On the Nobel committee's design filter.

Behe: Nobel Prize for Chemistry Begs the Question of Intelligent Design

David Klinghoffer

The 2016 Nobel Prize for Chemistry recognized the intelligent design (what else would you call it?) of artificial molecular machines. These "nano" machines are impressive as technical achievements. Yet they are also exceedingly simple, "cute" but "useless," as  Nature reported that "some chemists" say. "We need to convince [researchers] that these molecules are really exciting," as one scientist remarked.

Writing at CNSNews , Discovery Institute biochemist Michael Behe makes the point that Darwin advocates don't want to hear. If scientists need to be "convinced" that nano machines are "exciting" and useful, the same is surely not true when it comes to the molecular machines familiar to biologists. That's the nanotechnolgy that make continuing existence possible for chemists, Nobel Laureates, and every living creature on the planet:

Many of the pioneers of the [nanotechnology] field drew inspiration from molecular machines discovered in biology such as the bacterial flagellum, a whip-like outboard motor that can propel bacteria through liquid. Yet the molecular machines laboriously constructed by our brightest scientists are Tinkertoys compared to the nanotechnology found in living cells. That may change -- with the expenditure of much effort and brain power the chemists' machines may be improved in the future. But right at this very moment sophisticated molecular robot walkers à la Star Wars are transporting critical supplies from one part of your cells to others along molecular highways, guided by information posted on molecular signposts. Molecular solar panels that put our best technology to shame are found in every leaf. Molecular computer control systems run the whole show with a reliability that exceeds that of, say, a nuclear reactor. What's more, unlike the artificial molecular machines that were painstakingly assembled by chemists, cellular molecular machines assemble themselves. As an astonished science writer once put it: "The cell's macromolecular machines contain dozens or even hundreds of components. But unlike man-made machines, which are built on assembly lines, these cellular machines assemble spontaneously from their protein and nucleic-acid components. It is as though cars could be manufactured by merely tumbling their parts onto the factory floor." Now those are smart materials!

No one needs to labor to convince anybody that  kinesins  (walking transport proteins) are useful. It sounds like he's headed in a dangerous direction:

Here's a question that'll get you into trouble in a lot of places for asking it out loud: if brilliant scientists can manage to make only toy molecular machines, what does it take to make the sophisticated machinery of the cell? For the past several decades I and others have been arguing that the ultra-sophisticated systems at the foundation of life powerfully bespeak purposeful design -- and for the same reason that the much simpler machines made by Nobel prize winners do: it takes intelligence and planning to arrange multiple parts into a working machine.

Yeah, smart guy, but billions of years!

Critics retort that, given billions of years and the whole world to work with, Darwin's mechanism of random mutation and natural selection could do the job. But there's no good reason to think so. The best, most recent laboratory and field evolution experiments show that random mutation most often breaks or damages genes that already exist and, counterintuitively, that sometimes helps a species survive. Needless to say, a process which most often breaks genes isn't going to build much of anything.

What are you, Behe, some sort of creationist?

Another common objection I hear is that the conclusion that the molecular foundation of life was purposely designed has religious implications. But so what? Science is supposed to be a search for truth based on our best understanding of nature. Science isn't supposed to shy away from a conclusion just because it doesn't fit some people's philosophical preconceptions.

The sophisticated design of living nanotechnology exceeds by light years that of human nano-inventions. Yet evolutionists deny that the former offers scientific evidence of intelligent direction, even as the latter, child's play by comparison, obviously do. For reference, see the debate I highlighted yesterday on protein evolution between  Doug Axe and Keith Fox.

Dr. Behe's own work in illuminating the evidence for intelligent design is the subject of a new hour-long documentary,  Revolutionary: Michael Behe and the Mystery of Molecular Machines. It's available now on DVD or Blu-ray.

More waving away of evidence of design.

Evolving Protein-Protein Binding -- Not a Problem?

Cornelius Hunter 

Dennis Venema is a Fellow of Biology with BioLogos, where he writes a series of posts called "Letters to the Duchess" -- an allusion to Galileo's "Letter to the Grand Duchess Christina." In the past, I have looked at Professor Venema's articles on evidences for common descent (see here

 , 

 here

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 here

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 here

, 

 here

, and 

 here

).

In a recent  online discussion 

 with Venema, he made the erroneous claim that the mammalian immune system, with its search for, and production of, antibodies, is a good example of why evolving protein-protein binding sequences is not a problem. In fact the mammalian immune system is yet another enormous problem for the theory of evolution.

The mammalian immune system is not a good example because it is designed for this job of creating protein-protein binding sequences. It searches a well-defined design space extremely rapidly, and measures the success of its search experiments accurately and quickly. The fact that our immune system successfully designs antibodies in short order does nothing to address the problem of how random mutations occurring throughout the genome are supposed to have found myriad binding sequences, crucial for life. Venema also referred to another example that he has written about. Unfortunately this example also fails to demonstrate Venema's claim of "evolution producing a new protein-protein binding event."

The problem with evolving protein-protein binding is that too much gene sequence complexity is required to achieve the needed binding affinity. You could say it is an "all-or-none" type of problem.

