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Nerve Growth Gene Action Implicated In Depression

CognitiveScience Sunday, October 17, 2004 . This is a SciScoop post by Ricky James

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The scientists applied microarray technology, a powerful new tool used to create gene expression profiles, to biological samples from specific areas of the brain at autopsy. Recently deceased people who had suffered from major depressive disorder or bipolar disorder were compared to controls who had no mood disorder. Those with major depressive disorder had different amounts of fibroblast growth factors than the controls. Those with bipolar disorder did not show these differences.

Information gleaned from specific genetic profiles, however, can help pinpoint what biological mechanisms are impaired so that more specific drugs with fewer side effects can be developed, according to Jones.

“Targeted therapeutics made possible by these new technological approaches offer the dream of ‘personalized medicine,’ in which knowing each person’s genetic make-up can help determine how he or she should be treated,” said Prabhakara Choudary, adjunct professor of psychiatry in the UC Davis Center for Neuroscience, who is co-investigator of the study. “I think this study moves us one small step closer to that goal.”

Choudary also said that the fibroblast growth factor system may one day be useful in developing an accurate tool for diagnosing major depression.

18 Responses to Nerve Growth Gene Action Implicated In Depression

Anonymous

October 19th, 2004 at 8:05 am

Speaking personally, as a long-time sufferer of chronic major depression (through suicide attempts and hospitalizations), I’m uncomfortable with the assertion that depression “is a behavioral consequence of gene action”. Not that I disagree with this study, or countless others that suggest an organic component to major depression — not at all. I’m just uncomfortable with the implication that that’s what depression is, rather than that being part of what depression is. I think there’s also a component of depression that can be described as “learned patterns of negative or self-defeating thinking, which can be broken or un-learned given a lot of training and work.” The successful treatment of many major depression sufferers through cognitive behavioral therapy suggests this.

The degree to which organic origins of depression, versus maladaptive patterns of thought, are present in any single depression sufferer are of course going to vary from person to person. Indeed, it’s not even that easy to draw a boundary between the two, since biochemical depression helps reinforce bad thinking, while evidence exists that repeated bad thinking can effect brain chemistry. But I think it’s important to point out that organic brain issues are only part of the depression puzzle.

The reason that it’s important to point this out is twofold. First of all, many depression sufferers do not respond well to drugs, or spend a long time trying to find a drug that works well for them. The stress upon the biological component leaves many of these people thinking “so, maybe I’m not depressed after all; maybe I’m just a weak person,” which is counterproductive. And secondly, health insurers are trying very very hard to cast depression solely in the bio/chemical domain because they do not wish to pay for talk therapy of any kind, despite scads of evidence that a combination of drugs and therapy predicts the most favorable outcomes. To fight this, it’s important to resist depression being defined in such terms.

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rickyjames

October 19th, 2004 at 6:57 pm

Well, I think your approach is more valid than the two extremes that have been bandied about on this site in months past.  Depression IS a major puzzle with many components.  I agree it’s not just biochemical, and I stress it’s not just behavioral, either – there’s indeed a yin and yang aspect that is an interplay of both.  

I too have personally suffered from severe long-term depression but fortunately never QUITE got to the suicidal level like my mom did.  I was sure on the elevator with my finger hovering over the down button a few times, tho.  As far as the “learned patterns of negative or self-defeating thinking, which can be broken or un-learned given a lot of training and work”, I am SO with you on knowing what THAT’s like, with years of therapy to finally break that pattern.  SSRIs were literally a lifesaver in the meantime.  

Once again, I say to others reading this who are battling the demon of depression on their own:  You are not alone, and there is help to be had.  The first step is acknowledgement and acceptance not only that there is a problem, but that there is a solution as well.  It’s not an easy, or simple, solution – but definitely one worth pursuing.  Go for it.  Read.  Talk.  Act. Smile.  Live.

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mtigges

October 19th, 2004 at 9:26 pm

There have been vivid discussions on sciscoop about depression. There in fact has been some rather emotional reaction from those considering themselves afflected directed towards those not so unfortunate. The reason for it, the negative emotion, to me was quite puzzling. But interesting.

