Theme: Nobel Laureates

 
NOBEL LAUREATES

November 13, 2006
Physiology or Medicine 1922
Otto Fritz Meyerhof
"for his discovery of the fixed relationship between the consumption of oxygen and the metabolism of lactic acid in the muscle"

November 22, 2006
Physiology or Medicine 1964
Jacques Monod
"for their discoveries concerning genetic control of enzyme and virus synthesis"

November 29, 2006
Chemistry 1964
Dorothy Crowfoot Hodgkin
"for her determinations by X-ray techniques of the structures of important biochemical substances"

December 6, 2006
Chemistry 1930
Hans Fischer
"for his researches into the constitution of haemin and chlorophyll and especially for his synthesis of haemin"

December 13, 2006
Chemistry 1902
Hermann Emil Fischer
"in recognition of the extraordinary services he has rendered by his work on sugar and purine syntheses"

December 20, 2006
Physiology or Medicine 1953
Hans Adolf Krebs
"for his discovery of the citric acid cycle"

January 3, 2007
Physiology or Medicine 1982
Sune K. Bergström, Bengt I. Samuelsson, and John R. Vane
"for their discoveries concerning prostaglandins and related biologically active substances"

January 10, 2007
Physiology or Medicine 2004
Richard Axel and Linda B. Buck
"for their discoveries of odorant receptors and the organization of the olfactory system"

Theme

A Sense of Smell
Nobel Laureates: Richard Axel, Linda Buck
January 17, 2007
Physiology or Medicine 1998
Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad
"for their discoveries concerning nitric oxide as a signalling molecule in the cardiovascular system"

January 24, 2007
Chemistry 1978
Peter D. Mitchell
"for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory"


January 31, 2007
Chemistry 1988
Johann Deisenhofer, Robert Huber, and Hartmut Michel
"for the determination of the three-dimensional structure of a photosynthetic reaction centre"

February 7, 2007
Physiology or Medicine 1978
Werner Arber, Daniel Nathans, and Hamilton O. Smith
"for the discovery of restriction enzymes and their application to problems of molecular genetics"

February 14, 2007
Chemistry 1972
Christian B. Anfinsen
"for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation"

February 21, 2007
Physiology or Medicine 1930
Karl Landsteiner
"for his discovery of human blood groups"

February 28, 2007
Chemistry 1937
Walter Norman Haworth
"for his investigations on carbohydrates and vitamin C"

March 7, 2007
Physiology or Medicine 1948
Paul Hermann Müller
"for his discovery of the high efficiency of DDT as a contact poison against several arthropods"

March 14, 2007
Chemistry 1980
Paul Berg
"for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA"

Theme

Transcription
Nobel Laureate: Roger Kornberg
March 21, 2007
Chemistry 2006
Roger D. Kornberg
"for his studies of the molecular basis of eukaryotic transcription"

March 28, 2007
Physiology or Medicine 1943
Henrik Carl Peter Dam
"for his discovery of vitamin K"
Edward Adelbert Doisy "for his discovery of the chemical nature of vitamin K"

Theme

Blood Clotting
Nobel Laureates: Henrik Dam, Edward Doisy
April 4, 2007
Chemistry 1948
Arne Wilhelm Kaurin Tiselius
"for his research on electrophoresis and adsorption analysis, especially for his discoveries concerning the complex nature of the serum proteins"





April 11, 2007
Physiology or Medicine 1953
Fritz Albert Lipmann
"for his discovery of co-enzyme A and its importance for intermediary metabolism"

Theme

Pyruvate Dehydrogenase
Nobel Laureate: Aaron Klug
April 18, 2007
Chemistry 1982
Aaron Klug
"for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes"

April 25, 2007
Chemistry 1920
Walther Hermann Nernst
"in recognition of his work in thermochemistry"

May 2, 2007
Physiology or Medicine 1929
Christiaan Eijkman
"for his discovery of the antineuritic vitamin"


May 9, 2007
Physiology or Medicine 1947
Carl Ferdinand Cori and Gerty Theresa Cori, née Radnitz
"for their discovery of the course of the catalytic conversion of glycogen"

May 16, 2007
Chemistry 1907
Eduard Buchner
"for his biochemical researches and his discovery of cell-free fermentation"
[cell free synthesis of alcohol in yeast extracts: vitalism]

May 23, 2007
Physiology or Medicine 1994
Alfred G. Gilman and Martin Rodbell
"for their discovery of G-proteins and the role of these proteins in signal transduction in cells"


May 30, 2007
Physiology or Medicine 1968
Robert W. Holley, Har Gobind Khorana, and Marshall W. Nirenberg
"for their interpretation of the genetic code and its function in protein synthesis"

June 6, 2007
Chemistry 2004
Aaron Ciechanover, Avram Hershko, and Irwin Rose
"for the discovery of ubiquitin-mediated protein degradation"

June 13, 2007
Physiology or Medicine 1945
Sir Alexander Fleming, Ernst Boris Chain, Sir Howard Walter Florey
"for the discovery of penicillin and its curative effect in various infectious diseases"

June 20, 2007
Physiology or Medicine 1993
Richard J. Roberts and Phillip A. Sharp
"for their discoveries of split genes"

June 27, 2007
Physiology or Medicine 1937
Albert von Szent-Györgyi Nagyrapolt
"for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid"

July 4, 2007
Chemistry 1928
Adolf Otto Reinhold Windaus
"for the services rendered through his research into the constitution of the sterols and their connection with the vitamins"

July 11, 2007
Chemistry 1961
Melvin Calvin
"for his research on the carbon dioxide assimilation in plants"

THEME

Deoxyribonucleic Acid (DNA)
Nobel Laureates: Crick, Watson, Wilkins
July 18, 2007
Physiology or Medicine 1962
Francis Harry Compton Crick, James Dewey Watson and Maurice Hugh Frederick Wilkins
"for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material"




July 25, 2007
Physiology or Medicine 1902
Ronald Ross
"for his work on malaria, by which he has shown how it enters the organism and thereby has laid the foundation for successful research on this disease and methods of combating it"

and

Physiology or Medicine 1907
Charles Louis Alphonse Laveran
"in recognition of his work on the role played by protozoa in causing diseases"

August 1, 2007
Chemistry 1962
Max Ferdinand Perutz and John Cowdery Kendrew
"for their studies of the structures of globular proteins"

August 8, 2007
Chemistry 1903
Svante August Arrhenius
"in recognition of the extraordinary services he has rendered to the advancement of chemistry by his electrolytic theory of dissociation"

August 22, 2007
Physiology or Medicine 1971
Earl W. Sutherland, Jr.
"for his discoveries concerning the mechanisms of the action of hormones"

August 29, 2007
Chemistry 1937
Paul Karrer
"for his investigations on carotenoids, flavins and vitamins A and B2"

September 5, 2007
Chemistry 1938
Richard Kuhn
"for his work on carotenoids and vitamins"

September 12, 2007
Physiology or Medicine 1969
Max Delbrück, Alfred D. Hershey, and Salvador E. Luria
"for their discoveries concerning the replication mechanism and the genetic structure of viruses"

September 19, 2007
Physiology or Medicine 1933
Thomas Hunt Morgan
"for his discoveries concerning the role played by the chromosome in heredity"

September 26, 2007
Physiology or Medicine 1999
Günter Blobel
"for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell"


October 3, 2007
Physiology or Medicine 1983
Barbara McClintock
"for her discovery of mobile genetic elements"

October 10,2007
Chemistry 1909
Wilhelm Ostwald
"in recognition of his work on catalysis and for his investigations into the fundamental principles governing chemical equilibria and rates of reaction"

October 17, 2007
Chemistry 1926
The (Theodor) Svedberg
"for his work on disperse systems"

October 24, 2007
Chemistry 1946
James Batcheller Sumner
"for his discovery that enzymes can be crystallized"
[crystallization of urease from jack bean]

October 31, 2007
Physiology or Medicine 1959
Arthur Kornberg
"for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid"

November 7, 2007
Physiology or Medicine 1909
Emil Theodor Kocher
"for his work on the physiology, pathology and surgery of the thyroid gland"

November 14, 2007
Chemistry 1975
John Warcup Cornforth
"for his work on the stereochemistry of enzyme-catalyzed reactions"

