Glycogen Storage Diseases

Type 0: Hypoglycemia due to lack of glycogen synthase [OMIM 240600, OMIM 138571]

Glycogen synthase is the enzyme required for glycogen synthesis [Glycogen Synthesis]. There are two forms of the enzyme; liver and muscle. The muscle form is found in many different tissues but the liver version of the enzyme is only found in liver cells. Mutations in the gene for the liver enzyme (GTS2) cause glycogen storage disease type 0.

The disease is usually recognized in infants who have very low blood sugar (hypoglycemia) after a short fast. The low sugar is due to the fact that there's no store of glycogen in the liver. In normal cases, the liver stores glucose as glycogen right after a meal then breaks it down as blood glucose is depleted. In the absence of liver glycogen synthase the maintenance of blood sugar levels is impaired.

Here's what OMIM has to say about typical cases.

Gitzelmann et al. (1996) described 3 children with liver glycogen synthase deficiency from 2 German families and compared the observations with the previously published 3 families comprising 8 patients. The 2 index cases presented with morning fatigue, had ketotic hypoglycemia when fasting which rapidly disappeared after eating, and hepatic glycogen deficiency with absent or very low hepatic glycogen synthase activity. Metabolic profiles comprising glucose, lactate, alanine, and ketones in blood were typical for hepatic glycogen synthase deficiency. Symptoms were rapidly relieved and chemical signs corrected by introducing frequent protein-rich meals and nighttime feedings of suspensions of uncooked corn starch. The discovery of oligosymptomatic and asymptomatic sibs suggested that there are persons with undiagnosed hepatic glycogen synthase deficiency. Gitzelmann et al. (1996) stated that the disorder should be sought in children who, before the first meal of the day, present with drowsiness, lack of attention, pallor, uncoordinated eye movements, disorientation, or convulsions, and who have hypoglycemia and acetone in the urine.

Type I: Von Gierke's Disease: Deficiency in glucose 6-phosphatase [Ia OMIM 232200, Ib OMIM 602671, Ib OMIM 232220, Ic OMIM #232240]

The synthesis of glucose (gluconeogenesis) in the liver ends with glucose 6-phosphate. It can be stored as glycogen in the liver for use later on or it can be converted to glucose. Glucose is then secreted into the blood stream where it can be taken up by muscle cells. The cycling of glucose between muscle and liver is called the Cori Cycle.

One of the key enzymes is glucose 6-phosphatase. This is the enzyme that removes the phosphate group from glucose 6-phosphate to make free glucose. In mammals, this enzyme is located in the membranes of the endoplasmic reticulum. The enzyme is part of a complex that includes a glucose 6-phosphate transporter (G6PT) and a phosphate transporter. G6PT moves glucose 6-phosphate from the cytosol to the interior of the ER where it is hydrolyzed to glucose and inorganic phosphate. Phosphate is returned to the cytosol and glucose is transported to the cell surface (and the bloodstream) via the secretory pathway.

The other enzymes required for gluconeogenesis are found, at least in small amounts, in many mammalian tissues. By contrast, glucose 6-phosphatase is found only in cells from the liver, kidneys, and small intestine, so only these tissues can synthesize free glucose. Cells of tissues that lack glucose 6-phosphatase retain glucose 6-phosphate for internal carbohydrate metabolism.

Defects in glucose 6-phosphatase affect mostly liver and kidneys where stored glycogen can accumulate to high levels due to the fact that it can't be broken down to free glucose for secretion into the blood stream. Glycogen storage disease Ia results from mutations in the catalytic subunit of glucose 6-phosphatase (G6PC gene) while Ib and Ic are caused by mutations in the transporter subunits.

The major problem is hypoglycemia (low glucose) and lactic acidemia due to inefficient conversion of lactic acid to free glucose. These can be fatal but nowadays the symptoms are treated by feeding carbohydrates at regular intervals throughout the day and though a gut tube at night. This is an autosomal recessive disease.

Type II (Pompe Disease): Deficiency of α-glucosidase [OMIM #232300, OMIM 606800]

Glycogen granules are taken up by lysosomes where they are broken down by a pathway that's different from the normal glycogen degradation pathway. One of the key lysosomal enzymes is α1,4-glucosidase. Mutations in the gene for this enzyme cause glycogen storage disease type II.

This is a very severe form of the disease. Although glycogen breakdown in lysosomes is relatively minor in terms of overall glycogen metabolism, the inability to process glycogen granules leads to their accumulation in lysosomes and consequent disruption of many important lysosomal functions. This disruption takes place in all cells and all tissues.

In the classic cases, infants are inactive and hypertonic with enlarged hearts. Death usually occurs before the first year, usually from heart failure. An adult onset version is known. It usually begins with respiratory difficulties and often ends in death from ruptures of the arteries or respiratory failure.

Type III: (Cori Disease): Defects in glycogen debranching enzyme [OMIM 232400, OMIM 610860]

The glycogen debranching enzyme is required for the complete mobilization of glucose from glycogen. The standard glycogen phosphorylase enzyme will lop off glucose residues until it come to within for residues of a branch point in the glycogen chain. This produces a truncated glycogen molecule known as limit dextrin.

