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Monday, March 18, 2013

Estimating the Human Mutation Rate: Biochemical Method

This is the second in a series of posts on human mutation rates and their implication(s). The first one was ...
What Is a Mutation?

There are basically three ways to estimate the mutation rate in the human lineage. I refer to them as the Biochemical Method, the Phylogenetic Method, and the Direct Method.

The biochemical method relies on the well-known fact that the vast majority of mutations are due to errors in DNA replication. Since we know a great deal about the replication complex and the biochemistry of the reactions, we can calculate a mutation rate per DNA replication based on this knowledge. The details are explained in a previous post [Mutation Rates]. I'll give a brief summary here.

The overall error rate of DNA polymerase in the replisome is 10-8 errors per base pair. Repair enzymes fix 99% of these lesions for an overall error rate of 10-10 per bp. That means one mutation in every 10 billion base pairs that are replicated.

Theme

Mutation

-definition
-mutation types
-mutation rates
-phylogeny
-controversies
The human haploid genome is 3.2 × 109 bp. [How Big Is the Human Genome?] [How Much of Our Genome Is Sequenced? ]. That means that on average there are 0.32 mutations introduced every time the genome is replicated. In the male, there are approximately 400 cell divisions between zygote and the production of a sperm cell.1 This gives a total of about 128 new mutations in every sperm cell. In the female, there are about 30 cell divisions between zygote and the production of egg cells. That's about 10 new mutations in every egg cell.

Adding these together gives us about 138 new mutations in every zygote. Let's round this down to 130. Thus the estimate from the Biochemical Method is ..

130 mutations per generation


[Image Credit: Wikipedia: Creative Commons Attribution 2.0 Generic license]

1. This depends on the age of the man when he has children. The value used here is approximately the average for a 30 year old man.

Monday's Molecule #200

This is the 200th Monday's Molecule. I started this series back on November 13, 2006. Today's molecule is a repeat of that first one. Let's see if readers in 2013 can do better than those in 2006! The last "Monday's Molecule" was puromycin [Monday's Molecule #199]. The winners were Bell Gunn and River Jiang. River needs to contact me by email to set up a lunch date. I'm going to try and treat all the previous winners this week so if I owe you a lunch you should get in touch right away to collect.

The mystery molecule is an aldohexose. There are 16 different aldohexoses. The structures and names of 8 of them are show below in order to help you out.

This is a tough one. You have to know several carbohydrate naming conventions and you have to understand Fischer projections. Good luck.



Post your answer as a comment. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.)

Sunday, March 17, 2013

Michael Behe in Toronto: "Evidence of Design from Biology"

Michael Behe gave a talk on the second day of his visit to Toronto (November 16, 2012). This event was sponsored by religious groups even though Intelligent Design has nothing to do with religion—it's strictly a scientific theory.

The video of his first talk is: "What Are the Limits of Darwinism?". Here's his second talk entitled "Evidence of Design from Biology." There were about 100 people in the audience. I'd guess that half of them were supporters and half were skeptics.

Here's the summary of his talk.
  • Design is not mystical. Deduced from physical structure of a system
  • Everyone agrees aspects of biology appear designed
  • There are structural obstacles to Darwinian evolution
  • Grand Darwinian claims rest on undisciplined imagination
  • Bottom line: Strong evidence for design, little evidence for Darwinism



Happy Saint Patrick's Day!

One of the cool things about studying your genealogy is that you can find connections to almost everyone. This means you can celebrate dozens of special days. In my case it was easy to find ancestors from England, Scotland, Netherlands, Germany, France, Spain, Poland, Lithuania, Belgium, Ukraine, Russia, United States, and, of course, Ireland.

We will be celebrating St. Patrick's Day today. It's rather hectic keeping up with all the national holidays but somebody has to keep the traditions alive!

Here's my Irish connection.1 The shortest connection is to the parents of my grandmother. My great-grandfather was Thomas (Keys) Foster, born in County Tyrone on September 5, 1852. He immigrated to Canada in 1876. Thomas married Eliza Ann Job, born in Fintona, County Tyrone on August 18, 1852. She immigrated to Canada in 1877.

Thomas and Eliza settled in Saskatchewan in 1883 and that's where my grandmother was born. Other ancestors in this line came from the adjacent counties of Donegal (surname Foster) and Fermanagh (surnames Keys, Emerson, Moore) and possibly Londonderry (surname Job).

My paternal grandfather's father was William Findley Docherty (1852-1920). Many of his ancestors were Irish but his DNA was considerably diluted by contamination from Scots.

That makes me at least one quarter Irish2 and entitles me to drink beer and wear green. My children, however, are only one eighth Irish. They aren't allowed to drink beer.


Happy St. Patrick's Day (2011)
Happy St. Patrick's Day (2010)
Happy St. Patrick's Day (2009)
Happy St. Patrick's Day (2008)
Happy St. Patrick's Day (2007)
Niall Nóigiallach - Niall of the Nine Hostages


1. You don't have to be Irish or have Irish ancestors to celebrate St. Patrick's Day.

2. With the proviso that my Irish great-grandparents are probably descended from English setters who came to Ireland in the 1600s. I usually don't mention this on St. Patrick's day.



Saturday, March 16, 2013

The Purpose of "The Scientific Dissent from Darwin" List

A few years ago the IDiots tried to collect a list of credible scientists who supported creationism. They created a statement called "The Scientific Dissent from Darwin." It goes like this ...
We are skeptical of claims for the ability of random mutation and natural selection to account for the complexity of life. Careful examination of the evidence for Darwinian theory should be encouraged.
Only an IDiot would claim that supporters of this statement are also creationists. Many atheist scientists, including me, would agree with the statement. Nevertheless, if you look at the list of people who signed [Scientific Dissent from Darwin List] you'll not find very many evolutionary biologists because we all know that the IDiots will misuse this list.

A few days ago someone named Joshua Youngkin posted to Evolution News & Views (sic) in response to a question about the list. According to Youngkin, the list "is a thorn in the side of those who say there's no scientific debate over whether evolution works in a completely naturalistic fashion."

Why is that? The statement doesn't say anything about god or naturalism. This is exactly the kind of doubletalk you expect from IDiots.

