Stochasticism Part 2: Biological Amplification [New]
I’m still on the Off Topic series.
The context of this diary is primarily cellular. We’ve moved up a level of biological scale from the previous diary, Transition. Some may suggest that the molecular and cellular scales also define the non-living/living divide (if such a thing actually exists). That topic is beyond the scope of this diary. [Besides, I tend to piss off the philosophers when I talk about the meaning of life, so let’s get better acquainted before we tear the lid off that one.]
One of the minor mysteries in biophysical chemistry is how cells manage to elicit sudden changes in various metabolic and physiologic characteristics, traits, or phenotypes. These changes are in response to signals of fuel availability and physiological exigencies pertaining to the multi-cellular individual as implied by homeostasis. The cohort of human beings pondering these mysteries as a matter of career define the word “manage” in terms of macromolecular conformational changes, enzyme catalysis, and a wide range of interactions between macromolecules and with smaller molecules. The shorthand jargon term for this is mechanism. These are not new questions. They have bugged us ever since the first moving cells were observed.
The question becomes: How do cells organize the molecules within them in order to accomplish the functions that these have been observed to fulfill?
This discussion is in context of all the caveats this community can conjure.
Reductionists search for irreducible dichotomies because they need a foundation (a base camp) from which to begin climbing back, up the mechanistic trail left by those searching for answers to How? They were (are) foiled by the fractal essence of the nested realities uncovered with great care and very skillful means. Posing and investigating questions of purpose, function and meaning, uncovers the conjunction between a purposeful array of these mechanisms. These responses, imbued with direction, spin, character, flavor and charm, are more subtle than engineering. But the prevailing winds of the hyper-Capitalist global market place in which (most) current scientific research is conducted, pushes everything toward potential profit-making paradises just over the horizon. So we rarely get around to Why? But this place is not like the others. It is time to Merge.
To a protein biochemist Why? is a way of asking about function. The question becomes: What roles do particular molecules have in maintaining the various physiological functions of cells, in culture and inside the multi-cellular organisms that constitute their natural environment? This is an extremely utilitarian perspective and any answers uncovered should be interpreted with that notable caveat firmly in mind. That the experimental data published in peer reviewed journals is tinged with the pressures of the market-place is another reason to reconsider extension of these mechanisms to less well-investigated levels of biological complexity. That said, the discussion has barely begun.
Proteins are amazing little shape-shifters that make things happen. These buggers are the workers that implement the genetic bosses’ business plans (so to speak in a potentially analogous tone). In other than political terms, the nucleic acids are the storage media and the proteins (along with lipids and carbohydrate) are the read/write device. The biological twist on the latter analogy is that at the root, the storage media encodes the creation of the parts that, together, comprise the disk drive. Watch Videodrome if you want a graphic version of this analogy (but don’t watch it twice!).
Despite the wide array of molecular mechanisms, each intricately described in terms of how many fractions of an Angstrom atoms move relative to each other, no single enzyme discussed in peer reviewed journals had properties that could account for the bulk of the cellular properties that were routinely observed in other laboratories and discussed in a different set of peer-reviewed journals. In retrospect the answer seems obvious. That’s how it is in the sciences. Understanding how something works, more precisely the act of uncovering how things work, normalizes those mechanisms and they become part of our collective knowledge database. (Thomas Kuhn did not see this, or underrated it, IMHO). Paradigms are nested (PDF), not mutually exclusive or incommensurate. It’s a reflection of how we humans were “raised up” by the whiles of our evolutionary history. The physical aspects of nesting are seen in “fossilized” genes and “vestigial” organs, which would appear as something like a brachial cul de sac within the finer structure of the tree of life.
Some folks climb up mountains to see what it looks like while the sun is high. Others let their mind conceive of what it is like at the active site of an enzyme while the substrate levels are on the rise. The natural beauty is stunning, like the pictures from Hubble or whatever natural wonder is found in your backyard. That much is true (enough). The shapes of these things are basically the same. The shapes of sand dunes are in every snow drift. Truly it is a matter of scale. Each is different, too, of course but the lay of the land; the schematics, reflect similar contours; analogous forces. Mountains are a very apt analogy for biological structure and mechanism because they clearly depict the intersection of multiple time frames (lifetimes) in a visual model that connects with (almost) every one. Mountains are built on the scale of plate tectonics, yet produce flash floods within minutes and influence weather patterns on the scale of months. Metabolic pathways (and the proteins that regulate them) were built on the scale of evolution, yet work to clear post-meal glucose spikes from healthy human circulation within 30 minutes, and also orchestrate the arc of a single human lifetime. Shouts (or mumbles) of “Timing is everything” barely suffice, even if delivered with a cynical sneer and an “I told ya so” glare. I am humbled before the prowess of these natural mechanisms and beseech each molecule to take me as apprentice, that I might learn their ways and dream about practicing their trades.
