Into the Textbooks It Goes

 
This week's issue of Science contains an important paper.

Maier, T,, Leibundgut, M. and B. Nenad (2008) The Crystal Structure of a Mammalian Fatty Acid Synthase. Science 321:1315-1322.

We've known for a long time that this is a very important enzyme and that it's a classic example of a little protein machine combining the activities of may different enzymes in order to carry out the complex reactions of fatty acid synthesis. Here's how I described it in the last edition of my book ...

In bacteria, each reaction in fatty acid synthesis is catalyzed by a discrete monofunctional enzyme. This type of pathway is known as a type II fatty acid synthesis system (FAS II). In animals, the various enzymatic activities are localized to individual domains in a large multifunctional enzyme and the complex is described as a type I fatty acid synthesis system (FAS I). The large animal polypeptide contains the activities of malonyl/acetyl transferase, 3-ketoacyl-ACP synthase, 3-ketoacyl–ACP reductase, 3-hydroxyacyl–ACP dehydratase, enoyl–ACP reductase, and thioesterase. It also contains a phosphopantetheine prosthetic group (ACP) to which the fatty acid chain is attached. Note that the malonyl CoA:ACP transacylase enzyme shown in Figure 16.3 is replaced by a transferase activity in the FAS I complex. This transferase catalyzes a substrate loading reaction where malonyl CoA is covalently attached to the ACP-like domain on the multienzyme polypeptide chain. The eukaryotic enzyme is called fatty acid synthase.

The structure (shown below) will be going right into the textbooks.

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Citation Classic: Recombinant DNA

 
Read John Dennehy's citation classic for this week at This Week's Citation Classic: Genetic Engineering. The paper is one of the first examples of genetic engineering and recombinant DNA technology. Before you go, try and guess when the paper was published. Was it before you were born or after?

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[Photo Credit: Protesters at the National Academy of Sciences Forum on Recombinant DNA from The Maxine Singer Papers]

Sue Blackmore on Teaching Critical Thinking

 
Susan Blackmore is an interesting person. According to her Website ...

Sue Blackmore is a freelance writer, lecturer and broadcaster, and a Visiting Lecturer at the University of the West of England, Bristol. She has a degree in psychology and physiology from Oxford University (1973) and a PhD in parapsychology from the University of Surrey (1980). Her research interests include memes, evolutionary theory, consciousness, and meditation. She practices Zen and campaigns for drug legalization.

Sue Blackmore no longer works on the paranormal.

Yesterday she published an article in The Guardian (UK) [Opening Minds].

Should science teachers in Britain challenge their students' religious beliefs? Is it their right? Is it even their duty?

I say yes. This is (amongst much else) what education is for; to teach children how to think for themselves. And thinking for yourself is challenging, especially if your previous beliefs were based on dogma and ancient books.

This may illustrate one of the ways that education in the UK differs from that in the USA.

I don't mean that science teachers should belittle religious beliefs, or scoff at them, or even tell students they are wrong. They need not even mention religion or creationism. What they must do is explain so clearly how natural selection works that those students, like one or two in Dawkins' series, begin to feel the terrifying impact of what Darwin saw. This realisation will change them. It will challenge what mummy and daddy told them, it will cry out against what they heard in chapel or synagogue or mosque. It will help immeasurably in their ponderings on human nature, the origins of life and the meaning of existence. This is growing up. This is learning. This is the process that skilful science teachers need to initiate, encourage, and help sensitively to guide.

They should never shy away from challenging their students' religious beliefs and opening their minds, because understanding the world through science inevitably does just that.

I'm all for challenging students to think. Problem is, you'd better make sure you know what you're talking about. I'd like to challenge Sue Blackmore to stop thinking about Darwin, Dawkins and natural selection and start thinking about the 21st century version of evolution.

Next question is, how do we evaluate students in such a course? Can they still pass if they reject evolution and critical thinking?

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[Hat Tip: RichardDawkins.net]

The Earth's Axis Has Shifted by 26°!

 
Friday's Urban Legend: FALSE

Today's dose of non-critical thinking comes from the August 9th issue of New Scientist [Tilting Earth Cover up].

WORRIED by hurricanes, earthquakes and volcanoes? Wondering what to blame? Would you believe that these have all been linked to the Earth's axis shifting by 26 degrees in two stages, one in late 2004 and one in early 2005?

How is it, you may well ask, that you didn't notice? It's because the US government covered it up, as you will learn at http://axischange.wordpress.com. Apparently the Global Positioning System broke down at these times and it was kept secret.

Even bigger laughs can be had at Divulgence.net.

Apparently Phil Plait of Bad Astronomy dealt with this issue some time ago.

Bad Astronomy points out that if the Earth's axis had shifted that much, we would have been in sunlight at midnight, whereas in fact it was quite definitely dark. What's more, even if we didn't look out of the window, we would surely have spotted the satellite TV blinking off as the satellite dishes ceased to point to where the satellites are.

I'd like to link to Phil's posting on this issue—does anyone have a URL? Here's the link to Bad Astronomy [Tilt!]

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Knowing How to Learn

The August 9, 2008 issue of New Scientist contains an important commentary by A.C. Graying on The importance of knowing how.

The key point is in the third paragraph ...

So although everyone coming out of an educational system should at least know the periodic table, the salient dates of world history, the fundamentals of geography, and other kinds of basic information, they are much more in need of knowing how to find things out, how to evaluate the information they discover, and how to apply it fruitfully. These are skills; they consist in knowledge of how to become knowledgeable.

