Nobel Laureate: Edward Lewis

 

The Nobel Prize in Physiology or Medicine 1995.

"for their discoveries concerning the genetic control of early embryonic development"

Edward B. Lewis (1918 - 2004) won the Noble Prize for his studies on the genetics of Drosophila melanogaster, especially the homeotic mutants in the bithorax complex. These are the mutations that cause transformation of the 3nd thoracic segment into the 2nd, giving rise to a fly with four wings instead of two.

The significance of this work can't be underestimated. It led to our modern understanding of development and evolution. Thanks to Lewis, we now know that small changes in the regulation of gene expression can have large effects on phenotype. It means that the number of mutations required to make the difference between mice and humans, for example, may be far less that what people imagined 50 years ago.

Edward Lewis shared the prize with Christiane Nüsslein-Volhard and Eric Wieschaus. Here's what the press release said about Lewis.

THEME:
Nobel Laureates

The fly with the extra pair of wings

Already at the beginning of this century geneticists had noted occasional malformations in Drosophila. In one type of mutation the organ that controls balance (the halteres), was transformed into an extra pair of wings (Fig. 2). In this type of bizarre disturbance of the body plan, cells in one region behave as though they were located in another. The Greek word homeosis was used to describe this type of malformations and the mutations were referred to as homeotic mutations.
Figure 2.

Fig. 2. Comparison of a normal and a four-winged fruit fly. The third thoractic segment has developed as a duplicate of the second due to a defectic homeotic gene. In the normal fly only the second segment develops wings.

The fly with the extra pair of wings interested Edward B. Lewis at the California Institute of Technology in Los Angeles. He had, since the beginning of the forties, been trying to analyze the genetic basis for homeotic transformations. Lewis found that the extra pair of wings was due to a duplication of an entire body segment. The mutated genes responsible for this phenomenon were found to be members of a gene family ( bithorax-complex) that controls segmentation along the anterior-posterior body axis (Fig. 3). Genes at the beginning of the complex controlled anterior body segments while genes further down the genetic map controlled more posterior body segments (the colinearity principle). Furthermore, he found that the regions controlled by the individual genes overlapped, and that several genes interacted in a complex manner to specify the development of individual body segments. The fly with the four wings was due to inactivity of the first gene of the bithorax complex in a segment that normally would have produced the halteres, the balancing organ of the fly (Fig 3). This caused other homeotic genes to respecify this particular segment into one that forms wings.

Edward Lewis worked on these problems for decades and was far ahead of his time. In 1978 he summarized his results in a review article and formulated theories about how homeotic genes interact, how the gene order corresponded to the segment order along the body axis, and how the individual genes were expressed. His pioneering work on homeotic genes induced other scientists to examine families of analogous genes in higher organisms. In mammalians, the gene clusters first found in Drosophila have been duplicated into four complexes known as the HOX genes. Human genes in these complexes are sufficiently similar to their Drosophila analogues they can restore some of the normal functions of mutant Drosophila genes.

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[The book is a tribute to Edward Lewis, edited by my colleague Howard D. Lipshitz.]

[Image Credit: California Institute of Technology]

Two Examples of "Alternative Splicing"

THEME:
Transcription
Last week I bumped into a colleague who teaches in our third year molecular biology course. I was lamenting about the sad state of science these days and we got to talking about alternative splicing. I repeated my complaint that much of the predicted alternative splice variants are artifacts. It makes no sense that conserved genes would be producing alternative protein variants that are species specific. I am convinced that the EST databases are full of artifacts and that most predicted splice variants do not exist.

My colleague was shocked. He is firmly convinced that most human genes express a number of different protein products that are produced as the result of alternatively spliced mRNA precursors. I asked him if he had ever looked at his favorite genes to see if the predicted variants make any sense. The ones that I've looked at certainly don't. (Join in the fun: see the challenge below.)

My colleague is very knowledgeable about the genes for the major subunits of eukaryotic RNA polymerase since it was his lab that cloned the first one. I suggested that he look at the predicted alternative splice variants of the two human genes and let me know if he is still convinced that these variants make biological sense. I'm not sure he will do it so let's take a look ourselves.

Eukaryotic RNA polymerase is a complex protein machine consisting of ten different subunits. Two of the subunits, Rpb1 and Rbp2, are more commonly known as A and B. In the human genome they are encoded by the genes POLR2A and POLR2B respectively [RNA Polymerase Genes in the Human Genome].

If you click on the Entrez Gene URLs you will end up at a page that summarizes what is known about the gene. Down the right-hand side of the page there are links to several other webpages, including a link to AceView, a database of alternative splice variants. Before following this link to the POLR1A variants, let's note that on the annotated Entrez Gene website there are no alternative splice variants listed. Apparently someone has decided that the predicted variants are probably artifacts.

Go to the AceView page for AceView POLR2A. The first thing you see is a short explanation.

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 11 spliced variants.

AceView summary
Note that this locus is complex: it appears to produce several proteins with no sequence overlap.
Expression: According to AceView, this gene is expressed at very high level, 4.8 times the average gene in this release. The sequence of this gene is defined by 537 GenBank accessions from 518 cDNA clones, some from breast (seen 40 times), marrow (29), head neck (19), brain (18), eye (18), leukopheresis (18), lung tumor (18) and 132 other tissues. We annotate structural defects or features in 13 cDNA clones.
Alternative mRNA variants and regulation: The gene contains 29 different introns (28 gt-ag, 1 gc-ag). Transcription produces 13 different mRNAs, 11 alternatively spliced variants and 2 unspliced forms. There are 7 probable alternative promotors and 5 non overlapping alternative last exons (see the diagram). The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, overlapping exons with different boundaries, alternative splicing or retention of 4 introns. 337 bp of this gene are antisense to spliced gene pluvu, raising the possibility of regulated alternate expression.
Protein coding potential: 10 spliced and the unspliced mRNAs putatively encode good proteins, altogether 11 different isoforms (3 complete, 4 COOH complete, 4 partial), some containing domains RNA polymerase Rpb1, domain 1, RNA polymerase, alpha subunit, RNA polymerase Rpb1, domain 3, RNA polymerase Rpb1, domain 4, RNA polymerase Rpb1, domain 5, RNA polymerase Rpb1, domain 6, RNA polymerase Rpb1, domain 7, Eukaryotic RNA polymerase II heptapeptide repeat [Pfam]. The remaining 2 mRNA variants (1 spliced, 1 unspliced) appear not to encode good proteins.

Here's the figure showing the various predicted alternatively spliced transcripts and the various different proteins.


It's really difficult to imagine that any of these are biologically relevant. How could a small bit of the large RNA polymerase subunit ever be part of the RNA polymerase protein complex? It's not a surprise that the Entrez Gene annotators have ignored these predictions.

If, as I believe, most of the small ESTs on which these predictions are based are artifacts, then the overall pattern makes sense. What you see are examples of splicing errors where an intron has not been correctly removed. These extremely rare splicing errors are copied into cDNA during construction of EST libraries and specifically selected by screening out all the correctly spliced mRNAs. (That's how you make most EST libraries.)

