Wednesday, September 12, 2012

SCROOGE McDUCK, FOLDING NUCLEOTIDES AND 'JUNK DNA'

Here is a quote from a post that I wrote more than five years ago,

"At the moment, the great majority of the three billion nucleotides that make up the DNA in each and every one of the one hundred trillion cells of your body, is considered to be 'junk' DNA, because scientists have not, as yet, found a use for it.  It is considered to probably be a vestige of centuries and centuries of evolutionary mistakes.  Knowing that God is neither wasteful nor frivolous, and that there were really no evolutionary mistakes, (we humans, just celebrating our perhaps one hundred thousandth birthday on this planet, have the audacity to consider the dinosaur, who thrived here for one hundred sixty million years, to be an evolutionary mistake); that, in some way, the quality of our existence today, is built on the knowledge gained, the materials created and the progeny produced by all that preceded us; I suggest that there is a yet to be discovered purpose to each and every one of those three billion nucleotides and to the manner in which they are folded into the nucleus of each of our one hundred trillion cells."

What follows is an article from the New York Times that I came upon last week:

Bits of Mystery DNA, Far From ‘Junk,’ Play Crucial Role

By Gina Kolata

Published: September 5, 2012
Among the many mysteries of human biology is why complex diseases like diabetes, high blood pressure and psychiatric disorders are so difficult to predict and, often, to treat. An equally perplexing puzzle is why one individual gets a disease like cancer or depression, while an identical twin remains perfectly healthy.Now scientists have discovered a vital clue to unraveling these riddles. The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches.
The findings, which are the fruit of an immense federal project involving 440 scientists from 32 laboratories around the world, will have immediate applications for understanding how alterations in the non-gene parts of DNA contribute to human diseases, which may in turn lead to new drugs. They can also help explain how the environment can affect disease risk. In the case of identical twins, small changes in environmental exposure can slightly alter gene switches, with the result that one twin gets a disease and the other does not.
As scientists delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered a complex system that controls genes. At least 80 percent of this DNA is active and needed. The result of the work is an annotated road map of much of this DNA, noting what it is doing and how. It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.
“It’s Google Maps,” said Eric Lander, president of the Broad Institute, a joint research endeavor of Harvard and the Massachusetts Institute of Technology. In contrast, the project’s predecessor, the Human Genome Project, which determined the entire sequence of human DNA, “was like getting a picture of Earth from space,” he said. “It doesn’t tell you where the roads are, it doesn’t tell you what traffic is like at what time of the day, it doesn’t tell you where the good restaurants are, or the hospitals or the cities or the rivers.”
The new result “is a stunning resource,” said Dr. Lander, who was not involved in the research that produced it but was a leader in the Human Genome Project. “My head explodes at the amount of data.”
The discoveries were published on Wednesday in six papers in the journal Nature and in 24 papers in Genome Research and Genome Biology. In addition, The Journal of Biological Chemistry is publishing six review articles, and Science is publishing yet another article.
Human DNA is “a lot more active than we expected, and there are a lot more things happening than we expected,” said Ewan Birney of the European Molecular Biology Laboratory-European Bioinformatics Institute, a lead researcher on the project.
In one of the Nature papers, researchers link the gene switches to a range of human diseases — multiple sclerosis, lupus, rheumatoid arthritis, Crohn’s disease, celiac disease — and even to traits like height. In large studies over the past decade, scientists found that minor changes in human DNA sequences increase the risk that a person will get those diseases. But those changes were in the junk, now often referred to as the dark matter — they were not changes in genes — and their significance was not clear. The new analysis reveals that a great many of those changes alter gene switches and are highly significant.
“Most of the changes that affect disease don’t lie in the genes themselves; they lie in the switches,” said Michael Snyder, a Stanford University researcher for the project, called Encode, for Encyclopedia of DNA Elements.
And that, said Dr. Bradley Bernstein, an Encode researcher at Massachusetts General Hospital, “is a really big deal.” He added, “I don’t think anyone predicted that would be the case.”
The discoveries also can reveal which genetic changes are important in cancer, and why. As they began determining the DNA sequences of cancer cells, researchers realized that most of the thousands of DNA changes in cancer cells were not in genes; they were in the dark matter. The challenge is to figure out which of those changes are driving the cancer’s growth.
“These papers are very significant,” said Dr. Mark A. Rubin, a prostate cancer genomics researcher at Weill Cornell Medical College. Dr. Rubin, who was not part of the Encode project, added, “They will definitely have an impact on our medical research on cancer.”