Further degradation of glycogen requires the activity of the debranching enzyme which actually has two separate activities: a glucanotransferase activity that transfers glucose residues from the end of one branch to the end of another, and a glucosidase activity that chops off the last glucose residue on a branch. The gene is the AGL gene (amylo-1,6-glucosidase, 4-α -glucanotransferase) in humans and the GDE gene (glycogen debranching enzyme) in many other species.

There are several subtypes of type III glycogen storage disease. They all result from mutations in the AGL gene. The most common type is IIIa where debranching activity is missing in both liver and muscle cells [see The Cori Cycle]. Patients have muscle weakness and liver problems similar to those in von Gierke's Disease (type I) but the symptoms are milder and not usually life threatening.

In type IIIb the deficiency in debranching enzyme is only detectable in liver. This is probably due to lower production of functional enzyme that only affects liver cells where more debranching enzyme is needed than in muscle cells.

Types IIIc and IIId are quite rare. They only affect the glucanotransferase activity (IIIc) or the glucosidase activity (IIId).

Type IV (Anderson Disease): Deficiency in glycogen branching enzyme [OMIM #232500, OMIM 607839]

Glycogen storage disease IV is caused by a deficiency of glycogen branching enzyme (amylo-(1,4 → 1,6)-transglycosylase). This is the enzyme that adds new branches for glycogen during synthesis. A deficiency in this enzyme results in reduced ability to store glucose residues in glycogen.(This is the enzyme responsible for the wrinkled pea phenotype that Gregor Mendel studied. [ Biochemist Gregor Mendel Studied Starch Synthesis.)

The disease is severe according to OMIM.

Glycogen storage disease type IV is a clinically heterogeneous disorder. The typical 'classic' hepatic presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular presentation of GSD IV is distinguished by age at onset into 4 groups: perinatal, presenting as fetal akinesia deformation sequence (FADS) and perinatal death; congenital, with hypotonia, neuronal involvement, and death in early infancy; childhood, with myopathy or cardiomyopathy; and adult, with isolated myopathy or adult polyglucosan body disease (Bruno et al., 2004). The enzyme deficiency results in tissue accumulation of abnormal glycogen with fewer branching points and longer outer branches, resembling an amylopectin-like structure, also known as polyglucosan (Tay et al., 2004).

Type V (McArdle Disease): Deficiency of muscle glycogen phosphorylase [OMIM 23600, OMIM 608455]

Glycogen phosphorylase is the enzyme that degrades glycogen [Glycogen Degadation]. Deficiencies in the muscle form of the enzyme lead to severe muscle cramps. Patients are not able to perfom strenuous exercise. The lack of muscle glycogen phosphorylase prevents breakdown of glycogen in muscle and consequent lack of glucose to fuel ATP production via glycolysis. One of the characteristic symptoms is an absence of blood lactate since muscle cells are unable to convert glycogen to glucose and then to lactate.

Muscle tissue breaks down due to lack of ATP leading to general weakness, especially in adults. The disease is not fatal; in fact, it is relatively harmless as long as patients avoid exercise.

Type VI (Hers Disease): Deficiency in liver phosphorylase [OMIM 23700]

Deficiencies of the liver form of glycogen phosphorylase are not as harmful as deficiencies of the muscle version (type V). The disease is inherited as an autosomal recessive and it's due to mutations in the gene for the liver form of glycogen phosphorylase.

The symptoms are mild compared to other forms of glycogen storage disease, giving rise to enlarged liver with mild hypoglycemia, mild ketosis, and retarded growth.

Type VII (Tarui Disease): Muscle phosphofructokinase deficiency [OMIM #232800, OMIM 610681]

According to OMIM,

Glycogen storage disease VII is an autosomal recessive metabolic disorder characterized clinically by exercise intolerance, muscle cramping, exertional myopathy, and compensated hemolysis. Myoglobinuria may also occur. The deficiency of the muscle isoform of PFK results in a total and partial loss of muscle and red cell PFK activity, respectively. Raben and Sherman (1995) noted that not all patients with GSD VII seek medical care because in some cases it is a relatively mild disorder.

Muscle phosphofructokinase (PFKM) is an enzyme required for glycolysis. When glycolysis is blocked in muscle cells glycogen cannot be broken down and there is no abundant supply of ATP available for muscle activity.

Type IXa (X-linked liver glycogenosis): Deficiency of liver phosphorylase kinase [OMIM 306000

Phosphorylase kinase is the enzyme that phosphorylates glycogen phosphorylase in order to regulate its activity [Regulating Glycogen Metabolism]. Defects in the phosphorylase kinase gene (PHK) cause glycogenstorage disease type IXa&mdash a very mild form of the disease according to OMIM.

Deficiency of liver phosphorylase kinase (PHK; ATP:phosphotransferase; EC 2.7.1.38) produces one of the mildest of the glycogenoses of man. The clinical symptoms include hepatomegaly, growth retardation, elevation of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase, hypercholesterolemia, hypertriglyceridemia, and fasting hyperketosis (Schimke et al., 1973; Willems et al., 1990). With age, these clinical and biochemical abnormalities gradually disappear and most adult patients are asymptomatic.

