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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.

Was Charles Darwin an Agnostic Atheist?

 
Let me say, right at the start, that I really don't care whether Charles Darwin was a deist, an agnostic, an atheist, or something else entirely. He died on April 19, 1882. That was a very long time ago. And the truth of evolution does not depend on what Darwin may or may not have believed about God.

Still, it's of some historical interest to learn what Darwin thought of religion. My own opinion is that these speculations are never going to be satisfactorily answered because Darwin was not always candid about his beliefs, for Emma's sake.

It may come as a bit of a surprise to find me favorably recommending an article on Uncommon Descent but this article by Flannery deserves your attention: Theist, Agnostic, Atheist: Will the Real Charles Darwin Please Stand Up?.

It's not going to make my agnostic friends happy but I think it's a pretty good analysis of Darwin's beliefs. I especially like the emphasis on the fact that his grandfather wasn't religious and his father (Robert) was an atheist. I'm pretty sure that his brother, Erasmus, was a nonbeliever as well. It strains credibility to imagine that Darwin was ever a religious man.


November 11, 2009

 
Today is Remembrance Day in Canada. It's a day to remember that war is evil and horrible. It's a day to remember that war represents the ultimate failure of a civilization.

War is not glorious. People who kill other people are not heroes. The people they kill are not heroes. We are shamed when we turn average citizens into murderers. We lament their deaths because it means we have failed in our responsibility to maintain peace. They paid the price of our failure.

Soldiers are a necessary evil, like prison guards. The long range goal of a humane society is to eliminate armies (and prisons). Once a year, on this day, we need to think about how far we are from achieving that goal and what we can do to make it a reality.

We need to remember our past—the dirty, ugly, face of death and destruction—and resolve never to repeat it. We need to apologize to those men and women we forced to endure those horrors. We need to promise our children that we won't make them go to war.

No war is necessary. Tanks, bombers, and battleships are not necessary. I dream of an eleventh day of the eleventh month when, at the eleventh hour, no cannons are fired, no soldiers are marching, and no fighter planes are flying overhead. That will be a day to remember.

The greatest generation will be the one that avoids war. Perhaps our children's children will be that generation.


[Photo: Dresden, February 14, 1945]

[Poster by Lorraine Schneider (1925-1972), for the Los Angeles organization Another Mother for Peace, 1967.]

Tuesday, November 10, 2009

The Positive Argument for Intelligent Design Creationism

 
I've often been critical of the arguments made by IDiots Intelligent Design Creationists. They consist mostly of claims that evolution can't happen.

It's only fair that I point you to a rebuttal of this point of view by none other than Casey Luskin [Misrepresenting the Definition of Intelligent Design].
Scott Minnich and Stephen Meyer also explain the positive argument for design:
Molecular machines display a key signature or hallmark of design, namely, irreducible complexity. In all irreducibly complex systems in which the cause of the system is known by experience or observation, intelligent design or engineering played a role the origin of the system … in any other context we would immediately recognize such systems as the product of very intelligent engineering. Although some may argue this is a merely an argument from ignorance, we regard it as an inference to the best explanation, given what we know about the powers of intelligent as opposed to strictly natural or material causes. (“Genetic analysis of coordinate flagellar and type III regulatory circuits in pathogenic Bacteria,” in Proceedings of the Second International Conference on Design & Nature, Rhodes Greece (2004).)
Let's see if I've got this right. We know about lots of irreducibly complex systems, such as the Krebs cycle and the bacterial flagella, that could easily have arisen by evolution. Nevertheless, according to the IDiots, we have to conclude that all such systems can only have been created by God.

That's what passes for a positive argument for Intelligent Design Creationism. I assume it's the best they've got.


Monday's Molecule #143: Winner

 
The creature is a nematode, specifically a Soybean cyst nematode. The relevant Nobel Prize was to Johannes Fibiger who got for it "discovering" that the nematode Spiroptera carcinoma causes cancer. This species is now called Gongylonema neoplasticum and it doesn't cause cancer. Oops!

The first person to get it right was Linda Zhang, a former student at the University of Toronto who will soon be on her way to graduate school at the University of Hong Kong. The undergraduate winner is Kirill Zaslavsky, a Neuroscience student at the University of Toronto.

Many others got the right answer. It was easier than I thought it would be.



Sometimes it's almost impossible to find an image of a specific molecule that honors a Nobel Laureate. This is another one of those times.

This spectacular photograph shows a particular kind of creature and its egg. You need to identify the phylum to which this species belongs and then use that as a clue to come up with an appropriate Nobel Laureate. Your answer should include the particular species that is associated with the Nobel Prize as well as the Nobel Laureate. Be careful, I want the modern name of the species—not the old name that was used when the Nobel Prize was announced.

