The Best Flowering Plant

 
Tulips are the best flower according to Jane and Michael on Beer with Chocolate. Jane and Michael may have been slightly influenced by their Birthday Adventure in Holland.

Much as I hate to disagree with my offspring (), tulips are not the best flowering plant. Dandelions (from the French dent de lion - lion's teeth) are the best plant.

Not only are dandelions beautiful, they are hardy and ubiquitous. They can grow almost anywhere with a minimum of care. In fact, you have to make special efforts to get rid of them—something you would only do if you have an extreme anti-dandelion prejudice. These days, civic governments throughout Canada are banning herbicides in order to save the dandelion. (You don't see anyone doing that for tulips, do you Jane?)

The most common species of dandelion is Taraxacum officinale.

The flowers are pretty. You can eat the leaves. The leaves will cure many diseases. You can make wine with dandelions. A company in Belgium called Brasserie Fantôme even makes a dandelion beer called Fantôme Pissenlit. (= wet the bed, from dendelion's medicinal properties).

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DNA Replication in E. coli: The Solution

In an earlier posting I described a problem that we often use to encourage critical thinking in our undergraduates. The problem is how can E. coli divide faster that the time it takes to replicate it's chromosome? [DNA Replication in E. coli: The Problem]

Recall that DNA replication always begins at an origin of replication. In bacteria there is usually one origin per chromosome or plasmid. (Eukaryotic chromsomes have multiple origins.)

The replisomes assemble at the origin and then move in opposite directions around the chromomome until the meet at the termination region. Each replisome moves at a rate of 1000 nucleotides per second and it takes about 38 minutes to complete one round of replication. But E. coli can divide every 20 minutes. That's the problem.

The firing of an origin is controlled by regulatory proteins. These proteins trigger the assembly of replisomes at the origin sequences. When most of us are first presented with this problem we think in terms of the events occurring sequentially. Thus, a chromosome is copied, the daughter chromosomes segregate, and a new round of replication begins.

This isn't what happens when the cells are dividing rapidly. Instead, a new round of replication begins at the "future origin" before the current round of replication is completed. At any given instant, there can be six or eight replication forks synthesizing DNA simultaneously inside the cell.

In order for the cell to divide every 20 minutes, all that is required is that a round of replication terminate every 20 minutes. This means that origins fire every 20 minutes. When the daughter chromosome segregate into daughter cells, they are already partially replicated in preparation for the next cell division.

Here's how Fossum et al. (2007) describe the solution in a recent paper in EMBO Journal.

The bacterium Escherichia coli has a single chromosome that is replicated from a single origin (oriC), bidirectionally to the terminus, once per division cycle (Kornberg and Baker, 1992). The cell cycle of slowly growing bacteria is quite similar to that of eukaryotic cells (Boye et al, 1996), with the G1, S and G2/M phases of bacteria termed B, C and D, respectively. E. coli (and certain other bacteria) is capable of very rapid growth in rich medium, with doubling times as short as 20 min. The replication time, however, remains long, with approximately 60–90 min required to replicate and segregate the chromosome. Therefore, the cell cycle is more complicated during rapid growth (Figure 1). If the time it takes to synthesize and segregate the daughter chromosomes (C+D) exceeds one generation time, a new round of replication must be initiated before the previous round is completed (Cooper and Helmstetter, 1968). Thus, initiation occurs at two origins in the 'mother' cell. It can even occur in the 'grandmother' cell at four origins if the time it takes to replicate and segregate the chromosome exceeds two generations. These initiations at two or four origins occur simultaneously, as one event per division cycle (Skarstad et al, 1986). While E. coli and Bacillus subtilis are two examples of bacteria capable of performing multifork replication, other bacteria, such as Caulobacter crescentus, are not. Eukaryotic cells do not replicate with overlapping cycles, but do initiate DNA replication at multiple replication origins, and thus perform a different kind of multifork replication, with the multiple forks on the same copy of the genome (Diffley, 2004).