Phosphorylase kinase consists of α, β, γ, and δ sunbuits each of which is encoded by specific genes. Defects in the α subunit gene (PHKA) are what causes glycogen storage disease type IXa. There are two different genes for α subunits on the X chromosome: one for the liver specific version of the enzyme (PHA2) and one for the muscle specific version of the enzyme (PHA1). Mutations in either one cause the disease, which is why it is called an X-linked glycogen storage disease.

99 Years and Counting

At this time next year, the Department of Biochemistry at the University of Toronto will be celebrating its 100th anniversary with a symposium and a party. Everyone is invited!

Our department was the first biochemistry department in Canada and one of the first in the world [Biochemistry at the University of Toronto - A Short History]. Readers are invited to submit examples of older biochemistry departments if you can find them

The first chair of the department, Archibald Byron Macallum, was appointed in 1907 for the 1907-08 academic year. We've decided to celebrate at the end of the 2007-2008 academic year.

Former students, staff, faculty, post-docs and anyone else who has ever been associated with the department will meet here for several days in May 2008. We expect to play host to guests from every biochemistry department in Canada and from many other places throughout the rest of the world.

Nobel Laureate: Eduard Buchner

 
The Nobel Prize in Chemistry 1907.

"for his biochemical researches and his discovery of cell-free fermentation"



Eduard Buchner (1860-1917) won the Nobel Prize in 1907 for discovering that cell free extracts of yeast could convert sugar to ethanol. This was one of the greatest discoveries in biology [Fermentation: Synthesis of Ethanol]. The presentation speech outlines the importance of the discovery so I'll quote a large part of it below. This speech was never actually delivered because the award ceremony had to be cancelled due to the death of King Oscar II just two days earlier.

... it has been found possible to lift the veil which hitherto covered the phenomena of organic life. Thus a very large number of substances, which at the time in question it was assumed could only be formed by living organisms, can now be prepared synthetically. When, however, it is a matter of the inner course during the formation and conversion of these substances in living beings, we have to admit that our knowledge is still very far from complete. To be sure, it is no longer said that the living being is governed by a special "life force", but very often we have to make do even today with another expression which, in its actual meaning, does not differ very much from the first. It is frequently said now that this or that process should be regarded as a "life phenomenon" or "life expression" in certain cells. Regrettably we have to recognize that in this we are to a great extent merely providing a word instead of a deeper insight. It is certainly true that the frontier territories in which chemical research is now struggling to penetrate the complicated, mystic phenomena of life have in many respects advanced far beyond where it stood in 1813. Meanwhile, it still remains a fact that we owe considerable unconditional recognition to a work which in this field has taken experimental chemical research a sure step farther.

This is applicable to the work which is now the subject of the Prize award.

In a few words I shall try to explain to you what it is about.

For a long time chemists have been paying great attention to the phenomena which we now call fermentation. Under this name we include a number of chemical processes which occur in living beings and for which they are of the greatest importance. Usually these are decomposition processes in which compound substances are split under the influence of agents which we call ferments. These ferments act, so to speak, by their mere presence. Without being themselves transformed, they cause certain definite changes in other substances, the effect of each ferment being limited to a certain substance or a certain group of substances. It is an important property of ferments that, precisely under such circumstances as obtain in living beings, they exert a powerful action, whilst under others they frequently and easily become ineffective. Since, on the other hand, by means of other chemical aids, chemical processes can be brought about which appear similar to the actions of the ferments-several examples of which are available-it often happens that for this purpose agents are necessary whose nature makes them quite foreign to, and often incompatible with, conditions in living beings.

In very recent times, particularly, the advancement of our knowledge has made it probable that there are processes which are fermentative to a particularly high degree, which bring about the conversion of substances in living beings and which thus control this condition of life. Just as chemical science has during the past century acquired an extensive knowledge of the composition and structure of organic substances, so a thorough knowledge of the nature and action of ferments is now essential, in order that this science may be in a position to master the laws of the formation and dissociation of substances within the organism.

Meanwhile, we know these ferments up to now only by the effects they produce. Their inner nature and the constitution of their substance are still unknown to us. It is to be hoped, however, that a solution to this puzzle may be the subject of a future Nobel Prize.

A number of fermentations have been readily observable. This relates, for example, to the ferments which occur in dissolved state in the secretions which are discharged into the digestive system and exert such a great influence there. It has thus been possible to gain very considerable experimental experience concerning these fermentations.

Another group of fermentations, however, had been seen to occur only in the presence of living cells. To this group belonged, among others, the decomposition of sugar into alcohol and carbon dioxide, under the action of ordinary yeast. The connection between this fermentation and the presence of live yeast cells appeared so irresolvable that this fermentation process was regarded as an "expression of life" by the cells. This process thus appeared to be inaccessible to more detailed research.

Through Pasteur this view was accepted and generally adopted in scientific circles.

