Ann Gauger moves the goalposts

We've been discussing Ann Gauger's claim that evolution is impossible because she was unable to transform a modern enzyme into another related one by changing a small number of amino acids.

I pointed out that this is not how evolution works. In some cases, you can easily show that two enzymes with different specificities can evolve from a common ancestor that could carry out both reactions. Such enzymes are said to be "promiscuous."

Here's Ann Gauger's latest post: In Explaining Proteins (and Life), Here's What Matters Most. She says ...

So now, let's address enzyme evolution and the divergence of enzymes to produce related families and superfamilies. Larry Moran says that modern enzymes evolved by specializing from a promiscuous ancestor. As evidence, he says modern enzymes can sometimes catalyze reactions with several substrates (the chemicals they bind to and change), and that it is possible to shift these enzymes to favor one substrate over another. He gives several examples or provides links to them.

Here's another place where he and I agree. Promiscuous enzymes can be shifted with just a few mutations to a new reaction specificity, provided the capacity for the reaction already exists in the starting enzyme, and each step is small and selectable. They can evolve easily, because they can already carry out the reaction in question. Larry Moran's description of the process is actually quite good, despite the digs he takes at us.

It strikes me that Larry Moran would know we agree with him on these points if he had read our papers.

So, what's the problem?

Turns out that changing one related enzyme into another with a different specificity wasn't the goal of her experiment. Here's what she was really trying to do ...

The Big Problem

Here's the big problem -- the arrival of novelty.

Novelty or innovation means the appearance of something not already present. It's the opposite of promiscuity. So a way to create novelty is absolutely essential to explain modern cells, as I will demonstrate.

...

Here's the heart of the matter. Promiscuity cannot solve the problem of novelty. Mutation, natural selection, and drift cannot drive the creation of novelty of all those new protein folds. That's what Doug Axe and I have been testing all along, from Doug Axe's 2004 paper to this most recent one. Based on our experiments, the problem of how innovation originates remains unsolved.

Now I get it (not). What she and Doug Axe were really trying to do was to intelligently design an entirely new enzyme.

They failed.

Therefore Intelligent Design Creationism is falsified.

That seems logical to me.

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How to become a better teacher (not)

Here's a video by Dr. Lodge McCammon. He has a website: lodgemccammon.com. Here are his credentials.

Dr. Lodge McCammon is an educational innovator. His career began in 2003 at Wakefield High School in Raleigh, North Carolina, where he taught Civics and AP Economics. McCammon received a Ph.D. from NC State University in 2008 and continued his work by developing innovative practices and sharing them with students, teachers and schools across the world. McCammon is a musician who spends much of his time in the recording studio composing curriculum-based music. His songs and related materials can be found in Discovery Education Streaming. He is also an education consultant who provides professional services, including keynote speeches, presentations, curriculum development, and a variety of training programs.

Watch the video and discuss. I think you can guess what I think. I reject one of the basic premise; namely that online courses are taught by the very best teachers. How do we know who is the best teacher just by watching videos?

Here's a question for your consideration. It concerns "reflective teaching." Imagine that you record yourself teaching an incorrect version of the citric acid cycle or a flawed version of the Central Dogma of Molecular Biology. How many times do you have to watch that video to recognize that what you are teaching is wrong? Is it more than three? Less than ten?

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On the meaning of pH optima for enzyme activity

The students in my lab course measured the activity of trypsin at different pH's. They discovered that the enzyme was most active at a pH of about 8.0-8.5 and that activity fell off rapidly at pH values above and below this optimum. This is consistent with results in the published literature (see figure from Sipsos and Merkel, 1970). Here's the exam question ...

What was the pH optimum of trypsin activity? Can you explain this in terms of the normal biological function of the enzyme and the physiological conditions under which it is active? Do you expect there to be a strong correlation between the optimal pH of an enzyme’s activity and the pH of the cell/environment where it is active?

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Sipos, T., and Merkel, J. R. (1970) An effect of calcium ions on the activity, heat stability, and structure of trypsin. Biochemistry, 9:2766-2775 [doi: 10.1021/bi00816a003]

On the specificity of enzymes

Most biochemistry students are taught that enzymes are highly specific. It's certainly true that the stereospecificity of some enzymes is extraordinary but is it true in general? Here's one of the exam questions that the students in my course had to answer ....

All three of the enzymes (trypsin, alcohol oxidase, β-galactosidase) that you assayed in the past three months are active with several different substrates substrates. Is this behaviour typical or are most enzymes highly specific? Aminoacyl tRNA synthetases are the classic examples of enzymes that are highly specific. Why? Do aminoacyl-tRNA synthetases ever make mistakes?

