Defense in the blood

Authors Avatar

Defense in the blood

A system of this kind cannot just be allowed to free-wheel. The success of the coagulation process is due to the finely tuned modulation and regulation of all of the partial proteolytic digestions that occur. Too little or too much activity would be equally damaging for the organism. Regulation is a central issue in blood coagulation. 
Torben Halkier (1992, 104)

I. Summary

In Darwin's Black Box: The Biochemical Challenge to Evolution I devoted a chapter to the mechanism of blood clotting, arguing that it is irreducibly complex and therefore a big problem for Darwinian evolution. Since my book came out, as far as I am aware there have been no papers published in the scientific literature giving a detailed scenario or experiments to show how natural selection could have built the system. However three scientists publishing outside science journals have attempted to respond. The first is Russell Doolittle, a professor of biochemistry at the University of California at San Diego, member of the National Academy of Sciences, and expert on blood clotting. Second is Kenneth Miller, a professor of cell biology at Brown University and author of Finding Darwin's God (Miller 1999). The third scientist is Keith Robison, who at the time of his writing was a graduate student at Harvard University.

I will give their arguments below and my response. Here is a brief summary.

1) Professor Doolittle argued that new laboratory work showed two components of the blood clotting cascade could be eliminated ("knocked-out") from mice and the mice got along fine without them. However, Doolittle misread the laboratory work: the double knock-out mice have severe problems and have no functioning blood clotting system. They are not models of evolutionary intermediates.

Although anyone can misread a paper, in my opinion the fact that an expert cited a recent and contradictory journal article, instead of a publication directly addressing the evolution of blood clotting, shows that there are indeed no detailed explanations for the evolution of blood clotting in the literature and that, despite Darwinian protestations, the irreducible complexity of the system is a significant problem for Darwinism.

2) Although embedded in a lengthy description of how blood clotting and other systems work, Professor Miller's actual explanation for how the vertebrate clotting cascade evolved consists of one paragraph. It is a just-so story that doesn't deal with any of the difficulties the evolution of such an intricate system would face. Even so, in the one paragraph Miller proposes what looks like a detrimental or fatal situation, akin to the knock-out mice (above) that lack critical components.

3) Keith Robison proposed that a cascade might begin with a single enzyme with three different properties. Upon duplication of the gene for the enzyme, the duplicate loses several of the properties, resulting in a two-component cascade. Repetition of the scenario builds cascades with more components. Although intriguing, the scenario starts with a complex, unjustified situation (the enzyme with multiple abilities) that already has all necessary activities. What's more, the proposed gene duplication and several steps needed to lose function are "neutral," unselected mutations. Stringing together several very specific neutral mutations to build a complex system is vastly improbable and amounts to intelligent design.

II. Russell Doolittle's Criticism

a. Mice lacking clotting factors have severe health problems

In its issue of Feb/March 1997 Boston Review featured a symposium discussing Darwin's Black Box and Richard Dawkins' Climbing Mount Improbable. Among the dozen essays contributed by academics was one by University of California-San Diego biochemist Russell Doolittle (Doolittle 1997); (Prof. Doolittle's essay can be found at ). I had devoted a chapter of Darwin's Black Box to the blood-clotting cascade, asserting that it is irreducibly complex and so does not fit well within a Darwinian framework. Doolittle, an expert on blood clotting, disagreed. Prefacing a discussion of globin homology, he remarked that "the genes for new proteins come from the genes for old ones by gene duplication," later adding "This same kind of scenario can be reconstructed for a host of other physiological processes, including blood clotting." Then, citing a paper by Bugge et al. (Bugge et al. 1996) entitled "Loss of fibrinogen rescues mice from the pleiotropic effects of plasminogen deficiency," he commented:

Recently the gene for plaminogen [sic] was knocked out of mice, and, predictably, those mice had thrombotic complications because fibrin clots could not be cleared away. Not long after that, the same workers knocked out the gene for fibrinogen in another line of mice. Again, predictably, these mice were ailing, although in this case hemorrhage was the problem. And what do you think happened when these two lines of mice were crossed? For all practical purposes, the mice lacking both genes were normal! Contrary to claims about irreducible complexity, the entire ensemble of proteins is not needed. Music and harmony can arise from a smaller orchestra. (Doolittle 1997)

The implied argument appears to be that the cited work shows the clotting system is not irreducibly complex, so a simpler clotting cascade might be something like the one that lacked plasminogen and fibrinogen, which could be expanded into the modern clotting system by gene duplication. Perhaps there are other stable systems of lesser complexity, and the entire cascade could then be built up by small steps in what is thought to be the typical Darwinian pattern. However, that interpretation depends on a mistaken reading of Bugge et al. (1996).

Bugge et al. (1996) note that the lack of plasminogen in mice "results in high mortality, wasting, spontaneous gastrointestinal ulceration, rectal prolapse, and severe thrombosis. Furthermore, plasminogen-deficient mice display delayed wound healing following skin injury." On the other hand, if the gene for fibrinogen is knocked out, the result is failure to clot, frequent hemorrhage, and that "pregnancy uniformly results in fatal uterine bleeding around the tenth day of gestation." (Suh et al. 1995) The point of Bugge et al. (1996) was that if one crosses the two knockout strains, producing plasminogen-plus-fibrinogen deficiency in individual mice, the mice do not suffer the many problems that afflict mice lacking plasminogen alone. Since the title of the paper emphasized that mice are "rescued" from some ill-effects, one might be misled into thinking that the double-knockout mice were normal. They are not. As Bugge et al. (1996) state in their abstract, "Mice deficient in plasminogen and fibrinogen are phenotypically indistinguishable from fibrinogen-deficient mice." In other words, the double-knockouts have all the problems that mice lacking only fibrinogen have: they do not form clots, they hemorrhage, and the females die if they become pregnant. They are definitely not "[f]or all practical purposes . . . normal." (Doolittle 1997) (Table 1)

Join now!

Table 1. Symptoms of mice lacking clotting factors.

The probable explanation is straightforward. The pathological symptoms of only-plasminogen-deficient mice apparently are caused by uncleared clots. But fibrinogen-deficient mice cannot form clots in the first place. So problems due to uncleared clots don't arise either in fibrinogen-deficient mice or in mice that lack both plasminogen and fibrinogen. Nonetheless, the severe problems that attend lack of clotting in fibrinogen-deficient mice continue in the double knockouts. Pregnant females still perish.

An important lesson exemplified by Bugge et al. (1996) is that it can be worse for the health of an organism to have an active-but-unregulated ...

This is a preview of the whole essay