The unforgettable service done by Pasteur is that he showed that there are living organisms which are the originators of putrefaction and fermentation and of a number of processes which are of very great significance. Pasteur, who was distinguished not only by the genius of his ideas but also by an eminent talent as an experimenter, also tried - particularly as regards ordinary alcohol fermentation - to investigate the intrinsic interrelationship in this process. In particular he tried to answer the question whether the fermentation of alcohol was due primarily to a ferment produced by the yeast cells, in which case this ferment must be separated from them and be able to work independently of the presence of live yeast cells. His experiments, however, like those of others, concerning the occurrence of such a soluble ferment gave a negative result. Pasteur's view was thus considered to be confirmed, namely that the chemical process in alcoholic fermentation was a life expression by the yeast cells, and was thus inextricably linked with their life. This view prevailed for several decades.

At the same time as Pasteur earned for himself undying fame by his brilliant exposition of the significance of living beings as the ultimate cause of such processes, he put a brake on the progress of science in this field by the vitalistic concept of the actual course of fermentation. So long as fermentation was regarded as an "expression of life", and hence a phenomenon inseparable from life, there was little hope of being able to penetrate more deeply into the question of its course. It should be noted that this was of all the greater importance as it concerned not only alcoholic fermentation but a large group of important processes.

Under these circumstances it can easily be understood that a great sensation was created when E. Buchner, after many years' work, succeeded in showing that alcoholic fermentation could be produced from the juices expressed from yeast cells, free from live cells. He demonstrated incontrovertibly that this fermentation was due to a ferment produced by the yeast cells, from which it can be separated. Fermentation is not a direct expression of life by yeast cells; the cells can be killed and destroyed, while the ferment remains.

By Buchner's work, the fermentation mentioned and various other processes analogous to it have been freed from the shackles which previously held them and which prevented any progress in research. Now, no special difficulty is encountered in obtaining from yeast cells and various other cells an ample amount of powerfully active cell substance which is free from live cells. Numerous clarifying investigations into its properties have also been made, partly by Buchner himself and partly by others. Hitherto inaccessible territories have now been brought into the field of chemical research, and vast new prospects have now been opened up to chemical science.

Fermentation: Synthesis of Ethanol

 
Monday's Molecule #26 was actually three molecules: pyruvate, acetaldehyde, and ethanol. They're part of the pathway from sugar to ethanol.

In the first part of the pathway glucose is converted to pyruvate by the standard reactions of glycolysis. In the presence of oxygen the end product, pyruvate, will be oxidized to acetyl-CoA and CO₂ by pyruvate dehydrogenase. Acetyl-CoA will enter the citric acid cycle to complete the oxidation of glucose. There are several other fates of pyruvate including the conversion to lactate or ethanol. Both of these pathways take place in the absence of oxygen. They are called fermentation pathways.

The ability of yeast to ferment grapes and other fruits has been known for several millenia. Yeast cells can take the sugar from fruit (or grain) and convert it to pyruvate. If you mix yeast and fruit in a container that doesn't have much oxygen then the yeast cells will obligingly produce ethanol, a compound that has proven to be useful in the human diet. Yeast also produces CO₂ under these conditions and shown in the pathway above.

Today we know all about the enzymes that carry out these reactions but one hundred years ago things were less clear. It wasn't certain that fermentation could occur outside of living cells.

In one of the major conceptual advances in biology, Eduard Buchner (in 1897) was able to ferment sugar using a cell free extract of yeast. The reason why this was such an important discovery is that it removed all doubt about vitalism and the possibility that life was some special property outside of chemistry. Buchner showed that the production of ethanol from sugar was just a series of chemical reactions that did not need a living cell. This led directly to the discovery of enzymes and the elucidation of their properties. In a very real sense Buchner is the father of biochemistry [Nobel Laureate: Eduard Buchner].

Marks Are Posted!

 
The grades for my biochemsitry course have just been released to the students. I've already got several email messages from students who are complaining about their marks. One student got "only" 84% and wants to know how to petition for more marks. One student failed the final exam and ended up with a C- for a final grade. She thinks this is unfair.

Sigh. Why do we have to go through this every year? Is it just my students or does eveyone have this problem?

Alister McGrath

Last night I went to hear Alister McGrath speak on the topic Deluded about God? Responding to Richard Dawkins' God Delusion. He was in town as part of a conference organized by Wycliffe College, an evangelical Anglican graduate school of theology at the University of Toronto [Refresh!].

The people who attended the conference are not fans of Richard Dawkins and neither is Alister McGrath. McGrath is a Professor of Theology at Oxford University (UK). The lecture consisted almost entirely of quotations from Dawkins followed by statements that Dawkins has not proven his case; or the issue is still being debated; or Dawkins has misrepresented true religion (i.e. Anglicanism). There were very few actual attempts to rebut the Dawkins arguments. For this audience it seemed to be sufficient to simply state that Dawkins is wrong. If you want to see what kinds of points McGrath raised, then read this review of McGrath's upcoming book called The Dawkins Delusion! [Deluding Who About What?].

