Nobel Laureate: Richard Kuhn

 

The Nobel Prize in Chemistry 1938.

"for his work on carotenoids and vitamins"



In 1938, Richard Kuhn (1900-1967) won the Nobel Prize in Chemistry for his work on the structure of several different vitamins, including the carotenoids [Vitamin A (retinol)] and the B₆ family [Pyridoxal Phosphate and the Vitamin B6 Family].

The award overlaps considerably with the prize for the previous year [Nobel Laureate: Paul Karrer], which suggests that the prize committee may have been pressured to recognize Kuhn after slighting him in favor of Karrer. The two men were friendly competitors for many years and much of their work is similar.

Kuhn was not able to accept the prize in 1938 because at the time he was working at Heidelberg University and the political situation did not allow him to travel to Sweden. There was no formal presentation speech but the following account of his work is posted on the Nobel Prize website.

When Richard Kuhn in 1926 took over the Chair for General and Analytical Chemistry at the Federal Institute of Technology Zurich he set in motion a comprehensive series of investigations into the so-called conjugated double bonds which make up the essential arrangement of the atoms of the polyenes.

The group of the diphenylpolyenes had at this time aroused especial interest because the presence in the carotenoid Crocetin of a chain of double bonds had been successfully demonstrated. Kuhn's sixth report on conjugated double bonds already contains structure determinations of polyene dyes from vegetable materials. With his syntheses of over 300 new materials belonging to this group Kuhn has by no means sought merely to liberate new substances. In this work he was much more concerned to clarify the general relationships between the chemical structure of these unsaturated substances and their optical, dielectric, and magnetic properties. The results which he has obtained in this respect form the starting-point for new lines of development in organic chemistry.

Kuhn's work on polyenes led him straight into the chemistry of the carotenoids. In 1930 Karrer clarified the constitution of carotene. The elementary composition of carotene, C40H56, had previously been ascertained by Willstätter. In 1931, R. Kuhn (at that time already Professor at Heidelberg), Karrer in Zurich, and Rosenheim in London discovered simultaneously and independently of each other the fact that the carotene in carrots consists of two separate components: one of these, b-carotene, rotates the plane of polarized light to the right, while the other, a-carotene is optically inactive. In 1933 Kuhn discovered a third carotene isomer which was called g-carotene.

The great physiological and biological significance of carotene lies in the fact that it is hydrolysed in the liver of certain animals so that from one molecule of b-carotene or from two molecules of a-carotene two molecules of Vitamin A, Axerophtol, are formed. This substance is necessary for growth in higher animals and especially for maintaining the normal condition of the mucous membranes.

With several collaborators Kuhn carried out a large number of investigations into the occurrence of carotenoids in the animal and vegetable kingdoms. Among his most important results, his discoveries of the following carotenoids and their structure determination should be mentioned:

Physalien from berries of species of Physalis, Helenien, Flavoxanthin, isolated from species of Ranunculus, Violaxanthin from Viola tricolor, unstable Crocetin from saffron, Taraxanthin, Cryptoxanthin from Zea Mays Rubixanthin.

Kuhn also had an important share in establishing the composition of Rodoxanthin and Astaxanthin as well as in discovering the connection of this latter carotenoid with the chromoproteids of the Crustaceans.

Of great interest also are the many contributions Kuhn and his school have made to the perfection of the chromatographic method which is one of the most important aids to the isolation and synthesis of the different representatives of the carotenoid group.

Kuhn's second great field of activity concerns the clarification of the Vitamin B complex. Kuhn has the great merit, together with von Szent-Györgyi and Wagner-Jauregg, of having been the first to isolate the extraordinarily important substance Vitamin B2 (Lactoflavin or Riboflavin). He has made very important contributions to the elucidation of the chemistry of this substance.

From 5,300 litres skim milk Kuhn and his collaborators succeeded in liberating about 1g of a pure yellow substance, Lactoflavin, whose composition was found to be C17H20O6N4. A breakdown product of the Lactoflavin, which was called Lumiflavin, could be identified with a substance previously prepared from the yellow ferment occurring in yeast. By drawing up a structural formula for Lumiflavin later confirmed in various ways, Kuhn furnished a key to the chemical clarification of Lactoflavin. He himself demonstrated the Lumiflavin formula, which had been found by analytical methods, by a synthesis - namely through the condensation of an odiaminobenzene derivative with Alloxan.