Figure 1:Replication pattern of rapidly growing E. coli wild-type cells. Cells (yellow) with chromosomes (blue lines) and origins (black squares) are drawn schematically to show the number of replication forks and origins at different stages of the cell cycle. In this example, initiation of replication occurs at four origins at the same time as cell division (bottom). A young cell therefore contains four origins and six replication forks (upper left). As replication proceeds, the oldest pair of forks reach the terminus and the two sister chromosomes segregate. The cell then contains four origins and four replication forks (upper right). Initiation then occurs again at 4 origins and generates 8 new forks giving a total of 12 forks, as cell division approaches (bottom). Because there will be cell-to-cell variability, some cells will contain eight origins before they divide, whereas cells that divide before initiation of replication will contain only two origins (not shown). However, the majority of the cells in the culture will contain four origins.

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Fossum, S., Crooke, E. and Skarstad, K. (2007) Organization of sister origins and replisomes during multifork DNA replication in Escherichia coli. EMBO J 26:4514–4522 [doi:10.1038/sj.emboj.7601871]

Gene Genie #31

 
The 31st edition of Gene Genie has been posted at Adaptive Complexity [Capitalists, Genetic Tests and Your DNA].

Everyone knows there is a lot of crazy stuff on the internet, but did you know there is a lot of great writing about genes, genetics, and human diseases? And believe it or not, sometimes these pieces are written by people who know what they're talking about. If you're looking for what's new in human genetics, you've come to the right place.

Welcome to the 31st Gene Genie, a blog carnival dedicated to great blogging about human genes and how they impact our health. This Mother's Day edition includes an in-depth highlight of the growing industry of personalized genetics.

The beautiful logo was created by Ricardo at My Biotech Life.

The purpose of this carnival is to highlight the genetics of one particular species, Homo sapiens.

Here are all the previous editions .....

1. Scienceroll
2. Sciencesque
3. Genetics and Health
4. Sandwalk
5. Neurophilosophy
6. Scienceroll
7. Gene Sherpa
8. Eye on DNA
9. DNA Direct Talk
10. Genomicron
11. Med Journal Watch
12. My Biotech Life
13. The Genetic Genealogist
14. MicrobiologyBytes
15. Cancer Genetics
16. Neurophilosophy
17. The Gene Sherpa
18. Eye on DNA
19. Scienceroll
20. Bitesize Bio
21. BabyLab
22. Sandwalk
23. Scienceroll
24. biomarker-driven mental health 2.0
25. The Gene Sherpa
26. Sciencebase
27. DNA Direct Talk
28. Greg Laden’s Blog
29. My Biotech Life
30. Gene Expression
31. Adaptive Complexity

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On the Evolution of the Blood Clotting Pathway

Theme

Blood Clotting
Last year I spent some time studying blood clotting. You can read the series of postings by clicking on the "Theme" link.

One of the reasons for reading up on this topic was because the creationists were promoting it as another example of something that could not evolve. Micheal Behe was one of those creationists.

The data is now in. Russel Doolittle has been working on the evolution of the clotting cascade and the latest results incorporate the information from the lamprey genome. Suffice to say, Behe's claims have been decisively refuted.

Ian Musgrave has the scoop in an excellent article on Panda's Thumb [Behe vs Lampreys: A modest proposal]. This should put an end to ignorant speculation about the non-evolvability of the blood clotting pathway. Or, to be more precise, it should put an end to such speculation by any intelligent, rational, person.

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Blogger’s Code of Conduct

 
If you're not going to follow the Blogger's Code of Conduct, this is what you're supposed to put on your blog.

This is an open, uncensored forum. We are not responsible for the comments of any poster, and when discussions get heated, crude language, insults and other "off color" comments may be encountered. Participate in this site at your own risk.

Don't say you haven't been warned.

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Something to look forward to ....

 

ATHEISTS and agnostics are decent people whose tormented souls will burn for all eternity in the scorching fires of hell, Britain's biggest catholic said last night.

Cardinal Cormac Murphy O'Connor said non-believers should be respected, right up to the point of death when they will finally come face to face with Satan and his blood-soaked pitchfork.

He told a conference in London: "Those without faith should not be shunned or abused. Jesus and Beelzebub are already cooking something up for them, don't you worry about that."

Gee, I wonder how he feels about Jews and Muslims?

The one good thing about all of this is that my agnostic friends will be there to keep me company. It will serve them right for not making up their minds about Beelzebub.