November 21, 2007
Physiology or Medicine 1964
Konrad Bloch and Feodor Lynen
"for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism"

November 28, 2007
Physiology or Medicine 1992
Edmond Fischer and Edwin Krebs
"for their discoveries concerning reversible protein phosphorylation as a biological regulatory mechanism"

December 5, 2007
Physiology or Medicine 1955
Hugo Theorell
"for his discoveries concerning the nature and mode of action of oxidation enzymes"

December 12, 2007
Chemistry 1947
Sir Robert Robinson
"for his investigations on plant products of biological importance, especially the alkaloids"

December 19, 2007
Chemistry 1997
Paul Boyer and John Walker
"for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)"

January 9, 2008
Chemistry 1915
Richard Willstätter
"for his researches on plant pigments, especially chlorophyll"

January 16, 2008
Chemistry 1989
Sidney Altman
"for their discovery of catalytic properties of RNA"

January 23, 2008
Chemistry 1989
Thomas R. Cech
"for their discovery of catalytic properties of RNA"

January 30, 2008
Chemistry 1984
Bruce Merrifield
"for his development of methodology for chemical synthesis on a solid matrix"

February 6, 2008
Physiology or Medicine 1965
"for their discoveries concerning genetic control of enzyme and virus synthesis"
François Jacob

February 13, 2008
Physiology or Medicine 1965
"for their discoveries concerning genetic control of enzyme and virus synthesis"
André Lwoff

March 5, 2008
Chemistry 1954
"for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances"
Linus Pauling

March 12, 2008
Physics 1915
"for their services in the analysis of crystal structure by means of X-rays"
Sir William Henry Bragg and Lawrence Bragg

March 19, 2008
Chemistry 1974
"for his fundamental achievements, both theoretical and experimental, in the physical chemistry of the macromolecules"
Paul Flory

April 2, 2008
Chemistry 1918
"for the synthesis of ammonia from its elements"
Fritz Haber

April 9, 2008
Chemistry 2003
"for structural and mechanistic studies of ion channels"
Roderick MacKinnon

April 23, 2008
Chemistry 1957
"for his work on nucleotides and nucleotide co-enzymes"
Lord Alexander Todd

April 30, 2008
Physiology or Medicine 1947
"for his discovery of the part played by the hormone of the anterior pituitary lobe in the metabolism of sugar"
Bernardo Houssay

May 7, 2008
Physiology or Medicine 2000
"for their discoveries concerning signal transduction in the nervous system"
Arvid Carlsson and Paul Greengard

May 14, 2008
Physiology or Medicine 1958
"for their discovery that genes act by regulating definite chemical events"
George Beadle and Edward Tatum

May 21, 2008
Chemistry 1970
"for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates"
Luis Leloir

May 28, 2008
"for their preparation of enzymes and virus proteins in a pure form"
Wendell Stanley

June 4, 2008
Physiology or Medicine 1950
"for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects"
Edward Kendall, Tadeus Reichstein and Philip Hench

June 11, 2008
Chemistry 1872
"for their contribution to the understanding of the connection between chemical structure and catalytic activity of the active centre of the ribonuclease molecule"
Stanford Moore and William Stein

June 18, 2008
Physiology or Medicine 1972
"for their discoveries concerning the chemical structure of antibodies"
Gerald M. Edelman and Rodney R. Porter

June 25, 2008
Physiology or Medicine 1987
"for his discovery of the genetic principle for generation of antibody diversity"
Susumu Tonegawa

July 2, 2008
Physiology or Medicine 1929
"for his discovery of the growth-stimulating vitamins"
Sir Frederick Gowland Hopkins

July 9, 2008
Chemistry 2003
"for the discovery of water channels"
Peter Agre

July 16, 2008
Physiology or Medicine 1974
"for their discoveries concerning the structural and functional organization of the cell"
George E. Palade

July 23, 2008
Chemistry 1943
"for his work on the use of isotopes as tracers in the study of chemical processes"
George de Hevesy

July 30, 2008
Physiology or Medicine 1958
"for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria"
Joshua Lederberg

August 6, 2008
Physiology or Medicine 1973
"for their discoveries concerning organization and elicitation of individual and social behaviour patterns"
Karl von Frisch, Konrad Lorenz, Nikolaas Tinbergen

August 13, 2008
Physiology or Medicine 1922
"for his discovery relating to the production of heat in the muscle"
Archibald Hill

August 24, 2008
Physiology or Medicine 1977
"for the development of radioimmunoassays of peptide hormones"
Rosalyn Yalow

August 27, 2008
Chemistry 1929
"for their investigations on the fermentation of sugar and fermentative enzymes"
Arthur Harden

September 3, 2008
Chemistry 1929
"for their investigations on the fermentation of sugar and fermentative enzymes"
Hans Karl August Simon von Euler-Chelpin

September 10, 2008
Chemistry 2002
"for his development of nuclear magnetic resonance spectroscopy for determining the three-dimensional structure of biological macromolecules in solution"
Kurt Wüthrich

September 17, 2008
Physiology or Medicine 1931
"for his discovery of the nature and mode of action of the respiratory enzyme"
Otto Heinrich Warburg

September 25, 2008
Physiology or Medicine 2002
"for their discoveries concerning 'genetic regulation of organ development and programmed cell death'"
Sydney Brenner, H. Robert Horvitz, and John E. Sulston

October 1, 2008
Physiology or Medicine 1959
"for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid"
Severo Ochoa

October 8, 2008
"for his discovery of Prions - a new biological principle of infection"
Stanley Prusiner

October 16, 2008
"for their discoveries concerning the genetic control of early embryonic development"
Christiane Nüsslein-Volhard and Eric F. Wieschaus

October 21, 2008
"for the discovery of the production of mutations by means of X-ray irradiation"
Hermann Joseph Muller

October 29, 2008
"in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances"
Albrecht Kossel

November 5, 2008
"for their preparation of enzymes and virus proteins in a pure form"
John Howard Northrop

November 13, 2008
Physiology or Medicine 1995
"for their discoveries concerning the genetic control of early embryonic development"
Edward Lewis

November 19, 2008
Literature 1930
"for his vigorous and graphic art of description and his ability to create, with wit and humour, new types of characters"
Sinclair Lewis

November 27, 2008
Physiology or Medicine 1988
"for their discoveries of important principles for drug treatment"
George Hitchings and Gertrude Elion

December 3, 2008
Physiology or Medicine 2000
"for their discoveries concerning signal transduction in the nervous system"
Eric Kandel


December 10, 2008
Chemistry 1980
"for their contributions concerning the determination of base sequences in nucleic acids"
Walter Gilbert


December 17, 2008
Chemistry 1980
"for their contributions concerning the determination of base sequences in nucleic acids"
Fred Sanger


December 17, 2008
Chemistry 1990
"for his development of the theory and methodology of organic synthesis"
Elias Corey


January 14, 2009
Physiology and Medicince 1936
"for their discoveries relating to chemical transmission of nerve impulses"
Sir Henry Hallett Dale and Otto Loewi


January 21, 2009
Physiology or Medicince 1936
"for their discoveries concerning the humoral transmittors in the nerve terminals and the mechanism for their storage, release and inactivation"
Ulf von Euler and Julius Axelrod


January 29, 2009
Chemistry 2008
"for the discovery and development of the green fluorescent protein, GFP"
Osamu Shimomura


February 5, 2009
Chemistry 2002
"for their development of soft desorption ionisation methods for mass spectrometric analyses of biological macromolecules"
John B. Fenn and Koichi Tanaka


February 11, 2009
Physiology or Medicine 1974
"for their discoveries concerning the structural and functional organization of the cell"
Christian de Duve


February 20, 2009
Chemistry 1993
"for contributions to the developments of methods within DNA-based chemistry: for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for protein studies"
Michael Smith


February 26, 2009
Chemistry 1993
"for contributions to the developments of methods within DNA-based chemistry: for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for protein studies"
Kary Mullis


March 4, 2009
Physiology or Medicine 1923
"for the discovery of insulin"
Frederick Banting and J.J.R. Macleod


March 11, 2009
Chemistry 1958
"for his work on the structure of proteins, especially that of insulin"
Fred Sanger


March 19, 2009
Chemistry 1960
"for his method to use carbon-14 for age determination in archaeology, geology, geophysics, and other branches of science"
Willard Libby

March 25, 2009
Physiology or Medicine 1952
"for his discovery of streptomycin, the first antibiotic effective against tuberculosis"
Selman Waksman

April 1, 2009
Nobel Prize in Chemistry 1905
"in recognition of his services in the advancement of organic chemistry and the chemical industry, through his work on organic dyes and hydroaromatic compounds"
Adolf von Baeyer

April 8, 2009
Nobel Prize in Physiology or Medicine 2007
"for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells"
Mario Capecchi, Martin Evans, and Oliver Smithies


April 16, 2009
Physiology or Medicine 1951
"for his discoveries concerning yellow fever and how to combat it"
Max Theiler


April 23, 2009
Physiology or Medicine 2001
"for their discoveries of key regulators of the cell cycle"
Sir Paul Nurse

May 1, 2009
Physiology or Medicine 1908
"in recognition of their work on immunity"
Paul Ehrlich

---

OK. Everyone take a deep breath ....