In prostate cancer, for example, his group found mutations in important genes that are not readily attacked by drugs. But Encode, by showing which regions of the dark matter control those genes, gives another way to attack them: target those controlling switches.
Dr. Rubin, who also used the Google Maps analogy, explained: “Now you can follow the roads and see the traffic circulation. That’s exactly the same way we will use these data in cancer research.” Encode provides a road map with traffic patterns for alternate ways to go after cancer genes, he said.
Dr. Bernstein said, “This is a resource, like the human genome, that will drive science forward.”
The system, though, is stunningly complex, with many redundancies. Just the idea of so many switches was almost incomprehensible, Dr. Bernstein said.
There also is a sort of DNA wiring system that is almost inconceivably intricate.
“It is like opening a wiring closet and seeing a hairball of wires,” said Mark Gerstein, an Encode researcher from Yale. “We tried to unravel this hairball and make it interpretable.”
There is another sort of hairball as well: the complex three-dimensional structure of DNA. Human DNA is such a long strand — about 10 feet of DNA stuffed into a microscopic nucleus of a cell — that it fits only because it is tightly wound and coiled around itself. When they looked at the three-dimensional structure — the hairball — Encode researchers discovered that small segments of dark-matter DNA are often quite close to genes they control. In the past, when they analyzed only the uncoiled length of DNA, those controlling regions appeared to be far from the genes they affect.
The project began in 2003, as researchers began to appreciate how little they knew about human DNA. In recent years, some began to find switches in the 99 percent of human DNA that is not genes, but they could not fully characterize or explain what a vast majority of it was doing.
The thought before the start of the project, said Thomas Gingeras, an Encode researcher from Cold Spring Harbor Laboratory, was that only 5 to 10 percent of the DNA in a human being was actually being used.
The big surprise was not only that almost all of the DNA is used but also that a large proportion of it is gene switches. Before Encode, said Dr. John Stamatoyannopoulos, a University of Washington scientist who was part of the project, “if you had said half of the genome and probably more has instructions for turning genes on and off, I don’t think people would have believed you.”
By the time the National Human Genome Research Institute, part of the National Institutes of Health, embarked on Encode, major advances in DNA sequencing and computational biology had made it conceivable to try to understand the dark matter of human DNA. Even so, the analysis was daunting — the researchers generated 15 trillion bytes of raw data. Analyzing the data required the equivalent of more than 300 years of computer time.
Just organizing the researchers and coordinating the work was a huge undertaking. Dr. Gerstein, one of the project’s leaders, has produced a diagram of the authors with their connections to one another. It looks nearly as complicated as the wiring diagram for the human DNA switches. Now that part of the work is done, and the hundreds of authors have written their papers.
“There is literally a flotilla of papers,” Dr. Gerstein said. But, he added, more work has yet to be done — there are still parts of the genome that have not been figured out.
That, though, is for the next stage of Encode.

This article is written from the perspective of research

scientists and it has an emotionally mixed message.  On 


the one hand there is a certain excitement that this huge 

new source of possibly helpful information is now 

available, and on the other hand there is a sense of 

frustration.  It's like they thought they almost had their 

arms around this monster (the human genome) and now 

they find the problem is thousands, perhaps millions, of 

times more complicated than they had originally thought.


I remember reading a comic when I was a kid which 


featured Scrooge McDuck.  If you don't remember, Scrooge


was Donald Duck's impossibly rich and incredibly stingy 


uncle.  One day Scrooge heard some noise from the street 


in front of his mansion.  A parade was in progress hailing 


some sultan as 'the richest man in the world."  After the 


parade,  they installed a large marble statue of the sultan in 


the town park on a pedestal on which was carved "the 


richest man in the world."  Now Scrooge took great offense 


at this (although why he should have, being a duck, did not 


occur to me at the time I first read it), so Scrooge quickly


built a much larger statue right near the sultan's proclaiming 


Scrooge McDuck as "the richest man in the world." Of


course the sultan responded with an even larger statue; 


McDuck built a silver statue; the sultan built a gold statue;


McDuck, a platinum statue, and so on, and so forth.  In the 


end the poor sultan dressed solely in a barrel (if you are too


young to remember, wearing only a barrel was a symbol of 


abject poverty dating back to the Depression Era), the 


sultan came knocking on Scrooge McDuck's door and was 


let in to a huge vault, the size of an Olympic swimming 


pool, that had merely a few piles of coins lying about.  