Some of these have been revealed by the work of J Ferrell, his co-workers and others that describe cellular traits, such as sensitivity to particular extracellular compounds, in terms of the organized interaction of macromolecules (signal transduction, we call it). By similar arguments, it was also possible to account for the progression through cell cycle. One common aspect of these mechanisms is the requirement that a massive response be initiated by some critical signal. Partial responses (to less than critical signals) are not induced. The rationale for this kind of regulation is generally presented in terms of energy and raw material. It is very wasteful of both resources were a cell to proceed partially down the pathway to duplicating its entire genome and checking it for copy errors, not to mention all the rest of the cellular organelles and cytoskeleton, only to reverse course or halt. The cell has to commit, there’s no turning back (other than surviving another turn of the cycle). Likewise for response to hormones and other such compounds, as these often induce massive changes in cellular function and/or growth.
Although many individual enzymes have tremendous cooperative mechanisms, none could account for the observed cellular traits. By nesting the protein kinases (what of phosphatases?) into a cascade, the pathway amplifies the signal from the interaction between receptor and ligand to > 10,000 active molecules of protein kinases by the “end”. But that is not the end of the story. The PKs (PPs) also mediate the appropriate cellular responses that satisfy the signals. The molecular responses are coordinated and thereby alter traits at the cellular level, effectively amplifying the response with regard to biological scale. This apparent amplification of scale, from molecular to cellular, is mirrored by the function of pancreatic beta islets that orchestrate systemic metabolism (homeostasis) by way of blood-borne molecules that act on multiple distal tissues such as muscle and liver.
Another example of scale amplification is the feed/fast cycle in mammals, well any animal really, but we humans prefer to study ourselves, and lab mammals are as close as our evolving brain will allow us to get (most of the time). Consider that all the food you eat on a daily basis is disposed of through the molecular metabolic pathways maintained inside the cells that comprise your body. These include the parts that make feces, urine and sweat. Obviously these are regulated in the temporal sense and coordination of a particular sort is required to maintain a human being for 80 some years. Of course, your cells and the molecules nested within each one are still not quite you, are they? Let alone an ecosystem, or a culture.
The analogies are shifting into focus, yes? It is certainly accurate to refer to the internet, the WWW, and cable TV as “signal transduction” mechanisms. Splayed across the newspapers and web-sites we see that these appear also to function as “amplification” mechanisms. Is it not also accurate to describe the Jasmine Revolution as a “massive response” to a 30-50 years long “signal”? Ultimately, I find these analogies comforting and empowering because they offer us an out as the world closes in. Situations can change quickly, we may not need incrementalism. That should not be interpreted as complacency. We need to maintain the “signals”. We need to maintain to social/political “signals”. We need to build associations between people (the “parts” that comprise the cultural “whole) that will amplify those signals. Moreover, we need to shape the pathways so that when the switches flip, they land where we had hoped. One element of this is embodied in the QH posted David (Reclaiming the Politics of Freedom) and it is rhetorical at the root.
This subject was broached toward the end of Open Left and in regard to the negative example of the attempted assassination in AZ, which may have been a response to the stream of rhetorical noise (another word of stochastic phenomena) broadcast 24/7/365 by those with intentions that oppose the progressive/liberal vision of a cooperative future. I see the Spring blooms of Jasmine as a net positive response, the shape/structure of which it shares with the negative example described. My hope is that by describing something of how these mechanisms appear to operate, I might marshal a few of my fellow humans to view their individual (and collective) actions in the context of everybody else. We need to figure a way to use chaos and instability to our advantage and to provide a purpose to our “noisy” debates and discussions. Recognizing the stochastic nature of the context in which we exist is a beginning.
What Do You Think?
16 Responses to 'Stochasticism Part 2: Biological Amplification'
Leave a Reply
You must be logged in to post a comment.
William Timberman [New]
Tuesday, 12 Apr, 2011 at 9:57 am
Conjure. We conjure, you evaluate. Doesn’t seem like a fair deal to me. ;-) That said, I pretty much agree with your conclusions. It’s also fun to watch them being worked at from a different angle. The toleration of chaos is the key to a lot of things, I think, not least of which is a sense of how the ancient enemy, entropy, can be held at bay. Ars gratia artis, in other words.
Tuesday, 12 Apr, 2011 at 11:27 am
I’m a sucker for alliteration :)
I assure you, William, much of what goes into these Off Topic diaries is very much like conjuring, especially in the shamanic sense.
