develop cosmologies that might provide a frame and guide to further scientific inquiry; and while these are not "strictly scientific" in the methodological sense, it has been noted that in order for science to proceed with its work, it needs more capable basic conceptualizations when the existing concepts seem no longer to offer fresh possibilities for further development. BTW, both scientists and philosophers construct cosmologies.
As Edward R. Harrison writes (in The Science of the Universe, 1995):
"We do not know, and in our wildest dreams cannot imagine the true nature of the Universe ... Cosmology is the study of universes. In the broadest sense it is a joint enterprise by science, philosophy, religion and the arts that seeks to gain understanding of what unifies and is fundamental."
A-G and I both find the conjecture that there are more than 4 dimensions persuasive. But then so did Kaluza, Klein, and their followers. No one I know of thinks that 11D string theory is not science, but rather a new philosophical school.
I gather the string theorists have yet to "observe" any of these extra dimensions yet. But no one I know of accuses them of having pink unicorns under their beds, or that what they are doing is a pitiful subset of your much grander speculation, which "posits" the existence of 69 dimensions.
Dear Patrick, for all I know there may be 69 dimensions. Then again, can we totally rule out the possibility that there may be infinite dimensions? Basically all I'm prepared to "rule out" here is the sufficiency of only 4 dimensions -- 3 of space and 1 of time -- as capable of explaining what we already observe about the nature and evolution of the Universe. FWIW.
Not in my experience.... ;-)
As for your posts, LW, I confess that I see a lot of my old self in them. There is a certain pleasure in raising your own personal mind above everything else in the universe, and calling it "logic." As I said, I recognize myself in this ... and it's somewhat embarrassing to watch. The problem is, you don't know everything -- none of us does -- and so even your "logical" worldview is based primarily on faith that others are correct, even for most of the stuff you'd say "we" know. You're excoriating A-G and betty for their "assertions," but somehow you are unable to see that you're guilty of the same thing.
The fact of the matter is, there are things even in our own experience that are not fully accessible through logic. Indeed, your discussion with Alamo-Girl should stand as proof of that -- she is saying things that you reject as "not logically provable." Of course, you also cannot logically prove they are wrong, and have said as much. As such, regardless of which one of you is ultimately correct (if either of you is), there are certain things that are simply inaccessible to your logic. That's a serious problem for your position -- indeed, fatal, as it contradicts your claim.
Logic also has a very difficult time dealing with things like poetry, music, or painting. There are certain mechanical and/or logical processes associated with these arts, but their real power lies in their evocation of something deep within us -- and the responses they evoke are not fixed even for the individuals who see or hear them. Probably the worst "art criticism" I ever read was some objectivist attempting to deal with a piece of abstract art. I don't recall the piece now, but it was actually quite good -- just not accessible to the objectivist who was lamely attempting to savage it on the grounds of its "irrationality," which I took as a confession that this particular critic simply didn't like abstract art, and was trying to dress up a visceral response in an intellectual tuxedo.
What I specifically had in mind there was the motion of galaxies -- observable motion -- which have apparently insufficient mass to account for such motion. Thus, from such objectively observable data, the hypothesis that "dark matter" may exist to account for the situation.
Like you, I do expect that as technological advances permit, science will be able to "see more." Notwithstanding, the possibility occurs to me that certain real things may only be observable indirectly; that is, in their effects.
That's certainly the case, as with nuclear physics. We don't "see" protons and such. But we observe their effects. I'm considering all of that part of the observable world. It's a slight verbal stretch.
No matter how finely calibrated our observation tools may become, such phenomena may not ever be directly observable in principle because of the fact that, as creatures whose minds seem to be organized in terms of 4D frameworks, we may not be capable of directly "seeing outside" of 4D; and the point is hypothetically such objects may never be capable of isolation within 4D space-time, because they are not the result of causes within 4D space-time.
That's a bit fancy for me. I'm a simple man, and I guess that I'm stuck with what I've got to work with here in our good ol' 4D setup.
Meanwhile, we humans develop cosmologies that might provide a frame and guide to further scientific inquiry; and while these are not "strictly scientific" in the methodological sense, it has been noted that in order for science to proceed with its work, it needs more capable basic conceptualizations when the existing concepts seem no longer to offer fresh possibilities for further development. BTW, both scientists and philosophers construct cosmologies.
I think the usual sequence of events, at least in contemporary science, is that the cosmological model is constructed to fit the evidence. I'm not aware that cosmologies get framed ahead of the evidence. But I don't pretend to know this with certainty.
A-G and I both find the conjecture that there are more than 4 dimensions persuasive. But then so did Kaluza, Klein, and their followers. No one I know of thinks that 11D string theory is not science, but rather a new philosophical school.