PZ Myers does not seem to be a fan of McGrath either as he pointed out in a posting this morning [Somebody needs to write a book called "The McGrath Delusion" now].

McGrath's main points were,

1. Atheism is a religion just like Christianity. Both require faith.
2. Science cannot prove that God doesn't exist.
3. Religion isn't all bad.
4. The Dawkins version of religion isn't the one most people believe in.

These are all boring points, and, to be fair, the audience of 150 people was not receiving them with enthusiasm except for the "amen" crowd in the first few rows.

McGrath made one additional point that I'm hearing more and more frequently. He claims that the plethora of recent books on atheism is evidence that the atheists are frightened. They think they're losing the battle and that's why they have to get out books to rally the troops.

According to McGrath, Christianity is on the rise and that's why the atheists are scared. The atheists can't understand why religion hasn't disappeared yet. At the end of the lecture we were allowed to submit written questions. One that got through the screening asked about the clear increase in the number of non-believers in polls over the past thirty years. (In Canada the number of non-believers has gone from about 2% to almost 20% in some recent polls.) McGrath responded that these polls were very deceptive because they weren't really recording atheists but people who were abandoning organized religion in favor of a more personal spiritual religion. That's why the polls don't reveal the real truth; namely, that Christianity is winning and atheists are scared.

The real reason for the recent books is the exact opposite of what McGrath wants to believe. Atheism is more and more popular and it's time for all non-believers to come out of the closet. As Dawkins points out, ten years ago he never would have been able to sell copies of a book called The God Delusion but today it's on the best seller list and Dawkins, Hitchins, Harris, Dennett and other atheists are on television every single day. It's the Christians who should be worried and in spite of the bravado last night, I think they are.

I'm sure McGrath would object to my characterization of his talk but to me it seemed very defensive. He was reacting to the Dawkins book and making rather banal attempts to defend Christianity against the assault of rationalism (his term). This is not something I've seen before at a conference of believers. The Christians in the audience were told in no uncertain terms that they have to get their act together and learn how to mount a sophisticated, rational defense of their beliefs. (Strange that they would need this call to arms if they're winning the war, isn't it?)

BTW, McGrath is another one of those former "atheists" who have converted to Christianity. This seems to be the new badge of "honor" among theologians. He makes this point several times and compares himself to Antony Flew. The fact that Flew has not converted to Christianity is only one of several dozen errors in the lecture. See [Deluding Who About What?] for a list. McGrath is still making the same errors.

Theistic Evolution According to Francis Collins

 
Another kerfuffle over Theistic Evolution has broken out in response to PZ Myers' complaint about Mitt Romney [Mitt Romney, theistic evolutionist…and this is supposed to be a good thing?]. I've been reading the comments over at Good Math, Bad Math [Religion != ID]. There are others such as the discussion on Primordial Blog [Theistic Evolution].

Update: PZ asks someone to explain to him the difference between Theistic Evolution and Intelligent Design Cretionism [Romney redux]. So far nobody's been able to do it. Stay tuned, read the comments over on Pharyngula.

Part of the problem is that we don't have a universally agreed upon definition of Theistic Evolution. The Wikipedia site does a pretty good job of covering all the possibilities [Theistic Evolution] based mostly on the original statement by Eugenie Scott [The Creation/Evolution Continuum] who says ....

Theistic Evolution is the theological view that God creates through evolution. Astronomical, geological and biological evolution are acceptable to TEs They vary in whether and how much God is allowed to intervene -- some come pretty close to Deists. Other TEs see God as intervening at critical intervals during the history of life (especially in the origin of humans), and they in turn come closer to PCs. In one form or another, TE is the view of creation taught at mainline Protestant seminaries, and it is the official position of the Catholic church. In 1996, Pope John Paul II reiterated the Catholic TE position, in which God created, evolution happened, humans may indeed be descended from more primitive forms, but the hand of God was needed for the creation of the human soul. (John Paul II, 1996).

As I stated in my essay [Theistic Evolution: The Fallacy of the Middle Ground], the true deist end of the continuum does not conflict with science but most other versions do.

Let's look at the version promoted by Francis Collins in his book The Language of God. This version seems to be closer to the popular versions than the benign deist versions. Collins lists six premises of Theistic Evolution (page 200).

1. The universe came into being out of nothingness, approximately 14 billion years ago.
2. Despite massive improbabilities, the properties of the universe appear to have been precisely tuned for life.
3. While the precise mechanism of the origin of life on earth remains unknown, once life arose, the process of evolution and natural selection permitted the development of biological diversity and complexity over very long periods of time.
4. Once evolution got under way, no special supernatural intervention was required.
5. Humans are part of this process, sharing a common ancestor with the great apes.
6. But humans are also unique in ways that defy evolutionary explanation and point to our spiritual nature. This includes the existence of the Moral Law (the knowledge of right and wrong) and the search for God that characterizes all human cultures throughout our history.

I'd also add one further point to this list since it's an important part of the conflict between science and religion that characterizes the Collins' version of Theistic Evolution.

