Nobel Laureate Charles Nicolle

The Nobel Prize in Physiology or Medicine 1928

"for his work on typhus"

Charles Jules Henri Nicolle (1886 - 1936) was a French scientist who studied typhus while he was Director of the Pasteur Institute in Tunis. He realized that patients suffering from typhus were usually contageous but when they entered the hospital they were no longer contageous after a bath and a change of clothes. This led him to conclude that the disease was being spread by something in the clothing and lice were a prime suspect.

He soon confirmed his hypothesis by infecting chimpanzees and showing that the disease could be transferred by lice from one infected chimp to another uninfected animal. Further research showed that the disease was actually being transferred by microbes in lice excrement and through insect bites. In addition to lice, mites and fleas can also transmit various forms of typhus.

Nicolle was not able to develop a vaccine against typhus. Even today there is no effective vaccine available but the disease can be treated by antibiotics, especially doxycycline. [See Monday's Molecule #246]

It's pretty amazing to think that the cause of such a horrible disease was only discovered in the lifetime of our parents or grandparents (or great-grandparents).

Here's part of the Award Ceremony Speech.

THEME:
Nobel Laureates

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

In awarding the 1928 Nobel Prize for Medicine to Dr. Charles Nicolle, Director of the Pasteur Institute at Tunis, the Caroline Institute wished to pay tribute to a man who has realized one of the greatest conquests in the field of prophylactic medicine, i.e. the vanquishing of typhus.

... The disease has been known since the beginning of all time. The plague which devastated Attica, especially Athens in the year 430 B.C., and which Thucydides describes in his work on the Peloponnesian War, was most likely an epidemic of typhus. The picture that the great historian draws of the disease agrees in certain respects, down to the smallest details, with the clinical picture we were able to observe during the Great War. Epidemics followed one another without respite during the great wars of the sixteenth and seventeenth centuries. At the end of the Thirty Years’ War, typhus raged over the whole of Central Europe. The Napoleonic Wars caused the disease to flare up again. In the general disorganization which followed the Grand Army’s retreat from Russia, typhus claimed innumerable victims amongst the troops and amongst the civilian population. Further epidemics broke out during the Crimean War and the Russo-Turkish War, affecting both sides.

With the progress of civilization and during the period of peace and prosperity which, in all, lasted from the end of the nineteenth century until 1914, typhus seemed of its own accord to have become restricted to certain remote regions of Europe and to certain extra-European countries where, from time immemorial, the disease had existed endemically.

At the beginning of this North Africa was among these non-European countries where the disease had been a veritable national scourge for several centuries. As soon as he took up his appointment as Director of the Pasteur Institute at Tunis, young Dr. Charles Nicolle was immediately brought into contact with the scientific and practical problems that typhus had created in this country.

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Photo Credit: The figure is from Wikipedia.

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Nobel Laureate: Vincent du Vigneaud

The Nobel Prize in Chemistry 1955

"for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone"

Vincent du Vigneaud (1901-1978) was an American biochemist who was awarded the Nobel Prize in Chemistry in 1955 for his work on biological molecules containing sulfur, especially methionine cystine, and biotin. The prize was for solving the structure of the peptide hormone oxytocin and synthesizing an active molecule. (See Monday's Molecule #244.) From 1938 to 1967 Vigneaud's lab was at Cornell Medical College in New York City.

Here's part of the Presentation Speech.

THEME:
Nobel Laureates

Underneath the brain, there is a small, well-protected gland, the pituitary gland. In man it is about as big as a bean. There are secreted several hormones, that is, substances which regulate important physiological functions. spite of its small size, the pituitary gland is made up of several distinct parts with different functions. We are interested here in the posterior lobe, which contains two substances called oxytocin and vasopressin. The former stimulates the contractions of the uterus and also the lactation, the latter raises the blood pressure and regulates the function of the kidneys. As early as in 1933, when rather impure preparations from the posterior lobe were used in experiments, du Vigneaud found a high percentage of sulphur, which seemed to be correlated to the physiological activity.

Using the experimental methods, which the development of science has put at his disposal and making the best of his own intimate knowledge of the organic chemistry of sulphur, du Vigneaud has step by step forced his way. Both hormones were isolated in a state of purity, and it was found that they are built up from amino acids in the same way as proteins, but with a far lower molecular weight. Such compounds are, as distinguished from real proteins, called polypeptides. The nature of the amino acids and their positions in the molecule could be determined. The sulphur is present in cystine. The two hormones have a very similar structure; both contain eight amino acids, connected to a chain, which at one point is closed to a ring. The molecule has some resemblance to a figure six or nine, where the loop contains five amino acids and the “tail” three. Two sulphur atoms, linked to each other, form a part of the ring.

The design of the molecule was thus known. It remained to build it up by synthesis and check the correctness of the design. That was perhaps the most difficult part of the work. The interest was first concentrated on the synthesis of oxytocin. Step by step the amino-acid chain was built up with the two sulphur atoms in the proper positions, one at the end of the chain and the other near the middle. At last the ring was closed by formation of a bond between the sulphur atoms. Now followed the most thrilling moment, the testing of the chemical properties and the physiological activity; perhaps there had been some mistake after all. It turned out, however, that the synthetic polypeptide was identical with the natural product.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Nobel Laureates Michael Brown and Joseph Goldstein

The Nobel Prize in Physiology or Medicine 1985

"for their discoveries concerning the regulation of cholesterol metabolism"

Michael S. Brown and Joseph L.Goldstein won the Nobel Prize in 1985 for discovering the low-density lipoprotein (LDL) receptor, a cell surface protein that binds lipid-protein complexes containing cholesterol. (See Monday's Molecule #243.)

Here's part of the Press Release.

THEME:
Nobel Laureates

Michael S. Brown and Joseph L. Goldstein have through their discoveries revolutionized our knowledge about the regulation of cholesterol metabolism and the treatment of diseases caused by abnormally elevated cholesterol levels in the blood. They found that cells on their surfaces have receptors which mediate the uptake of the cholesterol-containing particles called low-density lipoprotein (LDL) that circulate in the blood stream. Brown and Goldstein have discovered that the underlying mechanism to the severe hereditary familial hypercholesterolemia is a complete, or partial, lack of functional LDL-receptors. In normal individuals the uptake of dietary cholesterol inhibits the cells own synthesis of cholesterol. As a consequence the number of LDL-receptors on the cell surface is reduced. This leads to increased levels of cholesterol in the blood which subsequently may accumulate in the wall of arteries causing atherosclerosis and eventually a heart attack or a stroke. Brown and Goldstein’s discoveries have lead to new principles for treatment, and prevention, of atherosclerosis.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Nobel Laureate: Aziz Sancar

The Nobel Prize in Chemistry 2015.

“for mechanistic studies of DNA repair”

Aziz Sancar won the 2015 Nobel Prize in Chemistry for his contributions to the study of DNA repair.

