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Being Consistent with Selection
Published on January 1, 2004 By Phil Osborn In Pure Technology
Ok... You heard it here first. I suspect.

Update: April 22, 2004

UCI (University of California, Irvine) had a Dr. Thompson this Tuesday speaking on her specialty, Huntington's Disease, and the genomics thereof. If you ever get a chance to hear this lady, do it. She is not only very smart and very good at communicating, but she is also a FOX! Definitely some genes worth preserving there, which is my only motivation, of course....

Anyway, turns out that there are about 10% of the Huntingtons victims who do not have an apparent genetic background. The disease is basically related to a genetic sequence that gets repeated too many times and makes too much of a protein, leading to all kinds of terrible results, including psychiatric/behavioral symptoms such as paranoia, depression, and others, and a general physical deterioration, involving loss of weight and a dance-like trembling. The damage to the brain and CNS is dramatic and progressive.

Fortunately, Dr. Thompson has made real progress in identifying the pathways of the actual damage and is at least partially responsible herself for a number of successful drug interventions in transgenetic mice with Huntingtons, as well as fruit flies. These drugs are now going into clinical trials for safety with humans, and there is every indication that the disease will be successfully treated in the near future.

So, meanwhile, related to the more general subject of this blog article, I asked her after the talk if she had considered the idea that the 10% might be a result of Darwinian selection within the cytoplasm of a germ cell. I could tell that this was a new idea for her, as she kind of jumped back a few inches, her great big eyes that a man could just drown it widened even more, and suddenly you could see the wheels turning. Not that I had much more to say on the subject, especially as my focus was drifting, but I at least wanted to see her reaction, and possibly plant the suggestion, in the hopes that it might pay off. (My phone number is available by special request, Dr. Thompson....)

The reason that I suspect that the Darwinian hypothesis I'm advancing might apply is that the protein encoding sequence itself varies typically in length from generation to generation, which itself ought to make one wonder... I mean, IF it varies, and it does, dramatically, then how come we don't see a whole LOT MORE Huntington's???? DUH... OK, it is pretty stable for most of the population, but for the people who carry the disease genetically, the length varies between generations. So, there has to be a mechanism that controls the number of repeats of the gene, right? And it looks like it's that mechanism that is failing.

So, is this a special case, or is there a more general Darwinian contest going on within the cell over which gene sequences get expanded, reverse transcribed, etc.? And, BTW, do Huntington's patients also show variations in the number of repeats of other genes? Shades of Lamark. Anyway, that's as far as my analysis goes for the moment. I wonder what kind of odds and pre-pay-off sale of rights I could negotiate on my share of the Nobel at this point? End of update. We now return you to the past....

We know that whenever a species acquires an ecological niche, it then focuses most selection energy on intraspecies competition. Giant male elk battle each other a lot more than wolves. Internal competition is necessary to keep species that already have a huge acquired advantage in their niche from degenerating and becoming vulnerable to a takeover by some competiing speciesr or overpopulatiing. In Vanuatu, ritual canibalism kept human populations stable, for example, over many centuries, in spite of ample resources of food.

So, what about cells, internally? Recent information - the subject of major articles in "Scientific American" - tells us that all that "junk DNA" that makes up over 90% of our genetic material may not be junk after all, (a position I argued in support of for the past three decades). In fact, the junk is coding for small fragments of RNA, among other things. Considering all the things that these fragments are good for, some of which have been identified - but millions probably remain, it suddenly occurred to me to use standard selection analysis on the inside of the cell.

Suppose that what goes on inside the cell is again a competition for resources - material and energy - by various cellular components? The various potential cellular configurations and structures battle over strategies, attempting to shut off DNA sections that work against them and turn on those that support them. This is a complication to the whole picture of cellular machinery that will not please many of the more deterministic researchers, if true. But how could it NOT be true?

You heard it here, first.

Comments
on Jan 02, 2004
In a universe that is overwhelmingly chaotic, it is no surprise that the "junk" in DNA is pernicious and unpredictable.
on Jan 10, 2004
Or that some trolls will jump at any opportunity... Personally, I like trolls, barBQued, fried, roasted or in the shell. But, that's not an argument. (Yes it is!) No it's not! An argument consists of a set of clearly defined premises leading to conclusions by means of logical inference. (No, it's not.) Listen, you fool, just denial is not an argument. It adds nothing to the discussion. It's just a waste of time designed to infuriate. (No, it's not!) .... with apologies to Monty Python....

Arthur Koestler had some interesting ideas about genetic programming. Early on - I think late '60's, I began looking at genes as computing machinery, partially due to Koestler's influence, I'm sure. I suspect that there are all kinds of interesting things happening in the cell that evolved much the way neural nets work, which makes the process of decoding them all that much more difficult. There may be adaptive systems scattered through the genome that monitor certain important complex derivatives of major cellular processes and exert a controlling influence.

We now know that a whole lot of gross physiology is not deterministically predictable from a person's mere DNA. The influence of environmental as well as essentially random selections coming from such places as the small RNA/junk DNA may cause major differences in what genes are turned on or off. Then, there is the distribution of different strains of mitochondria throughout the body, an ever-changeing mix, as some strains cause early cell die-off or fail to provide sufficient energy in a particular organ or tissue area. Which is just one of several major reasons why clones are no more identical than "identical" twins.

True, they will be, on average, more grossly similar in appearance, and often in many other characteristics, than the general population. But differing expressions of genes as well as different mitochondrial populations will add to the differences already caused by environment and by personal choices.