At the beginning of 1939 Kuhn made his second significant discovery in relation to the Vitamin B complex. Together with Wendt, Andersag, and Westphal, he succeeded in isolating that component of the Vitamin B complex which is designated Vitamin B6, the antidermatitis vitamin, and in a remarkably short time he was able to establish its chemical composition and structure (Ber., 71 (1938) 1534; 72 (1939) 309). The substance which Kuhn thus elucidated, which he called Adermin, proved to be 2-methyl-3-hydroxy-4,5 -dihydroxymethylpyridine.

The Role of Ultraconserved Non-Coding Elements in Mammalian Genomes

Ultraconserved elements are stretches of DNA that are 100% identical in mouse, rat, and human genomes. In order to qualify as an ultraconserved element, the length has to be greater than 200 bp. This eliminates most sequences that might be identical by chance.

The most interesting elements are those that fall outside of coding regions. These ultraconservative elements are most likely to be involved in regulating gene expression or some other essential feature of non-coding DNA. The fact that they are identical in species who last shared a common ancestor 100 million years ago is powerful evidence of adaptation.

Ahitiv et al. (2007) set out to test this hypothesis by selecting four examples of ultraconservative elements for further analysis. They discovered that the elements function as tissue specific enhancers in a test designed to look at how they control expression of a maker gene in mouse embryos. The results are shown in Figure 1 (left) of their paper, which was just published in the open access journal PLoS Biology.

The figure shows the genomic location of the four ultraconserved elements; uc248 (222 bp), uc329 (307 bp), uc467 (731 bp), and uc482 (295 bp).

Of these, uc467 is the most remarkable because it is 731 bp in length and resides in the last intron of the DNA polymerase alpha 1 gene (POLA1) on the human X chromosome. The enhancer trap experiment shows that this segment of conserved DNA directs expression of the marker gene in embryonic brain cells (shown as the dark blue area in the embryo above the 467 site). This is usually taken as evidence of specific regulatory sequences that bind transcription factors.

Ahituv et al. then deleted the four ultraconserved sequences from the mouse genome using standard knockout technology. Mice that were homozygous for the knockouts showed no evidence of any defect compared to wild-type mice. In other words, the ultraconserved elements seemed to be completely dispensable—a result that is not consistent with their extreme conservation.

THEME:
Junk DNA
What are the possible explanations? It's possible that the authors missed a phenotype that can only be detected outside the laboratory. It's also possible that the sequences really aren't conserved because they perform an important function but for another reason. Here's how the authors explain their results,

Based on the compelling evidence that ultraconserved elements are conserved due to functional constraint, it has been proposed that their removal in vivo would lead to a significant phenotypic impact [7,8]. Accordingly, our results were unexpected. It is possible that our assays were not able to detect dramatic phenotypes that under a different setting, for instance, outside the controlled laboratory setting, would become evident. Moreover, possible phenotypes might become evident only on a longer timescale, such as longer generation time. It is also possible that subtler genetic manipulations of the ultraconserved elements might lead to an evident phenotype due to a gain-of-function-type mechanism. All four elements examined in this study demonstrated in vivo enhancer activity when tested in a transgenic mouse assay (Figure 1) [6], which would suggest regulatory element redundancy as another possible explanation for the lack of a significant impact following the removal of these specific elements. Just as gene redundancy has been shown to be responsible for the lack of phenotypes associated with many seemingly vital gene knockouts, regulatory sequence redundancy [22] can similarly provide a possible explanation for the lack of a marked phenotype in this study. While our studies have not defined a specific need for the extreme sequence constraints of noncoding ultraconserved elements, they have ruled out the hypothesis that these constraints reflect crucial functions required for viability.

[UPDATE: Ryan Gregory at Genomicron discusses the same paper with a more thorough coverage of the background information and the relevance to junk DNA (Ultraconserved non-coding regions must be functional... right?). R. Ford Denison at This Week in Evolution has some thoughts on the paper (If it's junk, can we get rid of it?")]