Later on in the post Joshua Youngkin says,
The Dissent from Darwin statement counters and preempts any claim that (1) there is no scientific dissent over how evolution happens, by what means, that is, or that (2) it is unscientific to be skeptical of the proposition that natural selection and random mutation together satisfactorily explain the development of life over time.
There are plenty of ways to "preempt" such a false claim. Reading the scientific literature is one.

The list does serve one important purpose and for that we are truly thankful. It's the best list of Ph.D IDiots that I know of. It's easy to find your local IDiots using a simple word search. For example, I found these names from the University of Toronto: Stephen J. Cheesman Ph.D. Geophysics and Alfred G. Ratz Ph.D. Engineering Physics. Unfortunately, as I pointed out some years ago [I'm not a Darwinist, but I Ain't Signing], neither of these gentlemen are listed in the university phone book and they are not on the University website so we don't know what they are up to these days.

Project Steve with 1249 signatures, is an excellent parody of the creationist list.


Friday, March 15, 2013

On the Meaning of the Word "Function"

A lot of the debate over ENCODE's publicity campaign concerns the meaning of the word "function." In the summary article published in Nature last September the authors said, "These data enabled us to assign biochemical functions for 80% of the genome ...." (The ENCODE Project Consortium, 2012).

Here's how they describe function.
Operationally, we define a functional element as a discrete genome segment that encodes a defined product (for example, protein or non-coding RNA) or displays a reproducible biochemical signature (for example, protein binding, or a specific chromatin structure).
What, exactly, do the ENCODE scientists mean? Do they think that junk DNA might contain "functional elements"? If so, that doesn't make a lot of sense, does it?

Ewan Birney tried to address this definitional morass on his blog [ENCODE: My own thoughts] where he says ....
It’s clear that 80% of the genome has a specific biochemical activity – whatever that might be. This question hinges on the word “functional” so let’s try to tackle this first. Like many English language words, “functional” is a very useful but context-dependent word. Does a “functional element” in the genome mean something that changes a biochemical property of the cell (i.e., if the sequence was not here, the biochemistry would be different) or is it something that changes a phenotypically observable trait that affects the whole organism? At their limits (considering all the biochemical activities being a phenotype), these two definitions merge. Having spent a long time thinking about and discussing this, not a single definition of “functional” works for all conversations. We have to be precise about the context. Pragmatically, in ENCODE we define our criteria as “specific biochemical activity” – for example, an assay that identifies a series of bases. This is not the entire genome (so, for example, things like “having a phosphodiester bond” would not qualify). We then subset this into different classes of assay; in decreasing order of coverage these are: RNA, “broad” histone modifications, “narrow” histone modifications, DNaseI hypersensitive sites, Transcription Factor ChIP-seq peaks, DNaseI Footprints, Transcription Factor bound motifs, and finally Exons.
That's about as clear as mud.

We all know what the problem is. It's whether all binding sites have a biological function or whether many of them are just noise arising as a property of DNA binding proteins. It's whether all transcripts have a biological function or whether many of those detected by ENCODE are just spurious transcripts or junk RNA. These questions were debated extensively when the ENCODE pilot project was published in 2007. Every ENCODE scientist should know about this problem so you might expect that they would take steps to distinguish between real biological function and nonfunctional noise.

Their definition of "function" is not helpful. In fact, it seems deliberately designed to obfuscate.

Let's see how other scientist interpret the ENCODE results. In a News & Views article published in Nature last September, Joseph R, Ecker (Salk Institute scientist) said ...
One of the more remarkable findings described in the consortium's 'entré' paper is that 80% of the genome contains elements linked to biochemical function, dispatching the widely held view that the human genome is mostly 'junk DNA.'
That makes at least one genomics worker who thinks that "biochemical function" and junk DNA are mutually exclusive.

Recently a representative of GENCODE responded to Dan Graur's criticism [On the annotation of functionality in GENCODE (or: our continuing efforts to understand how a television set works)]. This person (JM) says ...
Q1: Does GENCODE believe that 80% of the genome is functional?

As noted, we will only discuss here the portion of the genome that is transcribed. According to the main ENCODE paper, while 80% of the genome appears to have some biological activity, only “62% of genomic bases are reproducibly represented in sequenced long (>200 nucleotides) RNA molecules or GENCODE exons”. In fact, only 5.5% of this transcription overlaps with GENCODE exons. So we have two things here: existing GENCODE models largely based on mRNA / EST evidence, and novel transcripts inferred from RNAseq data. The suggestion, then, is that there is extensive transcription occurring outside of currently annotated GENCODE exons.
There's another scientist who thinks that 80% of the genome has some biological activity in spite of the fact that the ENCODE paper says it has "biochemical function." I don't think "biological activity" is compatible with "junk DNA," but who knows what they think?

Since this person is part of the ENCODE team, we can assume that at least some of the scientists on the team are confused.

The Sanger Institute (Cambridge, UK) was an important player in the ENCODE Consortium. It put out a press release on the day the papers were published [Google Earth of Biomedical Research]. The opening paragraph is ...
The ENCODE Project, today, announces that most of what was previously considered as 'junk DNA' in the human genome is actually functional. The ENCODE Project has found that 80 per cent of the human genome sequence is linked to biological function.
It looks like the Sanger Institute equates "biochemical function" and "biological function" and it looks like neither one is compatible with junk DNA.

I think the ENCODE leaders, including Ewan Birney, knew exactly what they were doing when they defined function. They meant "biological function" even though they equivocated by saying "biochemical function." And they meant for this to be interpreted as "not junk" even though they are attempting to backtrack in the face of criticism.

Function Wars
(My personal view of the meaning of function is described at the end of Part V.)

The ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57-74. (E. Birney, corresponding author)

Thursday, March 14, 2013

Anonymous Nature Editors Respond to ENCODE Criticism

There are now been four papers in the scientific literature criticizing the way ENCODE leaders hyped their data by claiming that most of our genome is functional [see Ford Doolittle's Critique of ENCODE ]. There have been dozens of blog postings on the same topic.

The worst of the papers were published by Nature—this includes the abominable summary that should never have made it past peer review (Encode Consortium, 2012).

The lead editor on the ENCODE story was Brendan Maher and he promoted the idea that the ENCODE results showed that most of our genome has a function [ENCODE: The human encyclopaedia]
The consortium has assigned some sort of function to roughly 80% of the genome, including more than 70,000 ‘promoter’ regions — the sites, just upstream of genes, where proteins bind to control gene expression — and nearly 400,000 ‘enhancer’ regions that regulate expression of distant genes.