I have no ability to comprehend depression or the suffering of afflicted and their loved ones. The emotional discourse that I allude to involved someone similar to me, I think; someone that couldn’t comprehend depression. I think it comes down to what kind of a toolset you have. I simply don’t have a framework withen which I can effectively rationalize about depression. It reminds me of a choice line Bones delivered to Spock in “The Voyage Home” … do I need to suffer from depression in order to discuss it with you? I’ve up to this point stayed far away from these conversations.

As my undirected rambling no doubt has tipped you off enough to judge for yourself, I have had just enough tonight to toss in my 2 cents. But maybe it’s only worth half a cent at this point.

I trust R James. Having never met him, I don’t know him, but he definitely fronts himself as trustworthy. I know enough about him to know that in his life he hasn’t any reason to suffer depression. Withen the bounds of “acceptable for happiness” my judgement is his life and his lifes work rates highly. So it is with outside observation that I have to, reluctantly, admit there must be something to this depression thing.

I don’t, nor have I ever suffered from depression. I mean to say that I don’t understand it. And I have been in the camp that argues … “suck it up, cheer up, love thy neighbour.” Find happiness. As silly as it sounds, I think I’ve changed my mind reading here. I haven’t sought information about depression, merely because it doesn’t rate in my sphere of interest, but this site does because of it’s range. And so I’ve been presented with the opportunity to learn a little. And it’s been enough.

Heed Rickys advice.

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calia

October 20th, 2004 at 8:17 am

I know why it is important to understand where people are coming from no matter what their particular hardship happens to be.   But is it too much to take into consideration that critical thinking sometimes requires that one expose psychological and or physical conditions to deeper scrutiny?

Is it really a matter of being too hard-nosed?  Or are we possibly in a particular difficult situation due to not being willing/able to go far enough?

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Anonymous

October 20th, 2004 at 12:41 pm

Hi. I’m the ULF that replied to the original post.
There are a lot of things that your post brought to mind, and I’m trying hard to impose some sort of structure on them so that what I’m saying doesn’t come across as disjoint/unrelated ramblings. If some of it seems that way, I apologize in advance.

First of all, just to add another datapoint to the list of people who probably shouldn’t have depression, but do, I think it’s fair to say that on the basis of my accomplishments and the things I’ve been blessed with in my life, I don’t have much of a “reason” to be depressed. I have a Ph.D. in astrophysics from a major research institution; my dissertation won an award. I’ve subsequently done research, some of which has been pretty well known in my little corner of my field, at some of the most prestigious research establishments in the U.S. Before grad school, I spent years as a volunteer “Incident Commander” running large-scale emergency operations (mostly, backcountry search and rescue operations) for the National Park Service and state authorities, and also acted as an EMT for a reasonably busy local EMS responder. I was pretty successful in both of those pursuits; it’s fair to say that there are people alive now who would not be were it not for my efforts and the efforts of friends with whom I worked. Most importantly of all, I have family and friend who I love dearly, and who in my better moments I’m able to realize love me as well.

I also have depression — a depression that’s resulted in two suicide attempts and one full and one partial hospitalization. I had to leave a field I loved, and had trained for for over a decade, simply because I found it so hard to focus my mind on what I was doing anymore that I wasn’t accomplishing anything at all. If I made it in to work at all, it was to sit at my desk, stare into space, and possibly hide my tears. Other days, it was a major accomplishment to simply get out of bed. I don’t have any good external reason to be like this; I’ve had a lot and I’ve accomplished a lot. And much of what I’ve accomplished has been pretty goddamned hard, hard enough that in my better moments I’m able to tell myself “you know you are not weak.” But here I am.

You ask whether you have to suffer from depression to discuss it with someone who is depressed. To me, it depends on what the intent of the discussion is. I don’t think one can truly understand anything without experiencing it — whether it be depression or love or grief or joy of discovery. It’s similar for empathy; without experiencing the same sort of pain as someone else, I don’t know how one can empathize with them. But a partial understanding, and sympathy rather than empathy, are both possible and worthwhile.

At the same time, while I sit here and say “yes, depression is real” and “partial understanding and sympathy are both possible and worthwhile,” I feel like it would be intellectually dishonest of me to not say that it’s a tough road to hoe. Put bluntly, it’s very challenging to be supportive of someone suffering from depression without supporting the depression itself.