One or two mutations will not generally do the job -- you usually need more mutations before the two proteins stick together very well. And stick together they must, on a massive scale, in order to perform their necessary tasks. Even the simplest, unicellular, organisms contain massive protein machines, consisting of dozens of different proteins binding together to perform crucial life functions.

The study Venema referred to did a beautiful job in confirming this "all-or-none" character of protein-protein binding sequences. The study showed that in order for a viral protein to perform a relatively simple switch from one protein to a very similar protein required four types of mutations. Anything less and no dice.

The twist in this study was that subsets of the four mutation types were apparently useful for a different function (strengthening the binding affinity to the original protein). So while in general the evolution of protein-protein binding sequences is astronomically difficult because too many simultaneous mutations are required, in this case the four mutation types could be accumulated, with useful benefit realized at some of the intermediate steps.

This is not a general result. It is not a revolutionary new finding that reverses our understanding of protein-protein binding sequences.

It confirms our knowledge, and adds a fascinating outlier case where the "all-or-none" character is circumvented by intermediate functions that fortuitously "push" the design in the right direction. As the study explains:

The "all-or-none" epistasis among the four canonical phage mutations implies that it would have been unlikely for the new function to evolve on the scale of our experiments, except for the lucky fact that some of the mutations were beneficial to the phage in performing their current function, thereby pushing evolution toward the new function.

The study provides no indication that the untold thousands upon thousands of protein-protein binding problems in molecular biology would enjoy this type of setup. And if they did, oh what a suspicious sign of design that would be.

Venema is mistaken in his attempt to recruit this study as a solution to the evolution of protein-protein binding sequences. Strangely, not only had Michael Behe provided his explanation of the study, but Venema was aware of it at the time of his writing. Venema explained that in his next article he would address Behe's explanation, but in fact Venema simply rehashed Behe's original explanation for why protein-protein binding is a problem for evolution. Venema did not address Behe's explanation but simply concluded that Behe's original explanation must be false because, after all, this new study demonstrates the evolution of just such protein-protein binding sequences.

This is an unfortunate misuse of a study that most readers will not understand. Venema has force-fitted the study into an evolutionary proof.

Additional Problems

In addition to the basic problem of serendipity, this confirmation of the "all-or-none" character of protein-protein binding sequences was possible only with a very contrived, designed, laboratory experiment. Simply put, a virus population was provided with a willing and well-fed host to live off. In the meantime, many more host targets awaited the virus population. So a few mutations helped the viruses infect the initial hosts, and mere single additional mutation then allowed the viruses to infect the second group of hosts.

It was, again, an entirely artificial, laboratory environment, that wasn't even intended to replicate a realistic evolutionary environment. Venema nowhere explained this.

Second, the study also discovered even more serendipity. Not only were there "luckily" intermediate fitness benefits, but the finding of the four mutations types also required certain mutations in the host genome. Without them, no dice.

Finally, it is worth noting that across the many different virus populations used in the experiment, the virus protein in question did not incur any synonymous mutations. The study attempted to explain this as a sign of selection:

First, all 248 independent mutations in the 51 sequenced J alleles were nonsynonymous, whereas the expected ratio of nonsynonymous to synonymous changes is 3.19:1 under the null model for the ancestral J sequence. This great excess is evident even if we include only the 82 nonsynonymous mutations in the 24 isolates that did not evolve the new receptor function.

This is suspicious. According to evolutionary theory, a lack of selection will be manifest in relatively few nonsynonymous mutations. So the ratio of normalized nonsynonymous mutations-to-normalized synonymous mutations (the so-called Ka/Ks ratio) will be less than unity. On the other hand, strong selection will be manifest in relatively many nonsynonymous mutations. So the Ka/Ks ratio will be greater than unity.

A high Ka/Ks ratio, and hence an inference of strong selection, should be due to relatively many nonsynonymous mutations. In this study, however, it is in the synonymous mutations where the surprise comes. There were zero. In other words, the Ka/Ks ratio is infinity. To pass this off simply as a sign of strong selection is not good science, even within the normal science of evolutionary theory.

It's irreducible complexity all the way down II

Newfound Genetic Code-in-Code Regulates Stress Response
Evolution News & Views 

There are 64 combinations in the genetic code (43), because there are four bases arranged in threes. Each triplet codon codes for one amino acid, of which there are 20 normally used in proteins. This mismatch of 64 versus 20 has been called degeneracy, and has long been a mystery. Some amino acids have a single codon, but others can be coded by up to six codons. Is this redundancy just a "frozen accident," as Francis Crick thought? Could there be functional reasons why a gene would specify one codon instead of another?

In the past, we examined growing evidence for function in the degeneracy. Last year we learned that different codons work at different rates, providing a "speed limit" mechanism for protein formation. In 2014, Casey Luskin wrote about how differing codons provide the cell with "translational pausing" that affects folding rates with phenotypic effects. The prior year, we saw that alternate codons have effects on circadian rhythms. In 2011, contributor Jonathan M. discussed additional evidences of fine-tuning in the mismatch. As Luskin said, "The theory of intelligent design predicts that living organisms will be rich in information, and thus it encourages us to seek out new sources of functionally important information in the genome."

