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Wednesday, 1 March 2017

Lamarck's gold?

Epigenomics "Gold Rush" Is Underway
Evolution News & Views 

More than a century ago, hardy individuals dropped everything to search for Klondike gold. Today, a new breed of adventurers is changing course to search for a different kind of gold: information at a scale so tiny, it couldn't be read until recently. It's called "non-genetic information."

Biochemists are as excited as prospectors without having to haul packs up remote snowbanks. More secrets of the cell are coming to light, revealing new levels of regulation in the burgeoning field of epigenetics. In Nature, Cassandra Willyard expresses the fervor that is growing in labs around the world: "An epigenetics gold rush: new controls for gene expression." As she reports on "How rediscovered chemical tags on DNA and RNA are shaking up the field," she uses the word excited or exciting five times. It began in 2008, she explains:

At the time, biologists were getting excited about the epigenome -- the broad array of chemical marks that decorate DNA and its protein scaffold. These marks act like a chemical notation, telling the cell which genes to express and which to keep silent. As such, the epigenome helps to explain how cells with identical DNA can develop into the multitude of specialized types that make up different tissues. The marks help cells in the heart, for example, maintain their identity and not turn into neurons or fat cells. Misplaced epigenetic marks are often found in cancerous cells. [Emphasis added.]
What's new is the assignment of RNA tags to the glossary of non-genetic information. Geneticists were familiar with methyl tags on DNA and histone proteins (the "histone code"), but only recently were these tags recognized as functional elements on the bases of RNA as well.In January, we shared one  of those discoveries: a tag named m6a that affects the stability of messenger RNA (mRNA). The number and position of tags on the mRNA affect its lifetime, and consequently its activity. Jaffrey's team considered this "dynamic and reversible epitranscriptomic mark" an instance of "epitranscriptomic information that determines the fate of mRNA."

Willyard now has more examples to share. Dr. Chuan He, a chemist at the National Institutes of Health, and his colleague Chao Pan at the University of Chicago set out to look for "chemical notation" on RNA molecules. When they started working together in 2009, He and Pan knew of about 100 chemical tags on RNA, but "nobody knew what they did." How often are major discoveries made by expecting function? Look what has happened with that focus:

Nine years later, such research has given birth to an 'ome of its own, the epitranscriptome. He and others have shown that a methyl group attached to adenine, one of the four bases in RNA, has crucial roles in cell differentiation, and may contribute to cancer, obesity and more. In 2015, He's lab and two other teams uncovered the same chemical mark on adenine bases in DNA (methyl marks had previously been found only on cytosine), suggesting that the epigenome may be even richer than previously imagined. Research has taken off. "I think we're approaching a golden age of epigenomics and epitranscriptomics," says Christopher Mason, a geneticist at Weill Cornell Medical College in New York City. "We can actually start to see all these modifications that we knew have been there for decades."
Their experience mirrors the downfall of the junk DNA myth. Non-coding DNA had been known for many years, but only when researchers intentionally looked for function did the golden age come. Now a new vein of gold is being found in long-ignored RNA tags (some of them known since 1974), but it required breaking out of old dogmas.

The governing rule of molecular biology -- the central dogma -- holds that information flows from DNA to messenger RNA to protein. Many scientists therefore viewed mRNA as little more than a courier, carrying the genetic information encoded in a cell's nucleus to the protein factories in the cytoplasm. That's one reason why few researchers paid much attention to the modifications made to mRNA.
Some of the delay is excusable. Scientists didn't have the tools we have now for "powerful mass spectrometry and high-throughput sequencing techniques," Willyard explains. Even with those tools, the work remains difficult. We can only wonder, though, if 'gold fever' might have accelerated the development of the tools.

In about 2010, the reversible m6a mark was discovered. "To He, it seemed like proof of an RNA-based system of gene regulation." The hidden gold veins started to shine under the flashlights. Further studies "revealed more than 12,000 methylated sites on mRNAs, originating from 7,000 genes."

The maps showed that the distribution of m6A is not random. Its location suggested that the mark might have a role in alternative splicing of RNA transcripts, a mechanism that allows cells to produce multiple versions of a protein from a single gene.
Since then, researchers have uncovered the molecular machines controlling the tags. "Each requires a writer to place it, an eraser to remove it and a reader to interpret it," Willyard says; "As the identities of these proteins emerged, scientists have come to understand that m6A affects not only RNA splicing, but also translation and RNA stability." They started finding function all over the place.

This change in mRNA content, which He calls a transcriptome switch, requires precision and careful timing. He thinks that the methyl marks might be a way for cells to synchronize the activity of thousands of transcripts.
By now, labs from Tel Aviv to Boston to Pasadena had gold fever. Researchers wanted to learn how different tissues tag their RNAs, and how the marks differ between organisms from algae to humans. Why, for instance, were some of these marks easier to find in bacteria than mammals? Earlier researchers had walked right past the gold veins.