If I've got it right, those 11 dimensions are what it takes, mathematically, to unite general relativity with quantum mechanics. So it's an exotic model to achieve the hope of uniting two kinds of physics that otherwise seem not to unite. I guess if I had worked out the math, I'd be so delighted that I'd proudly proclaim my accomplishment as being significant. But from where I sit, the "necessity" of those 11 hypothetical dimensions could just as easily be used to assert that you just can't unite GR with QM. But I don't pretend to know.
I gather the string theorists have yet to "observe" any of these extra dimensions yet. But no one I know of accuses them of having pink unicorns under their beds, or that what they are doing is a pitiful subset of your much grander speculation, which "posits" the existence of 69 dimensions.
Frankly, I get very close to doing just that. Anyway, I love ya', BB.
I'd have to disagree with you on this. Many theoretical predictions are confirmed or discarded on the basis of experiments contrived and carried out precisely to test the prediction, and that extends to cosmologies (they're still trying to confirm some of Einstein's predictions about gravity, for example). So at some level, these things are framed ahead of the evidence -- although of course not in the absence of all evidence.
String theory is one of those animals: it may be true or not -- but it definitely proposes a multi-dimensional cosmology in the absence of direct evidence.
Well, of course the theoretical models make predictions that can be tested. If they didn't, they wouldn't be scientific models. And as you say, such models are based on at least some evidence. And here I mean verifiable evidence. And they must be consistent with all known evidence, or they're dead on arrival.
What I meant to say earlier is that cosmological models based on nothing at all (that is, no verifiable evidence) aren't of much use to the scientific enterprise. No one needs my jocular "69 dimensions" on the shelf, awaiting some discovery that will make it useful.
In my worldview, knowledge goes way beyond the ability of science to observe much less logic to verify.
All of the following are outside the reach of science and logic: forgotten pain of childbirth, love, joy, peace, patience, kindness, goodness, gentleness, faithfulness, self-control and most especially, the indwelling Spirit Himself.
One thing I have to add is all such dimensions are nevertheless part of space/time. The same is true of all geometries which exist at or before the big bang in any cosmology.
It doesn't matter how many spatial or temporal dimensions are added - or the geometry of them - or the ordering of them - they would all still not suffice to encompass "all that there is". That is the point we making.
Geometry itself is illuminating. All cosmologies require it, therefore there is always a beginning - an uncaused cause. So even if one is unable or unwilling to entertain the existence of universals, qualia, non-physical phenomenon, spirits or God --- one is nevertheless stuck with a beginning.
Geometry also is illuminating concerning the physical realm. Fields exist because of the geometry. No geometry, no energy/matter, no physical objects or physical life - no scientists or logicians demanding proof.
Because geometry exists and it has a beginning, how could anyone conclude that "objective truth" can be obtained by any method (such scientific observation or logical proof) from within that geometry?
It's actually constrained by the requirements that the known particle families have to be allowed, the known forces have to appear and the current geometry of the known universe. There is a significant amount of evidence for string theory. The latest formulation has 13 dimensions and is called m-brane or m theory.
On the negative side, it predicts new particles that have never been observed, new dimensions that have never been observed and is dependent on the initial conditions used. It involves a whole lot of mathematics.
I'm betting string theory is superceded by one of the quantum gravity theories in our lifetimes (hopefully).
We’ve already gone the full nine yards on the discussion of universals over several hundred posts. Evidently you are of the mindset that a tree falling in the forest makes no sound if noone hears it. If that’s the way you chose to see things, then so be it. I look at the soundwaves in the CMB and see sound existing long before any biological life and therefore utterly disagree with you and thus, we have no common ground and therefore, nothing useful to explore.
A clarification to Einstein’s statement that ”reality is an illusion, albeit a persist one”. In physics, "realism" refers to the idea that a particle has properties that exist even before they are measured.
I am glad to hear you don’t demand proof of my worldview because you realize it cannot be done. We remain stalled however in comparing worldviews because you have not yet clarified what you believe to be “all that there is”.
I previously had thought you were a materialist, a metaphysical naturalist like several other correspondents here who see “all that there is” as that which occurs in nature, i.e. can be observed microscope to telescope.
Then when you said to betty boop ”There is no such separation between spirit and 4D space/time, can't be tested, can't be proven. “ I took it that your definition of “all that there is” is that which can be (logically) proven, i.e. can’t be proven therefore it doesn’t exist. It appears though that you object to that as well.
Until you clarify your view of reality any further discussion of your other comments is pointless.
No, not "false per se." At least you're not getting that from me. I've always attempted to be very clear, when discussing "my side," to say that there may indeed be more than that which is objectively observable and verifiable, but that such would, of necessity, be outside of science. In my post 1000, for example, I used phrases like: "the crude limitations imposed by objective verifiability," and "the scientist's limited version of reality." I've never been able to successfully communicate about this. However, I think I'm clear at this point about "your side," and where the fundamental differences are that distinguish our views.