Here's a clue. The Nobel Prize was awarded in the last century, not the current one. Here's another clue, outside of the Nobel Peace prize and the mini-Nobel Prize in Economics, this award is probably the biggest mistake that the prize committee has ever made.

The first person to identify the molecule and name the Nobel Laureate(s) wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are six ineligible candidates for this week's reward: Joshua Johnson of Victoria University in Australia, Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany, Jason Oakley a biochemistry student at the University of Toronto, Dima Klenchin of the University of Wisconsin, Madison, Alex Ling of the University of Toronto, and Bill Chaney of the University of Nebraska.

Joshua, Dima, and Bill have all agreed to donate their free lunch to an undergraduate. Consequently, I have three extra free lunches for deserving undergraduates. I'm going to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch. If you can't make it for lunch then please consider donating it to someone who can in the next round.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

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


[Photo Credit: Wikipedia]

PZ Myers Gets It Wrong

 
Discover magazine sponsored a contest where you had to produce a two minute video explaining evolution. The judge was PZ Myers. Here's how PZ explains his choice [see The Winner: Evolution in Two Minutes].



Oh dear. Repeat after me, PZ, evolution is not natural selection!

This is, indeed, the 21st century, and not the Victorian England of Charles Darwin. We now know that evolution is any change in the frequency of alleles in a population. We know that for evolution to occur the change has to be genetic. We know that populations evolve, not individuals. We know that there are two main mechanisms of evolution: natural selection, and random genetic drift. It's a good idea to mention that variation within a species (population) arises from spontaneous mutations that create gene variants called alleles. That's what needs to be explained in two minutes.

Here's the winning video from Scott Hatfield, a high school biology teacher, and, more importantly, a blogger at Monkey Trials. Scott's a cool guy but it's not the video I would have chosen.



2009 AAAS Kavli Science Journalism Awards

 
The American Association for the Advancement of Science has just announced the Kavli Science Journalism Awards for 2009. It's a very interesting group of winners. Among them is Carl Zimmer, who won in the category "Large Newspaper—Circulation of 100,000 or more."

Awards are nice, but the problem with science journalism awards is that they are decided by a panel of science journalists. What this means is that the awards are for good journalism and not necessarily for good science. As most Sandwalk readers know, I'm not happy with the way science is presented to the general public and my main complaint about science writers is that they don't do a very good job of getting the science right. (Many scientists aren't much better, but that's a different issue.)

If we are going to award good science journalism, don't you think that one of the main criteria should be whether the reporting is scientifically accurate? If you accept that premise, then the next question is who should make that call.

Take Carl Zimmer's articles for example. One of them was Now: The Rest of the Genome published in The New York Times in November 2008. This is an article about genes and genomes and the main point is that our concept of a gene is in trouble in light of recent discoveries in genomics.

Carl's article is better than most but it still misrepresents the modern status of a gene and the importance of phenomena like alternative splicing and epigenetics [Genes and Straw Men]. There's no doubt in my mind that Carl is the best of the science writers who could have written about this subject but I'm still troubled by the fact that the prize committee was probably incapable of evaluating the accuracy of the science in his article.

The award is sponsored by AAAS. What would be wrong with having a few scientists as judges?

From the press release ...
"The AAAS awards have long recognized the importance of high-quality science journalism across the board," said Cristine Russell, president of the nonprofit Council for the Advancement of Science Writing. "The Kavli Foundation’s decision to endow the awards is particularly important at a time when accurate, insightful writing about science is threatened by rapid changes in the media marketplace. The future of this program is now assured as a new generation of journalists tackles important science developments and their impact on society.
I don't know Cristine Russel but she's promoting these awards as examples of "accurate, insightful writing about science." I'd love to know who determines whether the reporting is accurate. How does she know they were scientifically accurate?


Boycott Science.org

 
We all get spam in our mail box and usually there's nothing you can do about it. This time there is. I got this message today.
Subject: Award Acknowledgment for sharing great PHYSICS information to the public

Dear Blog Owner,

Our website Science.org is a informational databases and online news publication for anything and everything related to science and technology. We recently ran a poll asking our website users regarding what online informational resources they use to keep up to date or even to simply find great information. It seems many of our users have labeled your blog as an excellent source of Space information. We have reviewed your blog and must say, we absolutely love the information you have made available to the public and would love to make your blog a part of our top science blogs. After browsing your blog, our research team has decided to award you a Top science Blogs award banner.