---

Ahituv, N,, Zhu, Y., Visel, A., Holt, A., Afzal, V., Pennacchio, L.A., and Rubin, E.M. (2007) Deletion of Ultraconserved Elements Yields Viable Mice. PLoS Biol 5(9): e234 doi:10.1371/journal.pbio.0050234.

Denyse O'Leary's New Book

 
We've been waiting with baited bated^* breath but the big day has finally arrived. Denyse O'Leary announces that we can now buy her new book The Spiritual Brain [ Just released - a neuroscientist's case for the existence of ... the soul!].

The first author is Mario Beauregard, a scientist at the Université de Montréal (Canada). According to Denyse, Beauregard is one of the "One Hundred Pioneers of the Twenty-First Century" selected by World Media Net. What the heck is "World Media Net"? Canadian Cynic also wants to know The hilarity just never ends].

Beauregard (and O'Leary) have solved the mind-body problem. It turns out that there's more going on inside the brain than just the firing of neurons. Apparently, your brain is capable of contacting a different reality during intense religious experiences.

Beauregard uses the most sophisticated technology to peer inside the brains of Carmelite nuns during a profound spiritual state. His results and a variety of other lines of evidence lead him to the surprising conclusion that spiritual experiences are not a figment of the mind or a delusion produced by a dysfunctional brain.

I'm not going the buy the book. If someone wants to read it I'd be happy to see a review from a real scientist.

^* I actually knew that "baited" was wrong but I typed it anyway. For an explanation of what "bated" means see World Wide Words.

Pyridoxal Phosphate and the Vitamin B6 Family

 
Vitamin B₆ is actually a family of related molecules consisting of a six-membered ring with a single nitrogen atom. The various members differ only in the group attached to position 4 of the ring. The ring is called a pyridine ring and the various derivatives are named after the pyridine ring (see below and Monday's Molecule #41). The most common vitamin B₆ molecules are pyridoxal or pyridoxamine. They are widely available from plant and animal sources and it's unusual for human diets to be deficient in vitamin B₆.


By definition, a vitamin is a compound that humans can no longer synthesize. Some vitamins act directly as cofactors or coenzymes but many them serve as precursors for the synthesis of the final product. This is true of the B₆ vitamins. They are rapidly converted to pyridoxal 5′-phosphate (PLP). Humans have retained the ability to catalyze this conversion.

PLP is a cofactor that's bound to many enzymes in the cell where it participates in a number of different reactions. The most important reactions are those involving transfer of amino groups from one molecule to another. There is a large class of transaminases that require PLP.

The transaminases are required for amino acid synthesis and for synthesis of many neurotransmitters such as serotonin and epinephrine. An example of a transamination reaction is shown below. Note that PLP is covalently bound to the enzyme through a lysine side chain. An amino acid donates its amino group to PLP in an exchange reaction giving rise to pyridoxamine phpsphate (PMP), which remains firmly bound to the enzyme. The entire sequence of reactions can then be reversed using any α-keto acid as a substrate to generate a new amino acid.

Many of the transaminases are evolutionarily related. Similarly, the transaminases are often related to enzymes that catalyze different PLP-reactions such as isomerizations and decarboxylations. The evidence indicates that a primitive PLP-enzyme gave rise to a number of different enzymes that make use of the basic mechanism shown below. The enzymes differ in a few amino acids that bind the substrates.

The Evolution Poll of Sandwalk Readers

 
The poles are closed and the results are in. Richard Dawkins is the clear winner (boo!).

The good news is that 87% (499/573) Sandwalk readers have legitimate scientific views of evolution (Dawkins + Gould + Futuyma). Only a small number of readers are creationists or proponents of theistic evolution.

The bad news is that most readers are split between three different views of evolution. Some people have asked me to explain these three views so here's a brief summary of how I distinguish between Dawkins, Gould, and Futuyma.

Richard Dawkins holds the Charles Simonyi Chair for the Public Understanding of Science at Oxford University (UK). In his first book, The Selfish Gene (1976), he promoted the idea that evolution can be viewed as a competition between genes. This concept was amplified in The Extended Phenotype (1982) where he also answered the main criticism of the selfish gene concept. Dawkins' most popular book was The Blind Watchmaker, first published in 1986. In that book he made the case for design by natural selection and attempted to dismiss, or minimize, all other mechanisms of evolution. The emphasis on the power of natural selection was expanded in Climbing Mt. Improbable (1996).