One of my points, however, is that “entropy” and its modern day cousin “chaos” are not our enemies. They are fundamental forces in the (multi)universe, at least as far a few generations of humans can figure. These forces are at work, everyday, and in many ways. They are not foreign or rare. We humans need to embrace these forces, not simply tolerate them.
William Timberman [New]
Tuesday, 12 Apr, 2011 at 11:36 am
Yeah, I meant tolerate in the sense that a plant tolerates a certain climate — not so very far from your use of embrace. And chaos in my usage isn’t the chaos of thermodynamics — i.e., an increase in randomness — but rather something like the Rite (riot?) of Spring, or the birth of a star, which can certainly seem random when you’re in the midst of them.
Tuesday, 12 Apr, 2011 at 11:47 am
Got it.
A more accurate term for what I mean by “chaos” is chaos theory. I admit, such is rather poorly defined by chemists. mathematicians and physicists. As you suggest, its much more like the birth of a star, or the enlightenment of a mind. How these grandious theories relate to the Riots of Spring and the Scent of Jasmine is even less well-defined. Even so, we see it everyday and at the root, science is about observation.
Mark [New]
Tuesday, 12 Apr, 2011 at 1:32 pm
Of course, what makes chaos theory interesting isn’t the chaos itself, but how order naturally emerges from chaos. It turns out the second law of thermodynamics has a rebellious child constantly pushing the other way.
Just as a refrigerator actually produces heat overall, emergent order never violates the second law of thermodynamics, but it sure seems like it does if you focus on just a subsection of the environment. Star, planet and galaxy construction, cloud formation, evolution, “El Niño” and related weather triggers all emerge from chaos naturally, even has chaos itself remains and, thermodynamically at least, increases overall.
Tuesday, 12 Apr, 2011 at 1:57 pm
Exactly.
Part of these “mechanisms” that we are describing is to try and drill down into how all those organized things emerge from the chaos. For me, “naturally” is too vague. I mean, isn’t everything that happens in the universe “natural”? (I mean everything, even “food” manufactured in factories).
Way Off Topic Food for Digression: Why is a beaver-built dam considered more “natural” than the Hoover Dam?
Mark [New]
Tuesday, 12 Apr, 2011 at 2:36 pm
Yep.
There are differences, of course, in degrees of planning. Does a beaver mean to build a dam, or is it just following instinct step by step without a clue to why or even what it is doing? For a beaver, I guess there is real thought involved, at least to some degree. But what about a spider and its web or ants and their tunnels.
Or humans and their cities? The ant might mean to move some dirt, but doesn’t remotely understand the overall consequences. The same could be said for the actions most people take.
Hoover was obviously meant to be built, but that only pushes back the “meaning” one or two steps. Were we meant to have the ability to plan like that?
Or from another angle, from time to time I argue that evolution is intelligent, just slow. If you were like those guys on Star Trek that moved at the speed of light, living your whole life in less minute of normal time, could you tell people were intelligent?
Tuesday, 12 Apr, 2011 at 2:48 pm
So, thought and planning are not natural?
There are other species besides humans that appear to think abstractly enough to figure out how to make and use tools. As far as the documentaries show, these are learned behaviors, not pure instinct.
If thinking and planning are not natural processes, albeit ones (apparently) expressed by only a few species within the biome, then where did they come from? Is it possible for a biological entity to develop “unnatural” traits? One might point to a bicycle riding bear as an example, but the talent was natural to bears and brought forth by training (harsh, nasty training).
Mark [New]
Tuesday, 12 Apr, 2011 at 3:07 pm
Nope.
[Here where I have to be careful about my instinct to take one side and pursue it. You'll note I agree with you completely, which a re-reading of above will show.]
Like all such discussions, the question eventually falls to definitions. Many people use the word ‘natural’ to mean not planned. Like your concentric circles, everything is natural, eventually. But specific acts have different degrees of planning.
For example, one can claim that suburbs emerge ‘naturally’ from the invention of the automobile.
Regardless of what word you want to use, I think it is vital (in fact, the whole point of your series) to understand how order emerges unintended from chaotic events. With that understanding, you can work to lightly bend the natural (quoted or not) results, which is easier and better than fighting against what ‘naturally’ ‘wants’ to happen.
Tuesday, 12 Apr, 2011 at 4:37 pm
Excellent answer!
I understand that we agree. Questions are one fruitful way scientific-types move. We are exploring here, not (necessarily) debating.