Miracles do not pose an irreconcilable conflict for the believer who trusts in science as a means to investigate the natural world, and who sees that the natural world is ruled by laws. If, like me, you admit that there might exist something or someone outside of nature, then there's no logical reason why that force could not on rare occasions stage an invasion. On the other hand, in order for the world to avoid descending into chaos, miracles must be very uncommon.

I think points #2 and #6 and the issue of miracles, all impinge on science. This is why Theistic Evolution conflicts with science although we all admit that the conflict is less obvious that the conflict between science and Young Earth Creationism.

What's at stake here is the separation of science and religion discussed by Stephen Jay Gould in Rock of Ages. He proposed that science and religion could be Non-overlapping Magisteria (NOMA). What this means is that religion is okay as long as it sticks to things that do not conflict with science. I'm not a big fan of NOMA but the basic concept is worth adopting as a point of discussion. Does the Collins version of Theistic Evolution respect the NOMA Principle?

Here's how Gould describes it (pages 93-94).

The fallacies of such fundamentalist extremism can be easily identified, but what about a more subtle violation of NOMA commonly encountered among people whose concept of God demands a loving deity, personally concerned with the lives of all his creatures—and not just an invisible and imperious clockwinder? Such people often take a further step by insisting that their God mark his existence (and his care) by particular factual imprints upon nature. Now science has no quarrel whatsoever with anyone's need or belief in such a personalized concept of divine power, bu NOMA does preclude the additional claim that such a God must arrange the facts of nature in a certain set and predetermined way. For example, if you believe that an adequately loving God must show his hand by peppering nature with palpable miracles, or that such a God could only allow evolution to work in a manner contrary to to facts of the fossil record (as a story of slow and steady liner progress toward Homo sapiens for example), then a particular and partisan (and minority) view of religion has transgressed into the magisterium of science by dictating conclusions that must remain open to empirical test and potential rejection.

So, what do you think, dear readers? Does the idea that the universe is "precisely tuned for life" involve a transgression of religion into the proper domain of science? Does the idea that "humans are also unique in ways that defy evolutionary explanation" violate NOMA? Are miracles compatible with science?

I think the Collins version of Theistic Evolution is not compatible with science and therefore Collins has not resolved the conflict between science and religion. I think that most versions of Theistic Evolution conflict with science. The only version that's compatible is one that should be called Deistic Evolution.

Monday's Molecule #26

 


Today's molecule is actually three molecules. Name all three. The trivial names will do since they're very well known but if you can supply the correct chemical names that would be good.

As usual, there's a connection between Monday's molecules and this Wednesday's Nobel Laureate(s). This one is even easier than last week's. The reward (free lunch) goes to the person who correctly identifies both the molecule and the Nobel Laureate(s). (Previous free lunch winners are ineligible for one month from the time they first collected the prize. There are no ineligible candidates for this Wednesday's reward since Dunbar bought me lunch on Thursday. Therefore, technically, he did not collect a prize.)

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

The Bigs

 

My favorite son¹ works on computer games with a whole team of people in Vancouver. The trailer for their latest game is just out. It's professional baseball and it looks amazing. See it at The Bigs. (Gord does stadia, you can see what else he does at Gordon Moran.)

1. Also my only son.

My Ideal US Presidential Candidate

 
I don't get a vote but I decided to take the quiz anyway [2008 SelectSmart.com Presidential Candidate Selector]. I'm pretty happy with the result, it corresponds to my impression of the candidates. Initially I was impressed with John Edwards but that was a mistake. If I had a vote today it would probably go to Al Gore (if he were running) or Dennis Kucinich.

The ABC Nightline "Debate"

 
Just in case you haven't seen the "debate" here are the YouTube videos for your enjoyment. I'm sure the "intellectual" believers will disown Kirk Cameron and Ray Comfort but I wonder if they really could do a better job?

The "Coke Can" proof of the existence of God is a classic. Watch it in the second clip. It's hard to believe that Ray Comfort's intended audience can be stupid enough to fall for that argument but I have to assume that Comfort knows who he's talking to. After all, he convinced Kirk Cameron and he has years of experience preaching to average Christians.

The Emperor's New Clothes and the Courtier's Reply

I recently referred to the "Courtier's Reply", a term invented by PZ Myers to rebut the claims of believers who insist that their superstitious beliefs are ever so much more sophisticated than the simple version that Dawkins attacks.

PZ's response deserves much more publicity because it goes to the heart of the debate between rationalism and supersition. I'm going to post his original Courtier's Reply below (without permission, but I'm sure he'll understand) but before doing so I need to remind everyone about the original fairy tale [The Emperor's New Clothes].

THE EMPEROR'S NEW CLOTHESby Hans Christian Anderson

Once upon a time there lived a vain Emperor whose only worry in life was to dress in elegant clothes. He changed clothes almost every hour and loved to show them off to his people.

Word of the Emperor's refined habits spread over his kingdom and beyond. Two scoundrels who had heard of the Emperor's vanity decided to take advantage of it. They introduced themselves at the gates of the palace with a scheme in mind.

