Tangled Bank #87

 

The latest version of the Tangled Bank has been posted on Balancing Life [Tangled Bank #87].

I really like the article on "Standing on the shoulders of giants." It explains what Newton really meant when he wrote that to Hooke. Look it up.

THEME: Pyruvate Dehydrogenase

Pyruvate dehydrogenase is one of the most important enzymes in the cell. It catalyzes the reaction that converts pyruvate to acetyl-CoA with the release of CO₂.

Acetyl-CoA is the molecule that enters the citric acid cycle (Krebs Cycle) to be broken down to two additional molecules of CO₂.

April 16, 2007
Monday's Molecule #22 (pruvate). The series began with an unknown molecule that turned out to be pyruvate.

April 17, 2007
Pyruvate. A more complete description of the properties of pyruvate.

(April 18, 2007)
Pyruvate Dehydrogenase Reaction. This posting described the reaction catalyzed by pyruvate dehydrogenase.

April 18, 2007
The Structure of the Pyruvate Dehydrogenase Complex was described in some detail, including the techniques used to elucidate it.

April 18, 2007
Nobel Laureate: Aaron Klug. Aaron Klug worked out the technique used to describe the structure of the pyruvate dehydrogenase complex.

April 20, 2007
Some Bacteria Don't Need Pyruvate Dehydrogenase. There are other ways to catalyze the formation of acetyl-CoA.

April 20, 2007
Pyruvate Dehydrogenase Evolution. The evolution of the genes encoding the pyruvate dehydrogenase subunits is explained.

April 20, 2007
Human Genes for the Pyruvate Dehydrogenase Complex. Identifying the genes for the subunits of the complex.


April 23, 2007
Regulating Pyruvate Dehydrogenase. How pyruvate dehydrogenase is regulated, including the effect of the inhibitor dichloroacetate (DCA).

August 31, 2007
Dichloroacetate (DCA) Website Shut Down by the FDA

August 3, 2012
On the Evolution of New Enzymes: Completely Different Enzymes Can Catalyze Similar Reactions

Dennett on Adaptationism

I've been trying to avoid the discussion of Dawkins vs Gould until the results of the poll are in (see left-hand margin). Those of you who voted for Dawkins will need some major reorientation to bring you into the 21st century. My task is enormous. (I know who you are!)

But since I brought up Daniel Dennett in reference to the aquatic ape just-so story [Aquatic Ape Speculation], I couldn't resist quoting him from Darwin's Dangerous Idea. After outlining the main points in favor of the speculation Dennett says,

The details—and there are many, many more—are so ingenious, and the whole aquatic-ape theory is so shockingly antiestablishment, that I for one would love to see it vindicated. That does not make it true, of course.

The fact that its principal exponent these days is not only a woman, Elaine Morgan, but an amateur, a science writer without proper official credentials in spite of her substantial researches, makes the prospect of vindication all the more enticing. The establishment has responded quite ferociously to her challenges, mostly treating them as beneath notice, but occasionally subjecting them to withering rebuttal. ... I have often asked them just to tell me, please, exactly why Elaine Morgan must be wrong about the aquatic-ape theory. I haven't yet had a reply worth mentioning, aside from those who admit, with a twinkle in their eyes, that they have often wondered the same thing.

We all love an underdog but this is going too far. The fact that Dennett can't see what's wrong with the aquatic ape speculation suggests that his understanding of evolution and how it works is vastly overrated. He then goes on to prove it.