(Christianity is supposed to be one of the monotheistic religions. Could someone who is an expert please explain Beelzebub? Is he/she a god or just some minor supernatural being like Gabriel?)

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[Hat Tip: RichardDawkins.net]

Reciting the Lord's Prayer in Ontario's Legislature

 
Premier Dalton McGuinty started the debate in February when he called for a study of the current practice [Lord's Prayer review ordered].

Queen's Park Bureau Chief
In a bid to separate church and state – or, in this case, province – Premier Dalton McGuinty wants to end the practice of reciting the Lord's Prayer in the Ontario Legislature.

McGuinty surprised observers at Queen's Park this morning by appealing for an all-party committee to replace the prayer.

"I believe it is time for Ontario's Legislature to better reflect Ontario's reality and celebrate our diversity," the premier wrote to the leaders of the Progressive Conservatives and New Democrats.

"It is time to move beyond the daily recitation of the Lord's Prayer in the Ontario Legislature to a more inclusive approach that reflects 21st century Ontario," he said, noting the prayer was last updated in 1969.

"Our counterparts in other provinces and the federal government have adjusted their customs to reflect the diversity of the population.

"The members of the Ontario Legislature reflect the diversity of Ontario – be it Christian, Jewish, Hindu, Muslim, Sikh or agnostic. It is time for our practices to do the same. That is the Ontario way," McGuinty wrote.

This sounds pretty enlightened. Later on we learned that McGuinty had in mind multiple prayers and not just abolishing the practice altogether.

The committee has been struck. One of the first things they did was to set up a website. Within days the website crashed from the volume of submissions [Proposal to scrap Lord's Prayer crashes gov't website]. Can you guess who was responding? Yes, that's right, thousands of people who want to keep the Lord's Prayer in the legislature. It doesn't matter to them if we have Jewish, Muslim, Hindu, Buddhist, and atheist MPP's. No sireee. They all have to say the Lord's Prayer before doing any business in the house. That's only fair.

Naturally, it's the Conservatives who are leading the charge to stifle tolerance and promote bigotry. The latest example is a column from one of the editors of The National Post [John Turley-Ewart: Ontario shouldn't ditch the Lord's Prayer]. You won't believe the silliness of his argument ...

Christians across the province see the Premier's move as a sop to those who think saying the prayer is inconsistent with multiculturalism. Those who disapprove of such a move include Premier McGuinty's own mother. But that has not caused the Premier to waver in his position for change. He is on record saying: "We've got a responsibility to ensure that all people feel truly at home here."

But the move has left many Christians in Ontario wondering if the province is still their home; if it is a place that is in tune with the Christian principles that have informed the province's political and economic values — values that underpin Ontario's success story as a democratic, prosperous province. The Lord's Prayer, recited by Catholics and Protestants alike, is more than words that pay homage to God.

It represents a piece of common ground that Catholics and Protestants could agree on -- a daily ritual that helped in whatever small way to break down the intolerance that existed between the majority Protestants and minority Catholics who founded the province.

In its own small but important way, the recital of the Lord's Prayer is a symbol of the tolerance that has made Ontario the great place it is today to live. That Premier McGuinty would consider dropping the prayer in the name of tolerance is, thus, ironic. It would do a disservice to the province's history and its Christian heritage.

Ontario should keep the Lord's Prayer, add other prayers from different faiths if thought appropriate, and avoid the folly of dismissing history for feel good, fuzzy visions of multiculturalism.

Hmmm ... let's see if I understand this correctly. Forcing atheists to recite, or listen to, the Christian prayer every day, is a symbol of "tolerance."

Earth to John Turley-Ewart ... you are promoting bigotry and intolerance. If you want your Christian friends to say the Lord's Prayer then let them say it by themselves in the privacy of their offices before going to the House to do Ontario's business.

Just because a majority of MPP's may be Christians is no reason for the majority to force their religion on everyone else. That's not the Canadian way.

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Amino Acids and the Racemization "Problem"

Amino acids come in two different "flavors" depending on the orientation of atoms bound to the central α-carbon. The two possibilities are L- and D- configurations. In the examples shown here, you can see that the two forms of serine, L-serine and D-serine, are mirror images of each other. These forms are called stereoisomers because they contain the same atoms with different mirror image arrangements.