In 2013, He's postdoc Fu had found an intriguing paper from the 1970s, which showed that algal DNA contains methylated adenine. "Nobody ever knew the function, and nobody ever followed up," Fu says.
Fu and a colleague started looking for these marks in algae, and found it in more than 14,000 genes. "And the distribution wasn't random," Willyard points out. It clustered near start sites for transcription. The postdocs reasoned that the mark "might be promoting gene activation." And so it was. Then they discovered that the marks are present in higher animals, too, but at low levels. Catch the fever:

Greer's lab head, Yang Shi, knew that He had uncovered 6mA in algae, and asked him for help. When He heard what Shi had found, he was excited. "We decided we're going to do this together," He says. A couple of months later, He met a researcher in China who had found 6mA in the fruit fly Drosophila. "I almost fell to the floor," He says. In April 2015, the three papers came out simultaneously in Cell.
Andrew Xiao, who studies epigenetics at Yale University in New Haven, Connecticut, read the articles with interest. Xiao and his colleagues had identified 6mA in mammalian cells, but they hadn't published their results. "Literally we thought nobody will take interest in this field," Xiao says. The Cell articles proved him wrong. "We realized we should hurry up."

And thus it goes. Marks are found to appear, surge, then disappear, indicating they act like a "molecular switch" during development. "His paper was absolutely a bombshell," one researcher exclaimed, reacting to clear evidence that a certain tag is functional. Another calls the work "incredibly exciting." Willyard continues the gold rush metaphor in a section, "Mining for more marks." They're talking like excited miners looking into their gold pans.

"We are only in the beginning of the story," Rechavi says. And as the techniques improve, scientists will be able to see these marks more clearly. The wealth of research possibilities makes Mason feel "euphoric", he says. "It's like the most exciting time to be working in the field."
Sound familiar? Vestigial organs must be leftovers of evolution; wait: they have a function! Noncoding DNA strands must be leftovers of evolution: wait, they have a function! These useless tags on RNA, "nobody knew the function, and nobody ever followed up." Wait! There's gold in them thar hills!

For an encore, look at this article from the National Institute of Standards and Technology (NIST) , "Start codons in DNA and RNA may be more numerous than previously thought." It's a bad-news, good-news story about the fall of another dogma. This one is about so-called "start codons" at the beginnings of genes. "It was previously thought that only seven of the 64 possible triplet codons trigger protein synthesis." But then, to their surprise, Stanford and NIST researchers found that some genes were being expressed without start codons.

To the best of their knowledge, no one had ever systematically explored whether translation could be initiated from all 64 codons. No one had ever proved that you cannot start translation from any codon.
"We kind of all collectively asked ourselves: had anyone ever looked?" said Hecht. A further review of available literature on the topic indicated that the answer was no....

The implications of the work could be quite profound for our understanding of biology.

"We want to know everything going on inside cells so that we can fully understand life at a molecular scale and have a better chance of partnering with biology to flourish together," said Stanford professor and JIMB colleague and advisor, Drew Endy. "We thought we knew the rules, but it turns out there's a whole other level we need to learn about. The grammar of DNA might be even more sophisticated than we imagined."

Needless to say, this discovery opens up additional vistas of information and control in the genome. Also, needless to say, these articles are strangely silent about Darwinian evolution.

Advocates of intelligent design should be pleased but unsurprised by these discoveries. And not to push the gold rush analogy too far, but we note that back in the day, many prospectors who set out for their journey to Alaska and the Klondike did so by way of Seattle. They equipped themselves and embarked just blocks away from what are today Discovery Institute's offices.


We're not saying, "We told you so" (although we did). Instead, let's all capitalize on the excitement of this gold rush. Isn't the search for function more rewarding than tossing unknown phenomena to the junk pile? ID is delightedly to point the way for the gold rushers to likely veins, with the modest reminder, Knowing how minds create hierarchical levels of information, you can expect to find functions similar to those in computer networks -- only even more sophisticated.

Long dead,human exceptionalism is gradually being buried unlamented.

Peter Singer Thinks Intellectually Disabled Less Valuable than Pigs

Wesley J. Smith

In his apologetics for infanticide, Princeton bioethicist Peter Singer has used a baby with Down syndrome as an example of a killable infant based on utilitarian measurements. (He actually supports infanticide because babies -- whether disabled or not -- are, in his view, not "persons.")

To Singer, moral value primarily comes from intellectual capacities, and that means developmentally and cognitively disabled human beings (also, the unborn and infants) have less value than other human beings, and indeed, a lower worth than some animals.

Were society ever to adopt Singer's bigoted anti-human exceptionalism views, it would mark the end of universal human rights, opening the door to tyrannical campaigns against the most weak and vulnerable -- you know, the kind of people that the Singers of the world deem resource wasters.

It would also break the spine of unconditional love, as our children would have to earn their place by possessing requisite capacities.

Consider the recent statements by Singer, published in the Journal of Practical Ethics, in which he explains why he would adopt out a child with Down syndrome. He then expresses a profound bigotry against people with cognitive and developmental disabilities (emphasis added):

For me, the knowledge that my [hypothetical Down] child would not be likely to develop into a person whom I could treat as an equal, in every sense of the word, who would never be able to have children of his or her own, who I could not expect to grow up to be a fully independent adult, and with whom I could expect to have conversations about only a limited range of topics would greatly reduce my joy in raising my child and watching him or her develop.

"Disability" is a very broad term, and I would not say that, in general, "a life with disability" is of less value than one without disability. Much will depend on the nature of the disability.

But let's turn the question around, and ask why someone would deny that the life of a profoundly intellectually disabled human being is of less value than the life of a normal human being. Most people think that the life of a dog or a pig is of less value than the life of a normal human being.