Misconceptions about Random Genetic Drift

Genetic Drift

Evolutionary change that occurs by random sampling of different alleles from one generation to the next. This causes nonadaptive evolutionary change.

Jerry Coyne
"Why Evolution Is True"
There seem to be two important themes in the current pedagogical literature on science education. One of them is about student-centered learning—a concept I think we should all adopt. The other is about student misconceptions and how to deal with them. Much of the literature suggests that misconceptions need to be confronted and corrected. They can't be corrected by simply presenting the "correct" information. You need to actually address the misconception and show why it is wrong. This is a form of "teach the controversy" and that's not going to sit well with many American supporters of evolution.

Here's an interesting paper on "Biology Undergraduates’ Misconceptions about Genetic Drift" (Andrews et al., 2012). The abstract covers all the important points.

Barry Arrington Demonstrates IDiot Logic

A few years ago Barry Arrington came up with this killer argument against evolution [see Question: How Can We Know One Belief Selected for By Evolution is Superior to Another?].
Theist: You say there is no God.
Evolutionary Materialist [EM]: Yes.
Theist: Yet belief in God among many (if not most) humans persists.
EM: I cannot deny that.
Theist: How do you explain that?
EM: Religious belief is an evolutionary adaption.
Theist: But you say religious belief is false.
EM: That’s correct.
Theist: Let me get this straight. According to you, religious belief has at least two characterizes: (1) it is false; and (2) evolution selected for it.
EM [looking a little pale now, because he’s just figured out where this is going]: Correct.
Theist: You believe the Neo-Darwinian Synthesis [NDS] is true.
EM: Of course.
Theist: How do you know your belief in NDS is not another false belief that evolution has selected for?
EM: ___________________

Our materialist friends are invited to fill in the blank.

Wednesday, March 13, 2013

Ford Doolittle's Critique of ENCODE

Ford Doolittle has never been one to shy away from controversy so it's not surprising that he weighs in against the misleading publicity campaign launched by ENCODE leaders last September (Doolittle, 2013). Recall that Ewan Birney and other prominent members of the consortium promoted the idea that our genome contained an extensive array of regulatory elements and that 80% of our genome was functional [Ewan Birney: Genomics' Big Talker] [ENCODE Leader Says that 80% of Our Genome Is Functional] [The ENCODE Data Dump and the Responsibility of Scientists].

This is the fourth paper that's critical of the ENCODE hype. The first was Sean Eddy's paper in Current Biology (Eddy, 2012). The second was a paper by Niu and Jiang (2012), and the third was a paper by Graur et al. (2013). In my experience this is unusual since the critiques are all directed at how the ENCODE Consortium interpreted their data and how they misled the scientific community (and the general public) by exaggerating their results. Those kind of criticisms are common in journal clubs and, certainly, in the blogosphere, but scientific journals generally don't publish them. It's okay to refute the data (as in the arsenic affair) but ideas usually get a free pass no matter how stupid they are.

In this case, the ENCODE Consortium did such a bad job of describing their data that journals had to pay attention. (It helps that much of the criticism is directed at Nature and Science because the other journals want to take down the leaders!)

What's Wrong with This Statement?

Read the following statement from the Wikipedia article on the Genetic Code.
... the genetic code used by all known forms of life is nearly universal with few minor variations. This suggests that a single evolutionary history underlies the origin of the genetic code.
What wrong with this statement? Cornelius Hunter says that the statement "... is false—at least from a scientific perspective" [Here is Why the DNA Code is a Problem]. Can you guess why this IDiot would make such a claim?

In contrast, an anonymous source at Uncommon Descent asks, "Does the Genetic Code Bear A Signature of Intelligence?." He/she posts the following abstract ...
It has been repeatedly proposed to expand the scope for SETI, and one of the suggested alternatives to radio is the biological media. Genomic DNA is already used on Earth to store non-biological information. Though smaller in capacity, but stronger in noise immunity is the genetic code. The code is a flexible mapping between codons and amino acids, and this flexibility allows modifying the code artificially. But once fixed, the code might stay unchanged over cosmological timescales; in fact, it is the most durable construct known. Therefore it represents an exceptionally reliable storage for an intelligent signature, if that conforms to biological and thermodynamic requirements. As the actual scenario for the origin of terrestrial life is far from being settled, the proposal that it might have been seeded intentionally cannot be ruled out. A statistically strong intelligent-like “signal” in the genetic code is then a testable consequence of such scenario. Here we show that the terrestrial code displays a thorough precision-type orderliness matching the criteria to be considered an informational signal. Simple arrangements of the code reveal an ensemble of arithmetical and ideographical patterns of the same symbolic language. Accurate and systematic, these underlying patterns appear as a product of precision logic and nontrivial computing rather than of stochastic processes (the null hypothesis that they are due to chance coupled with presumable evolutionary pathways is rejected with P-value < 10–13). The patterns display readily recognizable hallmarks of artificiality, among which are the symbol of zero, the privileged decimal syntax and semantical symmetries. Besides, extraction of the signal involves logically straightforward but abstract operations, making the patterns essentially irreducible to natural origin. Plausible ways of embedding the signal into the code and possible interpretation of its content are discussed. Overall, while the code is nearly optimized biologically, its limited capacity is used extremely efficiently to pass non-biological information.

According to Uncommon Descent, the article is written by two scientists. They turn out to be two mathematicians from the Republic of Kazakhstan [The “Wow! signal” of the terrestrial genetic code].

Can you guess why the IDiots would believe such a ridiculous claim?

I wonder if Cornelius Hunter thinks this is science?


Monday, March 11, 2013

Monday's Molecule #199

The last "Monday's Molecule" was phycoerythrin [Monday's Molecule #198]. The winner was Piotr Gasiorowski.

This week's molecule can do some very bad things to certain cells. You just have to give the common name and briefly explain what it does and how it works.

Post your answer as a comment. I'll hold off releasing any comments for 24 hours. The first one with the correct answer wins. I will only post mostly correct answers to avoid embarrassment. The winner will be treated to a free lunch.

There could be two winners. If the first correct answer isn't from an undergraduate student then I'll select a second winner from those undergraduates who post the correct answer. You will need to identify yourself as an undergraduate in order to win. (Put "undergraduate" at the bottom of your comment.)

