Sunday, October 02, 2011

Double Jeopardy Against Evolution

It is difficult today to talk about “The Evolution Theory”: There are many proposed evolutionary theories, as evolutionary scientists try to skirt the evidence against evolution provided by math, science and new knowledge.
Most evolution theories rely on two concepts: the concept of random mutations, and the concept of change by adaptation. Both concepts further rely on the process of elimination, which says that those individuals that are not viable, or less able to cope, will be unable, or less likely, to grow and reproduce.
The concept of random mutations has been analyzed and demonstrated impossible, for patterns or systems over a certain complexity (Maximum Complexity Limit for Random Generation, or MCLRG) in the article: “You do not need a book, but only a word”. The impossibility of random mutations as a mechanism for generating new species, or generating any one of the many systems or sub-systems required for the survival of an animal species is so compelling, that we must discard random mutations as part of any scientific argument for evolution.
The process of genetic adaptation to the environment involves changes in the genetic information of an individual that are passed to an individual’s progeny. Since this process cannot happen through random mutations, then genetic changes must happen (through a mechanism yet to be conceived) during an individual’s growth to maturity and before reproduction.
If genetic changes are not driven by chance, then other reasons must prompt it. Some suggestions are: a) the individual need (necessity) to better develop and survive in the struggle of life, or b) a pattern of repeated incidents, or experiences that force an individual to change itself.
Both concepts are similar, but the first is driven internally, while the other involves repeated external events that force the individual to react.
The blood coagulation sub-system, which is present in all blood circulating mammal species, presents a double challenge to evolutionary processes:
1.                  The blood coagulation sub-system is “irreduceable” and the quantity and organization of information required to define it is above the MCLRG limit, and
2.                  It is a system which cannot be “recognized as useful” by any non-intelligent process which might be conceived, until it is too late to generate one.
Thus we can state that the blood coagulation sub-system of any blood circulating animal species could neither have been generated through genetic mutations nor through genetic adaptation.
Explanation of point number 1.
The blood coagulation sub-system (part of the blood circulation system of blood-circulating animal species) is in many ways irreduceable. We will focus here on just one of the mechanisms of the coagulation sub-system: the “coagulation cascade” mechanism. This mechanism (and its description) is irreduceable, because it needs to be described as a specific and unbroken sequence of chemical reactions.
Furthermore, in our calculation we consider just two aspects of complexity: the type of chemical involved and the order (or sequence) of its intervention. We do not consider the amount of time of the intervention, or the quantity of each chemical needed. Describing these other aspects would be even more complicated.
In the coagulation cascade at least 37 chemicals, enzymes and proteins (24 Factors, plus at least 8 Co-factors and 5 Regulators) come into play at the exact moment and are highly dependent on each other in order to work. If any of these factors were not present, the coagulation process could not happen. Some of the Factors are chemicals that need to be present in their original form, such as Fibrogen (Factors I) and Prothrombin (Factor II), and are “activated” at the right time into Fibrin (Factors Ia) and Thrombin (Factor IIa).
Note that the coagulation cascade process itself cannot happen by chance every time an individual is in the process of losing blood, but it has to be pre-determined and described in the genetic information of each blood circulating individual. In addition, note that we will not try to explain or even guess the details of such description in the genetic code, but we only need to determine the complexity of such description, at least as it relates to the number of variables involved, to find the probability of it being generated by a random process within a certain time (Point number 1).
We have excluded from our calculation the additional chemicals involved in Fibrinolysis (introduced below), which may also be thought as part of the coagulation cascade mechanism.
To be very safe, we will also exclude any possible “dependent variable” (For example, we will exclude “activated” factors, such as Fibrin, which is dependent on Fibrogen). We will also exclude the TF and the TFPI factors.
This reduces the number of independent chemicals to only 25 (12 Factors, 8 Co-factors and 5 Regulators) that need to intervene in a specific sequence in the coagulation cascade.
Reducing the “cascade” to a sequence is also a simplification, as the order of chemical interventions, in reality, is not mono-dimensional (see the coagulation cascade diagram).
By following the same reasoning presented in “You do not need a book…” we can think of these 25 chemicals in a specific sequence as characters in a specific string (or “word”), describing our simplified coagulation cascade.
Next, we need to find how many choices are available for each “character” (that is, the “keyboard” in our analogy). How many descriptions of chemicals can a random process generate? Theoretically any chemical that can be produced. This number could be very big.
To be safe, we will assume that we have only 35 chemicals to choose from. These are only some of the chemicals we know are involved in the coagulation cascade, excluding the TF and the TFPI factors, excluding the chemicals involved in Fibrinolysis and other coagulation mechanisms, and excluding all the other chemicals that could possibly be generated in that environment.
After applying all of these simplifications, considering only 35 chemicals to choose from, the number of trials (occurrences) required to possibly generate our chemical sequence (our 25 character “word” describing a simplified coagulation cascade) through a random process is 3525, which is about 4 x 1038. This number is twenty orders of magnitude bigger than the MCLRG limit. This proves that a simplified description of the coagulation cascade mechanism of the blood coagulation sub-system could not be generated by a random process generating one occurrence every second, given as much time as the age of the universe.
Just for comparison, if we only used 12 Factors in our calculation (excluding all the Co-factors and all the Regulators), then the number of occurrences required would drop to 3512. This number is still three times larger than the MCLRG limit and would be enough to prove our point.
You might have guessed by now that the blood coagulation sub-system is much more complex than just the coagulation cascade mechanism. If you want to know a little more about it, you can check the overview in the APPENDIX below, or you can check the literature on the subject.