"Ah, ha," exclaimed the sultan, leaping for joy, "so you're 

broke, too!" "Don't be ridiculous," responded Scrooge 

McDuck, "this is only my petty cash vault," and he led the 

sultan through another door at the far end of this vault 

into a chamber the size of a football stadium where there 

were literally acres of cash and gold coins piled to the 

ceiling.


The sultan was dressed down for his arrogance in thinking 


that he had more money than any one in the world, when 


he had merely a fraction of McDuck's fortune.  What of the 

arrogance of evolutionary theorists who are constantly 


trying to 'simplify' the creation of life and the  

transcendent complexity of living organisms so that it can 

fit into their sad little theory of life being the outcome of 

a linear series of random replication 'mistakes?'  Darwin, 

without any modern optic technology available to him, 

thought that a cell, and therefore a single celled creature, 

which he considered to be the beginning of life, was an 

undifferentiated sac of albumen. 


Are you aware of the complexity of a living cell? Of a single 


celled creature, which has a genetic system and


which transcribes, translates its genetic code and which 


folds and manufactures and delivers the resultant proteins 


with the same precision that we do ours? Which senses its 


environment, has a way of distinguishing what is to be 


approached and eaten from what is to be avoided? Which


digests food, eliminates wastes, has a complete metabolic 


system that makes all these processes possible, replicates, 


and grows, and has a gene sharing system which is 


available to it when necessary and is so wondrously 


complex that it rivals anything that we humans accomplish 


biologically today (please read my posts 'Wonder' and 


'Evolution'), and which has, within its membranes,


thousands upon thousands of protein molecules, molecules


which this cell manufactured itself, each and every one of


which is, itself, a high tech, biological machine whose 


precisely engineered shape, precise pattern of charges, 


and precisely arranged chemical components allows it to 

do an absolutely specific task necessary to the survival of 

the cell.


And this, according to all geological evidence, was the very 


'simple' beginning of life, that Darwinists refer to, and 


occurred at the moment that the surface of the planet was


cool enough (below the temperature of boiling water) to 


sustain microbial life. There is no evidence whatsoever of 


so-called pre-biotic pools of organic matter slowly 


accumulating over millions of years to form such a cell. 

How could organic matter accumulate into this 

synchronized complexity?  In fact, there are no traces  of 

organic matter at all prior to these four billion year old 

traces of microbes. How could there be? In the boiling 

hot, meteor bombarded, tornado infested environment of early earth,

organic material would last no longer than it would take to


boil an egg (a raw egg, by the way, is precisely that, 


unprotected organic matter).  Even in our much more stable 


environment, organic matter of all life is protected from the 


elements by membranes and systems to control internal 


temperature and nutrient and water levels.



This is the same community that celebrated when it was 


discovered that only three thousand stretches of nucleotides 


were actual genes and which was eager to pronounce the


rest, close to three billion nucleotides, 'junk.'  Their theory is 


laughably inadequate to explain the complexity of life as we


know it, and much more inadequate to explain the 


complexity of life as 'they' know it.  This is why, I believe,


this amazing complexity is not taught in basic biology 


classes.  It is not hard to understand.  You can get it simply 


by knowing the number of molecules, and the precision of 


these processes, without having to memorize all the 


thousands of names that researchers have assigned to 


every chemical and organelle involved. The problem is not


that it is difficult to grasp, but that  it is wondrous, and 


evolutionary biologists who are committed to the idea that


everything about living organisms including their origin is


explainable by simple scientific laws and by the slow but 


random accumulation of accidents, do not want students to


feel overwhelmed, wondrous or awestruck by the 


transendent complexity of their own bodies......Too bad!


