Nobel Laureate: Eric Kandel

 

The Nobel Prize in Physiology or Medicine 2000.

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

Eric R. Kandel (1929 - ) won the Noble Prize in 2000 for his work on understanding the biochemistry of memory. He discovered that short term memory in the sea slug Aplysia depended on the phosphorylation and dephosphorylation of proteins and that the regulation of these covalent modifications was under the control cyclic AMP mediated signal transduction pathways.

Kandel shared the prize with Arvid Carlsson and Paul Greengard.

Here's what the press release says about Kandel's work

THEME:
Nobel Laureates

Eric Kandel

Sea slug, a model system for learning
A phosphorylation of proteins has great importance also for the discoveries for which Eric Kandel is rewarded, that is for revealing molecular mechanisms, important for the formation of memories. Eric Kandel started to study learning and memory in mammals, but realized that the conditions were too complex to provide an understanding of basic memory processes. He therefore decided to investigate a simpler experimental model, the nervous system of a sea slug, Aplysia. It has comparatively few nerve cells (around 20.000), many of which are rather large. It has a simple protective reflex that protects the gills, which can be utilized to study basic learning mechanisms.

Eric Kandel found that certain types of stimuli resulted in an amplification of the protective reflex of the sea slug. This strengthening of the reflex could remain for days and weeks and was thus a form of learning. He could then show that learning was due to an amplification of the synapse that connects the sensory nerve cells to the nerve cells that activate the muscle groups that give rise to the protective reflex.

Short and long term memory
Eric Kandel showed initially that weaker stimuli give rise to a form of short term memory, which lasts from minutes to hours. The mechanism for this "short term memory" is that particular ion channels are affected in such a manner that more calcium ions will enter the nerve terminal. This leads to an increased amount of transmitter release at the synapse, and thereby to an amplification of the reflex. This change is due to a phosphorylation of certain ion channel proteins, that is utilizing the molecular mechanism described by Paul Greengard.

A more powerful and long lasting stimulus will result in a form of long term memory that can remain for weeks. The stronger stimulus will give rise to increased levels of the messenger molecule cAMP and thereby protein kinase A. These signals will reach the cell nucleus and cause a change in a number of proteins in the synapse. The formation of certain proteins will increase, while others will decrease. The final result is that the shape of the synapse can increase and thereby create a long lasting increase of synaptic function. In contrast to short term memory, long term memory requires that new proteins are formed. If this synthesis of new proteins is prevented, the long term memory will be blocked but not the short term memory.

Synaptic plasticity, a precondition for memory
Eric Kandel thus demonstrated that short term memory, as well as long term memory in the sea slug is located at the synapse. During the 1990's he has also carried out studies in mice. He has been able to show that the same type of long term changes of synaptic function that can be seen during learning in the sea slug also applies to mammals.

The fundamental mechanisms that Eric Kandel has revealed are also applicable to humans. Our memory can be said to be "located in the synapses" and changes in synaptic function are central, when different types of memories are formed. Even if the road towards an understanding of complex memory functions still is long, the results of Eric Kandel has provided a critical building stone. It is now possible to continue and for instance study how complex memory images are stored in our nervous system, and how it is possible to recreate the memory of earlier events. Since we now understand important aspects of the cellular and molecular mechanisms which make us remember, the possibilities to develop new types of medication to improve memory function in patients with different types of dementia may be increased.

Figure 4.
A sea slug, Aplysia, has a simple nervous system and a gill withdrawal reflex that Eric Kandel has utilized to study learning and memory.

Figure 5.
A schematic description of how molecular changes in a synapse may produce "short term memory" and "long term memory" in the sea slug, Aplysia. The figure shows a synapse that is affecting another synapse. Short term memory can be produced when a weak stimulus (thin arrows in the left lower part of the figure) is causing a protein phosphorylation of ion channels, which leads to a release of an increased amount of transmitter. For a long term memory to be created, a stronger and more long-lasting stimulus is required (bold arrows in the figure). This causes an increased level of the messenger molecule cAMP, which causesa further activation of protein kinases. They will phosphorylate different proteins and affect the cell nucleus, which in turn will issue orders regarding the synthesis of new proteins. This may lead to changes in the form and function of the synapse. The efficacy of the synapse can then be increased and more transmitter released.

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[Photo Credit: Eric Kandel: Wikipedia]

Dancing to the Music

 
I have a confession to make. Every Monday night Ms. Sandwalk and I go dancing. We are taking beginner's social dancing at the local community center. This is the fifth time we've taken the beginners' classes.

