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Friday 13 May 2016

Unhyped.

Richard Lenski and Citrate Hype -- Now Deflated
Michael Behe 

Dishonesty comes in degrees, from the white lie told to spare another's feelings to criminal fraud for one's own financial gain. Somewhere in the middle lies hype in science. Certainly a bit of innocent, accentuate-the-positive spinning of research results can help a scientist catch people's attention. Unfortunately, that can escalate into hucksterism that seriously exaggerates the importance of the work.

Most scientists aren't even tempted to try it, because most areas of research aren't sexy enough to pull it off. It is a problem, however, for those who work on topics that catch the news media's attention: cures for cancer; cloning; grand theories of the universe; and, of course, evolution.

Which brings us to Michigan State's Richard Lenski. As longtime readers of Evolution News and Views well know, to study evolution, for more than 25 years Lenski's lab has continuously grown a dozen lines of the bacterium E. coli in small culture flasks, letting them replicate for six or seven generations per day and then transferring a portion to fresh flasks for another round of growth. The carefully monitored cells have now gone through more than 60,000 generations, which is equivalent to over a million years for a large animal such as humans. (It's dubbed the Long Term Evolution Experiment -- LTEE.) As I've written before, the work itself is terrific. However, the implications of the work are often blown seriously out of proportion by a cheerleading science news media eager for stories to trumpet.

In 2008 Lenski's group reported that after more than 15 years and 30,000 generations of growth one of the E. coli cell lines suddenly developed the ability to consume citrate, which for technical reasons had been present in the liquid culture medium. Later work by the Michigan State team showed the ability was due to the duplication and rearrangement of a gene for a protein that normally imports citrate into the cell, but only when no oxygen is present. The mutation allowed the protein to work when oxygen was present, as it was throughout the LTEE.

It was an interesting, if modest, result -- a gene had been turned on under conditions where it was normally turned off. But the authors argued it might be pretty important. In their paper they wrote that the mutant's ability could be the result of "historical contingency" -- that is, a rare, serendipitous event that might alter the course of evolution. They also remarked that, since an inability to use citrate in the presence of oxygen had been a characteristic used to help define E. coli as a species, perhaps the mutation marked the beginning of the evolution of a brand new species.

One scientist who thought the results were seriously overblown was Scott Minnich, professor of microbiology at the University of Idaho and -- full disclosure -- a colleague of mine as a Fellow at Discovery Institute's Center for Science & Culture. Minnich knew that decades ago the microbiologist Barry Hall had isolated an E. coli mutant that could also use citrate after only a few weeks of growth (also cited in Lenski's paper), and that other studies had shown mutants could be isolated rapidly if they were selected directly -- that is, if they were grown where the only available food source was the selecting substrate such as citrate, rather than a mixture of the selecting substrate plus glucose, as in Lenski's experiment.

So Minnich's lab re-did the work under conditions he thought would be more effective. The bottom line is that they were able to repeatedly isolate the same mutants Lenski's lab did as easily as falling off a log -- within weeks, not decades. In an accompanying commentary highlighting the Idaho group's paper in the Journal of Bacteriology, the prominent UC Davis microbiologist John Roth and his colleague Sophie Maisnier-Patin agreed that Lenski's "idea of 'historical contingency' may require reinterpretation."

Richard Lenski was not pleased. Although in a response on his blog he acknowledged up front that the Idaho group's science was "fine and interesting," he insisted that yes the mutation was too historically contingent. Roth and Maisner-Patin's comments to the contrary supposedly represented "a false dichotomy." After all, historical contingency just "means that history matters," and whether Lenski's cells developed the mutation clearly depended on how they had been treated in his lab. Ipso facto, it was contingent.

But of course it's vacuous to say simply that "history matters." Any near-certain outcome can be prevented if necessary conditions for it to occur aren't present. A ball will always roll down a hill -- unless someone puts a barrier in front of it. The fact that the Minnich lab easily and repeatedly obtained the same results with multiple bacterial strains and growth conditions shows they are not some special example of historical contingency, if that phrase has any nontrivial meaning at all. Rather, under the right conditions it's a humdrum, repeatable result.

