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Thursday, September 04, 2008

Why Is ATP an Important Energy Currency in Biochemistry?

For many years the answer to this question seemd obvious. As described by Fritz Lipmann, ATP has "high energy" bonds. When these bonds are cleaved by hydrolysis a large amount of free energy is released and this energy can be captured and used to perform useful work.

By the mid-1960s this concept was being challenged by biochemists with a deeper appreciation of thermodynamics and chemistry. For example, Albert Lehninger1 wrote in Bioenergetics (1965).
The High-Energy Phosphate Bond—a Misnomer

Those phosphorylated compounds having a relatively high free energy of hydrolysis, such as ATP, phosphocreatine, and phosphopyruvate, are often spoken of as having high-energy phosphate bonds, and such bonds are universally designated by the symbol ~P. These expressions have been very useful and handy to biochemists, but they can be very misleading to the beginner. The term "high-energy phosphate bond" is an unfortunate misnomer because it implies that the energy spoken of is in the bonds and that when the bond is split, energy is set free. This is quite wrong. In the ordinary usage of physical chemistry, bond energy is defined as the energy required to break a given bond between two atoms. Actually relatively enormous energies are required to break chemical bonds, which would not exist if they were not stable. The term "phosphate bond energy" thus does not refer to the true bond energy of the covalent linkages between the phosphorus atom and the oxygen or nitrogen atom. The term "high energy phosphate bond" means only that the difference in energy content between the reactants and the products of hydrolysis is relatively high: the free energy of hydrolysis is not localized in the actual chemical bond itself. It is regrettable that this use of these terms is so deeply ingrained by long usage, but it will not matter if we keep this true meaning in mind.
Lehninger goes on to explain why the standard Gibbs free energy of ATP hydrolysis is such a large negative number. His version is out-of-date so I'll give the modern view from a textbook that I'm very familiar with2 ...

We're discussing the following reaction

ATP + H2O → ADP + Pi          ΔG°′ = -32 kJ mol-1
Several factors contribute to the large amount of energy released during hydrolysis of the phosphoanhydride linkages of ATP.
  1. Electrostatic repulsion among the negatively charged oxygen atoms of the phosphoanhydride groups of ATP is less after hydrolysis. (In cells, ΔG°′hydrolysis is actually increased [made more positive] by the presence of Mg2+ which partially neutralizes the charges on the oxygen atoms of ATP and diminishes electrostatic repulsion.)
  2. The products of hydrolysis, ADP and inorganic phosphate, or AMP and inorganic pyrophosphate, are better solvated than ATP itself. When ions are solvated, they are electrically shielded from each other. The decrease in the repulsion between phosphate groups helps drive hydrolysis.
  3. The products of hydrolysis are more stable than ATP. The electrons on terminal oxygen atoms are more delocalized than those on bridging oxygen atoms. Hydrolysis of ATP replaces one bridging oxygen atom with two new terminal oxygen atoms.
The three contributions are: electrostatic repulsion; solvation effects; and resonance stabilization. The one most responsible for the large negative Gibbs free energy change is the solvation effect. The energies of solvation of ADP and inorganic phosphate are much greater than that of ATP, making hydrolysis to its products a more favorable state.

UPDATE:Under standard conditions the concentrations of substrates and products are equal (1M). Under those conditions, the reaction will proceed to the right until the concentration of ADP is very much higher than that of ATP. When the reaction reaches equilibrium the rates of the forward and reverse reactions are equal and ΔG = 0. At that point, there is no net free energy gain from hydrolysis of ATP. The only reason ATP is an energy currency inside cells is because the system is maintained (regulated) far from equilibrium. In fact, the concentration of ATP inside cells is higher than than that of ADP and the actual free energy change is even more negative than -32 kJ mol-1 [see The Demise of the Squiggle].

1. See Good Science Writers: Albert Lehninger.

2. Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Prentice Hall, Upper Saddle River N.J. (USA)

The Demise of the Squiggle

Fritz Lipmann is often credited with discovering ATP but that's not correct. He won his Nobel Prize for discovering Coenzyme A [The Nobel Prize in Physiology or Medicine 1953].

However, it's fair to say that Lipmann made some of the most important contributions to our understanding of ATP as an energy currency. His classic 1941 paper in Advances in Enzymology was entitled "Metabolic Generation and Utilization of Phosphate Bond Energy." In that paper he introduced the concept of an energy-rich phosphate bond designated by a squiggle (~). Thus ATP could be represented as


to show that it had two such high energy bonds. The cleavage of either bond is accompanied by a large release of energy that's available to do work. The idea that ATP contained some special bonds with high energy was very attractive and the concept ruled in biochemistry textbooks for several decades. Indeed, there are still many courses and websites that still use the squiggle.

The concept is extremely misleading and came under attack by many biochemists in the 1950s and 60s. According to these biochemists, the correct way of looking at ATP as an energy currency is to recognize that the overall reaction of hydrolysis is associated with a large negative Gibbs free energy change.