 
It's just another small step towards understanding development and regulation. We've been expecting it for months [Reprogramming Somatic Cells].

It's not that big a deal. Frogs were cloned from somatic cells over 40 years ago. Sheep and lots of other animals have also been cloned from somatic cells. We know that somatic cells can be reprogrammed. Now we know a little bit more about how to do it.

This is not the end of an "ethical" dilemma. Lots of countries were already allowing work with human embryos to create embryonic stem cell lines. We've got lots of them. Sure, it means that the USA will have a better excuse to continue to block embryonic stem cell research but given the political climate that was probably going to happen anyway.

We're not helping science by turning this into a circus and creating false expectations of medical cures just around the corner. A little perspective is in order here.

---

Tangled Bank #93

 
The latest version of the Tangled Bank has been posted on from Archaea to Zeaxanthol [Tangled Bank #93].

Ahoy me mateys and welcome to the 93rd edition of the Tangled Bank, humbly hosted by yours truly. For those of you returning to from Archaea to Zeaxanthol, welcome back. For those new to my blog, let me give you a quick introduction.

---

Bacteria Genomes Are Degrading

 
At one point in his talk last night Kirk Durston mentioned the bacterial flagella. He acknowledged that the "Darwinists" have proposed an evolutionary pathway from a Type III secretory structure to flagella.

This pathway is improbable, according to Durston, because flagella are more complicated than secretory pores so flagella have to evolve first.

What? Yes, that's right. Scientists have now shown that the most primitive bacteria were very complex and evolution has been all downhill from then on. Modern bacteria are less complex. Thus the type III secretory apparatus had to evolve from the more complex bacterial flagella. (The actual situation is complicated [Evolution in (Brownian) space: a model for the origin of the bacterial flagellum]. What I'm addressing here is the claim of general loss of information in bacterial evolution.)

I suggested that this was bull not correct and Durston responded with a slide showing the scientific papers that proved it. The most important paper was

Mira, A., Ochman, H. and Moran N.A. (2000) Deletional bias and the evolution of bacterial genomes. Trends Genet. 17:589-96. [PubMed]

I asked Durston what would happen if I called Nancy Moran (no relation, that's her above) and asked her whether she agreed that primitive bacteria were complex and all modern bacterial lineages are losing information. He affirmed that she would and that's what modern evolutionary biologists are saying. There are other papers that say the same thing. He accused me of not being aware of them.

This is the abstract of the Mira et al. (2000) paper.

Although bacteria increase their DNA content through horizontal transfer and gene duplication, their genomes remain small and, in particular, lack nonfunctional sequences. This pattern is most readily explained by a pervasive bias towards higher numbers of deletions than insertions. When selection is not strong enough to maintain them, genes are lost in large deletions or inactivated and subsequently eroded. Gene inactivation and loss are particularly apparent in obligate parasites and symbionts, in which dramatic reductions in genome size can result not from selection to lose DNA, but from decreased selection to maintain gene functionality. Here we discuss the evidence showing that deletional bias is a major force that shapes bacterial genomes.

I think it's pretty obvious from the abstract that they're discussing a particular problem in bacterial evolution; namely selection for small compact genomes. This point is clear in the paper as well.

At no point in the paper do the authors suggest anything close to what Durston says. There's no mention of primitive bacteria having the full complexity of all modern species including the myxobacteria and photosynthetic bacteria etc. Why in the world do the Intelligent Design Creationists have to lie about things like this? (I assume it's a lie because the only other possibility is ignorance and a Ph.D. student in biophysics can't be stupid enough to misunderstand such a key principle of evolution, right?)

Naturally in a forum like this Durston had me at a disadvantage. He was displaying the scientific papers and I had to admit that I had not read them recently enough to comment. The point was not lost on some members of the audience. The atheist scientist was trumped by the religious graduate student who was more aware of the scientific literature.

"Frustrating," doesn't begin to cover it ...

---

Kirk Durston's Proof of God

 
I went to the lecture in Denyse O'Leary's course last night [I'm Going to a Lecture on Intelligent Design]. As promised, the guest speaker was Kirk Durston, a graduate student in biophysics at the University of Guelph.

It was a very frustrating experience. Like most Intelligent Design Creationists, Durston was all over the map in terms of spreading lies and misconceptions about science. This scattergun approach seems to be very successful for them. I assume it's because no one person can address all of the problems with their presentation. Most people will catch one or two flaws but they'll assume that everything else has to be correct.

I'll come back to some of these lies in another posting but right now I'd like to explain his main argument.

Kirk Durston has a background in computer science and his project has to do with analyzing the sequences of conserved gene families.

The Intelligent Design Creationist part of his study relies heavily on the work of Douglas Axe (Axe, 2000; Axe, 2004). Axe is head of Biologic Institute a "research" company in Redmond, WA (USA) with ties to the Discovery Institute [We're in Trouble Now].

The papers Axe published in the prestigious Journal of Molecular Biology represent work he did as a post-doc in Cambridge UK. The goal was to show that the probability of a protein adopting a particular three-dimensional fold is very, very low.

Durston is pursuing this line of work and he described it in his talk last night with plenty of equations and diagrams. There were about 15 people in the room and it's almost certain that nobody other than me had any idea what was going on. But it all sounded very sophisticated.

As it turns out, not understanding the science shouldn't have been such a big deal since the form of his argument was obviously silly. At least I thought it was obvious. Here's the way it went ...

1. By making assumptions A, B, C, and D and constructing equations E and F he is able to predict that no protein will have more than X amount of information.


2. By making a few assumptions about protein families it is possible to measure the amount of information in a folded domain by plugging the data into his equations. It turns out that most proteins have more than X information.


3. Therefore God exists (i.e., the protein must have been intelligently designed).

This are (at least) two major flaws in this argument and it doesn't take an expert in computer science or biochemistry to detect them.

First, when you formulate a scientific hypothesis you test it against scientific reality. If the predictions of your hypothesis are not fulfilled then your hypothesis is falsified. At that point it's back to the drawing board. You need to reconsider your assumptions or your equations because they were not successful. That's how science is done but that's not how Intelligent Design Creationism is done.

Second, the sudden appearance of God in the conclusion is illogical. There's no mention of God intelligent design in the premise. It just pops out of the argument without any warning. This is not how logic works and it's certainly not how science works.

I tried to point this out last night but nobody in the audience was paying attention and Durston was in no mood to discuss logic after having spent close to two hours practicing something else.

We have a word to describe people who can't construct a simple logical argument. It seems to have slipped my mind .... what is it ..... oh, yeah, now I remember ... IDiot.

---

Axe, D. (2000) Extreme Functional Sensitivity to Conservative Amino Acid Changes on Enzyme Exteriors. J. Mol. Biol. 310:585-595.

axe, D. (2004) Estimating the Prevalence of Protein Sequences Adopting Functional Enzyme Folds. J. Mol. Biol. 341:1295-1315.

Nobel Laureates: Konrad Bloch and Feodor Lynen

 

The Nobel Prize in Physiology or Medicine 1964.

