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Is the body a bureaucracy or an economy?
Published on December 26, 2004 By Phil Osborn In Pure Technology
Some time in that past few years, I got to hear Dr. Douglas C. Wallace, the Donald Bren Professor of Biological Sciences and Molecular Medicine at UCI discuss his research on mitochondria, the energy organelles that power all our cells. Wallace is the generally acknowledged top-gun worldwide in mitochondrial research. I posed him a hypothesis, during Q & A, which I had come up with on my own to explain an interesting anomoly.

Background: We all have various different variants of mitochondrial DNA within us, scattered semi-randomly in our various tissues and organs. The mitochondria has its own DNA, BTW, independent of the DNA in the nucleus of the cell. And, each cell has many, many mitochondria to power it, each with its own DNA history. Almost all of it comes from the mother's side - the egg. Occasionally some sperm mitochondrial DNA may sneak in, but not much or often. Thus, it is possible to independently confirm genetic drifts in populations using the mitochondrial DNA for the female side and Y-chromosomes for the male, and some of Dr. Wallace's research has been in the field of tracing population movements in humans through prehistory, by genetic analysis.

The anomaly comes in the following form: It turns out that the good mitochondria tend to come to be replaced by successively inferior breeds as we age. Not all mitochondria are equal. Some are totally useless and parasitical, merely eating to reproduce and contributing nothing to the cell's energy budget. Others are Schwartzeneggar Mitochondria - real powerhouses. Mutations occur and get passed along. If there are too many of the bad kind, the cell becomes non-functional or dies. When the egg divides to form an embryo which divides again and again to form the foetus, which becomes the child from more divisions, which becomes the adult, etc., each new division is another cast of the dice of mitochondrial inheritance.

So, identical twins are not. One may have inherited all bad mitochondrial DNA (mDNA) in a particular organ or tissue - say the heart...

So the interesting question is WHY the weak, bad mDNA ends up dominating with aging. AND, I had a solution. I hypothesized that the good mDNA wore the cells out, as they did a disproportionate amount of the work, while the weaker, slower mDNA lasted longer, so that we had lots of energy in youth, to make up for stupidity, right? Then the slower, perhaps less free-radical generating mDNA dominated through adulthood, until the really weak mDNA was all that was left, in old age.

Sounds plausible? Explains the facts? Makes sense? Yes, yes and yes - and Dr. Wallace complimented me on this. However, it has the fatal flaw of being WRONG!!!

Ok, what actually happens - although it makes little sense - is that the cells with weak mDNA, lacking energy, get the signal or decide themselves to solve the problem by dividing, which may offer a temporary solution, admittedly, but seems to only exacerbate problems long term. The strong, efficient, energetic cells never see any need to divide.

Well, things stood at that point in my thinking for some time. It just didn't compute. WHY would evolution have selected for this kind of behavior? So, one night I was thinging about fellow anarchist Jarret Wollstein's superlative analysis of the problem of the squeeky wheel. When does the police department get more funding - when crime goes up or when crime goes down? Here we have an unfortunate principle of bureaucracy in all forms. The least successful departments get the budget increases. So, failure on every level is rewarded, and, being rewarded, tends to replicate and be emulated. State's tend to get more and more inefficient as a consequence, until they destroy the societies that finance them. In the market, a company may go through the same devolution, but it usually has better tools of internal analysis, as its motivation is profit. Also, only that one business tends to fail, while the state drags everything down with it.

So, my breakthrough was when I realized I could apply this to the human body. Voila! A NEW theory of aging. Consider the body as a political state, with all kinds of internal feedback loops to try to prevent runaway positive feedback, etc., but still, fundamentally a top-down hierarchy. Systemic flaws creep in because the internal information structure is never perfect. The model cannot model itself at some point, and then the body starts rewarding failure. Then we get overweight, diabetes, other auto-immune problems (which may or may not fall under this paradigm), and a host of yet unidentified system flaws that lead us further and further away from real balance and require more and more energy expenditure to correct or compensate for.

We've seen this kind of counter-intuitive system failure before in the body, as in the case of damaged heart tissue. Instead of simply repairing the damage from a minor infarction, the damaged area tends to spread over time until the entire heart fails. This is a failure in programming on the part of the body's system control, and it tends to lend support to the idea that large portions of physiological functions behave more like a rigid bureaucracy than a self-correcting market.

While a lot of bad feedback loops may bring up specific remedies - like the state requiring that schools meet certain academic goals or lose funding - there are many others that are missed in the evolutionary selection process, and eventually the body system falls more and more into the territory of rewarding failure, which perpetuates itself until the entire system collapses. Perhaps only when we do some real system intervention - essentially bringing intelligent oversight to the system - will we be able to fully countervene this systemic flaw.

Now will somebody please knock this argument down for me?