ATP + H2O → ADP + Pi          ΔG°′ = -32 kJ mol-1

It's the system, including reactants and products, that is associated with the large negative free energy change. The only reason ATP is useful as an energy currency is because the concentration of ATP is maintained at high levels relative to ADP + Pi inside the cell. As a matter of fact, the actual Gibbs free energy change in vivo is closer to -48 kJ mol-1.

If the system were allowed to reach equilibrium then ΔG°′ = 0. Think about what this means. At equilibrium those ~P "high energy" bonds are still being broken but there's no useful energy being produced.

Does this mean that the strength of a chemical bond depends on the relative concentration of reactants and products? Of course not. What it means, in the words of someone who knew Friz Lipmann, is that his understanding of basic thermodynamics was rudimentary.

The arguments over the proper way to think about ATP raged back and forth in the scientific literature for over thirty years. For the most part Lipmann did not participate in the squiggle debates, he left his defense to others. It's fair to say that there was no knock-out blow that ended the fight. Gradually people began to realize that the squiggle—and the concept of a high energy bond—were unfortunate at best and possibly misleading to the point of being counter-productive. The squiggle has been dropped from most (all?) textbooks.

So, how do we explain the fact that ATP hydrolysis is associated with a large release of energy under conditions found inside the cell? If it's not because of some special "high energy" bond, then what is it? See Why Is ATP an Important Energy Currency in Biochemistry?.

Here's a couple of articles on the history of the squiggle:

Fritz Lipmann

Power, Sex, Suicide: Mitochondria and the Meaning of Life: The elusive squiggle (p.80>)

Here are some websites that still refer to "high-energy" bonds and still use the squiggle. It's interesting that most of these sites include a modest disclaimer, stating that there's no such thing as a "high-energy bond" but they then go on to talk about high energy bonds using the squiggle notation.

Rensselaer Polytechnic Institute

Columbia University

University of Connecticut

Online Textbook: Department of School Education, Govt. of Tamil Nadu, India

[I am indebted to my colleague Byron Lane for explaining the history to me. He was a post-doc in the Lipmann lab during the 1950s where he was in a position to observe the debate first-hand. Byron kindly gave me copies of the relevant papers. Our discussion began when we realized that the kinds of scientific debates that were common in the past are no longer occurring even though there are many controversies bubbling beneath the surface. We don't know why. Does anyone?]

Tangled Bank #113

The latest issue of Tangled Bank has been published on En Tequila Es Verdad [The Tangled Bank #113: A Labor Day Carol].
Blogging across the parallel universes brings not only rewards but a burden of responsibilities. I learned this to my chagrin one day in 2112, on Tangled Bank #113, a beautiful little terraformed world in Parallel U. Gamma, named in honor of the great Charles Darwin. Certain theories of time travel had recently been overturned. My physicist friend Yoo Chung burst in my door shortly after creating a time travel device that utilized the wormholes he once doubted.

"Dana! Grab your Smack-o-Matic and hurry!" he shouted, arms flailing like dear little windmills. "Darwin never published Origin in Parallel U. Cappa. Now the backward denizens of that universe have stolen a U-Skipper from the anthropologists sent to observe them and are planning to unleash ignorance bombs throughout the multiverse! There's no time to lose!"

Send an email message to if you want to submit an article to Tangled Bank. Be sure to include the words "Tangled Bank" in the subject line. Remember that this carnival only accepts one submission per week from each blogger. For some of you that's going to be a serious problem. You have to pick your best article on biology.

Wednesday, September 03, 2008

Good Science Writers: Albert Lehninger

Albert Lehninger (1917 - 1986) was a biochemist whose main research interest was the production of energy by mitochondria. His second book, Bioenergetics was published by W.A. Benjamin Inc. in 1965 as part of a series of biochemistry books by well-known scientists. One of the other books in the series was Molecular Biology of the Gene by James D. Watson. Neil Paterson of W.A. Benjamin was the man behind getting these scientists to write books for the general public and students.

Later, when Neil Patterson had moved to Worth Publishers, he persuaded Lehninger to write a textbook and the first edition of Biochemistry was published by Worth in 1970. Following Lehninger's death in 1986, the book, now called Lehninger Principles of Biochemistry was taken over by David Nelson and Michael Cox and the current publisher is W.H. Freeman and Company.

Lehninger's writing was characterized by an emphasis on basic chemical principles and his style was crisp and unapologetic. He is not mentioned by Richard Dawkins in his book: The Oxford Book of Modern Science Writing but that's no surprise because many well-known textbook authors are not recognized as good science writers.

The first excerpt comes from Bioenergetics )pp. 18-20).
The First Law [of thermodynamics] tells us that energy is conserved; every physical or chemical change must satisfy this principle. However, there is another fundamental aspect of energy exchange which is not explained by the First Law. A simple example will serve to illustrate the problem.