Here's what AceView says about the gene for the other large subbunit [AceView: POLR2B].

RefSeq annotates one representative transcript (NM included in AceView variant.a), but Homo sapiens cDNA sequences in GenBank, filtered against clone rearrangements, coaligned on the genome and clustered in a minimal non-redundant way by the manually supervised AceView program, support at least 9 spliced variants.

One again, AceView notes that the annotated human genome has ignored the predicted alternative plice variants but maintains that there are at least nine of them.

Here's the figure, decide for yourself whether this is credible.


There are several well-known examples of human genes producing different protein variants due to alternative splicing. The ones I can think of off the top of my head are the genes for class I antigens, α-tropomyosin, and calcitonin. I'm sure there are half a dozen others.

Here's the challenge. See if you can find a human gene for a well-studied protein where the structure of the protein is known and there are multiple protein variants derived by alternative splicing. I bet that readers of Sandwalk can't find very many where the predicted variants many any sense and are likely to be biologically significant.

What does this mean? Whenever you look at your favorite well-studied gene you see that the predictions of alternative splicing are silly. So why should we believe the genome wide analyses? Is it just a coincidence that the more we learn about a given gene the most we become willing to reject the ESTs as artifacts? Or is it possible that alternative splicing is mostly confined to those genes that have not been well studied?

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Genes and Straw Men

Just in case there's someone who doesn't understand the concept of "straw man," here's a good description from Wikipedia: Straw Man.

A straw man argument is an informal fallacy based on misrepresentation of an opponent's position.[1] To "set up a straw man," one describes a position that superficially resembles an opponent's actual view, yet is easier to refute. Then, one attributes that position to the opponent. For example, someone might deliberately overstate the opponent's position.[1] While a straw man argument may work as a rhetorical technique—and succeed in persuading people—it carries little or no real evidential weight, since the opponent's actual argument has not been refuted.[2]

The term is derived from the practice in ages past of using human-shaped straw dummies in combat training. In such training, a scarecrow is made in the image of the enemy, sometimes dressed in an enemy uniform or decorated in some way to vaguely resemble them. A trainee then attacks the dummy with a weapon such as a sword, club, bow or musket. Such a target is, naturally, immobile and does not fight back, and is therefore not a realistic test of skill compared to a live and armed opponent. It is occasionally called a straw dog fallacy, scarecrow argument, or wooden dummy argument.[citation needed] In the UK, it is sometimes called Aunt Sally, with reference to a traditional fairground game.

You'd be surprised how often this fallacy comes up—and it's not just IDiots who use it.

The other day I attended a seminar by Jacek Majewski of McGill University (Montreal, Quebec, Canada). The subject was alternative splicing.

As most of you already know, this is a controversial field. Many people believe that alternative splicing is very common and that 50-70% of all human genes produce multiple versions of proteins due to alternative splicing. Majewski is one of those people.

Others, I am one, believe that much of the data is based on artifacts—especially expressed sequence tag (EST) artifacts. We believe that there are some very well established, and well-studied examples of alternative splicing but these represent only a small percentage of the total genes in the human genome.¹ We'll call these two groups the "splicing is common" advocates and the "splicing is rare" advocates.

The "common" group likes to think of themselves as the leading edge of a paradigm shift. They believe that alternative splicing is so common that it requires a new way of looking at biology. Unfortunately, in their haste to promote the new paradigm, they often misrepresent the other side. As a matter of fact, the very existence of a legitimate scientific controversy is often deliberately overlooked because they set up a straw man that is easily refuted.

Here's an example. In Majewski's seminar he started by describing the current "dogma" of one gene-one enzyme. According to him, most biologists are wedded to the idea that each gene makes a single protein. They believe, according to Majewski, that the intermediate step of mRNA synthesis is unimportant. He even showed a slide illustrating the dogma. It represents the old paradigm.

At the end of the seminar I pointed out that we have been teaching a different version of information flow for over thirty years. I mentioned that all the leading textbooks talk about splicing and alternative splicing and, furthermore, this material has been in the textbooks for 25 years (e.g. Genes II by Benjamin Lewin published in 1983). I asked him if he actually knew any scientists who believed in the dogma that he described. His response was confusing but he didn't back down.

Why is this important? Because most of the "common" advocates focus on convincing us that alternative splicing is real rather than focusing on whether it is common. By refuting the straw man they hope to bolster their case for the prevalence of alternative splicing. But they do no such thing. Most scientists are well aware of alternative splicing and have been for decades. The dispute is not over whether it occurs but whether it is common. The straw man version of the opposition does not exist.

I was prompted to write about this form of rhetorical device by reading an article in Monday's New York Times. The article (Now: The Rest of the Genome) was written by Carl Zimmer. Most of you know what I think of Carl Zimmer. He is one of the best science writers on the planet [Carl Zimmer at Chautauqua] but this time he slipped up.

Zimmer writes about Sonja Prohaska, a bioinformatician at the University of Leipzig in Germany.

... new large-scale studies of DNA are causing her and many of her colleagues to rethink the very nature of genes. They no longer conceive of a typical gene as a single chunk of DNA encoding a single protein. “It cannot work that way,” Dr. Prohaska said. There are simply too many exceptions to the conventional rules for genes.

It turns out, for example, that several different proteins may be produced from a single stretch of DNA. Most of the molecules produced from DNA may not even be proteins, but another chemical known as RNA. The familiar double helix of DNA no longer has a monopoly on heredity. Other molecules clinging to DNA can produce striking differences between two organisms with the same genes. And those molecules can be inherited along with DNA.

The gene, in other words, is in an identity crisis.

I don't think there are any significant number of biochemists or molecular biologists who literally believe that every gene encodes a single protein. Everyone I know understands that there are ribosomal RNA genes, tRNA genes, and genes for all kinds of small RNAs. Everyone I know understands alternative splicing. (On the other hand, nobody I know thinks that epigenetics is any threat to our definition of a gene.)

If the gene has an identity crisis, which it does, it's not because of ignorance of these phenomena, it's because we can't all agree on a good definition. My own preference is to define as a gene as, "A gene is a DNA sequence that is transcribed to produce a functional product" [What Is a Gene?] and I've been using that definition in my own textbooks since 1989.

It's sad to hear that up until recently Sonja Prohaska and her colleagues believed in a long-discredited definition of a gene. It suggests that throughout her undergraduate and graduate education she never heard of ribosomal RNA genes or alternative spicing. (She got her Ph.D. in 2005.) Either that or she's deliberately setting up a straw man.

Carl Zimmer goes on to describe recent work on the analysis of the human genome, especially the work done by the ENCODE project.

Encode’s results reveal the genome to be full of genes that are deeply weird, at least by the traditional standard of what a gene is supposed to be. “These are not oddities — these are the rule,” said Thomas R. Gingeras of Cold Spring Harbor Laboratory and one of the leaders of Encode.