Michael Behe in Toronto: "What Are the Limits of Darwinism?"

Michael Behe was in Toronto a few months ago (November 2012). He gave three talks while he was here. You can read my summaries at: Michael Behe In Toronto: Part 1,
Michael Behe in Toronto: Part 2, and Michael Behe in Toronto: Part 3. (You can also check out My Posts on Michael Behe)

The first talk was quite private and it was not recorded. The second talk, on a Thursday evening, was in one of the main lecture theaters in my building. There were at least 400 people in the audience. This talk was on the "Limits of Darwinism" and it was recorded. You can watch it in the video below.

Sunday, March 10, 2013

Not Believing in God(s) Is Terrible and Utterly Tragic

Imagine a typical1 citizen of a country in Western Europe. She doesn't believe in god(s) and neither did her parents or grandparents. How should she feel? Should she be depressed and overcome with a sense of hopelessness because there are no god(s) to save her?

Yes, according to Damon Linker who recently reviewed a book by A.C. Grayling [Where are the honest atheists? ]. The subtitle is: "That godlessness might be both true and terrible is something that the new atheists refuse to entertain."

Hmmm ... he's right about that. I haven't entertained the notion that not believing in imaginary beings might be "terrible." Why should I? Here's his answer ...

Bad Science in National Science Foundation (USA) Press Release

Jonathan Eisen is becoming one of my favorite bloggers. He alerts us to a horrible press release published recently by the National Science Foundation (USA):How to Thrive in Battery Acid and Among Toxic Metals.

It talks about a strain of red algae called Galdieria sulphuraria that has apparently inherited many genes from bacteria by lateral gene transfer. Here's how the press release hypes the result ...
The scientists made an unexpected discovery: Galdieria's genome shows clear signs of borrowing genes from its neighbors.

Many genes that contribute to Galdieria's adaptations were not inherited from its ancestor red algae, but were acquired from bacteria or archaebacteria.

This "horizontal gene transfer" is typical for the evolution of bacteria, researchers say.

However, Galdieria is the first known organism with a nucleus (called a eukaryote) that has adapted to extreme environments based on horizontal gene transfer.

"The age of comparative genome sequencing began only slightly more than a decade ago, and revealed a new mechanism of evolution--horizontal gene transfer--that would not have been discovered any other way," says Matt Kane, program director in the National Science Foundation's (NSF) Division of Environmental Biology, which funded the research.

"This finding extends our understanding of the role that this mechanism plays in evolution to eukaryotic microorganisms."

Galdieria's heat tolerance seems to come from genes that exist in hundreds of copies in its genome, all descending from a single gene the alga copied millions of years ago from an archaebacterium.

"The results give us new insights into evolution," Schoenknecht says. "Before this, there was not much indication that eukaryotes acquire genes from bacteria."
A "new mechanism of evolution" that was only revealed a decade ago by genome sequencing? Jonathan Eisen explains why this is so very wrong. You should read his post: Ugg - story about gene transfer/evolution based on NSF press release has a NASA-esque smell. I agree 100%. We've got to put and end to this kind of ridiculous hype and misrepresentation. It's damaging to science.1

The published results are interpreted as novel but only in the sense that the genes acquired from bacteria are (presumably) directly related to enhanced fitness (Schönknecht et al., 2013). Here's what the authors say in the paper.
Eukaryotic innovations usually arise through gene duplications and neofunctionalizations, which lead to expansion of existing gene families (8). In contrast, archaea and bacteria commonly adapt through horizontal gene transfer (HGT) from other lineages (9). HGT has also been observed in some unicellular eukaryotes (10); however, to our knowledge, horizontally acquired genes have not been linked to fitness-relevant traits in free-living eukaryotes
That point is reiterated in the summary.
These findings for G. sulphuraria mirror the results of a previous systematic study, which showed that proteobacterial adaptation relies on the horizontal acquisition of genes that function at the bacteria's interface to the environment (19). Whereas the importance of HGT for evolution of Bacteria and Archaea is well established, adaptation of a eukaryotic extremophile by gene transfer from Bacteria and Archaea is unexpected and shines a new light on the evolution of unicellular eukaryotes.
There's nothing about a new mechanism of evolution in the actual paper.


[Image Credit: Gerald Schönknecht]

1. Ed Yong gets it right: How the Lord of the Springs Survives Where Most Things Die, demonstrating, once again, that good science writers can cut through the hype and lies.

Schönknecht, G., Chen, W.H., Ternes, C.M., Barbier, G.G., Shrestha, R.P., Stanke, M., Bräutigam, A., Baker, B.J., Banfield, J.F., Garavito, R.M., Carr, K., Wilkerson, C., Rensing, S.A., Gagneul, D., Dickenson, N.E., Oesterhelt, C., Lercher, M.J., and Weber, A.P. (2013) Gene Transfer from Bacteria and Archaea Facilitated Evolution of an Extremophilic Eukaryote. Science 339:1207-1210. [PubMed] [doi: 10.1126/science.1231707]

Saturday, March 09, 2013

John Witton Will Pay You $1000 to Answer One of His Questions

John Witton doesn't know much about biochemistry, genetics, or evolution but he's willing to learn. He will pay you $1000 (US) if you can answer any one of the six questions he has posed. He made this offer in the comments to my post: Saturday, February 28, 1953.

Here's what he said ...
I have been known to cause some problems on other forums, for obvious reasons, but I had hoped that on this forum we will be able to get to the bottom of the problems such as" vitalism vs entropy barrier, self assembly of proteins, self-cell membrane formation, metabolism first vs RNA world, why did evolution need 600 types of mangoes and how did they evolve and why?

Why did Larry Moran and Craig Venter evolve to baldness only on the part of the scalp but they have retained their bushy hair on the side and lower back of their scalp????

For those who answer one of these question logically, I am willing to pay $1000.00
I offered to answer two questions; the one on self assembly of proteins and the one on why male pattern baldness evolved. I suggested that John Witton could send the check to a neutral third party and that we could agree on a judge who would decide whether I had answered the questions satisfactorily. I recommended Michael Behe as the judge for the first question and Michael Denton as the judge for the second question.