Sancar was born in Turkey in 1946 and got his MD degree from the Faculty of Medicine of Istanbul University. He then went on to get a Ph.D. with Claud S. Rupert at the University of Texas at Dallas in 1977. The Rupert lab worked on DNA repair and Sancar's thesis topic was the photoreactivating enzyme in E. coli. The photoreactivating enzyme was an enzyme that repaired DNA damage.

Sancar eventually secured a position at the University of North Carolina, Chapel Hill where he worked on excision repair and on photoreactivation. He is best known for his study of the mechanism of photolyase, the enzyme that repairs thymine dimers. [see Monday's Molecule #242] Photolyases are present in bacteria, protozoa, fungi, plants, and most animals. The gene for photolyase has been lost in placental mammals.

The information on the Nobel Prize website describes the career of Aziz Sancar.

THEME:
Nobel Laureates

Aziz Sancar’s fascination with life’s molecules developed while he was studying for a medical degree in Istanbul. After graduating, he worked for a few years as phycisian in the Turkish countryside, but in 1973 he decided to study biochemistry. His interest was piqued by one phenomenon in particular: when bacteria are exposed to deadly doses of UV radiation, they can suddenly recover if they are illuminated with visible blue light. Sancar was curious about this almost magical effect; how did it function chemically?

Claud Rupert, an American, had studied this phenomenon and Aziz Sancar joined his laboratory at the University of Texas in Dallas, USA. In 1976, using that time’s blunt tools for molecular biology, he succeeded in cloning the gene for the enzyme that repairs UV-damaged DNA, photolyase, and also in getting bacteria to over-produce the enzyme. This work became a doctoral dissertation, but people were hardly impressed; three applications for postdoc positions resulted in as many rejections. His studies of photolyase had to be shelved. In order to continue working on DNA repair, Aziz Sancar took up a position as laboratory technician at the Yale University School of Medicine, a leading institution in the field. Here he started the work that would eventually result in the Nobel Prize in Chemistry.

By then it was clear that bacteria have two systems for repairing UV damage: in addition to light-dependent photolyase, a second system that functions in the dark had been discovered. Aziz Sancar’s new colleagues at Yale had studied this dark system since the mid-1960s, using three UV-sensitive strains of bacteria that carried three different genetic mutations: uvrA, uvrB and uvrC.

As in his previous studies of photolyase, Sancar began investigating the molecular machinery of the dark system. Within a few years he had managed to identify, isolate and characterise the enzymes coded by the genes uvrA, uvrB and uvrC. In ground-breaking in vitro experiments he showed that these enzymes can identify a UV-damage, then making two incisions in the DNA strand, one on each side of the damaged part. A fragment of 12-13 nucleotides, including the injury, is then removed.

Aziz Sancar’s ability to generate knowledge about the molecular details of the process changed the entire research field. He published his findings in 1983. His achievements led to an offer of an associate professorship in biochemistry at the University of North Carolina at Chapel Hill. There, and with the same precision, he mapped the next stages of nucleotide excision repair. In parallel with other researchers, including Tomas Lindahl, Sancar investigated nucleotide excision repair in humans. The molecular machinery that excises UV damage from human DNA is more complex than its bacterial counterpart but, in chemical terms, nucleotide excision repair functions similarly in all organisms.

So, what happened to Sancar’s initial interest in photolyase? Well, he eventually returned to this enzyme, uncovering the mechanism responsible for reviving the bacteria. In addition, he helped to demonstrate that a human equivalent to photolyase helps us set the circadian clock.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Atheism is a catastrophe for science according to Michael Egnor

Michael Egnor doesn't like atheists. He got a bit upset about a recent post by PZ Myers so he responded on Evolution News & Views (sic) with: Atheism Is a Catastrophe for Science.

Modern theoretical science arose only in the Christian milieu. Roger Bacon, Copernicus, Galileo, Newton, Kepler, Faraday, Pasteur, Maxwell and countless other pioneers of the Scientific Enlightenment were fervent Christians who explicitly attributed the intelligibility in nature to God's agency, and even 20th-century scientists like Einstein and Heisenberg and Schrodinger and Rutherford and Planck attributed nature to intelligent agency. Einstein famously explained his quest: "I want to know God's thoughts..."

Vanishingly few great scientists have attributed the world to "undirected processes." Atheism, in fact, has a dismal record in science. For much of the 20th century, a third of humanity lived under the boot of atheist ideology. What was the great science produced by atheist scientists in the Soviet Union? What are the scientific contributions of Communist China and Cuba and Vietnam and Albania? Compare the scientific output of East Germany (atheist) to that of West Germany (Lutheran and Catholic). Compare the scientific output of North Korea (atheist) to that of South Korea (Christian and Buddhist).

The fact is that during the 20th century atheist ideological systems that "assum[ed] that the world is a product of natural, undirected processes" governed a third of humanity. What's the scientific "track record" of atheism? Atheism had its run: it heralded a scientific dark age in any nation unfortunate enough to fall under its heel. Atheism is as much a catastrophe for science as it is a catastrophe for humanity. The only thing atheist systems produced reliably (and still produce reliably) is corpses.

Google is my friend. I found a Wikipedia article on List of nonreligious Nobel Laureates. Here are the Nobel Laureates in science who didn't believe in any gods. This is part of the "scientific track record of atheism."

Chemistry
Svante Arrhenius
Paul D. Boyer
Frédéric Joliot-Curie
Irène Joliot-Curie
Richard R. Ernst
Herbert A. Hauptman
Roald Hoffmann
Harold W. Kroto
Jean-Marie Lehn
Peter D. Mitchell
George Andrew Olah
Wilhelm Ostwald
Linus Pauling
Max Perutz
Frederick Sanger
Michael Smith
Harold Urey

Physics
Zhores Alferov
Hannes Alfvén
Philip Warren Anderson
John Bardeen
Hans Bethe
Patrick Blackett
Nicolaas Bloembergen
Niels Bohr
Percy Williams Bridgman
Louis de Broglie
James Chadwick
Subrahmanyan Chandrasekhar
Marie Curie
Pierre Curie
Paul Dirac
Albert Einstein
Enrico Fermi
Richard Feynman
Val Logsdon Fitch
James Franck
Dennis Gabor
Murray Gell-Mann
Vitaly Ginzburg
Roy J. Glauber
Peter Higgs
Gerard 't Hooft
Herbert Kroemer
Lev Landau
Leon M. Lederman
Albert A. Michelson
Konstantin Novoselov
Jean Baptiste Perrin
Isidor Isaac Rabi
C. V. Raman
William Shockley
Erwin Schrödinger
Jack Steinberger
Igor Tamm
Johannes Diderik van der Waals
Eugene Wigner
Steven Weinberg
Chen-Ning Yang

Physiology and Medicine
Julius Axelrod
Robert Bárány
J. Michael Bishop
Francis Crick
Max Delbrück
Christian de Duve
Howard Florey
Camillo Golgi
Frederick Gowland Hopkins
Andrew Huxley
François Jacob
Sir Peter Medawar
Jacques Monod
Thomas Hunt Morgan
Herbert J. Muller
Élie Metchnikoff
Rita Levi-Montalcini
Hermann Joseph Muller
Paul Nurse
Ivan Pavlov
Richard J. Roberts
John Sulston
Albert Szent-Györgyi
Nikolaas Tinbergen
James Watson

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The 2015 Nobel Prize in Chemistry: was the history of the discovery of DNA repair correct?