It was this community that announced with glee that they 


had found God and God was the genetic code; that the 


code consisted of only three thousands strands of 


nucleotides among the three billion found in each cell, and 


that as soon as they had figured out the sequencing of the 


human genome, they would complete their understanding of


the mechanics of life.  Sorry, my neo-Darwinist friends, you


thought you had found God, but you had only found his 


petty cash drawer.  Yes, the genetic system is magnificently


complex and magnificently coordinated; but the timing


system of the firing of those genes is exponentially more


so. Every different organ of your body, every different


organelle within each cell, every stage of development from


a fertilized ovum to an adult, is dependent on this firing 


system; not just on the genes, but on which genes are fired 


and when they are fired.



When scientists study the firing of genes they look at an


adult organism and study all the stimuli that are responded 


to by gene firing which leads to enzyme production.  We eat


something, or we do a physically demanding task, or we 


experience a big drop or rise in temperature.  These stimuli 


trigger a whole series of reactions which lead to a 'trigger' 


molecule bonding with a nucleic acid molecule within the


nucleus of the cell leading to transcription, translation,


protein folding,and protein delivery.  A system that is very


complex, absolutely precise and brilliantly constructed.  But 


all this pales compared to the firing of genes involved in the 


development of an organism from fertilized egg to new born.  


In this process billions of genes are fired every day in 


absolutely precise and coordinated sequences.  It is so 


impossibly complex that researchers dare not even 


approach it. 




So let's look again at the information uncovered in this 

article. There are three billion nucleotides folded, or coiled in 


each cell in the body.  There are one hundred trillion cells.


When the DNA strand of each single cell is unspooled that 


will yield an impossibly thin string (only a few atoms wide) 


that is, according to the above article, ten feet long.  I had 


previously heard that the strand was about a meter long. In 


that same article it said that if all the strands from every cell 


in a human body, in your body, were arranged end to end,


 that would create a strand that would stretch to the sun (not 


the moon) and back.  If, indeed, each individual cellular 


segment is ten feet rather than a meter, that would make


the accumulated length long enough to stretch to the sun


and back three times. That would be 558 million miles of


nucleotides, or, going in the other direction, a strand that


would stretch past Jupiter and half way to Saturn.


Understand, I am not talking about the accumulated DNA of 


humanity, which would be seven billion times as long (or 


slightly less than seven hundred thousand light years), but


just the DNA strands in your own individual body.  



Now I knew that the strands were coiled differently in


different cells. Why?  The protein 'trigger' molecule must 


find the right nucleotide to bind to in order to begin the 


process of transcription.  The ten foot strand of three billion


nucleotides have to be coiled so tightly that  there is still


room within the nucleus for the trigger molecules to float


around in the nuclear fluid. However, because of the 


tightness of the coil, only a small percentage of the genes 


and their triggers are accessible.  In, for instance, cells of 


the adrenal glands, the genes that carry the code for 


adrenal cortical hormone must be easily accessed.  In 


salivary glands, the genes for salivary enzyme must be 


accessible.  Each type of cell has its own special function


and manufactures a particular set of proteins unique to that


type; so the DNA must be folded in a way that makes all 


the genes and all the trigger nucleotides for the genes that


are commonly manufactured by that cell easily accessible


to the trigger protein molecules for those genes. There are


over two thousand types of cells; therefore there are at 


least two thousand different folding patterns.  Further


research may discover that the folding patterns may be


more specialized than that, and may be related not just to 


the specific type of cell, but to it's location in the body and 


the unique genetic demands that are made on that particular 


cell.



What I didn't realize, that I learned from this article, is that 


the triggers for certain genes may be thousands or even 


millions of nucleotides away from the actual gene, but 


because of the way the strand is folded, that trigger winds


up, although on a different portion of the strand, right next


to, or even abutting the gene.  That means that these, at 


least two thousand different folding patterns of, I remind 


you, three billion nucleotides, is so specific that the triggers


found perhaps several feet from the gene, wind up, after 


the coiling, right next to or abutting the gene; and they must 


abut the gene or the whole transcription process could not 


move forward.