John Witton agreed. On Saturday, March 2, 2013, he said ...
I’m glad you took the bait Larry…for the lack of better word in English… You are not a very good bluffer though…I’m hoping you don’t play poker and bet large sums of money… Anyway, even though you are paddling back from some of the issues I have presented you know you can’t explain, I’m still going to pursue this transaction, since I can still nail you on those two issues you feel comfortable with…You have nothing to lose...or it might be a little bit of pride, which is fine with me… So, this is what I’m doing. I am sending two cheques $1000.00 US each to Michael Behe and Michael Denton with the explanation of our agreement. They may not like writing extensive explanation as to their judgment or nothing at all, except Larry or John is the winner in their view. We just have to accept that.
Then on Monday he said ...
I have contacted both Behe and Denton. I have emailed the Discovery Institute regarding our arraignment. Even The Star is interested, if Behe participates... I don't think anybody takes you seriously Larry... We'll see.. You seem to be a big mouth that writes text books nobody understands, even you ...;)
I checked with Michael Behe on Thursday but he still had not heard from John Witton. I wasn't able to find out how to contact Michael Denton ... I'm waiting for Witton to send me the contact information since he already got in touch. (If anyone has an email address please send it to me.)

As it turns out. Witton had the stomach flu so he didn't send the checks. I'm sure he'll send them as soon as he feels better. (Apparently the flu strain comes from Canada!)
Larry is right. I have not sent the cheques or the paper to Behe or Denton yet... I'm sick with a bad case of stomach flu...You don't have to believe me... I will try to contact you when I'm better...Sorry to all my supporters...
According to Witton he now "got Larry by the balls." I thought I should let all my enemies know about this so they can watch the spectacle. Some Sandwalk readers might want to help John by answering one of the other questions for $1000.

While we're waiting for John Witton to keep his word, you might enjoy this video of Robert Shapiro (not John Witton) questioning the work on the origin of life. It was posted by John Witton so presumably he likes it.



Friday, March 08, 2013

Former Canadian Senator Pat Carney Has Trouble Getting Along with Atheists

Last Sunday (March 3, 2013) CBC radio aired a discussion on "Does religion have a place in public life?" The host was Rex Murphy. You can listen to the entire thing at: Does religion have a place in public life?.

I want to draw your attention to a segment where former Canadian Senator Pat Carny talks about her esperience with atheists. (Carney was a cabinet minister under Prime Minister Brian Mulroney.) The excerpt is embedded below. If it doesn't work, click on Pat Carney MP3.

Here how she begins ...
... you're debating the wrong question. It's not the role of religion in public institutions. it's the difficulty of being a person of faith working with people who haven't any ... any religion. And I'm speaking as someone with 27 years in parliament ...
It gets worse. She claims that atheists simply don't share her values, such as the Golden Rule, therefore you can't find common ground when trying to make policy.

All I can say is that it's a damn good thing she doesn't live in Western Europe because those secular societies clearly don't exhibit any of the values she holds so dear.





[Hat Tip: Thanks to Tony Burns for preparing the audio excerpt.]

Thursday, February 28, 2013

Saturday, February 28, 1953

Friday night, after cutting out the cardboard bases, still deep in defeat Watson went home and then to the theatre. Saturday morning, February 28, he came in, cleared a place to work, got out his cardboard cutouts.
Though I initially went back to my like-with-like prejudices, I saw all too all too well that they led nowhere. When Jerry [Donohue] came in I looked up, saw that it was not Francis, and begin shifting the bases in and out of various other pairing possibilities. Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair held together by at least two hydrogen bonds. All the hydrogen bonds seem to form naturally; no fudging was required to make the two types of base pair identical in shape.1
Watson stumbled into this part of the solution visually, from a shape, a representation, and that had happened several times before; that is the way his mind works. Note two of the four kinds of bases have the same contour. Watson found that the purine adenine, a fused double ring with other atoms fringing it at several points, could form two hydrogen bonds with the pyrimidine thymine, a single ring, when he placed the two cutouts side by side in the right way. The bond were the correct length, and were straight lines, N—H--O or N--H—N, as Pauling's model-building precepts required. Guanine and cytosine made hydrogen bonds the same way. The pairing could not be switched, however, for then the various atoms around the fringes got in each other's way. But when an A-T pair was laid on top of a G-C pair, the two compound shapes were exactly congruent. Such pairs could fit inside the backbones without bulges or pinches.

Donahue said these pairs agreed with what he knew. Crick, when he came in, immediately pointed out that the way the bases in these pairs would attach to their sugars meant that the two backbones ran in opposite directions, just as they had to do. Each chain could include both purines and pyrimidines, with pairs flipped over. That satisfied the dyadic symmetry. Chargaff's ratios were satisfied, too. The bases could appear in any order on one chain. Once that order was fixed, though, the base pairing, guanine always with cytosine and adenine with thymine, determined a complementary order on the opposite chain.

That morning, Watson and Crick knew, although still in mind only, the entire structure: it had emerged from the shadow of billions of years, absolute and simple, and was seen and understood for the first time. Twenty angstrom units in diameter, seventy-none billionths of an inch. Two chains twinning coaxially, clockwise, one up the other down, a complete turn the screw in 34 angstroms. The bases flat in their pairs in the middle, 3.4 angstroms and a tenth of a revolution separating a pair from the one above or below. The chains held by the pairing closer to each other around the circumference one way than the other, by an eighth of a turn, one groove up the outside narrow, the other wide. A melody for the eye of the intellect, not a note wasted. In itself, physically, structure carried the means of replication—positive to negative, complementary. As the strands unwound, at double template was there in the base pairing, so that only complementary nucleotides could form bonds and drop into place as the daughter strands grew. ... one doubts, of course, that Crick and Watson altogether realized, that morning, what they had seen. "We have discovered the secret of life," Crick told everyone within earshot over drinks that noon at the Eagle. It was not the entire secret of life, yet truly for the first time at the ultimate biological level structure had become one with function, the antimony dialectically resolved. The structure of DNA is flawlessly beautiful.

Horace Freeland Judson
The Eighth Day of Creation Expanded edition 1996, pp. 148-150
Cold Spring Harbor Laboratory Press



1. James D. Watson, The Double Helix, p. 194

Friday, February 22, 2013

Living on Lava

The Big Island (Hawaii) is one giant pile of lava from five different volcanoes. The large one, slightly below center in the photo, is Mauna Loa and it is still an active volcano. You can see streaks of old lava flows spreading out from the summit. Mauna Kea, the slightly higher volcano above center, is now dormant.1 The active volcano that tourist visit is Kilauea, below and to the right on Mauna Lao.