Lenski also tried to split hairs over the question of speciation. He faulted Minnich for writing skeptically of Lenski's citrate mutation, "This was interpreted as a speciation event." Lenski countered that in their initial paper his group had only been wondering out loud if the mutant would "eventually become" a distinct species. It's a process, not an event, you see. But Minnich's group had cited two publications in their paper that backed up their take on things. The first was a review paper where Lenski himself described the experiment and then remarked coyly, "That sounds a lot like the origin of species to me. What do you think?" (Wink, wink, nudge, nudge.)

The second was Elizabeth Pennisi's puff piece in Scienceon the LTEE in 2013 where she wrote (presumably after consulting with Lenski) "because one of E. coli's defining characteristics is the inability to use citrate for energy in the presence of oxygen, the citrate-consuming bacteria could be seen as a new species." If Lenski plays fast and loose with the public's perceptions of his work, he shouldn't complain when he's called on it.

In a disgraceful move, Lenski impugned Scott Minnich's character. Since he's a "fellow of the Discovery Institute" sympathetic with intelligent design, the skeptical discussion in Minnich's paper (which underwent thorough peer review by an excellent journal that chose to highlight it with commentary from eminent scientists) "suggests an ulterior nonscientific motive." (Apparently Lenski himself can speculate about all sorts of grand possibilities, ulterior-motive free.) You see, the Idaho scientists had the temerity to write, "A more accurate, albeit controversial, interpretation of the LTEE is that E. coli's capacity to evolve is more limited than currently assumed."

Well, perhaps someone personally involved in the work might see unending possibilities. But what should an objective observer call a situation where the exact same mutations occur time and time again? -- Limitless? Where a problem has no other solution except the one found? -- Flexible? Where deletion of either of the genes (citT or dctA) involved in the mutation prevents citrate utilization, as Minnich's group showed? -- Resourceful? Where none of the other thousands of genes in the cell can substitute? -- Inventive? Where even the easily obtainable mutation has apparently been of little use in nature? Earth-shaking?

With regard to citrate evolution, the Minnich lab's results have revealed E. coli to be a one-trick pony. And, as I've written previously, in other respects Lenski's own work has shown that E. coli evolves in his lab overwhelmingly by damaging loss-of-function and decrease-of-function mutations.


If that isn't "more limited than currently assumed," it's close enough. The take-home lesson is that, although the unvarnished work itself is great, the hype surrounding the LTEE has seriously misled the public and the scientific community. It's far past time that a pin was stuck in its balloon.

On Darwinian storytelling re: The emergence of the human race.

Does the Evidence Point to Mankind's Fully Natural Origin?
Denyse O'Leary 

n 2009, Mayor Bloomberg of New York held a special ceremony to laud the recently discovered fossil Ida (pictured above), said to be the "missing link" between humans and other primates. Bloomberg was

standing beside Ida's glass box, his arm around the shoulders of a school girl who was wearing a T-shirt with the TV tie-in logo: "The Link. This changes everything."

The Guardian's correspondent quipped, "The main thing Bloomberg was presumably hoping this would change was his prospects of winning an unprecedented third term as New York mayor." Bloomberg did win, but the Ida fossil was not so lucky; claims for it were shortly retrSignificantly, Bloomberg thought Ida improved his re-election chances before the fossil experts had spoken. And that she wouldn't have harmed his career if she failed their tests. Real and imagined "human evolution" is now so integral to our culture that demand outpaces authenticity. The disappointing history of Sahelanthropus, Orrorin, and Ardi, all hailed in 2001 as human ancestors, attests to the frustrating search for "missing links." Sediba, another supposed ancestor, fared no better in 2013. A science writer at Wired, not known for intelligent-design sympathies, derides the ceaseless buzz as "ancestor worship."

