REVIEW of Christina Riggs, The Beautiful Burial in Roman Egypt:

OUP's page

Reviewed by David Frankfurter, University of New Hampshire (davidTf@unh.edu)
Word count: 1616 words

How Egyptian was Roman Egypt? The question has dominated quarters of Classics, Art History, and Ancient History for over a century. The perpetuation of classical Egyptian iconography on temples suggests a fundamental religious conservatism, while papyrological documentation reflects extensive Hellenism.

But for some decades -- since at least Glen Bowersock's Hellenism in Late Antiquity -- the most exciting work has sought to de-polarize Egyptianism and Hellenism as forces and instead to explain the ways that Egyptian traditions could be revitalized through Hellenism and Hellenism appropriated in Egyptian terms. Thus in recent years the scholar of Roman Egypt has had to reckon with such carefully nuanced studies as Fowden's Egyptian Hermes, Venit's Monumental Tombs of Ancient Alexandria, Dieleman's Priests, Tongues, and Rites, as well as the many essential essays of Jan Quaegebeur.1 Into this lively scholarship on the interplay of Egyptian and Hellenistic traditions in the Roman period comes this impressive and richly documented book by Christina Riggs, the new curator of Egyptology at the University of Manchester Museum. The book covers the varying uses of Egyptian, Greek, and Roman imagery in that most conservative of subcultures, mummification workshops.

more at BMCR

Cellular Respiration Ninja Enzymes

 
Here's a student video presentation of glycolysis and respiration. It's much better than most [e.g., An Example of High School Biochemistry]. However, there are two errors in the video. The first one is fairly serious. The second one is less serious but it's something we cover in my class and it helps illustrate a fundamental concept about how certain reactions work. The second error was very common in most biochemistry textbooks in the past but it's been eliminated from the majority of 21st century textbooks. Can you spot both errors?



[Hat Tip: Greg Laden]
[Hint: What are the products produced by glycolysis and by the Krebs cycle?]

Penicillin Resistance in Bacteria: After 1960

 
The widespread appearance of penicillin-resistant bacteria by 1960 prompted the introduction of new drugs that could not be degraded by newly evolved β-lactamases [see Penicillin Resistance in Bacteria: Before 1960].

The most important of these new drugs are the cephalosporins, modified β-lactams with bulky side chains at two different positions. These drugs still inhibit the transpeptidases and prevent cell wall formation but because of the bulky side chains they cannot be hydrolyzed by β-lactamases. Thus, they are effective against most of the penicillin-resistant strains that arose before 1960.

Other drugs, such as methicillin, were modified penicillins. They also had modified side chains that prevented degradation by the β-lactamases.

It wasn't long before cephalosporin- and methicillin-resistant strains began to appear in hospitals. As a general rule, these strains were not completely resistant to high doses of the new class of drugs but as time went on the resistant strains became more and more immune to the drugs.

The new version of drug resistance also involves the transpeptidase target but instead of developing into β-lactamases they evolve into enzymes that can no longer bind the cephalosporins. Usually the development of resistance takes place in several stages.

There are many different transpeptidases in most species of bacteria. The are usually referred to as penicillin-binding proteins or PBP's. Often the first sign of non-lactamase drug resistance is a mutant version of one PDP (e.g., PDP1a) and subsequent development of greater resistance requires the evolution of other PDB's that don't bind the drug. In the most resistant strains there will be one particular PDB (e.g., PDB2a) that is still active at high drug concentrations while the other transpeptidases will be inhibited.

Resistant enzymes have multiple mutations, which explains the slow, stepwise acquisition of drug resistance. An example is shown in the figure. This is PDP1a from Streptococcus pneumoniae (Contreras, et al. 2006) and the mutant amino acids are displayed as gold spheres. Most of the mutations do not affect the binding of the drug but those surrounding the entry to the active site are crucial. The necessary amino acid substitutions are numbered in the figure. You can see that they line the groove where the cephalosporin drug (purple) is bound. The effect of the mutations is to prevent the bulky β-lactam from inhibiting the enzyme. This is a very different form of drug resistance than the evolution of degradation enzymes that characterized the first stage of penicillin resistant bacteria.