Dawkins is the leading exponent of adaptationism—or Ultra-Darwinism—the idea that everything interesting in evolution can be explained by adaptation. This is especially true of traits that give rise to visible phenotypes. Dawkins is not very interested in macroevolution and he dismisses punctuated equilibria and species sorting. He believes, along with most adaptationists, that macroevolution is just an extension of natural selection acting on populations. (See RichardDawkins,net for a complete list of books and articles.)

Stephen Jay Gould was Alexander Agassiz Professor of Zoology at Harvard University from 1967 until his death in 2002.

He published Ontogeny and Phylogeny in 1977 where he made the case for a relationship between development and evolution. In The Mismeasure of Man (1981) he criticized biological determinism. Wonderful Life (1989) described the Burgess Shale fossils and explained Gould's ideas about the role of chance and contingency in evolution. In 2002, Gould published The Structure of Evolutionary Theory where he attempts to explain macroevolution, punctuated equilibria, and species sorting. These are part of Gould's hierarchical approach to evolutionary theory. Gould identifies himself as a pluralist—one who recognizes many different mechanisms of evolution that can give rise to important and interesting features. He tends to place much more emphasis on chance and accident in evolution than Dawkins.

Gould, along with Niles Eldredge, is famous for the concept of punctuated equilibrium. This is the idea that much of the change in the characteristics of species is concentrated in brief speciation (by cladogenesis) events.

Gould wrote a regular column for Natural History magazine and many of his articles have been collected in a series of anthologies: Ever Since Darwin, The Panda's Thumb, Hen's Teeth and Horse's Toes, The Flamingo's Smile, Bully for Brontosaurus, Eight Little Piggies, Dinosaur in a Haystack, Leonardo's Mountain of Clams and the Diet of Worms, The Lying Stones of Marrakech, and I Have Landed. Some of his essays and some of his scientific articles are widely cited. (For a complete list see SJG Archive.)


Douglas J. Futuyma is a Professor of Ecology & Evolution at the State University of New York at Stoney Brook. He is best known for his textbooks on evolution; Evolutionary Biology (1998) and Evolution (2005). His major research interests are evolutionary theory [see Hypotheses, Facts, and the Nature of Science] and the interactions of plants and insects [see Insect Pests: Resistance and Management].

Futuyma's view of evolution is different from that of Richard Dawkins because Futuyma is interested in random genetic drift and speciation. Futyuma is much more aware of population genetics than Dawkins or Gould and he (Futuyma) frequently refers to it in his books and papers. Unlike Gould, Futuyma is skeptical of punctuated equilibria and particularly species selection/sorting, although, ironically, he is credited with proposing the best explanation of the connection between cladogenesis and evolution.

You can check out some of Futuyma's ideas in this interview. In response to the question, "Is natural selection the only mechanism of evolution?", Futuyma replies,

No, certainly not. There cannot be evolution without genetic variation in the first place. So there must be mutation and often recombination to generate the different genotypes or the different versions of the genes, known as alleles, which then may or may not make a difference in the ability of an organism to survive and reproduce. You can’t have any evolutionary change whatever without mutation, and perhaps recombination, giving rise to genetic variation. But once you have genetic variation, there are basically two major possibilities:

First, there is simply no difference between the different genotypes or different genes in their impact on survival or reproduction, and in that case, you can have random changes of one versus the other type in a population or a species until eventually one replaces the other. That is an evolutionary change. It happens entirely by chance, by random fluctuations. That is what we call the process of genetic drift.

Genetic drift is very different from possibility number two, natural selection, which is a much more consistent, predictable, dependable change in the proportion of one gene vs. another, one genotype vs. another. Why? Simply because there is some consistent superiority, shall we way, of one genotype vs. another in some feature that affects its survival or some feature affecting its reproductive capabilities.

Neither Gould or Dawkins would respond in this way. Dawkins would admit to random genetic drift but downplay its importance. Gould would focus on higher mechanisms of evolution like species sorting.

