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Showing posts with label Nobel Prize. Show all posts
Showing posts with label Nobel Prize. Show all posts

Tuesday, September 20, 2016

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


Friday, November 13, 2015

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.


Friday, November 06, 2015

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.

Wednesday, October 07, 2015

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.


Saturday, August 20, 2011

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.








Tuesday, November 23, 2010

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.


Tuesday, October 12, 2010

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."


Tuesday, October 05, 2010

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.


Wednesday, December 02, 2009

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.




Wednesday, November 11, 2009

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.


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.

Thursday, November 05, 2009

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 Laureates
I 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.


[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.

Tuesday, November 03, 2009

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.


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.

Wednesday, October 14, 2009

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.


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.

Friday, October 09, 2009

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."


Wednesday, October 07, 2009

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.


Monday, October 05, 2009

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.


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.

2009 Nobel Prize in Physiology or Medicine

 
The 2009 Nobel Prize in Physiology or Medicine goes to Elizabeth Blackburn, Carol Greider, and Jack Szostak "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase."

These scientists were on everyone's short list so there's no great surprise here.

Read all about it on the Nobel Prize website. Here's the press release.
Press Release

5 October 2009

The Nobel Assembly at Karolinska Institutet has today decided to award
The Nobel Prize in Physiology or Medicine 2009 jointly to

Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak

for the discovery of

"how chromosomes are protected by telomeres and the enzyme telomerase"

Summary

This year's Nobel Prize in Physiology or Medicine is awarded to three scientists who have solved a major problem in biology: how the chromosomes can be copied in a complete way during cell divisions and how they are protected against degradation. The Nobel Laureates have shown that the solution is to be found in the ends of the chromosomes – the telomeres – and in an enzyme that forms them – telomerase.

The long, thread-like DNA molecules that carry our genes are packed into chromosomes, the telomeres being the caps on their ends. Elizabeth Blackburn and Jack Szostak discovered that a unique DNA sequence in the telomeres protects the chromosomes from degradation. Carol Greider and Elizabeth Blackburn identified telomerase, the enzyme that makes telomere DNA. These discoveries explained how the ends of the chromosomes are protected by the telomeres and that they are built by telomerase.

If the telomeres are shortened, cells age. Conversely, if telomerase activity is high, telomere length is maintained, and cellular senescence is delayed. This is the case in cancer cells, which can be considered to have eternal life. Certain inherited diseases, in contrast, are characterized by a defective telomerase, resulting in damaged cells. The award of the Nobel Prize recognizes the discovery of a fundamental mechanism in the cell, a discovery that has stimulated the development of new therapeutic strategies.

The mysterious telomere

The chromosomes contain our genome in their DNA molecules. As early as the 1930s, Hermann Muller (Nobel Prize 1946) and Barbara McClintock (Nobel Prize 1983) had observed that the structures at the ends of the chromosomes, the so-called telomeres, seemed to prevent the chromosomes from attaching to each other. They suspected that the telomeres could have a protective role, but how they operate remained an enigma.

When scientists began to understand how genes are copied, in the 1950s, another problem presented itself. When a cell is about to divide, the DNA molecules, which contain the four bases that form the genetic code, are copied, base by base, by DNA polymerase enzymes. However, for one of the two DNA strands, a problem exists in that the very end of the strand cannot be copied. Therefore, the chromosomes should be shortened every time a cell divides – but in fact that is not usually the case

Both these problems were solved when this year's Nobel Laureates discovered how the telomere functions and found the enzyme that copies it.
Telomere DNA protects the chromosomes

In the early phase of her research career, Elizabeth Blackburn mapped DNA sequences. When studying the chromosomes of Tetrahymena, a unicellular ciliate organism, she identified a DNA sequence that was repeated several times at the ends of the chromosomes. The function of this sequence, CCCCAA, was unclear. At the same time, Jack Szostak had made the observation that a linear DNA molecule, a type of minichromosome, is rapidly degraded when introduced into yeast cells.