We are staying at the Hilton resort in Waikaloa. It is built on the lava flow from 1859 where it spilled into Kiholo bay [The 1859 eruption of Mauna Loa and its human impact].

This is the dry side of the island and the surrounding area is very desert-like. As you can see from the photo I took (below), the resort area is not desert at all. That lush vegetation requires constant watering. (I don't know were the water comes from.) You can also see the parts of the lava flow that have not been transformed. It's very impressive to see it up close.

The photos are from the balcony of our apartment. When we woke up today there was snow on the top of the mountain. The temperature here is about 30°C (or 86°F for the only major country that isn't metric.2)







[Hat Tip: Ms. Sandwalk took the photos of snow-capped Mauna Loa with her telephoto lens.
1. That's where the Hawaiian observatories are located.
2. Liberia and Burma are the other two countries that aren't metric.

Wednesday, February 20, 2013

Wakiki Beach

This is a view of Wakiki Beach in Honolulu, Hawaii. I took it from LuLu's Surf Club where I was eating fish tacos and drinking Hawaiian beer. (The fish tacos were horrible. The beer was acceptable.)

I took a few more photos of the beach while we were strolling along the path behind the beach. It was a beautiful day with temperatures hovering around 28°. We stayed in a hotel a few blocks away 'cause we couldn't afford the big hotels that were right on the beach.




USS Arizona

The USS Arizona (BB-39) is an American battleship built during World War I. It was modernized and upgraded in 1930.

The Arizona was hit by a Japanese bomb during the attack on Pearl Harbor on Dec. 7, 1941. The magazine in her forward turret exploded and the ship sank within minutes. The explosion killed 1,177 of her crew. The ship was not salvageable, unlike most of the other ships sunk on that day. The USS Arizona Memorial was built over the remains of the ship to honor the men who died in the attack. Here's an aerial view of the memorial.

We visited the USS Arizona Memorial on Thursday Feb. 14, 2013 and I've included some of my photos. Click to enlarge, especially the last two photos.







Saturday, February 16, 2013

USS Missouri

The USS Missouri is an American battleship commissioned in June 1944, toward the end of World War II. It served as the flagship of the American Third Fleet under Admiral William F. Halsey, Jr. In early August 1945, the Missouri was bombarding installations on the coast of Japan when the atomic bombs were dropped.

On September 2, 1945 the Missouri was docked in Tokyo harbor. Japanese representatives signed the surrender documents that formally ended World War II. The brass disk (below) is the site where the signing took place.

On Thursday (Feb. 14, 2013) we visited the Battleship Missouri Memorial in Pearl Harbor, Hawaii.







Friday, February 15, 2013

Hawaiian Cuisine

I think it's important to sample the local customs whenever you travel. In this case, I'm on a mission to experience genuine Hawaiian cuisine.

We began on the first full day of our visit with a delicious spam & egg bun at a small cafe in Honolulu near the beach at Waikiki. The spam had just the right flavor (I thing it was genuine Hormel spam, probably made in the USA.) I actually prefer Prem but it's much hared to find.



Tuesday, February 12, 2013

Guess Where I'm Going?

We're leaving tomorrow to visit a place I've never been. I'm really looking forward to it, especially the "red bits" in the image.

I may be too "busy" to post much in the next two weeks.



Monday, February 11, 2013

PZ Myers Can't Write About Evolutionary Psychology

PZ Myers wants to write a serious post about evolutionary psychology but he can't.

Why not? Here's what he said on Kate Clancy tackles Evolutionary Psychology.
I’ve still got plans to post more on this subject, but an unfortunate event has blocked me. I was going to make my next post on evolutionary psychology one that focused on some of the papers, and in particular, I wanted to discuss a good paper or two, so that I could start off on the right tone. And people sent me links and papers.

Only problem: they were all awful. Every one. I couldn’t believe that even these papers that some people were telling me were the best of the bunch were so lacking in rigor and so rife with unjustified assumptions. I read through about a dozen before I gave up in disgust and decided that there were better things to do in my time.

I’d ask again, but I was burned so badly on that last go-round that I’d have a jaundiced view of any recommendation now.
I understand his pain. I've often asked for good examples of evolutionary psychology and gotten nothing but garbage. For example, an evolutionary psychologist named Gad Saad once sent me a list of The Great, Profound, and Valuable Works of Evolutionary Psychology. At some point we have to question the value of an entire field if it can't come up with even a handful of high quality papers.


Sunday, February 10, 2013

Craig Venter Discusses the Tree of Life

I don't know where this clip comes from or when it was made but it's being promoted on YouTube as "Dr. Craig Venter Denies Common Descent in front of Richard Dawkins!" The link was posted by someone in a comment to a previous post on Sandwalk.

Everything that Ventor says is correct. He didn't need to quibble about the universality of the genetic code but it's true that there are variants.

His point about the tree of life is correct, especially in a discussion about the origin of life. It's unfortunate that Richard Dawkins repeatedly makes such an issue about the tree of life because he's on shakey ground when he does that. I assume that Dawkins hasn't studied the problem. However, he's in good company since most scientists don't understand the problems with the early tree of life. The early history of life looks more like a bush with many interconnecting branches due to horizontal gene transfer [The Tree of Life].

Here's a video of the complete debate. The relevant part, according to the creationists, begins at 9 mins.



Saturday, February 09, 2013

Darwin's Dead Idea and the Man Who Helped Kill It

A new book has just been published. The title is "Darwin's Dead Idea and the Man Who Helped Kill It." Here's the description on Amazon.
"Darwin’s Dead Idea and the Man Who Helped Kill It" makes for highly engaging reading. Witness the fascinating journey of a smart, inquisitive adolescent rejecting his school’s ask-no-questions religious indoctrination into a mathematician, philosopher, and scientist of the highest order, one who today is powerfully and persuasively challenging academia’s reigning answer to the questions that haunt us all: Where did we come from? Why is there something rather than nothing? A leading spokesman for the scientific theory that is shattering materialist assumptions about reality and the origin of life, Dr. William Dembski responds to probing questions from James Barham, general editor of TheBestSchools.org. That interview forms the core of DDI. Dembski’s forthright and humbly restrained responses reveal the courage, perseverance, and original thinking that have made him a lightning rod in the scientific community. The heated controversy surrounding intelligent design theory dramatically confirms Machiavelli’s observation that there is nothing more difficult to carry out nor more doubtful of success, nor more dangerous to handle, than to initiate a new order of things. DDI introduces readers to one of the stellar lights of the new order of things now emerging on the horizon.
I'm speechless.


