Title Author Date

Substitution of Argument Musgrave, Ian Apr 07, 2005

>The article of Ion Musgrave substitutes the >main argument of Doolittle vs. Behe: IC.
>Beside the incorrectness in saying that Fib-/Pl- mice are normal ("practically" etc.)

They don't die at birth, gain weight at wild-type rates,live lives of normal extent, don't bleed to death when cut and repair wounds at wild-type rates. If that's not practically normal, (look at the graphs and picture
again) then what is.

>the main flaw of Doolittle logic is >his "Contrary to claims about irreducible >complexity, the entire ensemble of proteins is >not needed. Music and harmony can arise from a >smaller orchestra".

>It is no wonder that Fib-/Pl- mice are doing >better than Fib- or Pl-: the ENTIRE system >does not function (let's forget about the >inability to bring offspring). And the one-by->one (yin-by-yang) addition of factors results
>in severe disorders.

Now there is a logical problem here. How can the mice do better if the entire system fails to function? If the entire system failed to function the mice should be dead shortly after birth, yet they are not.

>Does Fib-/Pl- prove the absence of IC? No. >They prove only the fact that underdone system >is worse than no system at all.

No, in complete absence of the system, the mice die at birth of complete intra-organ haemorage. The Fib -/-, Plg -/- and Fib, Plg -/- not only fail to die at birth, but actually reach reproductive age (just, in the case of
the Plg -/- mice), and have a reasonable ability to heal wounds and not bleed to death.

>Mark Perakh has got the Doolittle false proof >very well: he uses this "small orchestra" >example to "prove" that clotting system is not >IC-system at all.

Rather, it shows that IC is a rather incoherent concept (don't forget the Whales with their complete lack of Factor XII, who do just nicely).

[continued]

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Title Author Date

Substitution of Argument Musgrave, Ian Apr 08, 2005

[continued]
>Using this argument as a template I could >argue that a car is not IC (or doesn't have >IC) because if a car without brake is >dangerous, car without ignition and wheels is >not, besides, I'm still normal because I can >use my bike (=platelets)! So who talks about >car as an IC?

This is a completely invalid analogy, and completely misunderstands how clotting works. Ordinary serum proteins substituting for fibrin to stabilise and platelet plug is not the same as using a bicycle instead of a car. As in many things in biology there is no sensible mechanical analog of the clotting system. A closer (but still flawed) analogy is that it is like using wall paper paste and a rubber patch to seal a punctured tyre, rather than rubber cement and a rubber patch.

What it does show is that it is easy to equivocate on what is part of the
clotting system. The fibrin producing system, by itself, is not enough. In an ordinary clot, the fibrin mesh (the rubber cement) that plugs the gap binds together platelets (the rubber patch). In a fibrin deficient mouse,
ordinary serum proteins help bind the platelets together, not well, but well enough for the mouse to avoid bleeding to death. In a platelet
deficient mouse, fibrin alone forms a poorly stabilised clot, not a good clot, but enough for the mouse to avoid bleeding to death (like using rubber cement alone without the patch, this works for small leaks). So an
alleged IC system can work (barely) in the complete absence of one or other arm.

Again, in a modern vertebrate with a high pressure circulatory system, knocking out of parts of the clotting system makes it function very poorly, knocking out some parts is very lethal. But the clotting system didn't
evolve in modern vertebrates, it evolved in something like amphioxus, which
does very well with a simple "globbing" system (like using wall paper paste alone to plug a hole in a weakly inflated rubber tube, successively adding bits to a simple system would not have the same impact as removing a well tuned piece from a more advanced system. Adding globbing to the tunicate haemocyte plug system would only improve it (like using wall paper paste and cloth wrapping to plug a hole in a weakly inflated rubber tube), millions of years of evolution have fine tuned this primitive system to make it cope with high pressure circulation systems (rubber cement and
rubber patches). Mice these days are now dependent on the fibrin globbing system and the platelets, descendents of haemocytes working together (although they can do without it in the lab), but their distant ancestors started out with something much simpler.