On what basis, then, could they hold that the life of a profoundly intellectually disabled human being with intellectual capacities inferior to those of a dog or a pig is of equal value to the life of a normal human being? This sounds like speciesism to me, and as I said earlier, I have yet to see a plausible defence of speciesism. After looking for more than forty years, I doubt that there is one.

Invidious discrimination exists when equals -- e.g., all human beings -- are denigrated as unequal based on some category that the bigot believes reduces the status of the discriminated against human, e.g., racism, sexism, and Singer-style discrimination against people with cognitive or developmental disabilities.

But human beings and animals do not inhabit the same moral realm. It is not wrong or discrimination to view and treat us differently than we do them.

Moreover, the very concept of "speciesism" -- used liberally in animal rights activism and bioethics -- is inherently and invidiously anti-human because it reduces us to so many carbon molecules with no inherent value beyond our cognitive capabilities at the moment of measurement. To repeat myself, the idea of speciesism, like utilitarianism, makes universal human rights impossible to sustain intellectually.

Assuming such utilitarian values would destroy the principles of Western civilization. And never mind the real capacities of many people with Down, whom Singer mischaracterizes, or their extraordinary loving natures -- which I have yet to see Singer opine much about. To Singer, intellect trumps all.

That's bigotry any way you look at it, no different from racism, except that his victims are less able to defend themselves.

I have always found it odd that Singer faces little of the opprobrium society metes out to other bigots. Indeed, he was brought to Princeton from Australia and given one of the world's most prestigious chairs in bioethics precisely because of these attitudes.

Despite supporting the propriety of killing babies, I have no doubt that Singer will continue to be the New York Times' favorite philosopher.

Tuesday, 28 February 2017

On faith in Jah and his Christ:The Watchtower Society's commentary.

BELIEF IN JESUS ESSENTIAL

Anthony: Hi, Tim. It’s good to see you again.
Tim: It is good to see you too.
Anthony: I brought the latest issues of The Watchtower and Awake! for you. I think you will really enjoy the articles in these magazines.
Tim: Thank you. Actually, I’m glad you came by today because there is something I want to ask you.
Anthony: Sure, what is it?
Tim: The other day, I was speaking with a coworker. I told him about the pamphlets you gave me and how interesting they are. But he said that I shouldn’t read them because Jehovah’s Witnesses do not believe in Jesus. Is that true? I told my coworker that I would ask the next time you visited.
Anthony: Well, I’m glad you asked me. It’s good that you are going straight to the source. After all, what better way is there to find out what a person believes than to ask the person himself?
Tim: That’s what I figured.
Anthony: The truth is, Jehovah’s Witnesses most certainly believe in Jesus. In fact, we feel that exercising faith in Jesus is vital to salvation.
Tim: I thought you did, but when my coworker said that you don’t believe in Jesus, it made me curious. I guess you and I never really discussed it before.
Anthony: May I show you some Bible verses that highlight the importance of exercising faith in Jesus? These are verses that Jehovah’s Witnesses often use in their ministry.
Tim: OK.
Anthony: A good place to start is with Jesus’ own words recorded at John 14:6. These words are part of a conversation that Jesus had with one of his apostles. We read: “Jesus said to him: ‘I am the way and the truth and the life. No one comes to the Father except through me.’” According to that verse, what is the only way to approach the Father?
Tim: Through Jesus.
Anthony: Correct. And Jehovah’s Witnesses firmly believe that. Let me ask you this: From what you know about God’s requirements, when a person prays, in whose name should he offer the prayer?
Tim: In the name of Jesus.
Anthony: I agree. And that’s why every prayer I offer is said in Jesus’ name. The same is true of all the prayers of Jehovah’s Witnesses.
Tim: That’s good to know.
Anthony: Another scripture we might consider is John 3:16. That verse is so important that it has been called the Gospel in miniature. The idea is that if you could take everything that was written about Jesus’ earthly life and ministry and boil it down to one verse, this would be it. Maybe you would like to read this scripture.
 Tim: OK. It says: “For God loved the world so much that he gave his only-begotten Son, so that everyone exercising faith in him might not be destroyed but have everlasting life.”
Anthony: Thank you. Are you familiar with this verse?
Tim: Yes, I’ve heard it a lot, and I often see it quoted on signs and billboards.
Anthony: It is a famous verse. Looking at it carefully, notice what Jesus said. He said that God’s love makes it possible for humans to enjoy everlasting life—but only if we do what?
Tim: Exercise faith.
Anthony: Yes. Specifically, faith in the only-begotten Son, Jesus Christ. And this point—that faith in Jesus opens the way to everlasting life—is made right here on page 2 of the magazine I brought you. Regarding the purpose of The Watchtower, it says that among other things, this magazine “promotes faith in Jesus Christ, who died so that we might gain everlasting life and who is now ruling as King of God’s Kingdom.”
Tim: Well, there you go. Right in your own magazine is proof that Jehovah’s Witnesses believe in Jesus.
Anthony: Precisely.
Tim: So, then, why do people say that you don’t believe in Jesus?
Anthony: There are probably a number of reasons why people say that. In some cases, people say it simply because they have heard other people say it. Or they may have been taught this misconception by their minister.
Tim: I’m just thinking here—maybe some people say that you don’t believe in Jesus because you call yourselves Jehovah’s Witnesses, notJesus’ Witnesses.
Anthony: That could be a reason too.
Tim: Why do you talk about Jehovah so much?