Why Do University Press Releases Continue to Spread Misinformation?

There's a very interesting paper that's just been published online in ScienceExpress. The work is by Haung et al. (2013) from the Broad Institute at Harvard and MIT (Boston, Massachusetts, USA). These workers looked at the genomes of 70 different malignant melanomas and discovered that fifty (50) of them had mutations in the promoter region of the gene TERT (telomerase reverse transcriptase). The mutations created a new binding site for transcription factors resulting in a 2-4 fold increase in transcription of the gene.

Here's a picture of the gene from the Ensembl website [TERT]. The position of the transcription start site (P) is shown and the approximate position of the two mutations (M) is just upstream.


It's good that mutations affecting melanomas have been identified but the result isn't totally unexpected. We've known for fifty years that mutations in the promoter regions of genes can affect expression. Even in humans, such mutations have been widely studied; for example, lactase persistence is due to mutations in enhancer regions of the lactase gene.

Let's look at the press release from the Broad Institute [Genomic "dark matter" yields major melanoma discovery]. It's written by Paul Goldsmith who writes ...
"This new finding represents an initial foray into the 'dark matter' of the cancer genome," said Levi Garraway, senior associate member of the Broad, and associate professor of medicine at Dana-Farber, the article’s senior author.
WTF! Since when have promoters and enhancers been called "dark matter"? And why isn't it mentioned, or even hinted at, in the published paper?
Only about 1% of the human genome provides the blueprint for the body’s proteins. The remaining "non-coding" portion of the genome, sometimes referred to as dark matter, is poorly understood. Scientists have only recently begun exploring the relationship between these regions and the body’s cellular structure and processes.
We have an excellent understanding of the human genome [What's in Your Genome?]. This press release implies that only 1% of the genome is understood and the rest is mysterous "dark matter." We've known for decades that most of this DNA is junk (defective transposons). We know about pseudogenes, genes that encode functional RNAs, regulatory regions (including enhancers), introns, centromeres, defective viruses, telomeres, origins of replication, and several other functional parts of the genome.

I don't believe that the senior author of this study, Levi Garraway, actually believes what he is quoted as saying. If it were true then why didn't he put it in the paper? Why is there nothing in the paper about the importance of revealing mysterious "dark matter"?

Why do press releases have to be so misleading?


Huang, F.W., Hodis, E., Xu, M.J., Kryukov, G.V., Chin, L., and Garraway, L.A. (2013) Highly Recurrent TERT Promoter Mutations in Human Melanoma. Science published online January 24 2013 [doi: 10.1126/science.1229259

IDiot Quote of the Day

This is for all of you who really miss Saturday morning cartoons. It's from a post by David Klinghoffer who is upset about the way some people are treating Thomas Nagel [New York Times on Thomas Nagel's "Dangerous Sympathy for Intelligent Design"].
One of the take-aways here is not only the progress ID is making in scientific and general culture, but specifically among liberal thinkers. That makes it a lot harder to pigeonhole us in time-honored Darwinian fashion as right-wing Christian fundamentalists, creationists and the like. This may be the chief source of outrage from the Darwin community. Deprived of that old crutch, these guys will be forced to argue with us and explain in detail why ID, not creationism yet again, is wrong. Of course that's something that most have stubbornly, and tellingly, refused to do.
I have been arguing with these IDiots for over twenty years. They stubbornly, and tellingly, refuse to listen. Isn't that strange?


Coming Soon to a Theater Near You - "The Unbelievers"

I wonder if Richard Dawkins and/or Lawrence Krauss will win an Academy Award?




Not All Atheists Are Skeptics

PZ Myers posted an article last week that was part of an ongoing discussion about the role of atheism in the skepticism movement. The title of his post was: Atheists are skeptics. I covered that debate in an earlier post [Skeptics Must Be Atheists].

Now I want to discuss whether all atheists must be skeptics.

The answer is "no." Atheists are people who don't believe in any god(s). There are millions of atheists all around the world who have grown up without any belief in god(s). Their parents didn't believe, their grandparents didn't believe, and they live in a secular culture. Many of these atheists are taken in my homeopathy, fear of GMOs, and various conspiracy theories. They aren't critical thinkers and they aren't skeptics.

Let's not fall into the trap of assuming that all atheists have grown up as believers and have recently lost their faith. That's just not accurate.


Skeptics Must Be Atheists

The skeptic movement has been in a bit of a turmoil over the past few years. One of the problems concerns the role of atheism in the movement. Many people think that outspoken criticism of religion (i.e. Gnu Atheism) is not a necessary part of skepticism. I agree—just as you don't have to be an outspoken critic of chiropractors to be a skeptic.

However, that doesn't mean that belief in god(s), or belief in the grandiose claims of chiropractors, is compatible with skepticism. They aren't.

PZ Myers and Steve Novella are debating this issue. The latest round is from last week on Pharyngula: Atheists are skeptics. (His title is wrong ... more about that in another post.¹) Novella is one of those skeptics who think that skepticism requires scientific thinking [Bigfoot Skeptics, New Atheists, Politics and Religion] but he also believes that the scientific way of knowing has limits and that belief in god(s) falls outside of those limits. The "limit" is, as we all know, methodological naturalism. (Novella's main interest is quack medicine.) Here's how he describes one of the attributes of a skeptic ...

Friday, February 08, 2013

Skip the Acknowledgements Slide!

Joshua Schimel blogs at Writing Science. His latest post recommends that we stop ending our talks with a boring slide that lists all funding sources and everyone who may have contributed to the project [Why do people blow the punchline in scientific talks? The destructive effect of acknowledgements slides].

I never thought about this before. He makes a good point.


[Hat Tip: Mike the Mad Biologist ]

The Proper Role of Scientific Societies

Scientific societies are made up of groups of scientists who band together for various legitimate purposes such as organizing meetings, publishing journals, promoting their speciality, and lobbying for funds. The credibility of a society depends on its area of expertise. They lose credibility when they take positions on issues outside of their discipline.