I refer to the point of your last paragraph as “synergy”. How to work with natural forces to weight the probabilities of what we want to happen in such a way that they actually emerge from the chaos.The danger is that we understand so little about these forces that our actions end up weighting other (unintended) probabilities.
To me that is the basis of tool-use. Using the tool weights the probabilities toward the desired outcome. When a crow sticks a sharpened twig into a hole to pull out a tasty insect, the intent is to make it more probable that it will eat. When humans build highrise apartment buildings, or suburban subdivisions, their intent (at one level) is to make it more probable that they will have shelter.
None of these are the only mechanism that can weight the probabilities. The reaction diagram in Transition tells us that there are many pathways between the states (hunger/satiety; exposure/shelter) and that it is the catalysts that determine which path is taken.
If we truly intend to rework the infrastructure of our culture (as came up on the QH about transit systems earlier today) we need to figure out how to catalyze that transition by a pathway that is in accord with the social morals we would like our culture to embody. I don’t know whether humans will be able to pull it off, but I don’t have any other options when one gets right down to it.
David [New]
Tuesday, 12 Apr, 2011 at 2:38 pm
Why did the Natural History Museum used to contain Native American artifacts?
Natural isn’t used just to distinguish human from animals and plants, but also “civilization” from the “uncivilized”.
Tuesday, 12 Apr, 2011 at 2:51 pm
OK. Now we may be getting somewhere.
Humans are civilized and animals less so, or uncivilized. Is that where you are heading?
David [New]
Tuesday, 12 Apr, 2011 at 4:32 pm
I think more that the idea of naturalness helps define us – it serves a role in identity formation (and this is all an observation – not a description of my own views).
Also, going off Mark’s point above, naturalness is also used to distinguish that which need be defended from that which need not. Think libertarianism – markets are natural, government action is an intervention that must be justified. This obviously stacks the deck in favor of a political position, yet many liberals accept it unthinkingly. One of the great insights of legal realism was that there is always government action – in creating and protecting property rights, enforcing contracts, etc. Thus lack of government action is not the touchstone of freedom.
Tuesday, 12 Apr, 2011 at 5:16 pm
Well, out of respect for my anarchist tendencies, I might go so far at the say that government must be justified through its actions.
Markets are natural, at least in the sense that humans have been trading things for (almost) as long as we have been human. That some humans have figured out how use that natural tendency of humans as a means to exploit them is unique in humans mostly as a function of scale and duration. I see it as a kind of rational symbiosis, when it works well. Biological symbiosis has been traced to molecular pathways (bioswitches again) and it seems that one trait humans have (uniquely?) developed it the ability to attempt to design and construct very elaborate devices (tools) based on rational implementation of mechanisms observed in the natural world. (whatever that is! :)) Of course, the more elaborate the scheme, the more likely it is to produce unintended consequences and provide those of malicious intent the opportunity for exploitation. Symbiosis and parasitism are a spectrum, I think.
At the same time, from a larger concentric circle, the passing of a single primate species by their own wasteful ways, detrimental rates of resource consumption and saturating their environment with garbage, is another milestone like the one we saw back down the road a ways, “Dinosaurs”, I think it said.
That’s when the word nest comes into play, with all of its comfort intact. That the larger circles exist does not ablate the smaller. I’m too tired to look up the refs right now, but CG Jung has a riff or two about the “little in the big” and the “young in the old” that say it much better than I can.
David [New]
Wednesday, 13 Apr, 2011 at 7:58 pm
The idea of markets as natural is actually a claim that they are pre-political. That idea doesn’t make sense. Markets involve property, contracts, money – all products of law. It’s more a claim about the present than a historical one. It ends up obscuring certain kinds of coercion (i.e. all private coercion and some types of government coercion) and then objects to others. That is a hollow view of freedom, as opposed to one that I mentioned in the last QH. I have never understood why it matters whether one is restricted by government or a non-governmental actors – either way, one’s freedom is limited. Only those who already enjoy the full protections of law could imagine any additional government action would necessarily lead to less freedom. Those who lack those protections know better.
Wednesday, 13 Apr, 2011 at 11:12 pm
The rudimentary market of two or three artisans trading their utilitarian wares, or figuring out that they could make more arrows more quickly by breaking the task into parts and specializing the work. I’d bet that many of the things you listed developed in response to the tensions arising out these rudimentary, face-to-face quid pro quo proto-markets. They all ways to establish a standard and a means to negotiate exchanges of goods.
Coercion is a spectrum,where it crosses the line and what price tag we are willing to affix to our freedom, reasonably speaking of course, it a personal and community choice. One key, I think it to figure out how to value people in a way that isn’t analogous to the market place. Like “price tag” or “vacation”.