Blackburn presented her results at a conference in 1980. They caught Jack Szostak's interest and he and Blackburn decided to perform an experiment that would cross the boundaries between very distant species (Fig 2). From the DNA of Tetrahymena, Blackburn isolated the CCCCAA sequence. Szostak coupled it to the minichromosomes and put them back into yeast cells. The results, which were published in 1982, were striking – the telomere DNA sequence protected the minichromosomes from degradation. As telomere DNA from one organism, Tetrahymena, protected chromosomes in an entirely different one, yeast, this demonstrated the existence of a previously unrecognized fundamental mechanism. Later on, it became evident that telomere DNA with its characteristic sequence is present in most plants and animals, from amoeba to man.

An enzyme that builds telomeres

Carol Greider, then a graduate student, and her supervisor Blackburn started to investigate if the formation of telomere DNA could be due to an unknown enzyme. On Christmas Day, 1984, Greider discovered signs of enzymatic activity in a cell extract. Greider and Blackburn named the enzyme telomerase, purified it, and showed that it consists of RNA as well as protein (Fig 3). The RNA component turned out to contain the CCCCAA sequence. It serves as the template when the telomere is built, while the protein component is required for the construction work, i.e. the enzymatic activity. Telomerase extends telomere DNA, providing a platform that enables DNA polymerases to copy the entire length of the chromosome without missing the very end portion.

Telomeres delay ageing of the cell

Scientists now began to investigate what roles the telomere might play in the cell. Szostak's group identified yeast cells with mutations that led to a gradual shortening of the telomeres. Such cells grew poorly and eventually stopped dividing. Blackburn and her co-workers made mutations in the RNA of the telomerase and observed similar effects in Tetrahymena. In both cases, this led to premature cellular ageing – senescence. In contrast, functional telomeres instead prevent chromosomal damage and delay cellular senescence. Later on, Greider's group showed that the senescence of human cells is also delayed by telomerase. Research in this area has been intense and it is now known that the DNA sequence in the telomere attracts proteins that form a protective cap around the fragile ends of the DNA strands.

An important piece in the puzzle – human ageing, cancer, and stem cells

These discoveries had a major impact within the scientific community. Many scientists speculated that telomere shortening could be the reason for ageing, not only in the individual cells but also in the organism as a whole. But the ageing process has turned out to be complex and it is now thought to depend on several different factors, the telomere being one of them. Research in this area remains intense.

Most normal cells do not divide frequently, therefore their chromosomes are not at risk of shortening and they do not require high telomerase activity. In contrast, cancer cells have the ability to divide infinitely and yet preserve their telomeres. How do they escape cellular senescence? One explanation became apparent with the finding that cancer cells often have increased telomerase activity. It was therefore proposed that cancer might be treated by eradicating telomerase. Several studies are underway in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity.

Some inherited diseases are now known to be caused by telomerase defects, including certain forms of congenital aplastic anemia, in which insufficient cell divisions in the stem cells of the bone marrow lead to severe anemia. Certain inherited diseases of the skin and the lungs are also caused by telomerase defects.

In conclusion, the discoveries by Blackburn, Greider and Szostak have added a new dimension to our understanding of the cell, shed light on disease mechanisms, and stimulated the development of potential new therapies.

Elizabeth H. Blackburn has US and Australian citizenship. She was born in 1948 in Hobart, Tasmania, Australia. After undergraduate studies at the University of Melbourne, she received her PhD in 1975 from the University of Cambridge, England, and was a postdoctoral researcher at Yale University, New Haven, USA. She was on the faculty at the University of California, Berkeley, and since 1990 has been professor of biology and physiology at the University of California, San Francisco.

Carol W. Greider is a US citizen and was born in 1961 in San Diego, California, USA. She studied at the University of California in Santa Barbara and in Berkeley, where she obtained her PhD in 1987 with Blackburn as her supervisor. After postdoctoral research at Cold Spring Harbor Laboratory, she was appointed professor in the department of molecular biology and genetics at Johns Hopkins University School of Medicine in Baltimore in 1997.

Jack W. Szostak is a US citizen. He was born in 1952 in London, UK and grew up in Canada. He studied at McGill University in Montreal and at Cornell University in Ithaca, New York, where he received his PhD in 1977. He has been at Harvard Medical School since 1979 and is currently professor of genetics at Massachusetts General Hospital in Boston. He is also affiliated with the Howard Hughes Medical Institute.

References:

Szostak JW, Blackburn EH. Cloning yeast telomeres on linear plasmid vectors. Cell 1982; 29:245-255.
Greider CW, Blackburn EH. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 1985; 43:405-13.
Greider CW, Blackburn EH. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 1989; 337:331-7.