... those ignorant of history are not condemned to repeat it; they are merely destined to be confused.

Stephen Jay Gould
Ontogeny and Phylogeny (1977)Back when the Nobel Prize in Chemistry was announced I was surprised to learn that it was for DNA repair but Phil Hanawalt wasn't a winner. I blogged about it on the first day [Nobel Prize for DNA repair ].

I understand how difficult it is to choose Nobel Laureates in a big field where a great many people make a contribution. That doesn't mean that the others should be ignored but that's exactly what happened with the Nobel Prize announcement [The Nobel Prize in Chemsitry for 2015].

In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.

Maybe it's okay to ignore people like Phil Hanawalt and others who worked out mechanisms of DNA repair in the early 1960s but this description pretends that DNA repair wasn't even discovered until ten years later.

I published links to all the papers from the 1960s in a follow-up post [Nature publishes a misleading history of the discovery of DNA repair ].

By that time I was in touch with David Kroll who was working on an article about the slight to early researchers. He had already spoken to Phil Hanawalt and discovered that he (Hanawalt) wasn't too upset. Phil is a really, really nice guy. It would be shocking if he expressed disappointment or bitterness about being ignored. I'll do that for him!

The article has now been published: This Year’s Nobel Prize In Chemistry Sparks Questions About How Winners Are Selected.

Read it. It's very good.

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Canada's new Minister of Science, Kirsty Duncan, is NOT a Nobel Prize winner

Canada has a new government under the Liberal Party and a new Prime Minister, Justin Trudeau. I'm very excited about this change. I'm a member of the Liberal Party of Canada and I voted for the Liberal Candidate in my riding.

One of the big changes is supposed to be increased transparency of government, more openness with the press, and a promise to base decisions on evidence and science. In other words, truth is supposed to be the new buzzword on Parliament Hill. Trudeau's new cabinet even has a Minister of Science, unlike previous cabinets.

Nobel Prize for DNA repair

Tomas Lindahl, Paul Modrich, and Aziz Sancar shared the 2015 Nobel Prize in Chemistry for "for mechanistic studies of DNA repair" [Nobel Prize, Chemistry 2015].

Here's some of the press release.

In the early 1970s, scientists believed that DNA was an extremely stable molecule, but Tomas Lindahl demonstrated that DNA decays at a rate that ought to have made the development of life on Earth impossible. This insight led him to discover a molecular machinery, base excision repair, which constantly counteracts the collapse of our DNA.

Aziz Sancar has mapped nucleotide excision repair, the mechanism that cells use to repair UV damage to DNA. People born with defects in this repair system will develop skin cancer if they are exposed to sunlight. The cell also utilises nucleotide excision repair to correct defects caused by mutagenic substances, among other things.

Paul Modrich has demonstrated how the cell corrects errors that occur when DNA is replicated during cell division. This mechanism, mismatch repair, reduces the error frequency during DNA replication by about a thousandfold. Congenital defects in mismatch repair are known, for example, to cause a hereditary variant of colon cancer.

What about Phil Hanawalt?

Meanwhile, in other news: Discovery and Characterization of DNA Excision Repair Pathways: the Work of Philip Courtland Hanawalt ...

In 1963, Hanawalt and his first graduate student, David Pettijohn, observed an unusual density distribution of newly synthesized DNA during labeling with 5-bromouracil in UV-irradiated E. coli. These studies, along with the discovery of CPD excision by the Setlow and Paul Howard-Flanders groups, represented the co-discovery of nucleotide excision repair.

And Wikipedia [Philip Hanawalt] says,

Philip C. Hanawalt (born in Akron, Ohio in 1931) is an American biologist who discovered the process of repair replication of damaged DNA in 1963. He is also considered the co-discoverer of the ubiquitous process of DNA excision repair along with his mentor, Richard Setlow, and Paul Howard-Flanders. He holds the Dr. Morris Herzstein Professorship in the Department of Biology at Stanford University,[1] with a joint appointment in the Dermatology Department in Stanford University School of Medicine.

Here's what Hanawalt himself says about discovering DNA excision repair [The Awakening of DNA Repair at Yale] ...

Upon joining the faculty at Stanford University in late 1961 as Research Biophysicist and Lecturer, I returned to the problem of what UV did to DNA replication, now that we knew the principal photoproducts. I wanted to understand the behavior of replication forks upon encountering pyrimidine dimers, and I was hoping to catch a blocked replication fork at a dimer. Using density labeling with 5-bromouracil and radioactive labeling of newly-synthesized DNA, we were able to observe partially replicated DNA fragments in E. coli [13]. However, in samples from UV irradiated bacterial cultures, the density patterns of nascent DNA indicated that much of the observed synthesis was in very short stretches, too short to appreciably shift the density of the DNA fragments containing them [14]. I communicated these results to Setlow by phone and learned that he had just discovered that pyrimidine dimers in wild type cells, but not in Ruth Hill’s UV sensitive mutant, were released from the DNA into an acid soluble fraction. We speculated in discussion that my student, David Pettijohn, and I were detecting a patching step by which a process of repair replication might use the complementary DNA strand as template to fill the single-strand gaps remaining after the pyrimidine dimers had been removed. At about the same time, Paul Howard-Flanders in the Department of Therapeutic Radiology at Yale had isolated a number of UV-sensitive mutants from E. coli K12 strains, and he was able to show that these mutants were also deficient in removing pyrimidine dimers from their DNA. The seminal discovery of dimer excision was published by the Setlow and Howard-Flanders groups, as the first indication of an excision repair pathway [15,16]. Of course, the excision per se is not a repair event but only the first step, since it generates another lesion, the gap in one strand of the DNA. We carried out more controls, to then claim that we had discovered a non-conservative mode of repair replication, constituting the presumed patching step in the postulated excision-repair pathway [17]. I later showed that DNA containing the repair patches could undergo semiconservative replication with no remaining blockage [18].

Richard Boyce and Howard-Flanders at Yale also documented excision of lesions induced by mitomycin C in E. coli K12 strains, indicating some versatility of excision repair [19]. In a collaboration with Robert Haynes, I found a similar pattern of repair replication after nitrogen mustard exposure to that following UV, and we concluded that “it is not the precise nature of the base damage that is recognized, but rather some associated secondary structural alteration …” We speculated that “[s]uch a mechanism might even be able to detect accidental mispairing of bases after normal replication,” thus predicting the existence of a mismatch repair pathway [20]. Mismatch repair was reported by Wagner and Meselson a decade later [21] and yet another excision repair mode, termed base excision repair, was discovered by Tomas Lindahl [22].