“I HAVE MADE YOUR NAME KNOWN”

Anthony: For one thing, we believe that it is important to use God’s personal name, Jehovah—just as his Son, Jesus, did. Consider what Jesus said in prayer to his Father. It’s recorded at John 17:26. Would you please read that verse?
Tim: Sure. “I have made your name known to them and will make it known, so that the love with which you loved me may be in them and I in union with them.”
Anthony: Thank you. Notice that Jesus said he had made God’s name known. Why do you suppose he did that?
Tim: Hmm. I’m not sure.
Exercising faith in Jesus is vital to salvation
Anthony: Well, maybe we could look at another scripture that sheds light on the matter. I am thinking of Acts 2:21. There we read: “Everyone who calls on the name of Jehovah will be saved.” Now, I’m sure you would agree that if calling on the name of Jehovah is a requirement for salvation, Jesus was no doubt aware of this requirement.
Tim: Yes, of course.
Anthony: So the salvation of his followers is one reason why it was important to Jesus that they know and use God’s name. And it’s one of the main reasons why we talk about Jehovah so much. We feel that it is important to make known God’s personal name and help others call on that name.
Tim: But even if people don’t know God’s name or use it directly, they still know who they’re talking about when they refer to God.
Anthony: That may be true. Even so, by telling us his personal name, God has made it easier for us to draw close to him.
Tim: What do you mean?
 Anthony: Think of it this way: We didn’t need to know Moses’ personal name. We could have known him simply as the man who parted the Red Sea or the man who received the Ten Commandments. Likewise with Noah—why know his name? He could have just been referred to as the man who built an ark and saved his family and the animals. For that matter, even Jesus Christ could have been known simply as the one who came from heaven and died for our sins. Right?
Tim: I suppose so.
Anthony: But God made sure that we knew the personal names of those individuals. There’s nothing that adds that special touch like a personal name. Even though we have never met Moses, Noah, or Jesus, just knowing their name makes these men more real to us.
Tim: I never thought of it that way before, but that makes sense!
Anthony: And that’s another reason why Jehovah’s Witnesses use God’s personal name so much. We want to help people build faith in Jehovah God as a real Person whom they can draw close to. At the same time, we place great emphasis on the role that Jesus plays in our salvation. Perhaps we could read one more scripture that drives home this point.
Tim: Sure.
Anthony: Earlier we read John 14:6. Remember, Jesus said that he is “the way and the truth and the life.” Let’s go back a few verses and notice his words found at John 14:1. Would you please read what Jesus said in the last part of that verse?

Tim: OK. It says: “Exercise faith in God; exercise faith also in me.”
Anthony: Thank you. Would you say, then, that true faith is an either-or matter? Is it a question of belief in Jesus versus belief in Jehovah?
Tim: No. Jesus said we need both.
Anthony: That’s right. And I am sure you would agree that it’s not enough just to say that we have faith in God and in Jesus. Really, we need to live our lives in a way that backs up that claim.
Tim: Definitely.
Anthony: But just how does a person demonstrate that he truly has faith in God and in Jesus? Maybe we can discuss that question another time. *
Tim: I would like that.
Do you have a particular Bible subject that you have wondered about? Are you curious about any of the beliefs or religious practices of Jehovah’s Witnesses? If so, do not hesitate to ask one of Jehovah’s Witnesses. He or she will be pleased to discuss such matters with you.

Saturday, 25 February 2017

Firing blanks?

Putting the RNA World Theory to the Test with "Pistol"
Evolution News & Views

Proponents of the RNA World theory for the origin of life need to produce the goods: RNA molecules that can store information and perform useful reactions and reproduce themselves and form spontaneously in a plausible prebiotic environment. A new candidate has emerged.

Behold Pistol: a "self-cleaving ribozyme," announced in the  Proceedings of the National Academy of Sciences. We know that the three authors from Yale -- Nguyen, Wang and Steitz -- think it is relevant to the origin of life, because they tell us so in the opening paragraph about the "Significance" of their paper.

Based on the "RNA world" theory, ribozymes likely carried out biochemical reactions long before organisms evolved to use protein enzymes as biocatalysts. The continued discovery of new structures for small self-cleaving ribozymes has shed light on conserved mechanisms in evolution, such as acid-base catalysis for self-cleavage reaction. Here, we present the crystal structure of a newly discovered class of self-cleaving ribozymes called Pistol and how it likely uses the phosphoester transfer mechanism for self-cleavage. The results presented here suggest that Pistol uses an evolutionarily conserved cleavage mechanism that is like other self-cleaving ribozymes, such as Twister, Hammerhead, Hairpin, and Hepatitis Delta Virus ribozymes. [Emphasis added.]
That's it? The ribozyme commits suicide? Like other ribozyme candidates? Next.

There's not much else to say. Still, let's read on and see if they can explain what on earth this Pistol has to redeem itself without shooting the RNA World in the foot. We searched for the phrases "RNA World" and "origin of life." The latter is not found. The former is only mentioned one more time in the Introduction:

The "RNA world" hypothesis speculates that RNA carried out the majority of biochemical reactions before the evolution of complex protein enzymes. Ribozymes are noncoding RNA that carry out catalytic activities. Unlike protein enzymes, only a handful of ribozymes have known biological functions. Their biological functions range from regulating gene expression (e.g., riboswitches) and performing peptidyl-transfer reactions (e.g., ribosome) to removing intron sequences in genes (e.g., self-splicing Group I intron ribozymes). The biological functions and mechanism of these ribozymes have been discovered through structural and biochemical studies.
So far, we learn that only a "handful" of ribozymes are known, they have some jobs to do in living cells, and the RNA World hypothesis "speculates." We would really like to see some testable science, not speculation.