Thursday, October 01, 2009

Nobel Prize Predictions

 
My colleague, Alex Palazzo, has just posted his annual list of potential Nobel Prize winners in the biological sciences [Gaze into the crystal ball - Nobel Prize Predictions].

I'm hoping for Ernest McCulloch and James Till for their discovery of stem cells. My second choice would be Harry Noller and some combination of others for their work on ribosome structure and function.

Post your prediction on Alex's new blog Transcription and Translation.

If you have time, you might want to correct his misguided views about scientific facts [Science - Building Models, Not Facts].



Tuesday, September 22, 2009

Nobel Laureate: Ivan Pavlov

 

The Nobel Prize in Physiology or Medicine 1904

"in recognition of his work on the physiology of digestion, through which knowledge on vital aspects of the subject has been transformed and enlarged"

Ivan Petrovich Pavlov (1849 - 1936) (Иван Петрович Павлов) won the Noble Prize in 1904 for his contribution to understanding the physiology and biochemistry of digestion. Part of his contribution was the discovery that some of the digestion enzymes needed to be activated before they could work in the stomach [Monday's Molecule #133].

Pavlov is famous for his work with dogs. Most people know of his studies on conditioned reflexes where he was able to show that the mere anticipation of food caused dogs to salivate. He is famous as one of the founders of modern psychology but the Nobel Prize was for a different study where he examined the stomach secretions of dogs by redirecting secretory ducts to the exterior where the secretions could be collected and analyzed. Pavlov was actually more of a biochemist than a psychologist!

Pavlov had a large, well-equipped lab with many workers. In that sense he was much more of a professional scientist than many of the other biological scientists of the late nineteenth century. Pasteur was another example. Many others, like Charles Darwin, worked alone and didn't seek out students.

The knowledge gained from his studies on digestion had no practical application in medicine. They simply advanced our understanding of how our bodies work. In presenting the Nobel Prize the presenter, Count K.A.H. Mörner, took pains to make this point clear and to pronounce it a good thing. Science for the sake of knowledge.

One gets the impression that the audience at the award ceremonies needed to hear that.

Here's part of the Presentation Speech that describes Pavlov's contribution.

THEME:
Nobel Laureates
In the early days opinions on the course of digestion were speculations as to what was termed as «cooking» or «grinding» in the stomach etc. So long as the digestive processes could not be observed or investigated directly in the stomach no real knowledge could be obtained. An accident turned physiological research in this field in a direction which has later become very important. In the 1820's a young man sustained a gunshot wound in the stomach and developed a gastric fistula which to some extent permitted the gastric processes to be studied. Observations were carried out on this man by the American physician W. Beaumont. This accidental path of investigation, allowing actual observation of processes taking place in the digestive tract, was later followed by many workers using animals. Technique is an important factor in such experiments and has been perfected in a masterly way by Pavlov, whose animals remain in good health, without any injury to the function of their digestive tract, permitting observation and systematic investigation over an almost unlimited period.

These methods for the study of the physiology of digestion established by Pavlov have been taken up by various physiological institutions, but above all much important work was performed in his own laboratory. From this has followed a far-reaching transformation of our knowledge in this field which has also been enriched by new fundamental facts.

The following may be mentioned as an illustration.

The digestive canal can be influenced in various ways by the nervous system. When we remember that the nervous system can induce not only the secretory processes as well as the movements of various parts of the system, but also can bring such processes to a standstill, that it controls the blood supply to these organs and that sensory nerves arise from them, we can get an idea of the complexity one encounters. The complications become still greater when it is realised that we must take into account not only nervous pathways having their origin in the brain or the spinal cord, but also the sympathetic nervous system, and that we have further to pay attention to the interdependence between the different parts of the digestive system through the nerves, so that variations in the behaviour of one may affect that in other organs.

It is in the nature of things that cognition of the scope and character of the functional interdependence of the nervous system and the digestive organs is of great importance to the knowledge of the physiology of these organs. It is also clear that one can only hope that answers to these complicated questions will advance step by step by much research. In this respect Pavlov has acquired very great merit. He has revealed new points of view and has fruitfully stimulated the solution of these problems, and through his methods has made it possible to reach conclusive analysis of them.


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.

[Photo Credit: Pasteur [Hulton Archive/Getty Images]