One of Hanawalt's students was Jonathan Eisen [Tree of Life]. I'll be interested in hearing what he has to say about this Nobel Prize. It seems unfair to me.

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Nobel Prize in ... 2060

This is my granddaughter, Zoë, standing outside the Stockholm City Hall where they hold the Nobel Prize banquet every year on December 10th.

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Nobel Laureates Become Pseudoscientists

 
There are several well-known examples of Nobel Laureates in science who later become enamored with quackery. Orac mentions a few on his blog in The Nobel disease strikes again.

Can you guess who holds the record for the swiftest turn around from getting the Nobel Prize to endorsing quackery? (Hint: mentor of Richard Dawkins).

Of course this record only applies to scientists who became quacks after getting the Nobel Prize. That lets Kary Mullis off the hook.

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Which Country Has the Best Brains?

 

BBC News has an article on which countries produce the most Nobel Prize winners: Which country has the best brains?.

So, which country has the best brains? I love the answer given by John Wilkins, "Surely not the one that cannot work out per capita rates of Nobel Prizes."

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2010 Nobel Prize in Physiology or Medicine

 
The 2010 Nobel Prize in Physiology or Medicine was given to Robert G. Edwards "for the development of in vitro fertilization". They should have added "in humans."

This is a technological achievement, one that was based on years of work with other animals.

I do not favor awarding Nobel Prizes for technology. I prefer to give the science prizes to those who have advanced our fundamental understanding of the universe. This prize is for medicine, which is technology, so it doesn't violate any rules. But in the past the prize in Physiology or Medicine has usually been for basic research.

It worries me that there may have been non-scientific motives behind this year's selection. We saw a horrid example of that last year when the Nobel Peace Prize was announced and I hope this isn't a trend.

Here's an example of how the award is being treated in the press [British IVF pioneer Robert Edwards gets Nobel Prize].

As well as leading to a host of new treatments for infertility, the work also founded the principles behind stem cell research, cloning and techniques that would allow couples to prevent passing on inheritable diseases to their children.

Christer Höög, professor of molecular biology at the Karolinska Institute in Stockholm, and a member of the Nobel Prize Committee, said the birth represented a "paradigm shift"

"It showed for the first time that it is possible to treat infertility," he said.

Prof Edwards' work was highly controversial at the time and there was strong opposition to what was seen as 'playing God' and the research had to be privately funded.

The good news is that the Vatican is really, really, pissed! [Vatican official criticises Nobel win for IVF pioneer]. I think it's because the Roman Catholic Church is pro-life.

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Vegetarian Nobel Laureates

I'm sure you've all been dying to know how many Nobel Laureates were vegetarians. Well, here's the answer. It was was on the back of a flyer received by one of the Skepchicks [An Appeal to Chickens and Other Logical Fallacies]. She's asking you to review the front part of the flyer to see how many logical fallacies you can identify.

It's interesting that only one Nobel Laureate won the Noble Prize for Physiology or Medicine. I guess the "logic" behind being a vegetarian isn't as obvious to biologists as it is to writers of fiction.

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Nobel Laureate: Johannes Fibiger

 

The Nobel Prize in Physiology or Medicine 1926

"for his discovery of the Spiroptera carcinoma"

Johannes Andreas Grib Fibiger (1867 - 1928) won the Nobel Prize for "proving" that gastric tumors could be caused by a nematode, Spiroptera carcinoma (now called Gongylonema neoplasticum). Unfortunately, later work showed that the nematode was not the cause of cancer, although it may contribute to a worsening of the symptoms.

This is one of the worst mistakes that the Nobel Prize committee has ever made in awarding a science prize. How did it happen?

Fiberger is rightly celebrated for his many important contributions to experimental medicine and for pioneering a modern version of clinical trials. When he learned of the work of Katsusaburo Yamagiwa, who induced cancer in rabbits by treating their skin with coal tar, he promoted Yamagiwa's results in Europe. Many people believe that Yamagiwa should have received the Nobel Prize.

Here is the entire Presentation Speech. The work sounds like something that deserves a Nobel Prize, doesn't it?
THEME:
Nobel Laureates

Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

Few diseases have the power of inspiring fear to the same degree as cancer. However, who would be surprised at that? How many times is this affliction not synonymous with a long, painful and grievous illness, how many times is it not equivalent to incurable suffering? It is therefore natural that we should strive to throw light upon its nature; but the road to this discovery is both long and difficult. Cancer always, in fact, presents the investigator with a number of obscure and unsolved problems. Thus the cause of cancer has for a long time baffled the penetrating studies of the most tireless research workers. Fibiger was the first of these to succeed in lifting with a sure hand a corner of the veil which hid from us the etiology of the disease; the first also, to enable us to replace with precise and demonstrable theories the hypotheses with which we had had to content ourselves.

For example, it had been thought for a long time that a causal connection existed between cancer and a prolonged irritation of some sort, mechanical, thermal, chemical, radiant, etc.; this supposition was supported by the incidence, sometimes verified, of cancer as an occupational disease. Cancer occurring in radiologists, chimney sweepers, workers in the manufacture of chemical products, establish so many examples of cancerous infection that one might believe they were provoked by radioactive or chemical irritation. However, each time experiment was resorted to in an attempt to provoke cancer in animals by irritants of this nature, it failed, and the animals refused to contract the disease.

Others, with all the more reason, sought to find in cancer the work of microparasites, for true neoplastic epizootics were thought sometimes to have been established in the animal world. But research into the pathogenic agent, the «cancer bacillus», and the experiments attempting to inoculate the disease had remained fruitless. Cancer has been equally attributed to other parasites, and notably to the worm. But, just as the attempts to provoke cancer, whether by inoculation or by irritation remained unproductive, in the same way it proved impossible to demonstrate experimentally that the disease was attributable to worms. These authorities who continued to support this thesis were, moreover, frequently considered to be fantasts. Because of the failure of attempts to establish, by experiment, the accuracy of any theory, there was no clear idea concerning the cause of cancer, and such in general was the position of this question. Then it was, in 1913, that Fibiger discovered that cancer could be produced experimentally.

It is of the greatest interest to follow Fibiger along the laborious path of his research. The first idea of his discovery, which was to make his name celebrated the world over came to him in 1907: he recorded in three mice in his laboratory (originating from Dorpat), a tumour, unknown until that time in the stomach; in the centre of the neoplasm he noted the presence of a worm belonging to the family of Spiroptera.