A single so-called gene, for example, can make more than one protein. In a process known as alternative splicing, a cell can select different combinations of exons to make different transcripts. Scientists identified the first cases of alternative splicing almost 30 years ago, but they were not sure how common it was. Several studies now show that almost all genes are being spliced. The Encode team estimates that the average protein-coding region produces 5.7 different transcripts. Different kinds of cells appear to produce different transcripts from the same gene.

With all due respect to Carl, these sentences contradict what he implied earlier on. Yes, it's true that scientists have known about alternative splicing for 30 years. In other words, they have known for at least that long that the old idea about one gene-one protein is incorrect. So what was the point of letting readers think that Sonja Prohaska's personal misunderstanding of a gene has any relevance?

As I mentioned above, the scientific controversy over alternative splicing is about how common it is and not about whether modern scientists recognize its existence. And it has nothing to do with the modern understanding of a gene since for the past 20 years everyone has incorporated alternative splicing into their understanding of a gene.

Thomas Gingras is clearly on the "common" side of the issue and not on the "rare" side. Unfortunately Zimmer doesn't do a good job of balance here. A better way to describe the results would be ...

Taken a face value, some of the published results from the ENCODE project suggest that, far from being a rare event, alternative splicing may be very common. In fact, some scientist think that most of our genes produce several different proteins due to alternative splicing. They even suggest that an average gene may produce five or six different alternatively spliced transcripts.

Other scientists dispute these results, pointing out that the predicted alternatively spliced transcripts make no sense for those genes that have been well-studied. These predictions are being quietly removed from the annotated human genome database. As more and more genes are being looked at, the number of proven protein variants gets smaller and smaller.

The original predictions rely heavily on the sequences of small bits of RNA called "ESTs" and it is becoming increasingly clear that many, perhaps most, ESTs are artifacts. It is quite possible that talk of changing paradigms is premature and the number of genes exhibiting alternative splicing may be closer to what scientists thought twenty years ago.

These are interesting times in genome research and, like all new fields, the preliminary results are exciting and provocative. Who knows whether the preliminary results will lead to new ways of looking at biology? Time will tell.

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1. I'm using the human genome as an example. The same arguments apply to other genomes.

[Image Credit The Information Paradox: A Favorite Theist Logical Fallacy: The Straw Man]

November 11, 2008

 
This is what the front campus of the University of Toronto looks like today, Remembrance Day 2008. This is the 90th anniversary of the end of World War I.

Each cross bears the name of one of 628 alumni, students, or faculty members who died in World War I. It reminds us of what happens when we fail to resolve our differences peacefully. War is the failure of peace.

The crosses remind us that war is evil and horrible. All of these lives were wasted in a war that never should have happened. War is not glorious. War is not something we should be proud of even though we may honor those individuals who answered the call, and sacrificed their lives, when the politicians and diplomats failed to do their duty.

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Enzyme Efficiency: The Best Enzyme

One of the first things you learn about enzymes is that they catalyze, or speed up, reactions that would normally take place at a much slower rate. This is a difficult concept for students to understand because they're used to thinking of biochemical reactions in terms of reactions that would never happen without an enzyme.

The trick in understanding the role of enzymes is to appreciate the difference in rates between the enzyme-catalyzed reaction and the spontaneous reaction. While it's true that all enzyme-catalyzed reactions would eventually proceed even in the absence of enzyme, the rate of the spontaneous reaction might be way too slow. We often emphasize that the spontaneity of a reaction can be determined from the thermodynamics (i.e. if ΔG <0 the reaction is spontaneous) but we sometimes forget to show real data on how fast such a reaction can occur under physiological conditions. Typical rates for enzyme-catalyzed reactions are described by a constant called k_cat.¹ These values are usually in the range of 100-1000 reactions per second but there are some enzymes than have rates of over 1,000,000 reactions per second.

Spontaneous reactions can often approach these rates but, as you might imagine, the ones that require enzymes are very much slower. Proteins, for example, will eventually break down into amino acids but the rate of the reaction is so slow that spontaneous protein degradation is not a problem in living cells. In order to degrade proteins for food, we need to make enzymes such as chymotrypsin, trypsin, pepsin, and elastin to do the job at a faster rate.

Most of the important metabolic reactions take years in the absence of enzyme. The spontaneous degradation of a protein, for example, takes about 100 years (rate constant ~ 4 × 10^-9). Since chymotrypsin catalzyes this reaction at a rate of about 1000 molecules per second, this means that the enzyme speeds up the reaction by a factor of more than 10¹¹ (100 billion times)!

This value (10¹¹) is sometimes called the catalytic proficiency of an enzyme although for technical reasons we won't go into here, the real measure of catalytic proficiency is higher by several orders of magnitude.¹ The catalytic proficiency of chymotrypsin is 2 × 10¹⁶.

Naturally, this invites a comparison with those enzymes showing the greatest rate enhancements. But there's a problem. You can measure spontaneous rates that are on the order of a few years because you don't have to wait until the reaction goes to completion. But if the spontaneous reaction takes hundreds of years it can be difficult to measure—even the most dedicated graduate student won't wait that long!

Fortunately there are a few tricks that will make the job easier. You can observe the spontaneous reaction at high temperatures, for example, and calculate what the rate would be at physiological temperatures. That's what Radzicka and Wolfenden did in 1995 when they reported that the spontaneous decarboxylation of ornithine 5′-phosphate (OMP) had a rate constant of 3 × 10^-16 s^-1. This is a half-life of 78 million years.

The enzyme that catalyzes this reaction is ornithine 5′-phosphate decaboxlyase and up until last week it was the record holder with a catalytic proficiency of 2 × 10²³. (OMP decarboxylase catalyzes an essential step in the synthesis of pyrimidine nucleotides that are required to make RNA and DNA.)

That record has now been broken. Lewis and Wolfenden (2008) studied a reaction catalyzed by uroporphyrinogen decarboxylase, an enzyme involved in the synthesis of porphyrins such as heme, the cofactor in hemoglobin, and the chlorophylls. There were able to model the reaction and determine that the rate of spontaneous decarboxylation is 9.5 × 10^-18 s^-1, which corresponds to a half-life of 2.3 billion years! Lewis and Wolfenden published a chart showing typical half-lives of spontaneous reactions.

The catalytic proficiency of uroporphyrinogen decarboxylase is 2.5 × 10²⁴, a new record.

Into the textbook it goes.

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1. A better description of an enzyme's real rate constant is k_cat/K_m.

Radzicka, A. and Wolfenden, R. (1995) A proficient enzyme. Science 267:90-93.

Lewis,C.A. Jr. and Wolfenden, R. (2008) Uroporphyrinogen decarboxylation as a benchmark for the catalytic proficiency of enzymes. Proc. Natl. Acad. Sci. (USA) published online November 6, 2008 [Abstract] [doi:10.1073/pnas.0809838105]

Saturday Night Live: Joan Baez

 
On Saturday night we went to see Joan Baez. She older than she used to be but still wonderful. I remember her from the 60s in spite of what they say.¹

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If you remember the 60s, you weren't there.