It is a distinction we offer to the blogs that our team feels is ahead of the curve in terms of content.

Thanks again for the great information and we look forward to the great responses your blog will receive from our site. Your blog presence will be very effective for our users (top science blogs).

We have put great efforts in making this decision to give deserving with award acknowledgment. For listing please reply to request banner.

Sincerely,
--
William Lee
Research team
Science.org
1 international blvd
Mahwah NJ USA - 07430
201 247 8553
editor.science@gmx.com
It turns out that Science.org is an actual website. Mr. Lee apparently believes that by lying to Blog Owners he can enhance the reputation of his website.

That ain't gonna work. Any website that emails such lies does not even deserve a link.



The Wreck of the Edmund Fitzgerald

 
Twenty-nine men died on November 10, 1975 when the S.S. Edmund Fitgerald sank in a storm on Lake Superior.




Monday, November 09, 2009

Amazon's Top Ten Science Books for 2009

 
Check out the Best of 2009 for two lists of the top ten science books. One list was chosen by "editors" and the other list was chosen by "readers."

There are some interesting differences ... and it's not what you expect.


[Hat Tip: Jason Rosenhouse whose book The Monty Hall Problem: The Remarkable Story of Math's Most Contentious Brainteaser made one of the lists.

Monday's Molecule #143

 
Sometimes it's almost impossible to find an image of a specific molecule that honors a Nobel Laureate. This is another one of those times.

This spectacular photograph shows a particular kind of creature and its egg. You need to identify the phylum to which this species belongs and then use that as a clue to come up with an appropriate Nobel Laureate. Your answer should include the particular species that is associated with the Nobel Prize as well as the Nobel Laureate. Be careful, I want the modern name of the species—not the old name that was used when the Nobel Prize was announced.

Here's a clue. The Nobel Prize was awarded in the last century, not the current one. Here's another clue, outside of the Nobel Peace prize and the mini-Nobel Prize in Economics, this award is probably the biggest mistake that the prize committee has ever made.

The first person to identify the molecule and name the Nobel Laureate(s) wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are six ineligible candidates for this week's reward: Joshua Johnson of Victoria University in Australia, Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany, Jason Oakley a biochemistry student at the University of Toronto, Dima Klenchin of the University of Wisconsin, Madison, Alex Ling of the University of Toronto, and Bill Chaney of the University of Nebraska.

Joshua, Dima, and Bill have all agreed to donate their free lunch to an undergraduate. Consequently, I have three extra free lunches for deserving undergraduates. I'm going to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch. If you can't make it for lunch then please consider donating it to someone who can in the next round.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

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


[Photo Credit: Wikipedia]

Friday, November 06, 2009

Ginkgo biloba

 
Ginko biloba is the only living species in the division (phylum?) Ginkgophyta. It is a species of deciduous tree that's only distantly related to to the other trees that we see around us. Some taxonomists classify it as a gymnosperm but that's not a universally recognized classification. It's certainly not an angiosperm (flowering plant).

Ginkgo is often called a "living fossil" because it resembles plants that date from 270 million years ago. The term is misleading because, like other "living fossils" Ginko biloba has evolved considerably since the time of its similar-looking ancestors.

The trees are either male or female. I recently visited a beautiful example of a female tree growing in the yard of Frank Lloyd Wright's house in Oak Park in the suburb's of Chicago. The tree was full of "berries" (technically not fruit), which were about to drop. I'm told that the berries are edible but not very pleasant. They smell like human feces. (The pun is obvious ... don't bother. )

I wish I'd been there a bit later 'cause ever since I learned about Ginkgo I've wanted to taste the berries.

All of the trees in North America have been deliberately planted by gardeners. The one in the yard of the Frank Lloyd Wright house was already there when Wright bought the property in 1889. It's estimated to be about 160 years old. They don't grow very well in most parts of Canada.

I was under the impression that the tree is native to some parts of China but recent genotyping of the trees suggests that even those trees may have been deliberately planted there by ancient monks.



Thursday, November 05, 2009

Charles and Camilla Are in Town

 
Charles and Camilla are visiting Toronto but you wouldn't know it if you didn't read the papers. Unless, of course, you just happen to be caught up in one of the mini traffic jams that are associated with such visits.

I witnessed one last night as several motorcycles and police cars with red and blue lights flashing, and sirens wailing, raced up University Avenue and around Queen's Park. They were escorting a convoy of half a dozen limos. I figure they were exceeding the speed limit by quite a bit.