Cheers! Ian

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Title Author Date

Substitution of Argument Wiolowan, Constantine Apr 24, 2005

Perhaps my poor English was the cause of total ignoring of my thesis.
The Behe's point is that blood clotting system (BCS) is irreducibly-complex, the knockout of some component knockouts the BCS' function.
The Doolittle's point was that the exemption of two key components of BCS does NOT effect the BCS's function, so the Fib and Plm are excessive factors.

Behe noted that Bugge's team had quite different results: while partial knockouts of BCS yield to severe disorders - hemorrhages or thromboses, the deficit of two "opposing" factors - Fib and Plm alleviated the severity.

But what does this mean? Again, it does NOT mean that BCS is not IC. What it does mean is that
1. The organism can survive somehow without BCS
2. The altogether blocking of BCS is better than partial blocking.

Again, our organism may survive without dozens of complex systems (e.g. olfactory, reproductive, etc.) But from this we cannot conclude that these systems are not (irreducibly) complex and are easily evolving via random mutations plus natural selection!

I frankly cannot understand why do you try to continue this dispute. Doolittle admitted that he misinterpreted Bugge's abstract. But instead of a calm "lifting" of an argument with "happy small orchestra" new fuel is added.

Now short comments on Ian's response.

>The Fib -/-, Plg -/- and Fib, Plg -/- not only fail to die at birth, but actually reach reproductive age (just, in the case of
>the Plg -/- mice), and have a reasonable ability to heal wounds and not bleed to death.

From the Bugge's article's abstract: "Plasminogen (Plg) deficiency in mice results in high mortality, wasting, spontaneous gastrointestinal ulceration, rectal prolapse, and severe thrombosis. Furthermore, Plg-deficient mice display delayed wound healing following skin injury, a defect partly related to impaired keratinocyte migration."

[continued]

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Substitution of Argument Wiolowan, Constantine Apr 24, 2005

[continued]

>What it does show is that it is easy to equivocate on what is part of the clotting system.
>The fibrin producing system, by itself, is not enough. In an ordinary clot, the fibrin mesh (the rubber cement)
>that plugs the gap binds together platelets (the rubber patch).

-I totally agree with this, but my point is: both irreducibly complex systems and "loosely-knit" systems with seemingly "excessive" elements are a challenge to a Darwinian, reductionist model of macroevolution.
The jump from simple Chordata with 0 genes of BCS to fishes with 28 genes within alleged 50 millions years, while being practically intact within half a billion succeding years is not explainable with "shuffle and test" hypothesis.
Any system has some sort of irreducible complexity. It infers from the very notion of a system. The ado about IC means that reductionists turn blind eyes to a problem. I can see either some kind of saltation or a creation to yield such intricate systems like hemostasis.

..Talking about amphioxis' clotting as a ancestor of the modern BCS and descending of platelets from haemocyte

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Title Author Date

Substitution of Argument Musgrave, Ian Apr 24, 2005

I won't reply to all the points raised, as simply reading the main article
deals with some of them, but some deserve more of a response.

[snip misreading of Bugge et al paper]
>But what does this mean? Again, it does NOT mean that BCS is not IC. What
it does mean >is that
>1. The organism can survive somehow without BCS
>2. The altogether blocking of BCS is better than partial blocking.

If this were true (which it is not), then this is a fatal blow for Behe's
thesis. Remember, if the clotting system is IC, then removal of any part
will cause that system to fail. This is Michael Behe's definition. If the
clotting system is IC, then removal of fibrinogen must cause the clotting
system to fail catastrophically, and the animals should bleed to death
shortly after birth, let alone survive surgical wounds. Now, if you can do
without the complete blood clotting system, and there are alternatives to
stop the animal bleeding to death, then the clotting system can be
assembled on the back of this scaffolding and Behe's argument is shot to
pieces.

But what has happened in these animals is that an important arm of the
blood clotting system has been eliminated. Again, according to Behe the
blood clotting system should fail catastrophically and the animals bleed to
death at birth. However, in the absence of fibrinogen, the pivotal last
step in forming a clot, mice can call on other plasma proteins to
substitute (albeit poorly) for the missing fibrinogen. Given the whole
point of the clotting system is to form clots; tangles of insoluble protein
and platelets that plug up holes and prevent bleeding, then since
fibrinogen deficient mice can form clots of a sort using standard serum
proteins and platelets, according to Behe's own definition, the clotting
system is not IC.