"for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism"

Konrad Bloch (1912-2000) and Feodor Lynen (1911-1979) received the Nobel Prize in Physiology or Medicine for their work in deciphering the cholesterol biosynthesis pathway.

Feodor Lynen is mainly responsible for working out the pathway from acetate (acetyl CoA) to mevalonate [How Lipitor® Works] while Konrad Bloch worked mostly on the rest of the pathway [How to Make Cholesterol][Making Squalene].

Last week's Nobel Laureate, John Cornforth, was rewarded for discovering the exact mechanisms that give rise to a stereospecific product [Nobel Laureate: John Cornforth].

The 1964 presentation speech was given by Professor S. Bergström, member of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

Since the start of the Nobel Foundation the professorial staff of the Karolinska Institute has chosen the prizewinners in Physiology or Medicine. This year the Karolinska Institute has been reorganized into a medical university and the duties of the professorial staff have been taken over by the medical faculty of the enlarged Karolinska Institute. As the last item on its agenda the professorial staff was to decide this year's Nobel Prizewinners in Physiology or Medicine and on October 15 Professors Konrad Bloch and Feodor Lynen were awarded the prize for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism.

The word cholesterol means gallstone and the reason for this name is that cholesterol was isolated almost 200 years ago from human gallstones. Another connection between cholesterol and human diseases has been established more recently. During the last decade there has been a lively discussion, also in the newspapers, about the correlation between atherosclerosis and the amount of cholesterol and other fats in diet and in blood. This discussion has perhaps concealed from many the fact that cholesterol is a necessary constituent of all our cells and that it fulfills important functions. The elucidation of its chemical structure is one of the foremost achievements in organic chemistry during the 1910's and 1920's. In 1928 the German chemists Windaus and Wieland received Nobel Prizes in Chemistry for their work on the structure of cholesterol and the closely related bile acids. The four-ring carbon skeleton characteristic of cholesterol was later found not only in a number of sterols of plant and animal origin but also in the precursors of vitamin D, in the male and female sex hormones, in the hormones from the adrenal cortex, etc.

Nothing was known about the way they were formed or about their interrelationships. When this year's prizewinners started their scientific career, Professor Hevesy had done his discoveries concerning the use of isotopes as tracers in the living organism. When first the stable and later the radioactive isotopes of hydrogen and carbon became available, they were first extensively used by a group at Columbia University that was headed by the late Rudolph Schoenheimer and in which Bloch played an important role. The work of the group with isotopically labeled compounds has laid the foundation of our general knowledge of the dynamic state in the living cell.

One of the fundamental discoveries was the elucidation of the role of acetic acid as a building block for cholesterol as well as fatty acids. Lynen, working in Wieland's laboratory on the metabolism of acetic acid, succeeded in isolating the so-called activated acetic acid, which is the precursor of all lipids in our body and the common denominator of a number of metabolic processes. With all possible refinements in the utilization of isotope techniques, Bloch and collaborators were able to show in a series of brilliant investigations how the two carbon atoms of acetic acid are used for the synthesis of a long hydrocarbon with thirty carbon atoms, squalene, which in turn is cyclized in a novel type of reaction to a steroid with thirty carbon atoms, lanosterol. This lanosterol is then transformed in a complicated series of reactions into cholesterol, which has twenty-seven carbon atoms. Of special interest are the reactions leading to the formation of the hydrocarbon squalene, and the elucidation of these reactions, which are common for the biosynthesis of many other lipids and natural products, is due not only to Bloch and Lynen and collaborators but also to Popjak and Cornforth in England and Folkers and co-workers in the U.S.A. In connection with this work Lynen made two other discoveries of great importance to our understanding of the mechanisms of cellular metabolism: the elucidation of the mechanism of action of the vitamin biotin and the determination of the structure of cytohemin.

At an early stage Bloch made another discovery of fundamental importance in showing that cholesterol is the precursor of bile acids and of one of the female sex hormones. These discoveries opened up a new field of research that has engaged a great number of scientists in different disciplines. We know now that all substances of steroid nature in our body are formed from cholesterol.

Mainly through the basic biochemical work of this year's prizewinners do we know today in detail how cholesterol and fatty acids are synthesized and metabolized in the body. These processes comprise series of reactions with a great number of individual steps. For instance, the formation of cholesterol from acetic acid is a process involving some thirty different steps. Derangements of this complicated mechanism of formation and metabolism of lipids are in many cases responsible for the genesis of some of our most important diseases, especially in the cardiovascular field. A detailed knowledge of the mechanisms of lipid metabolism is necessary to deal with these medical problems in a rational manner.

The importance of the work of Bloch and Lynen lies in the fact that we now know the reactions which have to be studied in relation to inherited and other factors. We can now predict that we, through further research in this field in the near future, can expect to be able to do individual specific therapy against the diseases that in the developed countries are the most common cause of death.



Professor Bloch, Professor Lynen. You have both started your research in Munich and you have proceeded the proud tradition of this town in a splendid way.

Feodor Lynen, you are now standing with dignity in the array of the earlier Munich Nobel Prizewinners, Adolf von Baeyer, Hans Fischer and Heinrich Wieland.

Konrad Bloch, you have like Emil Fischer and Richard Willstätter left Munich and continued your work in the New World.

I have made a very short summary of your successful research work in the field of lipids. You have provided us with detailed knowledge of many fundamental metabolic reactions. This knowledge forms the necessary basis for the study of the different medical problems in the field of lipid metabolism.

It can now be anticipated that in the near future we will learn how to deal with many of these diseases in a rational and successful way.

On behalf of the Caroline Institute I have the honour to congratulate you on your brilliant work and I now ask you to receive your prizes from the hands of His Majesty the King.

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[Photo Credits: Konrad Bloch plaque is from Wikipedia. Restricted photos of Feodor Lynen are available on ViewImages]

Best Lab Website

 
New Scientist is running a contest for the best laboratory website. The ten finalists are listed on the New Scientist website [Laboratory Website and Video Awards].

One of the finalists is the lab website of T. Ryan Gregory of Genomicron [Please vote for my lab website.].

Now, I'm not saying that you should hop on over to the New Scientist site and vote for Ryan Gregory just because he's such a nice guy and he's a blogger. And certainly not just because it's a Canadian lab. Of course you shouldn't do that. This is a legitimate scientific poll and heaven forbid that there would be any shenanigans in the voting. No siree, Bob.

You should carefully examine each and every one of the ten finalists and make an honest judgment about the best site. I choose Ryan Gregory's lab site as my #1 pick. If you don't want to waste time you can trust me and vote for him too. Pick the Emili lab site as your #2 choice 'cause Andrew Emili is a colleague of mine has the next best site.

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[Photo Credit: Gregory Lab: Genomic Diversity]

Two Cultures

Stephen Fry has posted a long description of a debate he had with an American aquaintance about global climate change [Getting Overheated]. You should read the whole thing but there's one part that caught my eye.

We must begin with a few round truths about myself: when I get into a debate I can get very, very hot under the collar, very impassioned, and I dare say, very maddening, for once the light of battle is in my eye I find it almost impossible to let go and calm down. I like to think I’m never vituperative or too ad hominem but I do know that I fall on ideas as hungry wolves fall on strayed lambs and the result isn’t always pretty. This is especially dangerous in America. I was warned many, many years ago by the great Jonathan Lynn, co-creator of Yes Minister and director of the comic masterpiece My Cousin Vinnie, that Americans are not raised in a tradition of debate and that the adversarial ferocity common around a dinner table in Britain is more or less unheard of in America. When Jonathan first went to live in LA he couldn’t understand the terrible silences that would fall when he trashed an statement he disagreed with and said something like “yes, but that’s just arrant nonsense, isn’t it? It doesn’t make sense. It’s self-contradictory.” To a Briton pointing out that something is nonsense, rubbish, tosh or logically impossible in its own terms is not an attack on the person saying it – it’s often no more than a salvo in what one hopes might become an enjoyable intellectual tussle. Jonathan soon found that most Americans responded with offence, hurt or anger to this order of cut and thrust. Yes, one hesitates ever to make generalizations, but let’s be honest the cultures are different, if they weren’t how much poorer the world would be and Americans really don’t seem to be very good at or very used to the idea of a good no-holds barred verbal scrap. I’m not talking about inter-family ‘discussions’ here, I don’t doubt that within American families and amongst close friends, all kinds of liveliness and hoo-hah is possible, I’m talking about what for good or ill one might as well call dinner-party conversation. Disagreement and energetic debate appears to leave a loud smell in the air.