Futuyma also thinks about the role of mutation in a different way than either Dawkins or Gould, especially Dawkins. While Dawkins is very much opposed to crediting mutations per se with any substantial influence on evolution, Futuyma is more sympathetic to a limited mutationism point of view. For example, when asked what would happen if the tape of life were re-played he says.

Of course, it wouldn’t be the same, because first of all, random processes are involved in the evolutionary process. For example, the origin of new mutations: a lot of evolution is dependent on particular mutational changes in genes that were very, very rare or unlikely, but that just happened at the right time, in the right species, in the right environment, but it need not happen that way. So, there’s this unpredictability.

This is very unlike Dawkins who is more inclined to think of evolution as design and strongly resists any attempt to sneak randomness into the equation. For the most part, Dawkins believes that all possible mutations will be available for selection so mutations can never determine the direction of evolution. Gould prefers to focus on developmental constraints as possible limits to the effectiveness of natural selection.

Monday's Molecule #41

 
Today's molecule is actually three related molecules. You have to name all three by giving the common names and the complete IUPAC names. There's a direct connection between these molecules and Wednesday's Nobel Laureate(s). (Hint: The Nobel Prize winner was not allowed to receive the prize.)

The reward goes to the person who correctly identifies the molecules 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 this week or next week. 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 molecules and the Nobel Laureate(s). 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.

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

UPDATE: The three molecules are:

1. pyridoxine: 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridine


2. pyridoxal: 3-hydroxy-5-(hydroxymethyl)-2-methyl-pyridine-4-carbaldehyde


3. pyridoxamine:
   4-(aminomethyl)-5-(hydroxymethyl)-2-methyl-pyridin-3-ol

Nomenclature for Vitamins B-6 and Related Compounds

Modern women are excellent gatherers

 
Here's an article form this week's New Scientist [Modern women are excellent gatherers]. I'd be curious to know what our adaptationist friends think about it. Is this a good example of how to do research?

Men hunted, women gathered. That is how the division of labour between the sexes is supposed to have been in the distant past. According to a new study, an echo of these abilities can still be found today.

Max Krasnow and colleagues at the University of California, Santa Barbara, have discovered that modern women are better than men at remembering the location of food such as fruit and veg in a market.

The researchers led 86 adults to certain stalls in Santa Barbara's large Saturday farmer's market, then back to a location in the centre of the market from where the stalls could not be seen. They were then asked to point to each stall's location. This requires dead reckoning - a skill that men may once have used to return from hunting, and one that men today still usually perform better than women in experiments. Despite this, the ...

The news report refers to a paper that will soon be published in Proc. Roy. Soc. B [New et al. 2007]. Here's the abstract.

We present evidence for an evolved sexually dimorphic adaptation that activates spatial memory and navigation skills in response to fruits, vegetables and other traditionally gatherable sessile food resources. In spite of extensive evidence for a male advantage on a wide variety of navigational tasks, we demonstrate that a simple but ecologically important shift in content can reverse this sex difference. This effect is predicted by and consistent with the theory that a sexual division in ancestral foraging labour selected for gathering-specific spatial mechanisms, some of which are sexually differentiated. The hypothesis that gathering-specific spatial adaptations exist in the human mind is further supported by our finding that spatial memory is preferentially engaged for resources with higher nutritional quality (e.g. caloric density). This result strongly suggests that the underlying mechanisms evolved in part as adaptations for efficient foraging. Together, these results demonstrate that human spatial cognition is content sensitive, domain specific and designed by natural selection to mesh with important regularities of the ancestral world.

As indicated in the news report, 86 adults (41 women and 45 men) were tested for their ability to remember the location of food stalls in a farmers market. The women were 9% better at this than the men.

The result confirms the authors' hypothesis that women are genetically superior at this task because of adaptation during our hunter-gatherer past.

Silverman & Eals (1992) argue that the female advantage on pencil-and-paper and desktop measures of object location memory reflects a selective pressure on ancestral women for plant-foraging efficiency. But their measures did not involve foods, tested spatial memory on a very small scale, and included no measure of vectoring; as a result, a female advantage on their measures is open to many alternative interpretations. For this reason, we deemed it important to examine whether a female advantage could be demonstrated on a task that closely resembles foraging for plant foods. From this theory, we predicted that women should remember the locations where they have previously encountered immobile resources (e.g. plants, honey) more accurately than do men.