Suppose we place two blocks of copper together, one hot and one cold, and seal them in an insulated container. The temperature of the hot block will fall and that of the cold block will rise until they both reach some intermediate temperature, which at equilibrium will be uniform throughout both blocks. The flow of heat and thus of energy from the hot block to the cold is spontaneous. However, if we put two identical blocks of copper, both at the same temperature, into such a container, we know that they will remain at the same temperature; we would never expect the temperature of one block to rise spontaneously and that of the other to fall. However, if this should happen, it would not violate the First Law because the energy lost by one block would be gained by the other; the total energy of the two blocks would remain the same.

It is quite clear from considering this example ... that spontaneous physical or chemical changes have a direction which cannot be explained by the First Law. In brief, all systems tend to approach equilibrium states in which temperature, pressure, and all other measurable parameters of state become uniform throughout. Once they reach such an equilibrium they no longer change back spontaneously to the nonuniform or nonrandom state. When the two blocks of copper in our model have reached exactly the same temperature, all the heat energy originally contained in the two blocks has been maximally randomized, and we know that it will never by itself "unrandomize." The Second Law of thermodynamics provides us with a new yardstick or criterion for predicting the tendency of a physical process to occur and the direction in which it will occur. First, it defines entropy as a randomized state of energy that is unavailable to do work. Second, it states that all physical and chemical processes proceed in such a way that the entropy of the system becomes the maximum possible. At this point there is equilibrium.
The second excerpt is from the first edition of Biochemistry (1970) pp. 276-278. (The second edition is shown in the figure.)
Complex organic molecules such as glucose, contain much potential energy because of their high degree of structural order; they have relatively little randomness, or entropy. When the glucose molecule is oxidized by molecular oxygen to form six molecules of CO2 and six of water, its atoms undergo an increase in randomness; they become separated from each other and may assume different locations in relation to each other. As a result of this transformation, the glucose molecule undergoes a loss of free energy, which is useful energy capable of doing work at constant temperature and pressure.

The free energy of glucose so released is harnessed by the cell to do work. Biological oxidations are in essence flameless or low-temperature combustions. As we have seen, heat cannot be used as energy source by living organisms, which are essentially isothermal, since heat can do work at constant pressure only when it can flow from a warmer to a cooler body. Instead, the free energy of cellular fuels is conserved as chemical energy, specifically the phosphate-bond energy of adenosine triphosphate (ATP). ATP is enzymatically generated from adenosine diphosphate (ADP) and inorganic phosphate in enzymatic phosphate-group transfer reactions that are coupled to specific oxidation steps during catabolism. Since the ATP so formed can now diffuse to those sites in the cell where its energy is required, it is thus also a transport form of energy. The chemical energy of ATP is then released during transfer of its terminal phosphate group(s) to certain specific acceptor molecules, which become energized and can do work.

[Photo Credit: Mitochondria and Neuroprotection—In Memory of Albert L. Lehninger]

ATP Is a Coenzyme

ATP (adenosine 5′-triphosphate) is the main energy currency in living cells. It undergoes a type of reaction called hydrolysis where one or two of the terminal phosphate groups are released.

These reactions are accompanied by a considerable release of energy and that's why ATP is such an important molecule. It is synthesized by a special reaction that is not the reverse of the hydrolysis reaction. Instead it utilizes the energy of a proton gradient across a membrane to make ATP [How Cells Make ATP: ATP Synthase]. Since ATP is very stable inside the cells it can serve as an energy storage molecule until it is ready to be used.

One of the important features of enzymes is their ability to couple reactions that would otherwise not occur. One of the ways that enzymes do this is by bringing together two different substrates to form a reactive intermediate. There are dozens of molecules that can be used in a wide variety of different reactions and these are referred to as coenzymes or cofactors. ATP is one of them.1

Here's an example of how ATP can be used to make a reaction proceed when it would otherwise not take place because it requires too much energy. The formation of glutamine from glutamate requires the attachment of an ammonia group to glutamate. This reaction will not take place inside the cell because the direct energy requirement is too high.

Instead, the enzyme glutamine synthetase utilizes the energy of ATP to make the reaction go in two steps.

In the first step, ATP is hydrolyzed to ADP and the phosphate group is attached to glutamate to make a "high energy" intermediate called γ-glutamyl phosphate. The enzyme does not release this product; it holds on to it until a molecule of ammonia enters the active site to displace the phosphate group and create glutamine. In this way the overall reaction can proceed because each of the intermediate steps is favorable. (Hydrolysis of ATP in step one and hydrolysis of γ-glutamyl phosphate in step two.)

The enzyme has coupled the overall hydrolysis of ATP to ADP + Pi to the formation of glutamine from glutamate. ADP will be used to synthesize another molecule of ATP so that the store of energy currency remains constant inside the cell.