Molecular and Cell Biology Carnival #4

 

The 4th issue of the Molecular and Cell Biology Carnival has been posted by steppen wolf at the skeptical alchemist [Molecular and Cell Biology Carnival #4].

Welcome to the fourth edition of the Molecular and Cell Biology Carnival! Let's get down to business right away...

Submit your articles here.

The previous editions are ...

1. the skeptical alchemist
2. Cotch.net
3. ScienceRoll
4. the skeptical alchemist

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Monday's Molecule #96

 
You haven't been very successful lately at guessing Monday's "Molecule" so this week is going to be an easy one. All you have to do is identify the molecules (plural) that are responsible for this strange looking fly. Just naming the genes will be sufficient.

This week's Nobel Laureate won the prize for his work on these genes (and several others).

The first one to correctly identify the molecules/genes and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are only two ineligible candidates for this week's reward: Bill Chaney of the University of Nebraska and Dima Klenchin of the University of Wisconsin. Since they are two of the three most frequent winners, the competition is a bit easier this week.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The mutant Drosohila melanogaster is called "bithorax" because it has two pairs of wings instead of just one pair. It actually doesn't have two thoraces, instead the 3rd thoracic segment is transformed into a duplicate of the second thoracic segment. The complete transformation requires two different mutations called bx, and pbx. Both mutations are in the regulatory region of the gene UBX and they affect expression of that gene. The Nobel Laureate is Edward Lewis.

The winner is Dale Hoyt from Athens, Georgia (USA).

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How 'molecular machines' kick start gene activation revealed

 
That's the title of a press release published on Biology News Net, and several other science news sites. Here's the opening sentence ...

How 'molecular machines' inside cells swing into action to activate genes at different times in a cell's life is revealed today (6 November) in new research published in Molecular Cell.

How could you not want to find out more? This sounds like a real breakthrough.

Try and guess what the new discovery is all about before reading on ...

From the website Biology News Net and Imperial College London ...

Genes are made of double stranded DNA molecules containing the coded information an organism's cells need to produce proteins. The DNA double strands need to be 'melted out' and separated in order for the code to be accessed. Once accessed, the genetic codes are converted to messenger RNAs (mRNA) which are used to make proteins. Cells need to produce particular proteins at different times in their lives, to help them respond and adapt to changes in their environment.

The new study outlines exactly how a molecular machine called RNA polymerase, which reads the DNA code and synthesizes mRNA, is kickstarted by specialised activator proteins. The scientists have discovered that RNA polymerase uses a tightly regulated internal blocking system that prevents genes from being activated when they are not needed.

I'm underwhelmed. How is science journalism ever going to be taken seriously if this is the sort of thing that university press offices publish?

We've known and understood the basics of transcription initiation by RNA polymerase and its activators for thirty years. This study concerns a minor variation of that process involving σ⁵⁴ in bacteria.

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Never Let Your Gas Tank Get Below Half Full

 
Friday's Urban Legend: True

How many of you have heard the story that you should always drive your car with the gas tank as full as possible? According to many, you should never let the gas in your tank fall below the half full mark on your gas gauge.

You probably thought this was a tale told by elderly wives—with apologies to old men who also tell tales.

Well, it turns out that there is actual, scientific, evidence to support this warning. Cliff Allen did the experiment according to the Sept. 13, 2008 issue of New Scientist [Petrol Gauge Challenge].

SLIGHTLY more practical routes to fuel economy occurred to Cliff Allen when he noticed that, according to his petrol gauge, the fuel in the top half of his tank lasted considerably longer than the bottom half. As any Feedback reader (and possibly only a Feedback reader) would, he investigated. Systematically.

Over several months he recorded the distances travelled using the fuel from the top and bottom halves. The average for the top was 400 kilometres (250 miles) and for the bottom a mere 300 kilometres (185 miles). Since then, he writes, "of course I have only used the top of my tank and have consistently achieved around 250 miles - I'm not stupid!"

Cliff was obviously keen to discuss this, at length, with his learned friends, "some of whom gained General Certificate of Secondary Education qualifications" at age 14. He was "mostly appalled at their incredulity and lack of interest".

However, his friend Alan suggested that the fact that petrol always comes out of the bottom of the tank causes it to use more petrol so we might benefit from turning the tank upside-down. John suggested the increased efficiency might be due to the height of the fuel, so the tank should be put on the roof. Mostyn proposed putting a brick in the tank, as this apparently works very well for saving water in toilet cisterns. Tony wants to make the top of the tank larger than the bottom, to increase the proportion of its volume at the top, and thinks a carrot shape would be optimal.

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P.S. for the irony impaired.

The Awesome Power of Prayer

 
James C. Dobson, Ph.D. is Founder and Chairman of Focus on the Family. He is not a fan of Barrack Obama and came to the realization that John McCain and Sarah Palin would be much better for the country.

Dobson urged his followers to pray [Dr. Dobson’s October Newsletter].

Regardless of your political views, I want to urge Christians everywhere to be in prayer about this election. There are many scriptural references wherein King David “inquired of God” when he was faced by troubling circumstances (1 Samuel 23:2,4; 30:8; 2 Samuel 2:1; 5:19,23). It is time for Christians everywhere to turn to Him for guidance and wisdom. Find some time to be still and listen to what He wants to tell you. The National Day of Prayer Task Force, led by my wonderful wife, Shirley, has embarked on a national campaign entitled “Pray for Election Day.” All around the country, individuals and groups are being encouraged to gather every Thursday leading up to Nov. 4 between 12 noon and 12:30 p.m. Spend time with the Lord, asking Him to guide and direct those privileged to cast a ballot. If you are able, I would also encourage you to fast and pray immed”ately before the election. After all, it was the Reverend Billy Graham who once said that “To get nations back on their feet, we must first get down on our knees.”20 Amen, Dr. Graham.

This election is about the future of the nation, but it will also go a long way toward determining the culture your children and grandchildren will come to know. I know you will vote with your children and your children’s children in mind. That certainly puts the election in a different light, doesn’t it?

Apparently God was listening. He answered their prayers on Tuesday. Here's how Tom Hess describes the result [‘We Need to Continue to be in Prayer for America’].

With an Obama administration forthcoming, Focus Action’s Tom Minnery says, “We’ve got a big challenge ahead of us.”

He and FRC Action President Tony Perkins encouraged CitizenLink viewers to remain hopeful of what God might do in the next four years — and to be in prayer.

“For those who have been praying for weeks, our responsibility does not end today,” Perkins said. “In Luke 18, Jesus said men should not lose heart, but they should pray. We need to continue to be in prayer for America.”

Minnery pointed out that in the Bible, God worked through pagan rulers such as Nebuchadnezzar, Darius and Cyrus to accomplish his purposes, and that values voters ought to begin praying for President-elect Obama.

“God can use any president for his own purposes,” Minnery said.

You can't make this stuff up.