If he's right, we worship what we do not know. Pop culture's Ascent of Man gives no hint of the disorganization and confusion of current human evolution studies.

Late last year, it was announced that the oldest assumed human sequence then published (400 kya) baffles experts because it belongs to an unknown group, one more like Denisovans (an extinct type of human) than Neanderthals. The DNA results from the "Pit of Bones" site in Spain were described as baffling (Nature), perplexing (BBC), hard to make sense of (The Scientist ), don't quite know what to make of it (New Scientist), and creating new mysteries (New York Times) instead of neatly clarifying human evolution. October of that year had already brought the news that the human remains found at Dmanisi, Georgia, showed that many "separate species of human ancestors" never really existed and "may now have to be wiped from the textbooks." "Separate species" of human ancestors (that nonetheless interbreed)? There are many definitions of "species," so the term can be flung around freely, if accompanied by suitable credentials.

One researcher in a discipline that tries to keep track of the general direction of findings (theoretical anthropogeny) recently found no consensus as to when the human race arose, after he offered colleagues a spread ranging from ~60,000 to ~500,000 years ago. In this context, it hardly seems worth mentioning that no known hominin (assumed human) is clearly an ancestor of both Neanderthals and current humans.

For all practical purposes, today's humans are orphans, seeking our roots via scraps and artifacts, many of unknown authenticity or significance. If we are convinced that any discovery we make is better than uncertainty, we are in a suitable frame of mind to explore the questions.

When interpreting accounts, we need to keep in mind several narrative biases that can become distortions. When it comes to us lay readers, the story already incorporates these distortions. Usually, we won't know what has been put in or left out in order to fit the narrative bias -- unless a new find provokes a crisis in which the facts just will not fit the mold. We saw several examples of that above, from 2013.

The controlling bias is fully natural evolution: Humans evolved over a long period of time from a shrew-like creature into our current state. There is much less evidence for this proposition than the TV documentaries would have us assume. Granted, the evidence is a bit better than for the multiverse (which obliterates the very idea of evidence). It's also a bit better than for origin of life by purely natural means, which is impossible in the known universe.

At least some parts of human evolution might have happened according to purely natural laws or the vagaries of circumstances. Put another way, we could assume so for the sake of argument, without immediately finding ourselves in trouble with the rules for logic or the evaluation of evidence. We will, however, find ourselves dealing with one very large problem indeed: Human evolution includes the origin of the human mind. Theoretical physicist Roger Penrose has said:

If you look at the entire physical cosmos, our brains are a tiny, tiny part of it. But they're the most perfectly organized part. Compared to the complexity of a brain, a galaxy is just an inert lump.
"Why aren't we more like chimps?," New Scientist asked plaintively in 2012, encapsulating the current perspective in six words, and implicitly ruling out alternative approaches to enquiry. Well, one way we are different is that we acquired a history, a history of choices made, skills learned, and insights passed on. Let us see what our found collection of scraps and artifacts can tell us.acted.

On science and metaphysics

One Long Argument -- Responding to VJ Torley on Human-Ape Common Descent
Cornelius Hunter 

At Uncommon Descent, VJ Torley has analyzed my criticism of S. Joshua Swamidass's recent article, "Evidence and Evolution." From this analysis, one would think that I mercilessly berated a poor fellow who was merely attempting to "extend an olive branch to creationists." After all, nowhere did Swamidass belittle or ridicule his opponents, and nowhere was there so much as a trace of smug superiority. And the guy is a Christian, not some atheistic reductionist. In fact, Swamidass does not even draw any conclusions in his article.

This is how Torley begins his article and unfortunately it gives those who have not read the two articles the wrong impression. I gave a lengthy, fact-based, scientific criticism of Swamidass's claims that was not dismissive or sarcastic. I did not accuse of Swamidass of belittling or ridiculing anyone, nor did I accuse him of smugness, academic or otherwise. And I did not question his religious beliefs. All of this was injected by Torley.