1. ATP was first discovered as an essential factor in fermentation and muscle contraction. Hans von Euler-Chelpin received the Nobel Prize in 1929 for recognizing the importance of adenosine phosphate "cozymases."

Nobel Laureate: Hans von Euler-Chelpin


The Nobel Prize in Chemistry 1929.

"for their investigations on the fermentation of sugar and fermentative enzymes"

Hans Karl August Simon von Euler-Chelpin (1873 - 1964) received the 1929 Nobel Prize in Chemistry for his work on fermentation, especially the recognition of a phosphorylated nucleoside as an important cofactor (cozymase). We now know that the most important cofactor is ATP.

Here's how von Eular-Chelpin describes the work in his Nobel Lecture.
By a long series of purification processes a preparation was obtained with a maximum activity - expressed in rational units - of ACo = 85,000, the starting material being characterized by ACo = 200. It was possible to convert this preparation into salts - salts of the alkaloids and of the alkaline-earth metals were used for the isolation - and cozymase can be recovered therefrom with practically unchanged activity4. The composition of the most highly purified product corresponds approximately to a so-called nucleotide, for it contains a sugar residue, a purine residue and phosphoric acid, and everything points to a close relationship with a substance occurring in muscle in small quantities, adenylic acid.
Hans von Euler-Chelpin was recognized by the Nobel Committee but he rarely gets credit in the textbooks for discovering ATP.

von Euler-Chelpin shared the 1929 Nobel Prize with last week's Nobel Laureate, Arthur Harden.

Nobel Laureates
The presentation speech was delivered on December 10, 1929 by Professor H.G. Söderbaum, Chairman of the Nobel Committee for Chemistry of the Royal Swedish Academy of Sciences. (All award ceremonies are held on Dec. 10th because Dec. 10, 1896 was the day Alfred Nobel died.)
Your Majesty, Your Royal Highnesses, Ladies and Gentlemen.

The fermentation of liquids containing sugar - there we have a chemical reaction older than all chemical science. The point of time when men first began to take this reaction into their service is really lost in the mists of antiquity, before the beginning of history. The peculiar and apparently self-caused process by which an innocent fruit juice is transformed with the active formation of scum, into a drink which is either stimulating or intoxicating according to the quantity partaken, attracted attention in the very earliest times; and to many peoples it appeared so wonderful that nothing less than the cooperation of a divinity seemed to them possible as an explanation.

Our enlightened time has scarcely the right to marvel at this, when we take into consideration how long a time science has since required to obtain an acceptable conception of the nature of fermentation. Here we stand face to face with one of the most complicated and difficult problems of chemical research. Little more than a couple of centuries separate us from the time when men first began to perceive that the fermenting substance was sugar, which under the influence of a certain something was decomposed, with carbonic acid and ethyl alcohol as the final products of the decomposition.

But what this "something" was, and how it worked, still remained unsolved questions, long defying the most penetrating attempts at interpretation. It was not until our own days that it has been vouchsafed to us to have a fairly satisfactory answer to these questions, but even here the process of development has been slow, toilsome, and it took place, so to speak, in several instalments.

In carrying out the provisions of Alfred Nobel's Will, the Swedish Academy of Sciences has already once before had its attention directed to this sphere of research. That was in 1907, when Eduard Buchner was awarded the Nobel Prize in Chemistry for his discovery of non-cellular fermentation. At the time complaints were raised in certain quarters against this award as being insufficiently justified. Seen in the perspective of distance in time, however, Buchner's discovery has more and more stood out as a line of demarcation between two different epochs, pointing the way to a new phase in the history of the chemistry of fermentation.

Buchner's discovery marked the final decision in a long struggle between two distinct schools - one, the older one, represented by Justus von Liebig the other, the younger one, represented by Louis Pasteur. According to the former school, fermentation was a purely chemical process, evoked by an unorganized ferment with unstable properties, which were imparted to the fermenting substance and thereby brought about its decomposition. According to the latter school, it was rather a physiological process, inseparably connected with the vital act of a microorganism known as the "fungus of fermentation". Buchner's discovery made it evident that to some extent both were right, but also to some extent both were wrong, and, consequently, that the truth lay between the two.

But the value of the discovery makes itself known in a still more definite way through the impulse it has given to later research. In fact, during the last three decades that research has made such great advances, has given such an enlarged insight into the mechanism of the process of fermentation, that the Academy of Sciences has found the time ripe once again to award a Nobel Prize in this department. In so doing the Academy has deemed it right to divide equally the Nobel Prize in Chemistry for the present year between Professor Arthur Harden and Professor Hans von Euler.

Buchner assumed in the yeast juice the presence of a uniform ferment or enzyme, known as "zymase".

When, however, Harden and his fellow-workers filtered a quantity of Buchner's yeast-juice through a gelatine filter, known as an "ultrafilter", and thereby split it up into two fractions (a filtrate and a sediment that did not pass through the filter), the curious state of things occurred that neither of these fractions was any longer able to bring about fermentation, but that after being mixed with one another they recovered that capacity.