Today, Charles is accompanying Camilla to Dundurn castle in Hamilton. The great house was built by Sir Allan Napier MacNab who happens to be Camilla's great-great-great grandfather. MacNab was Prime Minister of the Province of Ontario and was a member of the ruling elite that William Lyon Mackenzie opposed in the 1837 "rebellion."

This is Camilla's first visit to Canada. Charles has been here too often.

The couple will be opening the Royal Agricultural Winter's Fair before flying back to England.

For those of you interested in genealogy, here's how Camilla is related to MacNab.

Allen Napier MacNab (1798-1862)
m. Mary Stuart (1812-1846)
      Sophia Mary MacNab (1832-1917)
      m. William Coutts Keppel (1832-1894)
            Honourable George Keppel (1865-1947)
            m. Alice Frederica Edmonstone (1869-1947)
                  Sonia Rosemary Keppel (1900-1986)
                  m. Roland Calvert Cubbitt (1899-1962)
                        Honourable Rosalind Maud Cubbitt (1921-1994)
                        m. Bruce Middleton Hope Shand (1917- )
                              Camilla Rosemary Shand (1947- )
                              m. (1) Andrew Henry Parker-Bowles
                                    (2) Charles, Prince of Wales



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.

"Dr." Charlene Werner on Homeopathy

 
This video illustrates the extreme stupidity of those who believe in homeopathy.

The person who posted the video on YouTube recently received the following letter.
I thought you would like to know that you will be contacted by Dr Werner's Attorney shortly regarding her video. The posting of this video is in violation of copyright laws. We are aware that you have had this video up since March of '08 however I suggest you delete it immediately.

Jayson Patrick
This immediately triggers the Streisand Effect. Won't these people ever learn? No, of course not, that's because they are stupid.

Watch if you dare.





Tuesday, November 03, 2009

Monday's Molecule #142: Winner

 
The diagram should remind you of the cell cycle and the 2001 Nobel Prize in Physiology and Medicine. Since I already covered Tim Hunt and Paul Nurse, this must be about Lee Hartwell. That means the molecule must be "start" or CDC28.

The winner is Bill Chaney of the University of Nebraska. He has agreed to donate his free lunch to an undergraduate. Unfortunately, there weren't any undergraduate who got the right answer this week so I still have three free lunches to give away.




Sometimes it's almost impossible to find an image of a specific molecule that honors a Nobel Laureate. This is one of those times.

The diagram provides all the clues necessary to identify an important process and then to identify a particular molecule associated with this week's Nobel Laureate.

You must name the molecule and the Nobel Laureate. Be careful 'cause it's easy to make a mistake and name someone who has already been the subject of a Monday's Molecule.

The first person to identify the molecule and name the Nobel Laureate(s) wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only six ineligible candidates for this week's reward: Frank Schmidt of the University of Missouri, Joshua Johnson of Victoria University in Australia, Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany, Jason Oakley a biochemistry student at the University of Toronto, Dima Klenchin of the University of Wisconsin, Madison and Alex Ling of the University of Toronto.

Joshua and Dima have agreed to donate their free lunch to an undergraduate. Consequently, I have two extra free lunches for deserving undergraduates so I'm going to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch. If you can't make it for lunch then please consider donating it to someone who can in the next round.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

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



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.

Monday, November 02, 2009

Monday's Molecule #142

 
Sometimes it's almost impossible to find an image of a specific molecule that honors a Nobel Laureate. This is one of those times.

The diagram provides all the clues necessary to identify an important process and then to identify a particular molecule associated with this week's Nobel Laureate.

You must name the molecule and the Nobel Laureate. Be careful 'cause it's easy to make a mistake and name someone who has already been the subject of a Monday's Molecule.

The first person to identify the molecule and name the Nobel Laureate(s) wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only six ineligible candidates for this week's reward: Frank Schmidt of the University of Missouri, Joshua Johnson of Victoria University in Australia, Markus-Frederik Bohn of the Lehrstuhl für Biotechnik in Erlangen, Germany, Jason Oakley a biochemistry student at the University of Toronto, Dima Klenchin of the University of Wisconsin, Madison and Alex Ling of the University of Toronto.

Joshua and Dima have agreed to donate their free lunch to an undergraduate. Consequently, I have two extra free lunches for deserving undergraduates so I'm going to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch. If you can't make it for lunch then please consider donating it to someone who can in the next round.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

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


A Confused Philosopher (Part II)

I've written a lot about Michael Ruse over the past few years. Mostly I'm upset by his lack of understanding of modern evolutionary theory [A Confused Philosopher, Down with Darwinism!, Darwinism at the ROM].