I understand this difference. Here in Canada we're half way between Europe and America in terms of debate tactics. In some cases you can have lots of fun carrying on in a "British" tradition. But from time-to-time you encounter some people from the "American" cultural tradition and they take great offense at such behavior.

The problem is especially acute when dealing with creationists. They are very good at politely lying and spreading misinformation with a pleasant smile on their faces. They are ever so respectful of the "other side" while, at the same time, implying that all scientists are really stupid.

But when you try and call them on their lies you are immediately dismissed for being rude and uncivilized. The average "Christian" will only tolerate polite discourse and by that they mean non-confrontational. As long as you tells lies in a quiet polite voice it's okay.

We also see the problem when discussing militant atheists. People like Richard Dawkins and Christopher Hitchins are just behaving normally in the culture in which they were raised. It's Americans who see this as a particularly disrespectful way of behaving. That's why American atheists are so often opposed to the so-called militant atheists and think they're hurting the cause.

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[Hat Tip: RichardDawkins.net]

[Photo Credit: stephenfry.com]

How Lipitor® Works

 
In previous postings we learned how cholesterol is made from squalene and squalene is made from the six carbon compound mevalonate [How to Make Cholesterol] [Making Squalene].

Today we'll cover the synthesis of melavonate from three molecules of the 2-carbon compound acetate.

When acetate is involved in biosynthesis reactions it is "activated" by forming a thioester linkage to coenzyme A ("thio" means sulfur). Coenzyme A was discovered by Nobel Laureate: Fritz Lipmann.

The first step in the pathway is the joining of two molecules of acetyl CoA to make the 4-carbon compound acetoacetyl CoA. Note that this molecule is still joined to coenzyme A. In the second step, another acetyl group is transferred to acetoacetyl CoA to make the 6-carbon molecule 3-hydroxyl-3-methylglutaryl CoA (HMG CoA). HMG-CoA was Monday's Molecule.

The last step is cleavage of the thioester linkage between the 6-carbon compound and CoA releasing mevalonate.

This last step is catalyzed by an enzyme called HMG-CoA reductase. This is an oxidation-reduction reaction where the reduction of HMG-CoA is coupled to the oxidation of NADPH. This enzyme is regulated inside the cell and this controls the biosynthesis of cholesterol since mevalonate is an essential intermediate in the pathway.

Lipitor® and similar drugs control cholesterol synthesis by inhibiting the enzyme HMG-CoA reductase. If we draw the substrate in a way that shows its structure, you can see that Lipitor® and Mevacor® resemble the business end of the molecule—the part that's cleaved by the enzyme. These drugs are effective inhibitors because they bind to the active site of the enzyme.



The class of HMG-CoA reductase inhibitors is called statins. They are used to control serum cholesterol levels in the hopes of reducing the risks of coronary heart disease. There don't seem to be any serious side effects to inhibiting mevalonate production in spite of the fact that mevalonate is required for synthesis of some hormones and of the essential cofactor ubiquinone [Ubiquinone and the Proton Pump].

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Parental Guidance Suggested

 

This rating was determined based on the presence of the following words:

* dead (2x)
* sex (1x)

I wonder what kind of rating I would get if Sandwalk were rated in France? Do they have a "milquetoast" rating?

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Swift Boat Funder T. Boone Pickens Reneges On John Kerry Million Dollar Offer

 
Anyone who spoke out against the war in Viet Nam and who knew Jane Fonda would get my vote. Especially if the other choice was someone who didn't even like Jane Fonda.

Do you remember the Swift Boat campaign against John Kerry? You should. It's going to be important in the next year since we're very likely to see something similar in the next Presidential election campaign.

One of the founders of Swift Boat Veterans for Truth (sic) has just offered one million dollars if Kerry can prove that there was even one lie in the ads they placed on television. Kerry takes up the challenge but, it seems as though there's some fine print ... [ Swift Boat Funder T. Boone Pickens Reneges On John Kerry Million Dollar Offer]. Imagine that.

Pickens supports Rudy Giuliani so it's unlikely that Giuliani will be swiftboated. Hmmm, I wonder who the target will be ....

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[Hat Tip: Canadian Cynic]

I'm Going to a Lecture on Intelligent Design

 
Denyse O'Leary is teaching a course on Intelligent Design at the University of St. Michael's College, University of Toronto [Denyse O'Leary's University Course on Intelligent Design].

The outline of the course was posted on Post-Darwinist [ COURSE: By Design or by Chance? An introduction to the intelligent design controversy].

Students in the course are allowed to invite a guest for one lecture and one of my friends, who shall remain nameless for now, has urged me to come along. By all accounts the course is going well and Denyse is presenting both sides of the controversy.

Tonight's lecture is ...

Session 5. Intelligent design: What the ID proponents actually say (and don’t say) Tuesday November 20, 2007

Michael Behe, author of Edge of Evolution (2007), sees actual design where, for example, Richard Dawkins, author of The Blind Watchmaker, sees the illusion of design. Who’s right? Are they both wrong?

Guest: Kirk Durston, biophysics PhD candidate at the University of Guelph.

Kirk Durston (right) is the National Director of the New Scholars Society. According to his biography on their website,

KIRK DURSTON, B.Sc (Physics), B.Sc. (Mech. Eng.), M.A. (Philosophy), Ph.D. Candidate (Biophysics) at the University of Guelph.

Kirk Durston is the National Director of the New Scholars Society. He is currently a Ph.D. candidate in Biophysics at the University of Guelph, specializing in the application of information to biopolymers. His other interests include amateur astronomy, wilderness canoeing & camping, and landscape photography & art.

What is it about creationists that they always seem to have multiple redundant degrees? In this case he has two Bachelor's degrees. What's with that?

It's easy to find out what Kirk believes because there's a Statment of Faith on the website.

The sole basis of our beliefs is the Bible, God's infallible written Word, the 66 books of the Old and New Testaments. We believe that it was uniquely, verbally and fully inspired by the Holy Spirit, and that it was written without error (inerrant) in the original manuscripts. It is the supreme and final authority in all matters on which it speaks.We accept those large areas of doctrinal teaching on which, historically, there has been general agreement among all true Christians. Because of the specialized calling of our movement, we desire to allow for freedom of conviction on other doctrinal matters, provided that any interpretation is based upon the Bible alone, and that no such interpretation shall become an issue which hinders the ministry to which God has called us.

Jeffrey Shallit had a few things to say about Kirk Durston on Recursivity [Kirk Durston: Apologist for Genocide]. This is going to be an interesting lecture.

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Who Was Adam?

 
One of the regular contributers to the comments section of Sandwalk has suggested we read Who Was Adam? by Fazale Rana and Hugh Ross. Apparently this is a very good explanation of how evolution is compatible with the Bible.

Hugh Ross is the ruler of Reasons to Believe, an organization that promotes the integration of science and fundamentalist Christianity. Here's part of their Statement of Faith.

We believe the Bible (the 66 books of the Old and New Testaments) is the Word of God, written. As a "God-breathed" revelation, it is thus verbally inspired and completely without error (historically, scientifically, morally, and spiritually) in its original writings. While God the Holy Spirit supernaturally superintended the writing of the Bible, that writing nevertheless reflects the words and literary styles of its individual human authors. Scripture reveals the being, nature, and character of God, the nature of God's creation, and especially His will for the salvation of human beings through Jesus Christ. The Bible is therefore our supreme and final authority in all matters that it addresses.

Fazale (Fuz) Rana is a biochemist who works for Hugh Ross at Reasons to Believe.

I've seen Hugh Ross in action when he was here for a two day symposium organized by Denyse O'Leary and some of her friends. Hugh Ross is a genuine kook with nothing to say that's even remotely interesting to scientists. I don't know about Fazale Rana. Has anyone read this book?

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Gene Genie #20

 

The 20th edition of Gene Genie has just been published on Bitesize Bio [Gene Genie #20].