Stereoisomers cannot be interconverted without breaking covalent bonds. They are distinct molecules. Almost all amino acids in living organisms are L-amino acids. Proteins are almost exclusively composed of L-amino acids and not D-amino acids.

The α-carbon atom of amino acids is chiral, or asymmetric. You need at least one chiral atom in a molecule in order to have stereoisomers. One amino acid (glycine) does not have a chiral α-carbon so there is only one configuration of glycine.

When amino acids are synthesized in a chemistry laboratory, you often end up with a mixture of equal amounts of L- and D- stereoisomers. When you examine the amino acids found in meteorites and in the vicinity of stars, you find a mixture of both stereoisomers. These are called racemic mixtures since the process of converting one stereoisomer into another is called racemization.

Now, the fact that amino acids in living organisms are all L- forms is not a problem since the L-amino acids are the only ones that are synthesized in any appreciable amounts. All of the amino acid biosynthesis pathways produce only L- forms and not D- forms. This is not unusual since enzyme catalyzed reactions are usually sterospecific. It's not a surprise that modern proteins are composed of L-amino acids because those are the only ones available inside the cell.

The "problem" arises when we start to think about how life arose in the first place. The general assumption is that life arose in a warm pond containing a racemic mixture of L- and D- amino acids. If that is true then how did life evolve to select exclusively L-amino acids? Most of the proposed solutions to these questions make assumptions about how the primordial soup could have spontaneously come to have a preference for L-amino acids over D- amino acids.

I'd like to propose another way of thinking about this problem.¹

Let's assume there was a primordial soup where amino acids came together spontaneously to form short peptides. In the beginning, the soup contained racemic mixtures of the D- and L-forms of amino acids. These molecules were formed spontaneously by the kinds of chemical reactions that are simulated in the laboratory.

Some of the random peptides acted as catalysts for chemical reactions. This is observed in modern-day experiments. One kind of reaction, amino acid synthesis, would have been especially favorable since it created more amino acids and led to more peptides.

The simplest pathway to more amino acids is the formation of glycine, probably by adding an amino group to acetate or glycerol. (This pathway no longer exists.) The next simplest is the conversion of pyruvate (a common three carbon organic acid) to alanine—a fairly simple transamination reaction.

In modern cells, this reaction is catalyzed by sophisticated transaminases but in the beginning it would have been catalyzed by short peptides that formed spontaneously in the primordial soup. Such reactions are stereospecific, the modern reaction only produces L-alanine and never D-alanine (well, hardly ever!). Let's assume that a similar reaction in the beginning produced, by chance, L-alanine.

Another simple pathway is from oxaloacetate (a common four carbon organic acid) to aspartate. Both of these reactions require a relatively simple addition of ammonia to a keto group and both reactions could have been catalyzed (inefficiently) by the same peptide.


As I mentioned above, enzyme catalyzed reactions tend to be stereospecific so it's likely that the early products were L-alanine and L-aspartate from the same enzyme. They could have been D-alanine and D-aspartate, but they weren't. As the concentrations of glycine, L-alanine and L-aspartate increased there were more and more peptides formed and the new peptides were enriched in these two particular L-amino acids.

Other simple amino acid synthesis reactions were catalyzed in the primordial soup. The most likely one is the synthesis of serine from glycerol or glycerate (common three carbon organic alcohols or organic acids). Again, the enzyme catalyzed reactions will only produce one isomer of the amino acid and there might have been selection for those parts of the soup that made L-serine (instead of D-serine) because the L-serine could more easily combine with L-alanine and L-aspartate to make many more peptides. In this case, the specificity of the reaction derives from selecting D-glycerate over L-glycerate as the substrate.

L-serine is the precursor to L-cysteine so it's likely that L-cysteine was also one of the early amino acids to accumulate in the primordial soup. This was an important addition to the repertoire since L-cysteine has a sulfur group and that leads to many more possibilities for catalytic active sites in the peptides. Note that once L-serine began to accumulate in the soup it led directly to the stereospecific L-cysteine. You can't make D-cysteine from L-serine so there's no racemization problem once L-serine accumulates.