Fibiger did not succeed at first in proving a relationship existing between the formation of the neoplasm and the worm. The attempts to provoke a cancer in healthy mice by making them ingest neoplastic tissue from diseased mice, and containing worms or eggs, failed completely. Fibiger then had the idea that perhaps this worm, like many others, underwent part of its evolution from an egg to an adult individual in another animal, which served as an intermediate host. After numerous and vain attempts to find again mice attacked by the tumours seen in 1907 - he unsuccessfully examined more than 1000 animals - Fibiger eventually discovered in a sugar refinery in Copenhagen mice who exhibited in considerable numbers the type of tumour he was seeking; in these tumours he found once again the worm he had observed in 1907. The factory was at this time infested with cockroaches, and Fibiger was then able to establish that the worm in its evolution used these cockroaches as intermediate hosts. The cockroaches ingested the excreta of the mice, and with them the eggs of the worm. These developed in the alimentary tract of the cockroaches into larvae, which, like the trichina, were distributed into the muscles of the insects where they become encapsulated. The cockroaches were in their turn eaten by the mice and in the stomach the larvae transformed into the adult form.

By feeding healthy mice with cockroaches containing the larvae of the spiroptera, Fibiger succeeded in producing cancerous growths in the stomachs of a large number of animals. It was therefore possible, for the first time, to change by experiment normal cells into cells having all the terrible properties of cancer. It was thus shown authoritatively not that cancer is always caused by a worm, but that it can be provoked by an external stimulus. For this reason alone the discovery was of incalculable importance.

But Fibiger's discovery had a still greater significance. The possibility of experimentally producing cancer gave to the particular research into this illness an invaluable and badly needed method, lacking until this time, allowing the elucidation of some of the obscure points in the problem of cancer. Fibiger's discovery also gave remarkable impetus to research. Whereas research had, in many respects, entered upon a period of stagnation, Fibiger's discovery marked the beginning of a new era, of a new epoch in the history of cancer, to which the fruitful research made by him gave fresh vigour. From his discoveries we have continued to march forward and have gained valuable ideas as to the nature of this illness.

It is thus that Fibiger has been and will remain a pioneer in the difficult field of cancer research. «To my mind», says the famous English expert on cancer, Archibald Leitch, to name only one of the numerous critical commentators on Fibiger's research, «Fibiger's work has been the greatest contribution to experimental medicine in our generation. He has built into the growing structure of truth something outstanding, something immortal, quod non imber edax possit diruere.» It is for this immortal research work that Fibiger is today awarded the Nobel Prize for Medicine for 1926.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Nobel Laureate: Lee Hartwell

 

The Nobel Prize in Physiology or Medicine 2001

"for their discoveries of key regulators of the cell cycle"

Leland H. Hartwell (1939 - ) won the Nobel Prize for his contributions to understanding the cell cycle. His discovery of the regulatory molecule CDC28 led to the idea of "checkpoints"—steps in the cell cycle where specific action is needed to progress to the next stage.

Hartwell shared the 2001 Nobel Prize with Paul Nurse and Tim Hunt.

Some of you may think that elucidation of the cell cycle in yeast isn't such a big deal. You would be wrong. No only did this work stimulate a huge field of study in yeast, but the genes and the pathways uncovered in yeast are similar to those in other eukaryotic cells. This is a case where fundamental basic science has lead to a deep understanding of how life works at the molecular level.

THEME:
Nobel LaureatesI already posted the press release under Nobel Laureate: Sir Paul Nurse. It's a very good description of the work that was done by all three Nobel Laureates.

Here's an excerpt from the Presentation Speech.

This year's Nobel Laureates have discovered the key regulators of the cell cycle, cyclin dependent kinase (CDK) and cyclin. Together these two components form an enzyme, in which CDK is comparable to a "molecular engine" that drives the cell through the cell cycle by altering the structure and function of other proteins in the cell. Cyclin is the main switch that turns the "CDK engine" on and off. This cell cycle engine operates in the same way in such widely disparate organisms as yeast cells, plants, animals and humans.

How were the key regulators CDK and cyclin discovered?

Lee Hartwell realized the great potential of genetic methods for cell cycle studies. He chose baker's yeast as a model organism. In the microscope he could identify genetically altered cells - mutated cells - that stopped in the cell cycle when they were cultured at an elevated temperature. Using this method Hartwell discovered, in the early 1970s, dozens of genes specific to the cell division cycle, which he named CDC genes. One of these genes, CDC28, controls the initiation of each cell cycle, the "start" function. Hartwell also formulated the concept of "checkpoints," which ensure that cell cycle events occur in the correct order. Checkpoints are comparable to the program in a washing machine that checks if one step has been properly completed before the next can start. Checkpoint defects are considered to be one of the reasons behind the transformation of normal cells into cancer cells.

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[Photo Credit: Susie Fitzhugh and the Fred Hutchinson Cancer Research Center]

The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Nobel Laureates: Archer Martin and Richard Synge

 

The Nobel Prize in Chemistry 1952.

"for their invention of partition chromatography"




Archer John Porter Martin (1910 - 2002) and Richard Laurence Millington Synge (1914 - 1994) won the Nobel Prize in Chemistry for their work on separating substances by partition chromatography.

The technique they developed was called paper chromatography but today there are many other, more effective, versions of partition chromatography. The example shown below is from Monday's Molecule #134 and it's taken from an article on paper chromatography.

In this example, a soluble extract of pigments from plant leaves is spotted at the bottom of a piece of paper and the end with the sample is placed in a suitable solvent such as a mixture of acetone and ether. The solvent rises up the paper by capillary action taking the dissolved pigments with it. The trick is to choose a solvent mixture where the pigments (or other compounds) are differentially soluble so they migrate at different rates and separate on the paper.

The theory behind partition chromatography is complex. It used to be part of graduate courses in biochemistry.

I still remember taking Chemistry 542 back in 1969 and learning about Craig's ideas of counter-current distribution. We even covered the Martin & Synge 1941 paper in the Biochemical Journal (Biochem J. 35:1358). I still have my notes.

And I still get anxious whenever I hear the words "theoretical plates."

Martin & Synge, and others, developed techniques for separating amino acids and this was the basis of the sequencing technology employed by Fred Sanger for determining the amino acid sequence of insulin.

Back in 1952 it must have seemed unusual to be awarding a Nobel prize for chromatography. That's why the first part of the Presentation Speech explains why the discovery is important.

THEME:
Nobel Laureates

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen.

This year's Nobel Prize in Chemistry is awarded for the discovery of a method for the separation of substances from complicated mixtures.

How can it happen, one may ask, that something apparently so commonplace as a separation method should be rewarded by a Nobel Prize? The answer is that from the very beginnings of chemistry until our own time, methods for separating substances have occupied a key position in this science. Even today, in Holland, chemistry is called "Scheikunde", or "the art of separation", and even today some of chemistry's most important advances are linked to the invention of new methods for separating various substances.

Chemistry today is to a large extent concentrated upon the study of natural products, which are obtained from animals, plants, or even bacteria and other microorganisms. A starting material of this type contains a great number of widely varied substances, some simple, others more complicated. The first thing the chemist must do is to isolate the substances he is interested in from the material and prepare them in a pure state. The next step is, if possible, to identify these substances and find out what they consist of and how they are built up from simple constituents.