Specifically, the RNA World hypothesis needs to satisfy four requirements:

A ribozyme must form spontaneously in plausible prebiotic conditions. No intelligent design allowed.

It must be able to replicate itself before the first cell appears, so that natural selection can kick in.

It must do something useful for a future living organism.

It must store the information on how to do that useful something. (Note: cutting yourself in half is a poor candidate for a useful function.)

A self-cleaving RNA like Pistol misses the boat on at least three of these requirements. In living cells, the Pistol class of ribozymes does have a function, participating in the destruction of other RNA molecules (while committing suicide in the process). The authors say:

Small self-cleaving ribozymes have been discovered in all evolutionary domains of life. They can catalyze site-specific RNA cleavage, and as a result, they have relevance in gene regulation.
But having a function now in cells tells us nothing about any prebiotic ribozyme, because Pistol is synthesized from DNA. How could a naked RNA in a primordial soup emerge without any help from encoded information?

We learn from a paper in   Nature Chemical Biology that Pistol was discovered in 2015. It was a rare find.

Enzymes made of RNA catalyze reactions that are essential for protein synthesis and RNA processing. However, such natural ribozymes are exceedingly rare, as evidenced by the fact that the discovery rate for new classes has dropped to one per decade from about one per year during the 1980s. Indeed, only 11 distinct ribozyme classes have been experimentally validated to date. Recently, we recognized that self-cleaving ribozymes frequently associate with certain types of genes from bacteria. Herein we exploited this association to identify divergent architectures for two previously known ribozyme classes and to discover additional noncoding RNA motifs that are self-cleaving RNA candidates. We identified three new self-cleaving classes, which we named twister sister, pistol and hatchet, from this collection, suggesting that even more ribozymes remain hidden in modern cells.
We learn a little more about what Pistol does from a paper in the journal RNA (2015):

Self-cleaving ribozymes are widespread across all domains of life and their architectural diversity is unmatched by any other type of natural catalytic RNA. These ribozymes have the ability to cleave their ribose-phosphate backbone at specific sites via internal phosphoester transfer with rate constants that typically exceed 10 million fold over that of spontaneous RNA degradation. The nine known self-cleaving ribozyme classes are able to accomplish this function by using a variety of structures that form unique catalytic cores....
All of this is irrelevant to the origin of life. We've only been told that RNA ribozymes are exceedingly rare, and they are not nearly as versatile as protein enzymes. All the ribozymes described have been found in living cells, coded by DNA for specific functions. But in the primordial soup could it happen? In the Illustra film Origin, Ann Gauger explains how delicate RNA is in the lab. How much more unlikely would it form spontaneously in the "absolute mess" of the chemical soup, as Paul Nelson describes the primordial ocean? Tim Standish adds, "If you just look at an RNA molecule, it seems to fall to pieces" -- even faster in water!

In Susan Mazur's book The Origin of Life Circus, leading origin-of-life researchers describe the utter disaster of the RNA world scenario in one-on-one interviews she recorded in person.

Lawrence Krauss tells her (p. 35): "The question is, can RNA result naturally? That's been a big stumbling block."

David Deamer tells her (p. 43) that the RNA and DNA monomers don't link up naturally: "the laws of thermodynamics do not allow them to polymerize because there is a tremendous energy barrier to getting them to form bonds." That's especially true in water, he says, which breaks down (hydrolyzes) RNA.

Sara Walker tells Mazur that researchers need to move away from the RNA World, "because most of the origin-of-life community don't think that's the definitive answer." Walker herself says, "I don't see how an RNA world with only RNA can work" (p. 68).

Loren Williams tells her the original RNA World ("all RNA, all the time, and nothing else") is unreasonable and dead. RNA can't have done everything originally claimed. "Another problem is related to the origin of RNA itself. Where did RNA come from? Where did RNA precursors come from?" (p. 96).

Steven Benner tells Mazur (p. 81), "we don't know how useful function is distributed among sequence spaces. You have 4 raised to the power of 100 different sequences of RNA 100 nucleotides long. We don't know how productive function is distributed there compared to destructive function." Chances are destructive processes are increased as much as productive processes, he adds. On page 151-152, Benner lists four major "paradoxes" of the RNA world: the tar problem, the water problem, the entropy problem and the destruction problem.

RNA-world champion Nick Hud has abandoned the idea that RNA would form on its own. He's looking for candidates of not only proto-RNA, but "pre-proto-RNA" because, as Mazur reminds him, "RNA itself falls apart" (p.87).

Stuart Kauffman tells Mazur that they "tried for 40 years to get single-stranded RNA molecules to replicate, perhaps hundreds of chemists, and they all failed. It should work. But it hasn't. And after 40 years or 50 years, you think - maybe it's the wrong idea. People really tried hard" (p. 111).

Jack Szostak ups the time estimate to 60 years that researchers have worked on this problem of non-enzymatic replication. "The problem is RNA falls apart," he says (p. 218).