What do I mean by that? This is something that takes most depression sufferers a long time to accept deep down (and many never do): if things are going to change (that is, get better than they are), they’re going to change because of things the depression sufferer does. They’re not going to change magically on their own, and they’re not going to change because of something someone else does. If they change, it will be because of changes in what the person who has depression is doing. This is obvious when you think about it: for example, for antidepressants to have any effect at all, the person suffering from depression has to be willing to take them, and has to do so. For therapy to be of significant benefit, the patient has to go, has to take it seriously, has to open up, has to be honest, and has to work hard. The responsibility for getting better falls to the depression sufferer.

Many people with depression resist this consciously, and I think most depression sufferers spend at least some of their time with depression resisting this subconsciously. I know I have. Part of it is that if one is not careful, speaking to a depression sufferer of “responsibility” can sound like you’re speaking of “blame.” The analogy with someone going into physical therapy after an accident is useful: it was not your fault that a drunk driver hit your car, and it’s not your fault that right now you can’t walk normally; but you have the power to change that, and nobody else can do it for you. Are you going to do it?

Another reason why people with depression can resist responsibility is that this decision — the decision that “it’s not going to get better unless I do things to make it better, so that’s what I’m going to do” — takes clarity of thought and mental strength of will, and those are exactly the qualities that depression attacks. Perhaps the single worst thing about depression is that the qualities it affects most strongly are exactly the qualities needed to fight it. It’s hard to say “I’m seizing the day; I’m going to do things that help to ameliorate my depression” when it’s taking everything you’ve got to just get into the shower.

So this is why I say friends/acquaintances of depression sufferers have a tough road to hoe. “Cheer up! Just feel better!” is unhelpful, even hurtful; but so is “I understand you feel lousy; go ahead and go back to bed.” Better is “it’s not your fault you have depression, and you are not a bad person for having depression; but it is possible to feel better, even happy, provided you’re willing to start taking very small steps down the long, hard (but ultimately worth it) road. And I know it’s very very hard. But it’s worth it.” But on some days, some depression sufferers really don’t wanna hear that (I know I have days when I don’t). And sadly, some depression sufferers won’t wanna hear it at all.

Finally, you say that you’ve noticed negative emotion from people who identify themselves as suffering from depression towards people who do not. I don’t doubt it. For one thing, depression sufferers understandably react negatively to people saying the “just feel better!” cliches to them. Other times, people are saying much more constructive things (e.g. all the stuff I wrote above), but communicate it poorly so that it sounds like “just feel better!”, or are speaking to a depression sufferer who’s not ready to hear it and so is incorrectly hearing “it’s your fault you’re depressed” instead.

There’s a lot more relevant stuff I could say, but this is already way too long. I hope some of it is interesting or useful to you or someone.

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Anonymous

October 20th, 2004 at 1:06 pm

I’m not entirely sure I understand what it is you’re asking, and I want to be sure before I write a bunch of stuff that ends up having nothing to do with what you mean to say.

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rickyjames

October 20th, 2004 at 1:17 pm

Your post is deeply insightful and on target on a most crucial topic, please feel free to continue.  In case you missed it, SciScoop recently ran a major poll on the subject of depression which generated a huge response, as well as a number of relevant articles over the past months and years.

Currently just outside the entrance to my subdivision is a billboard I pass daily that reads “Mental Illness: It’s a brain disorder and it’s treatable.”  I feel strongly about spreading that word and doing my bit for casting my paltry light into the vast darkness surrounding this topic.  I’ve certainly had my share of contact with this blight, which in many ways seems to afflict the intelligent among us more severely.  I’m convinced the human brain is a VERY precisely tuned turbo-charged high-output biochemical engine and any evolutionary / genetic tweaks to make it go “faster” are going to cause other parts of it “run hot” and “squeak” from the resulting “friction”.  So to speak.    

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rickyjames

October 20th, 2004 at 1:27 pm

Sorry, I can’t help myself, and I certainly mean absolutely no disrespect to you, Cal.  Dear ULF, you will find that trying to zero in on Cal’s points is an exercise in Lorenzian relativity…

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calia

October 21st, 2004 at 8:52 am

Either knowing (or having) too much is likely a cause for distress and depression in some people. (I.e. when is enough ever “enough”)

But since I CLEARLY do not suffer as a result of knowing too much, it would be kind of you, R, to create a link to explain what ‘Lorenzian relativity’ is.  I’m guessing it’s in reference to something I’ve done that has driven you crazy.  