I'm also annoyed at the accommodationist position that Ruse takes from time to time and his support for the Courtier's Reply. He's one of those people who think that there are very sophisticated arguments for the existence of God—arguments that most atheists can't refute.

Ruse's latest foray into this philosophical mine field was just published in The Guardian: Dawkins et al bring us into disrepute.

It's a pile of crap but Jerry Coyne [Ruse gibbers on. . . .] and PZ Myers [Schisms, rifts, and apologia for insanity] have already proven that beyond a shadow of a doubt.

Ruse moved from the University of Guelph to a university in Florida so he could avoid mandatory retirement. Perhaps he should consider voluntary retirement?


[Image Credit: The photo is from Paul Nelson on the Intelligent Design website. It refers to Ruse's idea that evolution is a form of religion.]

Charles Darwin's Brave New World: A Dangerous Idea

 
I watched the first part last night on The Nature of Things with David Suzuki. It was pretty good, although the emphasis on how Darwin was afraid to discuss his ideas got a bit tedious.

I'm also skeptical about the film's claim that evolution caused Darwin to abandon religion. It's worth remembering that his father (Robert) and his grandfather (Erasmus) were well-known skeptics about religion and Darwin's brother, Erasmus, was not religious. Darwin hung out with a lot of people who were questioning religion even though they knew nothing about evolution.




Sunday, November 01, 2009

Falling Back

 
Last night was the night we turned our clocks back one hour in Canada and the USA. It's easy to remember whether we lose an hour or gain an hour because even school children learn the phrase "Spring forward, Fall back." ("Fall" is the local jargon for "Autumn.")

For most people, this concept of adjusting your clocks twice a year is terribly confusing. Do you understand it?

Here's a short quiz to test your knowledge of time.

What do Australians do at this time of the year?
  1. turn their clocks back one hour
  2. turn their clocks forward one hour
  3. don't adjust their clocks
  4. who cares what happens in Vienna?

What is the astronomical reason for turning our clocks back one hour?
  1. there is no astronomical reason for adjusting our clocks
  2. the rotation of the Earth slows down when it nears apogee
  3. there aren't exactly 24 hours in a day
  4. clocks run slower when the Earth is farther from the sun

What happened last night in Saskatchewan?
  1. people turned their clocks back one hour
  2. people turned their clocks forward one hour
  3. nobody adjusted their clocks
  4. who cares what happens in Saskatchewan? (and where is it?)

If you normally catch the 7:33 commuter train, what will you do tomorrow?
  1. take the 6:33 train
  2. take the 8:33 train
  3. get on the 7:33 train as usual
  4. call in sick

What happens to the international date line at this time of year?
  1. it moves 15° east
  2. it moves 15° west
  3. it stays right where it is but "midnight" becomes 1 AM during the winter months
  4. nothing happens to the international date line

Did you ....
  1. get one hour less sleep last night?
  2. get one hour more sleep last night?
  3. slept exactly the same amount as the night before
  4. stayed up all night celebrating?

Mr. Big has an appointment to meet his accountant tomorrow at 12 noon. His secretary sent him an email message on Friday telling him that the appointment would have to be delayed by two hours. Mr. Big forgot to adjust his watch, so on Monday morning it was out of sync with the rest of the world. Assuming he got the email message, what time will he show up for the appointment according the adjusted clock in the accountant's office?
  1. 11 AM
  2. 12 noon
  3. 1 PM
  4. 2 PM
  5. 3 PM

Which, if any, of the following count as valid and rational objections to daylight saving time, assuming it is properly implemented?
  1. farmers will have to feed their animals in the dark
  2. children will have to go to school before the sun rises
  3. it wastes electricity
  4. you lose an hour's sleep in the summer
  5. it reduces crime
  6. it disrupts international flight schedules
  7. it's unnatural to adjust time
  8. it causes health problems by messing with your circadian rhythm



Saturday, October 24, 2009

Chicago

 
I'm in Chicago with Ms. Sandwalk and another couple who we hang out with. We have a wonderful time at the art gallery, took the architectural boat tour and ate delicious deep dish pizza.










Are You Sexually Attracted to Male Musk Deer?

 
The other day I had to get up and move to new seat on the subway. The cause of my discomfort was a young woman who reeked of musk—the scent that male musk deer (Moschus moschiferus) use to attract females. I don't know why this woman wanted attention from female musk deer but I was pretty sure she wasn't going to find any on the subway.