L-glutarate (from alpha-ketoglutartic acid, a common five-carbon organic acid) is another good candidate for the primitive amino acids. (It's quite possible that L-alanine, L-asparate, and L-glutamate were all made by the same primitive enzyme using very similar 3, 4, and 5-carbon substrates.)


At this point there would have been all kinds of peptides containing various combinations of L-alanine, L-aspartate, L-serine, glycine, L-cysteine, and L-glutamate since these six amino acids have become much more abundant that the ones formed spontaneously by uncatalyzed reactions that produce a racemic mixture. This is probably the time when there was a shift to encoding peptides in a sequence of nucleotides.

This is an important point. The shift to more and more complex peptides did not have to take place in a random mixture of both forms of all 20 amino acids. It could have taken place under conditions where there was already a significant enrichment of a small number of L-amino acids due to catalytic biosynthesis from non-amino acid precursors.

There's some suggestive evidence to indicate that the primitive genetic code was much simpler than the one we see today and may have only had codons for the six initial amino acids. The other L-amino acid synthesis pathways arose later on and the genetic code expanded when codons were "stolen" from the precursors of these new L-amino acids.

One of the primitive codons for aspartate, for example, might have been AXX (any codon beginning with A). L-aspartate is the precursor to: L-lysine (AAA, AAG), L-asparagine (AAU, AAC), L-threonine (ACX), L-methionine (AUG), and L-isoleucine (AUU, AUC, AUA). The idea is that the new amino acids were originally synthesized on L-aspartate that was attached to its tRNA and they were incorporated into proteins at some positions in place of L-asparate. (This hypothesis on the origin of the genetic code was developed by my former colleague Jeff Wong. The idea came to him while teaching an undergraduate course in biochemistry ... but that's another story.)

Note that many amino acids are made from pre-existing amino acids. Once you have a supply of L-aspartate, for example, it follows that the derivatives will also be L- forms. There's no need to postulate that the preferential use of L-asparagine, L-threonine, L-methinione, and L-isoleucence, in contrast to the D- forms, arose independently. This greatly reduces the probability problem that most people are hung up on.

I don't have any good ideas about how the transition to encoded peptides happened but that's not the real point of this speculative posting.

The real points are ....

1. The most primitive catalysts were probably not very big. They were probably composed of mixtures of L- and D-amino acid residues.
2. The first important step was synthesis of new stereospecific amino acids which meant that the process was no longer dependent on the original pool of compounds that formed spontaneously.
3. The first peptides and polypeptides (proteins) probably contained only six amino acids. These are the amino acids that can be easily made from readily available precursors.

If you think about the origin of life in this way it will help you to understand why biochemists don't think the "racemization problem" is a real problem. This scheme will also help you to understand why some *particular* amino acids came to be enriched in proteins and not all of the other amino acids that were in the primordial soup in the very beginning. (There are far more than 20 amino acids.)

The original choice of the first L-amino acids over their D-isomers was probably an accident. It could just as easily have been the D- amino acids.

UPDATE: I now believe that Metabolism First and the Origin of Life is a more likely explanation for the origin of life. Please ignore references to "primordial soup" in the essay above. My conversion doesn't change the point. In the beginning very simple amino acids were spontaneously synthesized in restricted environments around thermal vents. By chance, the first chiral amino acid, alanine?, may have been L-alanine. All other may have been synthesized using L- amino acid precursors and this explains the the racemization problem.

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1. This is a modified version of an article that was originally posted on talk.origins in January, 2004.

DNA Replication in E. coli: The Problem

I've started reading microcosm by my favorite science writer, Carl Zimmer [Buy This Book!]. Watch for a review, coming soon.

I was mildly disappointed to see Carl repeat a common myth about DNA replication in E. coli on page 29. Since we often use this myth to teach critical thinking in our undergraduate classes, I thought it would be worthwhile to discuss it here.

Today I'm going to present the problem and let everyone think about a possible solution. On Sunday, I'll publish the answer. (If you know the solution, you are not allowed to post it in the comments—I'll delete those comments. You can ask for clarification or speculate.)

Here's what Carl says at the top of page 29.

E. coli faces a far bigger challenge to its order when it reproduces. To reproduce, it must create a copy of its DNA, pull those chromosomes to either end of its interior, and slice itself in half. Yet E. coli can do all of that with almost perfect accuracy in as little as twenty minutes.