Otherwise, how should I know?

thanks

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rickyjames

October 21st, 2004 at 11:39 am

Well, first off, I misspelled his name: the guy I mean to be talking about is Lorentz, not Lorenz.  There are famous 19th Century scientists by both names and they even worked on the same things, so it’s easy to confuse the two of them.  

Anyway, Lorentz came up with many (but crucially, not all) of the basics of relativity theory a decade or more before Einstein did.  Lorentz  basically developed some (correct) equations (the Lorentz transformations) to explain away one specific problem, namely the seminal Michelson Morley Experiment of 1887.  These equations are now called “Lorentzian relativity” and are seen as an incomplete view of relativity – correct as far as they go, but they don’t go far enough to explain what really needs explaining.   Lorentz started from one PARTICULAR problem and came up with a SPECIFIC answer to that one problem.  Einstein read about everything Lorentz had done, then in 1905 started with a blank sheet of paper and came up with a GENERAL solution to ANY situation  associated with relativity.  That’s why Einstein and his math instead of Lorentz and his math is remembered as a household name today – Lorentz’s viewpoint was too narrow to be considered “truth”.

The other key analogy I was driving at was that it was Lorentz that first realized that different observers with wristwatches (one moving, one stationary) would be unable to agree on exactly what time it was because of the effects of relativity.  

Again, absolutely no disrespect intended, Cal.  I just often find understanding your writings and the points they’re making to be moving targets.  They are, however, always thought-provoking and very worthwhile.

 

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calia

October 22nd, 2004 at 8:15 am

General Relativity, I see now.  I do understand basic relativity principles.  I just thought that you were referring to something out of the ordinary.  (does explain why a search didn’t come up with anything useful tho)

If you want to to apply GR to personal experience, however, I’d suggest first that Relativity works because the laws of physics are basically uniform, correct?   So even tho events in life do impact various people differently, the principles that fix the errors in thinking, I believe, must at least offer the same results.  

True?

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rickyjames

October 22nd, 2004 at 9:07 am

Well, Cal, associating relativity and personal experience can branch off in two directions, one scientific/physical and the other philosophical.

In one sense relativity is all about personal experience because it defines what we are going to observe in a particular situation, and also defines how our observations will be unavoidably different from the observations of the exact same event by another observer elsewhere in space and time.  

In a philosophical/political sense, relativity is really about how there is no absolute “right”.  In this sense, relativity is a “politically liberal” rather than a “politically conservative” theory.  So you might say that Albert Einstein is an even bigger liberal than John Kerry, and that George Bush hasn’t a prayer of understanding the valid viewpoints of either.

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calia

October 22nd, 2004 at 10:34 am

I recognize what you’re saying about Relativity possibly branching off into different directions, categorically speaking.   But still, in the scope of any discussion, it is best to start with what one knows is true first, and then work his way outward to other ideas from that point.  

This is how I know, for instance, that evolution is [not true].  I began with physics, and then moved on to chemistry.   And somehow I know very well that I can make true and factual statements about both without including biology in the discussion at all.  The same cannot be said of biology.   (I learned this from W. Heisenberg, btw)  Making factual statements regarding biology absolutely cannot be done without including physics and chemistry concepts in an “accurate” description of the phenomena.  Based on such knowledge, how can any idea related to science be interpreted through evolution?  

It simply can’t.  Biology and or evolution cannot stand alone without sets of predominant principles that are more true than itself.  

Relativity, then, is only useful in any sort of a discussion if one notes what is true, uniform and consistent first.   So I can’t see that  Relativity, as a physics concept, has actually created an environment where there is no absolute right and wrong at all, though some people might interpret scientific principles that way regardless of what the principle might happen to be.  (and what the end result is expected to be)   It is their interpretation method which is flawed, and thus so  must the conclusion be.  

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rickyjames

October 23rd, 2004 at 7:18 am

From depression to relativity to evolution in one discussion.  That’s why I like this site, and why I wish there were a hundred posters like you, Cal, even if we respectfully agree to disagree.

I understand what you are saying about starting with basic sciences like physics and chemistry (which is really applied physics of atoms) and working up to biology and evolution.  The trend extends to even “softer” sciences like psychology and sociology – yeah, there’s science in there, but it becomes increasingly harder to justify it as such.  