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[Hat Tip: Primordial Blog]

It's Her Last Saturday in the Lab

 
Eva Amsen blogs at Expression Patterns on the Nature Network [Last Saturday]. My department will miss her when she leaves.

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Small Science Is Good Science?

 
I've been thinking a lot lately about what's wrong with science in the 21st century. Part of the problem is sloppy thinking that becomes apparent when you realize how many widely believed models are inconsistent with what we know about biology. I assume that similar problems occur in other disciplines.

One wonders if the proliferation of papers with huge numbers of authors is part of the problem. Maybe this fad of "multidisciplinary" science is part of the problem and not part of the solution? Is it possible to be an expert in two or more different disciplines?

I've seen plenty of example of biochemists and molecular biologists who publish papers about evolution without knowing much about evolution. Is this an isolated example?

Speaking of "big science," I was reminded of a paper published by Bruce Alberts back in 1985 in Cell. The title was "Limits to growth: In biology, small science is good science" (Alberts 1985).

These days, many people grow up believing that bigger is better. Giant factories that produce Wonder Bread have replaced thousands of corner bakeries, driven by the increased efficiency of scale. There is an unfortunate tendency to extend this view to the biological research community, and I have on occasion heard a major symposium speaker introduced in glowing terms as the coauthor of more than fifty papers per year. While I can admire the energy and management skills required to maintain a very large laboratory, the best biology is rarely done in this way. With a few notable exceptions, the biochemists and molecular biologists I most respect run relatively small laboratories and publish when they have something important to report. As I shall argue here, doing good science is very different from producing bread, and there are compelling reasons why large laboratories are in general less efficient and less interesting than smaller ones. To reflect this fact, I believe that changes in funding patterns and expectations would be useful in the biological sciences.

Some "big science" is good. The sequencing of the human genome, and other genomes, for example, was a big science project that benefited the entire biological community. But I'm not sure that significant advances in our understanding of how life works come from big labs. Does anyone have examples? What are the most significant conceptual advances to come out of big labs?

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Alberts, B.M. (1985) Limits to growth: In biology, small science is good science. Cell 41:337-338. [PubMed] [doi:10.1016/S0092-8674(85)80001-5]

Ignore, Reject, Answer? What to Do about Student Email Messages

 
Some of my colleagues are running courses where they ask students to write essays on science subjects. Part of the assignment is to contact a Professor in the discipline and get them to help with the scientific content of the essay. The idea is for the students to make sure they have their facts correct. A side benefit is that it gets the students in touch with active researchers.

Some of us object to this procedure on the grounds that if it became widespread there would be hundreds of students looking for Professors to help them on their assignment. Most Professors have other priorities, like teaching their own classes. To some extent, our colleagues who engage in this practice are downloading their teaching responsibilities onto others.

From 1992-2000 I ran a molecular biology course where the students had to write a major essay. They were told to do the research themselves but the instructors would be available if they need help with the interpretation of some papers. If necessary, we would put them in touch with an expert but only after the student had done enough work to ask intelligent questions on difficult material.

Here's an email message that was sent to my Sandwalk address last night. How should I respond? I don't feel comfortable ignoring the message. I will feel awkward if I refuse to help. I don't had time to answer the question—it's complicated and, besides, it's not my area of expertise.

Dear Professor Moran,

As part of a University assignment, I have been asked to email a group of experts to request their professional opinion on a particular question.

I have come to understand that a child with Dyspraxia should supplement their diet with a high dose of essential fatty acids. However, as non-Dyspraxic people age it is advised that they also should supplement their diet with these oils to combat age-related memory loss. Does this mean that people with Dyspraxia should augment their intake yet again when they age? If so, could this have an adverse effect on their health?

As your organisation came up in an internet search as being reputable, your answer to this question would be much appreciated.

I would like to thank you for taking the time to read this email and I hope to hear from you soon.

Yours sincerely,

This makes me angry. No matter what I do, I'm going to be disappointing a student who might really benefit from a reply. In my opinion the student's Professor is at fault for assigning such a task to the students.

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Barack Obama Will Save Religion in America

 
Frank Scaheffer writes in The Huffington Post [President Obama: Bad News For the New Atheists and Other Fundamentalists].

The Obama presidency is great news for almost everyone. It's bad news for some odd ideological bedfellows: the Religious Right and the so-called New Atheists.

Into the all or nothing culture wars, and the all or nothing wars between the so-called New Atheists and religion the election of President elect Obama reintroduces nuance. President elect Obama's ability to believe in Jesus, yet question, is going to rescue American religion in general and Christianity in particular, from the extremes.

There is no way to understand President elect Obama's victory as anything less than the start of not just a monumental political change but a spiritual revolution as well.

Who knew? I bet all atheists and agnostics are feeling pretty stupid right now knowing that they've been tricked by the slick-talking Obama.

And what is the "nuanced" spiritual revolution going to look like?

To the New Atheists who think that with the resounding defeat of the Religious Right, we are entering a secular age, think again. Obama will block your path. He'll do it for the same reason he'll make the Religious Right's paranoid fantasies about him soon seem shamefully ridiculous. That's because President elect Obama is that rarest of all rare people: a thoughtful, compassionate and likable statesman who also is a thoughtful, compassionate and likable religious believer.

Sounds like trouble. President Obama is going to block the path to a secular society. Gosh. I knew that American Presidents were leaders of the free world and the most powerful men (no women so far) on the planet but even I had no idea they were that powerful.

President-elect Obama brings another perspective to faith . It goes something like this:

How do cultures define themselves if not through ritual? In the "big moments" of life; birth, marriage, sickness, death "who" -- in the inimitable words of Ghost Busters -- "you gonna call?" As President elect Obama has said, and I paraphrase: Strip the human race of our spiritual language and what do we tell each other about hope?

As President elect Obama has pointed out, a world of all math but no poetry is not fit for human habitation. If everything feels flat and dull, stripped of mystery and meaning who will bother to do the science? Why bother, if all we're doing is serving those selfish genes for another round of meaningless propagation?

So does this faith always make "sense?" No. Because our perspective is from the inside, something like paint contemplating the painting of which it's a part. We're all in the same boat, all stuck on the same "canvas."

Ohmygod. Frank Shaeffer and Barack Obama have discovered the atheist dirty little secret. All of us atheists are flat and dull—we can't be born, get married, or die without calling upon God to help us.

Does anyone actually believe this stuff?

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[Hat Tip: RichardDawkins.net]

Evolution by Gene Duplication

Chymotrypsin (Monday's Molecule #95), trypsin, and elastase are enzymes that digest proteins in the stomach and intestine. All three enzymes have a similar mechanism of hydrolysis characterized by the presence of a catalytic triad of amino acid side chains consisting of aspartate, histidine, and serine residues. The serine side chain is directly involved in catalyzing the cleavage of proteins and that's why these enzymes are called serine proteases.

The three enzymes differ in specificity. Chymotrypsin cleaves foreign proteins primarily at tyrosine (Tyr) resides, trypsin is specific for cleavage at arginine (Arg) or lysine (Lys) resideus, and elastin cleaves at alanine (Ala) residues.