The first problem, the isolation, can indeed be difficult, as it is often a matter of preparing in a pure state substances which constitute only an extremely small fraction of the starting material and which have the disagreeable tendency of, so to speak, disappearing between one's fingers when one tries to get hold of them. It is here that Martin and Synge's method has enjoyed great success, especially in what is perhaps its most important form, and is called filter-paper chromatography.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Nobel Laureates: Erwin Neher and Bert Sakmann

 

The Nobel Prize in Physiology or Medicine 1991

"for their discoveries concerning the function of single ion channels in cells"

Erwin Neher (1944 - ) and Bert Sakmann (1942 - ) won the Nobel Prize for developing a technique to measure the voltage changes produced by single ion channels in cell membranes.

This is a remarkable achievement. The ion channel is in it's natural environment and the voltage change it produces is minuscule. The technique, called the "patch clamp", could not have been discovered without sensitive instruments developed in other disciplines.

1991 is part of the modern era on the Nobel Prize website so there's an excellent press release available to explain the award and describe the science. Here's the Press Release.
THEME:
Nobel Laureates

Summary

Each living cell is surrounded by a membrane which separates the world within the cell from its exterior. In this membrane there are channels, through which the cell communicates with its surroundings. These channels consist of single molecules or complexes of molecules and have the ability to allow passage of charged atoms, that is ions. The regulation of ion channels influences the life of the cell and its functions under normal and pathological conditions. The Nobel Prize in Physiology or Medicine for 1991 is awarded for the discoveries of the function of ion channels. The two German cell physiologists Erwin Neher and Bert Sakmann have together developed a technique that allows the registration of the incredibly small electrical currents (amounting to a picoampere - 10-12A) that passes through a single ion channel. The technique is unique in that it records how a single channel molecule alters its shape and in that way controls the flow of current within a time frame of a few millionths of a second.

Neher and Sakmann conclusively established with their technique that ion channels do exist and how they function. They have demonstrated what happens during the opening or closure of an ion channel with a diameter corresponding to that of a single sodium or chloride ion. Several ion channels are regulated by a receptor localized to one part of the channel molecule which upon activation alters its shape. Neher and Sakmann have shown which parts of the molecule that constitute the "sensor" and the interior wall of the channel. They also showed how the channel regulates the passage of positively or negatively charged ions. This new knowledge and this new analytical tool has during the past ten years revolutionized modern biology, facilitated research, and contributed to the understanding of the cellular mechanisms underlying several diseases, including diabetes and cystic fibrosis.

What Happens Inside the Cell?

Inside the cell membrane there is a well-defined environment, in which many complex biochemical processes take place. The interior of the cell differs in important respects from its outside. For example the contents of positive sodium and potassium ions and negatively charged chloride ions are quite different. This leads to a difference in electrical potential over the cell membrane, amounting to 0.03 to 0.1 volts. This is usually referred to as the membrane potential.

The cell uses the membrane potential in several ways. By rapidly opening channels for sodium ions the membrane potential is altered radically within a thousandth of a second. Cells in the nervous system communicate with each other by means of such electrical signals of around a tenth of a volt that rapidly travel along the nerve processes. When they reach the point of contact between two cells - the synapse - they induce the release of a transmitter substance. This substance affects receptors on the target cell, often by opening ion channels. The membrane potential is hereby altered so that the cell is stimulated or inhibited. The nervous system consists of a series of networks each comprised of nerve cells connected by synapses with different functions. New memory traces in the brain are for example created by altering the number of available ion channels in the synapses of a given network.

All cells function in a similar way. In fact, life itself begins with a change in membrane potential. As the sperm merges with the egg cell at the instant of fertilization ion channels are activated. The resultant change in membrane potential prevents the access of other sperm cells. All cells - for instance nerve cells, gland cells, and blood cells - have a characteristic set of ion channels that enable them to carry out their specific functions. The ion channels consist of single molecules or complexes of molecules, that forms the wall of the channel - or pore - that traverses the cell membrane and connects the exterior to the interior of the cell (Figure 1B and 1D). The diameter of the pore is so small that it corresponds to that of a single ion (0.5-0.6 millionths of a millimetre). An immediate change in the shape of the molecule leads to either an opening or a closure of the ion channel. This can occur upon activation of the receptor part of the molecule (Figure 1D) by a specific signal molecule. Alternatively a specific part of the molecule that senses changes in membrane potential can open or close the ion channel.

Figure 1. Registration of the flow of current through single ion channels using the recording technique of Neher and Sakmann. A schematically shows how a glass micropipette is brought in contact with the cell, and B, using a higher magnification, a part of the cell membrane, with ion channels, in close contact with the tip of the pipette. The interior of the pipette is connected to an electronic amplifier. C shows a channel in greater magnification with its receptor facing the exterior of the cell and its ion filter. D shows the current passing through the ion channel as it opens.

Neher and Sakmann Record the Electric Current Flowing Through a Single Ion Channel

It has long been known that there is a rapid ion exchange over the cell membrane, but Neher and Sakmann were the first to show that specific ion channels actually exist. To elucidate how an ion channel operates it is necessary to be able to record how the channel opens and closes. This appeared elusive since the ionic current through a single ion channel is extraordinarily small. In addition, the small ion channel molecules are embedded in the cell membrane. Neher and Sakmann succeeded in solving these difficulties. They developed a thin glass micropipette (a thousandths of a millimeter in diameter) as a recording electrode. When it is brought in contact with the cell membrane, it will form a tight seal with the periphery of the pipette orifice (Figure 1A, B). As a consequence the exchange of ions between the inside of the pipette and the outside can only occur through the ion channel in the membrane fragment (Figure 1B). When a single ion channel opens, ions will move through the channel as an electric current, since they are charged. Through a refinement of the electronic equipment and the experimental conditions they succeeded in measuring this "microscopical" current by laborious methodological developments during the seventies (Figure 1C).

How Does an Ion Channel Operate?

Ion channels are of different types. Some only permit the flow of positively charged sodium, potassium or calcium ions, others only negatively charged chloride ions. Neher and Sakmann discovered how this specificity is accomplished. One reason is the diameter of the ion channel, which is adapted to the diameter of a particular ion. In one class of ion channels, there are also two rings of positively or negatively charged amino acids. They form an ionic filter (see Figure 1D), which only permits ions with an opposite charge to pass through the filter. In particular Sakmann through a creative interaction with different molecular biologists elucidated how the different parts of the ion channel molecule(s) operate. Neher and Sakmann's scientific achievements have radically changed our views on the function of the cell and the contents of text books of cell biology. Their methods are now used by thousands of scientists all over the world.

The Study of Secretory Processes

Nerve cells, as well as hormone-producing cells and cells engaged in the host defence (like mast cells) secrete different agents. They are stored in vesicles enclosed by a membrane. When the cell is stimulated the vesicles move to the cell surface. The cell and vesicle membranes fuse and the agent is liberated. The mast cell secretes histamine and other agents that give rise to local inflammatory reactions. The cells of the adrenal medulla liberate the stress hormone adrenaline, and the beta cells in the pancreas insulin. Neher elucidated the secretory processes in these cell types through the development of a new technique which records the fusion of the vesicle(s) with the cell membrane. Neher realized that the electric properties of a cell would change if its surface area increased making it possible to record the actual secretory process. Through further developments of their sophisticated equipment the resolution finally permitted recording of each little vesicle fusing with the cell membrane.