Harden explained this by saying that a high-molecular enzyme, the zymase proper, was left on the filter, which let through a low-molecular complementary enzyme, which for the sake of brevity was called co-enzyme or co-zymase.

Another no less important advance is made in Harden's demonstration of the hitherto neglected part played by phosphoric acid in the process of fermentation. It has been found that a certain addition of phosphate gives rise to an equivalent amount of carbonic acid and ethyl alcohol. This effect is associated with the formation of one or more definite compounds between sugar and phosphoric acid - known as the "zymo-phosphates", amongst which a glucose monophosphate and a glucose diphosphate are to be regarded as the most important.

In the same measure as research in this department has made new conquests, a clearer and clearer insight has been gained into the importance of this discovery. In particular the work of von Euler and his pupils during the last few years greatly contributed to the unravelling of the mechanism of phosphorization.

The primary function of phosphoric acid in fermentation consists, according to von Euler, in the fact that in cooperation with an enzyme it gives rise to glucose monophosphate, identical with the monophosphate discovered by Harden and Robison. This phosphate afterwards undergoes a mutation in the presence of co-zymase, inasmuch as a glucose diphosphate and an active glucose are formed, after which the latter yields the necessary material for the subsequent stages of the fermentation.

This demonstration of the part of mutase played by the co-zymase, or in other words of the identity of co-zymase and co-mutase, is of fundamental importance, for it has fully revealed the central position in the process of fermentation of the complementary enzyme in question.

The researches of von Euler and his pupils have further led to the concentration of the co-zymase and to a far more exact study of its properties than had been previously possible. They have been able to determine approximately its molecular weight, which has been found to be about 490; and they have also been able to draw certain definite conclusions concerning its chemical nature, which make it highly probable that we have here what the chemists call a pentosenucleoside. The production of a co-zymase with a high activity has also shown in a brilliant manner the character of that enzyme as a specific activator.

Finally, what gives special interest to the study to the complicated reaction mechanism of the fermentation of sugar is that it has been possible to draw from it important conclusions concerning carbohydrate metabolism in general in both the vegetable and the animal organism.

The brief summary which has now been given, and which, in view of the scanty time allowed, has necessarily been extremely fragmentary, will in any case probably have shown that there is an extremely intimate connection between the researches of Harden and von Euler in this field. On the one hand, the fundamental discoveries of Harden have formed the precondition and point of departure for the various work of von Euler; and on the other hand, it is only the work of the latter that has made fully evident the importance of Harden's discovery.

Under such circumstances the Academy of Sciences has not hesitated this time to avail itself of the expedient that is offered by the Statutes of the Nobel Foundation of dividing the prize between two equally meritorious scientists.

Professor Harden. When the Royal Swedish Academy of Sciences resolved to adjudge to you, together with Professor von Euler, this year's Nobel Prize in Chemistry on account of your important contributions to our knowledge of alcoholic fermentation, the Academy had let herself guided by a firm conviction that these contributions had opened indeed a new chapter in the investigation of that very complicated matter.

It is with the most sincere gratification that I have the honour of conveying to you the congratulations of the Academy on this distinction, the outward signs of which you are now about to receive.

Professor von Euler. It is a great pleasure to the Swedish Academy of Sciences to be able to award this time the Alfred Nobel's Prize also to one of her members, and so much more since during a long series of years we have been in the position to follow from nearby your energetic, persevering, and systematic investigations. The Academy is also firmly convinced that the distinction which has fallen upon you today, will not contain for you the temptation to rest on laurels already obtained, but that on the contrary it will mean a stimulus to continued and, as we all hope, successful work in the service of biochemistry.

Evolution in Ontario Schools

The United Church Observer comments on the deficiencies of Canada's education system when it comes to teaching evolution Where's Darwin?].
“Nothing in biology makes sense except in the light of evolution,” wrote the late Ukrainian geneticist Theodosius Dobzhansky, who found evidence for evolution by studying the genetic varietals of fruit flies. To most scientists, Darwinian evolution is the unifying principle of biology, as solid and significant as Newtonian gravity or Copernican heliocentrism. But you wouldn’t guess it from its place in Canada’s school system.

In all but one provincial science curriculum, evolution is relegated to a single unit in a Grade 11 or 12 elective course taken by a sliver of each graduating class. It would not be a stretch to say the majority of Canadian high school students graduate without ever encountering Darwin’s theory of natural selection.
The situation in Ontario is a little more complicated than this statement suggests. There's plenty of opportunities in Grades 1-8 to learn about diversity, change and adaptation but unfortunately it's true that the word "evolution" isn't mentioned [The Ontario Curriculum Grades 1-8: Science and Technology, 2007]. I'm told by several teachers that they frequently talk about evolution even though it's not specifically mentioned in the curriculum guidelines. It would be much better to put the fundamental concept of biology in the provincial curriculum.