Norm Packard tells Mazur, "There are issues with the RNA world approach. The main one is how do you get RNA starting to get produced in the first place" (p. 297). He envisions an enzyme doing it. This speculation, of course, leads to an obvious problem: "But how do you get that enzyme?"

Pier Luigi Luisi is merciless in his attack, calling the RNA world a "baseless fantasy." Mazur puts his criticisms in bold print on pages 362-363, where he finds it "full of conceptual flaws," including its origin, the thermodynamics, the sequencing problem, the concentration problem, and more. The story of RNA turning into ribozymes he calls "chemical non-sense" (p. 363).

Luisi then makes a confession so bold, Mazur says, "It's remarkable to hear you say that."

The real problem is to make ordered sequences of amino acids, of or course ordered sequences of nucleic acids -- and on that the prebiotic RNA world is absolutely silent. But this view of the prebiotic RNA world is still the most popular. I think it is a case of social science psychology more than science itself.
We're reminded of Harold S. Bernhardt's description of the RNA world: "the worst theory of the early evolution of life (except for all the others)."

With these comments from leaders in the origin-of-life field in mind, we return to the Pistol paper. Don't you think it's a bit disingenuous of the authors to mention the RNA world? Given their findings only show programmed function within living organisms that build the ribozymes from the DNA code, what possible relevance does that have to a "baseless fantasy" with so many paradoxes and problems? Could they be engaging in "social science psychology more than RNA itself"?


You decide. We'll stick with the positive. We do know of a cause now in operation that can "make ordered sequences" of building blocks and get them to interact in functional ways. That cause (need one say?) is intelligence.

Engineering v.Darwin.

Doug Axe: Hidden Figures and the Engineering Challenge to Darwinism
David Klinghoffer


Ahead of tomorrow night's Academy Awards ceremonies, Doug Axe has an excellent post up at  The Stream on the film  Hidden Figures  and the engineering challenge to Darwinism. The film, with several nominations including Best Picture, is the story of African-American women who were math prodigies, or "computers," at NASA.

Hidden Figures -- the true story of three brilliant African-American women who proved themselves in a 1960s NASA culture dominated by white men -- is sure to inspire. The film is filled with emotive lessons, most powerfully a vindication of the hope that those who persevere honorably for a just cause will not be disappointed.
Another lesson, more pragmatic, occurred to me as the drama unfolded. Having migrated in my own career from the measurable-fact culture of engineering to the more descriptive culture of biology, I felt a tinge of nostalgia as I watched a roomful of nerds with their calculators and chalk boards working together to find the answer to a pressing question: How can we bring an orbiting astronaut back safely to Earth?

Notice the very pre-post-truth essence of that phrase find the answer. Engineers have always taken for granted that clearly posed questions have uniquely correct answers -- there to be found by anyone with the skill to find them, and unambiguously recognized as correct when found. The joy of Hidden Figures is that it sweeps away our prejudicial attitudes as to who might have these requisite skills.

Celebrating National Engineers Week here yesterday, Sarah Chaffee observed,"[E]ngineering and medicine differ from evolutionary biology in that they focus on how things work. Evolutionists can seem at times to disregard function, but doctors and engineers never can." Yes, there's a blurred, fudging quality to much of evolutionary thinking.

By contrast, Dr. Axe admires the steely, unforgiving nature of an engineer's calculations:

There's something comfortably reassuring about the existence of steel-hard facts -- assertions that either end all opposition by proving true or end all sympathy by proving false. Maybe there's even a hint of beauty here -- in the stark simplicity of people putting their heads and hands to a challenge in a way that either succeeds or doesn't, with no fuzziness in-between.
Of course, those who've turned fuzziness into a paid profession are apt to sense more threat here than beauty. A famous 1960s meeting demonstrated this, convened under the heading Mathematical Challenges to the neo-Darwinian Interpretation of Evolution. There, a group of slide-rule toting engineering types, unconcerned with matters of etiquette, tried to put the slippery blob of evolutionary theory through the grinder gears of hard reality. Among the Darwinists present was Harvard's Ernst Mayr, who (in protest) titled his talk: "Evolutionary challenges to the mathematical interpretation of evolution." Stick that in your gears, you nerdy engineers!

This is rather unforgiving of Dr. Axe:

Here's the steel-hard fact they most want to avoid:
The evolutionary explanation of life cannot stand up to NASA-style engineering scrutiny.

If you doubt this, please join me in testing it. Hand pick your Darwin sympathizers from the most esteemed places. It doesn't matter who they are, because all the pomp and prestige of the academic world is powerless to change hard facts. All claims of Darwin having discovered the only scientifically valid explanation of life get torn to tiny bits when you put them in the grinder.

The response to this challenge is sure to be either silence or protest. There won't be a nerdy evolutionary biologist who marches up to the chalkboard and does the math that saves the theory. The math has been done; the theory undone. Nor will there be a lab test that shows natural selection to be a worker of wonders. We've been there. Too many tests to count, and the blind watchmaker never showed up.

The protest will be familiar, organized around the usual defensive themes. Different sciences work differently! -- they'll say. It isn't reasonable to hold a historical science to engineering standards! -- they'll say. No practicing evolutionary biologist would accept your proposal as valid! -- they'll say.