What kind of a task would that be, to precisely fold one 


hundred trillion sets of three billion nucleotides?  If we 


assigned every person on the planet, say seven billion 


people, to work on this task, and we blew up the nucleotide 


strand several thousand times so that it was a size that


people could see, say the thickness of a pearl necklace 


with each nucleotide being a pearl, and since there are four 


different types of nucleotides that make up DNA, let's say


the pearls come in four different colors, white, black, pink 


and grey; then each person on the earth  would be given 


fifteen thousand necklaces (their one seven billionth share 


of the one hundred trillion strands found in each of the one 


hundred trillion cells of your body) each three billion pearls 


long.  Do you think that each person ,if there were room on 


the surface of the earth for all these enormous pearl 


strands, which there would not be (if the pearls measured 


fifty pearls per foot, then each of the fifteen thousand 


strands for each of the seven billion people on earth would


be over eleven thousand miles long!), do you think that


anyone would be able to fold fifteen thousand three billion 


pearl necklaces in an absolutely precise folding pattern if 


they devoted their entire lives to the endeavor?  Of course 


not.  They would have to fold one entire three billion pearl


necklace, an eleven thousand mile strand, each day for


forty-five years. I don't see how they could accomplish the 


precise folding of one necklace in a lifetime. And I remind 


you that these fifteen thousand strands, each eleven 


thousand miles long for every one of the seven billion people 


on this planet, represents the DNA folding, not for all of 


humanity, but just for one person, for you.



And that is just the physical impossibility of the task.  What 


of the precision?  Don't forget, the three billion pearl strand


has to wind up with exactly the right sequences on the 


outside of the coil to provide access to the right genes and


the right trigger molecules.  The folding must be absolutely 


precise, otherwise, when the strand gets folded over and 


over again the necessary sequences of gene pearls and


trigger pearls will wind up in the wrong place.  So no human 


could undertake such an endeavor without a plan, a design,


to follow; and you could imagine how complicated a plan for


folding a strand of three billion pearls, or nucleotides, or 


anything, would be.  So where is this plan?  It must be 


there.  Three billion nucleotides don't just fall into the exactly


right patterns of folds and turns randomly; and what over 


arching level of organization is there that distributes at least 


two thousand different folding patterns among the one 


hundred trillion developing cells?   There must be a 


guidance and that guidance must originate in a non-physical


idea and then materialize either directly into these different 


patterns, or into an intermediate, or astral, body of just 


positive and negative, or yin and yang energies, which 


guides the strands into place.



How could a spiritual idea simply manifest into something


physical? I can't explain it but I can point to a corresponding 


process where a spiritual, or non-physical idea or desire 


manifests into something physical. Every time you want to 


do something, that wanting, which is a non-physical, non-


measurable experience, the precise  thousands upon 


thousands of neurons  are fired, which begin a cascade of 


processes that winds up with you actually doing what you 


wanted to do. In the same way that human behavior and 


human creativity begin with a desire or an idea which is then


materialized; living beings, themselves, are the 


materialization of an idea which comes from a transcendent 


intelligence.



We all begin, at least all our equipment, our biological


apparatus, begins, from that one fertilized ovum.  The DNA 


in that ovum is folded in only one way.  As the genes 


mitotically divide so that that one egg becomes hundreds,


then thousands, then millions of different cells, what is the


governing principle behind the two thousand different 


foldings of the DNA?  Could the DNA, itself, be governing 


this?  Of course not.  DNA has to do with material, not 


shape.  Basically the same material that is in your arm


bone, is also in your  ribs and the bones of your big toes. 


How are the shapes of the 206 different bones of your body


determined?  It's the same material, made not only from 


the same genome, but from the same specific genes of that


genome.  The whole genetic system including the 


unfathomably complex firing system is the system by which


all the building materials get to exactly where they need to


be at the time they are needed during the development of 


the embryo.  How all that material is shaped into the bones


and eyes and hearts and livers and organelles within the 


cells, and blood vessels, and neurons and villi and sweat


glands, etc., etc., etc., is beyond the province of the genes.


So, by the way, is the amazing pattern of foldings, 


involutions, convolutions, twists and turns of the entire 


embryonic mass as it begins to develop.  Yes, each species 


goes through its own particular set of embryonic 


gymnastics, so that an ovum with a human genome will go 


through its own special set of acrobatics, and a chicken egg 


will go through its very different set.  These acrobatics then,


crucial to the entire shaping of the adult body, are related 


to the particular genome, but how could anyone say they 


were caused by that genome?