It is such an irreconcilable difference that there is no point in continuing this discussion beyond making the worldviews clear to the Lurkers who might interested in them.
Maybe so. But I'll miss the fun.
[But the only way to know what's out there is to scientifically observe it (or its unmistakable effects). All else is philosophy (nothing wrong with that). -- by PH] This is a great example. In the above construct, to "know" is equal to "scientifically observe". That is one worldview, but it is not mine. In my worldview, knowledge goes way beyond the ability of science to observe much less logic to verify.
Gotcha. Thanks for clarifying the situation.
The pointlessness for me is when a correspondent denies the existence of the non-physical altogether. That is the futility to which I was speaking.
But for non-philosopher me, there are many things which I "know" but which cannot be scientifically observed. Among them is the affection and respect I have for you, PatrickHenry.
placemarker
[PH creeps up behind A-Girl and gives her a big ol' hug.]
... there are many things which I "know" but which cannot be scientifically observed.
Part of everyone's communications fuzziness on this point may lie in the definition of what "knowledge" is. We certainly know what we subjectively experience. But -- just as Eskimos allegedly have dozens of words for different kinds of snow -- there are different kinds of "knowledge," so we need, but don't have, a sufficient vocabulary to express the variety. Therefore, unless we are unusually rigorous in our discussions, confusion is unavoidable.
Here's just a few of what I think are some different shades of knowledge:
1. Internal emotional state: I "know" I'm happy.So we often talk past each other. Ya know what I mean? It's semantics. Ya know?
2. Sensory perception of something external to me: I "know" my dog is lying at my feet.
3. Historical fact: I "know" Reagan was once President.
4. Prediction from scientific theory: I "know" there will be a partial solar eclipse this week.
5. Logical conclusion: I "know" the Pythagorean theorem is valid and true.
Good start on a list of types of knowing. I'm sure philosophy has big word name for some of these. There is also personal memory. "I know I had breakfast this morning."
Personal memory is notoriously defective when put to the test.
This brings up a subset of historical knowledge -- knowledge based on "objective" recording devices, such as cameras.
Most forms of knowledge, including the most personal experiences and memory, are subject to manipulation and fraud.
Indeed, it appears that “knowledge” is the focus of the discussion we are having with the correspondents on this thread - though until your post I was having difficulty putting a label on it.
Many posts ago I asserted that “objective truth” like “absolute morality” cannot be obtained from within space/time because everything is relative per se in space/time, including language. I also pointed to what we know that we cannot know in math and physics and qualia.
You have underscored some excellent examples of the language problem! Thank you.
In the math and physics, I pointed to Godel’s incompleteness theorem and Heisenberg’s uncertainty principle as examples of what we know we cannot know. Massless particles and dimensionality would also make for good examples. In language, I pointed to qualia which by definition must be experienced and cannot be fully expressed - pain/pleasure, good/evil, love/hate, etc. We discussed the pain, forgetfulness and joy of childbirth which is beyond the ability to describe.
The link you provided sums up the knowledge issue rather well:
The “philosophical skepticism” link from Wikipedia is very useful in conveying some of my points and some of LogicWings’ counter arguments. Here's an excerpt:
Philosophical skepticism (UK spelling, scepticism) is the philosophical school of thought in which one critically examines whether the knowledge and perceptions one has are true, and whether or not one can ever be said to have true knowledge…
Philosophical skepticism can be either the claim that we don't have knowledge, or that we can't have knowledge. It is one thing to say that we could, but unfortunately don't, have knowledge. It could be argued that Socrates held that view. He appears to have thought that if we continue to ask questions we might eventually come to have knowledge; but that we didn't have it yet. It is believed that some skeptics have gone further and claimed that true knowledge is impossible, for example the Academic school in Ancient Greece.
Skepticism can be either about everything or about particular areas. Skeptics who believe that no knowledge can be said to be absolutely true are sometimes referred to as global skeptics. The global skeptic argues that you cannot absolutely know something to be either true or false. Some believe global skepticism has great difficulty in supporting this claim, and criticise skepticism on the basis that it implies that knowledge is philosophically impossible.
Local skeptics deny that we do or can have knowledge of a particular area. They may be skeptical about the possibility of one form of knowledge without doubting other forms. Different kinds of local skepticism may emerge, depending on the area. A person may doubt the truth value of differnt types of journalism, for example, depending on the types of media they trust. People who doubt the possibility of inherently true knowledge of the physical world are sometimes referred to as external world skeptics.
Skepticism is the view that either we have not yet found absolute knowledge, or that we cannot have any propositional knowledge. It is thus critical of formal logic, which must inevitably be founded on propositions that lead to the discovery of the truth through logical argument.
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