"We are two very good tailors and after many years of research we have invented an extraordinary method to weave a cloth so light and fine that it looks invisible. As a matter of fact it is invisible to anyone who is too stupid and incompetent to appreciate its quality."

The chief of the guards heard the scoundrel's strange story and sent for the court chamberlain. The chamberlain notified the prime minister, who ran to the Emperor and disclosed the incredible news. The Emperor's curiosity got the better of him and he decided to see the two scoundrels.

"Besides being invisible, your Highness, this cloth will be woven in colors and patterns created especially for you." The emperor gave the two men a bag of gold coins in exchange for their promise to begin working on the fabric immediately.

"Just tell us what you need to get started and we'll give it to you." The two scoundrels asked for a loom, silk, gold thread and then pretended to begin working. The Emperor thought he had spent his money quite well: in addition to getting a new extraordinary suit, he would discover which of his subjects were ignorant and incompetent. A few days later, he called the old and wise prime minister, who was considered by everyone as a man with common sense.

"Go and see how the work is proceeding," the Emperor told him, "and come back to let me know."

The prime minister was welcomed by the two scoundrels.

"We're almost finished, but we need a lot more gold thread. Here, Excellency! Admire the colors, feel the softness!" The old man bent over the loom and tried to see the fabric that was not there. He felt cold sweat on his forehead.

"I can't see anything," he thought. "If I see nothing, that means I'm stupid! Or, worse, incompetent!" If the prime minister admitted that he didn't see anything, he would be discharged from his office.

"What a marvelous fabric, he said then. "I'll certainly tell the Emperor." The two scoundrels rubbed their hands gleefully. They had almost made it. More thread was requested to finish the work.

Finally, the Emperor received the announcement that the two tailors had come to take all the measurements needed to sew his new suit.

"Come in," the Emperor ordered. Even as they bowed, the two scoundrels pretended to be holding large roll of fabric.

"Here it is your Highness, the result of our labour," the scoundrels said. "We have worked night and day but, at last, the most beautiful fabric in the world is ready for you. Look at the colors and feel how fine it is." Of course the Emperor did not see any colors and could not feel any cloth between his fingers. He panicked and felt like fainting. But luckily the throne was right behind him and he sat down. But when he realized that no one could know that he did not see the fabric, he felt better. Nobody could find out he was stupid and incompetent. And the Emperor didn't know that everybody else around him thought and did the very same thing.

The farce continued as the two scoundrels had foreseen it. Once they had taken the measurements, the two began cutting the air with scissors while sewing with their needles an invisible cloth.

"Your Highness, you'll have to take off your clothes to try on your new ones." The two scoundrels draped the new clothes on him and then held up a mirror. The Emperor was embarrassed but since none of his bystanders were, he felt relieved.

"Yes, this is a beautiful suit and it looks very good on me," the Emperor said trying to look comfortable. "You've done a fine job."

"Your Majesty," the prime minister said, "we have a request for you. The people have found out about this extraordinary fabric and they are anxious to see you in your new suit." The Emperor was doubtful showing himself naked to the people, but then he abandoned his fears. After all, no one would know about it except the ignorant and the incompetent.

"All right," he said. "I will grant the people this privilege." He summoned his carriage and the ceremonial parade was formed. A group of dignitaries walked at the very front of the procession and anxiously scrutinized the faces of the people in the street. All the people had gathered in the main square, pushing and shoving to get a better look. An applause welcomed the regal procession. Everyone wanted to know how stupid or incompetent his or her neighbor was but, as the Emperor passed, a strange murmur rose from the crowd.

Everyone said, loud enough for the others to hear: "Look at the Emperor's new clothes. They're beautiful!"

"What a marvellous train!"

"And the colors! The colors of that beautiful fabric! I have never seen anything like it in my life!" They all tried to conceal their disappointment at not being able to see the clothes, and since nobody was willing to admit his own stupidity and incompetence, they all behaved as the two scoundrels had predicted.

A child, however, who had no important job and could only see things as his eyes showed them to him, went up to the carriage.

"The Emperor is naked," he said.

"Fool!" his father reprimanded, running after him. "Don't talk nonsense!" He grabbed his child and took him away. But the boy's remark, which had been heard by the bystanders, was repeated over and over again until everyone cried:

"The boy is right! The Emperor is naked! It's true!"

The Emperor realized that the people were right but could not admit to that. He though it better to continue the procession under the illusion that anyone who couldn't see his clothes was either stupid or incompetent. And he stood stiffly on his carriage, while behind him a page held his imaginary mantle.

Here's how PZ Myers describes those people who claim to have a much more intellectual version of religion; one that can not be as easily dismissed as the "simple" version that Richard Dawkins addresses. These people seem to think that by dressing up their superstitious beliefs in fancy language with philosophical references they can escape the simple fact the the Emperor has no clothes.