Today, we're not concerned about the 20 minute generation time but I note, for the record, that the average generation time of E. coli, in vivo, is about one day. I also want to mention that the 20 minute generation time is an extreme example that's achieved only under the most extraordinary circumstances. Typical generation times in the lab are about 30 minutes.

However, that's not the problem. Let's assume a generation time of 20 minutes.

In the next paragraph Carl says ...

The first step in building a new E. coli—copying more than a million base pairs of DNA—begins when two dozen different kinds of enzymes swoop down on a single spot along E. coli's chromosome. Some of them pull the two strands of DNA apart while others grip the strands to prevent them from twisting away or collapsing back on each other. Two squadrons of enzymes begin marching down each strand, grabbing loose molecules to build it a partner. The squadrons can add a thousand new bases to a strand every second.

What Carl is referring to the the assembly of replication complexes (replisomes) at the origin of replication. Once those complexes are assembled, replication fires off and proceeds in opposite directions (bidirectionally) until the two fork meet at the opposite side of the chromosome.



Carl is correct when he says that the forks move at 1000 nucleotides per second. Later on in his book he mentions that the size of the E. coli chromosome is 4,600,000 base pairs or 4,600 kb (p. 116). At 1000 nucs per second it would take 4600 second to replicate this DNA if there was only one replication fork. Since there are two, it will take 2,300 seconds.

You can do the math. This is 38 minutes. It is a correct number—it takes at least 38 minutes to replicate the E. coli chromosome, not 20 minutes as stated earlier. It is true that the generation time of E. coli can be as short as 20 minutes under extraordinary circumstances.

Here's the problem. How can E. coli divide faster than it can replicate it's chromosome?

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Ben Stein's Dangerous Idea

 
Uncommon Descent is the Intelligent Design blog of Bill Dembski, Denyse O'Leary and their friends. It represent the best that the IDiots have to offer.

Yesterday's posting by DLH is an example of the best sort of creationist reasoning. The posting is an extensive quotation from an article by Robert Meyer originally posted in New Alliance Magazine [Ben Stein’s Dangerous Idea]. Here are the first three paragraphs quoted on the blog ...

Ben Stein has a dangerous idea. His idea is that professors and teachers who express skepticism about Darwinism are likely to find themselves not granted tenure, castigated and ridiculed, and disqualified from the opportunity to have research papers published.
. . .
Having reviewed the movie myself, it appeared that Stein was trying to make the case for academic freedom, not attempted to convert anyone to a particular ideological position.

Stein, in fact, never makes it known what particular beliefs he holds personally, he merely makes it known that he is disgusted by the idea that someone could lose their job over honest doubts about Darwinism.

No, your eyes are not deceiving you. Re-read that last paragraph. For all we know Stein may be a secret evolutionist. He's only interested in academic freedom. It's just a coincidence that the phrase "No Intelligence Allowed" uses the same word as Intelligent Design.

Jeesh. And you wonder why we call them IDiots?

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Make Englishe the Only Offal Language

 
I'm with Orac and Orcinus on this one. This is just too delicious to resist.¹

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1. Although, as a notoriously bad speller, I have made some pretty similar mistakes on Sandwalk.

Congratulations Jason Rosenhouse!!!

 
A big event just happened at Evolutionblog—Jason Rosenhouse got tenure [Tenure!]. Congratulations Jason.

I'll let him describe the process ....

I got tenure! Yay! By my count it's been about fifteen years getting to this point. I started studying mathematics seriously in my last two years of college (a rather late start in this profession). Then it was five years of graduate school, three years as a post-doc in Kansas, and now five years at JMU. Pretty satisfying. Suddenly that obnoxious and contentless rejection letter I received a month ago on a paper the journal should have been honored to publish doesn't seem to sting so much. (I'll just patch it up and send it off to the next journal, where it will languish for ten months to a year. What do I care? It's not like I'm in any great hurry to publish anymore!)

So there you go. Guess now I can tell you what I really think...

I guess this is when we discover that Jason is really a closet IDiot.

UPDATE: It didn't take long ...

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Nobel Laureates: Arvid Carlsson and Paul Greengard

 

The Nobel Prize in Physiology or Medicine 2000.