I agree with this statement. The most important goal of a university education is, in my opinion, to teach students how to think. An important part of that goal is teaching students how to acquire reliable information.

Knowing how to evaluate information, therefore, is arguably the most important kind of knowledge that education has to teach. Some schools offer courses in it, and there are a number of books about it on the market. But only the International Baccalaureate makes critical thinking ("theory of knowledge") a standard requirement, and in this as in so many ways it leads the field, because critical thinking and evaluation of claims to knowledge should always be right at the centre of the educational enterprise.

I'm not so sure that the IB program is the only one that teaches critical thinking but I agree with the general idea here. I think every university should require that students take certain courses on logic and knowledge. These courses should be taught by philosophers.

I wonder whether the need for critical thinking lessons is more urgent in the humanities than the sciences because the latter, by their nature, already have it built in. The science lab at school with its whiffs, sparks and bangs is a theatre of evaluation; the idea of testing and proving is the natural order there, and the habits of mind thus acquired can be generalised to all enquiry.

When we talk of scientific literacy, one thing we should mean is acquisition of just this mindset; without it, too much rubbish gets through.

Hmm ... I don't think I would have had the gumption to claim that science students may be better at critical thinking than humanities students. I may think it, but writing it is a different story.

If true, the problem may be related to what passes for "postmodernism" in the humanities. Believe it or not, there are humanities Professors whose ideas about critical thinking are quite bizarre. I've met some of them. They think it's wrong to pick a side in an intellectual dispute because all sides are equally valid. They think that we can't really "know" anything. For them, I guess "knowing how to learn" is an oxymoron.

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[Photo Credit: Professor A.C. Grayling, Professor of Philosophy, Birkbeck, University of London UK.]

Is Your Name Steve or Stephanie?

 
If you answered "yes" to that question then you are one third of the way toward winning a huge prize. All you have to do is answer "yes" to two more questions: (1) do you have a Ph.D., (2) do you agree with the following statement ...

Evolution is a vital, well-supported, unifying principle of the biological sciences, and the scientific evidence is overwhelmingly in favor of the idea that all living things share a common ancestry. Although there are legitimate debates about the patterns and processes of evolution, there is no serious scientific doubt that evolution occurred or that natural selection is a major mechanism in its occurrence. It is scientifically inappropriate and pedagogically irresponsible for creationist pseudoscience, including but not limited to “intelligent design,” to be introduced into the science curricula of our nation’s public schools.

Check out Panda's Thumb for more details about Project Steve [Looking for Dr. 900].¹

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1. You don't have to be American (I think).

Critical Thinking Skills in Science

 
I start teaching a course next week on misconceptions and controversies in science. One of the goals is to teach critical thinking skills. I think we'll start out by discussing the objectives of the recently passed law in Louisiana. It looks like a good description of what we should be trying to do in university and it has the added advantage that we can segue right into creationist lies, cynicism, and hypocrisy.

AN ACT

To enact R.S. 17:285.1, relative to curriculum and instruction; to provide relative to the teaching of scientific subjects in public elementary and secondary schools; to promote students' critical thinking skills and open discussion of scientific theories; to provide relative to support and guidance for teachers; to provide relative to textbooks and instructional materials; to provide for rules and regulations; to provide for effectiveness; and to provide for related matters.

Be it enacted by the Legislature of Louisiana:

Section 1 R.S. 17:285.1 is hereby enacted to read as follows:

285.1 Science education; development of critical thinking skills

A. This Section shall be known and may be cited as the "Louisiana Science Education Act."

B. (1) The State Board of Elementary and Secondary Education, upon request of a city, parish, or other local public school board, shall allow and assist teachers, principals, and other school administrators to create and foster an environment within public elementary and secondary schools that promotes critical thinking skills, logical analysis, and open and objective discussion of scientific theories being studied including evolution, but not limited to evolution, the origins of life, global warming, and human cloning.

     (2) Such assistance shall include support and guidance for teachers regarding effective ways to help students understand, analyze, critique, and objectively review scientific theories being studied, including those enumerated in Paragraph (1) of this Subsection.

C. A teacher shall teach the material presented in the standard textbook supplied by the school system and thereafter may use supplemental textbooks and other instructional materials to help students understand, analyse, critique and review scientific theories in an objective manner, as permitted by the city, parish, or other local public school board.

D. This Section shall not be construed to promote any religious doctrine,promote discrimination for or against a particular set of religious beliefs, or promote discrimination for or against religion or nonreligion.

E. The State Board of Elementary and Secondary Education and each city, parish, or other local public school board shall adopt and promulgate the rules and regulations necessary to implement the provisions of this Section prior to the beginning of the 2008/2009 school year.

I ain't no lawyer but to me it looks like this is going to be a hard law to challenge in court. We all know its purpose—to promote religion—but its authors may have done a good job of phrasing it in a way that avoids a challenge.

Any lawyers out there?

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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 + P_i          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].

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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

AMP~P~P
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 + P_i          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 + P_i 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?.

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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!"

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Send an email message to host@tangledbank.net 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.

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.

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[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 + P_i 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.

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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.

THEME:
Nobel LaureatesThe 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.

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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.

Evolution
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).

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

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.

CFI STUDENT WELCOME PIZZA PARTY
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.

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