---

Chambers, H.F. (2003) Solving staphylococcal resistance to beta-lactams. Trends Microbiol. 11:145-148.

Contreras-Martel, C., Job, V., Di Guilmi, A.M., Vernet, T., Dideberg, O. and Dessen, A. (2006) Crystal structure of penicillin-binding protein 1a (PBP1a) reveals a mutational hotspot implicated in beta-lactam resistance in Streptococcus pneumoniae. J. Mol. Biol. 355:684-696.

Livermore, D.M. (2000) Antibiotic resistance in staphylococci. Int. J. Antimicrob. Agents 16:s3-s10.

Penicillin Resistance in Bacteria: Before 1960

 
The Nobel Prize for the discovery and analysis of penicillin was awarded in 1945 [Nobel Laureates: Sir Alexander Fleming, Ernst Boris Chain, Sir Howard Walter Florey]. It was about this time that penicillin became widely available in Europe and North America.

By 1946 6% of Staphylococcus aureus strains were resistant to penicillin. Resistance in other species of bacteria was also detected in the 1940's. By 1960 up to 60% of Staphylococcus aureus strains were resistant with similar levels of resistance reported in other clinically relevant strains causing a wide variety of diseases (Livermore, 2000).

Penicillins are a class of antibiotics with a core structure called a β-lactam. The different types of penicillin have different R groups on one end of the core structure. A typical examples of a penicillin is penicillin G [Monday's Molecule #30]. Others common derivatives are ampicillin and amoxicillin.

The original resistance to this entire class of drugs was caused mostly by the evolution of bacterial enzymes that could degrade them before they could block cell wall synthesis. (Recall that bacteria have cell walls and penicillin blocks cell wall synthesis [How Penicillin Works to Kill Bacteria].)
It seems strange that the evolution of penicillin resistance would require a totally new enzyme for degrading the drug. Where did this enzyme come from? And how did it arise so quickly in so many different species?

The degrading enzyme is called penicillinase, β-lactamase, or oxacillinase. They all refer to the same class of enzyme that binds penicillins and then cleaves the β-lactam unit releasing fragments that are inactive. The enzymes are related to the cell wall transpeptidase that is the target of the drug. The inhibition of the transpeptidase is effective because penicillin resembles the natural substrate of the reaction: the dipeptide, D-alanine-D-alanine.

In the normal reaction, D-Ala-D-Ala binds to the enzyme and the peptide bond is cleaved causing release one of the D-Ala residues. The other one, which is part of the cell wall peptidoglycan, remains bound to the enzyme. In the second part of the reaction, the peptidoglycan product is transferred from the enzyme to a cell wall crosslinking molecule. This frees the enzyme for further reactions (see How Penicillin Works to Kill Bacteria for more information).

Penicillin binds to the peptidase as well and the β-lactam bond is cleaved resulting in the covalent attachment of the drug to the enzyme. However, unlike the normal substrate, the drug moiety cannot be released from the transpeptidase so the enzyme is permanently inactivated. This leads to disruption of cell wall synthesis and death.

Resistant strains have acquired mutations in the transpeptidase gene that allow the release of the cleaved drug. Thus, the mutant enzyme acts like a β-lactamase by binding penicillins, cleaving them, and releasing the products. Although the β-lactamases evolved from the transpeptidase target enzymes, the sequence similarity between them is often quite low in any given species. This is one of the cases where structural similarity reveals the common ancestry [see the SCOP Family beta-Lactamase/D-ala carboxypeptidase]. It's clear that several different β-lactamases have evolved independently but, in many cases, a particular species of bacteria seems to have licked picked up a β-lactamase gene by horizontal transfer from another species. The transfer can be mediated by bacteriophage or plasmids.

---

Livermore, D.M. (2000) Antibiotic resistance in staphylococci. Int. J. Antimicrob. Agents 16:s3-s10.