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Using mass spec to find out how many protein-encoding genes we have

One of the other exam questions is based on an experiment students did with an enzyme they purified. They digested the enzyme with trypsin and then analyzed the peptides by mass spectrometry. They were able to match the peptides to the sequence databases to identify the protein and the species. The exam question is ...

Nobody knows for sure how many functional protein-encoding genes there are in the human genome. About 20,000 potential protein-encoding genes have been identified based on open reading frames and sequence conservation but it is not known if all of them are actually expressed. How can you use Mass Spec to find out how many functional protein encoding genes we have? [see the cover of Nature from May 29, 2014: click on about the cover]

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King Dick and PCR

The students in my lab course are writing their final exam. Prior to the exam they were given 22 questions and they knew that five of them would be on the exam. I thought that Sandwalk readers might enjoy coming up with answers to some of the questions.

The possible remains of King Richard III of England have recently been discovered. His identity has been confirmed by DNA PCR analysis. Descendants of his mother in the female line have the same mitochondrial DNA as King Richard. However, the results with the Y chromosome were surprising. None of the descendants in the all-male lineage had the same Y chromosome markers as King Richard. This is almost certainly due to something called a "false-paternity" event. (There are other ways of describing this event.) Given what you know about PCR, what are some possible sources of error in this analysis? Would you be prepared to go back in time and accuse one of the Kings of England of being a bastard? [Identification of the remains of King Richard III]

(The lab experiment was to analyze various foods to see if they were made from genetically modified plants.)

Note: It's extremely unlikely that the "false-paternity" event occurred in the lineage leading directly to any of the Kings and Queens of England.

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How many microRNAs?

MicroRNAs are a special class of small functional RNA molecules. The functional RNA is only about 22 nucleotides long and most of the well-characterized examples bind to mRNA to inhibit translation and/or destabilize the message.

The big questions for many of us are how many different microRNAs are there in a typical cell and how many of them have a real biological function. These questions are, of course, part of the debate over junk DNA. Are there thousands and thousands of microRNA genes in a typical genome and does this mean that there's a lot less junk DNA than some of us claim?

The journal Cell Death and Differentiation has devoted a special issue to microRNAs [Special Issue on microRNAs – the smallest RNA regulators of gene expression]. There are four reviews on the subject but none of them address the big questions.

That didn't stop the journal from leading off with this introduction ...

It is now well recognised that the majority of non-protein-coding genomic DNA is not “junk” but specifies a range of regulatory RNA molecules which finely tune protein expression. This issue of CDD contains an editorial and 5 reviews on a particular class of these regulatory RNAs, the microRNAs (miRs) of around 22 nucleotides, and which exert their effects by binding to consensus sites in the 3'UTRs of mRNAs. The reviews cover the role of miRs from their early association with CLL to other forms of cancer, their importance in the development of the epidermis and their potential as disease biomarkers as secreted in exosomes.

I'm not certain what the editors mean when they say that "it is now well recognised ..." I interpret this to mean that there are a large number of scientists who are completely uniformed about the structure of genomes and the debate over junk DNA. In other words, it is now well recognized that some scientists don't know what they are talking about.

I don't know any expert who would claim that 50% of large genomes consist of genes that specify regulatory RNAs involved in fine-tuning protein expression. Do you?

On a related issue, Wilczynska and Bushell begin their review with ...

Since their discovery 20 years ago, miRNAs have attracted much attention from all areas of biology. These short (~22 nt) non-coding RNA molecules are highly conserved in evolution and are present in nearly all eukaryotes.

Sequence conservation is an important criterion in deciding whether something is functional. In order to use conservation as a measure of function you have to establish some standards that let you distinguish between sequences that are "conserved" by negative selection and those that have drifted apart by random genetic drift.

What do Wilczynska and Bushell mean when they say that microRNAs are "highly conserved"? The most highly conserved genes exhibit about 50% sequence identify between prokaryotes and eukaryotes. They are almost identical within mammals. Other highly conserved genes are about 80% identical within animals (e.g. between insects and mammals). As far as I know, the sequences of most putative microRNAs aren't even similar within mammals and certainly not between mammals and fish.

The phrase "highly conserved" has become meaningless. It's now a synonym for "conserved" because nobody ever wants to just say "conserved" and they certainly don't want to say "moderately conserved" or "weakly conserved" even if it's the truth.

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Ann Gauger keeps digging

Ann Gauger and her creationist collaborator, Doug Axe, have been swapping amino acid residues in one kind of protein hoping to show that they cannot change it into another. They have deliberately ignored any clues that might be derived from assuming that evolution happened.

They have succeeded in their goal. None of their constructs have a different activity. They conclude that evolution is disproved.

Why fund basic science?

This video was the winner in the 2013 FASEB competition for "Stand Up for Science." The title was "Funding Basic Science to Revolutionize Medicine."