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Genetically Speaking All Races Are Equal

 
That's what the genetics expert, Crystal, told us in her video [Crystal Tells Us about the Human Genome] ...

Now, surprisingly enough, genetically speaking all races are equal. As a matter of fact, if you took a random sample of someone's DNA, just by looking at it you could not tell whether they were African-American, Caucasian, Asian or any other race.

I guess Crystal forgot to tell Price et al. (2007) because this is what they say in the abstract of the paper they just published in PLoS Genetics ...

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false positive or negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

So, not only can we distinguish Caucasians from Africans and Asians, we can also sort out different groups within Caucasians.

Isn't it amazing that scientists can do this when there's no genetic differences between races?

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Price, V. et al. (2007) Discerning the ancestry of European Americans in genetic association studies. PLoS Genet. In press. [doi:10.1371/journal.pgen.0030236.eor]

Judgment Day Online

 
Judgment Day is the PBS Nova show about the Dover trial. You can now watch it online in 12 episodes [Judgment Day].

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[Hat Tip: Monado at Science notes ( "Intelligent Design on Trial" comes to your computer)]

A World Without Writers

 

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[Hat Tip: Canadian Cynic]

Monday's Molecule #52

 
Today's molecule is a bit more complicated than some. Most of you probably haven't encountered it in your studies and those who have may have seen it drawn a bit differently. Your task is to give it a complete biochemical name as well as the shortened common name.

There's a direct connection between this molecule and Wednesday's Nobel Laureate(s).

The reward goes to the person who correctly identifies the molecule and the Nobel Laureate(s). Previous winners are ineligible for one month from the time they first collected the prize. There are three ineligible candidates for this week's reward. 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(s). Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

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

UPDATE: We have a winner! The molecule is 3-hydroxy-3-methylglutaryl-Coenzyme A, or HMG-CoA. Wait to see who the Nobel Laureate is tomorrow.

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Crystal Tells Us about the Human Genome

According to the YouTube profile ...

Crystal is graduated from Texas A&M University w/ a degree in agricultural leadership and development with an emphasis on genetics and bio-chemistry. She is currently a professional model.

Here's her website [crystalnicole.com]. There's not much on her website about DNA or genomes. On the other hand, there's a lot of Crystal. I suspect science isn't her main interest in life.

This is a video about the human genome. Crystal tells us lots of interesting things about the size of our genome, number of genes, junk DNA, whether the DNA of different races is the same etc. etc.

It makes my blood boil. A lot of the information is basically correct but there's no explanations. For example, we know why the rice genome has more genes than the human genome—it's not a mystery. Some of the information is wrong (e.g., similarities between different species). Some of it is misleading (e.g., the definition of a gene).

I assume that this is just a regurgitation of things that Crystal learned in class. Rather than detail all of the errors I'll leave it up to you. You can list them in the comments.

The question I want answered is whether this sort of video serves a useful purpose or not. Is it better to have such a thing on YouTube than nothing at all? (I think we can all agree that the ideal situation would be to have a similar video that was accurate.)

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[Hat Tip: Curious Cat and ScienceRoll]

John Wilkins Likes Sociobiology

 
Wilkins is reviewing a soon-to-be-published paper by David Sloan Wilson and Edward O. Wilson [The two Wilsons on sociobiology]. These two are on a recent tear promoting a new, acceptable, version of group selection. John Wilkins declares that, "I have recently (i.e., in the last five years) come to be an unflinching sociobiologist ..."

This may raise some eyebrows but, as usual, John threads his way through the minefield of misconceptions about sociobiology to arrive at a position that he can support. (I don't agree with him, but that debate is for another time.)

What I particularly like about John's posting is how he separates evolutionary psychology from sociobiology by pointing out the deep flaws in the discipline of evolutionary psychology.

Evolutionary psychology has two major flaws in my opinion. One is that it is almost always adaptationist even when no evidence of adaptiveness is available. Adaptation is, as G. C. Williams noted of group selection explanations, an onerous hypothesis, to be supported or not used. It is too easy to come up with "possible scenarios", let alone possible adaptations. Such explanations need to follow the evidence rather than use, as EvPsych does, a priori arguments from the self-evident truth of natural selection and the nature of evolution.

The second major flaw relates to this. On the (a priori) assumption that selection always favours modularity, EvPsychologists claim that most of the human behavioural repertoire and its underlying neurology is modular. Each module is, as the literature has it, "informationally encapsulated and domain specific", which roughly means that it does one thing well and only that thing, without hints from the rest of our cognitive and sensorimotor system.

I agree with John 100%, although I might add one or two other flaws. I'm not sure the Wilsons would agree, however. I wonder if John knows whether E.O. Wilson is as opposed to evolutionary psychology as he (John) is?

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Where Was Anderson Cooper?

 
The latest death toll from Bangladesh is 2200 and this number will almost certainly rise. Chris Mooney knew this was coming last Wednesday and he warned everyone to expect a disaster [Still No Weakening for Cyclone Sidr].

Why didn't CNN dispatch its crack team of hurricane reporters to the scene? And why, even now, is the news media treating this so lightly?

Yesterday I watched while the CNN anchors reported on the dead and injured and the millions of people who lost their homes. They then switched immediately to light-heated banter about elderly women playing basketball. We didn't see that kind of insensitivity during Katrina, did we?

Should there be a difference just because one hurricane is killing Americans while another is killing people in Bangledesh?


UPDATE: Death Toll Might Reach 10,000.

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[Photo Credits: AFP: Bangladesh cyclone dead number 2,200, millions destitute]

Adaptationist Award #2

 
Jonathan Eisen at The Tree of Life has just given out his second adaptationist award. This "award" goes to those who exemplify the famous Dr. Pangloss referred to in Gould and Lewontin (1979).

This award goes to David Brown for his article in the Washington Post. An article that begins with ...

It used to be a rule -- actually, more of an assumption -- that the genetic machinery of living organisms was never intentionally wasteful or inaccurate. It turns out this isn't always true, either.

I think you can already see why this award is so richely deserved but if you're still in doubt check out the posting [Adaptationomics Award #2 - Washington Post and David Brown].

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Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme. Proc. Roy. Soc. (London) Series B, 205:581-598. [OnLine Version]

John Dennehy's Citation Classic

 
John Dennehy's citation classic for this week is a paper by Volkin and Astrachan published in 1956. That's Elliot "Ken" Volkin on the left.

I was not aware of this paper but John makes a good case for its importance in the history of molecular biology. Volkin and Astrachan deserve more recognition for discovering messenger RNA (mRNA). Get on over to The Evilutionary Biologist and read about the private meeting between Francis Crick, Sidney Brenner, and François Jabob in Brenner's room at King's College in 1960 [This Week's Citation Classic].

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[Photo Credit: Oak Ridge National Laboratory]

Bruce Alberts in Toronto

 
My Ph.D. supervisor, Bruce Alberts, was in Toronto yesterday to receive an honourary Doctor of Science degree from the University of Toronto. We had a nice luncheon in the Upper Library at Massey College. That's Bruce Alberts on the right and my former Ph.D. student and co-author Marc Perry on the left. Three "generations" of Ph.D.'s.

I'm sure three-generation pictures are quite common but four- and five-generation photographs are more unusual. Does anyone have one?

Following the luncheon we were off to the Chancellor's Office to get "gowned" for the graduation ceremony. Yesterday was graduation day for Ph.D. and Masters degree students.

The students were lined up to enter Convocation Hall. There were 391 of them and later on we waited while each one was called to the stage to receive their degree.

The procession of faculty was quite impressive with all the gowns, finery, pomp, and circumstance. Here we are (below) all dressed up on the stage of Convocation Hall. From left to right, Katherine Whiteside, Dean of Medicine; Bruce Alberts, convocation speaker and honourary degree recipient; Jack Petch, Chair Governing Council; David Peterson, Chancellor; David Naylor, President; Susan Pfeiffer, Dean School of Graduate Studies; and half of me on the end. On the right I'm delivering the citation for Bruce Alberts.


Here's part of what I said,

Bruce was very successful at Princeton where he made major advances in working out the mechanism of DNA replication, laying the groundwork for future recognition as an outstanding scientist. He has also contributed greatly to our understanding of chromosomes. In 1995 he came to Toronto to receive a Gairdner Award for his scientific achievements. He has published over 150 scientific papers.