The main scent is due to muscone [see Monday's Molecule #127] and nowadays the muscone used in perfumes is completely artificial. But that wasn't always the case. Musk originally came from the scent glands of Asian musk deer [MUSK An Essay].
Only the mature male Moschus produces musk. The substance occurs in only one location on the deer's body: on its abdomen, just in front of its penis, is a hairy pouch known as the musk gland. This sac is about the size of a golf ball. It is composed of several layers of skin, with two openings immediately above the animal's urethra.

In the early summer, unripe liquid musk drains into the gland from the surrounding tissues, and is stored there for some weeks or months. During the course of this time, the musk - 30 grams of it or so - "matures" into a granular, waxy, reddish-brown substance with an extremely potent and familiar smell.

When the musk has ripened - shortly before the autumn rutting season - the deer begin to discharge it mixed with their urine, apparently to mark their territory and attract females. (This behavior is familiar to anyone who has come in contact with a tomcat that "sprays.") Even in winter, male musk deer have been reported to leave behind fragrant red snow, rather than yellow.
I'm told that humans of both sexes get turned on by this smell. If so, the woman on the subway is not only going to attract female musk deer but she's also going to get a lot of attention from both men and women of a different species. I guess it's a good thing that I freed up the seat next to her.

There ought to be rules about perfume, When a man or a woman is wearing too much, they should be told to go home and take a shower—with lots of unscented soap.


Friday, October 23, 2009

Picking a Religion

 
What if you are truly confused about what you believe and which group you should belong to? Here's a handy-dandy algorithm to help you decide. I got it from Friendly Atheist.



Thursday, October 22, 2009

Richard Dawkins' View of Random Genetic Drift

The Greatest Show on Earth is Richard Dawkins' latest book. It's his eighth book on evolution: the others are The Selfish Gene (1976), The Extended Phenotype (1982), The Blind Watchmaker (1986), River Out of Eden (1995), Climbing Mount Improbable (1996), Unweaving the Rainbow (1998) and The Ancestors Tale (2004).

I'm interested in the evolution of Richard Dawkins' ideas about evolution; in particular, his ideas about random genetic drift and mechanisms of evolution other than natural selection.

In Chapter 1 Dawkins says, "All reputable biologists go on to agree that natural selection is one of its most important driving forces, although—as some biologists insist more than others—not the only one."

This looks promising. Dawkins is saying— in chapter 1—that there are two mechanisms (driving forces) of evolution. He implies that he accepts random genetic drift as a "driving force" of evolution. (Assuming that random genetic drift is what he has in mind.) It's clear that "some biologists" have influenced him, although it's not clear from the sentence whether those biologists are "reputable"!

Since this is a book about the evidence for evolution, I eagerly anticipated his explanation of random genetic drift. Would it be as good as Jerry Coyne's?1 In fact, I was so eager that I couldn't wait. I jumped to the index to look under "random."

Nothing. Not to worry. The other important mechanism must be here somewhere. Is it indexed under "genetic"? No. What about "drift"? No, not there either.

What gives? How can you write a book about evolution in the 21st century without mentioning random genetic drift as an important mechanism of evolution? Even the other adaptationist, Jerry Coyne, has it in the index to Why Evolution Is True.

Maybe Dawkins uses another term for the second mechanism of evolution. I recalled that he often gets mixed up about the difference between neutral theory and random genetic drift. Let's see if "Neutral Theory" is in the index. Nope.

What about "Kimura"? Success at last! Check out page 332.

Page 332 is in the middle of a section on The Molecular Clock in Chapter 10. It seems a bit late to begin discussing the second mechanism of evolution, but, as I said before, it's promising that Dawkins even concedes that there is one.

Dawkins explains that the reason why there's a molecular clock is because the majority of changes at the genetic level are neutral and these changes are fixed in a regular, clock-like, albeit stochastic, process. He then goes on to say...
When the neutral theory of molecular evolution was first proposed by, among others, the great Japanese geneticist Motoo Kimura, it was controversial. Some version of it is now widely accepted and, without going into the detailed evidence here, I am going to accept it in this book. Since I have a reputation as an arch-"adaptationist" (allegedly obsessed with natural selection as the major or even only driving force of evolution) you can have some confidence that if even I support the neutral theory it is unlikely that many other biologists will oppose it!
I can't think of any serious biologists who would deny that neutral mutations exist. The essence of Neutral Theory, or Nearly Neutral Theory as it is currently called, is undoubtedly correct. The fact that Richard Dawkins accepts it in this book is not remarkable. What's remarkable is that he has to tell us that he accepts it, especially in a book about the evidence for evolution.