Explanation of point number 2.
The blood coagulation sub-system is different with respect to other systems because:
a.      An individual would not realize, or find out from repeated experiences that one such system is needed until an accident causing bleeding occurred.
b.      Such an accident would be always fatal, leaving no time for genetic adaptation.
How do we know that such an accident would always be fatal?
Hemophilia type A is a congenital disorder where people have lower levels of the clotting Factor VIII (Factor VIII deficiency). Hemophilia type B, a more serious form of the disorder, is the deficiency of Factor IX. Without treatment, the blood clotting process in people with hemophilia, especially type B, is slowed down.
In severe hemophiliacs even a minor injury can result in blood loss lasting days or weeks, or even never healing completely. In areas such as the brain or inside joints, this can be fatal or permanently debilitating.
Medical researchers tell us that before hemophilia could be medically treated it was fatal in people and that the average hemophiliac would not reach the age of maturity.
As we mentioned, hemophilia is the deficiency of one factor in the coagulation cascade examined under point 1, but not necessarily the lack of a Factor.
In our hypothetical case however, we are talking about the lack of all coagulation factors, the lack of all coagulation mechanisms, in fact the lack of the whole coagulation system. Thus there is no reason to believe that an internal or external beading in an individual without a coagulation system could stop for some undetermined reason, preventing the individual’s immediate death.
Point number 1 examined earlier, among other things, excludes the possibility that an individual could be born “by chance” with a functioning blood circulation sub-system. Thus if we exclude an intelligent process of generation, any and all species must have existed without a blood coagulation sub-system. Let’s take a healthy blood circulating individual without a blood coagulation sub-system: If this individual happens to grow to maturity and reproduce literally without a scratch, it will generate progenies without a blood coagulation sub-system. This is because no process of adaptation will initiate, as there is no “need” for a blood coagulation sub-system. Assuming otherwise would mean that genetic adaptations could be started without necessity, i.e.: “by chance”, thus falling within the category of random mutations, which have already been dismissed.
If instead the individual happens to start bleeding, then the adaptation process has to occur within the few minutes the individual is still alive, before it loses too much blood and dies. To be able to successfully procreate, our bleeding and dying individual would have to be a male, as its progeny could only be conceived and brought to gestation by a surviving female individual of the same species. However, because of the complexity shown in point 1, including the requirement for the presence of fully developed mechanisms to prevent exactly this event (a loss of too much blood), a genetic adaptation happening within minutes is also physically impossible.
For example, assuming that the process of genetic change is not random, but directed by some kind of “program”, then our bleeding individual, already under stress and in the process of dying within minutes, would have to:
-         develop all the specifics of a complete blood coagulation sub-system (without much help from its own genetic code, which never had such a system). There is no theory postulating that this can be accomplished at all, without involving random mutations. If one theory could be conceived, then even with an intelligent plan, all the right chemical and biologic elements, and within a favorable environment, this process (creating such plan using biological elements, not pen and paper or a computer) would involve chemical reactions and biological changes which would require more than a few minutes, then
-         from the specific plan of the coagulation system, the individual would have to develop the genetic information (amino-acid sequences) needed in the DNA describing the coagulation system as part of the DNA of its species’ genes, so that this individual’s progeny could develop a coagulation system at birth. This process would requires more than minutes, because of the slow speed of sequencing amino-acids and replicating DNA, then
-         transmit this new genetic information in its entirety to its own already existing sperm (no known process has been discovered or proposed that can do that) or discard all of the existing sperms and develop new ones to replace the old, processes that are conceivable, but could not physically be completed within a few minutes, because they involve physical movement and growth or replication of biological matter within the individual’s body, then
-         meet and attract a female partner, and then
-         successfully reproduce!
From the above reasoning and example, it seems obvious that any conceivable biological process initiated by an individual a few minutes before death would not have time to become part of that species’ genetic information.