Let them speak. Then remind them that the difference is simply one of seriousness. When we really need to know that something will work, tested-and-approved certainty has always been the standard. Evolutionists ignore that standard because they can. Storytelling works for them because they're all telling stories together. Their grand stories are all wrong, but as long as no one is dying in orbit, most people are content to let them carry on.

Merciless, but true. Evolutionary theory's authority rests on muzziness as to details, and on the public's being willing to overlook and forgive it, despite what Axe identifies in his book  Undeniable as our universal intuition of intelligent design in nature.


"Trust us," Darwinists in effect say. Trust our massive extrapolation to a grand theory from a spray of trivial observations (finch beaks, smaller voles, etc.). "Trust" is not a factor in engineering. Either you bring the astronaut safe and alive back to Earth, or you do not. There's no fudging that.

Friday, 24 February 2017

Trivial pursuit?

Smaller Voles: "Evolution in Action" Is Rare, Trivial
David Klinghoffer 

News from the  University of Zurich  is notable both for how underwhelming it is and for a "rare" admission. Researchers documented that as winter came earlier, snow voles got smaller. That seemed counterintuitive since, as the title of the publication in PLOS Biology asks rhetorically, "Bigger Is Fitter?"

Well, isn't it? Not so in this case, apparently. Why?

In principle, larger snow voles are fitter: They have better capabilities to survive and reproduce. Despite this positive correlation at the phenotypic level, however, a converse causal relationship was evident on the genotypic level. "The voles whose genetic make-up led to a lower body weight were the fittest, especially in years when the first winter snow fell earlier than usual," explains the biologist. This may be because lighter young are more likely to reach their final size before the weather deteriorates and winter comes.

Fine. Maybe so. But notice the welcome candor in announcing this result. Observing this cute mouse-like rodent getting a bit smaller seems to be pulled straight from the voluminous files of unimpressive evidence for Darwinian evolution's grand claims. Evolution is supposed to explain how fantastic novelties arise, not merely why a little animal gets a bit smaller (or bigger). Even such an instance, though, they say repeatedly, is "extremely rare."

Researchers from the University of Zurich have succeeded in documenting an extremely rare case of evolutionary adaptation "in action" among wild snow voles near Chur.

...

Although this process is well understood in breeding conditions and in the lab, it is still largely unclear how often and how rapidly it takes place under natural conditions. Examples of contemporary adaptive evolution remain extremely rare.

...

If the scientists had restricted their observations solely to phenotypic traits, such as body size and weight, this rare example of "evolution in action" in the wild would have remained hidden. [Emphasis added.]

And again, from the Abstract:

In natural populations, quantitative trait dynamics often do not appear to follow evolutionary predictions. Despite abundant examples of natural selection acting on heritable traits, conclusive evidence for contemporary adaptive evolution remains rare for wild vertebrate populations, and phenotypic stasis seems to be the norm.


So stasis is the "norm," and seeing "evolution in action" in the wild is "extremely rare." And where found, as it was here, one might add that it is pretty trivial. Perhaps they thought were weren't listening.

Third way=no way?

Munchausen Syndrome: Perry Marshall Debates Stephen Meyer on the "Third Way" of Evolution
Evolution News & Views 

Justin Brierly of the radio program Unbelievable? out of the U.K. is a gem of an interviewer, regularly bringing together advocates of competing views on biological origins for startlingly rich, serious, and civil discussion.

He's done that again now with  a program featuring our colleague Stephen Meyer and Perry Marshall, author of the book  Evolution 2.0. Meyer and Marshall were both present for November's  Royal Society meeting  and they debate whether the Third Way of Evolution folks, who organized the meeting, are hot on the trail of a replacement theory for failed neo-Darwinism.

Dr. Meyer, while respecting Third Way critiques of orthodox evolutionary thinking, argues that a more fundamental paradigm shift is called for by the scientific evidence -- namely an inference to intelligent design. Marshall promotes the Third Way view, and his slogan is "Darwinists underestimate nature, and Creationists underestimate God." (He puts ID "in that same camp," the "creationist" one, but we're not going to argue with him about that right now.) An electrical engineer with a background in marketing and sales, he explains his approach in terms of "market share."

I take the position I take, because if I take the old school Neo-Darwinist position I will lose market share every year as more and more things turn out to be orderly instead of random.
If I take the creationist or Intelligent Design/Discovery Institute position, I will lose ground every year as they explain more and more evolutionary steps with observable processes.

But if I take the Third Way view, my market share will grow and grow because the explanatory power of an integrationist, non-reductionist paradigm which also considers consciousness.

That may sound a bit crass. Meyer counters that science is about getting at the truth, not pursuing a "market."

I think a lot of what's driving Perry is what he was talking about with "market share." How do you position a more theistically oriented way of looking at the natural world to get people who are atheist or agnostic to take you seriously?
I think at the end of the day you have to set those things aside and say what is nature telling us, and then develop an understanding of both the origin and development of life that is consistent with the evidence.

The issue comes down to whether the information at the heart of biology can be accounted for without reference to a designing agent operating in the course of life's long history. As Marshal prefers to say, was this information required for biological innovation front-loaded in the first bacterial cells so that it comes from within the animal, not from a source without? Talking about the research of leading Third Way figure James Shapiro at the University of Chicago, Meyer identifies two key issues:

I also think Shapiro's work is extremely interesting, and it's certainly cutting some new ground in biology. What Shapiro is talking about -- and I discuss Shapiro's work and five of the other Third Way mechanisms that have been proposed, these non-neo-Darwinian mechanisms of evolutionary change -- in Darwin's Doubt in two of the key chapters of the book.
What I show there is invariably what is going on is these new mechanisms either presuppose unexplained sources of information, or they simply don't explain the origin of necessary information to get real anatomical novelty. In other words, there are limits on what these mechanisms can produce.