After the dancing lessons we go with our friends to the pub and eat honey garlic chicken wings and French fries covered with cheese and mayonnaise. Alcohol is consumed.¹

I'm finally getting the hang of the waltz. From time to time I can do the steps without counting out loud. There is, however, one small problem. According to Ms. Sandwalk I don't keep time to the music. Apparently I have no idea how to coordinate the steps and the beats. I'll have to take her word for it 'cause it seems okay to me.

As if I didn't feel bad enough, psa over on Canadian Cynic publishes a video proving that even birds can do it [Go Parrot, Go!].


This is really embarrassing.

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1. It may sound like a bribe but I assure you that I would undoubtedly be going to the dance lessons even if we didn't visit the pub afterward. (Like I have a choice?)

Priceless

 
Canadian Cynic keeps finding these wonderful examples of Conservative stupidity. This one is from The London Free Press [Harper's appeal to flag falls flat].

OTTAWA — An attempt by Stephen Harper to wrap himself in the flag and take a dig at the opposition coalition fell flat Tuesday.

The prime minister has been portraying the Liberal-NDP-Bloc Quebecois government-in-waiting as an unholy alliance of “socialists and separatists.”

During question period, he suggested the opposition parties staged their pact-signing ceremony Monday without a Canadian flag in the background because of the separatist Bloc.

“Yesterday, as part of the culmination of the machinations of the leader of the NDP, we had these three parties together, forming this agreement, signing a document and they wouldn’t even have the Canadian flag behind them,” he said.

“They had to be photographed without it because a member of their coalition does not even believe in the country.”

Video confirms that Harper was technically right. There wasn’t a Canadian flag in the background — there were two.

Wake up Conservatives. It's time to find a new leader before he makes you look any worse than you actually are right now. You are in danger of becoming a mockery of a political party comparable to what your predecessor, the Progressive Conservatives, looked like in December 1979.

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Quote of the Day

 
From A BCer in Toronto comes this quote of the day,

Governor General Michaelle Jean:

"The prime minister and myself need to have a conversation."

which prompts me to express my disgust and point everyone to a recent posting by Ms. Sandwalk [STOP using "Myself" incorrectly].

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Michaëlle Jean

 
This is Michaëlle Jean, the Governor General of Canada. She acts as Canada's Head of State. The Prime Minister is the head of government.¹ Sometime in the next few days Michaëlle Jean is going to have to make some serious decisions. She will have to decide whether to invite the Liberal-NDP coalition to form a new government if Stephen Harper and his Conservatives lose a vote of non-confidence next Monday. I think that's a no-brainer—she has to turn to the coalition.

More importantly, what will she do if Stephen Harper asks her to delay parliament for six weeks (the technical term is prorogue)? Everyone knows that Harper will only do this in order to avoid the non-confidence motion scheduled for Monday. That has never been done before and it is contrary to the standards of a parliamentary democracy. However, it is also important that the Governor General not put herself in the position of second guessing the advice of the Prime Minister. In my opinion, she will have to accept his request to prorogue parliament because to do otherwise is to set a dangerous precedent. The Governor General, like the Queen she represents, is a figurehead and not an active participant in government.

Hopefully, cooler heads will prevail and Harper won't abuse his position by requesting that parliament be suspended. Harper brought this problem upon himself by acting like a petulant, childish, bully and it's time for him to accept his fate and behave like an adult. That goes for his supporters as well.

Grow up Conservatives. You were stupid enough to force the opposition into a corner where they had only two choices, surrender and die, or unite against an unethical minority government. Much to your surprise, they were able to unite and now you must suffer the consequences of your own stupid mistake. Accept it with grace and dignity and stop acting like crybabies [Canadian Cynic].

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1. America is one of the few democracies that combine these two jobs.

Graduate Record Exams: Biochemistry, Cell and Molecular Biology

 
This is the time of year when some undergraduates are getting the results of the GREs (Graduate Record Exams) that they wrote in preparation for graduate school applications. I thought I'd take a look at the practice test for Biochemistry, Cell and Molecular Biology.

This isn't pretty. Many of the questions ask for specific details like what is the initial product of CO₂ fixation in C₃ plants? I know lots of departments that don't teach photosynthesis and CO₂ fixation so students in those departments are screwed.