Regulation of Ion Channel Function

Neher and Sakmann also used the electrode pipette to inject different agents into the cell, and they could thereby investigate the different steps in the secretory process within the cell itself (see above). In this way a number of cellular secretory mechanisms have been clarified such as the role of cyclic AMP (see Nobel Prize to Sutherland 1971) or calcium ions. For instance, we now have a better understanding of how the hormone levels in the blood are maintained at a certain level.

Also the basal mechanisms underlying the secretion of insulin have been identified. The level of blood glucose controls the level of glucose within the insulin-forming cell, which in turn regulates the level of the energy rich substance ATP. ATP acts directly on a particular type of ion channel which controls the electric membrane potential of the cell. The change of membrane potential then indirectly influences other ion channels, which permit calcium ions to pass into the cell. The calcium ions subsequently trigger the insulin secretion. In diabetes the insulin secretion is out of order. Certain drugs commonly used to stimulate insulin secretion in diabetes act directly on the ATP-controlled ion channels.

Many other diseases depend entirely, or partially, on a defect regulation of ion channels, and a number of drugs act directly on ion channels. Many pathological mechanisms have been clarified during the eighties through ion channel studies, for instance cystic fibrosis (cloride ion channels), epilepsy (sodium and potassium ion channels), several cardio-vascular diseases (calcium ion channels), and neuro-muscular disorders like Lambert-Eatons disease (calcium ion channels). With the help of the technique of Neher and Sakmann it is now possible to tailormake drugs, to achieve an optimal effect on particular ion channels of importance in a given disease. Drugs against anxiety act for instance on certain inhibitory ionic channels in the brain. Alcohol, nicotine and other poisons act on yet other sets of ion channels.

In summary, Neher and Sakmann's contributions have meant a revolution for the field of cell biology, for the understanding of different disease mechanisms, and opened a way to develop new and more specific drugs.

References

Alberts et al.: The Molecular Biology of the Cell. Garland Press, 1990, 2nd edition, pp. 156, 312-326, 1065-1084.

Grillner, S. I: N. Calder (ed.). Scientific Europe. Foundation Scientific Europe, 1990.

Grillner, S. & Hökfelt, T.: Svindlande snabb utveckling präglar neurovetenskapen. Läkartidningen 1990, 87, 2777-2786.

Rorsman, P. & Fredholm, B.B.: Jonkanaler - molekylär bakgrund till nervtransmission. Läkartidningen 1991, 88, 2868-2877.

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The images of the Nobel Prize medals are registered trademarks of the Nobel Foundation (© The Nobel Foundation). They are used here, with permission, for educational purposes only.

Shame on Norway!

 
The 2009 Nobel Peace Prize was announced today by Thorbjørn Jagland, Chairman of the Norwegian Nobel Committee. It goes to President Barack Obama, a man who has been President of the United States for about nine months and is currently conducting two simultaneous invasions and occupations of foreign nations.

The United States "peaceably" threatens both Iran and North Korea with possible military strikes if they do not stop developing a nuclear weapons program. The United States deploys the largest, most deadly, military force the world has ever seen and is in no hurry to reduce its size.

I think Obama is a wonderful choice for President of the USA. He is far, far, better than many others who have sought that office. However, it does not follow from that that he merits the Nobel Peace prize. He doesn't. The Norwegian Nobel Committee should be ashamed of themselves.

Here's the press release. The committee is confusing hope and hype with actual results. Let's hope the promise of a better world works out over the course of the next few years or we might look back on this award with shock and awe. At the very least, we should expect a serious reduction in the American nuclear weapons stockpile, right? And we should expect UN Nuclear inspection teams to be visiting the USA, Russia, France, Great Britain, China, India, Pakistan, and Israel.

Who's holding their breath?

The Nobel Peace Prize for 2009

The Norwegian Nobel Committee has decided that the Nobel Peace Prize for 2009 is to be awarded to President Barack Obama for his extraordinary efforts to strengthen international diplomacy and cooperation between peoples. The Committee has attached special importance to Obama's vision of and work for a world without nuclear weapons.

Obama has as President created a new climate in international politics. Multilateral diplomacy has regained a central position, with emphasis on the role that the United Nations and other international institutions can play. Dialogue and negotiations are preferred as instruments for resolving even the most difficult international conflicts. The vision of a world free from nuclear arms has powerfully stimulated disarmament and arms control negotiations. Thanks to Obama's initiative, the USA is now playing a more constructive role in meeting the great climatic challenges the world is confronting. Democracy and human rights are to be strengthened.

Only very rarely has a person to the same extent as Obama captured the world's attention and given its people hope for a better future. His diplomacy is founded in the concept that those who are to lead the world must do so on the basis of values and attitudes that are shared by the majority of the world's population.

For 108 years, the Norwegian Nobel Committee has sought to stimulate precisely that international policy and those attitudes for which Obama is now the world's leading spokesman. The Committee endorses Obama's appeal that "Now is the time for all of us to take our share of responsibility for a global response to global challenges.

What does the White House have to say? Surprisingly, Obama is being very candid.

"I am both surprised and deeply humbled," Obama said at the White House.

"I do not view it as a recognition of my own accomplishments. But rather as an affirmation of American leadership. ... I will accept this award as a call to action."

Obama said he did not feel he deserves "to be in the company" of past winners, but would continue to push a broad range of international objectives, including nuclear non-proliferation, a reversal of the global economic downturn, and a resolution of the Arab-Israeli conflict.

He acknowledged the ongoing U.S. conflicts in Iraq and Afghanistan, noting that he is the "commander in chief of a country that is responsible for ending" one war and confronting a dangerous adversary in another.

The Associated Press story seems to be typical of the responses from around the world [President Barack Obama wins Nobel Peace Prize]. I think this is going to make Obama's life more difficult, not easier. It may have the exact opposite effect to what well-meaning members of the prize committee expected. This will go down as one of the most controversial awards in recent memory.

Many observers were shocked by the unexpected choice so early in the Obama presidency, which began less than two weeks before the Feb. 1 nomination deadline and has yet to yield concrete achievements in peacemaking.

Some around the world objected to the choice of Obama, who still oversees wars in Iraq and Afghanistan and has launched deadly counter-terror strikes in Pakistan and Somalia.

Members of the Norwegian Nobel Committee said their choice could be seen as an early vote of confidence in Obama intended to build global support for his policies. They lauded the change in global mood wrought by Obama's calls for peace and cooperation, and praised his pledges to reduce the world stock of nuclear arms, ease American conflicts with Muslim nations and strengthen the U.S. role in combating climate change.

Aagot Valle, a lawmaker for the Socialist Left party who joined the committee this year, said she hoped the selection would be viewed as "support and a commitment for Obama."