The authors don't explain exactly how this adaptation might have happened. Presumably it went something like this ...

At some time in the ancient past all humans had a single allele for the (unknown) gathering gene. A mutation in this gene arose producing an allele where the ability to gather food was improved. Since women were the principle food gatherers, this mutant allele conferred a selective advantage on women who carried it: presumably because they didn't share their food with their friends who carried the old allele. Over time, the new allele became fixed (or very frequent) in women but men did not benefit.

The first three authors are in Departments of Psychology and the senior author is in a Department of Anthropology.

---

New, J., Krasnow, M.M, Truxaw, D. and Gaulin, S.J.C. (2007) Spatial adaptations for plant foraging: women excel and calories count. Proc. Roy. Soc. B. DOI 10.1098/rspb.2007.0826.

[Photo Credit: The drawing is "An artist’s impression of early Hunter-Gatherers" from Manx National Heritage]

Adaptationomics

 
Jonathan A. Eisen is an evolutionary biologist with a blog called The Tree of Life. He's also one of the authors of a new textbook on evolution published by Cold Spring Harbor Laboratories [A New Textbook on Evolution]. I'm about to order a copy.

I mention this because Eisen is a pluralist. He's as annoyed by adaptationist just-so so stories as I am. Over on the Dennett on Adaptationism thread I'm encountering commenters who question whether there really are modern scientists who believe in the adaptationist program. I can assure you there are. Eisen has discovered some of them in the field of genomics—he didn't have to look very hard—and he decided to label their approach adaptationomics [Adaptationomics Award #1 - Wolbachia DNA sneaking into host genomes]. This is tongue-in-cheek so don't all you adaptationists get your knickers in a knot.

Here's how Jonathan sets up the issue.

For years I have been fighting against the tide on the tendency for people doing genomics work to resort to silly adaptationist arguments for observations. The argument goes something like this. We sequenced a genome (or did some type of genomics). We made an observation of something weird being present (take your pick - it could be a gene order or a gene expression pattern or whatever). We conclude that this observation MUST have an adaptive explanation. We have come up one such adaptive explanation. Therefore this explanation must be correct.

Gould and Lewontin railed against this type of thing many years ago and others have since. Just because something is there does not mean it is adaptive (e.g., it could be neutral or detrimental). And even if something is adaptive, just because you can think of an adaptive explanation does not mean your explanation is correct.

And this is so common in genomics I have decided to invent a new word - Adaptationomics. And I am giving out my first award in this to Jack Warren and colleagues for their recent press release on their new study of lateral transfer in Wolbachia (plus it lets me plug their new study which is pretty ^$%# cool).

Does this sound familiar?

What did the authors say that makes them adaptationists? In order to understand their statement you have to be familiar with their findings. They discovered that the genome of a parasite (Wolbachia) has been integrated into the geonome of their insect host. There are several reasons why this might have happened. It could just be an accident, since these kind of recombinant events occur frequently and most insects don't carry a full complement of their parasite's genome. In other words, it could be junk.

On the other hand, the parasite genome could possibly confer some (unknown) selective advantage on the host. But here's the rub. When the author of the article, Julie Dunning Hotopp, was interviewed for the the Nature News article here's what she said.

You're talking about a significant portion of its DNA that is now from Wolbachia," says Julie Dunning Hotopp, a geneticist at the J. Craig Venter Institute in Rockville, Maryland, who led the study. "There has to be some sort of selection to carry around that much extra DNA."

That's a classic adaptationist statement. The result "must be" explained by natural selection. There are no other options. I agree with Jonathan Eisen, this is a fitting recipient of his new Adaptationomics Award.

Congratulations to Julie Dunning Hotopp.

Theories of Speciation

 
In order to understand real evolution you have to understand speciation. This fact usually comes as a great surprise to adaptationists who tend not to think of such things. (Or, if they do, they adopt a grossly simplified version of speciation based on adaptation.)