The Courtier's Replyby PZ Myers

I have considered the impudent accusations of Mr Dawkins with exasperation at his lack of serious scholarship. He has apparently not read the detailed discourses of Count Roderigo of Seville on the exquisite and exotic leathers of the Emperor's boots, nor does he give a moment's consideration to Bellini's masterwork, On the Luminescence of the Emperor's Feathered Hat. We have entire schools dedicated to writing learned treatises on the beauty of the Emperor's raiment, and every major newspaper runs a section dedicated to imperial fashion; Dawkins cavalierly dismisses them all. He even laughs at the highly popular and most persuasive arguments of his fellow countryman, Lord D. T. Mawkscribbler, who famously pointed out that the Emperor would not wear common cotton, nor uncomfortable polyester, but must, I say must, wear undergarments of the finest silk.

Dawkins arrogantly ignores all these deep philosophical ponderings to crudely accuse the Emperor of nudity.

Personally, I suspect that perhaps the Emperor might not be fully clothed — how else to explain the apparent sloth of the staff at the palace laundry — but, well, everyone else does seem to go on about his clothes, and this Dawkins fellow is such a rude upstart who lacks the wit of my elegant circumlocutions, that, while unable to deal with the substance of his accusations, I should at least chide him for his very bad form.

Until Dawkins has trained in the shops of Paris and Milan, until he has learned to tell the difference between a ruffled flounce and a puffy pantaloon, we should all pretend he has not spoken out against the Emperor's taste. His training in biology may give him the ability to recognize dangling genitalia when he sees it, but it has not taught him the proper appreciation of Imaginary Fabrics.

Richard Dawkins on the Agenda

 
The Agenda with Steve Paikin is an interview show on TVO (TV Ontario). I watch it quite often.

Lately I've been more and more annoyed at Steve Paikin for his naive, simplistic views of religion and it's importance in the modern world. A few weeks ago he had an entire week of shows about the "resurgence" of religion in Canada. A resurgence that apparently only he and his fellow believers can see.

The show on Thursday night was just about the last straw for me. His interview with Richard Dawkins and the panel discussion afterwards were so bad that I'm going to stop watching the show. You can see the entire hour of the May 10th episode at [Richard Dawkins | Can We Live by Reason Alone?].

Pay close attention to Jordan Peterson in the panel discussion at the end. He's a Professor of Psychology at the University of Toronto. He accuses Dawkins of being very simplistic and naive about religion—and by implication he (Jordan Peterson) has the correct, deeply intellectual, understanding of religion that would trump Dawkins in a debate. Trouble is, nothing coming out of the mouth of Peterson convinces me that his reasons for believing in superstition are any better than the reasons Dawkins criticizes in The God Delusion. Or, am I missing some incredibly sophisticated version of the Courtier's Reply that's way over my head?

I especially like the claim that all hell will break loose if religion is abolished. The interesting part about such claims is that they come from people who are completely ignorant of what's going on in Europe. We're about to find out what happens when a country abandons religion because Sweden and other European countries are very close to that point. If the true believers are correct then these countries will soon become dens of iniquity and depravity—in sharp contrast to very religious countries like the USA. I can't believe that one of my colleagues would make such a stupid statement in public.

UPDATE: Read the comments on Dawkins.net

Biochemist Gregor Mendel Studied Starch Synthesis

Starch is the plant equivalent of glycogen. It consist of long branched chains of glucose residues. Starch is often stored in roots and tubers but it is also deposited in seeds where it can be mobilized following germination.

Mendel didn't know it at the time but he was dealing with the genetics of starch synthesis while crossing peas in his garden.

One of the genetic traits that Gregor Mendel studied was round ( R) vs. wrinkled ( r) peas. The wrinkled pea phenotype is caused by a defect in the gene for starch branching enzyme. Starch synthesis is very similar to glycogen synthesis. The main polymerization enzyme is starch synthase and it works just like glycogen synthase [Glycogen Synthesis]. Both starch and glycogen synthesis require an additonal enzyme to create new branches. In plants this enzyme is starch branching enzyme.

In the absence of this enzyme, starch synthesis is partially blocked and the developing peas have a higher concentration of sucrose. (In plants, glucose is transported as the disacharide sucrose.) This causes the mutant peas to absorb more water than normal peas and they swell to a larger size. When the seeds begin to dry out the peas with the defective enzyme lose more water and their outer surface takes on a wrinkled appearance. One copy of the active gene for starch branching enzyme is sufficient so the presence of one defective allele has no observable phenotype. When two mutant alleles are present the wrinkled phenotype is expressed because there's no active starch branching enzyme. The mutant allele is recessive to the wild type allele.

For some strange reason Mendel is more famous for discovering this simple genetic rule than for his contributions to understanding starch metabolism.

Bhattacharyya, M. K., Smith, A. M., Ellis, T. H., Hedley, C., and Martin, C. (1990) The wrinkled-seed character of a pea described by Mendel is caused by a transposon-like insertion in a gene encoding starch-branching enzyme. Cell 60:115-122.

[©Laurence A. Moran. Some of the text is from Principles of Biochemistry 4th ed. ©Pearson/Prentice Hall]

Gosling Relocation

 
Eva is a Ph.D. student in our department. She has a really cool blog called easternblot (get it?). You have got to see what she posted today [Annual gosling relocation at York University].

I've only got one small problem. Do we really need more Canada geese?