Catherine Shaffer Responds to My Comments About Her WIRED Article

 
Over on the WIRED website there's a discussion about the article on junk DNA [One Scientist's Junk Is a Creationist's Treasure]. In the comments section, the author Catherine Shaffer responds to my recent posting about her qualifications [see WIRED on Junk DNA]. She says,

You might be interested to learn that I contacted Larry Moran while working on this article and after reading the archives of his blog. I wanted to ask him to expand upon his assertion that junk DNA disproves intelligent design. His response was fairly brief, did not provide any references, and did not invite further discussion. It's interesting that he's now willing to write a thousand words or so about how wrong I am publicly, but was not able to engage this subject privately with me.

Catherine Shaffer sent me a brief email message where she mentioned that she had read my article on Junk DNA Disproves Intelligent Design Creationism. She wanted to know more about this argument and she wanted references to those scientists who were making this argument. Ms. Shaffer mentioned that she was working on an article about intelligent design creationism and junk DNA.

I responded by saying that the presence of junk DNA was expected according to evolution and that it was not consistent with intelligent design. I also said that, "The presence of large amounts of junk DNA in our genome is a well established fact in spite of anything you might have heard in the popular press, which includes press releases." She did not follow up on my response.

His blog post is inaccurate in a couple of ways. First, I did not make the claim, and was very careful to avoid doing so, that “most” DNA is not junk. No one knows how much is functional and how much is not, and none of my sources would even venture to speculate upon this, not even to the extent of “some” or “most.”

Her article says, "Since the early '70s, many scientists have believed that a large amount of many organisms' DNA is useless junk. But recently, genome researchers are finding that these "noncoding" genome regions are responsible for important biological functions." Technically she did not say that most DNA is not junk. She just strongly implied it.

I find it difficult to believe that Ryan Gregory would not venture to speculate on the amount of junk DNA but I'll let him address the validity of Ms. Shaffer's statement.

Moran also mistakenly attributed a statement to Steven Meyer that Meyer did not make.

I can see why someone might have "misunderstood" my reference to what Myer said so I've edited my posting to make it clear.

Judmarc and RickRadditz—Here is a link to the full text of the genome biology article on the opossum genome: Regulatory conservation of protein coding and microRNA genes in vertebrates: lessons from the opossum genome. We didn't have space to cover this in detail, but in essence what the researchers found was that upstream intergenic regions were more highly conserved in the possum compared to coding regions, but also represented a greater area of difference between possums and humans.

This appears to be a reference to the paper she was discussing in her article. It wasn't at all clear to me that this was the article she was thinking about in the first few paragraphs of her WIRED article.

Interested readers might want to read the comment by "Andrea" over on the WIRED site. She He doesn't pull any punches in demonstrating that Catherine Shaffer failed to understand what the scientific paper was saying. Why am I not surprised? (Recall that this is a science writer who prides herself on being accurate.)

So, yes, this does run counter to the received wisdom, which makes it fascinating. You are right that the discussion of junk vs. nonjunk and conserved vs. nonconserved is much more nuanced, and we really couldn't do it justice in this space. Here is another reference you might enjoy that begins to deconstruct even our idea of what conservation means: “Conservation of RET regulatory function from human to zebrafish without sequence similarity.” Science. 2006 Apr 14;312(5771):276-9. Epub 2006 Mar 23. Revjim—If you have found typographical errors in the copy, please do point them out to us. The advantage of online publication is that we do get a chance to correct these after publication.

Sounds to me like Catherine Shaffer is grasping at straws (or strawmen).

For Katharos and others—I interviewed five scientists for this article. Dr. Francis Collins, Dr. Michael Behe, Dr. Steve Meyers, Dr. T. Ryan Gregory, and Dr. Gill Bejerano. Each one is a gentleman and a credentialed expert either in biology or genetics. I am grateful to all of them for their time and kindness.

I think we all know just how "credentialed" Stephen Meyer is. He has a Ph.D. in the history and philosophy of science. Most of us are familiar with the main areas of expertise of Michael Behe and none of them appear to be science.