"for their discoveries concerning signal transduction in the nervous system"

Arvid Carlsson (1923 - ) and Paul Greengard (1953 - ) received the Nobel Prize in Physiology or Medicine for their work on identifying dopamine as a neurotransmitter. They also showed that L-dopa [Monday's Molecule #70], a precursor of dopamine, could relieve the symptoms of dopamine depletion and help control the symptoms of Parkinson's disease. They shared the prize that year with Eric R. Kandel.

THEME:Nobel LaureatesThe presentation speech was given by Professor Urban Ungerstedt of the Nobel Committee at Karolinska Institutet. (The date was, of course, December 10th as always. This is the anniversary of Alfred Nobel's death.)

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

This year's Nobel Prize in Physiology or Medicine concerns the most complex structure in the universe that we know of - the human brain. It consists of 100 billion nerve cells, which is the same number of cells as the total number of human beings that have ever lived on this earth.

We talk about the "Internet revolution"; 35 million Internet users who communicate now and then - what is that compared to the nerve cells we all carry within ourselves! 100 billion nerve cells that communicate continuously.

It is this communication, "signal transduction in the nervous system," which is the subject of this year's Nobel Prize. A single nerve cell forms thousands of contact points, so-called synapses, with other nerve cells. In these synapses the nerve cells communicate by chemistry; one cell releases a transmitter, which reaches the other cell.

Professor Arvid Carlsson proved that dopamine is such a transmitter. The general belief was that dopamine was a precursor of other transmitters and of little functional importance. However, Professor Carlsson was able to show that dopamine existed in specific parts of the brain and concluded that it was a transmitter in its own right.

He then used a naturally occurring substance, reserpine, which empties the dopamine from the nerves, and found that the animals lost their ability to move. He realized that it must be possible to restore the dopamine levels with L-DOPA, a precursor of dopamine. In a conclusive, dramatic experiment he showed that the animals regained their ability to move when he gave them L-DOPA.

Reserpine had depleted dopamine and had given the animals the symptoms of Parkinson's disease, that is, rigidity and inability to move and react to stimuli in the environment. When the animals were given L-DOPA, dopamine was produced again in their brains. In this way the idea of treating Parkinson patients with L-DOPA was born. This enables millions of patients around the world to live a normal life.

Professor Paul Greengard showed what happens when dopamine and other similar transmitters stimulate a nerve cell. Receptors on the cell surface activate enzymes in the cell wall, which starts the production of second messengers. These messengers travel into the cell and activate a protein kinase, which starts to bind phosphate groups to other proteins, in this way altering their function. This leads, for example, to the opening of ion channels in the cell membrane and a change in the electrical activity of the cell.

Professor Greengard then showed that dopamine and other transmitters affect a central regulatory protein, which has been called DARPP-32. Like the conductor of an orchestra, it tells other proteins when and how to be activated.

This so-called "slow synaptic transmission" controls our movements and also those processes in the brain that elicit emotions or react to addictive drugs such as cocaine, amphetamine and heroin.

Professor Eric Kandel showed that transmitters of the same type as studied by Arvid Carlsson, via the protein kinases characterized by Paul Greengard, are involved in the most advanced functions of the nervous system such as the ability to form memories.

Imagine how difficult or impossible it must be to study how memory is formed in a human brain with 100 billion nerve cells. Eric Kandel, therefore, did something which is classical in all natural science: He chose to study a simpler model system, a sea slug, Aplysia, which has 20,000 nerve cells. He did it with the conviction that even primitive animals must learn in order to survive.

The sea slug has a withdrawal reflex protecting its gills. If they are touched repeatedly, they react less and less - just as human beings do when subjected to an unexpected touch. If, on the other hand, the touch is forceful the reflex is amplified and becomes stronger and stronger.

The habituation or amplification effect lasts only for a few minutes. One may say that the sea slug exhibits a short-term memory. If the forceful stimulus is repeated several times, the sensitization may remain for weeks, that is, the sea slug develops a long-term memory.

Professor Kandel was able to show that habituation to touching was due to changes in the synapse, the contact point between the nerve cells. During habituation less and less transmitter was released.

