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.
"YECs"
Just letting you know, there is more than that garden variety.
There is also the Non-Literalist stadnpoint (or more exactly, the literalist of the original texts in the Bible.)
Then the IDers come out to play and are the least grounded in religious affiliations of any sort.
I try to argue as an IDer and hold my faith as the second. I don't believe the evidence supports that our world is in fact only a few thousand years old. I also don't think the evidence supports that it was created in 6 days.
I DO think it was created in 6 yom, or periods of time. Set in motion a LONG time ago by 6 undetermined increments. We are currently in the 7th yom. God's rest.
Anywho, off subject(ish) but thats a more reprsentative viewpoint of FReepers.
Thanks for your time, hope you don't hate me in the futurer (or listen to much to other evo's stories about me:p ... esp DocStoch)
FRegards
-Mac
Good point. Although I believe, in fact, they largely are, if maybe in a confused way.
"I understand there is a problem of measurement here: who decides who is sane and who is insane. But in this case the majority rules, even if there is no way to prove the majority is right."
Anybody else catch moral relativism out of that?
I believe, in fact, they largely are, if maybe in a confused way.
That's entirely possible, even likely. (My earlier remark had more to do with theorists than with day-to-day practitioners.)
Perhaps interestingly in this context, I recall seeing surveys showing that theistic belief (though not necessarily the mainstream religions or any of those religions' orthodox theologies) tends to be more common among physicists (and, if I recall correctly, mathematicians) than among psychologists. Not that I'm recommending drawing any conclusions from that factoid, but I suspect that physicists are more inclined to be impressed by the sheer Platonic majesty of the universe :-).
As a Baptist I agree with Aquinasfan.
No Christian should elevate a Bishop, pastor or church above his own conscience. Each of us are responsible for our own actions directly to God. And as such, we have a responsibility to properly inform ourselves.
First, information theory is part of mathematics and thus when we are making an observation using information theory, it is mathematics per se.
Second, one cannot dismiss universals with a handwave (“I’ll skip a re-introduction of the realist-nominalist debate here”) when they are, by definition, part of “objective reality” for a realist.
Third, information is not corporeal – it is the reduction of uncertainty in the receiver – the action. Thus when we observe state changes in molecular machinery we are observing information (successful communication) and we can even measure the gain of information content in bits.
Fourth, the Shannon model suggests an inception for each successful communication. That is what Monist theorists cannot see. There are three possible inceptions: (a) interrupt such as the presence of food, change in temperature, radiation, (b) cycle or timing, and (c) will. Moreover, there are two types of will – (1) involuntary (2) voluntary.
It is not in the brain!
It is also observed in collectives of organisms which act as if one mind (ants, bees, etc.). The “will to live” also permeates throughout the molecular machinery of higher organisms. For instance, if a part of the heart dies (myocardial infarction) - the molecular machinery will continue to struggle to survive, routing blood flow around the dead tissue. A person can be “brain dead” and yet the rest of the body will struggle to survive and will succeed if a machine (respirator) is used to simulate the cyclic instruction of the brain.
Voluntary will includes abstraction, anticipation, mediation, intention. A thought experiment is to decide to move your finger to press a key on your keyboard to respond to me. Another is to consider what you are going to say. Another example is what a live bird does when it is dropped from a roof top along with a dead bird and a 12 lb cannonball, i.e. the live bird decides to fly away.
To the nominalist, green is in the eye of the beholder – a fabrication of the mind. (How nominalists can ever communicate at all is “beyond” me.) Likewise, pi is the invention of the mathematician – it doesn’t actually exist.
So returning to the question, how does science test a universal – I suggest that we realists can identify universals by observation, comparison and deduction – but that nominalists cannot test what they deny exists.
you said: If by "design theory" you mean "Intelligent Design," the difference is huge because the Theory of Evolution is disprovable while Intelligent Design is not. But if by "design theory" you mean the scientific application of Dynamic Systems Analysis to biological machines in order to determine the proper modeling construct that explains design, then there would be no difference.
Popperian falsification has no bearing on that observation.
Nevertheless, concerning the pursuit of science - there is no substantive difference between an unfounded assertion that “Nature did it!” and an unfounded assertion that “God did it!”. Either statement terminates investigation.