More importantly, I teach this in my introductory biology class but I tell the students that they don't have to memorize the details. They are allowed to bring their notes to the exam. I try to concentrate on basic principles and concepts and not on the names of enzymes and their specific reactants and products. In the case of CO₂ fixation, the important concepts have to do with the way rubisco works, the usable product of the reaction (not the initial product), and a general understanding of how the original reactant is regenerated. They have to understand the overall stoichiometry of the pathway and how the pathway is related to the pentose phosphate pathway.

Here's the problem. Are teachers like me hurting our students' chances of doing well on the GRE by discouraging rote memorization and regurgitation?

Even worse, I teach that concepts like exergonic and endegonic reactions are almost useless in most cases because most of the reactions in a pathway operate at near-equilibrium conditions where ΔG = 0. Several of the GRE questions ask about exergonic and endergonic reactions. My students will not do well on those questions.

How common is this? Do any other biochemistry teachers find that there's a conflict between what they teach and what is taught at most other schools?

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Monday's Molecule #99

 
Name this molecule. This time we need the common name and the systematic (IUPAC) name. A Nobel Prize was awarded for discovering how this molecule is related to your ability to remember its name and recognize the structure.

The first one to correctly identify the molecule and name the Nobel Laureate(s), wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are four ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin, Dale Hoyt from Athens, Georgia, Ms. Sandwalk from Mississauga, Ontario, Canada and Alex Ling of the University of Toronto. Dale and Ms. Sandwalk have offered to donate the free lunch to a deserving undergraduate so the first two undergraduates to win and collect a free lunch can also invite a friend. Alex gets the first one.

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" and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) 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. I reserve the right to select multiple winners if several people get it right.

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

UPDATE: The molecule is cyclic AMP (cAMP) or (1S,6R,8R,9R) -8-(6-aminopurin-9-yl) -3-hydroxy-3-oxo-2,4, 7-trioxa- 3λ5-phosphabicyclo [4.3.0]nonan-9-ol. The Noble Laureate is Eric Kandel. Several people guessed the molecule and Kandel but they added a second Nobel Laureate—one that I had already covered (usually Paul Greengard). Only one person picked up on the clue about memory and named Kandel alone. Congratulations to Timothy Evans of the Dept. of Neuroscience, University of Pennsylvania.

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Religious Freedom and Privacy

 
Phil Plait asks us to watch this video [Freedom of and from religion]. He says,

Watch this video. We need more like it. And I’m amazed some people can’t figure this out. it’s really pretty simple.

I'm one of those people who can't figure it out. I'm all for religious freedom. Everyone has the right to believe whatever they want as long as it doesn't interfere with the rights of others. This applies in all countries, not just in the USA.

But the video seems to imply something more when it talks about "privacy" and "respect." It sounds very much like they are advocating for protection from criticism and challenges to their beliefs.

Is this correct? Is it against the law in America to question religion or make fun of some of the most outrageous examples?

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Serious Question?

 
Nanopublic posted one of the covers of Onion Weekender with the lead story They tried to teach my baby science. Scary stuff.

If you follow the link to the Onion website you'll find all sorts of interesting Christmas gifts. If you're into giving things for Christmas just for the safe of buying presents then this is the place for you. I especially like this T-shift (below) that asks a very profound question.

I don't know the answer. I think you can start teaching them about Jesus when they are still kittens but chances are they'll never give up the idea that cats are the true gods.

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Greg Laden on "Race" (Again)

 
Greg Laden is one of those people who want to abolish use of the word "race" to define genetic subpopulations. He claims that there is no such thing in humans (or in other species). But even if it were biologically correct we shouldn't use the word because is has been misused by non-scientists.

Here's an example of his reasoning from The Scientific, Political, Social, and Pedagogical Context for the claim that "Race does not exist.".

The race concept has been very successful in its many nefarious applications, but this is not what I wish to speak about here. Rather, I want to acknowledge that a concept that divides humans into a particular set of groups in a useful way might be, well, useful and not such a bad thing. The fact that medical researchers use race to divide subjects, and find differences between races, and that these differences are important to know about, is important, even if it does not validate the races. What it means is that an unworkable race concept works sometimes, even if the races themselves don't exist. Nonetheless, it is reasonable to acknowledge that even though races don't really exist and many, if not most, applications of the race concept are obnoxious, it may be that its use is not entirely inappropriate all the time.

I will argue, however, that the down side of the use of race requires its abolition among scientists. Since race is usually not a biologically useful concept for humans (or many other species), and is never a truly valid concept, it is difficult to justify its use given the negative political and social consequences it carries.