Isn't the fact that the genome is folded into two thousand 


utterly precise and different patterns in each of the one 


hundred trillion cells of our bodies, clear proof that there is a


higher level of organization to the human body, or any living 


body, than the genes themselves?  Isn't it so clear from this 


that the material of a living body does not cause the shape 


of that body; anymore than the shape of the body causes 


the material within it?  Isn't it obvious that both the shape


and the material originate and are caused by an idea, an


idea that comes from the cosmic consciousness, from the 


Godhead, from the mind of God, or from whatever you want


to call it; but from something that transcends both material 


and shapes, something that is spiritual and that far, far 


surpasses in its ability to conceive and create, both human


intelligence and human technology?



I wish ENCODE the best of luck.  I hope they make 


discoveries that will cure a thousand diseases.  I hope they 


all win Nobel Prizes and make billions of dollars for their


respective pharmaceutical companies.  For me, what is


most wonderful about these discoveries, is how it reveals 


the utterly amazing biological equipment that we all share, 


the transcendent brilliance and technological mastery of the 


creator of this equipment, and the increasing clarity with 


each new discovery of modern research, of how laughably 


inadequate our pathetic little evolutionary theory of 


sequences of random replication errors is to explain the 


true majesty and brilliance of living organisms.




Please comment!    

6 comments:

Wiseman said...

I thought your post was quite good ... until you had to invent God at the end. It seems that because you don't understand how the evolutionary process (not random, by the way!)works you use the "God" idea as an intellectual gap filler. If you are open minded enough to start with the hypothesis that God doesn't exist, I think you will be even more in awe of nature and be excited about what next we might learn in understanding everything.
At least we both agree that it is all utterly amazing.

Matt Chait said...

Wiseman,
What is the creative process of evolution that results in the extraordinary complexity of living beings? Do you mean by it's "not random" that it is guided by natural selection? But natural selection doesn't create, it selects from existing alternatives. Enlighten me, oh, wiseman.
Matt Chait

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daddyo422 said...

I noticed the Wisemans disdain at
the notion of a higher existence
of sophisticated intelligence.That
is a sad commentary of the lack of
logic that human pride has brought
us to!I did find it sadly amusing
that YOU were accused of having a
closed mind.I used to build.The idea that these structures built themselves is rather comical.That
simple building materials could randomly direct themselves into a
basic house,for example,defies logic.Paul was certainly right &
that was in a time when everyone had a god of some sort.Very good post,I couldn't have posted it any better.

Stephen Wilson said...

As a builder,i find folks like the
Wiseman to be a curiosity.You posted a very good comment & at the
mere mention of God,you're accused of being closed minded.lol.As a builder i have found no one that
holds the thought that structures
are self built.When i postulate
that they could've,we both have a good laugh.I go on to explain that
it's ridiculous to even entertain such an idea,with full agreement.
Why how could these simple building materials position themselves to bring about a house on their own? I can sense contention building,no longer is it
funny.I get pretty much the same
response as did you,usually with
more anger.I've found that without common sense & logic,wisdom is not likely,no matter how much knowledge one has acquired.Ive been called every degrading name,
but plug ahead.I most often never
hear from them again,sad really.
Have you read any of Hector Parr's essays?You might really enjoy them.Hope to post with you again.
Encode is very exciting as i've
survived stage 4 lung cancer for
three years now.My Dr.s cannot
explain this & with 12 grandkids,
it hits very close to home.The reasons of which are obvious.

Matt Chait said...

Stephen and daddyo,

You both used the same and very telling analogy. Thank you. To continue it, once these materials build this house (the human body) by themselves, science has yet to discover anyone living in, using and enjoying this house. Where is the human being who inhabits this human body? Science describes in great detail the mechanical/electrical camera that is the human eye, but where is the being that looks through that camera to visually experience the world? Science goes on to describe that amazing mechanical/electrical recording device that is the human ear, but no one to use that ear to listen to the sounds of the universe. Even if you buy into this impossible method of building a house, there is nothing in science that allows this house to become a home.