Take Shapiro's work. He's describing ways in which organisms respond in real time to environmental stresses. Then they produce a response in the way that either they express pre-existing genetic information, or the way they ramp up the mutation rate in very specific parts of the genome to explore possibilities that are already latent in the genetic information.

So what he's talking about is a kind of pre-programmed adaptive capacity which he says is under "algorithmic control."

That's all extremely cool. It is very elegant the way organisms can do that, but the question that Shapiro doesn't address is: where does the pre-programming come from? Where does that algorithm come from? There's a higher level of informational programming at work that's presupposed in this whole process that he doesn't attempt to explain.

My concern about using this as an explanation for the whole of what we see in biological evolution is two-fold. First, you can't really propose that all this information is already in all these different organisms, and every organism has its own preprogramming to respond in different ways according to its organismal needs.

I don't think it's plausible to say that all this information could have been front-loaded in the circular chromosome of the bacterial cell at the point of the origin of life. Clearly you're going to need additional information at discrete points along the biological timeline.

Just getting from prokaryotes to eukaryotes requires an extensive reworking of the whole system of storage of genetic information. But secondly, and I think this is really a key thing, this is one of the key problems, it is the problem of epigenetic information.

Not all the information to build a body plan is in DNA. DNA codes for building proteins, but proteins have to be organized into bio-synthetic pathways that would characterize different kinds of cells and cell types.

Different cell types have to be organized into different tissues. Different tissues have to reorganize into different organs.

And organs and tissues have to be organized into whole body plans. The information for doing that is not solely in the DNA. Higher levels of information stored elsewhere are required to organize all those different levels of the biological hierarchy.

Shapiro is focusing on Natural Genetic Engineering, and has said he might get novel proteins out of this, but he's not going to explain the origin of a body plan. And that's the really crucial question biologically. Where did that higher-level innovation come from?

Both the Third Way crowd and their advocate Mr. Marshall position themselves as offering an alternative to Darwinism and ID. Marshall thinks Darwinists and ID theorists alike are missing what he plainly can see -- that evolution is real and a beautiful thing because it comes from within the organism, within the universe, itself.

On his website, Marshall has  helpfully transcribed the whole program, adding annotations of his own. He writes:

It's the biggest untold story in the history of science and the Neo-Darwinists have completely missed it. The creationists and the Discovery Institute have completely missed it as well. You would never know from reading a Richard Dawkins book or a Stephen Meyer book that you can get a completely new species in two years, and maybe even two days, from symbiogenesis or hybridization. Or that you can witness a radical innovation from a single cell in just 12 hours.
Neo-Darwinism is about miracles of randomness which can never be quantified or demonstrated. It's the biggest mistake in the history of science. And despite Meyer's insistence to the contrary,   Intelligent Design is still God of the gaps. The two are symmetrical. Neither offers you a mechanism that qualifies as empirical science. Neither helps the scientist do his real job, which is to explain every evolutionary step in reproducible detail.

And neither is telling you the REAL story -- that organisms possess tools of Natural Genetic Engineering and freedom to evolve on their own. It's the purpose of my book Evolution 2.0 to tell that story.

He refers to symbiogenesis  and hybridization. But how much of those processes are an organism simply activating pre-programmed information? This is not macroevolution in action. Where does that pre-programmed information come from? It cannot be from the organism itself, as Marshall suggests.

Why? On the issue of pre-programming or front-loading information, our new colleague, the paleontologist and now Center for Science & Culture Senior Fellow  Günter Bechly, notes three problems. He writes:

One of the problems with Marshall's approach is that we have brains: according to Marshall the intelligent design in the genome is not to be explained with the infusion of information from outside the system, but with the organisms (including bacterial cells!) themselves being the intelligent agents of their own design. Given the lack of any physical basis for such intelligence on the level of simple organisms like bacteria, this intelligence must be based on an immaterial mind.
This is clearly documented by Marshall's explicit endorsement of Robert Lanza's "Biocentrism," which is one of the many popular varieties of "monistic idealism meets quantum mysticism." However, if even bacteria can achieve incredible intelligence and information processing abilities without a material brain, why is intelligent behavior in animals positively correlated with the complexity of their neural system? Why do we need brains at all?

A second problem is that it is not the organism that is said to evolve but populations, which would even imply a kind of hive mind to make sense of Marshall's approach.

Finally, there is the Munchausen problem that intelligent agents cannot be their own designers, because they have to come into existence before they can design anything.

In the end the crucial question is: What makes more sense when you already have come to the conclusion that biological design is caused by immaterial intelligent agency: that bacteria and worms are intelligent minds and brilliant genetic engineers, or that the intelligent designer is the omniscient and omnipotent immaterial mind (God), in which Marshall believes anyway for different reasons?


That Munchausen reference is to the satirical story of Baron Munchausen lifting and thus rescuing himself and his horse, stuck in a mire, by pulling upward on his own hair. That's not going to work. It's an apt image for what's wrong not only with Marshall's argument but with the Third Way approach in general.