This has important political ramifications. Cyril Burt, co-founder of Mensa, did the largest study ever even attampted of twins separated at birth to determine the relative roles of heredity and environment, back in the 1920's. His results appeared to establish beyond a shadow of doubt that heredity was the major factor, which greatly pleased the British aristocracy, and so Burt essentially capitalized on their pleasure to become the most powerful figure in Commonwealth public education, responsible for a virtually worldwide system that tested children early on and then, on the basis of early testing, tracked students in various perparatory curricula, e.g., college vs. trade school.

In the late '60's, I believe, Burt died and someone found his original notes, which proved that he had fudged the date to get the results that would be politically popular. Meanwhile, several hundred million children had been given a much poorer educational opportunity than they otherwise would have.

Another factor to be taken into account in assessing the damage that Burt caused is that the main competitor to his brand of schooling was Montessori. Burt's system assumed that little could be done to enhance intelligence - perhaps 15%, at best, so it was pointless to spend resources on early childhood education. Montessori and Piaget later were ignored as fools who had already been debunked scientifically by Burt. It was only after the University of Chicago did the ground-breaking research on educational outcomes that lead directly to Head Start, that first Piaget, I think, and then Montessori became respectable.

Overall, then, the damage due to Burt's fraud amounts by now to something roughly comparable to the great political villains of the 20th century - Hitler, Stalin, Mao.

This example also illustrates some of the problems of "state science." State funding of the sciences has lead to many monumental frauds, of which Burt's is perhaps the worst in all history, but is just one of many. Today, compounding the problem, is the idiotic system of intellectual property that the U.S. especially is trying to force down the world's throat. This may well eventually lead to a nuclear exchange with China within a decade or two.

More on that later.
on Jan 12, 2004
Good stuff. I have always held, in my un-accredidated position, that the DNA is not stagnant but a living growing and dying thing. I observe how couples will tend to begin to have similar physiology of face and body shape over time, as if being molded by thier relationship in subtle physical ways. I hold that the person is changing constantly and each thought actually has relationship of the neuro-electrical charges with the DNA. Under this then a genius may be born true enough, but also may be created by the life experience. The only reason a person will tend to show the same string is because most humans are stagnant people, seldom so much as reading a book afer college, or changing hair style after age 30. It is this lack of changing habits which accounts for most of the stagnant DNA we observe of average people. But in a vibrant and actively changing life, the DNA is also adapting to the constant change by synchronizing with the person's life energy to 'grow' and 'adapt' to new environments and states of being. For example, a person who made a living as a woodsman and then goes to a desk job as foremen, will have different actions to sustain, therefore the DNA begins to be altered to accomodate the changes. Can you illuminate me on this more, I am at wahkonta@graffiti.net. Thanks for the thoughts.
on Jan 14, 2004
I'm just a fairly educated layman myself. (See my intro "What about ME?... ) However, I do recall all too well how the "experts" in the fields of gerontology and life-extension insisted up through the '80's that there couldn't be a "death gene," as there was no evolutionary advantage to one. Even if it served the interests of the gene pool, they insisted that evolution was via individuals, not species or other gene pools, so it wouldn't wash.


Meanwhile, around 1980, W. Donner Denkla demonstrated that if you blocked basic hormone control high enough in the hierarchy - such as by surgically removing the hypothalamus in mice - and then substituted hormone replacement at youthful levels, then those mice lived a whole LOT longer than normal, and very aged mice suddenly recovered youthful appearance and behavior.


But Denkla was ignored and noone even tried to replicate his work, because we already KNEW that there couldn't be a death gene.


However, I was an early computer user/programmer, and I spent a lot of time figuring out how feedback systems actually worked, and I could visualize Denkla's agument and see that it worked. He argued that each species had an optimal lifespan that was dictated by the need for genetic turnover and diversity. If there is a very basic death gene that turns most species off past a certain lifespan, and if some individual managed to bypass that gene via some new mutation, then those very long lived progeny of that individual would also live a long time, and acquire skills, experience, etc., that gave them a HUGE behavioral advantage over their competition, very quickly displacing all the short-timers, right? But then the climate would shift drastically, or some rare disease lurking in the background in some other gene pool would suddenly emerge, or any number of genetic shocks would be delivered that would wipe out 90% and then 90% and then 90% .... and then, because the gene turnover is so slow, the species would die... Thus, this death gene is interwoven very tightly in the most essential survival systems of our cells, and breaking the code is next to impossible - by chance.


By design, however, we should be able to spot the critical paths and block or alter them. However, it took a LONG time for that perspective to come around among scientific circles, because the old school couldn't think well in terms of complex systems. Why? Because they didn't come from any environment in which they directly experienced them and played around with them, as any programmer does....



on Apr 23, 2004
Good article with an interesting idea. You are right it would be very controversial, thinking of competition down to the cellular level.
on Jan 02, 2005
Hi, I just happened to find this article while doing a little surfing. When I was in college I created my own curriculum and called it "Biochemical Gerontology". The reason being that my university offered nothing in aging. I studied everything written. My conclusion was that Donner Denkla was the only person who was really "on to something", but as this article says, all the traditional old school thinkers and even the new ones already "knew" that that was ludicrous.@I even created some methods of proving it, but all I got when I tried to talk about it was the rolled eyes and smiles. The "system" where I was at, and I'm sure most other institutions, have the same gridlock when it comes to any true unique ideas even though everyone is familiar with the stories of Corpernicus, Edison, Bell, and so on. I'm not implying I'm anywhere close to being in the same league as those kinds of people, but I have run up against the idiocy of the political managers of science, and if it wasn't for them and the likes of them, the human race could have been on the moon 10,000 year ago. Anyone seriously interested in studing aging should become very familiar with Denklas work. Don