However, I don’t consider evolution a “soft” or “fuzzy” or “wrong” science at all.  The past fifty years of DNA research gives us hard scientific proof of its existence and principles.  The whole field of “molecular biology” has sprung up between chemistry and biology and is much more of a “hard” science like chemistry than a “soft” one like biology.  DNA mutation provides both the mechanism and the tracability to consider evolution in all living organisms including ourselves as a hard, bedrock scientific reality.  I maintain that anyone who states otherwise has a non-scientific political/religious agenda they’re pushing, period.

Now if I understand your argument right (and I never seem to), you’re saying that because evolution science REQUIRES molecular biology as a prerequisite, that somehow evolution science cannot “stand alone”.  Well, that’s true.  DNA  mutations don’t fall out of apple trees and hit you on the head to initiate a breakthrough “aha!” moment of discovery.  But just because evolution doesn’t “STAND ALONE” doesn’t make it WRONG.  The two are unrelated.  Any connection between the two is one YOU’VE made yourself for religious/personal reasons.

Now in a broader sense, NOTHING in science stands alone and is truly basic – even and especially not in physics, which is what we normally think of as the “first principles” science.  Consider gravity, something with which every human being throughout history has universal firsthand experience.  Nobody denies the existance of gravity like they deny the existance of evolution, solely because the former is (often literally painfully) obvious and the latter isn’t.   Yet even for something as intrusive and obvious as gravity, civilization for thousands of years had a variety of basic physics ideas about gravity that were flat out wrong and not even worth summarizing here until “the apple hit Newton on the head” and he came up with Newton’s Laws, which where the first consistent set of basic principles on gravity that everybody acknowledges their universal validity provable through repeated experiment.  

But even Newton’s Laws of gravity are an incomplete description if you begin to consider gravitational effects at places and circumstances other than beneath apple trees.  Start thinking about neutron stars and black holes and Newton isn’t good enough; you need Einstein and relativity theory to explain the “way things fall”.  

Now we’re looking beyond apple trees, beyond black holes, and starting to think about things like quantum foam and superstrings.  Neither Newton or Einstein is good enough to explain what we might see in these realms – and one day somebody with a bright idea in these areas will join the names of Newton and Einstein as household names, and give us capabilities far beyond accurate artillery and interplanetary navgation and GPS location systems.  Teleportation and warp drive, perhaps?

THe point is, NO AREA of science may be considered “most basic” or a “fixed and unchangible starting point”.  Rejecting other areas of valid science like evolution simply because they’re “not a basic science” shows a basic misunderstanding of what science is.  

Alluding to your last sentence, REAL progress in science isn’t just about identifying flawed final conclusions – it’s about identifying flawed initial assumptions.  THe mindset for accomplishing THAT is one that says all viewpoints have some merit, all sides must be considered, etc…er, a liberal viewpoint, not a rigid conservative one of absolute rights and wrongs.  

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calia

October 24th, 2004 at 11:21 am

“However, I don’t consider evolution a “soft” or “fuzzy” or “wrong” science at all.  The past fifty years of DNA research gives us hard scientific proof of its existence and principles.<<

Establish a WORKING food-chain out the existing fossil record then, if you can.  It is a basic physics requirement.  And if it can’t be done, the whole theory is suspect.

Is evolution a law comparable to gravity?  I don’t think so, Ricky.  Evolution is an idea that depends on a massive succession of other laws to be usable at all.  To be factual, it would have to not FLIP FLOP every time other disciplines show its original premises are worthless.  Mild adjustments to a theory are one thing, total revisions another.      

Based on all of the above, I know instinctively that this is and always has been a war of pure self-will, & not science.  

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rickyjames

October 25th, 2004 at 3:20 am

Huh.  Before you said evolution science was flawed because it depended on “upstream” basic hard sciences like physics and chemistry.  Now you say evolution science is flawed because it depends on “downstream” derived soft sciences like palentology and ecology.  Is that a flip flop?

What specific palentological food-chain discrepancy are you talking about?  I wasn’t aware there were any.  I say evolution science in humans (which is where your religious bone of contention, er, Adam’s rib, is) doesn’t depend on fossils and foodchains.  People aren’t in the middle of a food chain web unless they’re surfing in shark-infested waters or biking and hiking in puma country.  A food chain argument is an argument against exercising, not evolution.  

Remember always, Cal, that absence of evidence is not evidence of absence.  Gaps in the fossil record are a given; that we have fossils at all of a specific creature that lived tens and hundreds of millions of years ago is prectically a, well, miracle.  Deal with it.