Greg and I have been over this ground before. It think it's silly to pretend that races don't exist. That's carrying the anti-racist agenda too far.

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Best Canadian Sci/Tech Blog: Round Two

 
The first round of voting for the best Canadian Sci/Tech Blog is over.

As I said earlier, I voted for Bad Astronomy in the first round [Best Canadian Sci/Tech Blog]. I know Phil Plait isn't a Canadian, but he should be.

Here are the five finalists. I'm voting for Post Darwinist in order to make this contest look as silly as possible.

• Sync, the Tech & Gadgets Blog
• Synchro Blogue
• Post Darwinist
• DeSmogBlog
• Dusan Writer

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The Conservative Party Will Help You Write a Letter to the Editor

 
If you go to the Conservative Party website at Harper Leadership 08 you can get help in writing a letter to the editor. If you enter some sort of name and address you will eventually end up on a page that gives you the latest Conservative version of framing spin.

This is how Harper is going to avoid defeat when he faces the House of Commons. (Click on the image to see a larger version.)

The idea that the opposition parties don't have a mandate to from a coalition is particularly ironic given Stephen Harper's own position just a few years ago. Here's what is reported prominently on the front page of today's Toronto Star

But opposition MPs are accusing the Prime Minister of hypocrisy, charging that Harper is overlooking his own efforts to forge a coalition to replace Paul Martin’s minority Liberal government in 2004.

Harper, then Conservative leader, even joined with NDP Leader Jack Layton and Bloc Québécois Leader Gilles Duceppe to write then-governor general Adrienne Clarkson, urging her to look at "options" if Martin's government fell in the fall of 2004, mere months after it won a minority mandate on June 28.

"We respectfully point out that the opposition parties, who together constitute a majority in the House, have been in close consultation," read the Sept. 9, 2004, letter from the three leaders.

"We believe that, should a request for dissolution arise this should give you cause, as constitutional practice has determined, to consult the opposition leaders and consider all of your options before exercising your constitutional authority."

That message is in stark contrast to the one Harper delivered Friday night, when he charged that Liberals don't "have the right to take power without an election."

"The opposition has been working on a backroom deal to overturn the results of the last election without seeking the consent of voters. They want to take power, not earn it," he said in a statement.

Now Conservative MPs are being instructed to take that message to Canadians.

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[Hat Tip: Canadian Cynic: Because they really do need babysitting, that's why]

Is Superstition the Default Belief?

 
Are you getting tired of the modern mantra about religion—you know, the one that says it's wired into our genes and therefore probably correct or at least beneficial? I am.

So, apparently, is A.C. Graying who writes in Friday's Guardian (UK) [Children of God].

Earlier this week I had occasion to debate – if the soundbite culture of radio news permits that description – with a member of Oxford University's Centre for Anthropology and Mind the "findings" of its cognition, religion and theology project, to the effect that children are hardwired to believe in a "supreme being". The research is funded by the Templeton Foundation, an organisation keen to find, or to insert, religion into science and to promote belief in their compatibility – which, note, comes down to spending money on "showing" in the end that the beliefs of ancient goatherds are as good as modern physics.

Justin Barrett, a Christian and member of the centre's research team (whether it is research or propaganda is the moot question here) says with his colleagues on the centre's website:

"Why is belief in supernatural beings so common? Because of the design of human minds. Human minds, under normal developmental conditions, have a strong receptivity to belief in gods, in the afterlife, in moral absolutes, and in other ideas commonly associated with 'religion' … In a real sense, religiousness is the natural state of affairs. Unbelief is relatively unusual and unnatural."

This claim was the subject of Barrett's lecture at Cambridge, in which he exhibited his reasons for thinking that children are innately disposed to believe in intelligent design/creationism and a supreme being. His real reasons for thinking this, of course, are that he is a man of faith funded by a faith-based organisation; but the reasons he professed were that children have an innate tendency when small to interpret what happens in the world to be the outcome of purposive agency.

Now on this point he and I, an atheist funded by no organisation keen on promoting atheism, agree. Children's earliest experiences are of purposive agency in the adults and other people around them – these being the entities of most interest to them in their first months – and for good evolutionary reasons they are extremely credulous, not only believing that things must be acting as their parents do in being self-moving and intentional, but also believing in tooth fairies, Father Christmas, and a host of other things beside, almost all of which they give up believing before puberty, unless the beliefs are socially reinforced – as with religious and, to a lesser extent, certain other superstitious beliefs. Intellectual maturation is the process in important part of weaning oneself from the assumption that trees and shadows behave as they do for the same reason that one's parents, other humans, and dogs and cats do; it is every bit as natural a fact about children that they cease to apply intentionalistic explanations to everything as that they give them to everything, on the model of their parents' behaviour, in the earliest phases of development.