After demonstrating both Point 1. and Point 2. we can say that the blood coagulation sub-system of any blood circulating animal species could neither have been generated through genetic mutations nor through genetic adaptation.
If this is true, then evolutionary scientists will have to come up with some other hypothesis not only to explain the generation of relatively complex biological processes, but also for the formulation of their description in the genetic code.

An overview of the coagulation sub-system
We are not able to describe here the physiology of the coagulation sub-system in detail. We include only a simplified view of it, as we understand it, just to have an idea of its complexity, as it relates to the number of variables involved.
Coagulation begins almost instantly after an injury has damaged the endothelium lining of a blood vessel.
In all mammals, coagulation involves three mechanisms:
1.                  Vascular spasm: The smooth muscle in blood vessel walls contracts immediately where the blood vessel is broken. This response reduces blood loss for some time, while the other two mechanisms become active.
2.                  Platelet plug formation:  When blood platelets encounter a damaged blood vessel they form a "platelet plug" to help to close the gap in the broken blood vessel. This is the beginning of the process of the blood "breaking down" from is usual liquid form in such a way that its constituents play their own parts in processes to minimise blood loss.  The key stages of this process are called platelet adhesion, platelet release reaction, and platelet aggregation.
3.                  Blood clotting, a mechanism involving proteins (many coagulation factors).
Blood clotting must happen at a precise level: If blood clots too quickly or too easily, then thrombosis may occur. This is blood clotting in an unbroken blood vessel, which is dangerous and can lead to strokes or heart-attacks. Conversely, if the blood takes too long to clot, then hemorrhage may occur. In this case much blood may be lost from the blood vessels, which is also dangerous. The hereditary disorder haemophilia is a condition in which certain coagulation factors are missing from the blood, as a result of which the blood cannot form clots (without medical intervention).
Blood clotting happens in three stages:
a.                  Formation of Prothrombinase, which happens in two ways (see below);
b.                  Prothrombin is converted into the enzyme Thrombin: Prothrombinase (formed in stage one) converts prothrombin, which is a plasma protein that is formed in the liver, into the enzyme thrombin.
c.                  Fibrinogen is converted into Fibrin: In turn, thrombin converts fibrinogen (which is also a plasma protein synthesized in the liver) into fibrin. Fibrin is insoluble and forms the threads that bind the clot.
The formation of Prothrombinase happens in two ways:
a1.       An intrinsic pathway: This is initiated by liquid blood making contact with a foreign surface, i.e. something that is not part of the body; or
a2.       An extrinsic pathway: This is initiated by liquid blood making contact with damaged tissue.
These pathways follow a pattern called “coagulation cascade”, and include a common pathway, as represented in the diagram below:

Diagram 1: The Factors involved in the coagulation cascade.

The following factors and inhibitors participate in the coagulation cascade process, in a precise quantity and timely fashion. A full description of the process is beyond the purpose of this article:
1.      Factor I: fibrinogen
2.      Factor Ia: fibrin
3.      Factor II: prothrombin
4.      Factor Iia: thrombin
5.      Factor III: tissue thromboplastin (tissue factor and phospholipid)
6.      Factor IV: ionized calcium
7.      Factor V: occasionally called labile factor or proaccelerin
8.      Factor Va: The co-factor of Factor Xa
9.      Factor VII: occasionally called stable factor or proconvertin
10. Factor VIIa: This forms an activated complex with the Tissue Factor
11. Factor VIII: antihemophilic factor
12. Factor VIIIa: The co-factor of Factor Ixa
13. Factor IX: plasma thromboplastin component, Christmas factor
14. Factor IXa: forming the tenase complex with co-factor VIIIa
15. Factor X: occasionally called Stuart-Prower factor
16. Factor Xa: An activated Factor X
17. Factor XI: occasionally called plasma thromboplastin antecedent
18. Factor XIa: Factor XI Is converted into Factor Xia by Factor XIIa
19. Factor XII: Hageman factor
20. Factor XIIa: Factor XII converts into XIIa when in contact with the damaged surface
21. Factor XIII: fibrin-stabilizing factor
22. Factor XIIIa: activated Factor XIII forming covalent bonds that crosslink the fibrin polymers
23. Factor TF: tissue factor
24. Factor TFPI: tissue factor pathway inhibitor