As for drawing conclusions, yes, contrary to what Torley says, Swamidass draws conclusions. He states in no uncertain terms that the evolutionary story "is by far the best scientific explanation of our origins." In fact, the evidence is stunning:

What is the evidence for human common ancestry with apes? The strongest evidence is a series of stunningly accurate predictions about human genomes that have been confirmed in recent decades as the human and ape genomes have been sequenced.
Swamidass goes on to suggest that microevolution is sufficient to explain the evolution of humans from a small, ape-like creature.

Throughout, Swamidass uses a scientist-versus-theologian, Warfare Thesis perspective. Scientists simply refer to the data whereas theologians must adjust their sights, drop their denial, and grapple with the undeniable truths of evolution. To object is futile and attempts to explain humans as a product of design are "lawyerly":

A common lawyerly objection to this evidence is that these similarities are "equally" explained by common "design." As scientists, our response to this objection is data.
Perhaps the theologian "could look for errors in the scientific analyses," but even that would be futile:

Still, even if he [the theologian] found standing for quibbles here and there, the overall picture would remain the same and the evidence against common ancestry, at best, would be subtle and debatable.
Swamidass presents a story in order to "reduce the fear some feel when encountering evidence that might contradict their understanding of the Bible."

This is all Warfare Thesis, and Torley finds it to be "irenic in tone, easy to follow, deeply learned, and absolutely right."

On the other hand Torley throws occasional ad hominems my way and finds that my critique of Swamidass's piece was "polemical and curtly dismissive in tone." In fact, my criticism was about Swamidass's arguments. I pointed out that his scientific claims were erroneous and that ultimately his arguments relied on metaphysical claims.

This is not to say there cannot be improvements in my article. It is, after all, a blog post. I'm thankful for feedback and corrections to my errors. But Torley's casting of the two articles is simply a misrepresentation. It seems that his criticism of my post is, in fact, more applicable to his article.

What About the Science?

Torley next castigates me for ignoring the main scientific evidence Swamidass presents. And what is Torley referring to? A series of references Swamidass made. So instead of addressing the key scientific claims made by Swamidass (which I did), I am supposed to do an expansive analysis on several references Swamidass provided as backup.

In fact I was planning on getting to those references at some point, time permitting, as they are yet more examples of failed science. But Torley's requirements and criticisms are unrealistic.

Torley next quotes from one of Swamidass's references, imagines what my response would be, and argues with it. This is getting silly.

Torley finishes with a series of erroneous rebuttals, ad hominems, and straw-man arguments. To be sure, Torley makes some good tangential points, but they are unfortunately the minority.

Not surprisingly Torley shares Swamidass's theological convictions, which underwrite their claims. Their contrastive reasoning, if correct, proves their case. As Torley writes:

On a special creationist account of human origins, there is absolutely no reason to expect that humans would have what appear to be the remains of genes used for making egg yolks in their DNA -- just as there is no particular reason to expect that humans would be more genetically similar to chimps than rats are to mice -- or for that matter, than foxes are to wolves, or horses are to donkeys. [Emphasis in original.]
No reason. If Torley is correct here then, yes, we can safely conclude for evolution. Likewise:

Reasoning on Bayesian grounds, these striking and singular facts have a high probability on the hypothesis of common descent, but are surprising (and hence improbable) on a hypothesis of separate creation. One can only conclude that these facts lend scientific support to the hypothesis of common descent.
True enough. Such reasoning is perfectly valid, but it hinges on metaphysical premises. From a scientific perspective, evolution and common descent are unlikely to say the least, but from a metaphysical perspective, they are compelling.


Religion drives science, and it matters.

How the case for design is as plain as the nose on your face

Smelling Design
Evolution News & Views

How's this for an admission that design principles motivate scientific progress?