...

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[Hat Tip: RichardDawkins.net

Kill Him, Kill Him Dead

 
These are interesting times in Canada. We recently re-elected the Conservative Party as the party with the most seats in Parliament—but not a majority. That means Stephen Harper becomes Prime Minister of a minority government.

What this normally means is that the government has to craft legislation that will receive the support of a majority of the house. But that's not what Harper proposes to do. Instead he has come up with a proposal that promotes a hard-core right-wing agenda. He did this because he assumed that the Liberal party would be forced to support the government in spite of the fact that they are ideologically opposed to many of the items in the legislation. Harper thought that the Liberal party was in such desperate shape to avoid an election that they would vote for the devil.

Turns out he was wrong. In an extraordinary development, the three opposition parties—Liberals, New Democratic Party, Bloc Quebecois—have forged a coalition and announced they will vote against the government bill.¹ This will bring down the government. Stephen Harper will not be Prime Minister but there will not be an election. Instead, the coalition will form a new government.

Scott Reid of The Globe and Mail has a column in yesterday's paper that illustrates the seriousness of the crisis. It's unusual to see such language in a Canadian newspaper—especially The Globe and Mail—so I thought I'd reproduce part of his column here to show the world what is going on. I agree with Scott Reid. For the good of Canada Stephen Harper must be stopped before he does serious harm to the country.

First things first: take him out.

After all, Stephen Harper is the most dangerous animal lurking in the jungles of Parliament. He is a threat to the future viability of the Liberals. A blood simple opponent of the NDP and the only serious contemporary challenge to the Bloc Quebecois. Without him, his party is an unlikely combination of Reform Party leftovers, Harris refugees and Red Tory desperates. They don't matter or even exist without Mr. Harper. So before you think a moment longer, opposition leaders, think on that.

And if that's not compelling enough, remember: He doesn't play to win. He plays to conquer. Under his guidance, the public interest is always subjugated to his personal political advancement. And he poisons Parliament with an extreme, bare-fanged breed of partisanship that has no hope of repair until he is banished.

This becomes relevant because suddenly, he is weak. In fact, at this particular moment, he is almost unable to defend himself. Owing to a ridiculously ill-considered act of hubris, he has laid himself vulnerable to his opponents. Their imperative could not be more clear: kill him. Kill him dead. Do not, whatever you do, provide him with an opportunity to extend his hold on power. Because you can be damn certain he will never again be so reckless as to give you a chance to finish him off.

Fate tends to be grudging with gifts of this significance. To ignore it would be an error every bit as historic as the one Mr. Harper himself has made.

So don't get fancy. Don't get confused. And don't get weak in the knees. If you don't put Mr. Harper in his grave, he'll put you in yours.

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1. They will also vote in favor of a non-confidence motion put forward by the Liberal party.

Biochemistry on the Web: The Citric Acid Cycle

Here are some websites that discuss the Citric Acid Cycle [Krebs animation][Wikipedia].

This is one of the fundamental biochemical pathways yet both of these sites contain errors. This is the time of the year when I challenge the students in my introductory biochemistry class to find one single website that correctly shows the reactions of the citric acid cycle with all the correct substrates and products (including water and protons). There are two sites that don't count: ones with images from my book (Horton et al.) and ones that are direct copies of the International Biochemistry and Molecular Biology (IUBMB) website. In five years my students have not succeeded. Can any Sandwalk reader find one?

Here are the links to the IUBMB reactions. They all have the correct reaction at some location. You may have to follow one or more of the links to the reaction to see the complete, correct version.

Enzymes of the Citric Acid Cycle

citrate synthase [EC 2.3.3.1]
aconitase [EC 4.2.1.3]
isocitrate dehydrogenase [EC 1.1.1.41][EC 1.1.1.42]
α-ketoglutarate dehydrogenase [EC 1.2.4.2]
succinyl-CoA synthetase [EC 6.2.1.4][EC 6.2.1.5]
succinate dehydrogenase [EC 1.3.5.1]
fumarase [EC 4.2.1.2]
malate dehydrogenase [1.1.1.37]

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