The genes for the three enzymes are homologous and the structures of the three enzymes are very similar as shown below (left: chymotrypsin [PDB 5CHA], middle: trypsin [PDB 1TLD], right: elastase [PDB 3EST]).


The active sites of the enzymes are slightly different so that specificity depends on which amino acid side chains of the substrate protein fit into the binding pocket.


It's reasonable to suppose that the primitive enzyme could bind weakly to many different substrates and cleave many different kinds of proteins inefficiently. An ancient gene duplication allowed one copy of the gene to evolve toward a much more active enzyme that cleaved only at certain residues. A second gene duplication gave rise to a third enzyme that cleaved at another residue. Finally the remaining gene evolved into a very active enzyme that cut at a third position.

The end result was a set of three enzymes that could cut up any protein into small peptides that can be taken up by the cells lining the intestine. The original non-specific enzyme was slower and less efficient.

This is an example of evolution by gene duplication and the important point is that the ancestral gene probably encoded a non-specific enzyme that could carry out several different reactions with different substrates. It's not a question of the duplicated copy evolving an entirely new specificity. Instead, the duplicated gene usually "perfects" an already existing minor activity by becoming more specific. Meanwhile, the other copy can also be selected for enhanced specificity for another substrate.

This model also explains the evolution of lactate dehydrogenase and malate dehydrogenase (Evolution and Variation in Folded Proteins) and the pyruvate dehydrogenase family (Pyruvate Dehydrogenase Evolution).

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Nobel Laureate: John Howard Northrop

 

The Nobel Prize in Chemistry 1946.

"for their preparation of enzymes and virus proteins in a pure form"



John Howard Northrop (1891 - 1987) was a renowned protein chemist who developed techniques for purifying and crystallizing enzymes.

He shared the prize with James Sumner, who first showed that proteins could be crystallized and with Wendell Stanley who crystallized tobacco mosaic virus.

Most biographers note that Northrop was very interested in genealogy and was proud to point out that he was a direct descendant of Joseph Northrop who settled in New Milford Connecticut in 1636 (John H. Northrop). I don't know if any other Nobel Laureates can trace their North American ancestors back 400 years.

The significanc of Northrops work is summarized in this excerpt from the presentation speech on the Nobel Prize website.

THEME:
Nobel Laureates

Doctor John Northrop. You and your collaborators have developed the crystallization of enzymes and other active proteins into an art, of which you are the masters. The conditions for successful work in this field were explored by you, and in the course of that work interesting relationships between enzymes and related proteins were discovered, which may ultimately afford a clue to a fuller understanding of the mode of action of these substances.

We now know that trypsin, pepsin, and chymotrypsin are similar proteases that cleave other proteins. We also know that the active enzymes are derived from inactive precursors called zymogens. The zymogens (pepsinogen, trypsinogen, and chymtrypsinogen) are cleaved to remove part of the protein making the remainder into an acive enzyme. It's interesting to see how John H. Northrop described this discovery in his acceptance speech.

Formation of enzymes from their precursors. Pepsin, trypsin, and chymotrypsin are derived from inactive precursors. These precursors were isolated and crystallized and the formation of the active enzyme studied. The formation of pepsin from pepsinogen and trypsin from trypsinogen are autocatalytic reactions. These enzymes may therefore be "propagated", just as are bacteria. The formation of trypsin from trypsinogen may also be catalyzed by enterokinase, an enzyme of the digestive tract, or by an enzyme produced by a mold (Penicillium.) The formation of chymotrypsin from chymotrypsinogen is catalyzed only by trypsin, so far as is known. In all these reactions the increase in enzymatic activity is accompanied quantitatively by the appearance of the new enzyme protein which is quite different in all its properties from the original precursor. It seems to me that these results are perhaps the most convincing evidence that the enzymatic activity is actually a property of the protein molecule.

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What Does Change Look Like?

 
I'm glad Barrack Obama won the election. He is much less conservative than John McCain and much more likely to do good things for America.

Change is in the air, everybody is talking about a new direction for America under Barack Obama. What kind of changes can we expect? Here's a sample from last night's vote on several propositions [CNN.com].

This measure would amend the state constitution so that only a union between one man and one woman would be valid or recognized as a marriage in the state. A similar measure was on the ballot in 2006 but failed.

According to the exit poll [Arizona Prop.102], 67% of Protestants voted to ban gay marriage as did 51% of Catholics. About 13% of voters said they had no religion and 69% of them voted against Proposition 102.

This measure would prohibit unmarried "sexual partner[s]" from adopting children or from serving as foster parents. The measure specifies that the prohibition applies to both opposite-sex as well as same-sex couples.

According to the exit poll [Arkansas Initiative 1], the voters are evenly split between Democrats, Republicans, and Independents. Democrats voted against the initiative (52%) but the other two groups voted in favor of the ban. A majority of college graduates (52%) and those with postgraduate education (54%) voted in favor of the ban on adoptions.

This measure would amend the state constitution to specify that only marriages between one man and one woman would be recognized as valid in the state. If passed, the measure would trump a May 2008 ruling by the California Supreme Court that legalized same-sex marriage.

According to the exit poll [California Proposition 8], a majority of whites (53%) and Asians (53%) voted against Proposition 8 while a majority of African-Americans (70%) and Latinos (51%) voted in favor of the ban. Democrats (65%) and Independents (56%) were against the ban but 81% of Republicans voted in favor of the ban on gay marriage.

This measure would amend the state constitution to define the term "person" to include "any human being from the moment of fertilization." This definition would be applied to all aspects of the state constitution, including the provisions that ensure that no person has his or her life, liberty, or property taken away without due process of law. Thus, the measure would essentially have the effect of banning abortion.

According to the exit poll [Colorado Amendment 48], this amendment should have been approved by a substantial majority.

This measure would amend the state constitution to define marriage as a union between one man and one woman. In order to amend the Florida constitution, 60 percent of voters must vote in favor of the amendment.

According to the exit poll [Florida Amendment 2], 71% of Protestants and 66% of Catholics voted in favor of the amendment to ban gay marriage. A majority of Whites (60%), African-Americans (71%), and Latinos (64%) voted for the ban.

This measure would prohibit all abortions in the state except in cases where mother's life or health is at risk or in cases of rape or incest for pregnancies of less than 20 weeks. A similar measure that did not include exceptions for rape or the health of the mother was on the ballot in 2006, but was rejected by voters 44 to 56 percent.

According to the exit poll [South Dakota Initiative 11], only evangelical born-again Christians and conservative Republicans supported the initiative. A majority of all other groups voted against it.

This measure would allow terminally ill, competent, adult residents of the state to request and self-administer lethal medication prescribed by a physician. The person requesting to end his or her life must be medically predicted to have six months or less to live.