My point in bringing up the aquatic-ape theory is not to defend it against the establishment view, but to use it as an illustration of a deeper worry. Many biologists would like to say, "A pox on both your houses!" Morgan deftly exposes the hand-waving and wishful thinking that have gone into the establishment tale about how—and why—Homeo sapiens developed bipedalism, sweating, and hairlessness on the savanna, not the seashore. Their stories may not be literally as fishy as hers, but some of them are every bit as speculative, and (I venture to say) no better confirmed. What they have going for them, so far as I can see, is that they occupied the high ground in the textbooks before Hardy and Morgan tried to dislodge them. Both sides are indulging in adaptationist Just So Stories and since some story or other must be true, we must not conclude that we have found the story just because we have come up with a story that seems to fit the facts. To the extent that adaptationists have been less than energetic in seeking further confirmation (or the dreaded disconfirmation) of their stories, this is certainly an excess that deserves criticism. [my emphasis in red—LAM]

This is classic adaptationist thinking. It assumes, without evidence, that there must be an adaptationist explanation for every feature. Hairlessness, for example, must be explained by some sort of just-so story involving running on the savanna or wading by the seashore. All the stories seem silly—including the aquatic ape speculation—but since one of the stories must be true we shouldn't reject it just because it makes no sense. There's no room for a non-adaptationist explanation in such a worldview.

Let's see how a pluralist might approach this problem.

For many reasons, ranging from the probable neutrality of much genetic variation to the nonadaptive nature of many evolutionary trends, this strict construction [adaptationism] is breaking down, and themes of unity are receiving renewed attention. ... One old and promising theme emphasizes the correlated effects of changes n the timing of events in embryonic development. A small change in timing, perhaps the result of a minor genetic modification, may have profound effects on a suite of adult characters if the change occurs early in embryology and its effects accumulate thereafter.

The theory of human neoteny, often discussed in my essays (see my disquisition on Mickey Mouse in The Panda's Thumb), is an expression of this theme. It holds that a slowdown in maturation and rates of development has led to the expression in adult humans of many features generally found in embryos or juvenile stages of other primates. Not all these features need be viewed as direct adaptations built by natural selection. Many, like the "embryonic" distribution of body hair on heads, armpits, and pubic regions, or the preservation of an embryonic membrane, the hymen, through puberty, may be nonadaptive consequences of a basic neoteny that is adaptive for other reasons—the value of slow maturation in a learning animal, for example.

                        Stephen Jay Gould in How the Zebra Gets Its Stripes

If you are a Dawkins/Dennett adaptationist then your explanations are confined to the sorts of adaptationist just-so stories promoted by the likes of Elaine Morgan. If you are a pluralist like Gould, you have more choices. Some of the pluralist nonadaptationist explanations might be right. In this case I think Gould is more likely to be right about the evolution of hairlessness. Unfortunately, Dennet and his ilk can't imagine such explanations because it doesn't fit with their idea of how evolution works.

Cleopatra VII (69 BC - 30 BC)

 
According to some sources, Cleopatra committed suicide on this day in 30 BC [On this day: August 30]. Other sources say it was August 12th and still others claim that it was on the last day in August.

The situation was serious. The armies of Mark Antony and Cleopatra has just deserted to Octavian and Antony had committed suicide. Cleopatra was a prisoner in Alexandria. She had no hope of escaping Octavian.

Legend has it that she died after being bitten by an asp but it wasn't the modern asp, Vipera aspis, since that snake is only found in Europe. It's likely that the Romans used the word "asp" to describe all poisonous snakes. If it's true that Cleopatra used a snake to commit suicide then it was most likely the Egyptian cobra Naja haje that did the deed [Cleopatra’s Asp].

Corba venom contains a number of toxins and enzymes. For the biochemist, it's most famous for the presence of phospholipase A₂, an enzyme that cleaves glycerophospholipids, the main components of cell membranes. This leads to disruption and death of cells, especially red blood cells and lymphocytes in the blood stream. A picture of cobra venom phospholipase A₂ bound to a lipid molecule (left) can be found in most biochemistry textbooks.

Hyaluronidase is an enzyme found in many snake venoms. It degrades hyaluronic acid, a complex carbohydrate of the sort found in many glycoproteins. Hyaluronic acid is an important component of cartilage where it forms a central strand for attachment of proteoglycan molecules. The breakdown of cartilage lining the blood vessels leads to massive hemorhaging. The combination of phospholipase A₂ and hyaluronidase could eventually lead to death but it probably wasn't the immediate cause of death for Cleopatra. As it turns out, there are other things in the cobra venom that are even more lethal.