Evolution is only covered specifically in Grade 12 Biology [The Ontario Curriculum Grades 11 and 12: Science]. As mentioned in the United Church of Canada article, this course is only taken by a small percentage of students in Ontario high schools.

The curriculum looks pretty good (see below). I wonder how it compares with the curricula in typical American high schools? Does anyone know?

The fact that this material is required in Grade 12 Biology suggests that high school science teachers will probably be familiar with the basic concepts of evolution and I'd be surprised if it doesn't get brought up in other courses. After all, the same teachers that teach Grade 12 Biology are often teaching other courses as well.

The fact that the Province of Ontario curriculum is so strongly supportive of evolution in the Grade 12 curriculum indicates that the government doesn't have any doubts about the validity of evolution even though they may be a bit wishy-washy about mentioning it in the primary grades.
Overall Expectations
By the end of this course, students will:
• analyse evolutionary mechanisms, and the processes and products of evolution;
• evaluate the scientific evidence that supports the theory of evolution;
• analyse how the science of evolution can be related to current areas of biological study, and how technological development has extended or modified knowledge in the field of evolution.

Specific Expectations
Understanding Basic Concepts
By the end of this course, students will:
– define the concept of speciation and explain the mechanisms of speciation;
– describe, and put in historical and cultural context, some scientists’ contributions that have changed evolutionary concepts (e.g., describe the contributions – and the prevailing beliefs of their time – of Lyell, Malthus, Lamarck,Darwin, and Gould and Eldridge);
– analyse evolutionary mechanisms (e.g., natural selection, sexual selection, genetic variation, genetic drift, artificial selection, biotechnology) and their effects on biodiversity and extinction (e.g., describe examples that illustrate current theories of evolution, such as the darkening over time, in polluted areas, of the pigment of the peppered moth, an example of industrial melanism);
– explain, using examples, the process of adaptation of individual organisms to their environment (e.g., explain the significance of a short life cycle in the development of antibiotic-resistant bacteria populations).
– formulate and weigh hypotheses that reflect the various perspectives that have influenced the development of the theory of evolution (e.g., apply different theoretical models for interpreting evidence).

Developing Skills of Inquiry and Communication
By the end of this course, students will:
– outline evidence and arguments pertaining to the origin, development, and diversity of living organisms on Earth (e.g., evaluate current evidence that supports the theory of evolution and that feeds the debate on gradualism and punctuated equilibrium);
– identify questions to investigate that arise from concepts of evolution and diversity (e.g.,Why do micro-organisms evolve so quickly? What factors have contributed to the dilemma that pharmaceutical companies face in trying to develop new antibiotics because so many micro-organisms are resistant to existing antibiotics?);
– solve problems related to evolution using the Hardy-Weinberg equation;
– develop and use appropriate sampling procedures to conduct investigations into questions related to evolution (e.g., to determine the incidence of various hereditary characteristics in a given population), and record data and information;

Relating Science to Technology, Society, and the Environment
By the end of this course, students will:
– relate present-day research and theories on the mechanisms of evolution to current ideas in molecular genetics (e.g., relate current thinking about adaptations to ideas about genetic mutations);
– describe and analyse examples of technology that have extended or modified the scientific understanding of evolution (e.g., the contribution of radiometric dating to the palaeontological analysis of fossils).

[Hat Tip: John Pieret "Refried Great Northern Beans" who loves finding examples where other countries are as bad as his. ]

Tuesday, September 02, 2008

University of Toronto Secular Alliance


Please consider joining the University of Toronto Secular Alliance. Visit the University of Toronto Secular Alliance (UTSA) website for more information.

Meetings will be held every second Wednesday beginning Wednesday, Sept. 10th. Meetings last from 7pm-10pm in the All-Purpose Room at the Multi-Faith Centre (2nd floor, 569 Spadina Ave. entrance from Bancroft Ave.)

All interested students are invited to a welcome party at CFI.
Thursday, September 4th at 11:00 am - 3:00pm

Come to 216 Beverley st (just south of College at St. George) to meet other students interested in science, secularism and freethought. There will be information on the center's activities and student groups. Several universities will be represented including York University, The University of Toronto and Ryerson University.

There will be stimulating discussions and activities to introduce you to the centre's goals and mandate. We'll also have pizza, drinks and lots of fun games - including gaming consoles (with Guitar Hero! woo!) and board games (like Risk! awesome.) We are also inviting all CFI volunteers to join us for this event.

Drop in between 11 am - 3 pm.  $3 donation for BBQ - $1 for drinks; *FREE* to Friends of the Centre.

Spore and Evolution

Spore is a computer game that let's you "evolve" organisms beginning with a simple cell and moving "upwards" to creatures that can build spaceships. The game is designed by Will Wright whose previous credits include SimCity and The Sims.