John Wilkins tries to explain theories of speciation in his latest posting on Evolving Thoughts [Theories of Speciation]. John is a philosopher but don't let that fool you. He's an expert of speciation. The problem is, he explains it like a philosopher. :-)

Here's a nifty chart that I stole from John's article (he published it in his latest paper). If, after looking at the chart, it all becomes crystal clear to you then you have my sympathy. This is a very difficult problem but it can't be swept under the rug if you want to debate hierarchical theory and punctuated equilibria.

A genetic trigger for the Cambrian explosion unraveled?

 
Here's an interesting press release [A genetic trigger for the Cambrian explosion unraveled?]. This is the abstract, there's much more but I can't make sense of any of it.

A team of scientists led by young Croatian evolutionary geneticist Tomislav Domazet-Lošo from Ruder Boškovic Institute (RBI) in Zagreb, Croatia, developed a novel methodological approach in evolutionary studies. Using the method they named 'genomic phylostratigraphy', its authors shed new and unexpected light on some of the long standing macroevolutionary issues, which have been puzzling evolutionary biologists since Darwin.

We won't be able to discuss this "revolutionary" paper because it won't be published until November. The journal is Trends in Genetics, which is billed as "the most established monthly journal in Genetics."

RPM at Evolgen didn't seem to be too impressed either [Genomic Phylostratigraphy]. Go there if you want to see a list of the really best journals in genetics.

I wish there were some way of enforcing standards on places that issue scientific press releases. This one from the Ruder Boškovic Institute (RBI) is worse than useless.

Blog Day 2007

 
The rules for today are that we recommend five blogs you may not be reading on a regular basis. Here are my choices. Four Canadians and one honourary Canadian. How's that for chauvinism?

One of these is the most northern blog on my blogroll. Can you guess which one? One of the bloggers is very horny. Which one? One of the bloggers was recently at Montebello protesting George Bush (and what's-his-name, the Canadian Prime Minister). Two of them are Professors. One of them has the longest hair of any blogger I've met.

Mike's Weekly Skeptic Rant

Primodial Blog

Runesmith's Canadian Content

Genomicron

Sex, genes & evolution

Defining Irreducible Complexity

So many IDiots, so little time ....

Granville Sewell has posted a message on Uncommon Descent asking What if we DID find irreducibly complex biological features?. He writes,

In any debate on Intelligent Design, there is a question I have long wished to see posed to ID opponents: “If we DID discover some biological feature that was irreducibly complex, to your satisfication and to the satisfaction of all reasonable observers, would that justify the design inference?” (Of course, I believe we have found thousands of such features, but never mind that.)

If the answer is yes, we just haven’t found any such thing yet, then all the constantly-repeated philosophical arguments that “ID is not science” immediately fall. If the answer is no, then at least the lay observer will be able to understand what is going on here, that Darwinism is not grounded on empirical evidence but a philosophy.

Here's how Michael Behe defines irreducible complexity in Darwin's Black Box (p. 39).

By irreducibly complex I mean a single system composed of several well-matched, interacting parts that contribute to the basic function, wherein the removal of any one of the parts causes the system to cease functioning. An irreducibly complex system cannot be produced directly (that is, by continuously improving the initial function, which continues to work by the same mechanism) by slight, successive modifications of a precursor system, because any precursor to an irreducibly complex system that is missing a part is by definition nonfunctional.

There are many irreducibly complex systems in biology. One of my favorites is the citric acid cycle or Krebs cycle. This is a circular pathway of enzymes that oxidize acetate groups to two molecules of CO₂.


If you remove any one of the enzymes then there is no cycle and it will be impossible to oxidize acetyl groups to CO₂ and regenerate oxaloacetate. You cannot evolve a cycle for the complete net oxidation of acetate by starting with a more simple circular pathway then adding additional enzymes to improve the initial function; namely, the cyclic pathway of oxidation. Thus, by Behe's definition this is an irreducibly complex system whose function is to oxidize acetyl groups and regenerate the original precursor.

We have a damn good idea how the citric acid cycle evolved so the answer to Granville Sewell's original question is: no, the discovery of an irreducibly complex system does not justify the design inference. There are many ways of evolving irreducibly complex systems. This is the same answer that we've been giving for over ten years. Please try and keep up.