These other components of cobra venom include various cobra venom factors that interfere with the complement pathway leading to an extreme over-stimulation similar to that seen in septic shock. The venom also includes a number of neurotoxins that gain access to the central nervous system when blood vessels break down. The combination of all these proteins can cause death within minutes of receiving a cobra bite. However, many people survive cobra bites suggesting that the Cleopatra story may not be true.

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[The painting is The Death of Cleopatra by Reginald Arthur (d. 1896), 1892 [The Death of Cleopatra.]]

Genetic Discrimination in Denying Health Benefits

 
Hsien-Hsien Lei of Eye on DNA links to an article in the Los Angeles Times [U.S. military practices genetic discrimination in denying benefits].

The issue concerns a Marine who was discharged without medical benefits because he was found to have a genetic disease—in this case it was Von Hippel-Lindau syndrome.

Apparently the US military doesn't take responsibility for soldiers who develop medical problems as a result of a genetic pre-disposition.

The regulation appears to have stemmed from an effort to protect the armed services from becoming a magnet for people who knew they would come down with costly genetic illnesses, according to Dr. Mark Nunes, who headed the Air Force Genetics Center's DNA diagnostic laboratory at Keesler Air Force Base in Mississippi.

As you might expect, the lawyers got involved and some of these men and women have won some compensation from the US government. But some lost their case and they face bankruptcy.

Only in America.

There's a simple solution to all these disputes about health coverage and your genes. It's called universal health care. Try it. You'll like it. (Unless you're a lawyer.)

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[Photo Credit: The photograph shows Dr. Mark Nunes (center) with Jay Platt, a former US Marine Corps drill instructor (left) and Susannah Baruch, senior policy analyst at the Genetics and Public Policy Center (right). The panelists are discussing Genes in Uniform: Don't Test, Don't Tell.]

Ohmygod! These photographs are faked!

Jonathan Wells, the author of one of the stupidest books on Intelligent Design Creationism (Icons of Evolution) has just posted a message on the Discovery Institute website [Exhuming the Peppered Mummy]. Wells says,

The peppered myth died several years ago when scientists discovered that photos of peppered moths on tree trunks - used in most biology textbooks to convince students of Darwinian evolution - had been faked.

In his book he reveals the extraordinary deception that has confused thousands of biology students. The photographs of peppered moths on tree trunks were staged. In some cases dead moths were pinned to the tree trunks and in other cases the moths are alive but they were carefully positioned by scientists.

Can you believe it? Look at the pictures above. I bet you thought that some photographer had set up a camera and waited for years to photograph two moths—one black and one white—to land next to each other in the camera's field. Silly you. You've been fooled. Those moths have been deliberately staged. So much for the Theory of Evolution.

Now, as it turns out there's more to the peppered moth story than this "deception." The real issue is whether the moths spend significant amounts of time on tree trunks. But that's not the point that Wells choose to make in his posting. Instead, he emphasizes the "faked" photographs as though that's the most significant aspect of the peppered moth story. Maybe it is. Maybe Wells and his friends were totally taken in by the photographs in the biology textbooks. I wouldn't be surprised. After all, that's we we call them IDiots.

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[Photo Credit: The photographs are from bill.srnr.arizona. The original source is unknown.]

Aquatic Ape Speculation

 
Read all about the speculation concerning our aquatic ancestry in an impressively researched article by laelaps [Scuttling the Aquatic Ape Hypothesis]. This is a typical adaptationist just-so story. Even people who should know better, like Daniel Dennett, have fallen for it.

Animals and Research

 
There are lots of people who object to the use of animals in medical research. They're usually referring to warm fuzzy animals and not to fruit flies and nematodes, or even fish.

Some of these people write for prominent newspapers like The Guardian in the UK [Ivory tower mentality blamed for 50% rise in animal tests].