Wright and his company have been heavily promoting the game as a way of learning about evolution. As part of this promotion they have distributed free copies to many scientists in advance of the opening day of sales in retail stores. Here's how it's described on the Spore Website.
How will you create the universe?

With Spore you can nurture your creature through five stages of evolution: Cell, Creature, Tribe, Civilization, and Space. Or if you prefer, spend as much time as you like making creatures, vehicles, buildings and spaceships with Spore’s unique Creator tools.

CREATE Your Universe from Microscopic to Macrocosmic - From tide pool amoebas to thriving civilizations to intergalactic starships, everything is in your hands.

EVOLVE Your Creature through Five Stages - It’s survival of the funnest as your choices reverberate through generations and ultimately decide the fate of your civilization.
Time for a reality check. Spore is a computer game. It's purpose is to make bundles of money for Will Wright and his company. It may be an excellent game but it is NOT a way of learning about evolution. Evolution does not have a purpose or a direction.

Carl Zimmer has just published an article in The New York Times about Spore and computer simulations [Gaming Evolves]. Some scientists don't think the game reflects evolution.
Unlike the typical shoot-them-till-they’re-all-dead video game, Spore was strongly influenced by science, and in particular by evolutionary biology. Mr. Wright will appear in a documentary next Tuesday on the National Geographic Channel, sharing his new game with leading evolutionary biologists and talking with them about the evolution of complex life.

Evolutionary biologists like Dr. Near and Dr. Prum, who have had a chance to try the game, like it a great deal. But they also have some serious reservations. The step-by-step process by which Spore’s creatures change does not have much to do with real evolution. “The mechanism is severely messed up,” Dr. Prum said.

Nevertheless, Dr. Prum admires the way Spore touches on some of the big questions that evolutionary biologists ask. What is the origin of complexity? How contingent is evolution on flukes and quirks? “If it compels people to ask these questions, that would be great,” he said.
The object of the game is to "evolve" advanced creatures that the player "designs." What are the chances that the average player is going to appreciate the roles of contingency, and quirks? Probably so close to zero that it's not worth discussing.

I have a problem when we talk about games like Spore and real evolution in the same breath. I have a problem when someone like Will Wright is promoted on the National Geographic TV channel. The press release from National Geographic sounds ominous ..
(WASHINGTON, D.C. — AUGUST 21, 2008) In the newest creation from Electronic Arts Inc. (EA) and video game pioneer and "The Sims" mastermind Will Wright, Spore™ enables players to design a virtual galaxy of new life, such as a one-eyed web-footed creature with a snout, and then control their species' evolution. But how much real-world science is behind this groundbreaking new game? And what genetic connections do people share with a universe of strange organisms?

On Tuesday, Sept. 9, at 10:00 p.m. ET/PT, National Geographic Channel (NGC) presents the premiere of How to Build a Better Being, the companion documentary to the highly anticipated new video game Spore, which will be released nationally on Sunday, Sept. 7. The show, which is also included in the limited run of the collectable "Spore Galactic Edition," joins Wright and leading scientists in exploring the genetic information we share with all animals — even creatures we could never have envisioned. From prehistoric fish with wrists to 8-ton elephants with trunks, get powerful new insight into the origin of species and how our prized parts came to be. Then see how evolutionary creature-making is translated into a brave new world of gaming.

"What are the things that evolution has at its disposal to define a creature, to mix and match the parts, and eventually come up with a unique organism that's going to live its life and try to reproduce?" — Will Wright, gaming innovator
Some would argue that anything that promotes evolution is a step in the right direction. It's a valid point.

But why can't we have our cake and eat it too? Why can't we promote evolution but do it in a scientifically accurate manner? It's abundantly clear to all scientists that the general public knows little about evolution and what little they know is mostly wrong. Do we have to cater to those false impressions?

What effect is it going to have in the long run if we misrepresent science by pretending that evolution is progressive and ladder-like and leads eventually to us—or at least leads to intelligent animals? Is anyone else concerned about this?

The video clip below doesn't mention Spore. It looks like the same old evo-devo emphasis on semi-conserved regulatory genes and regulation of animal development as keys to understanding how humans evolved.

The Spore advertisement exploits the National Geographic connection.

Comment Policy on Sandwalk

I think it's time to re-state my policy on comments. I don't like censorship. That's why my policy is close to the one mockingly described at Draft Blogger's Code of Conduct.
We also decided we needed an "anything goes" badge for sites that want to warn possible commenters that they are entering a free-for-all zone. The text to accompany that badge might go something like this:

"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."
As a consequence of this policy, there are several very annoying people making comments on Sandwalk. I don't respond to comments from those people but others are free to do so.

There are two types of comments that will be removed from Sandwalk. These are cases where censorship is justified, in my opinion.

The first is outright spam of the sort that we all have to tolerate from time to time. If your comment serves no other purpose than to direct people to 30 different "free" travel websites, for example, then these comments will be quickly removed.