How is it moral relativism? People with brain disorders do not necessarily accept themselves as being defective. Do you have an objective way of proving that your reality is the true one?
You might be interested in reading the discussion of consciousness and extra dimensions on this other thread.
The word murd murder implies an immoral motive, not just the act of killing. If you believe that a specific act of killing is in self defense, or in the defense of your family, community or nation, then it is not murder.
Authorities seldom tell people to commit murder. They tell them what is necessary for defense.
Less than proving my point of view, more of proving my point.
You seem to grasp that yes, people who are not of sound mind may not percieve this fact. But you continued to say (in effect) "who's to say our point of view is correct?"
Citing that a disorder or illness will make you think you are correct. This is not true for the majority of us, but the mentally handicapped, the insane, the sick have just as valid a POV as you or I.
Your argument is that "if it feels 'right' it is"
Men do not murder other men and have it be "right". It is never "right" I don't care what world you live in. There are absolutes in morals.
Better make sure to cover the 10% of men who are red-green colorblind, too!
FWIW, you're touching on a different topic here, which is the moral implications of something like the theory of evolution. Can one really make a positive statement about the "moral propriety" of killing -- whether as murder or self-defense -- when the moral implications of evolution tend to support utilitarian principles?
Yeah, it's a topic for a different day, but since you'd already sorta brought it up...
Evolution has no moral implications. It's a scientific theory. I cannot for the life of me understand why so many people seem unable to escape the natrualistic fallacy. Are y'all so enslaved to popular culture you just can't get beyond "natural = good"?
Yes it does. Think about it a bit more, doc.
betty boop: If this is some kind of a test, and the question is: "Is there change [from?] outside of time?", my recorded answer would be: Yes. And No. It all depends on how you look at the problem. :^)
If true reality is timelessness - as Godel suggests (and to which I agree) - then what we sense as a timeline (and arrow of time) is an illusion, it is actually (to whatever extent it exists) a plane or membrane and thus physical causality can be violated.
String theory, in particular f-theory, gives us further insight from within our niche of space/time - the seemingly arbitrary four dimensions of human perception.
However, presuming true reality is timelessness (which is to say, from a Christian perspective, "in" God) - then physical causality and free will (participation in creation) are the permission of His will. IOW, predestination (strong determinism) is not mutually exclusive to free will in timelessness.
Conversely, if the metaphysical naturalists and Monists were correct - and reality is only that which exists "in" space/time then I would assert that predestination (strong determinism) is the only possible conclusion - because randomness is always the effect of a prior cause in that scenario, even Brownian motion. IOW, free will is the illusion to a metaphysical naturalist.
The problem here is an equivocal use of the term matter. Matter, in the Aristotelian sense, considered absolutely, is pure potentiality. It has no existence apart from "form," again in the Aristotelian sense, which is the principle of "act" or existence. Matter (when it is conjoined with form) is the principle of individuation.
The form/matter dichotomy helps to explain the problem of change. Aristotle solved the problem of change by postulating four causes: material, efficient, formal and final. Consider a block of marble being changed into a statue. The marble constitutes the material cause of the change, the "matter" which is effected by the change. The sculptor represents the efficient cause of the change, or the agent bringing about the change. The sculpture itself represents the formal cause of the change, the aspect of the change that brings about a new "whatness" (the sculpture). The final cause would be the purpose for which the statue is sculpted.
Form and matter represents the most fundamental division of existing things, apart from Being and non-being (wherein non-being has no actual existence, but only logical existence as the opposite of Being). All things, apart from God and the angels, are composites of matter and form. Matter, on one extreme, is pure potentiality and has no existence apart from form. God, on the other extreme, is pure act, with no admixture of matter or potency. Interestingly, angels are pure forms without matter, but are not pure act. God is categorically different from all other things in that His essence is pure act, His nature is Being.
Matter, in the modern sense, is the subject of deterministic natural processes. Such a theory makes a coherent explanation of consciousness and the truth of our knowledge impossible.
Yes. That's why I distinguished between murder and killing.
What shade of green?
I believe the bit you are reffering to is Alamo's point of universality.
She is referring to (correct me if I'm wrong here A-G) the "perfect" green. There are many represnetations of green, though to see it we
a) need to get a shade of green.
and
b) need to place the green on a medium to percieve it.
Care to show us just "green" js?
Not text colored green. Just green.
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