Nick Anthis at The Scientific Activist has exposed the myth expressed in the Guardian article [Animal Rights Activists Hijack the Brains of Three Respectable Scientists!]. So has PZ Myers over on Pharyngula [You can't replace animals with petri dishes and computers]. Now Abel Pharmboy at Terra Sigillata has jumped into the fray with a plug for the Foundation for Biomedical Research [Great Animal Research Poster]. I'm copying the poster from their website.

Normally I don't like the kind of rhetoric that's on the poster. I doubt very much that the statement is correct. However, it's an attention grabber and somebody needs to counter the animal activists with a different (gasp!) frame. My life and the lives of everyone in my building are much less comfortable because we have to worry about security on a daily basis. It's not Islamic terrorists that we fear, it's animal rights terrorists. There have been several incidents where property has been destroyed and one bomb has been exploded.

Nobel Laureate: Paul Karrer

 

The Nobel Prize in Chemistry 1937.

"for his investigations on carotenoids, flavins and vitamins A and B2"





In 1937, Paul Karrer (1889-1971) shared the Nobel Prize in Chemistry with Walter Norman Haworth. Karrer won the award fro his pioneering work on the structure of carotene [Monday's Molecule #40] and vitamin A (retinol).

Professor W. Palmær, Chairman of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences, delivered the presentation speech on on December 10, 1937. Only the part addressed to Karrer is quoted below.

The Royal Academy of Sciences has decided also to award to Professor Paul Karrer in Zurich one half of the Nobel Prize in Chemistry this year in recognition of his researches concerning carotenoids and flavins, and the vitamins A and B2.

Thus these two scientists have both worked on another common field of research, the vitamins. As I have already endeavoured to elucidate at some length the importance of making clear the chemical structure of the vitamins, taking vitamin C as an example, I may be somewhat brief regarding the brilliant discoveries made by Professor Karrer.

The carotenoids form a group of yellowish-red colouring matters, widely dispersed within the vegetable kingdom, which have obtained their name from the carrot in which they were first observed. The French name of the carrot is known to be carotte, while Karotte is one of the German names thereof. Carotenoids occur in various other red or yellow parts of vegetables, such as tomatoes, hips, turnips. The examination of these numerous substances was commenced by Karrer ten years ago, and he has succeeded in making clear their chemical structure. The mother substance is in itself a hydrocarbon of very complicated composition, i.e. a chemical compound consisting only of carbon and hydrogen. Its molecule consists of no less than 40 atoms of carbon and 56 of hydrogen. Other carotenoids also contain oxygen, as is the case, for instance, with astacene, which gives the red colour to boiled crayfish and to the "cardinal of the sea", the lobster. The colour of saffron and of paprica is likewise due to carotenoids.

The splendid research concerning the carotenoids, made by Karrer, received its coronation, when it led to the isolation, the production in a pure form and the determination of the chemical structure of vitamin A. This vitamin, which had been known to exist from its biological effects already since 1906 and the synthesis of which in a pure form had been tried in vain in many laboratories all over the world, was successfully isolated by Karrer in 1931 from cod-liver oil, and it was the first of the vitamins of which the chemical structure was clarified. It forms a growth factor, i.e. a substance necessary for the growth of the body. In 1929 von Euler found the same property existing in the carotine itself, and it has been proved since then that this is dependent on the circumstance that carotine, that is the dyestuff of the carrot, is a substance from which the animal body can in itself produce the vitamin A, which has a somewhat less complicated structure. It is also a medicine, as it prevents the serious disease of the eye called "dry eye" or xerophthalmia. Hence vitamin A has received the name of axerophthol.

Some words now regarding Karrer's researches on flavins and on vitamin B2, which were commenced in 1933. Flavins are natural substances of a light yellow colour which often glisten, or fluoresce to the green. One of them is vitamin B2, also called factoflavin, which was discovered by Warburg and Christian in the yellow respiratory ferment, and which has also been disentangled in regard to its chemical structure by Karrer. It constitutes likewise a growth factor, and Karrer's method of producing this compound has led to a technical production of the substance, which is of great biological importance. It contains, besides carbon, hydrogen and oxygen and also nitrogen.