WIRED on Junk DNA

Junk DNA is the DNA in your genome that has no function. Much of it accumulates mutations in a pattern that's consistent with random genetic drift implying strongly that the sequences in junk DNA are unimportant. In fact, the high frequency of sequence change (mutation plus fixation) is one of the most powerful bits of evidence for lack of function.

Catherine Shaffer is a science writer who describes herself like this on her website,

I am a writer specializing in biotechnology, genetics, genomics, and other molecular, biological sciences. I have experience with news and features. My strengths include a meticulous attention to detail, an absolutely fanatical devotion to scientific accuracy, and enthusiasm. Readers appreciate my clean, uncluttered prose; my crisp, novelistic style; and (sometimes) my zany sense of humor. I am a writer who always meets deadlines and is organized and dependable.

I studied biochemistry at the graduate level at the University of Michigan, and worked in the pharmaceutical industry for several years. I am especially knowledgeable about genomics, proteomics, biotechnology, drug discovery, and chromatographic separations.

She has written an article for WIRED on junk DNA [One Scientist's Junk Is a Creationist's Treasure]. Here's how the article begins,

Without your "junk DNA" you might be reading this article while hanging upside down by your tail.

That's one of the key findings of the opossum genome-sequencing project, and a surprising group is embracing the results: intelligent-design advocates. Since the early '70s, many scientists have believed that a large amount of many organisms' DNA is useless junk. But recently, genome researchers are finding that these "noncoding" genome regions are responsible for important biological functions.

The opossum data revealed that more than 95 percent of the evolutionary genetic changes in humans since the split with a common human-possum ancestor occurred in the "junk" regions of the genome. Creationists say it's also evidence that God created all life, because God does not create junk. Nothing in creation, they say, was left to chance.

"It is a confirmation of a natural empirical prediction or expectation of the theory of intelligent design, and it disconfirms the neo-Darwinian hypothesis," said Stephen Meyer, director of the Center for Science and Culture at the Discovery Institute in Seattle.

Advocates like Meyer are increasingly latching onto scientific evidence to support the theory of intelligent design, a modern arm of creationism that claims life is not the result of natural selection but of an intelligent creator. Most scientists believe that intelligent design is not science. But Meyer says the opossum data supports intelligent design's prediction that junk DNA sequences aren't random, but important genetic material. It's an argument Meyer makes in his yet-to-be-published manuscript, The DNA Enigma.

Hmmmm ... This is so confused that it's difficult to know where to begin. First, the connection between my junk DNA and whether I am an opossum completely escapes me. I don't know of any credible scientist who claims that it's changes in junk DNA that makes us so different from the common ancestor of opossums. (And none who claim that we are descended from opossums.)

Second, the implication that most junk DNA is turning out to have a function is completely false and the confusion about the difference between junk DNA and noncoding DNA is inexcusable from someone who claims to be an expert on genomics [see Noncoding DNA and Junk DNA, The Deflated Ego Problem].

Third, the idea that large amounts of evolution in junk DNA supports Intelligent Design Creationism is crazy. But, in fairness, I don't think Shaffer is making the connection between the sequence variation and Intelligent Design Creationism; instead, she's making the (factually incorrect) connection between the discovery of some functions in noncoding, nonjunk, DNA and Intelligent Design Creationism (IDC). I think Steve Meyer is suggesting that IDC predicts that junk DNA will have a function and that's why he's being quoted here in the article (see above).

Scientists have made several discoveries about what some call the "dark matter of the genome" in recent years, but they say the research holds up the theory of natural selection rather than creationism.

When sequences in noncoding DNA are conserved, this is taken as evidence of negative selection. In that sense, it supports the theory of natural selection. However, most of the sequence comparisons show that junk DNA is not conserved. This does not support the theory of natural selection. It supports Neutral Theory and the mechanism of evolution by random genetic drift.