>I frankly cannot understand why do you try to continue this dispute.
Doolittle admitted that he
>misinterpreted Bugge's abstract. But instead of a calm "lifting" of an
argument with "happy small orchestra" new fuel is added.

No, Doolittle didn't. Read his email again. Behe has misrepresented
Doolitle by omitting crucial sentences which clearly show Doolittle's
understanding of the situation. Behe should, at the very least, quote the
full text.

[snipage]
>>What it does show is that it is easy to equivocate on what is part of
the clotting system.
>>The fibrin producing system, by itself, is not enough. In an ordinary
clot, the fibrin mesh
>>(the rubber cement) that plugs the gap binds together platelets (the
rubber patch).

>-I totally agree with this, but my point is: both irreducibly complex
systems and "loosely-knit"
>systems with seemingly "excessive" elements are a challenge to a
Darwinian, reductionist model of macroevolution.

[continued]

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Title Author Date

Substitution of Argument Musgrave, Ian Apr 24, 2005

[continued]

Neither are challenges to evolution, both can be assembled by the known
mechanisms of evolution. Adding a simple protein "globbing" system to a
haemocyte patch is well with the capabilities of evolution, this can then
be elaborated on later by gene duplication and so on.

>The jump from simple Chordata with 0 genes of BCS to fishes with 28 genes
within alleged
>50 millions years, while being practically intact within half a billion
succeding years is not >explainable with "shuffle and test" hypothesis.

Amphioxus does have at least a thrombin. Ascidians don't have clotting
genes, but they DO have some complement genes (several of which are
trypsin-derived proteases), and the closest relative of the clotting system
is, interestingly enough, the proteases of the complement system (the MASPS
especially). The complement system is involved in immobilizing and lysing
invading microorganisms. This is relevant because in invertebrates with a
clotting system, they have a single enzyme, coagulase, which converts
coagulin to an insoluble form which tangles up the haemocytes. Coagulin
also is used to immobilise bacteria as part of the host defense. Fibrin is
also used to immobilise invading bacteria, and thrombin feeds into the
complement system, helping to activate complement C3.

While thrombin can activate the complement system, MASPS on the other hand
cleave fibrinogen to fibrin and activate Factor XIII, as well as being
inhibited by some of the thrombin inhibitors. Furthermore MASP binds to
(but does not cleave) a fibrinogen-like peptide in the Ascidian complement
system. It requires no stretch of the imagination to see how duplication of
the MASP arm of the simple ascidian complement system could result in a
primitive haemocyte globing system (as is seen in arthropod coagulin
systems) which is then refined by selection and elaborated by repeated
rounds of gene duplication, given that most of the clotting system is
basically duplicates of itself (there were at least two who genome
duplication evens between the protochordates and jawed vertebrates).

All this is quite simple, and given that gene duplication occurs rapidly,
could easily be accomplished in under 50 million years.

>Any system has some sort of irreducible complexity. It infers from the
very notion of a
>system. The ado about IC means that reductionists turn blind eyes to a
problem. I can see
>either some kind of saltation or a creation to yield such intricate
systems like hemostasis.

Take a closer look; most of the intricacy comes from repeated rounds of
duplication.

>Talking about amphioxis' clotting as a ancestor of the modern BCS and
descending of platelets from haemocyte

[continued]

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Substitution of Argument Musgrave, Ian Apr 24, 2005

This sentence is unfinished. But from what we know of ascidian and
amphioxus clotting, as well of the haemocyte-only and haemocyte/coagulin
systems of simple and advanced non-chordate invertebrates, the sequence of
events suggested is plausible. Especially with the functional and
structural homology of thrombin and MASP, and thrombin/fibrinogen playing
dual and complementary roles in the complement and clotting systems. I
previously used the example of the calcium activated trypsin in amphioxus
as a model for the start of a simple clotting system (and thrombin is also
calcium activated). The MASP system already exists in ascidians, and can
easily be modified to provide a protoglobing system for amphioxus, which
can be elaborated in agnathans until we have the complete system in jawed
vertebrates (see especially the references in my original post which go
into some detail about how this may be accomplished).

Cheers! Ian

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