In addition to the above factors and inhibitors, the following co-factors and regulators participate in the coagulation cascade process:

  • Calcium and phospholipid (a platelet membrane constituent) are required for the tenase and prothrombinase complexes to function. Calcium mediates the binding of the complexes via the terminal gamma-carboxy residues on FXa and FIXa to the phospholipid surfaces expressed by platelets, as well as procoagulant microparticles or microvesicles shed from them. Calcium is also required at other points in the coagulation cascade.
  • Vitamin K is an essential factor to a hepatic gamma-glutamyl carboxylase that adds a carboxyl group to glutamic acid residues on factors II, VII, IX and X, as well as Protein S, Protein C and Protein Z. In adding the gamma-carboxyl group to glutamate residues on the immature clotting factors Vitamin K is itself oxidized. Another enzyme, Vitamin K epoxide reductase, (VKORC) reduces vitamin K back to its active form, thereby providing a controlling effect inhibiting the maturation of clotting factors.


Five regulators keep platelet activation and the coagulation cascade in check. Abnormalities can lead to an increased tendency toward thrombosis:
  • Protein C is a major physiological anticoagulant. It is a vitamin K-dependent serine protease enzyme that is activated by thrombin into activated protein C (APC). Protein C is activated in a sequence that starts with Protein C and thrombin binding to a cell surface protein thrombomodulin. Thrombomodulin binds these proteins in such a way that it activates Protein C. The activated form, along with protein S and a phospholipid as cofactors, degrades FVa and FVIIIa. Quantitative or qualitative deficiency of either may lead to thrombophilia (a tendency to develop thrombosis). Impaired action of Protein C (activated Protein C resistance), for example by having the "Leiden" variant of Factor V or high levels of FVIII also may lead to a thrombotic tendency.
  • Antithrombin is a serine protease inhibitor (serpin) that degrades the serine proteases: thrombin, FIXa, FXa, FXIa, and FXIIa. It is constantly active, but its adhesion to these factors is increased by the presence of heparan sulfate (a glycosaminoglycan) or the administration of heparins (different heparinoids increase affinity to FXa, thrombin, or both). Quantitative or qualitative deficiency of antithrombin (inborn or acquired, e.g., in proteinuria) leads to thrombophilia.
  • Tissue factor pathway inhibitor (TFPI) limits the action of tissue factor (TF). It also inhibits excessive TF-mediated activation of FIX and FX.
  • Plasmin is generated by proteolytic cleavage of plasminogen, a plasma protein synthesized in the liver. This cleavage is catalyzed by tissue plasminogen activator (t-PA), which is synthesized and secreted by endothelium. Plasmin proteolytically cleaves fibrin into fibrin degradation products that inhibit excessive fibrin formation.
  • Prostacyclin (PGI2) is released by endothelium and activates platelet Gs protein-linked receptors. This, in turn, activates adenylyl cyclase, which synthesizes cAMP. cAMP inhibits platelet activation by decreasing cytosolic levels of calcium and, by doing so, inhibits the release of granules that would lead to activation of additional platelets and the coagulation cascade.

The Fibrinolysis mechanism

Eventually, blood clots are reorganised and reabsorbed by a process termed fibrinolysis. The main enzyme responsible for this process (plasmin) is regulated by various activators and inhibitors. 

Fibrinolysis is a process that initiates at the time of the injury and prevents blood clots from growing and becoming problematic. It also has a delayed effect, which eventually is used to re-absorb and digest the blood clots. 

Diagram 2: Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.
The following are some of the chemicals participating in the Fibrinolisys mechanism of the coagulation cascade process (in addition to those previously mentioned):
1.      tPA: Tissue plasminogen activator
2.      Urokinase
3.      Kallikrein
4.      a2-antiplasmin
5.      a2-macroglobulin

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