Meanwhile, we are still waiting for the explanation of the "other" mechanism of evolution. The one that was mentioned in Chapter 1 when he said that natural selection does not account for all of evolution. He can't have been thinking about "Neutral Theory" since that's not a mechanism of evolution. And he can't just have been thinking about a mechanism for fixing neutral mutations since he surely knows that the "other" mechanism can result in the loss of beneficial alleles and the fixation of detrimental ones.

Still waiting. What we see in Chapter 10 is an explanation of neutral mutations but no mention of random genetic drift—the mechanism responsible for fixing neutral mutations in a population. He does briefly mention on page 335 that neutral mutations can "go to fixation by chance." I get the impression that he goes out of his way to not name the other mechanism of evolution. You know what I'm referring to, it's the mechanism that gets a whole chapter to itself in all the evolutionary biology textbooks [Evolution: Table of Contents].

Dawkins concedes that the vast majority of the human genome consists of sequences that aren't genes. Here's how he puts it ...
It is a remarkable fact that the greater part (95% in the case of humans) of the genome might as well not be there, for all the difference it makes. The neutral theory applies even to many of the genes in the remaining 5%—the genes that are read and used. It applies even to genes that are totally vital for survival. I must be clear here. We are not saying that a gene to which the neutral theory applies has no effect on the body. What we are saying is that a mutant version of the gene has exactly the same effect as the unmutated version.
In other words, the vast majority of the DNA in our genome is junk. Mutations that occur in junk DNA will become fixed in spite of the fact that they are not seen by natural selection. This is what he means when he says that most mutations are neutral and it's equivalent to saying that the dominant mechanism of evolution, in terms of overall frequency, is random genetic drift and not natural selection. I just wish he'd come right out and say it.

It's a shame that Dawkins does not actually mention the mechanism by which those neutral mutations become fixed but instead continuously refers to neutral theory as the alternate mode of evolution. The general public needs to hear about random genetic drift and Dawkins is—like it or not—the most prominent evolutionist on the planet.

Dawkins has not changed his mind about the existence of these neutral mutations and he has not changed his mind about their importance. While they may exist, they are not important as far as evolution is concerned. He makes this very clear—once again—in this book.
As it happens, it is probably true to say that most mutations are neutral. They are undetectable by natural selection, but detectable by molecular geneticists; and that is an ideal combination for an evolutionary clock.

None of this is to downgrade the all-important tip of the iceberg—the minority of mutations that are not neutral. It is they that are selected, positively or negatively, in the evolution of improvements. They are the ones whose effects we actually see—and natural selection "sees" too. They are the ones whose selection gives living things their breathtaking illusion of design. But it is the rest of the iceberg—the neutral mutations which are in the majority—that concerns us when we are talking about the molecular clock.

As geological time goes by, the genome is subjected to a rain of attrition in the form of mutations. In that small portion of the genome where the mutations really matter for survival, natural selection soon gets rid of the bad ones and favors the good ones. The neutral mutations, on the other hand, simply pile up, unpunished and unnoticed—except by molecular geneticists.
This is the way the adaptationist dismisses non-adaptive evolution. It's not really of interest to real biologists. It's only interesting to molecular geneticists. And we all know that those people are not real evolutionary biologists!

Now we come to one of the most interesting sentences in the entire book; at least as far as I'm concerned. As most Sandwalk readers know, we have long debated whether or not visible mutations can be neutral. Once you have an observed phenotype, can you ever attribute it to neutrality? Many adaptationists argue that you can't.

Here's what Richard Dawkins says in his latest book.
It is also possible (although "ultra-Darwinists" like me incline against the idea) that some mutations really do change the body, but in such a way as to have no effect on survival, one way or the other.
This is progress. Back when he wrote The Extended Phenotype, in 1982, Richard Dawkins said.
The adaptationism controversy is quite different. It is concerned with whether, given that we're dealing with a phenotypic effect big enough to see and ask questions about, we should assume that it is the product of natural selection. The biochemist's "neutral mutations" are more than neutral. As far as those of us who look at gross morphology, physiology and behavior are concerned, they are not mutations at all. It was in this spirit that Maynard Smith (1976) wrote: "I interpret 'rate of evolution' as a rate of adaptive change. In this sense, the substitution of a neutral allele would not constitute evolution ..." If a whole organism biologist sees a genetically determined differences among phenotypes, he already knows he cannot be dealing with neutrality in the sense of the modern controversy among biochemical geneticists.
Finally, in 2009, Richard Dawkins admits that it is "possible" that visible mutations could be neutral. Hallelujah!

I'm looking forward to book #9.


1. Jerry Coyne's View of Random Genetic Drift

Evolution in Action and Michael Behe's Reaction

Of the many scientists who are trying to understand evolution, Richard Lenski stands out for his experimental approach. He has maintained stocks of E. coli growing under stressful conditions for over 40,000 generations.

