Series reviewing Douglas Axe's Undeniable

(Roger A. Sawtelle) #42

The way I understand Axe’s argument is that evolution is false because the proteins do not fold right. This argument has a serious problem in that it says that Nature and by implication the Creator of Nature, Who is God, cannot do some thing when we know that God can do whatever God chooses to do. Also if one bases one’s argument on current science, current science is subject to change, which seems to be what happened here.

Axe & Co. are looking for the God of the gaps, Who makes evolution work even if it can’t. Of course human thought often does not anticipate the way nature works, because our thoughts are not the same as God’s thoughts. However God does have thoughts and nature follows God’s thoughts. We use science to follow God’s thoughts, not to know before God knows.

Non-believers do not think that God designed evolution, but they cannot explain the rationality of the way nature works. For Christians it should be simple, God is the God of the Facts, not the God of the gaps.

(Dennis Venema) #43

Yep - I cite Vincent heavily in my review of Axe.

(T J Runyon) #44

I don’t see how Axe accuses you of relying on Torley for your review. You used him for one point. A point I think Axe would agree with

(Dennis Venema) #45

I found that odd as well.


Not only that, but their invisible being acting through unknown mechanisms somehow produced genomes and physical organisms in such a way that they look exactly like they evolved. Genomes and physical characteristics both fall into phylogenies that correlate with one another, exactly as we would expect from evolution. We see conservation of sequence in exons and genetic drift in introns. We see fossils with the exact mixture of features that we would expect to see in exactly the time periods we would expect to see them if evolution is true (e.g. Tiktaalik). None of this makes sense in Intelligent Design if a designer is constantly tinkering with organisms. Humans tinker with organisms all of the time, and we produce organisms that easily and obviously violate the phylogenies that evolution would produce.

(Brian J Miller) #48

In Axe’s JMB paper he references several studies which suggest protein rarity:

  1. Yockey, H. P. (1977). On the information content of cytochrome c. J. Theoret. Biol. 67, 345–376.
  2. Reidhaar-Olson, J. F. & Sauer, R. T. (1990). Function- ally acceptable substitutions in two a-helical regions of l repressor. Proteins: Struct. Funct. Genet. 7, 306–316.
  3. Axe, D. D. (2000). Extreme functional sensitivity to conservative amino acid changes on enzyme exteriors. J. Mol. Biol. 301, 585–596.
  4. Taylor, S. V., Walter, K. U., Kast, P. & Hilvert, D. (2001). Searching sequence space for protein catalysts. Proc. Natl Acad. Sci. USA, 98, 10596–10601.

He also contrasts “forward” approaches which start with random sequences and look for function and reverse approaches which start with actual proteins and then look at their local rarity. What are the best reverse studies which demonstrate lack of rarity? Also, what are the best examples of forward studies which generate sequences which demonstrate stable folds with something close to a genuine active site? And, do problems exist with the studies Axe cites?

(Peaceful Science) #49

Turns out the claim a stable fold is required is unwarranted. Also, especially if catalyst intermediate-stabilaization is understood, it’s clear that binding sites are conceptually equivalent to active sites. There is an immense number of studies from the 1.5 decades after your last ref that demonstrate selective binding is easy to find with far less resources that available in evolutionary history.

Moreover we know new function is exceedingly easy to evolve in mammals from cancer evolution.

The best reverse approaches are from analysis that takes coevolution into account, and thereby can capture interactions between mutations. There are wide range of approaches in this class, but they show the inference to rare function from mutational analysis of a few mutational effects function is incorrect.

Also very different sequences with the same structure or function are additiona evidence that the inference to functional rarity Axe makes is flawed.

(Peaceful Science) #50

That seems false. Given what we know of neutral theory, God could have been constantly tinkering and we see the data just as we do. Science is silent on God action, and more over we know the number of mutations he’d have to tinker with would be vastly outnumbered by neutral mutations.

(Dennis Venema) #51

I’ve always wondered what Axe thinks about the formation of high-affinity antibodies in the vertebrate immune system. Specific binding isn’t a “function”?

(Peaceful Science) #52

He would accurately point out its not an enzyme. However he would also incorrectly say that this a systme designed to produce high affinity, and therefore is not relevant

I would respond, the antibody system is just like evolution then, a system created by God to create new proteins.

I also remind him that the theory of intermediate stabilization predicts that antibodies, because the can adaptive ly bind things, can be catalysis. This is exactly what we find in Abzymes.