Karrer has thus succeeded in elucidating completely the nature of two of the vitamins, hitherto considered as so mysterious, and one of them is now produced artificially. A characteristic of this scientist is his open eye to the great and important problems as well as to their kernels, and the independent way in which he attacks the problems and pursues his new departures with the aid of his own methods.

There remain many questions to be studied regarding the way in which the vitamins cooperate in such processes of life as cannot be started without their presence.

A vitamin does certainly not produce the effect alone, however. The lactoflavin, for instance, combines, with the aid of phosphoric acid, with an albuminous substance, and only in this way the yellow respiratory ferment is formed. Its molecule contains about 200 times as many atoms as that of the vitamin itself. The yellow ferment is reckoned as belonging to the catalyzers, i.e. substances capable to accelerate a chemical reaction without undergoing any change themselves. Their action may be compared to that of a lubricating oil on a rusty machine. In this case the oxidation of certain substances present in the body is taking place, thus a kind of combustion, although of course much slower than for instance the burning of wood in a stove. We may perhaps compare the very effect of the vitamin to that of a key. A heavy door may thus resist the strongest blows and knocks, but can easily be opened by the aid of a small key - always provided that the right key is found.

The discoveries, which have now engaged our attention, touch upon the domain of Physiology as well as that of Chemistry, a circumstance which has found its expression in that they have been awarded Nobel Prizes in Medicine as well as in Chemistry. Often it is just within the borderland between two sciences, where efforts have been frequently made to establish demarcatory lines (although mostly in vain), that the important discoveries are to be found. In such cases it is evidently of small avail, generally speaking, to try to decide, even with the aid of the greatest acuteness, to which field of science such discovery should be properly attributed. The principal thing is, however, that the discoveries are recognized, if such be their value, and the classification of the prize awarded is a question of minor importance. In the present case it may be said, nevertheless, that the discoveries which have been awarded a prize in Chemistry are on the whole more chemically accentuated in their character than those which have received the prize in Medicine. In all the cases, however, such discoveries may be said to have "conferred the greatest benefit on mankind" in accordance with the intentions expressed in the will of Alfred Nobel....

Professor Karrer. The Royal Swedish Academy of Sciences has decided to confer upon you and Professor Haworth this year's Nobel Prize in Chemistry. In this way the Academy wishes to express to you her recognition for your brilliant investigations on carotenoids and flavins, as well as on vitamins A and B2. As a result of your work, the structure of a vitamin has for the first time been clarified. The structure of a second vitamin has also been cleared up, thus enabling its technical preparation.

I convey to you the congratulations of the Academy and request you to receive the prize from the hands of his Majesty the King.

Vitamin A (retinol)

 
There are four lipid vitamins: vitamin A, vitamin D, vitamin E, and vitamin K. Each of them contain rings and long aliphatic (—CH₂—) side chains. The lipid vitamins are highly hydrophobic, although each possesses at least one polar group. Ingested lipid vitamins are absorbed in the intestine by a process similar to the absorption of other lipid nutrients. After digestion of any proteins that may bind them, they are carried to the cellular interface of the intestine as micelles formed with bile salts. The study of these hydrophobic molecules has presented several technical difficulties, so research on their mechanisms has progressed more slowly than that on their water-soluble counterparts. Lipid vitamins differ widely in their functions.

Vitamin A, or retinol, is a 20-carbon lipid molecule obtained in the diet either directly or indirectly from β-carotene [Monday's Molecule #40]. Carrots and other yellow vegetables are rich in β-carotene, a 40-carbon plant lipid whose enzymatic oxidative cleavage yields vitamin A.


Vitamin A exists in three forms that differ in the oxidation state of the terminal functional group: the stable alcohol retinol, the aldehyde retinal, and retinoic acid. All three compounds have important biological functions. Retinoic acid is a signal compound that binds to receptor proteins inside cells; the ligand–receptor complexes then bind to chromosomes and can regulate gene expression during cell differentiation. The aldehyde retinal is a light sensitive compound with an important role in vision. Retinal is the prosthetic group of the protein rhodopsin; absorption of a photon of light by retinal triggers a neural impulse.