For an engineer, successful design of a new product needs to meet multiple objectives such as maximizing targeted mechanical performance and minimizing the cost. Some of these objectives are incompatible, thus tradeoffs are necessary. Similarly, living organisms are also constantly ... optimizing multiple objectives such as growth rate and resistance to environmental fluctuations. A central task for systems biology is to unravel the corresponding mechanisms, or the design principles ultimately determined..., especially how a system prioritizes the multiple objectives and makes necessary compromises.
That's a great quote except for the parts we left out. In the first ellipsis, the authors of a paper in PNAS insert these words: "[are also constantly] under selection pressure to maximize their fitness to the environment through [optimizing]..." The second ellipsis adds, "by evolution." But since engineers are neither under the pressure of natural selection nor working by blind chance, the extraneous words destroy the comparison, and thereby contribute nothing to the meaning.

The paper deals with an interesting problem in biology. Our noses contain millions of olfactory sensory neurons (OSNs). Each neuron expresses one and only one type of olfactory receptor (OR, a molecular machine that recognizes a particular odor molecule). There are hundreds, in some animals thousands, of different receptor types. How does each receptor get its fair share in the distribution? It's "one of the most intriguing problems in neurobiology," the authors say; "how can both monoallelic and diverse expression of OR be ensured at the same time?"

The answer "remains elusive after several decades of intensive investigations" -- until one thinks like an engineer. At a key point in the paper, despite other attestations about evolution, they make their breakthrough with these words: "Then from an engineering perspective, a better design to achieve single-allele activation is..." and so forth [emphasis added]. The body hits the optimization target successfully just like a good engineer. Actually, it does it better. Their simple model, flowchart and all, is less sophisticated than the nose itself.

The final paragraph nicely states the centrality of design principles in their research (and says nothing more about evolution):

In summary, we have constructed and analyzed a comprehensive model that revealed a mechanism for achieving diverse and monoallelic OR gene expression. A proper combination of mechanisms, but none of the individual one, can achieve the desired diverse and monoallelic OR expression. Given that multiobjective optimization is ubiquitous in biological systems, this synergetic and sequential application of different mechanisms is likely to be a general design principle on biological process regulation, and shed light on problems in other fields as well. This work aims at using a minimal model to reveal the essential elements that regulate the OR selection process. For example, [four examples given].... Future studies will reveal these possible fine-tuning elements and address its implications in other processes of gene regulations.
A statement from the University of Pittsburgh about this paper doesn't mention design or evolution, but summarizes the principle finding as "a basic physics principle called cooperativity, in which elements in a system influence the behavior of one another rather than function independently." The synergy between neurons the scientists witnessed gave them the chills. "We are amazed that nature has solved the seemingly daunting engineering process of olfactory receptor expression in such a simple way," one said.

Designed Winnowing

Another paper, this one in Current Biology, addresses the same problem from another angle. "A genetic approach in mice reveals a new facet of odorant receptor (OR) regulation," the summary begins. "Adventitious expression of multiple ORs activates post-selection refinement (PSR)." As the neurons sort themselves out in the olfactory epithelium during development, failures occur. Some neurons, contrary to the rules, express more than one receptor. Don't worry; a cleanup crew is on hand to take care of them:

Here we used a genetic approach in mice to reveal a new facet of OR regulation that corrects adventitious activation of multiple OR alleles, restoring monogenic OR expression and unique neuronal identity. Using the tetM71tg model system, in which the M71 OR is expressed in >95% of mature OSNs and potently suppresses the expression of the endogenous OR repertoire, we provide clear evidence of a post-selection refinement (PSR) process that winnows down the number of ORs. We further demonstrate that PSR efficiency is linked to OR expression level, suggesting an underlying competitive process and shedding light on OR gene switching and the fundamental mechanism of singular OR choice.
This paper had no use for Darwinian theory. The "selection" they speak of is not natural selection, but rather the initial choice of OR that each OSN expresses. How could a blind process know that expressing multiple ORs on the same neuron is a problem? How could it know what needs to be winnowed down? The paper calls this "Cleaning Up After Feedback." It sounds designed. "The process we describe here may represent a 'failsafe' mechanism," they say, when the normal process doesn't generate a single outcome like it's supposed to (e.g., one OR per neuron). Their summary explains why that might happen, and how the body is prepared to deal with it:

OR regulation generates >2,000 transcriptional outcomes, endowing an equal number of OSN identities. This extreme selectivity results from a slow initial phase, when individual OR alleles are infrequently activated, followed by a feedback stage halting the process and preserving singular choice. Mathematical modeling has determined parameters for activation and feedback that ensure a high probability of singular expression. These analyses also defined a failure rate, when activation proceeds too quickly, or feedback proceeds too slowly, resulting in neurons expressing multiple ORs. OSNs are unlikely to use feedback suppression to restore singular OR expression once more than one allele is activated. We have revealed a post-selection refinement (PSR) mechanism, which restores singular OR expression and unique neuronal identity.
This is a nice supplement to a previous article here on olfaction two months ago, where we learned how individual olfactory receptors (ORs) respond to not only the shape but vibrational energies of odor molecules, and then took a look down the line at the olfactory bulb to see how the switchboard maintains its complex wiring. Those were design features of the operational adult nose. Now, we see that the design principles of optimization, feedback, and refinement are at work in the initial setup stages of the neurons and their receptors. "From an engineering perspective," it's clearly design all the way down.

But Wait, There's More

Yes, another recent paper shows a nose for "design principles" without mentioning evolution. This paper from Harvard, published in PNAS, uses the phrase "design principle" three times. The authors wanted to understand how a relatively small number of receptors can produce so many scent sensations. Humans only have about 300 ORs but can discriminate at least 2,100 odorant molecules. Other animals, like dogs, have much higher sensitivity. How is this possible? It's by design. "Such remarkable molecular discrimination is thought to use a combinatorial code," we know from earlier studies. Once again, we find optimization (an intelligent design science) at work. The receptor arrays are optimized for natural odor statistics, these scientists discovered:

We study a simple model of the olfactory receptors from which we derive design principles for optimally communicating odor information in a given natural environment. We use these results to discuss biological olfactory systems, and we propose how they can be used to improve artificial sensor arrays.
There you have it. Not only do the authors finding design principles useful for understanding the nose, they look forward to how to copy those principles for artificial noses. The optimization, by the way, continues all the way to the brain:

The activity of a single glomerulus is thus the total signal of the associated receptor type, so the information about the odor is encoded in the activity pattern of the glomeruli. This activity pattern is interpreted by the brain to learn about the composition and the concentration of the inhaled odor. We here study how receptor arrays can maximize the transmitted information.
Using an "information theoretic approach" to quantify how well a receptor array matches the odor statistics in the environment, they even make predictions:

Using an information theoretic model, we show that a receptor array is optimal for this task if it achieves two possibly conflicting goals: (i) Each receptor should respond to half of all odors and (ii) the response of different receptors should be uncorrelated when averaged over odors presented with natural statistics. We use these design principles to predict statistics of the affinities between receptors and odorant molecules for a broad class of odor statistics. We also show that optimal receptor arrays can be tuned to either resolve concentrations well or distinguish mixtures reliably. Finally, we use our results to predict properties of experimentally measured receptor arrays.

Naturally, biological noses, whether in humans or fruit flies, with their "remarkable molecular discrimination" abilities, vastly outperform the sensitivities of "artificial nose" devices created so far. Codes -- optimization -- information: design principles are propelling research into the secrets inside your nostrils.

Thursday 12 May 2016

Epistemology vs. Darwin.

Evolution May Obscure Reality, Says a Cognitive Scientist and Evolutionist


Wednesday 11 May 2016

Genetic evidence for common ancestry?Or give us a miracle and we'll explain the rest.

Stunning Evidence for Common Ancestry? S. Joshua Swamidass on the Chimp-Human Divergence


As 'Just so' as it gets II

Rafting Monkeys "Fill a Gap" in Evolutionary Theory?


Tuesday 10 May 2016

Darwinism vs. the real world XXIX

Calcium's Role in the Body -- and a Note on the Origin of This Series