Bruce moved to the University of California at San Francisco in 1976. He served as Chair of the Department of Biochemistry & Biophysics during the time that it rose to become one of the leading biochemistry departments in the world. Bruce’s guidance and mentorship during that time contributed in no small part to the success of the department.

Among the many honours and awards he has received I’d like to single out a few others that relate to his scientific achievements. He holds an American Cancer Society Lifetime Research Professorship. He was elected to the American National Academy of Sciences in 1981. He is a Foreign Member of the Royal Society (London) and many other international societies.

Bruce’s interest in science education was apparent from the beginning. In 1983 he and his colleagues published the very first edition of his famous textbook Alberts et al. The Molecular Biology of the Cell. The book has become familiar to students all around the world. The fifth edition is due to be published in just a few weeks. The Molecular Biology of the Cell set a standard for textbook writing that few other books have matched. I dare say many of the students here have taken at least one course that used his book.

In 1993, Bruce left San Francisco and moved to Washington to become President of the National Academy of Sciences—a post he held for twelve years. During that time he was “First Scientist” in the USA and, arguably, the most influential scientist in the world.

Bruce soon became known as the “Education President” for his efforts to improve science education beginning in kindergarten and the primary grades. He is highly respected for his tireless efforts in bettering science education and research policies in the USA and around the world. This effort has continued since he left Washington. He has received numerous awards for his achievements in education including Outstanding Volunteer Coordinator in California schools, the Leadership in Education Award from Keystone Center, the Distinguished Service Award from the National Association of Biology Teachers, and the Victor Hamburger Outstanding Educator Prize from the American Association for Developmental Biology.

There are even more awards and honours, for example Bruce Alberts is a Commander of the Order of the British Empire.

Outstanding scientist, caring mentor, renowned author, and distinguished educator.

Mr, Chancellor, on behalf of the Governing Council, I ask you to confer the degree of Doctor Of Science, honoris causa, upon Bruce Alberts.

After the graduation ceremony we came back to the Biochemistry Department for a reception in Bruce's honour. Many of the graduate and undergraduate students showed up with copies of their textbooks and Bruce was delighted to sign them.

We had a wonderful, but short, visit. I hope he comes back again real soon.

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Are You as Smart as a Second Year University Student? Q2

 
Here's another question from my test.

In Icons of Evolution Jonathan Wells defines evolution as,

Biological evolution is the theory that all living things are modified descendants of a common ancestor that lived in the distant past.

Does this definition differ from the one you learned in biology class? Does it differ from the definitions of evolution commonly found in textbooks? Why does Wells choose this definition over any others?

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Are You as Smart as a Second Year University Student? Q1

 
Here's a question from last month's test in our class on the evolution/creationism debate. How would you have done?

Philip Johnson is one of the leading advocates of intelligent design creationism, He argues that science is unnecessarily atheistic because it requires methodological naturalism.

Creationists are disqualified from making a positive case, because science by definition is based on naturalism. The rules of science also disqualify any purely negative argumentation designed to dilute the persuasiveness of the theory of evolution. Creationism is thus out of court—and out of the classroom—before any consideration of evidence. Put yourself in the place of a creationist who has been silenced by that logic, and you may feel like a criminal defendant who has just been told that the law does not recognize so absurd a concept as "innocence."

Is this a good argument for intelligent design creationism? Explain your answer.

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The Johnson quotation is from Johnson, P.E. (1990) "Evolution as Dogma: The Establishment of Naturalism" first published in First Things 6:15-22. reprinted in Intelligent Design Creationism and Its Critics Robert T. Pennock ed.

Judgment Day

 
I just saw the show last night. I had to tape it on Tuesday night because the only way I could see it was on WCTS Seattle and that was too late for me to stay up [Judgment Day Is Coming].

The show was very good. I was impressed with the way it was edited and with the lack of unnecessary hype. The courtroom scenes were a bit silly but I can't think of any way to improve them short of making them look too theatrical. At least this way you weren't under any illusions that it was anything but a simulation.

I liked the emphasis on the divisions within the community. What it shows us is that no courtroom victory is going to make this issue go away. The creationists simply don't accept the results of the trial as having any relevance to their religion. Americans are going to have to go through this trauma several more times in the next few years.

I'm still a bit sad that programs like this have to go out of their way to show that evolutionists can be religious. There were obligatory scenes of Ken Miller in church and of one of the Dover evolutionist supporters teaching Bible class. This is a debate about science and religion. The whole point was to show that Intelligent Design Creationism is religion and not science. Evolution is science. So why is it necessary to focus on the religious beliefs of evolution supporters? Shouldn't their personal beliefs be irrelevant?

There are lots of interesting things on the Judgment Day website [NOVA: Judgment Day]. One of them is a brief talk by Ken Miller on "Science and Religion" (follow the link "Defining Science"). I wonder if most people agree with Miller's explanation of the supernatural and how it impinges on science?

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Framing Evolution

 
Clive Thompson wrote an article for Wired titled Clive Thompson on Why Science Will Triumph Only When Theory Becomes Law.

It falls into the category of "with friends like this who need enemies." Thompson is upset about the way in which creationists misuse the word theory.

This is the central argument of evolution deniers: Evolution is an unproven "theory." For science-savvy people, this is an incredibly annoying ploy. While it's true that scientists refer to evolution as a theory, in science the word theory means an explanation of how the world works that has stood up to repeated, rigorous testing. It's hardly a term of disparagement.

But for most people, theory means a haphazard guess you've pulled out of your, uh, hat. It's an insult, really, a glib way to dismiss a point of view: "Ah, well, that's just your theory." Scientists use theory in one specific way, the public another — and opponents of evolution have expertly exploited this disconnect.

We all agree that this is a problem when we're trying to explain evolutionary theory to the general public. We need to explain that a theory is not just some wide-eyed speculation but a solid explanation of facts that has stood the test of time. Theories are as good as it gets in science. The Theory of Natural Selection, for example, is not in dispute.

It's a pain to have to do this but it's our obligation as scientists to explain science correctly, right? Clive Thompson has another suggestion.

For truly solid-gold, well-established science, let's stop using the word theory entirely. Instead, let's revive much more venerable language and refer to such knowledge as "law." As with Newton's law of gravity, people intuitively understand that a law is a rule that holds true and must be obeyed. The word law conveys precisely the same sense of authority with the public as theory does with scientists, but without the linguistic baggage.

Evolution is supersolid. We even base the vaccine industry on it: When we troop into the doctor's office each winter to get a flu shot — an inoculation against the latest evolved strains of the disease — we're treating evolution as a law. So why not just say "the law of evolution"?

Best of all, it performs a neat bit of linguistic jujitsu. If someone says, "I don't believe in the theory of evolution," they may sound fairly reasonable. But if someone announces, "I don't believe in the law of evolution," they sound insane. It's tantamount to saying, "I don't believe in the law of gravity."

It's time to realize that we're simply never going to school enough of the public in the precise scientific meaning of particular words. We're never going to fully communicate what's beautiful and noble about scientific caution and rigor. Public discourse is inevitably political, so we need to talk about science in a way that wins the political battle — in no uncertain terms.

No, no, no! Theories are not laws and under no circumstances should scientists abandon science in order to score political points.

On the other hand, Mooney and Nisbet would be proud [What Is Framing?].

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[Photo Credit: Clive Thompson from University of British Columbia]

[Hat Tip: RichardDawkins.net]

Nobel Laureate: John Cornforth

 

The Nobel Prize in Chemistry 1975.

"for his work on the stereochemistry of enzyme-catalyzed reactions"




In 1975, Sir John Warcup 'Kappa' Cornforth (1917- ) won the Nobel Prize in Chemistry for elucidating the squalene biosynthesis pathway and other pathways that generate stereospecific products [Making Squalene]. The prize was shared with Vladimir Prelog for his work on the spereospecificity of chemical reactions.

Cornforth has been deaf since he was 20 years old but overcame his deafness to become an outstanding biochemist. He is a Professor at the University of Sussex (UK). He has written a brief history of the work on the cholesterol pathway (Cornforth 2002). Here's a remarkable interview with Cornforth from the Vega Science Programmes [How to be Right and Wrong].