This demonstrates by theory and example that selective binding is functionally equivalent to catalysis. The reason we do not select for enzymes in experiments is because it is exteremely difficult for humans to select for catalytic activity at remotely the same scale we can select for binding.

(Dennis Venema) #53

Yep. A lot of my students, when they learn about antibody formation, make this connection as well.


Going with the scenario that God acted directly on genomes . . .

I would argue that there are nearly infinite number of genetic changes that would produce a clear and obvious violation of the expected phylogenies. God could swap out entire genes or even gene families between very divergent species, which is exactly what humans do in many cases. At least to me, it begs the question as to why God would choose not to move genes all over the species tree, and why God would instead opt for an extreme minority of mutations that would not run contrary to what we would expect from evolution. It gives the appearance that God made the extra effort to make any tinkering invisible to humans.

(Peaceful Science) #55

@Joel_Duff’s article is here. It is quite good. Very thoughful.

(Jay Johnson) #56

Yes, well done @Joel_Duff. Romans 1 certainly seems to teach that all people have an “intuition” of God. There is plenty of proof for Paul’s assertion in the fact that all cultures throughout human history have believed that there is more to this world than we can see, as Joel pointed out.

Axe goes too far in asserting that this “intuition” takes a specific form, and – surprise! – that specific form is an argument from design. This reminds me a bit of Schweitzer’s criticism of the search for the “historical Jesus,” in which scholars examining the evidence tend to find a Jesus that looks a lot like themselves.

(Brian J Miller) #57

I had a wonderful conversation with a friend who is a biology professor south of me specializing in protein evolution. He gave some thoughtful feedback on the discussion of Axe’s work, so I will attempt to accurately convey all of his points along with some of my own thoughts.

One has to be very careful comparing different classes of proteins and generic claims of function. Many have the impression that proteins which function without fully folding into stable 3D configurations are suboptimal precursors to a fully folded, more evolved version. However this perspective is mistaken. The proteins in nature which function without a stable fold have actually “been optimized for multiple competing functional demands.” Their precise “looseness” is essential to their function, so they likely also represent extremely rare sequences of AAs.

Similarly, one must distinguish between any “function” and the specific functions performed by specific proteins which are needed for specific major adaptations. As an analogy, one could ask how likely would a child be able to craft a weapon out of a pile of garbage. The answer depends on what one means by “weapon.” Anyone could craft a sling shot out of a rubber strip and a few sticks. And, it might be useful for hitting a little brother ten feet away. However, the child would never be able to craft a high-precision riffle which Jason Borne could use to hit a target a mile away.

One of the most impressive experiments which started with random sequences was able to generate a chain which bound to ATP and catalyzed hydrolysis. The rarity of sequences for that function is somewhere around 1 in a trillion. I will refer to the chain as miniATPase. Let’s contrast this chain to the enzyme aconitase which changes citrate into cis-aconitate. This protein consists of over 700 amino acids compared to the less than 150 for miniATPase. I will focus on this example since it is part of the citric acid cycle which is a rather common metabolic pathway, and its activity is demonstrated beautifully by a YouTube video, which I encourage everyone to watch.

The enzyme performs several tasks:

  1. It binds to citrate, so the substrate resides at a precise location in a precise orientation. An neighboring Iron-Sulfur cluster helps stabilize the substrate electrostatically.
  2. Histone 101 donates proton to remove one OH group from the citrate. The enzyme is now altered.
  3. Serine 642 acts as a base by accepting a hydrogen from another location in the substrate. The enzyme is further altered.
  4. The interactions between the enzyme and the altered substrate flip the substrate upside down.
  5. Histone 101 binds to a proton from a passing water molecule, causing OH to attach to a new location in the substrate.
  6. Serine 642 returns a hydrogen atom to a new location in the substrate. The enzyme returns to its original state.
  7. The enzyme releases the substrate, so it can act on another citrate.

The successful conversion of citrate requires the right interactions, both chemical and electrostatic, to take place at the right times. Several amino acids have to be perfectly positioned, and the enzyme needs to have just the right stability, so the positioning is maintained, and the substrate can flip at the right time. Its activity only commences after the chain is perfectly folded. And, every step in the conversion process is essential. Since the enzyme alters during the first few steps, it must return to normal after the last steps, or it could reengineer other molecules. Therefore, it could not have evolved gradually, since the fold had to be highly optimized for all of the steps to proceed properly. The miniATPase example is like the slingshot from the analogy, and aconitase is like a high-precision riffle with a laser scope. Properly challenging Axe’s basic thesis requires one to focus not on the production of simple functions but on the most complex enzymes and other features required for novel adaptations.