According to the exit poll [Washington Initiative 1000], this initiative was supported by liberals (81%) and moderates (63%) and opposed by conservatives (66%). There are more liberals (29% of the voters) than in most states. Republicans (63%) voted against the initiative while Democrats (75%) and Independents (59%) voted for it.

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Asses on Panda's Thumb

 
It's probably not a coincidence that Panda's Thumb published a photo of a pair of asses today. See them at Equus asinus.

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Ken Ham and Jesus Visit Toronto

 
I forgot to mention that "Ken Ham" and "Jesus" were at P.Zed's talk on Friday night. Theo Bromine has photographic proof on the blog Thinking for Free [PZed Myers comes to TO].

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Anonymous Students and Their Grades

 
In Ontario we have to conform to the Freedom of Information and Protection of Privacy Act (FIPPA). What this means is that we cannot publish student names and grades. The University of Toronto guidelines are very clear on this matter [Q and A for Instructors under FIPPA]. We shouldn't even be publishing student numbers with grades.

I just checked with one of my colleagues to find out what the policy was when she graduated in 1949. She showed me the booklet put out by the university in 1949. Her name and grades were listed there. Furthermore, the names and rankings of all student were published in the newspaper.

I asked one of my students who attended high school in Europe. Her name and grades were published in the newspaper. I'm told that this practice continues in some European countries. Another of my colleague learned his medical school grades by reading the Glasgow newspaper in the early 1950s.

Assuming that FIPPA does not apply to the publication of university grades (an invalid assumption), should we publish student names and grades? What are the non-legal arguments for and against this policy?

I like the idea of publishing student's names and grades because it helps make them take responsibility for their activities at university. Very few people agree with me. They all think that a student has a right to privacy. Most of these people don't have a problem with publishing Professor's salaries and course evaluation results because the public has a right to know this information.

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[Photo Description: This is a photograph of the wall on the ground floor of my building. You can see the names and photographs of every student in the medical school graduating class.]

Today Is a Very Important Day

 
It's Sandwalk's second birthday. It was two years ago today that I posted the first message on Sandwalk [Welcome to my Sandwalk].

I started Sandwalk when PZ Myers convinced me that blogging wasn't just a fad. There was a real opportunity to discuss science, and other things, in the blogosphere. Since Nov. 4, 2006 I have published 2,253 postings—some of them have been quite popular and a few of them have been quite good (IMHO).

Sandwalk has grown into a moderate-sized blog with a number of regular readers. I'm particularly excited about the people who comment. They teach me a lot. I'm impressed by the quality of the discussion that goes on in the comments section of Sandwalk postings. This was something that I was hoping for when I started this blog.

A big thank-you to everyone who reads and comments. You've made it all worthwhile.

Here are the latest numbers.

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Please Help Me with My Homework

 
I get email messages like this on a regular basis ...

Hi Mr. Moran, My name is XXX and I am a student at YYY and I would like your help in my English Research Paper.

My task is to write a research paper about something that matters in America today, and I believe the situation surrounding the ID movement is something that really matters. I was wondering where would I be able to get the best information pretaining to the anti-ID, and I thought, why not get it from talk origins?

So Mr. Moran, I would greatly appreciate you helping me in my research paper by outlining and detailing why ID should not be allowed in classrooms or directing me to some one who can.

Thank you for your time, it is greatly appreciated.

I wonder how his teachers define "research"? Back in the olden days we used to read books and articles in order to prepare to write a research paper. Some of you may be familiar with books.

Why have things changed? Why do today's students think they can ask someone else to do all the work for them? Has it got something to do with entitlement, or is it more closely related to intelligence?

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A Canadian Perspective on Tomorrow's Victory

 
Read Is It Wednesday Yet? by psa on Canadian Cynic.

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Goodbye PZ Myers

 
There were about eighteen people at the farewell dinner for PZed and Skatje on Saturday night. We really enjoyed his visit.

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In Search of Spandrels

While looking for postings on the Maynard Smith fumble (Maynard Smith on Stephen Jay Gould) I came across this one, posted on talk.origins on Aug. 20, 1998. I had forgotten about my second search for the Spandrels paper.

This is a paper that every student of evolution should read. I can't think of a paper by Maynard Smith that falls into that category.

I recently found myself in the catacombs of the library archive far away from the stress of students writing their summer exams. It was very peaceful. It was also a place where creationists never go.

I must confess that my primary motivation for being there was work avoidance - I hate marking exams - but there was another reason as well. My secondary mission was to retrieve a pristine copy of the "Spandrels" paper so I could hand it out to my students. (My own copy had some embarassing margin notes that weren't fit for young eyes.)

There were many bound volumes of the Proceedings of the Royal Society of London (Series B). Did you know that this journal goes back over one hundred years? (That's even before I was born.) Did you know that you have to look in the stacks under "R", for "Royal", and not "P", for "Proceedings"? Did you ever wonder why librarians do that? My own theory is that they really don't want us to take out their books so they make it as difficult as possible to find something.

I was looking for volume 205 (1979). As usual, it was on the bottom shelf; way down at the level of my shoes. I had to get down on one knee and that's a lot of work. But at least volume 205 wasn't missing. With trembling hands I flipped the pages looking for the sacred text. Would it be there or would the pages have been cut out with a razor blade? Chances were good - pre-med students don't read about evolution.

Yes! There it was: "The Spandrels of San Marco and the Panglossian paradigm: a critique of the adaptionist programme" by S.J. Gould and R.C. Lewontin. They even spelled "programme" correctly! Off I went to the photocopy machine. Off I went to buy a new photocopy card. Back I came to the photocopy machine. Let's see now ... how much magnification will I need to fill an 8x11 page so I don't have to close the damn lid every time I copy a page? 125% should do it. Wrrrrr .... flash .... swish .... splat.

Maybe 120% would work ...

At last, page 598 was perfect. (Anyone want extra copies of the references from this paper?) I worked my way forward to page 581 fending off the librarian who insisted that I had to close the lid or I would ruin the photocopier - and my eyes (I'm not sure which was more important to her).

I was lucky there were three or four students to distract her. Behind my back I heard some mumblings about "eccentric" and "stubborn" but unfortunately I couldn't see exactly what was going on.

Hope I didn't miss anything interesting.

I knew that Gould had presented the paper at a meeting in London in December, 1978. Lewontin wasn't there because you have to fly to get to England and Lewontin thinks that if humans were made to fly then we would have evolved wings. So, who else was at the meeting? Did they publish papers in the same issue of the journal? Let's see ...

My thoughts were interrupted by some shouting in the line behind me. Guess I'd better get away from the photocopier. The machine seems to be making people angry.

Off I went to find a desk to sit down at. Found one. Off I went to the photocopier to retrieve my photocopy card. Back I came to the desk.

Someone was there. Found another desk. It had a banana peel on it.

Cool. All the papers are here. The meeting was called "The Evolution of Adaptation by Natural Selection" and it was organized by John Maynard Smith and R. Holliday. Orgel has a paper on evolution in vitro. The Charlesworths write about sex in plants. There's a paper by Maynard Smith on game theory and the evolution of behaviour. George Williams was present (more about him later). And guess who else? - Richard Dawkins!