I'm sure their hearts are in the right place but I fear that videos like this are really just contributing to the problem. It makes the case that basic research should be funded because ultimately it will pay off in technologies to improve human health. If you buy into that logic then it's hard to see why you should fund research on black holes or studies of plate tectonics.

Don't we have a duty to stand up for ALL basic research and not just research that may become relevant to medicine? Besides, if the only important basic research that deserves funding is that which has the potential to contribute to medicine, then shouldn't funding be directed toward the kind of "basic research" that's most likely to pay off in the future? Is that what we want? I don't think evolutionary biologists would be happy but everyone working with cancer cells will be happy.

The best argument for basic research, in my opinion, is that it contributes to our knowledge of the natural world and knowledge is always better than ignorance. This argument works for black holes, music theory, and for research on the history of ancient India. We should not be promoting arguments that only apply to our kind of biological research to the exclusion of other kinds of basic research. And we should not be using arguments that reinforce the widespread belief that basic research is only valuable if it leads to something useful.

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A creationist argument against the evolution of new enzymes

Intelligent Design Creationists have found it impossible to make a positive case for intelligent design and the existence of a supernatural designer. Instead, they concentrate on trying to prove that evolution is wrong. Turns out, they're not very good at that either.

The latest attempt is by Ann Gauger posting on the best Intelligent Design Creationist website.¹ She outlines her case at: Is Evolution True? Laying Out the Logic.

On the irrelevance of Michael Behe

Michael Behe is one of the few Intelligent Design Creationists who have come up with reasonable, scientific, defenses of creationism. I give him credit for that and for the fact that it often takes some effort to show why he is wrong.

However, when he has been proven wrong he should admit it and move on. He should instruct his fellow creationists to move on as well. That's not what happened with respect to his book on The Edge of Evolution. Last July he doubled down when a new study appeared that refuted his claims. Amazingly, Behe said that his ideas were vindicated. I questioned his logic in: CCC's and the edge of evolution and Michael Behe's final thoughts on the edge of evolution.

After a thorough discussion, we conclude that Behe is wrong about his edge of evolution. There's nothing in evolutionary theory, or in experimental results, that prevents the evolution of new functions with multiple mutations.

Now Ken Miller has posted an article making many of the same points [Edging towards Irrelevance]. Miller rightly demands an apology from Behe but his main point is that Michael Behe's recent behavior has made him largely irrelevant in the debate over Intelligent Design Creationism. I agree.

What this means is that there is nobody left in the Intelligent Design Creationist community who deserves serious attention from scientists. It will still be fun dealing with them but the game has become more like whac-a-mole than science. PZ Myers¹ makes the same point: Aren’t we all more than a little tired of Michael Behe?.

It's kinda sad.

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1. Unfortunately, PZ weakens his case by misrepresenting Behe's argument. PZ says, The hobby horse he’s been riding for the past few years is the evolution of chloroquine resistance in the malaria parasite: he claims it is mathematically impossible." That's just not true. Behe's entire case rests on the fact that chloroquine resistance is well within the edge of evolution. Behe has no problem with the evolution of chloroquine resistance.

How to revolutionize education

I believe that we need to change the way we teach. But not the way you probably think. Watch this video to see what's really important about teaching.

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Hat Tip: Alex Palazzo, who I hope will help us make the transition to 21st century teaching.

For the King

My son Gordon and his friend Colby are working on a new game called "For the King." It looks really cool. (I'm playing with an early version.)

Check out the website: IronOaks Games. They are also on Facebook: IronOaks Games. Twitter is @IronOakGames where you can make suggestions and follow development.

This is a game that reminds you of Hack and Nethack except with much better graphics. I think all the old people (like me) are going to like it. Ms Sandwalk asked for a carnival and got it (see below) and I'm pumping for a university.

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Nature criticizes science hyperbole and bad science writing

There's a very interesting editorial in the Oct 14, 2014 issues of Nature [see here]. It's about a scientific paper that turned out to be misleading and the role of science writers and journals in promoting that story.

The editors of Nature remind us that ...

Extraordinary claims, as the saying almost goes, demand more scrutiny than usual to make sure they stand up. That is how science works. Claim and counter-claim: intellectual thrust and experimental parry.

They report on an upcoming meeting meeting of the Council for the Advancement of Science Writing in Columbus Ohio. Apparently, this council is composed of scientists and journalists and the goal of the meeting is to search for "lessons learned by scientists and science writers" in light of their publicity campaign promoting the flawed paper.

The Nature editors note that ...

The first thing to highlight is that such a thing as the Council for the Advancement of Science Writing even exists. Too many scientists dismiss the media and journalists as sloppy and unwilling to engage in both detail and ambiguity. In fact, there can be no branch of journalism as self-scrutinizing and anxious about its performance as that which covers science. It is hard to imagine political and sports reporters taking the time to discuss so thoroughly what (if anything) they did wrong after one of their stories went belly-up.