Moreover, producing just once enzyme would not typically advantage an organism since most of the products of individual steps in metabolic pathways are useless without other enzymes to further process them. In fact, some intermediates are even toxic to the cell, so they have to be carefully ushered along to other enzymes. One cannot dismiss such challenges simply by referring to such comparatively easy tasks as antibody binding or the generation of other simple functions.

I asked my friend why critics of Axe’s research who specialize in protein evolution have not simply reproduced his experiment with what might be deemed as an improved approach. He responded by commenting that researchers who spend their careers attempting to create new protein folds or carefully study the properties of complex enzymes in nature know from everyday experience that actual enzymes like aconitase (not like miniATPase) are extremely rare. They instead simply believe that some pathway must exist to it from some ancestral protein, but this belief is based purely on faith.

My friend is very interested in this type of research. Would you please provide references and describe the specific examples to which you are referring? What is the most complex enzyme which was studied?

Also, one has be careful in assessing arguments made from comparing proteins in existing species, since they can easily fall into circular reasoning. Specifically, one could assume that undirected processes are responsible for the appearance of de novo genes or the differences between different proteins or other features in different species. And, then one could argue that the fact that those difference came about by natural processes demonstrates their power to create such features. The evidence presented depended on an assumption (the power of natural processes) that the evidence was meant to prove.

(Peaceful Science) #58

Happy to take this conversation offline with your friend directly. I’ll look forward to an email from him.

(T J Runyon) #59

Well darn. I was looking forward to reading your response to this

(Chris Falter) #60

I think Joshua @Swamidass will eventually come back with a response. I suspect he wants to avoid the kinds of communication problems that can happen when complex ideas get discussed in a forum. We have commentators here who suspect every ID proponent of being a closet YEC–or even worse, tolerating YEC views!–and therefore demand position statements on a variety of issues. Some folks manage to remain productive in such an environment, but others shut down. Why risk it?

(Peaceful Science) #61

@bjmiller appears to be communicating the argument of a scientist that prefers to remain anonymous. I entirely understand why that is the case for those making ID arguments. They risking losing their careers over this.

However, arguments by proxy are not an effective way forward. When I’ve explained my position in private to others in the past, and it turns into an argument by by proxy, it has not worked out well either (just look at ID movement’s response to @vjtorley for an example). It was thought that I was hiding my identity on purpose, rather than choosing not to argue a highly detailed and technical point in public.

In this case, it is easy to see the problems in the argument from the get go. For those unclear, I’d point you to @vjtorley’s article on this which I largely endorse on the science: I know Axe thinks that philosophers have no place in the conversation, but Vincent review requires response. For that review, where he quoted James Tour and myself at length, he was kicked out of Uncommon Descent (so much for the free exchange of ideas), and Axe dismisses it with an extremely disrespectful ad hominem in his response to a scientist.

This is fairly remarkable, because I cannot count the times I’ve been lectured by ID proponents about the need for scientists to listen to philosophers. So Axe’s rejoinder against @vjtorley (he is just a philosopher!) has heightened comic value for me. If that was a valid objection, Steven Meyers and Bill Demski (and the vast majority of ID sympathetic academics) should have just packed up and left this conversation a long time ago. Of course it is not a valid rejoinder, especially when the philosopher actually is explaining the science correctly.

Regardless, this is no different. It is legitimate to keep one’s identity anonymous in public, so it would make more sense to talk in private. I’m happy to engage and explain why Axe’s argument is entirely unconvincing, scientist to scientist. I am happy to talk in private about why this scientists rejoinder does not make the case. However, there is no real value in debating with someone not know who they are.

This is not a double standard. It is well known now that @vjtorley consulted with me on his article. If Doug Axe wants to engage with me in private about his work, and my objections to it, I am more than happy to do so. A public debate on a forum, that he himself is not even engaging, however, has very little value. In the past, when I have reached out to him, he has explained that he would rather take his argument forward with convincible non-scientists, than engage with me. So the lack of engagement here is his decision, not mine.

(Stephen Matheson) #62

The number of falsehoods in the piece was striking. That’s another reason the scientist should want to remain anonymous.