Now I have a question for the IDiots. If we can prove to your satisfaction that a particular system is irreducibly complex and demonstrate how it could easily have evolved, will you stop claiming that irreducibly complex systems can't evolve?

Dichloroacetate (DCA) Website Shut Down by the FDA

 
Dichloroloacetate (DCA) is a potent inhibitor of pyruvate dehydrogenase kinase [Regulating Pyruvate Dehydrogenase]. There have been suggestions in the scientific literature that the inhibition of this enzyme may lead to the death of cancer cells.

Over the years a minor cottage industry has grown up around the synthesis, sale, and promotion of DCA as a magic bullet for the cure of cancer. The lure of the drug is enhanced by the fact that it is so simple and can't be patented. Thus, according to its proponents, the drug companies don't want you to know about this fabulous cure because they can't make a profit. Abel Pharmboy at Terra Sigillata has written a lot about this drug [Perversion of good science].

THEME:
Pyruvate
Dehydrogenase
The problem is that the clinical trials have not been done and there's some danger of toxic effects when you take too much of the drug. The websites that sell DCA claim that it's only for animals but nobody is fooled by that ruse.

Now, according to New Scientist the FDA has ordered the main DCA website to cease selling DCA ['Cancer drug' site shut down]. When you go to the site at buydca.com you read the following disclaimer, " It is against US government law to sell substances with the suggestion that they are cancer treatments unless they are approved by the FDA."

A Blue Moon Is the Second Full Moon to Occur in a Single Calendar Month

 
Friday's Urban Legend: DEFINITELY FALSE, MAYBE

The term "blue moon" dates back to the middle ages where it meant something quite impossible. Over time the term came to be used in the phrase "once in a blue moon" to mean "it ain't ever going to happen" [Wikipedia: Blue Moon].

Gradually the phrase took on the meaning of something that happens rarely, instead of never. Following World War II there was an attempt to relate the term "blue moon" to a real astronomical event. The most common explanation was that a "blue moon" was the second full moon in the same calender month. The average time between two successive full moons is about 29.5 days. This means that you can have two full moons in any month except February. This will occur, on average, every two-and-a-half years. This year for example, you might have seen a "blue moon" in May, June, or July depending on where you live [The Blue Moon of 2007]. This interpretation of "blue moon" was promoted by Sky & Telespcope in 1946 and it was due to a misinterpretation of the Maine Farmer's Almanac of the preceding decade.

The Sky & Telescope website has a detailed explanation of the error [What 's a Blue Moon?].

So, if you accept the new definition of "blue moon" then the title statement is correct and this is an example of an urban myth that has transformed the meaning of a phrase. However, if you stick to the original meaning of the term then the title statement is false because a "blue moon" is about as likely as one made out of green cheese.

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[Photo Credit: The photograph of the "blue" moon is from miramiramazing]

Where Did Sea Anemones Get Human Genes?

 
A recent paper by Putman et al. (2007) discusses the newly completed genome of the starlet sea anemone Nematostella vectensis. Kevin Z, a marine biology researcher, blogged about this paper last month [Cnidarian Double Whammy: Anemone Genome Completed and a Worm Thats a Jelly!].

The IDiots were also interested in the paper because it reveals that humans and sea anemones share some genes. Someone named "dacock" posted a message on Uncommon Descent revealing that Darwinism had been overturned (again) [Where Did Sea Anemones Get Human Genes?].

I was going to blog about the stupidity of the IDiots but I just don't have time. Anyway, Kevin Z beat me to it [Anemone's Raise a Tentacle in Support of Evolution]. I don't agree with everything he says about the sea anemone genome and why the Intelligent Design Creationists get it wrong but it will have to do for now. Kevin's responses to some of the IDiots who posted comments over on Uncommon Descent are well worth the visit to his blog.

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[Photo Credit: The photograph of the starlet sea anemone and its description is from Summary of Professional Exchanges on Coral Genomics]

Putnam, H.M. et al. (2007) Sea Anemone Genome Reveals Ancestral Eumetazoan Gene Repertoire and Genomic Organization. Science 317: 86 - 94.

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?