The article then describes one recent study suggesting that some noncoding DNA is not junk (Lowe et al. 2007). It appears to be the justification for writing the article since it compares short stretches of sequences in the human and opossum genomes. This is not news so I won't bother commenting.

With scientists increasingly believing that so-called junk DNA regulates other genes, among other functions, creationists like Michael Behe, a biochemistry professor at Lehigh University in Pennsylvania and author of the controversial new book on intelligent design, The Edge of Evolution, are more than happy to point out their errors.

"From the very beginning Darwinism thought whatever it didn't understand must be simple, must be nonfunctional," Behe said. "It's only in retrospect that Darwinists try to fit that into their theory."

The concept of junk DNA is not based on ignorance in spite of what the IDiots say. It's based on good scientific evidence and deduction. Of course most IDiots wouldn't recognize scientific evidence even if it bit them on the ...

Is this just a way of getting in another quote from a prominent advocate of Intelligent Design Creationism? Why is Shaffer so interested in the IDiots? This seems to be more than just seeking out controversy since the proper way to do that would be to interview real scientists who can put the work into perspective and comment on it's significance (see below).

Part of the difficulty in studying junk DNA is that it's impossible to prove a negative, i.e., that any particular DNA does not have a function.

That's why T. Ryan Gregory, an assistant professor in biology at the University of Guelph, believes that nonfunctional should be the default assumption. "Function at the organism level is something that requires evidence," he said.

That's how a real scientist speaks [see A word about "junk DNA" and Comments on "Noncoding DNA and Junk DNA"].

This is getting to be a familiar pattern among science writers. Many of them seem to be incapable of sorting out the actual science from the rhetoric. In this case the problem is exacerbated by introducing IDiots as though their opinion had a bearing on the subject. Not only that, the poor science writing stands in sharp contrast to the claim that, "My strengths include a meticulous attention to detail, an absolutely fanatical devotion to scientific accuracy, and enthusiasm."

---

Lowe, C.B., Bejerano, G. and Haussler, D. (2007) Thousands of human mobile element fragments undergo strong purifying selection near developmental genes. Proc. Natl. Acad. Sci. (USA) 104:8005-8010. [PubMed]

University College London Restores Professor Colquhoun's Website

 
David Colquhoun has a website at University College London where he regularly debunks the claims of "medical" quacks. Recently a herbal medicine practitioner took offense at this debunking and threatened legal action against the university. The university responded by removing the website.

Today the website has been restored [DC's Improbable Science] and University College London has published a press release explaining why [Joint statement by Professor Colquhoun and UCL].

While it's encouraging that the university decided to restore the website, the fact that it buckled to pressure in the first place is disturbing. What's the point of academic freedom if you abandon it whenever you're threatened with a lawsuit?

UCL has a long and outstanding liberal tradition and is committed to encouraging free and frank academic debate. The evidence (or lack thereof) for the claims made for health supplements is a matter of great public interest, and UCL supports all contributions to that debate. The only restriction it places on the use of its facilities is that its staff should use their academic freedom responsibly within the law.

To this end, the Provost and Professor Colquhoun have taken advice from a senior defamation Queen’s Counsel, and we are pleased to announce that Professor Colquhoun’s website – with some modifications effected by him on counsel’s advice - will shortly be restored to UCL’s servers. UCL will not allow staff to use its website for the making of personal attacks on individuals, but continues strongly to support and uphold Professor Colquhoun’s expression of uncompromising opinions as to the claims made for the effectiveness of treatments by the health supplements industry or other similar bodies.

I'm curious about the "minor modifications" and I'm troubled by the prohibition against "the making of personal attacks on individuals." It seems to me that such a prohibition could be used in a way that inhibits academic freedom. For example, would it prohibit a university Professor from criticizing Tony Blair for the war in Iraq? Would it block any negative comments about Prince Charles (pictured at left)? Does it mean that the UCL website is completely devoid of any negative comments about Richard Dawkins?

Perhaps more importantly, does this mean that university Professors cannot point out on their websites the stupidity of administration officials such as UCL President and Provost Malcolm Grant?