"And I hope it will be an inspiration for all those that work with nuclear disarmament and disarmament," she told The Associated Press in a rare interview. Members of the Nobel peace committee usually speak only through its chairman.

The peace prize was created partly to encourage ongoing peace efforts but Obama's efforts are at far earlier stages than past winners'. The Nobel committee acknowledged that they may not bear fruit at all.

"He got the prize because he has been able to change the international climate," Nobel Committee chairman Thorbjoern Jagland said. "Some people say, and I understand it, isn't it premature? Too early? Well, I'd say then that it could be too late to respond three years from now. It is now that we have the opportunity to respond — all of us."

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2009 Nobel Prize in Chemistry

 
"for studies of the structure and function of the ribosome"

This one's not unexpected. Almost everyone knows that there should be a Nobel Prize for the ribosome [see Nobel Prize Predictions]. Problem is, Harry Noller was on most people's short list. He's been working on the problem since 1968 and has published more than 200 papers on ribosome structure and function. This is going to be a controversial decision.

Here's the press release.

Press Release

7 October 2009

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2009 jointly to

Venkatraman Ramakrishnan, MRC Laboratory of Molecular Biology, Cambridge,
United Kingdom

Thomas A. Steitz, Yale University, New Haven, CT, USA

Ada E. Yonath, Weizmann Institute of Science, Rehovot, Israel


"for studies of the structure and function of the ribosome"


The ribosome translates the DNA code into life

The Nobel Prize in Chemistry for 2009 awards studies of one of life's core processes: the ribosome's translation of DNA information into life. Ribosomes produce proteins, which in turn control the chemistry in all living organisms. As ribosomes are crucial to life, they are also a major target for new antibiotics.

This year's Nobel Prize in Chemistry awards Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for having showed what the ribosome looks like and how it functions at the atomic level. All three have used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome.

Inside every cell in all organisms, there are DNA molecules. They contain the blueprints for how a human being, a plant or a bacterium, looks and functions. But the DNA molecule is passive. If there was nothing else, there would be no life.

The blueprints become transformed into living matter through the work of ribosomes. Based upon the information in DNA, ribosomes make proteins: oxygen-transporting haemoglobin, antibodies of the immune system, hormones such as insulin, the collagen of the skin, or enzymes that break down sugar. There are tens of thousands of proteins in the body and they all have different forms and functions. They build and control life at the chemical level.

An understanding of the ribosome's innermost workings is important for a scientific understanding of life. This knowledge can be put to a practical and immediate use; many of today's antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive. This is why ribosomes are such an important target for new antibiotics.

This year's three Laureates have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering.

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IDiots and Telomeres

 
Today's Nobel Prize announcement has prompted the usual stupidity from the creationist crowd. They don't get things right very often but when they rush into print their track record is even worse. You'd think they would have learned by now.

Most, but not all, bacteria have circular chromosomes. This is undoubtedly the primitive condition of living cells—at least once life got underway.

The advantage of a circular chromosome is that it doesn't have any free ends. This is important for two reasons: (1) nucleases that chew up nucleic acids like to work on free ends so having a circular chromosome increases the stability of the chromosome, and (2) circular chromosomes avoid the problems with replicating the ends of DNA.

That last reason needs a little explanation. DNA replication is complicated because evolution has only produced one kind of polymerase enzyme—the kind that works exclusively in the 5′→3′ direction.¹ This creates a problem when replicating double-stranded DNA because the strands run in opposite directions.

The DNA replication complex (replisome) has evolved a solution to this problem as illustrated in the diagram. As replication proceeds from right to left, one of the strands is copied directly by a DNA polymerase molecule. This new strand is called the leading strand. The other strand is copied by a separate DNA polymerase molecule but it has to run backwards. That strand, the lagging strand, is made in short pieces that have to be stitched together. Every now and then a new lagging strand fragment (Okazaki fragment) is initiated using a special RNA primer.

This is not a very good design but it's the only thing that could evolve given that polymerases can only go in one direction. Most of us could have easily designed an better way of replicating DNA if we were in charge. While we were at it we could have designed nucleases that don't attack genes.

The DNA replication complex may be messy but it works. At least it works with circular DNA. When you have free ends there's a bit of a problem. Look at the diagram. You can see that when the replication fork reaches the end on the left, the leading strand will be complete. However, there will likely be a gap at the very end where the lagging strand didn't initiate a new Okazaki fragment. When the replisome dissociates this gap will persist.

As strands continue to be replicated over and over there will be a progressive shortening of the chromosome because of the inefficiency of the replication process.

There are several ways of handling this problem. Some bacteriophage with linear chromosomes form circles during replication in order to avoid shortening. In bacteria, there are two different mechanisms for dealing with the problem. Either the ends of the two strand are covalently joined, creating a hairpin, or a protein is covalently attached to the end of one strand [see Bacterial Chromosomes]. Either way is effective in preventing chromosome shortening during replication.

Eukaryotes have evolved a third mechanism. The ends of eukaryotic chromosomes have extensive repeat segments called telomeres. This works because the repeats can be shortened for many generations before the "business part" of the chromosome is affected. The repeats can also be extended from time to time by telomerase. This restores the parts that are lost during replication. The copying is crude, but effective. It uses an RNA template that's part of the telomerase.

The net effect is that telomeres protect the ends of eukaryotic chromosomes. This protection is due to the fact that cells have nucleases that can chew up DNA and because the DNA replication machinery has a built-in flaw that doesn't allow it to copy the very ends of double-stranded DNA. All in all you'd have to say that if this was designed then it must have been Rube Goldberg who built it!

This year's Nobel Prize in Physiology & Medicine was awarded to Elizabeth Blackburn, Carol Greider and Jack Szostak for their work on telomeres and telomerase.

Within hours, DLH posted an article n Uncommon Descent [DNA Preservation discovery wins Nobel prize].

Were one to design the encoded DNA “blueprint” of life, would not one incorporate ways to preserve that “blueprint”? The Nobel prize in medicine has just been awarded for discovery of features that look amazingly like design to preserve chromosomes ....

These telomeres can probably be shown to be essential to survival, and are likely to be irreducibly complex. If so, how can macro evolution explain the origin of this marvelous preservation feature that appears to be an Intelligent Design?

Chromosome ends need "protection" because the designer couldn't figure out how to have safe nucleases in a cell and couldn't figure out how to replicate the ends of double-stranded DNA molecules. Several different mechanisms have evolved for dealing with these problems. Telomeres are one solution.

The telomeric repeats evolved from internal repeat sequences. Telomerase is a reverse transcriptase and it likely evolved from a retrovirus-encoded reverse transcriptase. In Drosophila there are no telomers and there isn't a telomerase, Instead, the chromosome ends are protected by multiple copies of defective transposons.

The IDiots are going to have to look elsewhere for evidence of God.

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1. There are good reasons for this. They have to do with the acccuracy of DNA replication and proofreading, but that's a story for another posting.