Comments
on Dec 26, 2004

there are many others that are missed in the evolutionary selection process, and eventually the body system falls more and more into the territory of rewarding failure, which perpetuates itself until the entire system collapses


ive read some stuff that seems to indicate older vertebrate species--some fish and turtles in particular--dont seem to be nearly as susceptible to the whims of catabolism (whatever those may be).  im not challenging your supposition...just wondering how, why or if (supposing it's true for some fish and turtles) an advantageous cellular strategy could devolve or not be passed up the ladder?  

on Dec 27, 2004
I think that there is a kind of zero-sum-game going on on some level regarding the evolution of complexity. As the information in the DNA or mDNA increases, the rate of errors due to cosmic rays, quantum effects, mutagens, viruses, etc., also tends to increase, meaning that more effort must now be dedicated to information correction simply in order to hold place. More sophisticated systems for error-checking also evolve as they provide a competitive advantage, but they also have costs.

Early on, when nanotech was first being envisioned, Drexler and others proposed that a nanomachine be built that would enter cells and take an average of DNA to construct an internal model of the theoretically correct version. Then it would replicate itself and the crew of machines would check every cell, leaving a molecular datestamp, so that the machines wouldn't waste time rechecking, and correcting the DNA to match the model.

One problem with this are that the information is not simply contained in the DNA, but rather in a process involving RNA and meta-instructions that turn on or off specific DNA sequences, as in telling a cell that it is a muscle cell and not bone. One of the cellular symptoms of aging noted fairly early on is that cells de-differentiate, losing their precise identity, ultimately misreading their environment and the signals from the tissue surround and then possibly becoming cancerous. This can be due to specific mutations, or it can simply be a system failure in which the cell gets confused about what it is. Simply correcting the DNA may not help.

The body has a rather sophisticated set of correction procedures to deal with this already. If cells lose their identity and become renegades, then they will typically display anomolous proteins on their surfaces, which tells killer cells to destroy them. But this only postpones the problem, as eventually a mutation or system failure will occur that involves NOT displaying the markers, among many possibilities.

Anyway, to try to deal with y our comment, I guess that the best answer that I can come up with is that with a given level of error correction it is only possible to maintain just so much information intact in the face of random changes. So, yes, things get lost when priorities indicate something else gives more of a survival edge at that moment.
on Dec 30, 2004
I missed this thread, but anyway, regarding your theory of aging, it seems to have been arrived at deductively ,from macro to micro. It also poses a problematic analogy between biological cellular systems and political-structural systems. This you must agree , is a quantum leap which as they say , like comparing apples and coconuts so that we really will have difficulty linking them together. What about focusing on the cellular dynamics? What's this about telomeres ? That must be a significant finding consistent with aging worth finding about. What triggers their shortening as we age?
on Jan 03, 2005
Reply By: scatter629 I missed this thread, but anyway, regarding your theory of aging, it seems to have been arrived at deductively ,from macro to micro. It also poses a problematic analogy between biological cellular systems and political-structural systems. This you must agree , is a quantum leap which as they say , like comparing apples and coconuts so that we really will have difficulty linking them together. What about focusing on the cellular dynamics? What's this about telomeres ? That must be a significant finding consistent with aging worth finding about. What triggers their shortening as we age?

There are various models of control that we know about, and the medium is not the critical element. Rather the issue of how the information flows and what the processes are that deal with it are the essentials. Take a look at the original masterwork on Systems Theory, James Miller's "Living Systems." I heard a couple of talks by him giving an overview of his work in 1980, and one of his points was that upon investigation by the substantial team involved in developing "systems theory," they discovered that systems had a kind of what we would call today fracticality. That is, a whatever level or sublevel you examined a system, you tended to find the same basic functionality replicated again on that level. This applied to cells, organelles, organs, individual living creatures and societies of such. This is not an absolute rule, of course, but the issue of analogies is only relevant if the analogous model does not relate functionally to the subject to which it is applied. I use the political analogy for the elements of control process it illustrates.

Regarding telomeres. Also, around 1980, the then new Life Extension Foundation (lef), together with the Alcor Cryonics Society, put on a huge exposition at the Disneyland Hotel, in which a Chinese doctor that lef had been funding, discussed the results of his research, in brief that the Hayflick limit did not apply to cancer cells. This triggered a search for the mechanism that dictates how many times a cell can divide, which resulted in Geron Corporation discovering that there are these nonsense DNA caps on the ends of the chromosomes that wear off a little with each adult cell division. When they're gone, the divisions start eating into the active DNA and the cell dies or becomes senescent. Geron, BTW, now has a collection of experimental drugs that have the ability to add back telomeres length or block "telomerase," which is the material that cancer cells can produce that blocks the telomere from shrinking. So, they may already have a cure for cancer AND a method of making us immortal.