Now we have another fulfillment of that prediction. Research at MIT has found a "Newly discovered genetic code [that] controls bacterial survival during infections" (emphasis added). This code-in-a-code makes use of the redundant codons for signaling bacteria to switch on their stress response strategy: "to enter a dormancy-like state that allows them to survive in hostile environments when deprived of oxygen or nutrients." The team led by Peter Dedon, a professor of biological engineering at MIT, found this out by working with Mycobacterium bovis.

Basically, the codons affect their corresponding transfer-RNAs (tRNA) in different ways. Notice first how complex the transfer RNA system is:

Once a tRNA molecule is manufactured, it is altered with dozens of different chemical modifications. These modifications are believed to influence how tightly the tRNA anticodon binds to the mRNA codon at the ribosome.
In this study, Dedon and colleagues found that certain tRNA modifications went up dramatically when the bacteria were deprived of oxygen and stopped growing.

Experimenting on the bacterium's response to anoxic conditions, the researchers wondered if alternate codons made a difference. They knew that "the amino acid threonine can be encoded by ACU, ACC, ACA, or ACG," so they went hunting for possible connections to the stress response.

One of these modifications was found on the ACG threonine anticodon, so the researchers analyzed the entire genome of Mycobacterium bovis in search of genes that contain high percentages of that ACG codon compared to the other threonine codons. They found that genes with high levels of ACG included a family known as the DosR regulon, which consists of 48 genes that are needed for a cells [sic] to stop growing and survive in a dormancy-like state.
When oxygen is lacking, these bacterial cells begin churning out large quantities of the DosR regulon proteins, while production of proteins from genes containing one of the other codons for threonine drops. The DosR regulon proteins guide the cell into a dormancy-like state by shutting down cell metabolism and halting cell division.

Here, then, is powerful evidence for different effects when the same amino acid is encoded by an alternate codon. The work by Dedon's team is published in Nature Communications, an open-access journal.

Apparently the ACG codon affects the "wobble" of its corresponding tRNA and how tightly the amino acid is bound. This, in turn, affects the translation efficiency in the ribosome, thus regulating the dosages of protein products. They began to see a method in the madness of degeneracy, evident in the phrase "coordinated system":

Codon re-engineering of dosR exaggerates hypoxia-induced changes in codon-biased DosR translation, with altered dosR expression revealing unanticipated effects on bacterial survival during hypoxia. These results reveal a coordinated system of tRNA modifications and translation of codon-biased transcripts that enhance expression of stress response proteins in mycobacteria.
In the conclusion, they elaborate on this coordinated system, stating that it represents another genetic code:

There is emerging speculation for the existence of a 'code of codons' based on gene-specific codon usage patterns that can regulate translation. Among possible mechanisms linking environmental changes to codon-biased translation, recent studies have shown that the dozens of modified ribonucleosides in tRNA form a dynamic system that responds to cellular stress. We have shown that stress-specific alterations in tRNA wobble modifications, which can expand or limit tRNA decoding capabilities, facilitate decoding of cognate codons that are over- or under-used in mRNAs, which enhances translational elongation and leads to the selective up- and downregulation of the codon-biased genes.
The news report from MIT doesn't hesitate to call this a "newly discovered genetic code" or "alternate genetic code" with functional significance, constituting "another layer of control, mediated by transfer RNA, that helps cells to rapidly divert resources in emergency situations." Another biochemist comments on the significance of the discovery:

"The authors present an impressive example of the new, emerging deep biology of transfer RNAs, which translate the genetic code in all living organisms to create proteins," says Paul Schimmel, a professor of cell and molecular biology at the Scripps Research Institute, who was not involved in the research. "This long-known function was viewed in a simple, straightforward way for decades. They present a powerful, comprehensive analysis to show there are layers and layers, ever deeper, to this function of translation."
That's right out of intelligent design's list of predictions. As powerful as the evidence was for design in the genetic code's translation mechanism mediated by tRNA, it wasn't powerful enough. Now scientists are beginning to view "layers and layers, ever deeper" in its sophistication. "It is really an alternative genetic code, in which any gene family that is required to change a cell phenotype is enriched with specific codons," Dedon says. And he believes this is not an isolated case. "The researchers have also seen this phenomenon in other species ... and they are now studying it in humans."

Interested in other recent papers with design implications? Check these out:

Boris Zinshteyn and Rachel Green, writing for Science, think about "When Stop Makes Sense." They investigate why, contra the "standard" genetic code, "stop codons" sometimes specify amino acids. "The answers to this puzzle," they say, "may provide insights into translation termination and gene regulation in all eukaryotes."


Sandra Wolin, writing in the Proceedings of the National Academy of Sciences, investigates RNA modification enzymes that act as chaperones, helping tRNAs fold into the proper shape. "Because nucleotide modifications can also stabilize RNA structure and influence folding pathways," she says, "it will be both exciting and challenging to tease out the relative contributions of each function and the ways in which the two roles intersect and reinforce each other."