That's why many of us have been opposed to the accommodationist positions of the American Association for the Advancement of Science (AAAS) and other societies. These societies have no special expertise in epistemology/philosophy or religion yet they openly proclaim that science and religion are compatible. They should be neutral on that question. A (slight) majority of Sandwalk readers agree, according to a poll I took a few years ago [What Should Scientific Organizations Say about Religion?].

I wasn't alone in adopting this position. Jerry Coyne and PZ Myers also think that scientific societies should keep their nose out of areas that are outside of their mandate. We are united when it comes to opposing accommodationism.

Thursday, February 07, 2013

“This House Believes Religion Has No Place In The 21st Century”

Here's the video of last week's debate at the Cambridge Union debating society. The main event pitted Richard Dawkins against Rowan Williams, former Archbishop of Canterbury. The motion was that "This House Believes Religion Has No Place In The 21st Century." At the end of the debate a majority decided that religions does, indeed, have a place in the 21st century.



American Loons: #409 Jonathan Wells and #411 John West

Jonathan Wells has just been named to the Encyclopedia of American Loons: #409: Jonathan Wells. He joins another Discovery Institute Fellow, #411 John West.
Appallingly inane crackpot, infuriatingly dense, and reprehensibly dishonest, Wells’s lack of insight and inability to even pretend to begin to understand anything before he starts criticizing it based on personal dislike, is of almost epic proportions. Yet he continues to be shockingly influential.



Less than ideally honest chucklehead, and a prime case of every strand of cognitive bias channeled into a single-minded force of rage against reality. West should not be underestimated, however, as he has made serious contribution to undermining science and education.


WARNING: YOUR VALENTINE'S DAY TREATS MAY BE FILLED WITH GMOS - Support science by buying them right away before they are banned.

I received this email message today from Leslie Maloy, (lmaloy@hastingsgroup.com). It's stupid. It's an example of scientific illiteracy. There's no chance than food from genetically modified crops will do you any harm. You may want to oppose GMO crops for other reasons but to pretend that GMO crops will endanger your health is a lie.

It's stuff like this that's giving the environmental movement a bad reputation. Their anti-science positions are losing them support from the scientific community.
National Coalition Calls on Hershey and Mars to Label GMOs in Chocolates, Other Candy . Or Get Them Out Completely.

Washington DC -- February 7, 2013 -- What will you get your loved one this Valentine's Day? If genetically modified organisms (GMOs) in chocolates are not on your shopping list, you will want to know about GMO Inside's new push to get the nation's largest candy manufacturers-Hershey and Mars-to break up with GMOs in 2013.

GMO Inside, a campaign dedicated to advancing the right of consumers to know whether or not foods are genetically engineered, is calling on Hershey and Mars to either stop putting GMOs in Valentines candy and other products . or to start labeling the products as containing GMOs.

Hershey and Mars combined comprise nearly 70 percent of the U.S. chocolate market. The two companies are not shy about their love affair with GMOs; together they spent more than a million dollars to oppose GMO labeling in California in the November 2012 election. Hershey is reported to have spent $518,900 to defeat Prop 37 and Mars spent $498,350.

The reason these companies oppose GMO labeling so strongly is due to the fact that GMO ingredients are in their sweets; a label would surely make a consumer think twice about eating their favorite candy bar.

For example, these popular candies contain the following GMO-risk ingredients:
* Reese's Peanut Butter filled Hearts (Hershey) contain sugar, soy lecithin, and cornstarch
* Hershey Hugs contain sugar, soy lecithin and corn syrup solids
* Valentine's Colored M&M's (Mars) contain sugar, soy lecithin, cornstarch, and corn syrup
* Valentine's Snickers (Mars) contain soy lecithin, corn syrup, sugar, and partially hydrogenated soybean oil

GMO Inside also released a "Valentine's Day Villains" shopping guide for consumers who want to avoid GMOs treats for their Valentines. Go to www.GMOinside.org to get a list of candies to watch out for and also some non-GMO alternatives for your loved one

Genetically modified organisms have never been proven safe for consumption, and a growing body of studies is raising concerns around the health effects of eating them. GMOs are also increasing the use of toxic herbicides and causing harm to farmers in the US and abroad.

In Europe, where genetically modified ingredients are already required to be labeled, Hershey and Mars have adapted their recipes to formulate Kisses and M&Ms without GMOs. According to Confectionery News, Hershey products made for distribution in Europe will be formulated without GMO ingredients, in order to meet the requirements of major retailers which ban the sale of products with genetically modified ingredients and to satisfy increasing consumer concern about the safety of GMOs.

"Unless you can buy Hershey or Mars products in Europe, there is a high chance you could be giving your Valentine a treat with GMOs that endanger their health and the environment," said GMO Inside Campaign Director Elizabeth O'Connell, "To be safe, you should choose organic certified or Non-GMO Project Verified chocolate to show the loved ones in your life you really care."

Beyond the issue of GMOs, Hershey also has problems with child labor in the cocoa it sources. Though the company committed to certify its supply chain as 100 percent sustainable in October of 2012, there has been no further information about how the company plans to deliver on its promise to remove forced child labor from its supply chain over the next seven years.

"Consumers have a choice -- there is delicious chocolate from companies that are organic or verified through the Non-GMO Project, said Alisa Gravitz, president of Green America. "And you can make it doubly sweet by also looking for fair trade options. You'll be showing your sweetheart you care in every way. Refuse to buy GMO-laden chocolate this Valentine's Day."


Snow!!!

Climate change has been very good to Toronto because the increase in temperature during the winter is just enough to avoid snow. In the past decade we've had several winters where I hardly ever had to shovel.

That's all about to change. Tomorrow we're going to get hit with a big storm that's supposed to dump about 25 cm of snow. It's another one of those situations where bad things come from our neighbor to the south.

The city can cope—this is, after all, Canada—but it's probably not going to be a pleasant day. I'm planning to declare a personal snow day and stay home.

That means I won't be able to attend our meeting tomorrow evening [see, Join Us on Friday to Discuss "Thoughts on Science: Evolution versus Intelligent Design (Part I of an indefinite number of parts)"]. Check the Facebook page [Thoughts on Science 2: Evolution VS. Intelligent Design (Part I of an indefinite number of parts)] to see if Rufina is going to cancel the event.