“X is an idea that depends on a massive succession of other laws to be usable at all.”  Cal, name me ONE SINGLE AREA OF SCIENCE that can’t be substituted for X!  That’s my whole point in my last post!   If this fact bothers you, then abandon science as a pursuit and an interest and go beat on a log drum and chant to the rain god.  Or play an organ and pray to Jesus.  Whatever.

“To be factual, it would have to not FLIP FLOP every time other disciplines show its original premises are worthless.”  Duh.  To be SCIENTIFIC, it DOES have to flip flop every time other disciplines show original premises are worthless.  That’s what I meant when I said real progress in science comes from proving initial assumptions, not just final conclusions, are false. But forget about this truism (since you obviously have) – what specific premise of DNA mutation causing evolution has been totally revised to make evolution theory worthless, and how come you didn’t post a story about that discovery here on SciScoop?  I must have just flat out missed THAT press release…

This isn’t a war of “pure self will, not science” – it’s a war of YOUR self-will VERSUS science.  And so we’re back to Lorenzian relativity, both wearing wristwatches and arguing about what time it is.  You’re stuck stationary in a rut outside the Dayton Courthouse where the Scopes Trial was held just up the road from my boyhood home, and your clock reads somewhere in the 1920s.  I’m typing up new science stories as fast as I can, and my computer clock reads the 21st century.  Relativity theosry says we’ll never agree.  I’m moving on – see you later.

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calia

October 26th, 2004 at 8:52 am

“As the brilliant 17th-century scientist, mathematician and philosopher Blaise Pascal put it: “All human evil comes from a single cause, man’s inability to sit still in a room.

We need to do the most painful and difficult thing in all of life – which is to stand still and allow the anxiety of our wrong way of life to catch up with us. Don’t run away. Feel what you feel, see what you see, observe everything, but react to nothing – all with a wordless cry to God directly from your soul: Help me. Hang on to your faith that regardless of what problems, sin and corruption you see lurking inside, God can and will help you, if you’ll be faithful and watch. And somewhere, through that obedient stillness, from beyond time and space will come real understanding, and new “programming” from another dimension, called Grace.”  

“The media matrix” by David Kupelian

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calia

October 26th, 2004 at 9:03 am

cont.

“In the days prior to the evolution matrix program – that is, from the beginning of human life until Darwin came along in the mid-19th century – human beings would step outside their homes and survey with their eyes and minds the wonders of nature. They’d see majestic 400-year-old redwood trees, hummingbirds that were able to hover, and honeybees that somehow knew how to do a special figure-eight dance that would communicate to all of the other worker bees the precise location of the dancer’s newly discovered nectar source.

Looking in every direction, we humans beheld not only fantastic complexity, diversity and order, but also the supreme intelligence behind creation, as brashly evident as the noonday sun.

This ubiquitous natural wonderland caused man to acknowledge and honor the Creator of creation, as Copernicus did when he wrote, “[The world] has been built for us by the Best and Most Orderly Workman of all.” Or as Galileo wrote, “God is known … by Nature in His works and by doctrine in His revealed word.” Or as Pasteur confessed, “The more I study nature, the more I stand amazed at the work of the Creator.” Or Isaac Newton: “When I look at the solar system, I see the earth at the right distance from the sun to receive the proper amounts of heat and light. This did not happen by chance.”

Did not happen by chance?

Ever since Darwin and his successors succeeded in loading the evolution matrix program on mankind – a fantastic theory for which there is no proof, and many serious problems – when we now walk outside and look at the created universe, what do many of us see? Chance!

Although our eyes survey the same wonders of God’s creation that inspired faith in our predecessors, in our minds today we see only the meaningless result of millions of years of random, chance mutation. That’s what our minds “see” – the eternal dance of purposeless recombination of ever-more-complex forms, but all without meaning, without spirit, without love. And by direct implication we also “see” that man is not a fallen being needful of God’s saving grace, but merely the cleverest, most evolved animal of all. Since evolution by definition always results in improvement and advancement, man and all of his violent and lustful and selfish drives are perfectly normal and natural and … advanced. There is no good and evil, no Heaven and Hell – and man, as a highly evolved monkey, has no sin and no guilt – as these are logical impossibilities from the evolutionary point of view.”  -  Kupelian

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