The forceful stimulus that formed the long-term memory worked in a completely different way. Second messengers activated protein kinases that entered the cell nucleus and started the production of new proteins. This, in turn, brought about a change in the form and function of the synapse. What we call memory is, thus, elicited by direct changes in the billion of synapses that form the contact points between the nerve cells.

I am convinced that you and I will remember this Nobel ceremony for many years. This is because of the dopamine which Arvid Carlsson discovered, enabling the brain to react to what we see and hear; the second messengers that Paul Greengard described, carrying the signals into the nerve cell; and the memory functions that Eric Kandel found to be due to changes in the very form and function of the synapses.

Dear Arvid Carlsson, Paul Greengard and Eric Kandel. Your discoveries concerning "signal transduction in the nervous system" have truly changed our understanding of brain function. From Arvid Carlsson's research we now know that Parkinson's disease is due to failure in synaptic release of dopamine. We know that we can substitute the lost function by a simple molecule, L-DOPA, which replenishes the emptied stores of dopamine and in this way, give millions of humans a better life.

We know from Paul Greengard's work how this is brought about. How second messengers activate protein kinases leading to changes in cellular reactions. We begin to see how phosphorylation plays a central part in the very orchestration of the different transmitter inputs to the nerve cells.

Finally, Eric Kandel's work has shown us how these transmitters, through second transmitters and protein phosphorylation, create short- and long-term memory, forming the very basis for our ability to exist and interact meaningfully in our world.

On behalf of the Nobel Assembly at Karolinska Institutet, I wish to convey our warmest congratulations and I ask you to step forward to receive the Nobel Prize from the hands of His Majesty the King.

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[Photo Credits: The photo of Arvid Carlsson celebrating is from "The Nobel Prize did change my life!" . The photo of Paul Greengard with his wife Ursala von Rydingsvard is from The New York Times. Greengard used his prize money to fund an annual $50,000 award to an outstanding female medical researcher.

Healing Through Quantum Mechanics

 
Jeffrey Shallit at Recursivity posts about a chiropractor in Seattle who will heal you by using quantum mechanics [Your Daily Dose of Woo].

There's a comment on his blog that points to a quack right there in Kitchener/Waterloo who makes the same silly claims. Check it out. I've inserted a picture of the ECLOSION (Electro Physiological Feedback Xrroid) device from the Kuantum Power website. Wouldn't you just love to have one of those? It will even work on computers made by fruit companies.

These are more examples of the misuse of science. How can we combat this except by making sure we educate students properly? Judging by what I see at the University of Toronto, we aren't doing a very good job of teaching students how to think. I get the feeling that most of my colleagues aren't aware of the problem and those that are, don't care. I see lots of similar woo in the scientific literature.

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Misusing Science

 
Canadian Cynic has a new job that forces him to drive past a certain billboard every day [And now, two troublemakers that need no introduction ...].

CC links to the website of the billboard sponsor [Stop the Cover-up]. Here's what you see if you follow the link.


This is group of people who are opposed abortion. What they're saying is that women who choose abortion are more likely to get breast cancer. Specifically ...

It is a well established fact that abortion can increase a woman’s risk of developing breast cancer by denying her the protective effect of both a full-term pregnancy as well as breast-feeding. In addition, the abrupt, artificial termination of a healthy pregnancy leaves a woman with an increased number of vulnerable undifferentiated (immature) breast cells which are, in turn, exposed to the massive amounts of estrogen present during early normal pregnancy. Estrogen is a known cancer causing hormone.

Now, it doesn't take too much exposure to real science to recognize the problem with such claims. What they're doing is taking a little bit of truth and distorting it into something that's not the truth.

This sort of thing is very common these days. Everyone wants to bask in the glow of science even when they are doing their best to extinguish that glow. Everyone wants to have their cake and eat it too.

I hate to bring up the framing issue again but, at the risk of sounding like a broken record, this ad is exactly the sort of thing I fear when Nisbet and Mooney start preaching. There's no question in my mind that this ad is a good example of framing (=spin). I'm not sure how we distinguish between this approach and one were we all agree to use science to support certain policies on climate change, or certain approaches to dealing with creationism.

At what point do we draw the line between truth and lies? Who is going to be the judge of when that line is crossed?

UPDATE: Abortion and Breast Cancer: There Is no Link.

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