The presentation speech was delivered, in Swedish, by Professor Arne Fredga of the Royal Academy of Sciences.

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

The laureates in chemistry of this year have both studied reaction mechanisms, especially from a stereochemical, i.e. a geometrical point of view. In a chemical experiment some compounds are mixed, then something happens, and finally one can isolate one or more other compounds. What has really happened, and why, and how? The situation is as if someone had abbreviated a classical tragedy, say Hamlet, by showing only the opening scenes of the play and the final scene of the last act. The principal characters are introduced, then the scene closes and when the curtain rises again you see a number of dead bodies on the stage and a few survivors. Of course the spectators would like to know what has happened in the meantime.

What I have said is valid not least for enzymatic reactions. Many such reactions are perpetually going on in all living organisms; one could say that they really concern all of us although we don't observe them. When a chemist tries to find out what really happens, he often comes across the problem: right or left? It is the same in common life. If you leave Stockholm by Norrtull, you soon come to a place where the main road branches: the left branch leads to Oslo, the right one to Sundsvall or, if you like, to Haparanda.

Professor Cornforth has among other things studied the biological synthesis of the hydrocarbon squalene from six molecules of mevalonic acid. This hydrocarbon is necessary for the formation of steroids, which are of vital importance in many respects. The synthesis of squalene takes place in 14 steps and at each the enzyme must find the proper way. That means that there are just 214 = 16384 different routes and only one of them leads to squalene. If the enzyme should make a mistake in the first step (which it does not), the final result could be rubber or various other things but definitely not squalene. The problem at each step concerns which of two hydrogen atoms is to be eliminated, the right one or the left one. Professor Cornforth has shown which choice the enzyme makes at each of the 14 steps. For this purpose he has, with brilliant mastership, utilized the properties of the hydrogen isotopes: the ordinary hydrogen, the heavy hydrogen and the radioactive hydrogen. The lastmentioned isotope can only be used in tracer quantities, which means that only about one part per million of the participating molecules are radioactive. In a similar way, Professor Cornforth has studied several other biologically important reactions. All problems connected with the reaction mechanisms are not solved at that point, but the results constitute a very important step on the way.

Professor Prelog has worked in many fields of stereochemistry, and often the problems have been connected with the geometrical shapes of the molecules and their influence on the course of the reactions.

An impressive series of investigations deal with the "medium rings", i.e. molecules containing rings of 8 to 11 carbon atoms. Such rings are not rigid but rather limp. Parts of the ring which may seem rather distant may come into close contact with each other leading to unexpected reactions. Professor Prelog has been able to elucidate such reactions by utilizing the carbon isotopes.

Many important investigations refer to reactions between chiral molecules. The term chiral is derived from a word in ancient Greek, meaning hand. The molecules are unsymmetrical and may exist in two forms differing in the same way as a right hand and a left hand. The molecules are so small that you can't see them, but one can gain much knowledge by studying the reactions between chiral molecules of different kind.

Professor Prelog has also made important contributions to enzyme chemistry. He has studied enzymatic reactions on small molecules and in particular oxidation or reduction processes. The experiments may be more or less successful depending on how the enzyme and the other molecule fit together geometrically. By systematic experiments with various small molecules of well-defined shapes, it was possible to construct a "map" of the active part of the enzyme molecule. The results have recently been confirmed in a special case by Swedish scientists using x-ray methods.

Professor Prelog has also with ingenuity and penetration discussed and analysed the fundamental concepts of stereochemistry, not least the conditions for chirality in large and complicated molecules.

Professor Cornforth. Enzymatic reactions have always had a certain air of magic, perhaps witchcraft. Of course this is due to our imperfect knowledge of what really happens. This air of magic is, however, gradually dispersing, and your contributions, utilizing the isotopes of hydrogen, imply most striking advances. The handling of compounds with chiral methyl groups is an achievement of the highest intellectual standard.

Let me also express our admiration for the skill and perseverance with which you have pursued your work in spite of a serious physical handicap. Perhaps it had not been possible without the never-failing help and support of Mrs. Cornforth. I think she should not be forgotten on this day. In recognition of your services to chemistry and to natural science as a whole, the Royal Academy of Sciences has decided to confer upon you the Nobel Prize. To me has been granted the privilege to convey to you the most heartly congratulations of the Academy.

Professor Prelog. Ich habe hier versucht, einen Kurzbericht über Ihre wichtigsten Leistungen in der Stereochemie zu erstatten. Das war gewiss etwas schwierig. Ihre schönen Experimentalarbeiten erstrecken sich über weite Felder der heutigen organischen Chemie. Öfters haben Sie die Fortführung Ihrer Arbeiten anderen Forschern überlassen, und viele Chemiker hohen Ranges sind zurzeit auf den Gebieten tätig, die Sie einst eröffnet haben. Sie haben auch die fundamentalen Grundlagen der Stereochemie, besonders den Chiralitätsbegriff, in tiefsinnigen Auseinandersetzungen diskutiert und klargelegt.

In Anerkennung Ihrer Verdienste um die Entwicklung der Chemie hat die Konigliche Akademie der Wissenschaften entschlossen, Ihnen den Nobelpreis zu verleihen. Mir ist die Aufgabe zugefallen, Ihnen die wärmsten Glückwünsche der Akademie zu überbringen.

Professor Cornforth. In the name of the Academy I invite you to receive your prize from the hands of His Majesty the King.

Professor Prelog, Im Namen der Akademie bitte ich Sie aus den Händen Seiner Majestät des Königs den Nobelpreis in Empfang zu nehmen.

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Cornforth, J.W. (2002) Sterol biosynthesis: the early days. Biochem. Biophys. Res. Commun. 292:1129-38. [PubMed]

Making Squalene

 
Squalene is the essential precursor for making cholesterol [How to Make Cholesterol]. The pathway for synthesis of squalene is complicated and it was only worked out in second half of the last century.

The initial substrate is a compound called mevalonate. It's a six carbon branched organic acid. In a later posting we'll wee how cells make mevalonate and learn how that pathway can be controlled by Lipitor® and other drugs that regulate cholesterol levels.

Mevalonate is first phosphorylated by mevalonate kinase in a reaction that requires ATP.


The product of this reaction is mevalonate-5-phosphate and it is immediately phosphorylated again to produce the disphospate derivative. The next step removes the carboxylate group, which is released as a bicarbonate ion (CO₂ dissolved in water produces bicarbonate). This decarboxylation reaction is associated with the formation of a double bond at the end of the product molecule, isopentenyyl diphosphate. This is an important step in the pathway to squalene since squalene has a lot of carbon-carbon double bonds.

The five-carbon isopentenyl group of isopentenyl diphosphate is known as an isoprenyl unit. This molecule (isopentenyl diphosphate) is the source of isoprenyl units for many other biosynthesis reactions in addition to squalene synthesis. &Beta:-carotene and the lipid vitamin A (retinol) are good example of compounds with these isoprene units [Vitamin A (retinol)]. Ubiquinone is an absolutely essential cofactor in many important biochemical reactions an it has an isoprenoid tail [Ubiquinone and the Proton Pump]. Vitamin K, which is required for blood clotting, has a derived isoprenoid tail [THEME: Blood Clotting].

The pathway from isopentenyl diphosphate to squalene is complicated but the basic strategy is quite simple. The idea is to join two five carbon (C₅) isoprene units to make the C₁₀ molecule geranyl diphosphate. Then another C₅ isoprenyl unit is added to make C₁₅ farnesyl diphosphate. Finally, two molecule of farnesyl diphosphate are joined head-to-head to make C₃₀ squalene.


The difficult part of this reaction was figuring out the mechanism so that all of the double bonds would be in the trans conformation. Most of the work was done by John Cornforth who received the Nobel Prize in 1975 [Nobel Laureate: John Cornforth].

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Praying for Rain

 
Here's a video from CNN of Georgia Governor Sonny Perdue praying for rain [Georgia's governor prays for rain on Capitol steps]. It's the sort of thing you might expect from a tribe of hunter-gathers about 50,000 years ago. It didn't work very well back then. I wonder if it will work today?

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Free Your Mind

 

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[Hat Tip: PZ Myers]