The second is blatant promotion of commercial products on the pretext that they are relevant to the content of a posting. An example of the second type is the posting of a website for collagen creme in the comments section of an article about the biochemistry of collagen.

Alternating Generations

Check out When Ferns Don't Look Like Ferns by Christopher Taylor on Catalogue of Organisms. The concept of alternating generations is an important concept that everyone should understand.

All plants undergo alternation of generation to a greater or lesser degree. Here's an interesting way to think about the concept from the Biology course notes at the University of Miami.
If animals were to undergo alternation of generations, then imagine that you are the diploid individual (sporophyte). Your mother, the gametophyte, would be haploid, and would look completely different from you (maybe like a SmurfTM). Your grandmother would be diploid, and look like you. Your own offspring would look like your mama the SmurfTM, your grandchildren would look like you, and so on.

[Image Credit: Lewis & Clark]

Monday, September 01, 2008

Genes and Geography

Your DNA tells you who you are related to. This has led to projects that can trace your ancestors. Your DNA can also tell you where you've come from. This is because most of our ancestors didn't get out much. They tended to marry their cousins and close neighbors. Over many generations the people in a particular region came to resemble each other much more closely than they resembled people in other countries.

Razib at Gene Expression has been discussing the evolutionary implications of this kind of population genetics. See his latest posting and learn how to interpret the map shown below [Genetic map of Europe; genes vary as a function of distance].

Monday's Molecule #86

In honor of all those students who are returning to college this week's molecule is another simple one that should be familiar to every undergraduate taking an introductory biochemistry course. Your task is to identify the molecule and give me its correct common name—the one required on an exam—and the complete, correct IUPAC name.

There's a direct connection between today's molecule and a Nobel Prize. We are looking for the single person most responsible for identifying this molecule as an important part of a metabolic pathway. This person didn't know the exact structure but got the basic chemistry correct. Be careful, there are several possible candidates who haven't already been featured on Sandalk. I want the one person who best meets the criterion.

The first person to correctly identify the molecule and name the Nobel Laureate, 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. You know who you are.


Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) 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 no open.

UPDATE: The molecule is ATP of adenosine 5′-triphosphate. Lots of people got the molecule but nobody guessed the Nobel Laureate (Hans von Euler-Chelpin). There are no winners this week.

What the Heck?

Coturnix posted a video on A Blog Around the Clock. His posting, entitled Just replace '9/11' with 'POW'..., was critical of McCain and his running mate Sarah Palin. The main issue in the election, according to Coturnix and others, is race. If true, that's sad.

I tried to watch the video that Coturnix embedded in his blog and this is what I get ...

Isn't that interesting? Is this a joke or has the server at hulu has been set up to recognize and block IP numbers that are registered outside of the USA? Why?

Why Is Canada in Afghanistan?

The Toronto Star asked this question a few days ago. Here's the entire article from Our Man in Afghanistan. I've chosen to accompany it with a photograph of the Prime Minister of Canada shaking hands with Hamid Karzai. This is the same photo that Canadian Cynic used in Sorry ... why exactly are we over there again?.
My words fail. So here's Britain's The Independent:

"The Afghan president, Hamid Karzai, has pardoned three men who had been found guilty of gang raping a woman in the northern province of Samangan.

The woman, Sara, and her family found out about the pardon only when they saw the rapists back in their village.

“Everyone was shocked,” said Sara’s husband, Dilawar, who like many Afghans uses only one name. “These were men who had been sentenced and found guilty by the Supreme Court, walking around freely.”

Sara’s case highlights concerns about the close relationship between the Afghan president and men accused of war crimes and human rights abuses.

The men were freed discreetly but the rape itself was public and brutal. It took place in September 2005, in the run up to Afghanistan’s first democratic parliamentary elections.

The most powerful local commander, Mawlawi Islam, was running for office despite being accused of scores of murders committed while he had been a mujahedeen commander in the 1980s and a Taliban governor in the 1990s, and since the fall of the Taliban in 2001. Sara said one of his sub-commanders and body guards had been looking for young men to help in the election campaign.

“It was evening, around the time for the last prayer, when armed men came and took my son, Islamuddin, by force. I have eye-witness statements from nine people that he was there. From that niGht until now, my son has never been seen.”

Dilawar said his wife publicly harangued the commander twice about their missing son. After the second time, he said, they came for her. “The commander and three of his fighters came and took my wife out of our home and took her to their house about 200 metres away and, in front of these witnesses, raped her.”

Dilawar has a sheaf of legal papers, including a doctors’ report, which said she had a 17mm wound in her private parts cut with a bayonet. Sara was left to stumble home, bleeding and without her trousers."

Remind me again what Canadians are getting killed and mutilated for?
Exactly. All we're doing is propping up a government that's as corrupt as the group we are fighting. We are caught in the middle of a civil war and the best thing to do is to get the heck out and let the Afghans sort it out for themselves.