Indeed, that's admirable, but it's another example of journalistic hyperbole. I do not believe that this branch of journalism (science writing) is as "self-scrutinizing" as they would have us believe. I do not believe that science writers usually debate and discuss what they did wrong when a story goes belly-up.

But it may be true that science writers are increasingly "anxious" about their performance. Why are they so "anxious"? It's because they are doing a very sloppy job characterized by parroting press releases written by amateurs whose main goal is to promote their institution or by science journals that want publicity.

Science writers (and journals) used to get away with this but now ...

The (welcome) rise of the science blogger has fuelled this navel-gazing. Some bloggers seem to spend most of their time criticizing other science writers, or at least debunking examples of what they regard as inferior science writing. But they do lots of good stuff too. Although traditionalists lament the decline of science coverage in the mainstream press, a terrific amount of analysis and comment, much of it very technical, is happening online under their noses.

There's an interesting slip of the tongue in that paragraph. If science writers are really interested in self-scrutiny then they should welcome the arrival of a group of bloggers who point out their errors. This should be a "good" thing but the Nature editors clearly contrast this role (criticizing science writers) with other "good stuff" that bloggers do. Apparently the criticism of science writing doesn't count as "good stuff." It just makes science writers anxious—which they weren't before science bloggers came on the scene and pointed out what a bad job they were doing.

Nature then admits its complicity in hyping the event and not doing a proper skeptical analysis of the findings. The editors then get to an important issue.

Some may question the timing of the announcement, made when the paper was released on the Internet, not accepted or published by a journal, but at least the evidence was there to examine. If the scientists and the media both largely acted properly, then what should be discussed at next week’s meeting? It could do worse than start by screening the celebratory online video produced by ... and released to accompany the announcement. Scientists and journalists can include as many academic caveats as they like, but the sounds and images of champagne corks popping tend to render such statements of caution just that — academic.

There is a deeper issue here: science not by press conference but presented as an event. What in reality is a long, messy and convoluted process of three steps forward and two steps back is too easily presented as giant leaps between states of confusion and blinding revelation. At the heart of this theatre is the artificial landmark of a peer-reviewed paper. Fixed print schedules and releases to journalists under embargo (with or without champagne videos) help to lend the impression that the publication of a paper is the final word on a question — the end-of-term report on a scientific project that details all that was achieved.

I bet you're thinking that this is all about the ENCODE publicity campaign and how Nature was totally at fault for misrepresenting the data and hyping the false claims of the ENCODE Consortium.

Nope. It's about the discovery of gravitational waves—a paper that turns out to have been wrong because scientists didn't do the proper controls.

Meanwhile, Nature, and science writers in general, have yet to admit that they failed massively in September 2012 and they have done little to convince us "bad" bloggers that they are capable of self-scrutiny. This is serious because in this case Nature and its editors were very active participants in the making of videos and holding press releases [see How does Nature deal with the ENCODE publicity hype that it created?]. Let me remind you of the video PRODUCED BY NATURE featuring Senior Editor Magdalena Skipper in which she promotes the idea that most of the human genome is functional. [Note: I'm getting error messages when I try to run this video.]


Maybe there are other things that the Council for the Advancement of Science Writing could be talking about? Maybe there are other examples of bad science journalism that the editors of Nature should be addressing?

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Creationists trash Denmark

Denmark present a real problem for many Christians. It appears to be a successful secular society that has all but abandoned extreme forms of religion. These Christians can't figure out how a country could be moral if it's full of nonbelievers.

Vincent Joseph Torley (vjtorley) has found the answer [Is something rotten in the state of Denmark?]. He's responding to claims by Jerry Coyne that Denmark is a successful country.

Perhaps Coyne might be interested to read an eye-opening article by Carol Brown over at American Thinker on what is happening in Denmark. Ms. Brown paints a terrifying portrait of a society which is falling apart under the influence of religiously motivated violence. Crime in Denmark has exploded, and street gangs "have taken over large parts of Danish towns and cities. There are numerous "no go" zones where even the police are afraid to venture. Is this Coyne’s idea of a successful secular society?

Some morals to be drawn from Brown’s article:

1. Not all forms of religion are good; some are toxic.

2. Nature abhors a vacuum. Secularism is powerless to drive out toxic forms of religion.

3. The only proven way to drive out toxic forms of religion, and keep them out, is with wholesome forms of religion.

I was in Denmark for seven days and I never saw any sign of this sort of lawlessness or even heard about it. But maybe I was just in the wrong places? Or maybe it's not true? (Heavens!)

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