Did You Know That the Complexity of the Coagulation Mechanism Has Been Cited as Proof for the Existence of Divine Intervention?

By William Aird

Did you know that the complexity of the coagulation mechanism has been cited as proof for the existence of divine intelligence? At issue here is the explanatory framework behind the origin of biological complexity. Richard Dawkins famously introduced the landscape metaphor in his book, Climbing Mount Improbable, to illustrate the competing perspectives.1 According to the metaphor, complex design rests at the peak of the mountain. Dawkins called the mountain “Mount Improbable” because the species, organ or biological trait could not have reached the summit by chance alone.

There are two sides to the mountain. For many centuries, mankind could only recognize the side with the cliff. Reaching the summit required giant leaps through divine intervention, or single-generation macromutations. In 1859, with publication of his book Origin of Species, Charles Darwin exposed the other side of the mountain. It consisted not of a cliff, but rather of a gradual incline that was surmountable by the cumulative selection of chance mutations, a mechanism we now refer to as natural selection. Once at the summit, the trait carries the illusion of design.

The slow and steady march up the gradual incline is no picnic. Passage is governed by a series of unforgiving rules, or laws of nature. For one, every step must confer a survival or reproductive advantage. Second, the path is one-way; a species or trait cannot reverse course and get worse as a means towards eventual improvement. Finally, there are no sudden leaps or precipitous increases in ordered complexity.

Today, the coagulation mechanism metaphorically rests at the summit of the mountain. For those of us who studied the clotting cascade in medical school, we are fully aware of its awe-inspiring, not to mention intimidating, complexity. How remarkable, most of us would agree, that the mechanism arose through step-by-step modification and natural selection over the eons… what a marvel of evolutionary sculpting!

Creationists have a different take. My goodness, they claim, the clotting cascade is so complex that it could not possibly have arisen from small beginnings by a gradual series of incremental changes. Nope, they conclude, the clotting cascade is irreducibly complex. Like a mousetrap, the proper functioning of the coagulation mechanism is all or nothing: take away a single component and the whole system fails. The only route to the summit is by way of the cliff, and the only way up the cliff is on the shoulders of a divine creator.

Michael Behe, a Professor of Biochemistry at Lehigh University devoted an entire chapter in his book, Darwin’s Black Box, to the clotting cascade.2 In his book, he states that, “Blood coagulation is a paradigm of staggering complexity that underlies even apparently simple bodily processes. Faced with such complexity beneath even simple phenomena, Darwinian theory falls silent”. Behe went on to write: “The bottom line is that clusters for proteins have to be inserted all at once into the cascade. This can be done by postulating… the guidance of an intelligent agent.”

How do we even begin to address these assertions? We can ignore them, but that doesn’t help to mitigate the published misconceptions and deceptions, so readily accessible in the popular press. The Biological Sciences Department page on the Lehigh University website has a prominent disclaimer: “While we respect Prof. Behe’s right to express his views, they are his alone and are in no way endorsed by the department. It is our collective position that intelligent design has not basis in science”.3 Ouch.

Rather than censoring Behe, let’s take him on. Not because there is any merit to his position, but because, as noted by a famous biologist from the early 20th century, “nothing makes sense except in the light of evolution”.4  The first point to make is that irreducible complexity, which is defined as a system with several interacting parts that ceases to function when any one component is removed, is not evidence of divine creation. Biology is full of irreducible complexity – just think of the many single gene knockouts in mice that lead to embryonic lethality – but the interlocking nature of complex designs is as much a product of evolution as the single components themselves. Indeed, biological systems display non-linear dynamics and emergent properties such that the system cannot be understood by the studying the individual parts in isolation.

But does the coagulation system even meet the definition of irreducible complexity? The answer is no. The clotting cascade consists of sequential activation of a series of proenzymes or inactive precursor proteins (zymogens) to active enzymes. There are two arms to the clotting cascade: intrinsic and extrinsic. Both converge on the common pathway, which ultimately promotes thrombin generation and fibrin formation.

Humans who are deficient in one or another zymogen often have bleeding diatheses, but many can live a normal life and reproduce. Well, you might argue, these patients have some residual activity of their deficient factor, and perhaps that’s enough to keep them alive. However, genetically engineered mice who have complete loss of certain clotting factors, are also viable. Perhaps the most surprising is the mouse that lacks fibrinogen. They cannot make any fibrin plugs, yet they are viable, provided they are not subject to surgical procedures.5 The fact that a mammal can survive without any fibrinogen is the antithesis of irreducible complexity.

Second, despite the Creationists contention that the clotting cascade arose all at once, the evidence speaks otherwise. By examining the genomes of various classes of extant vertebrates, it is possible to infer the evolutionary history of the coagulation system. We learn that the clotting cascade first arose in an ancestral vertebrate some 600 million years ago. Moreover, the clotting cascade, as we recognize it in humans, did not evolve all at once. The extrinsic system appeared first (in jawless fish), followed by FIX (in jawed fish) and then the contact system (in amphibians) (see Figure below). This sequence of events is backed by strong biological plausibility: clotting is always initiated by the FVII of the extrinsic cascade, is amplified by FIX of the intrinsic pathway and is further accelerated by FXI, which lies downstream of the contact pathway.

The clotting cascade is absent in invertebrates and present (in one form or another) in all vertebrates. Therefore it evolved in the ancestral vertebrate some 600 million years ago, over a short time frame of 50-100 million years. The Creationists and their ilk have argued that the clotting cascade could not possibly have evolved over such a short period of time by step-by-step modification. This is what Dawkins refers to as the argument from personal incredulity: “Wow, so much to assemble in such a short period of time, there is no other explanation than Divine intervention!” Such intellectual laziness does little to further the discussion. Who is to say what is too short in evolutionary time? The fact that the clotting cascade arose quickly speaks to the power and versatility of gene duplications and exon shuffling and explains the high degree of homology between the various components of the clotting cascade.

Sadly, the clotting cascade has been adopted as a poster child by the Creationists. They looked for the most complex of systems in humans, and then represented it in ways that are disingenuous and lacking in intellectual gravitas. That is their purview. But the clotting cascade, having survived 600 million years and counting, has seen it all. It will continue its inexorable path up the mountain, to even greater heights, taking advantage of a beneficial mutation here and there, oblivious to all the commentary. Now that’s a sight to behold!

Increasing complexity of the clotting cascade during vertebrate evolution. In jawless fish, such as lamprey and hagfish, only the extrinsic pathway is present. Tissue factor (TF)-mediated activation of factor VII (FVII) results in activation of FX followed by prothrombin (PT), which then converts fibrinogen (Fbn) to fibrin). In jawed fish (gnathostomes), FIX, FVIII and FV are newly present. Now, FVII, once activated can activate FIX (cross-talk between extrinsic and intrinsic pathways), which together with FVIII, activates FX. In amphibians, the contact system emerges with FXI and FXII appearing. Finally, in mammals, duplication of the FXI gene results in separate genes for FXI and PK, and clotting cascade becomes connected with the kallikrein-kinin system. Adapted from Aird WC and Grant MA. Molecular evolution of the vertebrate blood coagulation system. In: Marder VJ, Aird WC, Bennett JS, Schulman S and White GC (eds). Hemostasis and Thrombosis: Basic Principles and Clinical Practice, Lippincott Williams & Wilkins, 2012.