During that time, the cells have been forced to adapt to conditions of low carbon source (glucose) and Lenski's group has been tracking the mutations that arise. In the past, they have done a heroic job of identifying new mutations but that job has become much easier with new technology. Now that rapid genome sequencing is possible it becomes feasible to sequence the genomes of bacteria that were preserved from earlier generations and determine every single mutation that arose.

Barrick et al. (2009) have published the result from just such an experiment. They sequenced the genomes of the original, ancestral, strain and samples of a single lineage from 2,000, 5,000, 10,000, 15,000 20,000 and 40,000 generations.

This information can address a number if issues as they explain in the introduction to their paper.
Genomic changes underlie evolutionary adaptation, but mutations—even those substituted (fixed) in evolving populations—are not necessarily beneficial.Variation in the rate of genomic evolution is also subject to many influences and complications.On the one hand, theory predicts that neutral mutations should accumulate by drift at a uniform rate, albeit stochastically, provided the mutation rate is constant. On the other hand, rates of substitution of beneficial and deleterious mutations depend on selection, and hence the environment, as well as on population size and structure. Moreover, the relative proportions of substitutions that are neutral, deleterious and beneficial are usually difficult to infer given imperfect knowledge of any organism’s genetics and ecology, in the past as well as in the present.

Experiments with tractable model organisms evolving in controlled laboratory environments minimize many of these complications and uncertainties15,16. Moreover, new methods have made it feasible to sequence complete genomes from evolution experiments with bacteria. To date, such analyses have focused on finding the mutations responsible for particular adaptations. However, the application of comparative genome sequencing to experimental evolution studies also offers the opportunity to address major conceptual issues, including whether the dynamics of genomic and adaptive evolution are coupled very tightly or only loosely.
At 20K generations, there were 29 single nucleotide polymorphisms (SNP) and 16 deletions, insertions, and chromosomal rearrangements (DIP) for a total of 45 different events (see figure). Not all of these contributed to adaptation and the rapid growth phenotype but many of them did. Some were mutations that inactivated a gene and some were amino acid substitutions that change activity of an enzyme.

The authors do not report the distribution of beneficial vs neutral mutations but the data suggests that most of the 45 mutations were beneficial. The authors do not tell us how many of these beneficial mutations destroyed the activity of a gene and how many just changed the activity of a gene product but it looks like there were about equal numbers of both kinds of mutations.

Much of the paper is about adaptive vs. non-adaptive mutations. At 40,000 generations there were 627 SNP and 26 DIP mutations. The increase was due, in part, to an increase in mutation rate because of a mutation in the mutT gene. One might expect that the initial adaptation would result in selection for beneficial alleles and that neutral alleles would accumulate by random genetic drift in subsequent generations (i.e. from 20K generations to 40K generations). This is probably what happened from 20K generations to 40K generations

In the first 20K generations the strain adapted rapidly to the low glucose concentration and from then on its rate of growth under these conditions increased more slowly. This could also be explained by the initial fixation of adaptive mutations followed by fixation of non-adaptive, neutral, alleles. The authors argue convincingly that this didn't happen. Instead, almost all of the first 45 mutations were probably adaptive. Presumably, the mutations that arose later on (between 10K and 20K generations) were much less beneficial (lower selection coefficient) than the ones that first appeared in the population. This is the interesting, and controversial, part of the paper.

This is a paper that the IDiots can't ignore because it's all about evidence for evolution. It doesn't come as a big surprise that Michael Behe already has a poting on the DISCO website: New Work by Richard Lenski.

There was a time a few years ago when you could predict that the IDiots would try to discredit such a paper. The new strategy seems to be the opposite. They agree with the conclusions and offer them as support for Intelligent Design Creationism.

Here's the latest example from Behe's posting.
Despite his understandable desire to spin the results his way, Lenski’s decades-long work lines up wonderfully with what an ID person would expect — in a huge number of tries, one sees minor changes, mostly degradative, and no new complex systems. So much for the power of random mutation and natural selection. For his work in this area we should be very grateful. It gives us solid results to point to, rather than having to debate speculative scenarios.
I don't think I need to comment on such stupidity.


Barrick, J.E., Yu, D.S., Yoon, S.H., Jeong, H., Oh, T,K., Schneider, D., Lenski, R.E., and Kim, J.F. (2009) Genome evolution and adaptation in a long-term experiment with Escherichia coli. Nature Oct 18. [Epub ahead of print] [PubMed] [doi: 10.1038/nature08480]