The Dawkins' paper is titled "Arms races between and within species" (R. Dawkins and J.R. Krebs). It goes on and on about the adaptive significance of arms races and the optimization of animals. I bet the Gould talk was not well received by Dawkins in 1978. :-)

The Williams paper is very interesting ("The question of adaptive sex ratio in outcrossed vertebrates"). He examines two popular theories of the adaptive control of sex ratio (why there are 50% males and 50% females). After looking at the detailed models and the available data he concludes,

Evidence from vertebrates is unfavourable to either theory and supports, instead, a non-adaptive model, the purely random (Mendelian) determination of sex.

Good for him. I wish I could have been at the meeting. Maybe there was a discussion. Flipping to the back of the book I find a petulant summary of the meeting written by A.J. Cain. You can tell he's really annoyed at something that went on in the meeting,

Ever since natural selection appeared on the scene, there have been those who voiced an a priori and dogmatic dislike of it. One classic example is George Bernard Shaw ... I suspect from my own work that natural selection may have been very much more important than anyone has realized up to now. If so, can these emotional and other rejections of it, or, more generally, the tendency of the human race to take a non-objective view of evolution and kindred topics, be explained by natural selection?

There is a possible evolutionary explanation, as yet untested, and no other scientific one that I know of.

Whew! The discussion must have been exciting. Let's see, it should be right at the end. Ah, here it is,

[It has not been possible to include the general discussion in this publication.]

Damn.

Gotta go, the banana peel is making me ill - it looks like it's been here since the day before yesterday. Is that a fruit fly? Off I go.

Back again. (Forgot my pen.) See ya.

Larry Moran

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Maynard Smith on Stephen Jay Gould

 
Someone resurrected an old quotation by John Maynard Smith in a comment on Good Science Writers: Stephen Jay Gould.

Here's how I replied on March 26m 2002 on the newsgroup talk.origins. It was at least the tenth time I had addressed this silly comment by Maynard Smith.

This is not a universally held view. LAM is no doubt familiar with John Maynard Smith's famous remarks about Gould:

"Gould occupies a rather curious position, particularly on his side of the Atlantic. Because of the excellence of his essays, he has come to be seen by non-biologists as the preeminent evolutionary theorist. In contrast, the evolutionary biologists with whom I have discussed his work tend to see him as a man whose ideas are so confused as to be hardly worth bothering with, but as one who should not be publicly criticized because he is at least on our side against the creationists. All this would not matter, were it not that he is giving non-biologists a largely false picture of the state of evolutionary theory."

As an aside, isn't that beautifully written?

Genes, Memes, & Minds JOHN MAYNARD SMITH November 30, 1995, New York Review of Books (the essay was a review of "Darwin's Dangerous Idea: Evolution and the Meanings of Life" by Daniel C. Dennett).

Unfortuantely JMS drops the issue at that point and has, so far as I know, never taken it up again.

He probably thought he had better things to do.

Either that, or he was very embarrassed by his inappropriate remarks and hopes that most people will forget about them. I wonder what Maynard Smith thinks of all those idiots in the AAAS who elected Gould President of the largest scientific society in the world? What in the world could Maynard Smith have been thinking when he invited Gould to Oxford to give a prestigious series of lectures on evolutionary theory?

For those interested in the background to all this, I can do little better than suggest reading Segerstråle's book "Defenders of the Faith", where she discusses the history of all this, the arguments between people like Lewontin, E.O. Wilson, Gould, Dawkins, etc. JMS comes out of it well - he was sat in the middle trying to makes sense of both sides.

Do you really think that Maynard Smith's remarks quoted above represent someone who's trying to make sense of Gould's side? Maynard Smith is firmly on the side of Dawkins in this debate. Like Dawkins, he has never given any indication that he understands the main issues. When Maynard Smith says that Gould is presenting a "largely false picture of the state of evolutionary theory" you should appreciate that what Maynard Smith is really saying is that Gould presents a picture that Maynard Smith disagrees with. Only Maynard Smith and his friends know about the *true* picture of evolutionary theory.

Gould is not nearly as arrogant as his opponents.

I've also noted on several occasions that just because Maynard Smith can't understand the complications of modern evolutionary theory doesn't mean that his simplistic version is correct.

In addition I've pointed out that Gould is often referenced in evolution textbooks for his contributions to pluralism, heterochrony, punctuated equilibria, progression, disparity, the tape of life, species selection, and spandrels. You have to look hard to find references to Maynard Smith.

To me that suggests that Maynard Smith is a man hardly worth bothering with.

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[Image Credit: Photograph of Stephen Jay Gould by Kathy Chapman from Lara Shirvinski at the Art Science Research Laboratory, New York (Wikipedia)]

Monday's Molecule #95

 
This is a very famous molecule, featured in all biochemistry textbooks. You have to identify the molecule—be careful there are several possibilities and it's easy to go wrong. You don't have to tell me the species. (Hint: the three red amino acid side chains are aspartate, histidine, and serine.)

This week's Nobel Laureate(s) won the prize for his work with this molecule (and several others).

The first one to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are only two ineligible candidates for this week's reward: Haruhiko Ishii, and Bill Chaney of the University of Nebraska.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: The molecule is chymotrypsin, not chymotrysinogen or pepsin or elastin. These proteins are called serine proteases because they have a catalytic serine residue in the active site. The Nobel Laureate is John Howard Northrop, the first person to purify and crystallize chymotrypsin. The first person to get it right was Dima Klenchin of the University of Wisconsin, who just recently fell off the ineligible list.

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Conservatives Approve Physical Violence

 
Normally I don't pay much attention to the Blogging Tories, a group of conservative Canadian bloggers. Canadain Cynic usually does a good job of finding the most ridiculous postings so we can all have a good chuckle from time to time [see She's so adorable, with that folksy racism of hers]. The average IQ of these blogging Tories seems to be significantly below 80.

"Hunter" is a female blogger from Alberta—Canada's version of Texas. She really doesn't like Barack Obama and has taken it upon herself to warn all Canadians about the perils of socialism. Here's an example of her latest posting [Coming to America].

Are Americans going quietly into socialism? Here is a good take on freedom of speech, and the 2nd Amendment:


Kind of says it all doesn't it.

Just in case some non-Americans are confused about the reference to the 2nd Amendment, let me remind you that it's the amendment Americans use to justify their right to have guns and shoot people who disagree with them.

It does say it all. Conservatives on both sides of the border seem to think it's acceptable to shoot someone who steals campaign signs. That says a lot about their mentality. Who wants to live in a society where such people have guns?

There are days when I secretly hope that McCain wins the election. Then maybe some of our conservative citizens from Alberta could move to Texas. This would benefit both Alberta and Texas.

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Mendel's Garden #25

 
The 25th edition of Mendel's Garden has just been posted on evolgen [Mendel's Garden #25].

After a few months¹ off, here's the return of Mendel's Garden.

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1. Six, to be exact.