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From Horton et al. Principles of Biochemistry, 4th ed. © 2007, Laurence A. Moran and Pearson/Prentice Hall

[Photo Credit: The picture of the carrots is from The Food Network.]

Cows into Whales

UPDATE:The Bad Idea Blog takes issue with Berlinksi's claim that he calculated at least 50,000 changes were required to change a cow into a whale (he stopped counting) [Berlinksi, whales, and why Intelligent Design can’t get no respect]. If Berlinski took ten seconds to write down each of these changes it would take him 5 days, assuming he wrote for 24 hours each day. How's that for a mathematical calculation!

Here's one of the chief IDiots, David Berlinski, expounding on how difficult it must be to change cows into whales. Berlinksi has a Ph.D. in philosophy and has written several books on mathematics. He is a Senior Fellow at the Center for Science & Culture (CSC).

Here's a free clue for the IDiots: cows didn't evolve into whales. Instead whales are the modern descendants of a primitive carnivore that lived over 50 million years ago. See the video at the PBS site for basic information on the evolution of whales—the sort of information that you'd expect anyone to know if they were going to criticize the scientific explanation for the evolution of whales [Whale Evolution]. Berlinski knows some of this history but he's missing the big picture. Berlinksi and most of his fellow fellows at the CSC don't know much about evolution and how it works. It's all a big mystery to them; but then, that's why they are IDiots.



[Hat Tip: The video was posted on the Discovery Institute website by Robert Crowther, who presumably believes that the evolution of cows from whales (sic) is important.]

Where Are the Musicians and the Poets?

 

Over on Tangled Up in Blue there's a posting about Country Joe McDonald and his new anti-war song [1,2,3 What Are We Fighting For?]. Country Joe was at Woodstock 39 years ago. He's an old geezer. So is Neil Young who is just about the only other singer to speak sing out.

The anti-war movement of the 60's was supported by all kinds of artists and some of their songs can still stir up powerful feelings today. Where are today's singers? Why are there no protest songs about the war in Iraq? Why are there no demonstrations in the streets and on the campuses? Where are the young firebrands and their passionate speeches? What's wrong with today's younger generation?

New Seven Wonders of the World

 

One of my colleagues just got back from Rio de Janeiro where he visited one of the New Seven Wonders of the World. It got me thinking about the others that were recently voted in. It's not a bad list but I think the Eiffel Tower and Stonehenge should have been on the list instead of Christ the Redeemer and the Colosseum.

And what about this? When it's finished it will be one of the most impressive structures that humans have ever made—especially when you consider the location. A somewhat greater challenge than Macchu Picchu, don't you think?

The international space station may turn out to be not very useful but then the Great Wall of China, the Eiffel Tower, and Christ the Redeemer weren't very useful either.

Blog Spam: What's the Point?

 


There must be some advantage to spammers who litter the comments section with spurious messages. They usually have a name that links to something. For example, today there was a poster named "Viagra" who put several comments on my blog. If you click on "Viagra" it takes you to a webpage (search2.site.io/index.html) with a list of Viagra related items.

Can someone explain the point of all this? What advantage to spammers get out of polluting blogs?

I left an example of this spam in the comments of the thread Science Policy Forum: Framing Science.

Monday's Molecule #40

 

Name this molecule. There's a short common name but it's not sufficient. You have to supply the complete IUPAC name in order to win the prize. There's a direct connection between this Monday's Molecule and Wednesday's Nobel Laureate(s).

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are two ineligible candidates for this Wednesday's reward. Both of them are waiting to collect their prize when September rolls around. The prize is a free lunch at the Faculty Club.

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 the Nobel Laureate. Correct responses will be posted tomorrow along with the time that the message was received on my server. This way I may select multiple winners if several people get it right.


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